Comparison of the solophenyl-red polarization method and the immunohistochemical analysis for collagen type III

In the present study, we have compared the staining pattern of the Solophenyl-Red 3 BL-method for the visualization of collagen type III with the immunohistochemical staining in serial sections from 7 skin wounds (wound age 3 days up to 4 weeks) to elucidate the specifity of the histochemical staining method. Large amounts of collagen type III were clearly detectable in the investigated wounds using the immunohistochemical technique. In the sections stained with Solophenyl-Red, however, only 3 out of 7 skin lesions showed a significant positive red staining at the wound margin or in the granulation tissue, while the adjacent normal connective tissue revealed a typical intensive staining. Using polarization microscopy no characteristic bright green fibrils, as reported for collagen type 111, could be seen in the wound areas without positive Solophenyl-Red staining. Since the localization of collagen type III detected by immunohistochemistry and the presumed distribution of this collagen type by the Solophenyl-Red method was not identical, the histochemical polarization method has to be regarded as non-specific for visualization of this collagen type

The time-dependent rearrangement of the epithelial basement membrane in human skin wounds

In 62 human skin wounds (surgical wounds, stab wounds and lacerations after surgical treatment) we analyzed the immunohistochemical localization of collagen IV in the epithelial basement membrane. In 27 of these wounds the distribution of collagen VII, which represents a specific component of the basement membrane of stratified epithelia, was also analyzed. We were able to demonstrate a virtually identical co-distribution of both collagen IV and VII in the wound area with no significant time-dependent differences in the appearance of both collagen types. Fragments of the epithelial basement membrane could be detected in the wound area from as early as 4 days after wounding and after 8 days a complete restitution of the epithelial basement membrane was observed. In all cases with a wound age of more than 21 days the basement membrane was completely reformed over the former lesional area. The period between 8 and 21 days after wounding was characterized by a wide variability ranging from complete restitution to deposition of basement membrane fragments or total lack of the epidermal basement membrane

Esmolol is noninferior to metoprolol in achieving a target heart rate of 65 beats/min in patients referred to coronary CT angiography: A randomized controlled clinical trial.

BACKGROUND: Coronary CT angiography (CTA) is an established tool to rule out coronary artery disease. Performance of coronary CTA is highly dependent on patients' heart rates (HRs). Despite widespread use of beta-blockers for coronary CTA, few studies have compared various agents used to achieve adequate HR control. OBJECTIVE: We sought to assess if the ultrashort-acting beta-blocker intravenous esmolol is at least as efficacious as the standard of care intravenous metoprolol for HR control during coronary CTA. METHODS: Patients referred to coronary CTA with a HR >65 beats/min despite oral metoprolol premedication were enrolled in the study. We studied 412 patients (211 male; mean age, 57 +/- 12 years). Two hundred four patients received intravenous esmolol, and 208 received intravenous metoprolol with a stepwise bolus administration protocol. HR and blood pressure were recorded at arrival, before, during, immediately after, and 30 minutes after the coronary CTA scan. RESULTS: Mean HRs of the esmolol and metoprolol groups were similar at arrival (78 +/- 13 beats/min vs 77 +/- 12 beats/min; P = .65) and before scan (68 +/- 7 beats/min vs 69 +/- 7 beats/min; P = .60). However, HR during scan was lower in the esmolol group vs the metoprolol group (58 +/- 6 beats/min vs 61 +/- 7 beats/min; P < .0001), whereas HRs immediately and 30 minutes after the scan were higher in the esmolol group vs the metoprolol group (68 +/- 7 beats/min vs 66 +/- 7 beats/min; P = .01 and 65 +/- 8 beats/min vs 63 +/- 8 beats/min; P < .0001; respectively). HR </=65 beats/min was reached in 182 of 204 patients (89%) who received intravenous esmolol vs 162 of 208 of the patients (78%) who received intravenous metoprolol (P < .05). Of note, hypotension (systolic BP <100 mm Hg) was observed right after the scan in 19 patients (9.3%) in the esmolol group and in 8 patients (3.8%) in the metoprolol group (P < .05), whereas only 5 patients (2.5%) had hypotension 30 minutes after the scan in the esmolol group compared to 8 patients (3.8%) in the metoprolol group (P = .418). CONCLUSION: Intravenous esmolol with a stepwise bolus administration protocol is at least as efficacious as the standard of care intravenous metoprolol for HR control in patients who undergo coronary CTA

Immunohistochemical localization of fibronectin as a tool for the age determination of human skin wounds

We analyzed the distribution of fibronectin in routinely embedded tissue specimens from 53 skin wounds and 6 postmortem wounds. In postmortem wounds a faint but focal positive staining was exclusively found at the margin of the specimens which dit not extend into the adjacent stroma. Vital wounds were classified into 3 groups. The first comprising lesions with wound ages ranging from a few seconds to 30 min, the second comprising those with wound ages upt to 3 weeks, and the third group with lesions more than 3 weeks old. Ten out of 17 lesions with a wound age up to 30 min showed a clear positive reaction within the wound area. Three specimens in this group were completely negative, while in 4 additional cases the result was not significantly different from postmortem lesions. These 7 cases were characterized by acute death with extremely short survival times (only seconds). In wounds up to 3 weeks old fibronectin formed a distinct network containing an increasing number of inflammatory cells corresponding to the wound age. In 2 cases with a survival time of 17 days and in all wounds older than 3 weeks fibronectin was restricted to the surface of fibroblasts and to parallel arranged fibers in the granulation tissue without any network structures. We present evidence that fibronectin is a useful marker for vital wounds with a survival time of more than a few minutes. Fibronectin appears before neutrophilic granulocytes migrate into the wound area. Since a faint positive fibronectin staining is seen in postmortem lesions and bleedings, we propose that only those wounds which show strong positive fibronectin staining also extending into the adjacent stroma should be regarded as vital

Stent-Based Retrieval Techniques in Acute Ischemic Stroke Patients with and Without Susceptibility Vessel Sign.

BACKGROUND AND PURPOSE Randomized controlled trials have challenged the assumption that reperfusion success after mechanical thrombectomy varies depending on the retrieval techniques applied; however, recent analyses have suggested that acute ischemic stroke (AIS) patients showing susceptibility vessel sign (SVS) may respond differently. We aimed to compare different stent retriever (SR)-based thrombectomy techniques with respect to interventional outcome parameters depending on SVS status. METHODS We retrospectively reviewed 497 patients treated with SR-based thrombectomy for anterior circulation AIS. Imaging was conducted using a 1.5 T or 3 T magnetic resonance imaging (MRI) scanner. Logistic regression analyses were performed to test for the interaction of SVS status and first-line retrieval technique. Results are shown as percentages, total values or adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULTS An SVS was present in 87.9% (n = 437) of patients. First-line SR thrombectomy was used to treat 293 patients, whereas 204 patients were treated with a combined approach (COA) of SR and distal aspiration. An additional balloon-guide catheter (BGC) was used in 273 SR-treated (93.2%) and 89 COA-treated (43.6%) patients. On logistic regression analysis, the interaction variable of SVS status and first-line retrieval technique was not associated with first-pass reperfusion (aOR 1.736, 95% CI 0.491-6.136; p = 0.392), overall reperfusion (aOR 3.173, 95% CI 0.752-13.387; p = 0.116), periinterventional complications, embolization into new territories, or symptomatic intracerebral hemorrhage. The use of BGC did not affect the results. CONCLUSION While previous analyses indicated that first-line SR thrombectomy may promise higher rates of reperfusion than contact aspiration in AIS patients with SVS, our data show no superiority of any particular SR-based retrieval technique regardless of SVS status

Beating the confusion limit: The necessity of high angular resolution for probing the physics of Sagittarius A* and its environment: Opportunities for LINC-NIRVANA (LBT), GRAVITY (VLTI) and and METIS (E-ELT)

The super-massive 4 million solar mass black hole (SMBH) SgrA* shows variable emission from the millimeter to the X-ray domain. A detailed analysis of the infrared light curves allows us to address the accretion phenomenon in a statistical way. The analysis shows that the near-infrared flux density excursions are dominated by a single state power law, with the low states of SgrA* limited by confusion through the unresolved stellar background. We show that for 8-10m class telescopes blending effects along the line of sight will result in artificial compact star-like objects of 0.5-1 mJy that last for about 3-4 years. We discuss how the imaging capabilities of GRAVITY at the VLTI, LINC-NIRVANA at the LBT and METIS at the E-ELT will contribute to the investigation of the low variability states of SgrA*.Comment: 19 pages, 5 figure, Conf. Proc. SPIE Astronomical Telescopes + Instrumentation 1 - 6 July 2012. Amsterdam No. 8445-

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Pharmaceuticals in sewage systems and surface waters – status quo

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First direct detection of an exoplanet by optical interferometry; Astrometry and K-band spectroscopy of HR8799 e

To date, infrared interferometry at best achieved contrast ratios of a few times $10^{-4}$ on bright targets. GRAVITY, with its dual-field mode, is now capable of high contrast observations, enabling the direct observation of exoplanets. We demonstrate the technique on HR8799, a young planetary system composed of four known giant exoplanets. We used the GRAVITY fringe tracker to lock the fringes on the central star, and integrated off-axis on the HR8799e planet situated at 390 mas from the star. Data reduction included post-processing to remove the flux leaking from the central star and to extract the coherent flux of the planet. The inferred K band spectrum of the planet has a spectral resolution of 500. We also derive the astrometric position of the planet relative to the star with a precision on the order of 100$\,\mu$as. The GRAVITY astrometric measurement disfavors perfectly coplanar stable orbital solutions. A small adjustment of a few degrees to the orbital inclination of HR 8799 e can resolve the tension, implying that the orbits are close to, but not strictly coplanar. The spectrum, with a signal-to-noise ratio of $\approx 5$ per spectral channel, is compatible with a late-type L brown dwarf. Using Exo-REM synthetic spectra, we derive a temperature of $1150\pm50$\,K and a surface gravity of $10^{4.3\pm0.3}\,$cm/s$^{2}$. This corresponds to a radius of $1.17^{+0.13}_{-0.11}\,R_{\rm Jup}$ and a mass of $10^{+7}_{-4}\,M_{\rm Jup}$, which is an independent confirmation of mass estimates from evolutionary models. Our results demonstrate the power of interferometry for the direct detection and spectroscopic study of exoplanets at close angular separations from their stars.Comment: published in A&