Bio-derived hydroxystearic acid ameliorates skin age spots and conspicuous pores.

INTRODUCTION: We report on the preparation and efficacy of 10-hydroxystearic acid (HSA) that improves facial age spots and conspicuous pores. METHODS: The hydration of oleic acid into HSA was catalyzed by the oleate hydratase from Escherichia coli. Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1 J cm-2 ) by immunohistochemistry on human ex vivo skin. UVB-induced expression of matrix metalloprotease-1 (MMP-1) was determined from full thickness skin by RT-qPCR. Modification of the fibroblast secretome by HSA was studied by mass-spectrometry-based proteomics. In a full-face, double blind, vehicle-controlled trial HSA was assessed for its effects on conspicuous facial pore size and degree of pigmentation of age spots in Caucasian women over an 8-week period. RESULTS: HSA was obtained in enantiomeric pure, high yield (≥80%). Collagen type I and type III levels were dose-dependently increased (96% and 244%; P < 0.01) in vitro and collagen type III in ex vivo skin by +57% (P < 0.01) by HSA. HSA also inhibited UVB-induced MMP-1 gene expression (83%; P < 0.01) and mitigated SBC induction (-34% vs. vehicle control) and reduced significantly UV-induced p53 up-regulation (-46% vs. vehicle control; P < 0.01) in irradiated skin. HSA modified the fibroblast secretome with significant increases in proteins associated with the WNT pathway that could reduce melanogenesis and proteins that could modify dermal fibroblast activity and keratinocyte differentiation to account for the alleviation of conspicuous pores. Docking studies in silico and EC50 determination in reporter gene assays (EC50 5.5 × 10-6  M) identified HSA as a peroxisomal proliferator activated receptor-α (PPARα) agonist. Clinically, HSA showed a statistically significant decrease of surface and volume of skin pores (P < 0.05) after 8 weeks of application and age spots became significantly less pigmented than the surrounding skin (contrast, P < 0.05) after 4 weeks. CONCLUSION: HSA acts as a PPARα agonist to reduce the signs of age spots and conspicuous pores by significantly modulating the expression of p53, SBC, MMP-1 and collagen together with major changes in secreted proteins that modify keratinocyte, melanocyte and fibroblast cell behavior.

INTRODUCTION: voici notre rapport sur la préparation et l'efficacité de l'acide 10-hydroxystéarique (AHS) qui atténue les taches de vieillesse faciale et améliore l'apparence des pores. MÉTHODES: l'hydratation de l'acide oléique en AHS a été catalysée par l'hydratase d'oléate à partir de l'Escherichia coli. Après un traitement par AHS, les collagènes de type I et de type III ont été analysés dans des fibroblastes dermiques humains primaires, ainsi que le taux de collagène de type III et de protéine p53, et les cellules provenant de coups de soleil (sunburn cells, SBC) après irradiation par UVB (1 J cm−2 ) par immunohistochimie sur de la peau humaine ex vivo. L'expression de la matrice métalloprotéase-1 (MMP-1) induite par les UVB a été déterminée à partir d'un échantillon de pleine épaisseur de peau par RT-qPCR. La modification du sécrétome des fibroblastes par l'AHS a été étudiée par analyse protéomique basée sur une spectrométrie de masse. Dans une étude du visage entier, en double aveugle, contrôlée par excipient, l'AHS a été évaluée pour ses effets sur la taille des pores apparents du visage et sur le degré de pigmentation de taches de vieillesse chez des femmes de race blanche sur une période de 8 semaines. RÉSULTATS: l'AHS a été obtenu à un haut rendement, énantiomérique pur (≥80 %). Les taux de collagènes de type I et de type III ont augmenté in vitro en fonction de la dose (96 % et 244 %; P < 0.01) et le collagène de type III dans de la peau ex vivo de +57 % (P < 0.01) lors d'un traitement par AHS. L'AHS a également inhibé l'expression génique MMP-1 induite par les UVB (83%; P < 0.01) et a atténuée l'induction des SBC (−34 % par rapport à l'excipient), et a réduit significativement la régulation à la hausse du p53 induite par les UV (−46% par rapport à l'excipient; P < 0.01) sur de la peau irradiée. L'AHS a modifié le sécrétome des fibroblastes avec des augmentations significatives des protéines associées à la voie WNT qui pouvaient réduire la mélanogenèse et des protéines qui pouvaient modifier l'activité des fibroblastes dermiques et la différenciation des kératinocytes pour une atténuation des pores apparents. Des études de docking in silico et la détermination de l'EC50 dans les dosages des gènes rapporteurs (EC50 5.5 × 9 10−6 M) ont identifié l'AHS comme un agoniste du récepteur-α activé par les proliférateurs de peroxysomes (peroxisomal proliferator activated receptor-α, PPARα). Cliniquement, l'AHS a permis une diminution statistiquement significative de la surface et du volume des pores de la peau (P < 0.05) après 8 semaines d'application, et les taches de vieillesse sont devenues significativement moins pigmentées par rapport à la peau environnante (contraste, P < 0,05) après 4 semaines. CONCLUSION: l'AHS agit comme un agoniste du PPARα pour réduire les signes de taches de vieillesse et l'apparence des pores par une modulation significative de l'expression de la protéine p53, des SBC, de la MMP-1 et du collagène avec des changements majeurs dans les protéines sécrétées qui modifient le comportement cellulaire des kératinocytes, des mélanocytes et des fibroblastes.

BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes.

Patients with asthma experience circadian variations in their symptoms. However it remains unclear how specific aspects of this common airway disease relate to clock genes, which are critical to the generation of circadian rhythms in mammals. Here, we used a viral model of acute and chronic airway disease to examine how circadian clock disruption affects asthmatic lung phenotypes. Deletion of the core clock gene bmal1 or environmental disruption of circadian function by jet lag exacerbated acute viral bronchiolitis caused by Sendai virus (SeV) and influenza A virus in mice. Post-natal deletion of bmal1 was sufficient to trigger increased SeV susceptibility and correlated with impaired control of viral replication. Importantly, bmal1-/- mice developed much more extensive asthma-like airway changes post infection, including mucus production and increased airway resistance. In human airway samples from two asthma cohorts, we observed altered expression patterns of multiple clock genes. Our results suggest a role for bmal1 in the development of asthmatic airway disease via the regulation of lung antiviral responses to common viral triggers of asthma.

Diagnostics and Therapy for Malignant (Degenerate) Colon Endometriosis - Three Case Reports.

Malignant degeneration of colon endometriosis is a very rare event. We report here on three cases. A 48-year-old woman with a 10-year history of endometriosis was treated for a rectal adenocarcinoma, a 61-year-old G1P1, who was operated at the age of 40 years for ovarian endometriosis and again at the age of 53 years for an endometriosis-associated endometroid ovarian carcinoma, presented for therapy for a lymph node recurrence of the ovarian cancer and, secondly, due to a malignantly degenerated rectum-sigmoid colon endometriosis; furthermore a 54-year old woman with a 21-year history of endometriosis was operated for malignant colon endometriosis. The tumour occurred during an adjuvant anti-oestrogen treatment with an aromatase inhibitor following surgical and radiotherapy for breast cancer. In all cases a radical cancer operation was followed by adjuvant chemotherapy and in one case with an additional radiotherapy. In the follow-up periods of 18 months, 2 and 5 years, respectively, all women remained free of recurrences. Although this is not a randomised controlled study due to the rare occurrence of such cases, a radical operation followed by individualised adjuvant therapy appears to be the treatment of choice.

Quantifying degradation of collagen in ancient manuscripts: the case of the Dead Sea Temple Scroll.

Since their discovery in the late 1940s, the Dead Sea Scrolls, some 900 ancient Jewish texts, have never stopped attracting the attention of scholars and the broad public alike, because they were created towards the end of the Second Temple period and the "time of Christ". Most of the work on them has been dedicated to the information contained in the scrolls' text, leaving physical aspects of the writing materials unexamined. They are, however, crucial for both historical insight and preservation of the scrolls. Although scientific analysis requires handling, it is essential to establish the state of degradation of these valued documents. Polarized Raman Spectroscopy (PRS) is a powerful tool for obtaining information on both the composition and the level of disorder of molecular units. In this study, we developed a non-invasive and non-destructive methodology that allows a quantification of the disorder (that can be related to the degradation) of protein molecular units in collagen fibers. Not restricted to collagen, this method can be applied also to other protein-based fibrous materials such as ancient silk, wool or hair. We used PRS to quantify the degradation of the collagen fibers in a number of fragments of the Temple Scroll (11Q19a). We found that collagen fibers degrade heterogeneously, with the ones on the surface more degraded than those in the core.

Fungal bioleaching of mineral components in a twentieth-century illuminated parchment.

In this work, we applied scanning electron microscopy (SEM), microanalysis and Raman spectroscopy to study the fungi inhabiting a richly illuminated parchment document and the damage induced by their activity. To that aim, we collected samples of fungal mycelium from the deteriorated areas on a removable adhesive tape specifically intended for lifting fungi without damaging the support. SEM analysis of the adhesive tape samples showed the co-occurrence of several species of fungi. One strain closely resembling Acremonium species was observed only in the tape micrographs but no agar cultures were obtained. Its fungal structures showed the production of abundant oxalates with an outstanding leaching of the calcium-based materials of parchment (typically manufactured with gypsum and lime). Needle-like crystals of calcium oxalate produced by the fungus forming a uniform and quite regular grid around conidial slimy heads were documented. As a result, the areas affected by moulds were weakened, stained and characterised by a powdery patina rich in calcium. Confocal µ-Raman confirmed the presence of oxalates while EDS showed the presence of calcium in crystals. We conclude that the defacement of the parchment was due to both collagenolytic activity, and to the biotransformation of calcium-based minerals by fungi.

Measurement of the fluence response of the GSI neutron ball dosemeter in the energy range from thermal to 19 MeV.

At high-energy particle accelerators, area monitoring needs to be performed in a wide range of neutron energies. In principle, neutrons occur from thermal energies up to the energy of the accelerated ions, which is for the present GSI (Gesellschaft für Schwerionenforschung) accelerator facility approximately 1-2 GeV per nucleon. There are no passive dosemeters available, which are designed for the use at high-energy accelerators. At GSI, a neutron dosemeter was developed, which is suitable for the measurement of high-energy neutron radiation by the insertion of a lead layer around Thermoluminescence (TL) detection elements (pairs of TL 600/700) at the centre of the dosemeter. The design of the sphere was derived from the construction of the extended range rem-counters for the measurement of ambient dose equivalent H(10). In this work, the dosemeter fluence response was measured in the quasi-monoenergetic neutron fields of the accelerator facility of the PTB in Braunschweig and in the thermal neutron field of the GKSS research reactor FRG-1 in Geesthacht. For the accelerator measurements, the reactions (7)Li(p,n)(7)Be, (3)H(p,n)(3)He and (2)H(d,n)(3)He were used to produce neutron fields with energy peaks between 144 keV and 19 MeV. The measured fluence responses are 27% too low for thermal energies and show an agreement with approximately 14% for the accelerator produced neutron fields related to the computed fluence responses (MCNP, FLUKA calculations). The measured as well as the computed fluence responses of the dosemeter are compared with the corresponding conversion coefficients.

TLR-2-mediated induction of vascular endothelial growth factor (VEGF) in cartilage in septic joint disease.

Bacterial arthritis is a progressive joint disease which includes rapid destruction of articular cartilage even after clearance of the causal factor. The resulting post-infectious arthropathy is mainly characterized by self-perpetuating joint destruction and extensive angiogenesis in the emerging pannus-like synovial membrane, but the underlying molecular mechanisms of the bacteria-initiated process remain incompletely understood. This study was conducted to elucidate the expression and regulation of angiogenic and cartilage-destructive vascular endothelial growth factor (VEGF) in septic arthritis. For that purpose, aspirates of synovial fluid from patients with pyogenic arthritis were examined for VEGF levels by ELISA. In vitro studies with primary and immortalized chondrocytes were performed to determine whether Gram-positive and Gram-negative bacteria induce VEGF expression, by using real-time RT-PCR, ELISA, and immunohistochemistry. Activation of the transcription factor AP-1 was assessed by EMSA experiments. The necessity of the Toll-like receptor-2 (TLR-2), ERK-1/-2, and AP-1 pathway for infectious VEGF induction in chondrocytes was examined by using specific blocking reagents. ELISA experiments revealed that aspirates of synovial fluid from patients with pyogenic arthritis contain elevated levels of VEGF. The in vitro results confirmed the transcriptional induction of VEGF in chondrocytes after bacterial challenge by real-time RT-PCR, ELISA, and immunohistochemistry. This activation was mediated by a TLR-2-, ERK-1/-2-, and AP-1-dependent pathway. The findings demonstrate the expression of Toll-like receptors on mesenchymal articular chondrocytes and reveal TLR-2-mediated VEGF induction in human chondrocytes after Gram-positive bacterial sensing. Since VEGF is a potent angiogenic and tissue remodelling factor, evidence that Toll-like receptors contribute to destructive arthropathy after microbial joint infection is provided. VEGF may be a therapeutic target in the future for the prevention of post-infectious cartilage degradation in articular joints.

A three si detector system for personnel neutron dosimetry developed by means of Monte Carlo simulation calculations.

The aim of this study was the development of an electronic detection system for personnel neutron dosimetry. Converter type silicon detectors were used for neutron detection. Measurements to obtain pulse height distributions were performed in neutron fields in the energy range from thermal to 14.8 MeV. They were compared with pulse height distributions calculated by means of Monte Carlo simulation programs, and their shapes and total count responses agreed very well. Based on these calculations a three-detector system for the measurement of the individual dose equivalent, Hp(10), was developed. Response functions of the system were calculated, and their dependence on angles from 0 degrees to 75 degrees was investigated. The detector system was exposed in several neutron fields and the agreement of the determined dose values with the reference dose values (0.1 mSv to 6 mSv) was better than a factor of 2, even for quasi-monoenergetic neutrons, and for angles in the range of 0 degrees, 30 degrees and 60 degrees. The detector system should be able to measure a dose range down to 10 microSv depending on the neutron energy.

Analysis of proximal femur DXA scans in growing children: comparisons of different protocols for cross-sectional 8-month and 7-year longitudinal data.

Dual-energy X-ray absorptiometry (DXA) is a widely used method for measuring bone mineral in the growing skeleton. Because scan analysis in children offers a number of challenges, we compared DXA results using six analysis methods at the total proximal femur (PF) and five methods at the femoral neck (FN). In total we assessed 50 scans (25 boys, 25 girls) from two separate studies for cross-sectional differences in bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) and for percentage change over the short term (8 months) and long term (7 years). At the proximal femur for the short-term longitudinal analysis, there was an approximate 3.5% greater change in bone area and BMC when the global region of interest (ROI) was allowed to increase in size between years as compared with when the global ROI was held constant. Trend analysis showed a significant (p < 0.05) difference between scan analysis methods for bone area and BMC across 7 years. At the femoral neck, cross-sectional analysis using a narrower (from default) ROI, without change in location, resulted in a 12.9 and 12.6% smaller bone area and BMC, respectively (both p < 0.001). Changes in FN area and BMC over 8 months were significantly greater (2.3%, p < 0.05) using a narrower FN rather than the default ROI. Similarly, the 7-year longitudinal data revealed that differences between scan analysis methods were greatest when the narrower FN ROI was maintained across all years (p < 0.001). For aBMD there were no significant differences in group means between analysis methods at either the PF or FN. Our findings show the need to standardize the analysis of proximal femur DXA scans in growing children.

Statistical power for the two-factor repeated measures ANOVA.

Determining a priori power for univariate repeated measures (RM) ANOVA designs with two or more within-subjects factors that have different correlational patterns between the factors is currently difficult due to the unavailability of accurate methods to estimate the error variances used in power calculations. The main objective of this study was to determine the effect of the correlation between the levels in one RM factor on the power of the other RM factor. Monte Carlo simulation procedures were used to estimate power for the A, B, and AB tests of a 2 x 3, a 2 x 6, a 2 x 9, a 3 x 3, a 3 x 6, and a 3 x 9 design under varying experimental conditions of effect size (small, medium, and large), average correlation (.4 and .8), alpha (.01 and .05), and sample size (n = 5, 10, 15, 20, 25, and 30). Results indicated that the greater the magnitude of the differences between the average correlation among the levels of Factor A and the average correlation in the AB matrix, the lower the power for Factor B (and vice versa). Equations for estimating the error variance of each test of the two-way model were constructed by examining power and mean square error trends across different correlation matrices. Support for the accuracy of these formulae is given, thus allowing for direct analytic power calculations in future studies.

Lifestyle determinants of bone mineral: a comparison between prepubertal Asian- and Caucasian-Canadian boys and girls.

The purpose of this study was to examine the difference in lifestyle and morphometric factors that affect bone mineral and the attainment of peak bone mass in 168 healthy Asian (n = 58) and Caucasian (n = 110) Canadian, prepubertal girls and boys (mean age 8.9+/-0.7) living in close geographical proximity. DXA (Hologic 4500) scans of the proximal femur (with regions), lumbar spine, and total body (TB) were acquired. We report areal bone mineral densities (aBMD g/cm(2)) at all sites and estimated volumetric density (aBMD, g/cm(3)) at the femoral neck. Dietary calcium, physical activity, and maturity were estimated by questionnaire. Of these prepubertal children, all of the boys and 89% of the girls were Tanner stage 1. A 2x2 ANOVA demonstrated no difference between ethnicities for height, weight, body fat, or bone mineral free lean mass. Asian children consumed significantly less dietary calcium (35%) on average and were significantly less active (15%) than their Caucasian counterparts (P<0.001). There were significant ethnicity main effects for femoral neck bone mineral content (BMC) and alphaBMD (both P<0.001) and significant sex by ethnicity interactions (P<0.01). The Asian boys had significantly lower femoral neck BMC (11%), aBMD (8%), and vBMD (4.4%). At the femoral neck, BMFL mass, sex, and physical activity explained 37% of the total variance in aBMD (P<0.05). In summary, this study demonstrated differences in modifiable lifestyle factors and femoral neck bone mineral between Asian and Caucasian boys.

Augmented trochanteric bone mineral density after modified physical education classes: a randomized school-based exercise intervention study in prepubescent and early pubescent children.

BACKGROUND: Of the few exercise intervention studies focusing on pediatric populations, none have confined the intervention to the scheduled physical education curriculum. OBJECTIVE: To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density (aBMD), in grams per square centimeter, of healthy third- and fourth-grade children. STUDY DESIGN: Ten elementary schools were randomized to exercise (n = 63) and control groups (n = 81). Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping, hopping, and skipping into twice weekly physical education classes. Control groups did regular physical education classes. At baseline and after 8 months of intervention, we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry (Hologic QDR-4500). Calcium intake, physical activity, and maturity were estimated by questionnaire. RESULTS: The exercise group showed significantly greater change in femoral trochanteric aBMD (4.4% vs 3.2%; P <.05). There were no group differences at other sites. Results were similar after controlling for covariates (baseline aBMD change in height, change in lean, calcium, physical activity, sex, and ethnicity) in hierarchical regression. CONCLUSIONS: An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton.

Improved blood preservation with 0.5CPD erythro-sol. Coagulation factor VIII activity and erythrocyte quality after delayed separation of blood.

BACKGROUND AND OBJECTIVES: Delay between blood collection and the separation of its components may result in lowered yield of factor VIII (FVIII) and loss of 2,3-biphosphoglycerate (2,3-BPG). This study was to see whether the use of 0.5 CPD resulted in better preservation of FVIII and maintenance of 2,3-BPG. MATERIALS AND METHODS: 55 units of blood were collected in 0.5CPD and 48 in CPD SAG-M. Ten of the collections were paired, so that the same donors were bled in a single session partly in an 0.5CPD system and partly in CPD SAG-M. After collection, the blood was promptly cooled to 20 degrees C and stored at that temperature for up to 24 h. RESULTS: Preservation of FVIII activity was significantly better in 0.5CPD compared with CPD. The content of von Willebrand factor was stable in the anticoagulant solutions for 24 h at that temperature. Plasma separated from both media had how levels of prothrombin fragment 1 + 2 and complement activation. Paired collections substantiated previous reports that red cell storage is significantly improved in 0.5CPD compared with CPD SAG-M with respect to 2,3-BPG and haemolysis. CONCLUSIONS: Red cell metabolism and oxygen-releasing capacity are kept at acceptable levels in 0.5CPD blood for 24 h at 20 degrees C before component separation. The concentration of red cell 2,3-BPG remained at normal or slightly subnormal levels during further storage in 0.5CPD at 4 degrees C for 2-4 weeks before gradual decay to an average of 39% at 48 days.

[Angiography during interventional procedures with carbon dioxide (CO2) (carbo-angiography) in patients with increased contrast media risk]. / Interventionsbegleitende Angiographie mit Kohlendioxid (CO2) (Carboangiographie) bei Patienten mit erhöhtem Kontrastmittelrisiko.

Within the last 18 months we examined 130 patients with known complications or contraindications using iodinated contrast media for angiography by using carbon dioxide as contrast agent in digital subtraction angiography technique. These were diagnostic pelvis-leg angiographies (n = 106) with simultaneous consecutive interventional radiologic therapy in 68 cases. In 19 dialysis access fistulas 11 angioplasties were performed in the same session. In 5 cases of renal allografts no interventional radiologic therapy was necessary. For CO2 application an electronic controlled special injector was used. Carbon dioxide has a number of advantages: no adverse reactions, nonallergenic and can be used several times without increasing risks and is cost-saving. CO2 angiography is a sensitive method, for detection vessel wall processes below the diaphragm. It can replace conventional angiography.

[Rehabilitation from the economic viewpoint--basic geriatric considerations]. / Rehabilitation unter ökonomischen Gesichtspunkten--Grundsätzliche geriatrische Anmerkungen.

Rehabilitation of the elderly on principle uses the same therapeutics as in younger people. But it will only be successful if the target will be realistic, i.e., the indication considers the individual functional capacity as well as psychosocial factors. Still often only partial success will be available. But carried out competently geriatric rehabilitation will be efficient as many reports-also from Germany-verify.