Characterization of the XIAP-Inhibiting Proanthocyanidin Fraction of the Aerial Parts of Ephedra sinica.

The X-linked inhibitor of apoptosis protein is a cellular protein that inhibits the activity of mammalian caspases and promotes resistance to apoptosis. The ethanol extract of the aerial parts of Ephedra sinica has been identified to possess inhibitory activity of the X-linked inhibitor of apoptosis protein by an in vitro fluorescence polarization assay using the BIR3 domain of the X-linked inhibitor of apoptosis protein. Bioactivity-guided fractionation identified proanthocyanidin-enriched fractions as the active principles. The most active fraction showed an IC50 value of 27.3 µg/mL (CI95: 25.9-28.9 µg/mL) corresponding to 9.6 µM (CI95: 9.1-10.1 µM) calculated by the use of the determined average molecular weight of 2853.5. Samples were analyzed by a thiolytic degradation/HPLC-MS assay, UHPLC-HRMS, and 1D NMR.The thiolytic degradation/HPLC-MS assay revealed a mean degree of polymerization of 9.5 ± 0.2 units (calculated average MW 2853.5) for the active fraction and 11.4 ± 0.6 units (calculated average MW 3437.0) for the most related inactive fraction. Chemical characterization identified (epi)gallocatechin (76.6 ± 1.0 % active; 80.7 ± 2.7 % inactive sample) and (epi)catechin units as building blocks. Interestingly, the investigated proanthocyanidins turned out to be a complex mixture of double linked A-type (binding 2-O-7″, 4-6″) and single linked B-type units.This study identified oligomeric proanthocyanidins as active principles of E. sinica in vitro by a fluorescence polarization assay and via protein fragment complementation analysis.

Aldosterone causes DNA strand breaks and chromosomal damage in renal cells, which are prevented by mineralocorticoid receptor antagonists.

Epidemiological studies exploring the connection between hypertension and cancer incidence find a higher cancer mortality in hypertensive patients, particularly elevated in hypertension associated with a stimulation of the renin-angiotensin-aldosterone system. Primary aldosteronism, with plasma aldosterone levels between 0.5 and 1 nM (18-36 ng/dL) and local aldosterone levels up to 500 nM (18,000 ng/dL), is now recognised as a more common cause for hypertension. We recently found angiotensin II to be genotoxic due to its induction of oxidative stress. Since aldosterone in higher concentrations also has oxidative effects, its potential genotoxic action in pig LLC-PK1 cells with properties of proximal tubules was analysed. DNA damage was evaluated by two test systems: the comet assay, and the micronucleus frequency test. The results showed that aldosterone concentrations starting from 10 nM (360 ng/dL) caused a significant increase of DNA damage monitored with the comet assay in LLC-PK1, while there was no change in cell vitality and proliferation. The micronucleus frequency test revealed that 10 nM aldosterone also leads to the formation of micronuclei. Furthermore, the formation of superoxide radicals in the cells by this aldosterone concentration could be detected with the superoxide-specific stain dihydroethidium. Further evidence for oxidative stress-induced DNA damage was its reversibility by the antioxidants tempol and catalase. Addition of the steroidal mineralocorticoid receptor antagonist spironolactone or the novel selective nonsteroidal antagonist (R)-BR-4628 reduced the DNA damage and the amount of superoxide radicals indicating a receptor-dependent process.

Role-playing for more realistic technical skills training.

Clinical skills are an important and necessary part of clinical competence. Simulation plays an important role in many fields of medical education. Although role-playing is common in communication training, there are no reports about the use of student role-plays in the training of technical clinical skills. This article describes an educational intervention with analysis of pre- and post-intervention self-selected student survey evaluations. After one term of skills training, a thorough evaluation showed that the skills-lab training did not seem very realistic nor was it very demanding for trainees. To create a more realistic training situation and to enhance students' involvement, case studies and role-plays with defined roles for students (i.e. intern, senior consultant) were introduced into half of the sessions. Results of the evaluation in the second term showed that sessions with role-playing were rated significantly higher than sessions without role-playing.

[Tension headache]. / Spannungskopfschmerz.

The life time prevalence of episodic tension headache ranges between 13-66%, of chronic tension headache between 1-3%. In most studies a slight preponderance of women was found. Approximately 20% of persons afflicted by tension headache seek for medical help. The costs of tension headache are mainly indirect ones due to lost work days. Increased pain sensitivity of the pericranial muscles, psychosocial stress and psychiatric disorders are discussed as main pathophysiological mechanisms. Taking into consideration the uncertainty of the entity "tension headache" tricyclic antidepressants and psychotherapy (biofeedback, stress management therapy, autogenic training) are effective. The superiority of a multicomponent therapy with tricyclic antidepressants and stress management therapy over pharmaceutical and psychotherapeutic treatment or placebo alone was demonstrated in one study.

Pre-nitrification by encapsulated nitrifiers--a possibility for self-sufficient energy operation of domestic WWTPs.

The overall energy consumption of domestic wastewater treatment plants (WWTPs) increases with treatment efficiency. Approximately 30 to 45 kWh per people equivalent and year is mostly necessary for advanced nitrogen and phosphorus removal, while the aeration contains the main part of approximately 60%. A new process using encapsulated nitrifiers on gel lens beads is introduced to overcome the high energy consumption of aeration. A more selective nitrification process was found at a nitrification rate of between 50 and 60 mg nitrogen per hour and litre reaction volume corresponding to a hydraulic retention time (HRT) of about 30 to 60 minutes while the soluble Chemical Oxygen Demand (COD) removal could be less than 30% depending on operational conditions of the bio-reactor. The latter enables internal use of wastewater's COD for a post denitrification. For the new process the energy consumption as well as total volume of bio-reactor are much less (approximately 30 to 50% for both) than conventional processes due to the low sludge age for COD and nitrate removal and the avoidance of internal wastewater recycle. Therefore, self-sufficient energy operation of domestic WWTPs operating with advanced treatment efficiency could become possible, if energy recovery by anaerobic sludge digestion is included.

Physician awareness of domestic violence: does continuing medical education have an impact?

One hundred currently practicing physicians were surveyed regarding screening and management of domestic violence to determine whether mandatory continuing medical education (CME) is likely to increase awareness of and response to domestic violence. The authors surveyed 25 family physicians and 25 obstetrician/gynecologists in each of two states, Florida and New Jersey. In addition, they polled 26 family practice residents in the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine program. Practices with a female physician were four times more likely to screen for domestic violence than practices with all male physicians. No difference existed in screening between family physicians and obstetrician/gynecologists; physicians in Florida and those in New Jersey; or attending physicians and family practice residents. Findings indicate that Florida's mandatory CME law does not appear to have made an impact on the management of domestic violence. Practices with a female physician were more likely to screen for domestic violence.

[Immunoglobulin transfer in the viable, newborn calf]. / Der Immunglobulintransfer beim vitalen, neugeborenen Kalb.

Parturitions of 26 dairy-cows were observed and the viability of the newborn calves assessed. Immediately after birth as well as after the first and forth colostrum intake a blood probe was taken from the neonates and investigated for the following parameters: blood gas, blood picture, total-IG, concentrations of IGG1, IGM and IGE, total proteins and albumin. Before each feeding a colostrum sample was assayed for the same parameters with the exception of blood gas, blood picture and albumin. A transferindex (KLOBASA et al., 1994) was calculated to investigate the absorption of TP, IG, IGG1, IGM and IGE. In some of the blood samples there was no IGE detectable, even after colostrum intake. High individual differences were striking and blood concentrations were not related to the milk contents or the time until first feeding. The total proteins were strongly correlated to the serum concentrations of IGG1, but only in samples taken after first colostrum feeding. Vital calves showed the following tendency: colostrum intake of less than 1 l within the first 15 hours after birth and/or colostrum intake with TP-concentrations of 80 I.U./l was partly compensated by increased absorption of TP. 24 hours after birth serum-immunoglobulinconcentrations were 6-12 mg/ml; weight gain was normal and no calf became ill. In 60% of cases the transferindex for IGM was higher than for IGG1 or IGE.

Glutamate-like immunoreactivity in identified neuronal populations of insect nervous systems.

Glutamate is considered to be the most likely transmitter candidate at excitatory synapses onto skeletal muscles of insects. We investigated the distribution of glutamate-like immunoreactivity (Glu-LI) in identified motor neurons of glutaraldehyde-fixed metathoracic ganglia of the locust in paraffin serial sections. The presumably glutamatergic fast and slow extensor tibiae motor neurons show Glu-LI, whereas other cells, including the GABAergic common inhibitory motor neurons and the cluster of octopaminergic dorsal unpaired median cells, show rather low levels of staining. Immunoreactivity of the fast extensor tibiae motor neuron is located in soma, neurites, axon, and the terminal arborizations. A double-labeling experiment on sections of the locust metathoracic ganglion showed that antisera against glutamate and GABA discriminate between the presumably glutamatergic and GABAergic motor neurons and that GABA-LI-positive neurons are low in Glu-LI. The results suggest that Glu-LI can be used as a marker for detecting potential glutamatergic neurons in insects under the present conditions. Application of the glutamate antiserum to sections of the honeybee brain revealed Glu-LI in motor neurons but also in certain interneurons. The most prominent populations of Glu-LI-positive cells were the monopolar cells and large ocellar interneurons, which are first-order interneurons of the visual and ocellar system. Several groups of descending interneurons also showed Glu-LI. The distributions of Glu-LI and GABA-LI are complementary in locust and bee ganglia. The high level of Glu-LI in certain interneuronal populations, as well as in identified glutamatergic motor neurons, suggests that insect central nervous systems may contain glutamatergic neuronal pathways.

Effects of dietary paraffin, squalane and sucrose polyester on residue disposition and elimination of hexachlorobenzene in rats.

Previous studies have shown addition of light liquid paraffin to enhance the elimination of organochlorine xenobiotics. In the present study the effect of paraffin on the elimination of [14C]hexachlorobenzene (HCB) was compared with the effect of possible alternative compounds, squalane and sucrose polyester (SPE). Four groups of 7 rats were fed a diet containing 1.5 ppm [14C]HCB for 4 days followed by 10 days on HCB-free diet. Thereafter one group (control) remained on this diet whereas the other 3 groups received a diet supplemented with 8% (w/w) paraffin, squalane or SPE, respectively. Radioactivity in urine and faeces was measured daily and at the end of the experiment in samples of abdominal fat, muscle, liver, kidney and blood. Dietary treatment with either paraffin, squalane or SPE markedly enhanced faecal excretion of [14C]HCB, whereas urinary excretion was not affected. Both the time course as well as the extent of faecal [14C]HCB elimination were similar in the treated groups. After 3 weeks of treatment the amount of [14C]HCB excreted with faeces was about three times higher in treated animals than in controls. The half-life (t1/2) of [14C]HCB elimination from the body was markedly decreased in treated animals (mean 34--38 days) compared to controls (110 days). [14C]HCB concentrations in some major tissues were significantly reduced to the same extent by all three dietary regimens. Thus squalane and SPE are as effective as paraffin in removing HCB from contaminated animals.