[Adherence to Phase III Cardiac Rehabilitation Programs: A Prospective, Randomized Comparison between a Conventionally Conducted Program and a Tai Chi-Based Program]. / Adhärenz in Herzgruppen: Ein prospektiver, randomisierter Vergleich einer konventionell durchgeführten Herzgruppe zu einer Tai-Chi-Herzgruppe.

INTRODUCTION: In patients with cardiac diseases, lifestyle changes such as an increase in physical activity are recommended to prevent further cardiac events. In Germany this is possible by attending outpatient heart groups. A problem inherent in these programs is the lack of adherence since more than two thirds of patients stop attending cardiac rehabilitation programs after six months. An alternative to the conventional implementation of heart groups is Tai Chi, which was found to improve adherence to cardiac rehabilitation programs in international studies. METHODS: Patients were randomly assigned to a conventional heart group or a heart group with Tai Chi exercises. At the beginning of the study, a medical history was taken and physical and instrumental tests were carried out, including an assessment of anxiety/depression (HADS questionnaire) and physical well-being (SD-12). Follow-up tests were performed every three months. RESULTS: Patients were 62.6 ±â€Š8.5 years old, the mean BMI was 28.6 ±â€Š62 kg/m(2), and the proportion of women was 29.8 %. The groups were different in terms of age (conventional heart group: 65.0 ±â€Š7.5; Tai Chi group: 59.9 ±â€Š8.9 years). Therefore, age-adjusted analyses were performed in addition to the planned analyses. Regarding the primary endpoint of the study, there was no difference between the groups. After twelve months, 50 % of subjects were active in the Tai Chi group and 48 % in the conventional heart group (odds ratio 0.92, p = 0.891). After adjustment for age by logistic regression, the odds ratio was 0.47 (p = 0.285). Furthermore, both the participation period in weeks (Tai Chi group: 43.3 ±â€Š26.0; conventional group: 45.5 ±â€Š24.2, p = 0.766) and the participation rate (Tai Chi group: 66.8 ±â€Š19.2 % Tai Chi, conventional group: 76.3 ±â€Š16.5 %, p = 0.074) did not differ between the two groups. A further analysis showed a non-significant trend for improvement of anxiety, depression and physical well-being in the Tai Chi group compared with the conventional group. CONCLUSION: The insight gained in international studies regarding a better adherence to Tai Chi-guided prevention programs was not transferable to heart group participants from Germany. However, there was a trend regarding a better mental condition in the Tai Chi group.

[Multicenter trial for sudden hearing loss therapy - planning and concept]. / Multizentrische Studie zur Hörsturztherapie - Planung und Konzeption.

Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

Selective regulatory effects of purine and pyrimidine nucleotides on vacuolar transport of amino acids.

The release of amino acids from their vacuolar store was studied in situ, i.e. in cells with selectively permeabilized plasma membrane and functionally intact vacuoles. As we previously described [Roos et al., J. Biol. Chem. 272 (1997) 15849-15855], this transport process is regulated by extravacuolar adenylates at their physiological concentrations. We now show, using our test object Penicillium cyclopium, that not only purine but also pyrimidine nucleotides are involved in the control of efflux of vacuolar phenylalanine. At 0.1 mM adenosine or guanosine phosphates inhibit, whereas cytidine or uridine phosphates stimulate the rate of efflux. At 1 mM the same nucleotides have no measurable impact on efflux but abolish the effects of other nucleotides present at 0.1 mM. This argues for at least two interacting binding sites with different nucleotide affinities. The minimum structural requirement for any of the observed effects is a non-cyclic ribonucleoside monophosphate. In intact cells, cytosolic concentrations of ATP (representing purine nucleotides) and CTP (representing pyrimidine nucleotides) are 1-2 mM and 0.05-0.2 mM, respectively. ATP is therefore assumed to dominate transport control and allow optimum efflux (and uptake) rates. Short-time starvation of carbon and nitrogen adjusts CTP and ATP at levels that cause declining efflux rates. During prolonged starvation both nucleotides fall below their transport-controlling concentrations and thus allow increasing rates of efflux from the still maintained vacuolar pool. Hence, efflux control under nutrient limitation includes an interplay of purine and pyrimidine nucleotides which precisely regulates the release of vacuolar amino acids and enables flexible adjustment to either amino acid saving or cell survival.

A redox-dependent, G-protein-coupled phospholipase A of the plasma membrane is involved in the elicitation of alkaloid biosynthesis in Eschscholtzia californica.

In cultured cells of California poppy formation of benzophenanthridine alkaloids can be triggered by a yeast elicitor preparation independently of the hypersensitive reaction. A plasma membrane (PM) bound phospholipase A (PLA) is likely to play a role in the signalling process: PLA activity was detectable in individual cells, cell suspensions and PM vesicles with the fluorogenic phospholipid bis-BODIPY FL C11-PC and was sensitive to known inhibitors of PLA2. In microscopic assays, enzyme activity increased after elicitor contact of cells that were pretreated with non-saturating concentrations of PLA2 inhibitors. In PM vesicles a PLA2-like protein as well as G alpha- and G beta-proteins were detected immunologically. Anti-G alpha or anti-G beta antisera or mastoparan stimulated PLA activity thus indicating a G-protein-controlled enzyme. Elicitation of alkaloid production was sensitive to aristolochic acid and enhanced by PLA2 products such as lysophosphatidylcholine and linolenic acid. Pretreatment of the cells with the artificial electron acceptors hexabromoiridate(V) or ferricyanide(III) reversibly abolished the effect of subsequent elicitation and reduced the activity of PLA both in intact cells and in PM vesicles. It appears, therefore, that PLA2 is a point of interference of redox control with the signal path.

Differences in cytotoxicity of native and engineered RIPs can be used to assess their ability to reach the cytoplasm.

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.

Dynamic compartmentation of vacuolar amino acids in Penicillium cyclopium. Cytosolic adenylates act as a control signal for efflux into the cytosol.

The regulation of amino acid transport from the vacuolar reservoir into the cytoplasm has been studied in hyphal cells of Penicillium cyclopium. To avoid artifacts caused by the isolation of vacuoles, efflux was examined "in situ," i.e. in cells whose plasma membranes were permeabilized for micromolecules by a treatment with nystatin. The ATP-dependent proton gradient and amino acid transport activities at the vacuolar membrane remained intact under these conditions. Accumulation of amino acids in the vacuole proved to be the result of a dynamic equilibrium of active, ATP-dependent uptake and energy-independent efflux. The latter was strongly accelerated after the vacuolar amino acid content had surpassed a threshold level. Efflux of vacuolar amino acids was specifically controlled by extravacuolar adenylates: ATP, 5'-adenylyl imidodiphosphate (an ATPase-resistant ATP-analogue), ADP, or AMP caused a strong inhibition in the concentration range around 200 micromol/liter, whereas both lower and higher concentrations allowed significant efflux rates. Estimates of the cytosolic adenylates (which consisted mainly of ATP) were close to 2 mmol/liter in glucose-metabolizing cells, which concentration allowed maximum rates of both vacuolar uptake and efflux. During 24 h of carbon and nitrogen starvation, the adenylate level decreased toward the efflux-inhibiting region around 200 micromol/liter, whereas 3-4 d of carbon and nitrogen starvation caused a further decline of the adenylate content, leading again to efflux-permitting concentrations. Thus, the cytosolic adenylate pool appears to effectively control the availability of vacuolar amino acids for the cellular metabolism.

Production and immobilization of a proteinase-reduced cyclodextrin glycosyltransferase preparation.

Cyclodextrin glycosyltransferase (CGTase) was produced by a 3-day cultivation of Bacillus macerans growing in a natural medium containing grated-potatoes. Besides CGTase the culture supernatant contained a mixture of serine proteinases with a predominant subtilisin-like activity. By fractionated precipitation with ammonium sulphate the CGTase (molecular mass approximately 70 kDa) was concentrated and largely separated from the proteinases (molecular mass approximately 28 kDa). Among the various immobilization methods and carrier materials tested the enriched CGTase was covalently bound preferably onto porous glass beads using glutardialdehyde as cross-linker. The discontinuous conversion of soluble starch into beta-cyclodextrin was carried out with native as well as immobilized CGTase over 24 h. The batch re-usability of the fixed enzyme proved to be at least 20 times with a residual CGTase activity of 65%.