Approximately 75% of cutaneous rosacea patients also suffer from an ocular involvement with blepharitis and meibomian gland dysfunction often presented as chalazia. Clinical symptoms are foreign body sensation, light sensitivity, burning and tearing.
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Accurate distinction of epithelioid hemangioma (EH) from its malignant mimics is paramount but it remains challenging due to its wide morphological spectrum and lack of objective molecular markers. FOSB oncogenic activation was recently identified as a key event in endothelial proliferation. We sought to investigate the FOSB staining pattern in EH with angiolymphoid hyperplasia with eosinophilia morphology (EH-AHLE) and to evaluate its value in differential diagnosis of epithelioid vascular tumors.
From the authors' files, 15 representative cases of EH-ALHE were selected and evaluated for their FOSB immunostaining pattern. Other vascular proliferations which can be morphological mimics were also tested: epithelioid hemangioendothelioma (EHE) (5 cases) and epithelioid angiosarcoma (EAS) (5 cases).
All 15 cases of EH-ALHE showed strong and homogeneous FOSB nuclear positivity in endothelial cells with ample cytoplasm and intracytoplasmic vacuoles. All cases of EHE and EAS lacked FOSB immunoreactivity or showed only incidental weak FOSB immunoreactivity in less than 5 nuclei per lesion.
FOSB immunohistochemistry is sensitive in the diagnosis of EH-ALHE, and allows differentiation from its histological mimics. An immunohistochemical panel including not only pan-cytokeratin AE1/AE3 and endothelial markers, but also FOSB, helps in the diagnosis of epithelioid vascular tumors.
Publication date: Available online 11 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Sebastian Fantini, Valentina Salsi, Vincenzo Zappavigna
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Publication date: Available online 5 March 2018
Source:Acta Histochemica
Author(s): Reza Khorramirouz, Jason L. Go, Christopher Noble, Soumen Jana, Eva Maxson, Amir Lerman, Melissa D. Young
ObjectivesSubcutaneous implantations in small animal models are currently required for preclinical studies of acellular tissue to evaluate biocompatibility, including host recellularization and immunogenic reactivity.MethodsThree rat subcutaneous implantation methods were evaluated in six Sprague Dawley rats. An acellular xenograft made from porcine pericardium was used as the tissue-scaffold. Three implantation methods were performed; 1) Suture method is where a tissue-scaffold was implanted by suturing its border to the external oblique muscle, 2) Control method is where a tissue-scaffold was implanted without any suturing or support, 3) Frame method is where a tissue-scaffold was attached to a circular frame composed of polycaprolactone (PCL) biomaterial and placed subcutaneously. After 1 and 4 weeks, tissue-scaffolds were explanted and evaluated by hematoxylin and eosin (H&E), Masson's trichrome,Picrosirius Red, transmission electron microscopy (TEM), immunohistochemistry, and mechanical testing.ResultsMacroscopically, tissue-scaffold degradation with the suture method and tissue-scaffold folding with the control method were observed after 4 weeks. In comparison, the frame method demonstrated intact tissue scaffolds after 4 weeks. H&E staining showed progressive cell repopulation over the course of the experiment in all groups with acute and chronic inflammation observed in suture and control methods throughout the duration of the study. Immunohistochemistry quantification of CD3, CD 31, CD 34, CD 163, and αSMA showed a statistically significant differences between the suture, control and frame methods (P < 0.05) at both time points. The average tensile strength was 4.03 ± 0.49, 7.45 ± 0.49 and 5.72 ± 1.34 (MPa) after 1 week and 0.55 ± 0.26, 0.12 ± 0.03 and 0.41 ± 0.32 (MPa) after 4 weeks in the suture, control, and frame methods; respectively. TEM analysis showed an increase in inflammatory cells in both suture and control methods following implantation.ConclusionRat subcutaneous implantation with the frame method was performed with success and ease. The surgical approach used for the frame technique was found to be the best methodology for in vivo evaluation of tissue engineered acellular scaffolds, where the frame method did not compromise mechanical strength, but it reduced inflammation significantly.
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Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Giovanna Liguori, Simona Tafuri, Chika Miyoshi, Masashi Yanagisawa, Caterina Squillacioti, Valeria De Pasquale, Nicola Mirabella, Alfredo Vittoria, Anna Costagliola
The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin, were originally described in the rat hypothalamus. Successively, they have been found in many other brain regions as well as in peripheral organs of mammals and other less evolved animals. The widespread localization of orexins accounts for the multiple activities that they exert in the body, including the regulation of energy homeostasis, feeding, metabolism, sleep and arousal, stress, addiction, and cardiovascular and endocrine functions. Both OXA and OXB peptides bind to two G-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R) receptor, though with different binding affinity. Altered expression/activity of orexins and their receptors has been associated with a large number of human diseases. Though at present evidence highlighted a role for orexins and cognate receptors in mammalian reproduction, their central and/or local effects on gonadal functions remain poorly known. Here, we investigated the localization of OXB and OX2R in the rat epididymis. Immunohistochemical staining of sections from caput, corpus and cauda segments of the organ showed intense signals for both OXB and OX2R in the principal cells of the lining epithelium, while no staining was detected in the other cell types. Negative results were obtained from immunohistochemical analysis of hypothalamic and testicular tissues from OX2R knock-out mice (OX2R−/−) and OX1R/OX2R double knock-out (OX1R−/−; OX2R−/−) mice, thus demonstrating the specificity of the rabbit polyclonal anti-OX2R antibody used in our study. On contrary, the same antibody clearly showed the presence of OX2R in sections from hypothalamus and testis of normal mice and rats which are well known to express the receptor. Thus, our results provide the first definite evidence for the immunohistochemical localization of OXB and OX2R in the principal cells of rat epididymis.
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Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Leniz F. Nurullin, Evgeny E. Nikolsky, Artem I. Malomouzh
It is generally accepted that gamma-aminobutyric acid (GABA) is a signaling molecule abundant in central synapses. In a number of studies though, it has been shown that GABA signaling functions in the peripheral nervous system as well, in particular, in the synapses of sympathetic ganglia. However, there exists no firm evidence on the presence of GABAergic signaling cascade in the intercellular junctions of the somatic nerve system.By the use of immunohistochemistry methods, in the synaptic area of cholinergic neuromuscular contact in rat diaphragm, we have detected glutamate decarboxylase, the enzyme involved in synthesis of GABA, molecules of GABA, and also GAT-2, a protein responsible for transmembrane transport of GABA. Earlier we have also shown that metabotropic GABAB receptors have overlapping localization in the same compartment. Moreover, activation of GABAB receptors affects the intensity of acetylcholine release. These data taken together, allows us to suggest that in the mammalian cholinergic neuromuscular junction, GABA is synthesized and performs certain synaptic signaling function.
Publication date: Available online 25 February 2018
Source:Acta Histochemica
Author(s): Lucio Díaz-Flores, Ricardo Gutiérrez, M.ª Pino García, M. González-Gómez, Francisco J. Sáez, Lucio Díaz-Flores, José Luis Carrasco, Juan F. Madrid
Sinusoidal hemangioma, characterized by interconnecting thin-walled vascular spaces, may present papillae/pseudo-papillae and zones that resemble intravascular papillary endothelial hyperplasia (IPEH). Our objectives are to explore the existence of zones in IPEH with sinusoidal hemangioma characteristics, the mechanism of papillary and septa formation in sinusoidal hemangioma and the comparison of this mechanism with that in IPEH. For these purposes, specimens of 4 cases of each entity were selected and studied by serial histologic sections and by immunochemistry and immunofluorescence procedures. The results showed a) zones with characteristics of sinusoidal hemangioma in IPEH cases, b) presence in both entities of papillae with a cover formed by a monolayer of CD34+ and CD31+ endothelial cells (ECs) and a core formed by either type I collagen and αSMA+ cells (presenting a pericyte/smooth muscle cell aspect) or thrombotic components, and c) a similar piecemeal angiogenic mechanism in papillary formation, including sprouting of intimal ECs toward the vessel wall itself or intravascular thrombi, formation of vascular loops that encircle and separate vessel wall or thrombus components, and parietal or thrombotic papillae development. The major differences between both entities were the number, arrangement and substrate of papillae: myriad, densely grouped, parietal and thrombotic papillae in IPEH, and a linear arrangement of predominant parietal papillae in sinusoidal hemangioma, originating septa (segmentation). In conclusion, sinusoidal hemangioma and IPEH are interrelated processes, which share morphologic findings and a piecemeal angiogenic mechanism, combining sprouting and intussusceptive angiogenesis, and leading to papillary formation and vessel segmentation.
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Publication date: Available online 1 February 2018
Source:Acta Histochemica
Author(s): Rahime Sekerci, Nuray Acar, Filiz Tepekoy, Ismail Ustunel, Nigar Keles-Celik
Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work.In our experimental study, a total of 35 (hypertensive group: 20, control group: 15) Rattus Norvegicus Wistar albino rats were used. In order to obtain our hypertension model, our experimental animals were given L-NAME together with drinking water for six weeks. After six weeks, the experimental procedures were terminated. Heart and kidney tissues of the hypertensive and control group were obtained. Expression of apelin and apelin receptor (APJ) was demonstrated by immunohistochemical and Western Blot protocols.Hypertrophic cardiac atrium of the hearts of the large cavities, interventricular septum and myocardium to the disintegration, as well as an increase in the diameter of the coronary artery has been observed. In general, kidney tissues of the hypertensive group showed narrowing in cortical renal structures and enlargement in structures in the renal medulla.As a result, in hypertensive cases, there was an increase in expression of Apelin and APJ receptor in heart tissue, and a decrease in expression of Apelin and APJ receptor in kidney tissue. We think that our findings may contribute to experimental or clinical studies related to hypertension and apelin.
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Publication date: Available online 11 March 2018
Source:Free Radical Biology and Medicine
Author(s): Arnold Groehler, Stefan Kren, Qinglu Li, Maggie Robledo-Villafane, Joshua Schmidt, Mary Garry, Natalia Tretyakova
Myocardial infarction (MI) is a life-threatening condition that can occur when blood flow to the heart is interrupted due to a blockage in one or more of the coronary vessels. Current treatments of MI rapidly restore blood flow to the affected myocardium using thrombolytic agents or angioplasty. Adverse effects including inflammation, tissue necrosis, and ventricular dysfunction are, however, not uncommon following reperfusion therapy. These conditions are thought to be caused by a sudden influx of reactive oxygen species (ROS) to the affected myocardium. We employed the model of left anterior descending artery ligation/reperfusion surgery in a rat model to show that ischemia/reperfusion injury is associated with the formation of toxic DNA-protein cross-links (DPCs) in cardiomyocytes. Mass spectrometry based experiments have revealed that these conjugates were formed by a free radical mechanism and involved thymidine residues of DNA and tyrosine side chains of proteins (dT-Tyr). Quantitative proteomics experiments have identified nearly 90 proteins participating in hydroxyl radical-induced DPC formation, including ROS scavengers, contractile proteins, and regulators of apoptosis. Global proteome changes were less pronounced and included increased expression of mitochondrial proteins required for aerobic respiration and biomarkers of sarcomere breakdown following ischemia/reperfusion injury. Overall, our results are consistent with a model where sudden return of oxygen to ischemic tissues induces oxidative stress, inflammation, and the formation of DNA-protein cross-links that may contribute to reperfusion injury by dysregulating gene expression and inducing cardiomyocyte death.
Publication date: Available online 10 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Romain Rivoirard, Julien Langrand-Escure, Mathieu Oriol, Fabien Tinquaut, Franck Chauvin, Chloé Rancoule, Nicolas Magné, Aurélie Bourmaud
ObjectiveTo describe the current state of knowledge concerning the quality of reporting in phase II clinical trials in oncology and to describe the various methods published allowing this quality evaluation.Methodsdatabases including MEDLINE and COCHRANE were searched. Reviews and meta-analyses analyzing the quality of the reporting of phase II trials in oncology were included. Descriptive analysis of the results was performed.ResultsThirteen publications were retained. Only 2 publications adopted a systematic approach of evaluation of the quality of reporting by overall scores. The Key Methodological Score (KMS), proposed by Grellety et al., gathering 3 items, seemed adapted for such an evaluation. A score of 3/3 was found in 16.1% of the 156 phase II trials analyzed by this score. The other reviews used a qualitative analysis to evaluate the reporting, via an analysis of a single criterion, generally the statistical plan of the study. This item was considered as having been correctly reported in less than 50% of the analyzed articles.ConclusionThe quality of reporting in phase II trials in oncology is a field that has been investigated very little (13 publications). When it is studied, the estimated level of quality is not satisfactory, whatever the method employed. The use of an overall score of evaluation is a path which should be pursued, in order to get reliable results. It also seems necessary to propose strong recommendations, which would create a consensus for the methodology and the reporting of these studies.
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Publication date: April 2018
Source:Neoplasia, Volume 20, Issue 4
Author(s): Tonje S. Steigedal, Jimita Toraskar, Richard P. Redvers, Marit Valla, Synnøve N. Magnussen, Anna M. Bofin, Signe Opdahl, Steinar Lundgren, Bedrich L. Eckhardt, John M. Lamar, Judy Doherty, Richard O. Hynes, Robin L. Anderson, Gunbjørg Svineng
Most cancer patients with solid tumors who succumb to their illness die of metastatic disease. While early detection and improved treatment have led to reduced mortality, even for those with metastatic cancer, some patients still respond poorly to treatment. Understanding the mechanisms of metastasis is important to improve prognostication, to stratify patients for treatment, and to identify new targets for therapy. We have shown previously that expression of nephronectin (NPNT) is correlated with metastatic propensity in breast cancer cell lines. In the present study, we provide a comprehensive analysis of the expression pattern and distribution of NPNT in breast cancer tissue from 842 patients by immunohistochemical staining of tissue microarrays from a historic cohort. Several patterns of NPNT staining were observed. An association between granular cytoplasmic staining (in <10% of tumor cells) and poor prognosis was found. We suggest that granular cytoplasmic staining may represent NPNT-positive exosomes. We found that NPNT promotes adhesion and anchorage-independent growth via its integrin-binding and enhancer motifs and that enforced expression in breast tumor cells promotes their colonization of the lungs. We propose that NPNT may be a novel prognostic marker in a subgroup of breast cancer patients.
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Publication date: Available online 10 March 2018
Source:Human Pathology
Author(s): Junko Aida, Tatsuro Ishizaki, Tomio Arai, Kaiyo Takubo
Endoscopic resection (ER) has become the standard therapy for superficial Barrett's carcinoma (BC) in Japan and other countries. Patients undergoing ER sometimes require additional treatment because of recurrence of lymph node metastasis (LNM). We attempted to clarify the histopathologic risk factors for LNM, and the difference between these risk factors for Japanese patients and the conventional risk factors documented for Western patients. This multi-center study included 12 leading institutions belonging to the Japan Research Society for Early Esophageal Cancer and Chromoendoscopy, and was based on a questionnaire designed to gather data on the features of superficial BC cases, except for high-grade intraepithelial neoplasia, treated at those institutions. These features were assessed using the standardized pathologic approach employed in Japan, whereby surgically and endoscopically resected specimens are cut into parallel slices 4–5mm and 2mm thick, respectively. Seventy-four surgically resected (SR) and 201 ER specimens were analyzed separately. Significant risk factors for LNM were almost the same as conventional risk factors, such as tumor size (cut-off value; 17.5mm) and depth, vessel infiltration, presence of poorly differentiated components, and the depth (cut-off value; 990μm) and width (cut-off value; 4300μm) of the submucosal component, in addition to growth pattern (a protruding or flat elevated pattern) and the presence of infiltrative growth. Histopathologic examination revealed that BC cases without invasion to the deep muscularis mucosae (DMM) had almost no risk of LNM. Detailed histopathologic evaluation of thin-slice preparations of ER specimens is considered highly important for prognostication.
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Publication date: 15 August 2018
Source:Food Chemistry, Volume 257
Author(s): H. Vojoudi, A. Badiei, A. Amiri, A. Banaei, G.M. Ziarani, K. Schenk-Joß
A simple, cheap and efficient method for pre-concentrating and separating Zn(II) ions from aqueous solutions and real samples has been designed. The method was implemented in a prototype featuring interchangeable chromatography-column-like cartridges, filled with meso-porous silica nanostructures, allowing easy exchange of the type and quantity of the sorbent. The adsorbents inside the column are held in place by means of porous polymer nano-fibre membranes. The effects of various parameters on the adsorption of Zn(II) ions from aqueous solutions were investigated. Maximal adsorption (∼99%) was found for Zn(II) ions amongst a mixture of Cu(II), Co(II), Ni(II), Ag(I), Au(III), Pd(II) and Pb(II) in aqueous solution. The procedure was tested for pre-concentrating and determining traces of zinc in real samples of meat, fish and hen marketed in Tehran. A desorption process using 0.5 mol L−1 HCl as eluent, showed ∼97% recovery of the Zn(II) ions adsorbed on the MSMPP sorbent.
Summary: Breast reconstruction that leaves no visible scars on the breast is possible for a subset of patients. This article reviews a cohort of 10 patients who underwent 14 autologous breast reconstructions. To achieve a reconstruction without visible breast scars, the mastectomy and autologous reconstruction are carried out through a periareolar incision. At the completion of the reconstruction, a small skin paddle is externalized through the mastectomy incision and in a subsequent stage entirely incorporated into a nipple areola reconstruction. Following completion of the breast and nipple areola reconstruction, a tattoo is performed that extends beyond the perimeter of the reconstructed areola and conceals all scars on the breast mound. The ideal candidate for this technique has a small or medium size breast, which is non- or minimally ptotic, and a donor site that can yield a flap larger than the volume of the native breast. In properly selected patients, this technique consistently yields high-quality results, which match or even surpass the aesthetics of the original breast.
Background: The lateral arm flap is used for composite defects in need of vascularized soft tissue, skin, and bone. From its original description, the distal humeral metaphysis can be included with the flap, supplied by the periosteal extensions of the posterior branch of the radial collateral artery. We sought to reexplore the anatomy of the lateral arm to determine its utility as a donor site for vascularized bone. Methods: Twelve fresh, silicone-injected cadaver dissections were performed. Arteriovenous anatomy, pedicle length and diameter, and anatomic variability as well as photo documentation was recorded. Results: The distal extent of the deltoid, lateral intermuscular septum and lateral humeral epicondyle were identified before the dissection. A septocutaneous perforator was consistently located 10 cm proximal to the lateral humeral epicondyle, which could be used for a skin paddle to monitor. Harvest of a 1.5 cm × 2 cm corticocancellous bone graft was performed. Average pedicle length was 9.1 ± 1.1 cm, and average pedicle diameter was 1.74 ± 0.52 mm. The inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm were consistently identified and preserved. Conclusion: The predictable anatomy of the lateral distal humerus make it an ideal donor site for small segments of vascularized bone.
Publication date: Available online 10 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Lars Norgen
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Publication date: Available online 10 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Y.Y. Go, P. Lancellotti
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Publication date: Available online 10 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): John D. Kakisis, George Geroulakos
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Ectodermal dysplasia (ED) is a heterogeneous group of disorders caused by mutations in at least thirteen genes. Recently, a study reported Palestinian patients with ED from consanguineous families with a homozygous mutation in KREMEN1 (Kringle-containing transmembrane protein 1) and proposed it to be a causative gene for the autosomal recessive ED 13, hair/tooth type (ECTD13; OMIM #617392). A Thai family, parents and two children affected with ED, was recruited. The study was exempted from review by the Institutional Review Board, Faculty of Medicine, Chulalongkorn University (IRB584/60). Written informed consents of each participant were obtained according to the Declaration of Helsinki. Mutation analyses were performed as described previously.
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Psoriasis is a prevalent chronic inflammatory disease associated with comorbidities, e.g. cardiometabolic diseases, inflammatory bowel disease, and depression that may share an inflammatory origin. Smoking increases the risk of psoriasis and the disease has also been linked to chronic obstructive pulmonary disease (COPD) and asthma, with evidence of shared inflammatory cytokine-mediated mechanisms. Moreover, subjects with psoriasis display increased risk of infections, especially respiratory infections including pneumonia. However, only a small single-center study of pulmonary function in subjects with psoriasis is available.
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We present the case of a 73-year-old-woman, admitted in 2014 for n erysipelas of the face (figure 1a) beginning 3 days before, with red oedematous papules of the left temple, hyperthermia and chills the day after. Clinical examination did not find lymphadenopathy or skin lesion especially at her left ear. Blood samples showed a raised C reactive protein (CRP) to 120 mg/L without leukocytosis. Antinuclear antibodies were negative. Viral serologies (HIV, hepatitis C and B, EBV, parvovirus B19, VZV, mumps), viral PCR assay (EBV, parvovirus B19, CMV, VZV) and bacterial blood cultures were all negative Histopathological findings revealed a reactive infiltrate without vasculitis and necrosis.
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patients with moderate to severe psoriasis are difficult to treat with topical therapy only and they usually require additional systemic therapy. Despite this, a significant percentage of patients on these therapies shows an inadequate response to these drugs. Treatment decisions are often difficult as they usually rely on subjective terms. Therefore, finding indicators that predict efectiveness or failure to classical systemic therapy is an urgent need. The objective of this study was to analyse whether the phenotype of peripheral blood mononuclear cells (PBMC) would be different in responder or non-responder patients to classical systemic therapy, and thus could be used as a efectiveness predictor of this therapy effectiveness. These predictor markers could help physicians to choose the best individualised treatment for psoriasis patients.
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In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward directed basal layer expansion. It is not known if this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC).
To characterize the prevalence of downward directed basal layer expansion of AKs adjacent to iSCC.
The epidermis overlying and adjacent to iSCCs was assessed histologically. We determined the histological grade (AKI-III), basal growth pattern (PROI-III) and accompanying parameters such as adnexal involvement.
Of 307 lesions, 52.4% of AKs were histologically classified as AKI, 38.1% as AKII, and 6.8% as AKIII (chi-squared; P<0.0001). 2.6% of adjacent epidermis did not show any atypical keratinocytes. The epidermis adjacent to iSCCs was classified as having a PROI basal growth pattern in 25.7%, PROII in 31.9%, and PROIII in 39.4% cases. 2.9% of AKs showed no basal growth (chi-squared; P<0.0001).118 (48.8%) AKs showed extension into adnexal structures. These AKs were graded as PROI in 18.6%, PROII in 30.5%, and PROIII in 50.8%. The epidermis above iSCCs could only be assessed for upwards directed growth and showed no significant differences in the three AK grades (P=0.4211).
Basal proliferative AKs as well as atypical keratinocytes restricted to the lower third of the epidermis are most commonly seen adjacent to iSCC with less evidence for full thickness epidermal dysplasia. Our study supports the important role of dysplastic keratinocytes in the epidermal basal layer and their potential association with iSCC.
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Our knowledge of Eosinophilic fasciitis (EF), also known as Shulman's syndrome, is limited, and its prevalence has not been estimated so far. We conducted a regional survey which aimed at estimating the prevalence of EF in Alsace, a Region in the North-East of France. We retrospectively collected EF cases from the first of January 1983 to the 30th of March 2015 among Alsace residents aged >18 years, then performed a capture-recapture analysis with the prevalent cases in 2015.
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Publication date: Available online 11 March 2018
Source:Acta Biomaterialia
Author(s): Jiang Wu, Zecong Xiao, Anqi Chen, Huacheng He, Chaochao He, Xintao Shuai, Xiaokun Li, Shengfu Chen, Yanxian Zhang, Baiping Ren, Jie Zheng, Jian Xiao
Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds.SignificanceDevelopment of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.
Publication date: Available online 3 February 2018
Source:Neuroscience Research
Author(s): Toshio Kosaka, Katsuko Kosaka
Secretagogin (SCGN) is a recently discovered calcium binding protein of the EF hand family, cloned from β cells of pancreatic island of Langerhans and endocrine cells of the gastrointestinal gland. SCGN characterizes some particular neuron groups in various regions of the nervous system and is considered as one of the useful neuron subpopulation markers. In the present study we reported that SCGN specifically labelled a particular neuronal cluster in the brainstem of the mice and rats. The comparison of the SCGN immunostaining with the choline acetyltransferase immunostaining and acetylcholinesterase staining clearly indicated that the particular cluster of SCGN positive neurons corresponded to the microcellular tegmental nucleus (MiTg) and the ventral portion of the cuneiform nucleus (CnF), both of which are components of the isthmus. The analyses in mice indicated that SCGN positive neurons in the MiTg and CnF were homogeneous in size and shape, appearing to compose a single complex: their somata were small comparing with the adjacent cholinergic neurons in the pedunculotegmantal nucleus, 10.5 vs 16.0 μm in diameter, and extended 2–3 slender smooth processes. SCGN might be one of significant markers to reconsider the delineations of the structures of the mouse, and presumably rat, brainstem.
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