Reversible low-light induced photoswitching of crowned spiropyran-DO3A complexed with gadolinium(III) ions.

Photoswitchable spiropyran has been conjugated to the crowned ring system DO3A, which improves its solubility in dipolar and polar media and stabilizes the merocyanine isomer. Adding the lanthanide ion gadolinium(III) to the macrocyclic ring system leads to a photoresponsive magnetic resonance imaging contrast agent that displays an increased spin-lattice relaxation time (T₁) upon visible light stimulation. In this work, the photoresponse of this photochromic molecule to weak light illumination using blue and green light emitting diodes was investigated, simulating the emission spectra from bioluminescent enzymes. Photon emission rate of the light emitting diodes was changed, from 1.75 × 10¹⁶ photons·s⁻¹ to 2.37 × 10¹² photons·s⁻¹. We observed a consistent visible light-induced isomerization of the merocyanine to the spiropyran form with photon fluxes as low as 2.37 × 10¹² photons·s⁻¹ resulting in a relaxivity change of the compound. This demonstrates the potential for use of the described imaging probes in low light level applications such as sensing bioluminescence enzyme activity. The isomerization behavior of gadolinium(III)-ion complexed and non-complexed spiropyran-DO3A was analyzed in water and ethanol solution in response to low light illumination and compared to the emitted photon emission rate from over-expressed Gaussia princeps luciferase

Controlled Delivery of Sdf-1 Alpha and Igf-1: Cxcr4(+) Cell Recruitment and Functional Skeletal Muscle Recovery

Therapeutic delivery of regeneration-promoting biological factors directly to the site of injury has demonstrated its efficacy in various injury models. Several reports describe improved tissue regeneration following local injection of tissue specific growth factors, cytokines and chemokines. Evidence exists that combined cytokine/growth factor treatment is superior for optimizing tissue repair by targeting different aspects of the regeneration response. The purpose of this study was to evaluate the therapeutic potential of the controlled delivery of stromal cell-derived factor-1alpha (SDF-1 alpha) alone or in combination with insulin-like growth factor-I (SDF-1 alpha/IGF-I) for the treatment of tourniquet-induced ischemia/reperfusion injury (TK-I/R) of skeletal muscle. We hypothesized that SDF-1 alpha will promote sustained stem cell recruitment to the site of muscle injury, while IGF-I will induce progenitor cell differentiation to effectively restore muscle contractile function after TK-I/R injury while concurrently reducing apoptosis. Utilizing a novel poly-ethylene glycol PEGylated fibrin gel matrix (PEG-Fib), we incorporated SDF-1 alpha alone (PEG-Fib/SDF-1 alpha) or in combination with IGF-I (PEG-Fib/SDF-1 alpha/IGF-I) for controlled release at the site of acute muscle injury. Despite enhanced cell recruitment and revascularization of the regenerating muscle after SDF-1 alpha treatment, functional analysis showed no benefit from PEG-Fib/SDF-1 alpha therapy, while dual delivery of PEG-Fib/SDF-1 alpha/IGF-I resulted in IGF-I-mediated improvement of maximal force recovery and SDF-1 alpha-driven in vivo neovasculogenesis. Histological data supported functional data, as well as highlighted the important differences in the regeneration process among treatment groups. This study provides evidence that while revascularization may be necessary for maximizing muscle force recovery, without modulation of other effects of inflammation it is insufficient.Kinesiology and Health Educatio

Evolution of phytosterols in Chardonnay grape berry skins during last stages of ripening

This study presents the results of rapid phytosterols analysis in grape skins during last stages of ripening. The analysis is related to the evolution of sterol content by comparison with ripening degree on two vineyards of Chardonnay grape variety in Burgundy: Meursault ler Cru and Hautes Cotes de Beaune. The characterization of sterols is realized by using combined gas chromatography-mass spectrometry from trimethylsilyl ethers of sterols. After optimization of extraction by azeotropic mixture (chloroform/methanol 2:1 v/v), the analysis allows to identify four sterols in grape skins: beta-sitosterol, campesterol, stigmasterol and lanosterol. In all the samples, beta-sitosterol is the major phytosterol (86 to 89 % of the total detected phytosterols). The evolution of phytosterols content during last stages of ripening shows a similar comportment of β-sitosterol, campesterol and stigmasterol in grape skins: the maturation induces a loss of phytosterols in grape skins. An increase of phytosterol contents occurs at peak maturity and can be related with over-maturation phenomenon. The relationship between phytosterol content in grape skins and S/A ratio indicates a markedly negative correlation

An Unusual Case of Pleuropulmonary Blastoma in a Child with Jejunal Hamartomas

We report a rare case of 9-month-old girl who presented with a choking episode and was found to have an incidental finding of a lung cyst and iron deficiency anemia leading to the diagnosis of pleuropulmonary blastoma (PPB) and a jejunal hamartoma. Our patient is the eighth that has been reported with the association of PPB with jejunal hamartoma and the first one in the radiological literature. PPB is the pulmonary analog of other dysontogenetic neoplasms in childhood. A biological sequence has been described with the three types of PPB to be interrelated as part of pathologic progression. PPB can be associated with other cysts and/or neoplasms in different organs. PPB is part of a hereditary neoplasia predisposition syndrome in up to 40% of cases. Mutations in DICER gene have been described with PPB. Hence, a pediatric patient diagnosed with PPB should be screened for associated conditions during childhood and adolescence including intestinal polyps. Obtaining family history for other neoplasms or cysts is important information that should raise the possibility of PPB in pediatric patients with cystic lung lesions. The presence of this syndrome should alert the clinician to screen and follow up patients and their relatives

A rat model of early stage osteonecrosis induced by glucocorticoids

<p>Abstract</p> <p>Background</p> <p>Glucocorticoid (GC)-induced osteonecrosis (ON) is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario.</p> <p>Methods</p> <p>To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis). Prednisone pellets (dosage of 1.82-2.56 mg/kg/day) were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E) staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate.</p> <p>Results</p> <p>The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes.</p> <p>Conclusions</p> <p>We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.</p

The effect of opioid therapy on sleep quality in patients with chronic non-malignant pain : a systematic review and exploratory meta-analysis

Current guidelines recommend opioid therapy to chronic non-malignant pain (CNP) patients when the benefits for pain and function outweigh risks. This systematic review examined the effects of opioid therapy on sleep – a valued functional outcome– in CNP. Electronic and hand searches of relevant studies up through July 2017 identified 18 eligible studies providing data from 3,746 CNP patients for analysis. Twelve of these studies were randomised controlled trials (RCTs) of up to 12-month in duration. Low-medium dosed oxycodone and transdermal fentanyl were the most tested therapies (n=4 each). Only two studies used objective sleep measure in addition to self-report ratings, questionnaires or sleep diary. Whilst calmer sleep with less body/leg movements and fewer awakenings could be achieved following opioid therapy, these might occur with increased sleep-disordered breathing and a much-shortened rapid eye movement (REM) sleep latency. Both the narrative synthesis and exploratory meta-analysis suggest that opioid therapy in CNP is associated with improved self-reported sleep quality. However, the effect is inconsistent, small (Standardised Mean Difference = 0.36), and may be accompanied by excessive daytime sleepiness. As a Cochrane-recommended assessment revealed “unclear” or “high” overall risk of bias for all studies, future opioid trials of stronger methodology and better reporting are needed to confirm and elucidate the effect

Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage

Nuclear pore complexes (NPCs) discriminate nonspecific macromolecules from importin and exportin receptors, collectively termed "karyopherins" (Kaps), that mediate nucleocytoplasmic transport. This selective barrier function is attributed to the behavior of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups) that guard the NPC channel. However, NPCs in vivo are typically enriched with different Kaps, and how they impact the NPC barrier remains unknown. Here, we show that two major Kaps, importinβ1/karyopherinβ1 (Kapβ1) and exportin 1/chromosomal maintenance 1 (CRM1), are required to fortify NPC barrier function in vivo. Their enrichment at the NPC is sustained by promiscuous binding interactions with the FG Nups, which enable CRM1 to compensate for the loss of Kapβ1 as a means to maintain NPC barrier function. However, such a compensatory mechanism is constrained by the cellular abundances and different binding kinetics for each respective Kap, as evidenced for importin-5. Consequently, we find that NPC malfunction and nucleocytoplasmic leakage result from poor Kap enrichment

Effect of FEM choices in the modelling of incremental forming of aluminium sheets

peer reviewedThis paper investigates the process of single point incremental forming of an aluminium cone with a 50-degree wall angle. Finite element (FE) models are established to simulate the process. Different FE packages have been used. Various aspects associated with the numerical choices as well as the material and process parameters have been studied. The final geometry and the reaction forces are presented as the results of the simulations. Comparison between the simulation results and the experimental data is also made

Decrease in ovalbumin-induced pulmonary allergic response by benzaldehyde but not acetaldehyde exposure in a guinea pig model

International audienceThe pulmonary effects of two environmentally relevant aldehydes were investigated in non-sensitized or ovalbumin (OA)-sensitized guinea pigs (GPs). Four-week-old male Hartley GPs, weighing about 400 g, were intraperitoneally injected with 1 ml of an NaCl solution containing 100 mug OA and 100 mg Al/(OH)(3). They were then exposed to either acetaldehyde (200 ppb) or benzaldehyde (500 ppb) (or 4 wk (6 h/d, 5 d/wk). At the end of exposure, GPs were challenged with an OA aerosol (0.1% in NaCl) and pulmonary functions were measured. The day after, guinea pigs were anesthetized and several endpoints related to inflammatory anti allergic responses were assessed in blood, whole-lung histology, and bronchoalveolar lavage (BAL). Sensitized nonexposed GPs showed bronchial hyperresponsiveness to OA and an increased number of eosinophils in blood and BAL, together with a rise in total protein and leukotrienes (LTB4 and LTC4/D-4/E-4) in BAL. In nonsensitized GPs, exposure to acetaldehyde or benzaldehyde did not induce any change in the tested parameters;, with the exception of irritation of the respiratory tract as detected by histology and an increased number of alveolar macrophages in animals exposed to acetaldehyde. In sensitized GPs, exposure to acetaldehyde induced a moderate irritation of the respiratory tract but no change in biological parameters linked to the inflammatory and allergic responses, In contrast, exposure to benzaldehyde induced a decrease both in OA-induced bronchoconstriction and in eosinophil and neutrophil numbers in BAL, an increase in the bronchodilatator mediator prostaglandin E-2 (PGE(2)) and a decrease in the bronchoconstrictor mediators LTC4/D-4/E-4. Further investigations are needed to determine if the attenuated response observed in sensitized GPs exposed to benzaldehyde is due to an alteration of the mechanism of sensitization or to a more direct effect on various mechanisms of the allergic response