The BRENDA enzyme information system-From a database to an expert system.

Enzymes, representing the largest and by far most complex group of proteins, play an essential role in all processes of life, including metabolism, gene expression, cell division, the immune system, and others. Their function, also connected to most diseases or stress control makes them interesting targets for research and applications in biotechnology, medical treatments, or diagnosis. Their functional parameters and other properties are collected, integrated, and made available to the scientific community in the BRaunschweig ENzyme DAtabase (BRENDA). In the last 30 years BRENDA has developed into one of the most highly used biological databases worldwide. The data contents, the process of data acquisition, data integration and control, the ways to access the data, and visualizations provided by the website are described and discussed.

HeartCycle: advanced sensors for telehealth applications.

Current treatment of Cardiovascular Disease (CVD)--the most frequent cause of hospitalization for people over 65--involves changes of diet and lifestyle, requiring in addition physical exercise to support these. Nowadays, patients receive sporadic feedback at doctor visits, or later on, when facing symptoms. The HeartCycle project aimed at providing 1) daily monitoring, 2) close follow up, 3) help on treatment routine and 4) decreasing non-compliance to treatment regimes. The present paper illustrates a new toolbox of advanced sensors developed within the HeartCycle project. Ongoing clinical studies support these developments.

[Invasive electrophysiology: complications, nightmares and their management]. / Invasive Elektrophysiologie: Komplikationen, Alpträume und deren Management--Rechtskardiale Katheterablationen.

Most minor side effects of ablation in the right atrium and right ventricle relate to femoral venous catheterization but there is a small risk of severe complications including atrioventricular (AV) block, damage of surrounding structures and thromboembolic events. Impairment of AV conduction can occur during ablation of atrioventricular re-entrant tachycardia, ablation of anteroseptal, mid-septal and parahisian accessory pathways, ablation of ectopic atrial tachycardia originating from the vicinity of the atrioventricular node and when ablating the septal isthmus for typical atrial flutter. Damage of the right coronary artery is a very rare complication after inferior isthmus ablation with high energy. The thromboembolic risk during and after cardioversion and ablation of atrial flutter is higher than previously recognized and anticoagulation therapy decreases this risk. The risk of perforation and tamponade during ablation in the right atrium and right ventricle is very low but particular caution is necessary in thin-walled structures such as the coronary sinus and the upper right ventricular outflow tract. Phrenic nerve injury can be avoided by pacing from the mapping electrode before application of radiofrequency energy at the right atrial free wall. Limitation of power output depending on the site of ablation and titration of energy application with continuous control of temperature and impedance should be considered to minimize the risk of complications.

[The efficacy of a combination herbal medicine in the treatment of functional dyspepsia. Meta-analysis of randomized double-blind studies on the basis of a valid gastrointestinal symptom profile]. / Wirksamkeit eines pflanzlichen Kombinationspräparats bei funktioneller Dyspepsie. Metaanalyse randomisierter Doppelblindstudien auf Basis eines validen gastrointestinalen Symptomprofils.

BACKGROUND AND AIM: Functional dyspepsia is a heterogeneous clinical entity of incompletely known etiology. Overall, four randomized double-blind studies from the nineteen-nineties investigating acute treatment of this condition with the combination herbal medicine Iberogast, are available. A meta-analysis of the studieswas carried out to evaluate the overall therapeutic effect. PATIENTS AND METHODS: In all four, triple-arm, controlled multicentre studies, the efficacy of 4 weeks of treatment with 3 x 20 drops daily, applied after a washout phase, was investigated, the primary efficacy parameter being a specific gastrointestinal symptom score. Of the 592 participants in the studies, 196 were treated with Iberogast, 131 with placebo, and 61 with cisapride as positive control. The remaining 204 patients, who were treated with an experimental herbal preparation of similar composition, were not admitted to the final analysis. RESULTS: While overall appreciable improvement of the clinically relevant symptoms of moderate severity was seen under treatment with the combination herbal preparation, the individual studies differed in terms of the statistical significance of the results obtained. The meta-analysis of studies revealed a clear therapeutic effect for the herbal medicine (p < 0.0001). CONCLUSION: The clinical experience with the combination preparation for the treatment of functional dyspepsia was confirmed by the meta-analysis of the modern double-blind studies.

An arm phantom: a digital simulation system for testing sphygmomanometers.

An arm phantom for testing non-invasive blood pressure measuring instruments under reproducible and real conditions has been developed. Signal records, recorded on patients and validated by a reference method, are played into the instruments to be tested using a combination of an electro-pneumatic and an electro-acoustic converter. For each of 90 patients a database contains records of at least three different kinds of signal: cuff pressure oscillations, Korotkoff sounds (except in neonates) and cuff pressure. As the inflation and deflation rate varies between different sphygmomanometers the control and synchronization of the signal output are ensured as a function of the instantaneous cuff pressure, measured continuously by the system. A segmented output procedure synchronizes the data flow during the test procedure. The records of blood pressure signals are separated in different signal groups, containing only one pressure oscillation and Korotkoff sound respectively, whereas the instantaneous cuff pressure determines the signal group to be selected. Suitable interfaces to the sphygmomanometers under test consist of two specifically developed signal converters, an electro-pneumatic converter and an electro-acoustic converter. The system generates both cuff pressure oscillations and Korotkoff sounds from real data earlier recorded on human subjects. It allows any inflation and deflation rate of the cuff pressure to be applied, considers the variability of the pulse rate occurring in the same data record and finally it allows the superposition of artefacts. The arm phantom can replace clinical trials. The possibility of testing the limits of the performance of sphygmomanometers has been considerably extended.

[The content of ascorbic acid in plasma and in 14 tissues of lambs of different ages during normal feeding and feeding restricted from time to time during the suckling period]. / Der Gehalt an Ascorbinsäure im Plasma und in 14 Geweben von Lämmern unterschiedlichen Alters bei normaler und bei zeitweise restriktiver Fütterung während der Säugeperiode.

In normally fed lambs (group 1) the content of ascorbic acid (AA) in the plasma on day 8, 18, 28, 38, 48, 60 and 100 after birth was the same as in lambs, that were fed on days 8 to 17 (group 2), 8 to 26 (group 3) and 8 to 35 (group 4) on the maintenance level. The restrictive feeding induced for a certain time a decrease in the glucose content of the plasma. In the lambs of group 2 and 3 there was no differences in the content of AA in 14 tissues compared to group 1. In the lambs of group 4 the body weight on the 35th day was only 54 and the mass of the hypophysis 60, of the lung 55.9, of the liver 51, of the heart 47.2, of the spleen 44.7 and of the kidney 38% of that of group 1; there was a tendency to a lower content of AA in most tissues. With increasing age the content of AA in the cerebrum, in the cerebellum, in the brain stem and in the testicles decreased; the highest content in the hypophysis was determined on day 180. The regulation of the synthesis of AA in the liver under normal and pathological conditions is discussed.

[The reliability of the measurement of non-invasive oscillometric blood pressure instruments]. / Zur Messsicherheit nichtinvasiver oszillometrischer Blutdruckmessgeräte.

METHODS: The performance of five oscillometric blood pressure monitors was tested by means of a simulator. The oscillometric signals of two healthy patients were replayed. These signals were superimposed by sinusoidal artefacts with increasing amplitude, to examine the influence of artefacts on the accuracy of the measurement. Each measurement was repeated 15 times. RESULTS: The artefacts taken for this examination did affect the scattering of each single measurement rather than the mean value of the repeated measurements. The results did get worse with decreasing signal-to-artefact ratio. However, some monitors are able to handle these artefacts better than others. CONCLUSION: It is obvious that the implemented software for the artefact treatment and the determination of blood pressure values differs from manufacturer to manufacturer. Some devices were able to separate relevant signals from artefacts better than others. The most critical point of the oscillometric method is the correct determination of the maximum amplitude of the oscillations, because it directly influences the accuracy of the displayed blood pressure values. The availability of a simulator to test automated sphygmomanometers has shown to be a good tool to examine the performance of these devices.

[The use of a hydrolysis residue from lysine production in a straw concentrate mixture for fattening lambs]. / Die Verwendung eines Hydrolyserückstandes aus der Lysinherstellung im Strohkonzentratgemisch für Mastlämmer.

The validity of residues from hydrolysis of soya bean meal for production of lysine was tested in a growth experiment with 2 groups of 25 cross breeding lambs as well as in a N-balance trial with 5 lambs. The animals in the growth experiment started with an average body weight of 25 kg. An industrially produced concentrate for lamb fattening was given to the animals of the control group. To the second group a straw-concentrate mixture was given, containing 30% straw, 52% barley, 5% soya bean meal, 5% dried beet pulp and 5% of hydrolysis residue. The mixture included 10.71 MJ ME resp. 5.51 MJ net-energy fat (cattle) and 166 g digestible crude protein per kg dry matter. The lambs of group 2 showed an 8% lower intake of DM, connected with a 26% intake of energy and 32% lower intake of DCP in comparison to the control group. The average daily body weight gain was 374 g for the control group and 241 g for group 2 respectively, the difference being statistically significant. The feed/gain ratio was in group 2 = 14% higher for energy and 6% higher for DCP than in the control group. The N-balance trial resulted in a N-retention of 25 percent of the N-intake. The results approved the possible use of 5% of the hydrolysis residue product for 2% crude protein in straw-concentrate mixtures for ruminants.

[The content of Hb in the blood and of different constituents in the plasma of lambs with low and normal increase in body mass]. / Untersuchungen über den Gehalt an Hb im Blut sowie an verschiedenen Bestandteilen im Plasma von Lämmern mit niedriger sowie mit normaler Zunahme an Körpermasse.

In lambs with a very restricted intake of nutrients and an increase of the body mass of less than 60 g per day (group A) and in those with an increase of more than 220 g/day (group B), analyses of components of the blood and the plasma were performed at certain intervals. In the lambs of group A an anemia developed in the course of 77 days. The concentrations of alpha-amino-N, non-protein-N, urea, glucose and insulin as well as the activity of the alkaline phosphatase of the plasma of the lambs of group A were always lower than those of group B. The beta-hydroxybutyrate concentration of the lambs of group A on the 7th and 21st day of the experiment was higher than that of group B. The concentrations of inorganic phosphate and iron in the plasma of group A at most points during the study were lower than that in group B.

[The effect of a restriction of the feed intake on the composition of the blood and on the development and composition of different tissues of sheep during growth. 2. The development of different tissues and the concentration of protein, DNA and RNA]. / Untersuchungen über den Einfluss einer Beschränkung der Nährstoffaufnahme auf die Zusammensetzung des Blutes sowie auf die Entwicklung und Zusammensetzung verschiedener Gewebe von Schafen während des Wachstums. 2. Mitteilung: Die Entwicklung verschiedener Gewebe sowie die Konzentration an Protein, an DNA und an RNA.

The concentration of protein in the cerebrum of sheep after a period of feed restriction (group 2) was lower (94.5 +/- 10.2) than in normally fed sheep of group 4 (101.4 +/- 9.4 mg/g wet weight). In the group 2 the concentration of protein in the M. longissimus dorsi and in the M. semimembranosus was also smaller. A high DNA-concentration was determined in the intestinal lymph nodes, in the spleen and in the lung. The DNA-concentration of the testes of group 2 (7.17 +/- 2.92) was higher than that of the group 4 (4.46 +/- 1.70 mg/g w. w.), also that of the renal fat tissue (0.39 +/- 0.18 resp. 0.20 +/- 0.09). The highest protein: DNA-relation in group 4 was found in the fat tissue (203.5: 1) and the lowest in the spleen (15.3: 1). A high RNA-concentration was analysed in the lymph nodes, in the spleen and in the lung. The RNA-concentration in the fat tissue of group 2 (0.34 +/- 0.13) was higher that that in group 4 (0.15 +/- 0.08 mg/g w. w.).

[The effect of a restriction of nutrient intake on the composition of the blood and on the development and composition of different tissues of sheep during growth. 1. The level of the hematocrit and hemoglobin in the blood, that of protein, alpha amino-N, remaining N, glucose, FFA, insulin, beta-hydroxybutyrate, Na, K, Ca, Mg, Pa, Fe, iron-binding capacity, Cu and Zn and the activities of ALT, AST, LDH, GGT and AP in plasma at slaughter]. / Untersuchungen über den Einfluss einer Beschränkung der Nährstoffaufnahme auf die Zusammensetzung des Blutes sowie auf die Entwicklung und Zusammensetzung verschiedener Gewebe von Schafen während des Wachstums. 1. Mitteilung: Der Gehalt an Hämatokrit und Hb im Blut, an Protein, alpha-Amino-N, Rest-N, Glucose, FFS, Insulin, beta-Hydroxybutyrat, Na, K, Ca, Mg, Pa, Fe, Fe-Bindungskapazität, Cu und Zn sowie an Aktivität der ALAT, ASAT, LDH, gamma-GT und der AP im Plasma bei der Schlachtung.

In lambs after weaning with a body weight of 16.3 +/- 1.5 kg (group 1) and in sheep after a period of fattening with an increase of the body weight of 72.2 +/- 13.6 (group 2), of 184.4 +/- 12.2 (group 3) respectively of 302.1 +/- 24.3 g per day (group 4) the concentration of the components mentioned in the title was analysed in blood and plasma. The hematocrit, the concentration of Hb in the blood and that of total protein, of nonprotein-N, of Na, of Ca, of the iron-binding capacity and of Zn as well as the activity of the 5 enzymes in the plasma of the sheep of group 4 were higher than that of the group 2. Stress by the transport and stunning increased the concentration of free fatty acids in the plasma. The significance of the results for the clinical-chemical diagnosis is discussed.

[Relationship between wool yield and cyst(e)ine level in blood plasma]. / Beziehungen zwischen Wollertrag und Cyst(e)ingehalt im Blutplasma.

Publications from Williams were the stimulation to study the relations between wool yield and cyst(e)ine concentration in blood plasma. Methodical experiments were carried out and the two methods used each provided clear results. At the same time the reversible binding of a part of the free cystine in the plasma with the plasma proteins and its effect on the analysis results might be considered. After an interpretation of the two methods their use is described taking into consideration the factors influencing the results of the analysis. It is concluded that the two methods are usable for the planned purpose.

[The nitrate content in milk]. / Zum Nitratgehalt in der Milch.

Analytical possibilities for nitrate determination in milk on the base of photometric methods are discussed. An automated method, similar to Nijhuis u. a. (1979), is proposed using flow stream analyser ADM 300. Natrium nitrate (5 g and 10 g/kg live weight resp.) was given to two dairy cows after morning feeding on the 1st and on the 3rd day of experiment. The increase of nitrate content in the milk was very quick, maximal concentrations after 2 h were found as 5.6 mg/l (animal 1) and 3.2 mg nitrate-N/l (animal 2). But nitrate also disappeared relatively quickly, after 24 h there only values were observed corresponding to normal range of 1 mg/l.

[The effect of energy concentration and source on the use of feed protein and NPN in lambs. 3. Allantoin excretion and microbial protein synthesis]. / Einfluss der Energiekonzentration und -quelle auf die Verwertung von Futterprotein und NPN bei Lämmern. 3. Mitteilung. Allantoinausscheidung und mikrobielle Proteinsynthese.

In an N balance experiment with male crossbreeding lambs at an age of 3 ... 4 months four different rations were given differing in energy concentration (high greater than 700 EFU cattle/kg DM and low less than 650 EFU cattle/kg DM) and in the energy source (sugar, starch or crude fibre) with crude protein intake being almost equal. The rations contained 2% urea. Microbial protein synthesis in the rumen was assessed according to ROTH and KIRCHGESSNER (1978) (1), RYS et al. (1975) (2) and BICKEL-BAUMANN and LANDIS (1986) (3) on the basis of allantoin excretion in urine. The highest ruminal protein synthesis quotas were 868 ... 921 mg protein N per kg LW0.75 in (2). In (3) 723 ... 766 mg protein N/kg LW0.75 were synthesized. From the 15N labelling of the supplemented urea and the excreted allantoin it could be calculated that 26 ... 40% of the microbial protein resulted from the urea-N of the ration. Despite a high crude protein content of the ration of between 16 and 17% in the DM and a relation of NPN: pure protein of 0.95 the utilization of the NPN in the ration was relatively high but slightly lower than the utilization of pure protein. The variants with higher energy concentration showed as a tendency higher allantoin excretion in spite of slightly lower dry matter intake and a slightly higher NPN utilization than the variants with lower energy concentration.

[Urea utilization in growing lambs. 7. NPN- and pure protein-N-utilization at various ages]. / Harnstoffverwertung wachsender Lämmer. 7. Mitteilung. NPN- und Reinprotein-N-Verwertung bei unterschiedlichem Alter.

The utilization quota of NPN and pure feed protein for body protein synthesis was calculated on the basis of N balance experiments with 15N labelled urea with the help of model concepts of a 3-pool model and its mathematical usage. In lambs weighing 13 kg, the efficiency of amino acid and nucleic acid synthesis in the non-amino acid N pool was 64%. This results in a total utilization quota for NPN and pure protein in the ration of 40% and 60%, resp. Lambs weighing 27 kg showed an efficiency in amino acid and nucleic acid synthesis in the non-AA N pool of 77% and in the AA N pool of 60%. The total utilization quota of NPN was 47% and that of pure protein 56%. The pure protein in the ration was thus about twice as well utilized for total protein synthesis and for protein synthesis for crude protein retention as the NPN compounds in the ration.

[Influence of energy concentration and source on the utilization of feed protein and NPN in lambs. 2. 15N balance and utilization of pure protein and NPN]. / Einfluss von Energiekonzentration und -quelle auf die Verwertung von Futterprotein und NPN bei Lämmern. 2. Mitteilung. 15N-Bilanz und Verwertung von Reinprotein und NPN.

In an experiment 12 lambs of the merino species were divided into 4 groups. The variants HE received 740 or 718 EFU cattle/kg DM and the variants NE 689 or 671 EFU cattle/kg DM. The different energy concentrations resulted from differentiated quotas of dried sugar beet chips and wheat starch supplements. Within the variants, sub-variants with (HESZ, NESZ) or without (HES, NES) sugar supplements were formed. Due to varied DM intake, the average energy intake in all groups was 42 EFU cattle/kg LW0.75. N balance experiments using 15N-labelled urea were carried out, and 15N accumulation of N excretion was projected to a steady state. The partial utilization of pure protein and NPN in the ration was ascertained with the help of a 3-pool compartment model of N utilization in ruminants. In the non-amino acid N pool HE utilized 84% of NPN and NE 77% for the synthesis of amino and nucleic acids. The efficiency of protein synthesis in the amino acid N-pool were in HESZ 64%, HES 70%, NESZ 70% and NES 73%, resp. The total utilization of NPN is the sum of the partial utilization in the two pools, whereas the total utilization of pure protein is calculated from the true digestibility and the efficiency of the utilization in the AA-N pool. The total utilization of NPN for the synthesis of protein for the protein pool amounted to 40/35/41/33% and that of pure protein to 54/51/49/50%. Energy intake being identical, energy concentration did not have an influence on the utilization of pure protein and NPN, whereas NPN utilization was better in rations containing sugar. The pure protein in the ration was by 19 ... 52% better utilized than NPN.