Endothelium‐dependent and endothelium‐independent effects of 1‐nitro‐2‐propylbenzene on rat aorta

A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO₂ group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1‐nitro‐2‐propylbenzene (NPB), a nitro compound containing the NO₂ in the aromatic ring. In aorta precontracted with KCl, NPB (1‐3000 μm ) induced full endothelium‐independent relaxation. In endothelium‐intact preparations, phenylephrine‐induced contractions were fully relaxed by NPB, effect unaltered by N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). In the concentration range of 30–300 μm , NPB slightly but significantly potentiated the phenylephrine‐induced contraction. Such potentiation was unaltered by the thromboxane‐prostanoid receptor antagonist seratrodast, but was abolished by endothelium removal or by preincubation of endothelium‐intact preparations with L‐NAME, ODQ or by ruthenium red and HC‐030031, blockers of subtype 1 of ankyrin transient receptor potential (TRPA₁) channels. Verapamil exacerbated the potentiating effect of NPB. The potentiating effect was undetectable in preparations precontracted by 9,11‐dideoxy‐11α,9α‐epoxymethanoprostaglandin F2α (U‐46619). Relaxation was reduced by ruthenium red while it was enhanced by HC‐030031. In conclusion, NPB has vasodilator properties but with a mechanism of action distinct from its analogues. Contrary to other nitro compounds, its relaxing effects did not involve recruitment of the guanylyl cyclase pathway. NPB has also endothelium‐dependent potentiating properties on phenylephrine‐induced contractions, a phenomenon that putatively required a role of endothelial TRPA₁ channels. The present findings reinforce the notion that the functional group NO₂ in the aliphatic chain of these nitro compounds determines favorably their vasodilator properties.     

Long‐Term Care Quality‐of‐Life Scale utility in community home care

This study aimed to test the utility of the Long‐Term Care Quality‐of‐Life assessment scale within community home care contexts and to compare the scale against the World Health Organization Quality‐of‐Life scale in terms of reliability and validity. Both scales were administered concurrently to 109 older adults receiving home care. Analysis revealed the Long‐Term Care Quality‐of‐Life scale to have good test–retest reliability, modest but acceptable internal consistency, and pairwise comparison between the Long‐Term Care Quality‐of‐Life and World Health Organization Quality‐of‐Life scales' scores suggesting moderate‐to‐strong correlation of criterion validity and comparability between scales. The results showed that the assessment of individual perceptions of life quality within home care contexts can be monitored and recorded, and that Long‐Term Care Quality‐of‐Life scale monitoring in home and residential care can identify opportunities for quality‐of‐life support and care continuity, even with transitions between care services and systems. The implications of the present study lie in having access to a validated quality‐of‐life assessment scale that can be used across care contexts to support evidence‐based practice, continuity of care, and acknowledgement of individual circumstances in services and care planning.     

Profound Sinus Node Dysfunction in Anti‐N‐Methyl‐D‐Aspartate Receptor Limbic Encephalitis

A form of limbic encephalitis associated with antibodies against the N‐methyl‐D‐aspartate receptor (NMDAR) was discovered in 2007. It is often a multistage illness that progresses from psychosis, memory deficits, seizures into a state of unresponsiveness with catatonic features, abnormal movements, autonomic, and respiratory instability. We present two cases of anti‐NMDAR encephalitis to highlight the cardiac complications and their management.     

Additive manufacturing of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] scaffolds for engineered bone development

A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable polyesters produced by various bacteria grown under unbalanced conditions, have been proposed for the fabrication of tissue‐engineering scaffolds. In this study, the manufacture of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] (or PHBHHx) scaffolds, by means of an additive manufacturing technique based on a computer‐controlled wet‐spinning system, was investigated. By optimizing the processing parameters, three‐dimensional scaffolds with different internal architectures were fabricated, based on a layer‐by‐layer approach. The resulting scaffolds were characterized by scanning electron microscopy, which showed good control over the fibre alignment and a fully interconnected porous network, with porosity in the range 79–88%, fibre diameter 47–76 µm and pore size 123–789 µm. Moreover, the resulting fibres presented an internal porosity connected to the external fibre surface as a consequence of the phase‐inversion process governing the solidification of the polymer solution. Scaffold compressive modulus and yield stress and strain could be varied in a certain range by changing the architectural parameters. Cell‐culture experiments employing the MC3T3‐E1 murine pre‐osteoblast cell line showed good cell proliferation after 21 days of culture. The PHBHHx scaffolds demonstrated promising results in terms of cell differentiation towards an osteoblast phenotype. Copyright © 2014 John Wiley & Sons, Ltd.     

18F‐Fluorine‐18‐l‐dihydroxyphenylalanine (18F‐DOPA) positive isolated peritoneal carcinomatosis from a MENII‐related medullary thyroid carcinoma. About an atypical metastatic site and utility of 18F‐FDOPA

A patient, operated for a medullary thyroid carcinoma (MTC) with a positive RET mutation, showed several peritoneal nodes on a computed tomography (CT), with increased Thyrocalcitonine. A ¹⁸F‐Fluorine‐18‐l ‐dihydroxyphenylalanine (18‐F‐FDOPA) positron emission tomography (PET/CT) showed isolated tracer uptake on the nodes. A biopsy confirmed that it was from the MTC, with the same RET mutation as in blood.     

Endothelial colony‐forming cells for preparing prevascular three‐dimensional cell‐dense tissues using cell‐sheet engineering

Vascular‐derived endothelial cell (EC) network prefabrication in three‐dimensional (3D) tissue constructs before transplantation is useful for inducing functional anastomosis with the host vasculature. However, the clinical application of ECs is limited by cell isolation from the existing vasculature, because of the requirement for invasive biopsies and difficulty in obtaining a sufficient number of cells. Endothelial colony‐forming cells (ECFCs), which are a subtype of endothelial progenitor cells in the blood, have a strong proliferative and vasculogenic potential. This study attempted to fabricate prevascular 3D cell‐dense tissue constructs using cord blood‐derived ECFCs and evaluate the in vivo angiogenic potential of these constructs. Human umbilical vascular endothelial cells (HUVECs) were also used in comparison with ECFCs, which were sandwiched between two human dermal‐derived fibroblast (FB) sheets using a fibrin‐coated cell‐sheet manipulator. The inserted ECFCs in double‐layered FB sheets were cultured for 3 days, resulting in the formation of network structures similar to those of HUVECs. Additionally, when ECFCs were sandwiched with three FB sheets, a lumen structure was found in the triple‐layered cell‐sheet constructs at 3 days after co‐culture. These constructs containing ECFCs were transplanted into the subcutaneous tissue of immune‐deficient rats. One week after transplantation, ECFC‐lined functional microvessels containing rat erythrocytes were observed in the same manner as transplanted HUVEC‐positive grafts. These results suggest that ECFCs might become an alternative cell source for fabricating a prevascular structure in 3D cell‐dense tissue constructs for clinical application. Copyright © 2013 John Wiley & Sons, Ltd.     

Activation of PAR‐2 Elicits NO‐Dependent and CGRP‐Independent Dilation of the Dural Artery

(Headache 2010;50:1017‐1030) Objectives.— The goal of this study was to determine the vascular effects of protease‐activated receptor‐2 (PAR‐2) activation in the rat cranial vasculature. Background.— The role of PAR‐2 in pain and inflammatory conditions has been established but the information available on its effects and receptor distribution in the trigeminal vascular axis is limited. We studied the dilatory function and expression of PAR‐2 in the neuro‐vascular circuit, critical in migraine pathogenesis. We also investigated the interaction of PAR‐2 with calcitonin gene‐related peptide (CGRP) and dural mast cells. Methods.— We used an improved model of intravital microscopy on the closed cranial window in rats to study the vascular effects of PAR‐2 activating peptides (PAR‐2 APs; SLIGRL‐NH₂, 2‐Furoyl‐LIGRLO‐NH₂) in the dural vasculature. Measurement of immunoreactive CGRP in skull halves and in trigeminal nucleus caudalis was done by using an enzyme‐linked immunosorbent assay. We also analyzed the presence of PAR‐2 in different migraine relevant tissues by quantitative real‐time PCR and Western blot analysis. Results.— PAR‐2 APs and trypsin induced a dose‐dependent increase in dural artery diameter. The topical application of a nonspecific nitric oxide synthase (NOS) inhibitor, L‐N^G‐Nitroarginine methyl ester, attenuated SLIGRL‐NH₂ responses. Olcegepant, a CGRP receptor antagonist, did not a have significant effect on the SLIGRL‐NH₂ responses, though exogenous CGRP responses were completely blocked. There was no significant release of CGRP from skull halves incubated with SLIGRL‐NH₂ as compared with those incubated with the corresponding negative peptide. Chronic mast cell degranulation did not change the vascular effects of PAR‐2 APs. mRNA and protein expression of PAR‐2 were found throughout trigeminovasuclar axis. Conclusion.— PAR‐2 activation leads to vasodilation of dural arteries and these responses are partially mediated by nitric oxide. As PAR‐2 is present throughout trigeminovasuclar axis, it may have a role in migraine pathogenesis, independent of CGRP and mast cell mediated mechanism.