Design of nanostructured hybrid materials: twin polymerization of urethane-based twin prepolymers.

Organic-inorganic hybrid materials with urethane functionalities were obtained by simultaneous twin polymerization of twin prepolymers in combination with the ideal twin monomer 2,2'-spirobi[4H-1,3,2-benzodioxasiline]. The twin prepolymers consist of a urethane-based prepolymer with reactive terminal groups which can react during the twin polymerization process. Nanostructured hybrid materials with integrated dialkylsiloxane crosslinked urethane structures, phenolic resin and SiO2 are obtained in a one pot process. The effects of the polymerization temperature as well as those of various catalysts and reagent ratios on the polymerization behavior were investigated. The molecular structures of the obtained materials were determined by 13C- and 29Si-{1H}-CP-MAS NMR spectroscopies. HAADF-STEM-measurements were performed to prove the distribution of silicon in the hybrid material.

[Individualization of exercise load control for inpatient cardiac rehabilitation. Development and evaluation of a HRV-based intervention program for patients with ischemic heart failure]. / Individualisierung der Belastungssteuerung in der kardiologischen stationären Rehabilitation. Entwicklung und Evaluation eines HRV-gesteuerten Interventionsprogramms für Patienten mit ischämisch bedingter Herzinsuffizienz.

BACKGROUND: The effective use of rehabilitation programs is of primary importance in order to improve the physical performance of cardiac disease patients. A modular program has been developed which is intended to structure and individualize conventional, exercise-based rehabilitation programs according to the individual needs and physical condition of each patient. The individualization of the program is based on detailed diagnostics before patients enter the program and daily measurements of heart rate variability (HRV) during cardiac rehabilitation. METHODS: A total of 30 patients with ischemic heart disease were randomly assigned either to the intervention group (IG), completing the modular individualized rehabilitation program [n=15, mean age 54.4±4.2 years and mean left ventricular ejection fraction (LVEF) 28.53±6.25%) or to the control group (CG) taking part in the conventional rehabilitation program (n=15, mean age 56.4±4.4 years and mean LVEF 27.63±5.62). Before and after the intervention, cardiorespiratory fitness was assessed by measurement of maximal oxygen consumption (relative VO2max) during bicycle ergometry and the 6-minute walk test (6-MWT). Pre-post comparisons of cardiorespiratory fitness indicators were used to evaluate the effectiveness of the rehabilitation program. In addition to the results of the basic clinical investigations and the cardiorespiratory testing, results of standardized HRV measurements of 10 min at morning rest served as criteria for program individualization. RESULTS: The relative VO2max increased significantly (p<0.05) in the IG whereas no change was found in the CG. Similar results were found for maximum power output during bicycle ergometry (p<0.01) and for 6-MWT distance (p<0.001). Although patients in the IG completed less aerobic exercise sessions than those in the CG (p<0.001) the physical performance of the IG improved significantly. DISCUSSION: The results prove the effectiveness and efficacy of the modular individualized rehabilitation program. They further suggest the need for an individual program matrix instead of a maximum performance matrix in cardiac rehabilitation. Individualization should be based on clinical and performance diagnostics before and accompanying assessments of training condition, e.g. by HRV measurements, during rehabilitation programs. Each patient should only perform those intervention programs which match the results of the basic clinical investigation and additional analyses during rehabilitation.

[Work-Related Setting Approach with Health Counselling Supports a Healthy Lifestyle of Long-Term Unemployed Persons]. / Arbeitsmarktintegratives Setting mit Gesundheitsberatung unterstützt gesundheitsförderlichen Lebensstil bei Langzeiterwerbslosen.

Unemployment is a major reason for health inequalties. In a pilot study (N=119), the acceptance and effectiveness of a low threshold health promotion intervention for older long-term unemployed persons were evaluated. Health counselling supported the participants in the development of a healthy lifestyle.

A wireless handheld probe with spectrally constrained evolution strategies for diffuse optical imaging of tissue.

We present a low-cost, portable, wireless diffuse optical imaging device. The handheld device is fast, portable, and can be applied to a wide range of both static and dynamic imaging applications including breast cancer, functional brain imaging, and peripheral artery disease. The continuous-wave probe has four near-infrared wavelengths and uses digital detection techniques to perform measurements at 2.3 Hz. Using a multispectral evolution algorithm for chromophore reconstruction, we can measure absolute oxygenated and deoxygenated hemoglobin concentration as well as scattering in tissue. Performance of the device is demonstrated using a series of liquid phantoms comprised of Intralipid(®), ink, and dye.

[Knowledge of school pupils about the HIV/AIDS topic at selected schools in Mecklenburg-Western Pomerania]. / Der Wissensstand von Schülern über das Thema HIV/AIDS an ausgewählten Schulen in Mecklenburg-Vorpommern.

AIM OF THE STUDY: The increasing numbers of new HIV diagnoses in Germany generate a need to measure the level of knowledge of the young generation about the issue of HIV/AIDS. METHODOLOGY: A survey was conducted of 769 pupils of different age groups and from different schools in Mecklenburg-Western Pomerania. Data analysis was performed using SPSS; statistically significant differences (p<0.05) were tested between the groups using the chi-square test. RESULTS: The level of knowledge within the sample differs: more precise knowledge is demonstrated by pupils following an awareness event (60%) and by pupils interested in HIV (69%) than by those who have attended no awareness event (40%) and those who have little interest in the issue (31%). Moreover, it was noted that grammar school pupils generally achieve better results than pupils from comprehensive and intermediate secondary schools. Furthermore, there are significant differences between the genders: girls give correct answers more frequently than boys and more often show an interest in the HIV/AIDS issue. In addition, age-specific differences are also identifiable: from the age of 14, there is a considerable increase in knowledge, which then remains static at the age of 16. AIDS education in biology lessons is common among pupils and 93% are familiar with this. Over 70% of pupils are unfamiliar with local AIDS awareness teams. CONCLUSIONS: There are significant gaps in the level of knowledge about methods of infection, particularly with respect to questions about the no risk areas, which should thus be particularly dealt with in awareness events. As to knowledge transfer, the pupils' interest should be aroused while taking the type of school, gender and age of the pupils into consideration. In the course of the school career, every pupil should take part in at least one awareness event since our survey showed that only 60% attended such an event. Local AIDS awareness teams should be more frequently active in the schools since 73% stated to be unfamiliar with them in our survey.

Effectiveness of four electronic apex locators to determine distance from the apical foramen.

AIM: To evaluate the accuracy of four electronic apex locators (EAL) in the apical region (0-3 mm short of the foramen) and to compare the precision of the readings on the display with the real position of the file in the root canal. METHODOLOGY: Twenty single-rooted extracted teeth with round root canals were used. The canal orifices were preflared, and the length to the major foramen was determined visually under a microscope. Canals were enlarged, so that a size 15 file fitted well inside the canal. Teeth were mounted in acrylic test tubes filled with physiologic saline solution. Electronic length was determined in the region between the major foramen and 3 mm short of it in 0.5 mm steps with the Dentaport ZX, Root ZX mini, Elements Diagnostic Unit and Apex Locator and Raypex 5 using files of size 10 and size 15. The data were analysed using linear regression between true length and EAL reading, Bland-Altman plots and nonparametric tests at a significance level of alpha = 0.05. RESULTS: The major foramen was detected by all EALs. With a measurement file positioned directly at the major foramen, meter readings were equivalent to a position 0.01-0.38 mm away. For the Dentaport ZX, a better accuracy using the size 15 file for the area 0-1.5 mm short of the apex was found. The differences in measurements between the two files were smaller for the other EALs. In linear regression, a good linearity for Dentaport ZX and Root ZX mini and moderate linearity for Elements Diagnostic Unit and Apex Locator and Raypex 5 were found. The slope of the measurement curve was too low (0.37-0.57) for the Raypex 5 and almost optimal for the Dentaport ZX (1.01-1.05). The Root ZX mini and the Elements Obturation Unit produced lower slope values and especially the Elements Obturation Unit revealed much higher SDs at the different measurement levels. CONCLUSION: Amongst the four EALs, the Dentaport ZX and Root ZX mini had the best agreement between true lengths and meter readings. For the Raypex 5, an interpretation of the colour-coded zones as distance to the foramen cannot be recommended and might lead to erroneous interpretations.

Effect of different time intervals between examinations on the reproducibility of ICDAS-II for occlusal caries.

AIM: To evaluate intra- and interexaminer reproducibility of ICDAS-II on occlusal caries diagnosis when different time intervals were allowed to elapse between examinations. A subsidiary aim was to determine whether collapsing the codes would influence this reproducibility. METHODS: The occlusal surfaces of 50 permanent posterior teeth were investigated by 3 trained examiners using ICDAS-II at baseline, 1 day, 1 week and 4 weeks after baseline. RESULTS: Weighted kappa values for intra- and interexaminer reproducibility were 0.76-0.93. CONCLUSION: The time span did not have a major impact on assessing intra- and interexaminer reproducibility. Collapsing ICDAS-II codes had no impact on examiner reproducibility.

[Sociomedical implications of the inability to commute in patients with cold urticaria]. / Sozialmedizinische Bedeutung der Wegefähigkeit bei der Kälteurtikaria.

One of the important functions of the dermatologist working within a social medicine framework is the determination of social security disability benefits. The primary decision deals with the question which type of work the applicant can be asked to do and to what extent. Depending on the results of the medical assessment, social security disability benefits may be approved given that other insurance criteria specific to the applicant have been met. The following case demonstrates for the first time that a significant idiopathic cold urticaria leads to a severe constraint on keeping employment due to the inability to commute. The scenario shows that the cold urticaria severely restricts social and professional interactions and that the reduced ability to commute to the place of employment must receive special consideration within the context of a sociomedical evaluation.

[Fluorquinolone associated tendon rupture]. / Achillessehnenruptur unter Fluorochinolonen.

We report the case of a 38-year-old patient with a rupture of the right Achilles tendon after physical exercise. A few days before he had been treated with ciprofloxacine 500mg bid for chlamydial urethritis. We discuss know risk factors for Achilles tendon ruptures and the possible contribution of ciprofloxacin and fluorquinolones in this case.

Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb.

Translationally controlled tumour protein (TCTP) is involved in malignant transformation and regulation of apoptosis. It has been postulated to serve as a guanine nucleotide exchange factor for the small G-protein Rheb. Rheb functions in the PI3 kinase/mTOR pathway. The study presented here was initiated to characterise the interaction between TCTP and Rheb biochemically. Since (i) no exchange activity of TCTP towards Rheb could be detected in vitro, (ii) no interaction between TCTP and Rheb could be detected by NMR spectroscopy, and (iii) no effect of TCTP depletion in cells on the direct downstream targets of Rheb could be observed in vivo, this study shows that TCTP is unlikely to be a guanine nucleotide exchange factor for Rheb.

Extracellular SH3 domain containing proteins--features of a new protein family.

In the year 1994, the protein MIA (melanoma inhibitory activity) was found to be strongly expressed and secreted by malignant melanomas and subsequent studies revealed that MIA has an important function in melanoma development and invasion. Multidimensional NMR-spectroscopy and x-ray crystallography revealed that recombinant human MIA adopts a Src homology 3 (SH3) domain-like fold in solution, a structure with two perpendicular antiparallel three- and five-stranded beta-sheets. SH3 domains are protein modules that are found in many intracellular signalling proteins and mediate protein-protein interactions by binding to proline-rich peptide sequences. Unlike previously described protein structures with SH3 domain folds, MIA is a secreted single-domain protein of 12 kDa that contains an additional antiparallel beta-sheet and two disulfide bonds. Furthermore, the charge surrounding the canonical binding site differs from that of classical SH3 domains. The two disulfide bonds are crucial for correct folding and function as revealed by mutation analysis. Therefore, MIA appears to be the first extracellular protein adopting an SH3 domain-like fold. MIA was shown to interact with fibronectin, and MIA-interacting peptide ligands identified by phage display screening are similar to the consensus sequence of type III human fibronectin repeats, especially FN14. Interestingly, recent data revealed that MIA can also directly bind to integrin alpha 4 beta 1 and alpha 5 beta1 and that it modulates integrin activity negatively. These findings suggest an interesting role of the SH3-domain proteins in the extracellular compartment. Recently, MIA homologous proteins with a sequence identity of 44% and a sequence homology of approximately 80% were determined (TANGO, MIA-2, OTOR). This clearly suggests that this structural device is used more frequently, in processes ranging from developmental changes to the interference of cell attachment in the extracellular matrix. Detailed studies are necessary to determine the exact function of the MIA homologous proteins. It will be interesting to know whether additional protein families can be identified which are secreted and carry SH3 domain-like modules, in addition to elucidate what the specific physiological targets of this protein family are.

Handling uncertainties in toxicity modelling using a fuzzy filter.

A fundamental concern in the Quantitative Structure-Activity Relationship approach to toxicity evaluation is the generalization of the model over a wide range of compounds. The data driven modelling of toxicity, due to the complex and ill-defined nature of eco-toxicological systems, is an uncertain process. The development of a toxicity predicting model without considering uncertainties may produce a model with a low generalization performance. This study presents a novel approach to toxicity modelling that handles the involved uncertainties using a fuzzy filter, and thus improves the generalization capability of the model. The method is illustrated by considering a data set dealing with the fathead minnow (Pimephales promelas) toxicity of 568 organic compounds.

Phenolphthalein and bisacodyl: assessment of genotoxic and carcinogenic responses in heterozygous p53 (+/-) mice and syrian hamster embryo (SHE) assay.

Phenolphthalein (800 and 2400 mg/kg/day by gavage and 2400 mg/kg/day by diet) and bisacodyl (800-500, 4000-2000, and 8000 mg/kg/day by gavage) were administered to 15 male and 15 female and 20 male and 20 female p53(+/-) mice respectively for 26 weeks to investigate the potential carcinogenicity of each compound. Toxicokinetic analyses confirmed systemic exposure. p-Cresidine was administered by gavage (400 mg/kg/day) and served as the positive control agent in each study. Dietary phenolphthalein reduced survival in both sexes and early deaths were attributed to thymic lymphoma. No bisacodyl-related neoplasms were observed. Regardless of route of administration to p53(+/-) mice, phenolphthalein but not bisacodyl was unequivocally genotoxic, causing increased micronuclei in polychromatic erythrocytes. In the Syrian hamster embryo (SHE) cell transformation assay, phenolphthalein caused increases in morphologically transformed colonies, thereby corroborating NTP's earlier reports, showing phenolophthalein has potential carcinogenic activity. Bisacodyl was negative in the SHE assay. Results of these experiments confirm an earlier demonstration that dietary phenolphthalein causes thymic lymphoma in p53(+/-) mice and show that (1) phenolphthalein causes qualitatively identical results in this transgenic model regardless of route of oral administration, (2) phenolphthalein shows evidence of micronucleus induction in p53(+/-) mice for up to 26 weeks, (3) phenolphthalein induced transformations in the in vitro SHE assay, and (4) bisacodyl in p53(+/-) mice induces neither drug-related neoplasm, nor micronuclei in polychromatic erythrocytes, and did not induce transformations in the in vitro SHE assay.

Marginal adaptation of partial crowns cast in pure titanium and in a gold alloy - an in vivo study.

The aim of the present study was to assess in vivo the marginal integrity of partial crowns cast in pure titanium and in a gold alloy. For this purpose, two groups of 25 molars were prepared for partial crowns and then restored with partial crowns cast in Degulor M gold alloy and in pure titanium. At a subsequent session, replicas were produced using a special impression-taking technique. The scanning electron microscope (SEM) technique was used to perform quantitative margin analysis (Tiffmess 1.8 program). The gold alloy partial crowns displayed significantly (P < 0.05) more continuous margin (marginal quality A, <50 microm), and the titanium partial crowns significantly more marginal quality B (50-100 microm) and C (>100 microm). The results show that better marginal integrity can be achieved with gold alloy than with titanium partial crowns. However, in practical terms the difference in marginal quality is only slight, so that the use of pure titanium for single-tooth restorations is justified.

Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC mouse skin papillomas expressing transgene-derived mRNA.

The Tg.AC transgenic mouse carries a v-Ha-ras transgene. Skin papillomas develop in Tg.AC mice upon repeated dermal application of tumor promoters and carcinogens. The transgene is inserted at a single site on chromosome 11 in a multiple-copy array. Although most of the >or= 40 copies are arranged in a direct-repeat orientation, two copies of the transgene are inserted in a palindromic, inverted-repeat orientation. Deletion of the palindromic transgene promoter sequence is associated strongly with and diagnostic of loss of phenotypic responsiveness to Tg.AC papillomagens, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, a loss of palindromic transgene sequence, in the absence of an observable reduction in copy number of the direct-repeat-oriented transgene sequence, is seen in DNA from papillomas when compared to genomic DNA from tail clips or skin samples away from the application site. Transgene-derived transcripts were detectable in all Tg.AC papillomas sampled. The transgene locus was hypomethylated in papillomas but not in samples from tail clips from the same animal or from skin samples away from the application site in responder Tg.AC mice, as shown by loss of resistance to digestion by HpaII. A cell line derived from a Tg.AC squamous cell carcinoma showed complete loss of the palindromic transgene sequence, hypomethylation of the transgene locus, and strong expression of v-Ha-ras mRNA. These data indicate that the palindromic transgene sequence, which appears to be necessary for initial responsiveness to tumorigens, may be susceptible to deletion during rapid cellular proliferation and is not required for transgene expression in later phases of papilloma growth.

Tg.AC genetically altered mouse: assay working group overview of available data.

In a Government/Industry/Academic partnership to evaluate alternative approaches to carcinogenicity testing, 21 pharmaceutical agents representing a variety of chemical and pharmacological classes and possessing known human and or rodent carcinogenic potential were selected for study in several rodent models. The studies from this partnership project, coordinated by the International Life Sciences Institute, provide additional data to better understand the models' limitations and sensitivity in identifying carcinogens. The results of these alternative model studies were reviewed by members of Assay Working Groups (AWG) composed of scientists from government and industry with expertise in toxicology, genetics, statistics, and pathology. The Tg.AC genetically manipulated mouse was one of the models selected for this project based on previous studies indicating that Tg.AC mice seem to respond to topical application of either mutagenic or nonmutagenic carcinogens with papilloma formation at the site of application. This communication describes the results and AWG interpretations of studies conducted on 14 chemicals administered by the topical and oral (gavage and/or diet) routes to Tg.AC genetically manipulated mice. Cyclosporin A, an immunosuppresant human carcinogen, ethinyl estradiol and diethylstilbestrol (human hormone carcinogens) and clofibrate, an hepatocarcinogenic peroxisome proliferator in rodents, were considered clearly positive in the topical studies. In the oral studies, ethinyl estradiol and diethylstilbestrol were negative, cyclosporin was considered equivocal, and results were not available for the clofibrate study. Of the 3 genotoxic human carcinogens (phenacetin, melphalan, and cyclophosphamide), phenacetin was negative by both the topical and oral routes. Melphalan and cyclophosphamide are, respectively, direct and indirect DNA alkylating agents and topical administration of both caused equivocal responses. With the exception of clofibrate, Tg.AC mice did not exhibit tumor responses to the rodent carcinogens that were putative human noncarcinogens, (di(2-ethylhexyl) phthalate, methapyraline HCl, phenobarbital Na, reserpine, sulfamethoxazole or WY-14643, or the nongenotoxic, noncarcinogen, sulfisoxazole) regardless of route of administration. Based on the observed responses in these studies, it was concluded by the AWG that the Tg.AC model was not overly sensitive and possesses utility as an adjunct to the battery of toxicity studies used to establish human carcinogenic risk.

Dermal carcinogenicity in transgenic mice: effect of vehicle on responsiveness of hemizygous Tg.AC mice to phorbol 12-myristate 13-acetate (TPA).

The Tg.AC mouse is being evaluated for use in short-term carcinogenicity bioassays. Because the dermal test protocol necessitates dissolving test agents we determined the effects of several solvents on responsiveness of hemizygous mice to dermal applications of the classical skin tumor promoter. phorbol 12-myristate 13-acetate (TPA). Mice of both sexes received dermal applications of either acetone (negative control) or TPA in various vehicles [acetone, 100% methanol, 70% and 100% ethanol, DMSO and mixtures of acetone and ethanol (1:1), acetone and DMSO (4:1 and 1: 1). and acetone and olive oil (4:1)]. Negative control animals did not exhibit papillomas. When administered in acetone. ethanolic or methanolic vehicles TPA caused prompt and robust papillomatous responses. TPA was also tumorigenic in all nonalcoholic vehicles, except the acetone-olive oil mixture. Papilloma responses were generally delayed when TPA was applied in the nonalcoholic solvents but the distinction between TPA-dosed and negative control groups was unequivocal. These results show that choice of vehicle may affect the quantitative and qualitative nature of the response of Tg.AC mice to TPA, but 8 of 9 vehicles proved satisfactory for delivery of TPA.

Assessment of cisplatin-induced nephrotoxicity by microarray technology.

Microarrays are a new technology used to study global gene expression and to decipher biological pathways. In the current study, microarrays were used to examine gene expression patterns associated with cisplatin-mediated nephrotoxicity. Sprague-Dawley rats received either single or seven daily ip doses of cisplatin (0.5 or 1 mg/kg/day) or the inactive isomer transplatin (1 or 3 mg/kg/day). Histopathological evaluation revealed renal proximal tubular necrosis in animals that received cisplatin for 7 days, but no hepatotoxic findings. Microarray analyses were performed using rat specific arrays containing 250 toxicity-related genes. Prominent gene expression changes were observed only in the kidneys of rats that received cisplatin for 7 days. Mechanistically, the gene expression pattern elicited by cisplatin (e.g., Bax upward arrow and SMP-30 downward arrow) suggested the occurrence of apoptosis and the perturbation of intracellular calcium homeostasis. The induction of multidrug resistance genes (MDR1 upward arrow, P-gp upward arrow) and tissue remodeling proteins (clusterin upward arrow, IGFBP-1 upward arrow, and TIMP-1 upward arrow) indicated the development of cisplatin resistance and tissue regeneration. Select gene expression changes were further confirmed by TaqMan analyses. Gene expression changes were not observed in the liver following cisplatin administration. In contrast to these in vivo findings, studies using NRK-52E kidney epithelial cells and clone-9 liver cells suggested that liver cells were more sensitive to cisplatin treatment. The discrepancies between the in vivo and in vitro results suggest that caution should be taken when extrapolating data from in vivo to in vitro systems. Nonetheless, the current study elucidates the biochemical pathways involved in cisplatin toxicity and demonstrates the utility of microarrays in toxicological studies.

Marginal adaptation of cast partial crowns made of pure titanium and a gold alloy under influence of a manual burnishing technique.

The aim of this study was to determine the marginal adaptation of partial crowns from pure titanium and a gold alloy after two different cementation techniques. Forty freshly extracted human molars were prepared and randomly divided in four groups. Two groups were restored with partial crowns using the gold alloy Degulor M*. In one group, the crowns were fixed on the tooth by using a zinc phosphate cement. In the other group the margins were additionally burnished by using a hand burnisher No. 660. In the other two groups, partial crowns from pure titanium were cemented in the same way. The marginal quality was determined by quantitative margin analysis in the SEM using a replica technique. Partial crowns from a gold alloy showed significantly (P < 0.05) more margin quality A (vertical marginal discrepancy < 50 microm) while partial crowns from pure titanium had significantly (P < 0.05) more margin quality B (vertical marginal discrepancy 50-100 microm) and over-extended margins (quality D). No significant (P < 0.05) difference was found between the conventional cementation technique and the technique with manual burnishing in both material groups.