Structure and dynamics of cationic surfactants intercalated in synthetic clays.
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Aluminum Silicates↗
Biomedical subjects
R Müller
Publications and source records attributed to R Müller.
Technical considerations for microstructural analysis of human trabecular bone from specimens excised from various skeletal sites.
The purpose of this study was to test the effect of repositioning, systematic displacements of the region of interest (ROI), and acquisition parameters (scan mode and integration time) on quantitative analysis of human trabecular bone microstructure at various skeletal sites, using microcomputed tomographic (microCT) technology. We investigated 28 cylindrical specimens of human trabecular bone (length 14 mm, diameter 8 mm) from four skeletal sites (femoral neck, greater trochanter, second lumbar vertebra, and distal radius). These specimens were selected from over 200 microCT measurements, in order to cover a large range of bone volume fraction (BV/TV) observed at each site. Cylindrical ROIs (length 6 mm, diameter 6 mm) were examined twice at an isotropic resolution of 26 microm, 8 weeks apart. In addition, comparative analyses were performed for displacements of the volumes of interest (VOIs) by 1, 2, 3, and 4 mm (83.4%, 66.6%, 50%, and 33.3% overlap), respectively. Eventually, comparative measurements were obtained at different resolution scan modes and integration times. The results show that microCT measurements are highly reproducible (range of the root mean square coefficient variation % (RMS CV%) = 0.64% to 1.29% for BV/TV at different sites). Displacements of the VOI of up to 4 mm generally led to non significant systematic differences in mean values of < 10%. When comparing various combinations of resolution scan modes and integration times, the use of an integration time of 100 ms was found to be preferable for determining microstructural parameters from human samples with this microCT scanner.
Aged↗
Experimental and finite element analysis of the rat ulnar loading model-correlations between strain and bone formation following fatigue loading.
The rat forelimb compression model has been used widely to study bone response to mechanical loading. We used strain gages to assess load sharing between the ulna and radius in the forelimb of adult Fisher rats. We used histology and peripheral quantitative computed tomography (pQCT) to quantify ulnar bone formation 12 days after in vivo fatigue loading. Lastly, we developed a finite element model of the ulna to predict the pattern of surface strains during compression. Our findings indicate that at the mid-shaft the ulna carries 65% of the applied compressive force on the forelimb. We observed large variations in fatigue-induced bone formation over the circumference and length of the ulna. Bone formation was greatest 1-2 mm distal to the mid-shaft. At the mid-shaft, we observed woven bone formation that was greatest medially. Finite element analysis indicated a strain pattern consistent with a compression-bending loading mode, with the greatest strains occurring in compression on the medial surface and lesser tensile strains occurring laterally. A peak strain of -5190 microepsilon (for 13.3N forelimb compression) occurred 1-2 mm distal to the mid-shaft. The pattern of bone formation in the longitudinal direction was highly correlated to the predicted peak compressive axial strains at seven cross-sections (r2 = 0.89, p = 0.014). The in-plane pattern of bone formation was poorly correlated to the predicted magnitude of axial strain at 51 periosteal locations (r2 = 0.21, p < 0.001), because the least bone formation was observed where tensile strains were highest. These findings indicate that the magnitude of bone formation after fatigue loading is greatest in regions of high compressive strain.
Animals↗
MHC-linked susceptibility to a bacterial infection, but no MHC-linked cryptic female choice in whitefish.
Non-random gamete fusion is one of several potential cryptic female choice mechanisms that have been postulated and that may enhance the survival probability of the offspring. Previous studies have found that gamete fusion in mice is influenced by genes of the major histocompatibility complex (MHC) region. Here we test (i) whether there is MHC-dependent gamete fusion in whitefish (Coregonus sp.) and (ii) whether there is a link between the MHC and embryo susceptibility to an infection by the bacterium Pseudomonas fuorescens. We experimentally bred whitefish and reared sibships in several batches that either experienced or did not experience strong selection by P. fluorescens. We then determined the MHC class II B1 genotype of 1016 surviving larvae of several full sibships. We found no evidence for MHC-linked gamete fusion. However, in one of seven sibships we found a strong connection between the MHC class II genotype and embryo susceptibility to P. fluorescens. This connection was still significant after correcting for multiple testing. Hence, the MHC class II genotype can considerably influence embryo survival in whitefish, but gamete fusion seems to be random with respect to the MHC.
Animals↗
[Transformation of inpatient treatment by the introduction of Diagnosis-Related Groups (DRG)--the positive effects of health policy research results].
Empirical researches about the results of health policy are rare. Almost, these researches take a look to very special aspects. Researches about the results of health policy is not very often demanded from the policy. In contrast to most legislation, the implementation of "diagnosis related groups" (DRG) will be realised in several steps. In these steps, there are several possibilities to correct the implementation if something is going wrong. With this background, the policy demands the researches about the results of the implementation of the DRG. Now, we are standing at the beginning of the process of the DRG implementation. It is not yet the time to provide assured empirical results about all the consequences of DRG. In spite of this, we found first hints: the implementation of DRG increases the work stress of nurses. As a result the quality of nursing could decrease.
Diagnosis-Related Groups↗
Efficient gene delivery with serum into human cancer cells using targeted anionic liposomes.
Success of human gene therapy depends upon the development of delivery vehicles or vectors, which can selectively deliver therapeutic genes to target cells with efficiency and safety. Previous studies have shown an efficient, systemic trans-gene expression in many cell lines (in vitro) by using an anionic liposomal vector, based on the composition of retroviral envelopes (artificial viral envelopes, AVEs). The AVE-liposomes and their complexes with plasmid (DNA) were characterized according to zeta potential measurements and transmission electron microscopy (TEM). We successfully demonstrated that AVE liposomes, dispersed in 10% serum-containing growth medium, efficiently delivered plasmid DNA to HuH-7 (human hepatoma cell line) cells. We assessed the utility of liver-targeted vesicles as a drug/gene delivery system for the treatment of liver diseases. We found that small unilamellar AVE vesicles containing 15 mol% digalactosyl diglyceride (DGDG) are efficiently targeted to the liver via the hepatic asialoglycoprotein receptor.
Carbohydrates↗
Her-2/neu-triggered intracellular tyrosine kinase activation: in vivo relevance of ligand-independent activation mechanisms and impact upon the efficacy of trastuzumab-based treatment.
Proteolytic cleavage of the Her-2/neu extracellular domain (ECD) has been shown to initiate receptor phosphorylation representing Her-2/neu activation in vitro. The present investigation was performed to evaluate the clinical relevance of ECD cleavage for Her-2/neu activation and the consequences of active intracellular Her-2/neu signalling reflected by tyrosine kinase phosphorylation in patients treated with the anti-Her-2/neu antibody trastuzumab. Sera from 62 patients receiving trastuzumab-based treatment for Her-2/neu overexpressing metastatic breast cancer were assessed for pretreatment ECD levels using an enzyme-linked immunosorbent assay. In parallel, Her-2/neu activation status of tumour specimens was assessed by immunohistochemistry using a Her-2/neu phosphorylation state specific antibody (PN2A) and correlated with the patients' ECD levels and clinical course of disease. Serum ECD levels were significantly higher in 15 (24%) patients with tumours exhibiting activated Her-2/neu as compared to those without detectable Her-2/neu phosphorylation (median 148.2 vs 28.5 ng ml(-1), P=0.010). Whereas response rate only showed a trend to be higher in patients with Her-2/neu-phosphorylated breast cancer (47 vs 34%, P=0.197), both uni- and multivariate analyses revealed that the median progression-free survival under trastuzumab-based treatment was significantly longer in patients with Her-2/neu-phosphorylated breast cancer-11.7 (95% CI 5.2-18.3) months-when compared to the progression-free survival of 4.5 (95% CI 3.4-5.6) months observed in patients with tumours lacking phosphorylated Her-2/neu (P=0.001). Proteolytic cleavage of the ECD represents a biologically relevant ligand-independent mechanism of Her-2/neu activation in vivo. The influence of Her-2/neu activation status upon the outcome of trastuzumab-based therapies merits further investigation in larger prospective trials.
Adult↗
Relationships between bioelectric impedance and subcutaneous adipose tissue thickness measured by LIPOMETER and skinfold calipers in children.
The aim of this study was to compare the relationships between bioelectrical impedance and thicknesses of adipose tissue measured by traditional skinfold caliper (double thickness) or a LIPOMETER device (single non-compressed thickness) in 9- to 12-year-old boys ( n=52) and girls ( n=44). In total, nine skinfolds (triceps, subscapular, biceps, iliac crest, supraspinale, abdominal, front thigh, medial calf, mid-axilla) were measured. Measurement for the thickness of subcutaneous adipose tissue layers (SAT-layers) by LIPOMETER were performed at 15 body sites (neck, triceps, biceps, upper back, front chest, lateral chest, upper abdomen, lower abdomen, lower back, hip, front thigh, lateral thigh, rear thigh, inner thigh, calf). Body bioelectrical impedance was measured with a multiple-frequency impedance device Multiscan-5000 (Bodystat, UK). Impedance at 50 kHz highly correlated with body mass ( r=-0.47 in boys, r=-0.46 in girls, r=-0.47 in total group). The relationship with body height was significant only in girls ( r=-0.42). Skinfold thicknesses measured by caliper did not correlate significantly with body impedance at 50 kHz. SAT-layers measured by LIPOMETER at triceps, front thigh, lateral thigh and rear thigh sites in boys and at the lateral thigh site in girls correlated significantly with body impedance measured at 50 kHz. Stepwise multiple regression analysis indicated that the iliac crest and front thigh skinfold thicknesses measured by caliper characterized only 5.7-12.0% of the impedance at 50 kHz in the total group ( n=96). From the measured 15 SAT-layers, the most significant was the lateral thigh layer which characterized 20.0%, 11.9% and 13.6% of the impedance at 50 kHz in boys, girls and the total group, respectively. It was concluded that the influence of subcutaneous adipose tissue on body impedance is relatively low in children. However, SAT-layers have a slightly higher influence on body impedance than skinfold thicknesses measured by caliper. The sum of skinfolds or SAT-layers did not correlate significantly with body impedance in any group.
Adipose Tissue↗
[DiGeorge syndrome/velcardiofacial syndrome: oral and maxillofacial surgery].
The DiGeorge syndrome/velocardiofacial syndrome is the most frequent chromosomal microdeletion syndrome. Partial deletion of chromosome 22q11 may lead to symptoms including facial dysmorphy, hypoparathyroidism, thymic aplasia, congenital heart disease, developmental retardation, and disturbance of speech development. According to the literature, 9% of patients have cleft palate, an additional 5% have a submucosal cleft, and a total of 32% show velopharyngeal insufficiency. We studied 64 children with a cleft, or with delayed speech development and a submucosal or occult cleft, for the presence of the 22q11deletion using fluorescent in situ hybridisation. Five patients had the 22q11 deletion. We conclude that patients presenting with nasal speech and additional anomalies should all be studied for the presence of submucosal or occult clefting and for the presence of the DiGeorge syndrome/velocardiofacial syndrome.
Adolescent↗
Long-term evaluation of paclitaxel-coated stents for treatment of native coronary lesions. First results of both the clinical and angiographic 18 month follow-up of TAXUS I.
The development of restenoses due to tissue proliferation within the stented segment is a major limitation of conventional stent implantations. Recently published studies have shown that drug-eluting stents effectively decrease the incidence of stent restenosis at 6 month follow-up as compared to bare metal stents. However, a persistent efficacy of this stent design beyond the 6 month period still needs to be proven. Therefore, in this study, we are demonstrating the first 18 month follow-up results of a Paclitaxel-coated coronary stent, based on the patient population of the TAXUS I study, a multicenter randomized study to evaluate both safety and efficacy of the Paclitaxel-coated NIRx stent as compared to an uncoated, bare metal stent. In this study we evaluated the long-term outcome of NIRx patients of our center, in which 20 out of 31 patients of the TAXUS I study with NIRx stent implantation have been enrolled. A clinical follow-up was available in 20 out of 20 patients (100%) 535 +/- 82 days post stent implantation (17.8 months). An angiographic follow-up was available in 14 out of 20 patients (70%) 580 +/- 77 days post stent implantation (19.1 months). The MACE rate at 18 month follow-up was 0.0%. There was no stent restenosis in the study group up to 18 month post drug-eluting stent implantation. There was one non-clinically driven target vessel revascularization due to a stent edge lumen renarrowing, which was subsequently calculated as a 43% diameter stenosis. Accordingly, this event was not regarded as MACE. The IVUS analysis of the study population has shown a decrease of the mean minimum lumen area from 8.45 mm(2) postinterventional to 6.87 mm(2) at 6 month follow-up with a relative mean maximum plaque area of 16%. At 18 month follow-up, there were no additional significant changes with a mean minimum lumen area of 7.16 mm(2) and a relative mean maximum plaque area of 13.4%. The reported results of the 18 month follow-up of TAXUS I are the first experiences demonstrating a persistent benefit of the Paclitaxel-coated NIRx stent. Therefore, this stent design seems to be safe and effective, even in long-term follow-up.
Aged↗
Human alpha2-macroglobulin: genotype-phenotype relation.
A pentanucleotide deletion polymorphism in the gene of alpha2-macrolgobulin (alpha2-M) is suggested to be associated with late-onset Alzheimer's disease (AD), though controversial results have been reported. The underlying assumption is that the intronic pentanucleotide deletion may affect the biological function and quantity of the inhibitor and thus contribute to the AD pathology. In the present study we have analyzed the distribution of the deletion polymorphism within a group of 227 healthy Caucasians. In parallel studies, we determined the plasma concentrations of total and transformed alpha2-M. A strong correlation of the total concentration of alpha2-M with age was ascertained (r(s) = -0.54, P < 0.001). However, no significant correlation between age and the genotypes (P = 0.68) was detected, and no statistically significant effect of the genotype on the concentrations of total and transformed alpha2-M was found (P = 0.49 and 0.96, respectively). A significant correlation was observed between total and transformed alpha2-M in the genotype groups Ins/Ins (r(s) = 0.56, P < 0.001) and Ins/Del (r(s) = 0.35, P < 0.004). Furthermore, in the entire data set, a significantly elevated concentration of total alpha2-M was found in females as compared to males (P = 0.003). There was a slight but nonsignificant difference in the genotype distributions between males and females (P = 0.14). To test the proposed existence of genotype-specific alterations of functional properties of alpha2-M, we isolated alpha2-M from the plasma of carriers with different genetic background and analyzed the alpha2-M subunit structure as well as the binding of the inhibitor to growth factors/cytokines, to amyloid-beta and to the receptor. The experiments failed to reveal any genotype-specific functional alterations of the alpha2-M. The absence of abnormalities in alpha2-M mRNA and protein suggests that the alpha2-M deletion polymorphism is probably not associated with functional deficiencies important in AD pathology. However, it can be speculated that the observed general age-related alpha2-M deficiency may lead to accelerated accumulation of amyloid-beta, which might be relevant to AD pathology.
Adult↗
Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys.
Using a clinically relevant regimen, this study investigated the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, biochemical markers of bone turnover, densitometry, histomorphometry, biomechanical properties, and bone concentration in aged ovariectomized monkeys. Sixty-six female cynomolgus monkeys, aged 9 years and older, were ovariectomized (OVX) or sham operated. Intravenous (iv) bolus injections of ibandronate at 10, 30, or 150 microg/kg or placebo were administered at 30-day intervals (corresponding to intervals of 3 months in humans), starting at OVX, for 16 months. OVX significantly decreased bone mass at the lumbar spine, proximal femur, femoral neck, and radius and increased bone turnover in a time-dependent manner, as assessed by dual energy X-ray absorptiometry, peripheral quantitative computed tomography, or histomorphometry. Ibandronate iv bolus injections administered at 30 microg/kg every 30 days prevented osteopenia induced by estrogen depletion. OVX-induced increases in bone turnover (as determined by activation frequency, bone formation rate, and biochemical markers of bone turnover, including urinary N-telopeptide and deoxypyridinoline excretion and serum values for osteocalcin and bone-specific alkaline phosphatase) were suppressed on treatment, and bone mass, architecture, and strength were preserved at clinically relevant sites. Treatment with high-dose (150 microg/kg/dose) iv bolus injections of ibandronate further increased bone mass and improved bone strength at both the spine and femoral neck, without adversely affecting bone quality. In contrast, treatment with a 10 microg/kg/dose only partially prevented the OVX-induced effects. These data support the potential for the long-term administration of ibandronate by intermittent iv bolus injections in humans to prevent osteoporosis and improve bone quality at clinically relevant sites.
Animals↗
An update on the diagnosis and treatment of sinusitis and nasal polyposis.
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Humans↗
[Telemetric system for measuring the pressure of the tongue on the palate].
The development of the upper jaw during growth is influenced by the function and position of the tongue and perioral soft tissues, and the pressures exerted by them. Accurate determination of the forces exerted by the tongue would provide relevant information about this influence. To date, our ability to obtain continuous recordings of the tongue pressure during certain functions is limited. In this paper, an easy-to-employ and accurate telemetric system for such functional measurements is presented. The system, consisting of four piezoresistive pressure sensors, a microcontroller, a telemetric module and batteries, is integrated within a removable orthodontic plate and transmits the measured data out of the oral cavity to a receiver.
Adult↗
A laser-based method to measure thermal nociception in dairy cows: short-term repeatability and effects of power output and skin condition.
To validate a laser-based method to measure thermal nociception in dairy cows (e.g., for the use in studies on stress-induced analgesia), we performed three experiments to observe the behavioral responses to a computer-controlled CO2 laser beam applied to the skin on the caudal aspect of the metatarsus. In Exp. 1, effects of power output (0, 1.3, 1.8, 2.2, 2.4 and 2.6 W) on nociceptive responses were examined using 18 dairy cows kept and tested in tie stalls. Increasing the power output affected the latencies to respond (decreasing latencies, P < or = 0.01), types of response (less nonresponding and more kicking, P < 0.0001), and behavior during (increasing frequency of tail flicking, P = 0.003) and between single laser exposures (increasing frequency of kicking, P = 0.02). Therefore, behavioral responses to a laser stimulus seem to be a valid measure of nociception in dairy cows. Repeatability within 15 min was investigated in Exp. 2 using n = 36 dairy cows kept and tested in tie stalls and a power output of 1.8 W. The variables' latency to move the exposed leg and frequency of tail flicking during laser exposure showed the highest level of repeatability (0.50 and 0.38, respectively). However, retesting at t = 15 min led to increased responses in terms of shorter latencies to respond (P < 0.05), increased kicking (P = 0.05), and tail flicking (P = 0.02), which probably can be explained by sensitization. Effects of power output (1.0 vs. 1.8 W) and skin condition (naked vs. intact) were examined in Exp. 3 on 11 group-housed dairy cows, tested just outside their home pen. Increasing the power output and shaving off hair led to increased responses as seen by shorter latencies to respond (P < 0.0001), less nonresponding (P < 0.0001), and increased kicking (P = 0.0003), as well as reduced intra- and interindividual variability (P < or = 0.04). In conclusion, the results of these experiments suggest that behavioral responses to laser stimulation are a valid and reliable measure of nociception in dairy cows, especially when applied on naked skin, both in the home environment and just outside a group pen. The fact that repeated testing in itself at t = 15 min led to increased responses means that the test will be a conservative measure of stress-induced analgesia.
Analgesia↗
Nonviral gene delivery to the lung with copolymer-protected and transferrin-modified polyethylenimine.
Polyethylenimine (PEI) has been shown to efficiently mediate topical gene transfer to the lungs after either direct intratracheal instillation or nebulisation. Recently, the protection of polyplexes with novel copolymers of poly(ethylene glycol) (PEG) via electrostatic interaction has been reported. In this study, such coated PEI polyplexes were investigated for their stability and interaction with human plasma and bronchoalveolar lavage fluid (BALF). Further, their potential for gene delivery to the mouse lungs in vivo was examined. Plasma protein and mucin adsorption was effectively inhibited when polyplexes were coated with the novel copolymers. Gene transfer efficiency of the coated PEI polyplexes decreased as compared with uncoated PEI polyplexes when administered intratracheally to the lung. The higher the molecular weight of the copolymerized PEG was, the stronger the observed gene transfer reduction. Gene transfer decreased presumably due to reduced interaction of the coated gene vectors with the cell surface. To circumvent this problem, transferrin was combined with PEI/DNA polyplexes for specific binding to the cell surface. In this case, gene transfer efficiency decreased. Gene transfer of the copolymer-protected and transferrin-modified gene vectors increased as compared with the copolymer-protected gene vectors alone but did not reach the level of uncoated gene vectors. These data show that copolymers could be used to effectively shield polyplexes from interaction with components of the airway surface liquid (ASL). Increased gene delivery was found upon transferrin modification of the coated PEI polyplexes suggesting a targeting effect.
Animals↗
The development of an improved carrier system for sunscreen formulations based on crystalline lipid nanoparticles.
The aim of this study was the in vitro evaluation of the efficacy of two different carrier systems for the molecular sunscreen benzophenone-3. One carrier system was a conventional o/w emulsion, the other consisted of highly crystalline lipid nanoparticles (CLN). It was observed that CLN act as physical sunscreens themselves and show improved photoprotection compared with a placebo emulsion with the same lipid content. Incorporation of a molecular sunscreen further improves the protection level in a synergistic way. This in vitro study based on the Transpore test by Diffey showed that the amount of molecular sunscreen can be decreased by up to 50% while maintaining the UV protection efficacy. Therefore, the use of CLN as an active carrier for sunscreens is a promising innovation.
Benzophenones↗
The influence of the crystallinity of lipid nanoparticles on their occlusive properties.
The aim of this study was the investigation of the correlation between the degree of crystallinity of solid lipid nanoparticle (SLN) dispersions and their occlusive effects. SLN dispersions with different crystallinity indices of the lipid matrix were produced, physicochemically characterized and their occlusion factor was determined after 6, 24 and 48 h. This study is based on the in vitro occlusion test by de Vringer. It could be shown that the occlusion factor depends strongly on the degree of crystallinity of the lipid matrix, i.e. this effect is proportional. Further, it could be shown that noncrystalline lipid nanoparticles, i.e. supercooled melts have no occlusive properties. Therefore, the desired degree of occlusivity can be achieved by choosing suitable lipids for the matrices of topical SLN formulations.
Calorimetry, Differential Scanning↗