Merkel cell carcinoma is a rare and aggressive neuroendocrine tumor that commonly arises in the skin. It is rare for it to occur in the testes. There are only seven cases of testicular Merkel cell carcinoma re...
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Σάββατο 5 Νοεμβρίου 2016
Recurrent Merkel cell carcinoma of the testis with unknown primary site: a case report
Saliva initiates the formation of pro-inflammatory macrophages in vitro
Source:Archives of Oral Biology, Volume 73
Author(s): Solmaz Pourgonabadi, Heinz-Dieter Müller, João Rui Mendes, Reinhard Gruber
ObjectivesSaliva can support oral wound healing, a process that requires a temporary inflammatory reaction. We have reported previously that saliva provokes a strong inflammatory response in oral fibroblasts. Bone marrow cells also give rise to macrophages, a heterogeneous subset of cell population involved in wound healing. Lipopolysaccharide (LPS) and interleukin 4 (IL-4) induce activation of pro-(M1), and anti-(M2) inflammatory macrophages, respectively. Yet, the impact of saliva on programming bone marrow cells into either M1 or M2 macrophages remains unclear .DesignHerein, we examined whether sterile saliva affects the in vitro process of macrophage polarization based on murine bone marrow cultures and RAW264.7 mouse macrophages.ResultsWe report that sterile saliva, similar to lipopolysaccharides, provoked a robust activation of the M1 phenotype which is characterized by a strong increase of the respective genes IL-12 and IL-6, based on a real-time gene expression analysis, and for IL-6 with immunoassay. Arginase-1 and Ym1, both genes characteristic for the M2 phenotype, were not considerably modulated by saliva. Inhibition of TLR4 signaling with TAK-242, blocking NFκB signaling with Bay 11-7085, but also autoclaving saliva greatly reduced the development of the M1 phenotype.ConclusionThese data suggest that saliva activates the TLR4 dependent polarization into pro-inflammatory M1 macrophages in vitro.
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Saliva initiates the formation of pro-inflammatory macrophages in vitro
Source:Archives of Oral Biology, Volume 73
Author(s): Solmaz Pourgonabadi, Heinz-Dieter Müller, João Rui Mendes, Reinhard Gruber
ObjectivesSaliva can support oral wound healing, a process that requires a temporary inflammatory reaction. We have reported previously that saliva provokes a strong inflammatory response in oral fibroblasts. Bone marrow cells also give rise to macrophages, a heterogeneous subset of cell population involved in wound healing. Lipopolysaccharide (LPS) and interleukin 4 (IL-4) induce activation of pro-(M1), and anti-(M2) inflammatory macrophages, respectively. Yet, the impact of saliva on programming bone marrow cells into either M1 or M2 macrophages remains unclear .DesignHerein, we examined whether sterile saliva affects the in vitro process of macrophage polarization based on murine bone marrow cultures and RAW264.7 mouse macrophages.ResultsWe report that sterile saliva, similar to lipopolysaccharides, provoked a robust activation of the M1 phenotype which is characterized by a strong increase of the respective genes IL-12 and IL-6, based on a real-time gene expression analysis, and for IL-6 with immunoassay. Arginase-1 and Ym1, both genes characteristic for the M2 phenotype, were not considerably modulated by saliva. Inhibition of TLR4 signaling with TAK-242, blocking NFκB signaling with Bay 11-7085, but also autoclaving saliva greatly reduced the development of the M1 phenotype.ConclusionThese data suggest that saliva activates the TLR4 dependent polarization into pro-inflammatory M1 macrophages in vitro.
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Possible association between successful intubation via the right nostril and anatomical variations of the nasopharynx during nasotracheal intubation: a multiplanar imaging study
Abstract
Purpose
Most reported cases of nasopharyngeal laceration following impingement during nasotracheal intubation involved tube insertion via the right nostril. We postulated that recesses on the posterior wall of the nasopharynx might be associated with tube impingement. Using multiplanar imaging and clinical statistics, we evaluated whether anatomical variations in the recesses are related to successful intubation via the right nostril.
Methods
Using multiplanar computed tomography (CT) images of 97 patients, we investigated the locations of recesses relative to the mid-sagittal plane, nasal floor plane and posterior end of the nasal septum, and their shapes. Incidents of impingement of the tube during nasotracheal intubation and the shapes of the fossa of Rosenmüller on CT images were retrospectively evaluated in 170 patients.
Results
Eustachian tube orifices were located approximately 10 mm laterally from the sagittal plane, and approximately 10 mm above the nasal floor plane. The fossa of Rosenmüller was vertically elongated and located 7 mm laterally from the mid-sagittal plane. Pharyngeal bursae were found in 15 % of the subjects. Patients with failed insertion via the right nostril due to impingement frequently had a wide opening of the fossa of Rosenmüller.
Conclusions
Successful intubation via the right nostril is related to the anatomy of structures on the posterior nasopharyngeal wall, particularly recesses located close to the path of nasotracheal tube insertion. Nasopharyngeal anatomical variations should be considered when one notices any resistance to advancement of the tube into the nasopharynx during nasotracheal intubation.
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Bilateral vallecular cysts
Publication date: Available online 5 November 2016
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Lucas Spina, Vinícius Zanin Martins, Julio Defaveri, Regina Helena Garcia Martins
http://ift.tt/2eq5EXp
Effects of exposure to 2100MHz GSM-like radiofrequency electromagnetic field on auditory system of rats
Publication date: Available online 5 November 2016
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Metin Çeliker, Abdulkadir Özgür, Levent Tümkaya, Suat Terzi, Mustafa Yılmaz, Yıldıray Kalkan, Ender Erdoğan
IntroductionThe use of mobile phones has become widespread in recent years. Although beneficial from the communication viewpoint, the electromagnetic fields (EMF) generated by mobile phones may cause unwanted biological changes in the human body.ObjectiveIn this study, we aimed to evaluate the effects of 2100MHz Global System for Mobile communication (GSM-like) electromagnetic field (EMF), generated by an EMF generator, on the auditory system of rats by using electrophysiological, histopathologic and immunohistochemical methods.MethodsFourteen adult Wistar albino rats were included in the study. The rats were divided randomly into two groups of seven rats each. The study group was exposed continuously for 30days to a 2100MHz EMF with a signal level (power) of 5.4dBm (3.47mW) to simulate the talk mode on a mobile phone. The control group was not exposed to the aforementioned EMF. After 30days, the Auditory Brainstem Responses (ABRs) of both groups were recorded and the rats were sacrificed. The cochlear nuclei were evaluated by histopathologic and immunohistochemical methods.ResultsThe ABR records of the two groups did not differ significantly. The histopathologic analysis showed increased degeneration signs in the study group (p=0.007). In addition, immunohistochemical analysis revealed increased apoptotic index in the study group compared to that in the control group (p=0.002).ConclusionThe results support that long-term exposure to a GSM-like 2100MHz EMF causes an increase in neuronal degeneration and apoptosis in the auditory system.
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Prevalence of areca nut chewing habit among high school children of Parsa district of Nepal
Publication date: Available online 5 November 2016
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Sartaj Singh Wazir, Pallak Arora, Shalini Kapoor, Raviraj Jayam, Sugandha Sharma, Trisha Rastogi
AimConsumption of areca nut products among school going children has become very common social evil in some areas of Nepal especially adjoining the Indian subcontinent. The aim of this study was to assess the prevalence of areca nut chewing habit among high school children in Terai belt of Nepal. The use of areca nut has become indigenous in this part and is being used by itself and in various formulations. The regular use of areca nut has been recognized as being carcinogenic to humans.Materials and methodsData on areca nut chewing habit among high school children was collected from 1359 students of age group 14–18 years from 13 schools of Parsa district of Nepal by random selection and the information was obtained from self administered questionnaire.ResultsThe results from this study shows that the areca nut chewing habit is significant among the students of Parsa district (30.4%) and the frequency of chewing plain Supari was reported to be high (81.6%) followed by pan masala (10.4%) and gutkha (08.0%) and the habit increased with age.ConclusionIt is mandatory to motivate the children not to initiate the habit and to enable the adolescent children to realize the potential health risk of areca nut products.
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Deoxynivalenol and its metabolite deepoxy-deoxynivalenol: multi-parameter analysis for the evaluation of cytotoxicity and cellular effects
Abstract
The mycotoxin deoxynivalenol (DON) contaminates agricultural commodities worldwide, posing health threats to humans and animals. Associated with DON are derivatives, such as deepoxy-deoxynivalenol (DOM-1), produced by enzymatic transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Using differentiated porcine intestinal epithelial cells (IPEC-J2), we provide the first multi-parameter comparative cytotoxicity analysis of DON and DOM-1, based on the parallel evaluation of lysosomal activity, total protein content, membrane integrity, mitochondrial metabolism and ATP synthesis. The study investigated the ability of DON and—for the first time of its metabolite DOM-1—to induce apoptosis, mitogen-activated protein kinase (MAPK) signalling, oxidative events and alterations of mitochondrial structure in porcine intestinal epithelial cells (IECs). The degree of DON toxicity strongly varied, depending on the cytotoxicity parameter evaluated. DON compromised viability according to the parameters of lysosomal activity, total protein content and membrane integrity, but increased viability according to assays based on mitochondrial metabolism and ATP synthesis. DON induced expression of cleaved caspase-3 (maximum induction 3.9-fold) and MAPK p38 and p42/p44 (maximum induction 2.51- and 2.30-fold, respectively). DON altered mitochondrial morphology, but did not increase intracellular ROS. DOM-1-treated IPEC-J2 remained unaffected at equimolar concentrations in all assays, thereby confirming the safety of feed additives using DON- to DOM-1-transforming bacteria. The study additionally highlights that an extensive multi-parameter analysis significantly contributes to the quality of in vitro data.
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Risk of failure of adenotonsillectomy for obstructive sleep apnea in obese pediatric patients
Publication date: January 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): C.J. Lennon, R.Y. Wang, A. Wallace, S. Chinnadurai
IntroductionPediatric obesity is a leading risk factor for obstructive sleep apnea (OSA), a condition commonly treated with adenotonsillectomy (T&A). It has been hypothesized that obesity increases a child's risk of failing T&A for OSA, however this relationship has not yet been quantified. The primary objective of this study was to investigate the relationship between obesity as measured by perioperative Body Mass Index (BMI) and persistent OSA following T&A as measured by polysomnography (PSG).Study designRetrospective chart review.MethodsPediatric patients who underwent T&A between Jan. 2004 and Jan. 2016 were included. We recruited both obese and non-obese patients to compare caregiver/self reported improvement. Obese patients were recruited from a weight management clinic and included if they had a BMI z-score >1.65 and had pre- and post-operative polysomnograms (PSGs). Control patients included those undergoing T&A for OSA at our institution with BMI <1.65. These patients were age matched to the obese patient population. Age, gender, perioperative BMI z-score, caregiver/self reported improvement, total Apnea-Hypopnea Index (AHI), and O2 saturation nadir were collected where available. Univariate linear regressions were calculated between perioperative BMI z-score and PSG data.Results26 obese study and 47 control subjects were identified for analysis. T&A resulted in statistically significant improvements in total AHI (p = 0.030) and nadir O2 saturation (p = 0.013) in obese subjects. There was no significant difference between the rate of caregiver/self reported improvement in the two groups. There was a statistically significant correlation between perioperative BMI z-score and the change in total AHI (p = 0.049). Within our population, for every increase by 0.1 in perioperative BMI z-score, the improvement in total AHI post-operatively decreased by 1.63 events/hr. Further, patients with BMI more than 3 standard deviations away from the age-derived normative mean received essentially no benefit from T&A alone.ConclusionsOur study established an inverse linear relationship between perioperative BMI z-score and improvement in total AHI with essentially no improvement in patients with BMI z-scores >3. Further studies are required to further elucidate this relationship and investigate the role of additional procedures in the initial management of OSA in obese children.
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The utility of a handheld metal detector in detection and localization of pediatric metallic foreign body ingestion
Publication date: January 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 92
Author(s): Javan Nation, Wen Jiang
ObjectiveTo test the ability of a handheld metal detector (HHMD) to identify the presence and location of ingested metallic foreign bodies (MFBs) in children.MethodsProspective case series enrolling children suspected of metallic foreign body ingestion presenting to the Emergency Department. Thirty-eight children were enrolled and the HHMD was used to detect the presence and location of a MFB. Results were compared to standard radiographic studies.ResultsThirty-seven of the 38 ingested foreign bodies were MFBs. Of the 37 MFBs, the HHMD positively identified 33, and 4 were missed by HHMD but identified on radiography. When positive, the location indicated by HHMD correlated 100% with radiograph. There were 33 true positives, 0 false positives, 4 false negatives, and 1 true negative. This resulted in a sensitivity of 89% (95% CI of 75%–96%) and specificity of 100% (95% CI of 2.5%–100%).ConclusionOur study demonstrates the accuracy of HHMD in the identification and localization of metallic foreign bodies. We propose an emergency room foreign body protocol that uses HHMD as an early screening tool in triage in order to expedite the process of obtaining Otolaryngology consultation and potentially shorten the wait time to the operating room or discharge. In instances were outside films are previously performed, HHMD use may be able to minimize the overall radiation exposure to children by obviating the need for repeat radiographs.As the sensitivity is not 100%, a negative HHMD screening does not negate the need for a standard radiograph in order to avoid missed MFBs. HHMD is best suited for detection of coins, which accounts for the majority of the MFB ingestions, and may not be suitable for all metallic objects since the amount of metal may decrease its sensitivity.
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Aneuploidy of a murine immortalized endothelial cell line, MS1
Publication date: Available online 5 November 2016
Source:Journal of Oral Biosciences
Author(s): Kyoko Hida, Nako Maishi, Dorcas Akuba-Muhyia Annan, Miyako Kondoh, Takayuki Hojo, Umma Habiba, Noritaka Ohga, Kosuke Ishikawa, Masumi Sato, Chisaho Torii, Misa Yanagiya, Masahiro Morimoto, Yasuhiro Hida, Masanobu Shindoh
ObjectivesWe have previously reported that tumor endothelial cells (TECs) are chromosomally abnormal. It is generally known that immortalized cells have chromosomal abnormalities. In this study, our objective was to compare chromosomal properties of an immortalized normal endothelial cell (NEC) line, MS1, and those of TECs, to assess the possible usefulness of MS1 cells as a surrogate for TECs, which have some experimental intractability as primary cultured endothelial cells.MethodsPrimary cultured NECs were isolated from murine dermis tissue. Fluorescence in situ hybridization was performed to analyze aneuploidy in MS1 cells and NECs. DNA damage response (DDR) activation was analyzed by γH2AX staining. We also tested the involvement of reactive oxygen species (ROS) in the chromosomal abnormalities of MS1 cells.ResultsMS1 cells showed a higher rate of aneuploidy than NECs did (91.6% versus 7.6%). A DDR was activated to a greater extent in MS1 cells than in NECs, judging by H2AX phosphorylation. ROS induced H2AX activation in MS1 cells, suggesting that ROS are involved in their DDR.ConclusionMS1 cells are aneuploid and activate H2AX to a greater extent than NECs do. MS1 cells resemble TECs in terms of the proliferative phenotype and aneuploidy. Thus, MS1 may be a good cell line for studies on the relation between chromosomal instability and a DDR in nonmalignant cells.
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Rapid prototyped patient specific guiding implants in critical mandibular reconstruction
Publication date: Available online 5 November 2016
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Patricia Stoor, Anni Suomalainen, Karri Mesimäki, Risto Kontio
Large tumours of the mandible need immediate reconstruction to provide continuity of the mandible, satisfactory function of the jaw, as well as an acceptable aesthetic outcome. In this prospective study we described the immediate reconstruction of the mandible using computer aided design and 15 rapid prototyped patient specific implants (PSI) in 14 patients suffering from benign or malignant tumours demanding continuity resection of the mandible. The scaffold PSI was filled with β-tricalcium phosphate granules and autologous bone. Microvascular reconstruction was additionally needed in 12/15 cases. The clinical follow-up was on average 33 months and the radiological follow up was on average 21 months.In nine cases the healing was uneventful. One patient lost the microvascular flap during the first postoperative week and one patient needed a revision due to perforation of the mucosa at the site of the PSI. Four patients had a major complication due to perforation of the mucosa leading to infection, which resulted in the total or partial removal of the PSI. The PSI seems to be a promising solution for treatment of patients demanding large reconstruction after mandible resection. The benefits are decreased rate of donor site complications and more accurate and prompt surgical procedure.
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Prevalence of infection with the use of β-tricalcium phosphate as a bone graft substitute during Le Fort I osteotomy
While grafting with bone substitutes has been shown to provide greater stability in maxillary advancements, infection remains a concern with any material that is placed in close proximity to the maxillary sinus. The purpose of this study was to evaluate the prevalence of infection in maxillary advancements in which a bone graft substitute (β-tricalcium phosphate; β-TCP) was placed at the time of surgery. This was a retrospective study of all maxillary osteotomies. Patients were divided into two groups: group 1 included maxillary osteotomies in which β-TCP was not used; group 2 included any maxillary osteotomy where β-TCP was used.
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Dental health and odontogenic infections among 6- to 16-year-old German students with special health care needs (SHCN)
Abstract
Objectives
This cross-sectional study aimed to assess dental health and odontogenic infections in students with special health care needs (SHCN) in the Free State of Thuringia, Germany.
Methods
From 1283 students with SHCN aged 6–16 years, 66.0 % (n = 848 of whom are 35.7 % females and 64.3 % males) with intellectual/learning disabilities (ID/LD), physical disabilities (PD), and sensory disorders (SD) participated after informed consent in oral examinations according to WHO standards. Dental caries was assessed by dmft/DMFT, odontogenic infections by pufa/PUFA. Fissure sealants (FS) were scored in permanent molars. Data were compared to regional and national reference data and analysed by t test and age-adjusted logistic regression models.
Results
Students with SHCN revealed 41.2 % caries prevalence in permanent and 31.7 % in primary teeth. Highest prevalence/experience of caries and odontogenic infections in primary teeth was recorded in 6–11-year-olds with PD (65.1 %/2.3 dmft; 14.0 %/0.3 pufa). Most affected permanent teeth were observed in students with ID/LD (12–16-year-olds 59.6 %/2.4 DMFT; 6–11-year-olds 2.8 %/0.03 PUFA). All odontogenic infections in 12–16-year-olds occurred in males; n = 9 students revealed n = 9 teeth with pufa/PUFA. Students with ID/LD aged 6–11 years exhibited lowest prevalence of FS (29.0 %) and mean of 0.8 FS. Students with SHCN suffered more than twice as frequent from untreated dental caries and benefited up to 29.0 % less from FS than peers without disabilities.
Conclusion
This first study investigating odontogenic infections of German students with SHCN revealed highest prevalence in primary teeth and in males. Oral health among students with SHCN is reduced, and FS are underutilized compared to German students without disabilities.
Clinical relevance
Reinforcing the application of FS in students with SHCN might contribute to reducing disparities in oral health.
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Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation
Source:Allergologia et Immunopathologia
Author(s): A. Loghmani, R. Raoofi, A. Ownagh, N. Delirezh
IntroductionAlthough the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure.Materials and methodsPlastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups.ResultsThe results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p<0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group.ConclusionThe asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases.
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Morbidité des prélèvements osseux autogènes en implantologie : revue de littérature de 1990 à 2015
Publication date: Available online 4 November 2016
Source:Revue de Stomatologie, de Chirurgie Maxillo-faciale et de Chirurgie Orale
Author(s): L. Costa Mendes, T. Sauvigné, J. Guiol
IntroductionL'os autogène est couramment employé pour les reconstructions osseuses pré-implantaires. Cinq sites de prélèvement sont fréquemment utilisés : la symphyse et le ramus mandibulaires, la crête iliaque, la calvaria et le tibia. Un des critères de choix entre ces sites est la morbidité du prélèvement. Le but de ce travail était d'analyser les complications de ces prélèvements en per- et postopératoire.Matériel et méthodesUne recherche automatique et manuelle sur Medline, couvrant la période de 1990 à 2015, a été réalisée. Les études sur sujets humains, en langue anglaise ou française, détaillant les complications liées aux prélèvements réalisés dans le cadre de la chirurgie pré-implantaire ont été incluses.RésultatsQuatre-vingt-trois études cliniques ou « case reports » ont été analysés. Les prélèvements iliaque, symphysaire et ramique étaient ceux entraînant le plus de douleurs et de troubles postopératoires de la sensibilité. Les prélèvements iliaques et tibiaux étaient compliqués de troubles de la marche au cours des premières semaines. De rares complications neurologiques ont été décrites suite à des prélèvements calvariaux.DiscussionBien que fréquemment utilisé, le prélèvement iliaque présente une morbidité non négligeable. Le prélèvement calvarial est celui ayant le moins de morbidité. Il doit être pratiqué par une équipe expérimentée afin de réduire le risque de lésion neurologique. Pour les prélèvements intra-oraux, le prélèvement symphysaire est de moins en moins utilisé. Le prélèvement ramique présente moins de complications et est bien accepté par les patients.IntroductionAutogenous bone is commonly used in pre-implant bone reconstructions. Five harvesting sites are frequently used: mandibular symphysis and ramus, iliac crest, calvaria and tibia. One of the deciding criterions among these sites is the donor site morbidity. The purpose of our work was to analyze the intra- and postoperative complications that may occur on the different donor sites.Material and methodsAn automatic and manual search on Medline covering the period 1990–2015 was made. Human studies, in English or French language, detailing the complications linked to bone harvest done for pre-implant surgery were included.ResultsEighty-three clinical trials or case reports were analyzed. Iliac crest, mandibular symphysis and ramus donor sites were afflicted with the highest pain scores and sensory disturbances. Iliac and tibial bone harvests were complicated by walk disturbances in the first weeks. Some rare neurological complications have been reported after calvarial bone harvest.DiscussionAlthough commonly used, iliac crest bone harvest is responsible for significant morbidity. Calvarial harvest is related to the lowest morbidity. It has to be performed by an experienced team in order to reduce the risk of neurologic injury. Regarding intraoral donor sites, mandibular symphysis becomes less popular. Mandibular ramus harvest has the lowest complication rate and is well accepted by patients.
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Dysplasie osseuse floride : gestion d’un cas symptomatique
Publication date: Available online 4 November 2016
Source:Revue de Stomatologie, de Chirurgie Maxillo-faciale et de Chirurgie Orale
Author(s): M. Maccotta, L. Radoï
IntroductionLa dysplasie osseuse floride est une pathologie fibro-osseuse rare et bénigne au cours de laquelle l'os est remplacé par du tissu fibreux et de l'os métaplasique. Elle peut rester longtemps asymptomatique et elle est le plus souvent découverte fortuitement lors d'un examen radiologique de routine. Parfois, les patients consultent à la suite d'une complication infectieuse.ObservationUne patiente de 62 ans édentée, s'est présentée en consultation pour une tuméfaction mandibulaire douloureuse empêchant l'insertion de sa prothèse amovible. L'examen clinique montrait une tuméfaction mentonnière avec une déformation antérieure des tables osseuses mandibulaires d'environ quatre centimètres de diamètre. S'y associaient une fistulisation intra-orale et une suppuration. L'examen radiologique montrait une lésion osseuse mixte soufflant les corticales vestibulaire et linguale et un séquestre osseux. L'examen biologique était normal et il n'y avait pas d'autres anomalies du squelette. La confrontation des examens clinique, radiologique et anatomopathologique a permis de poser le diagnostic de dysplasie osseuse floride. L'exérèse du séquestre osseux associée à une ostéoplastie de remodelage mandibulaire a été réalisée sous anesthésie générale. La prothèse amovible a été rebasée afin de guider la cicatrisation.DiscussionLa prise en charge chirurgicale d'une dysplasie osseuse floride n'est légitime qu'en présence de complications ne répondant pas à un traitement médical. Dans tous les autres cas, l'abstention thérapeutique et la surveillance prolongée sont primordiales.IntroductionFlorid osseous dysplasia is a rare and benign fibro-osseous pathology, in which bone is replaced by fibrous tissue and metaplastic bone. It can remain asymptomatic for a long time and is most often discovered incidentally during a radiological examination. Sometimes, patients are seen because of an infectious complication.ObservationAn edentulous 62 years-old woman was referred for a painful mandibular swelling preventing insertion of her removable denture. Clinical examination showed a chin swelling, a deformation of mandibular bone tables of approximately four centimeters in diameter, an intra-oral fistula and a suppuration. Radiological examination showed a mixed bone lesion blowing up the buccal and lingual cortical plates and a bone sequestrum. Blood test was normal and there were no other skeletal abnormalities. The diagnosis of florid osseous bone dysplasia was made thanks to the confrontation of the clinical, radiological and histological examinations. Excision of the bone sequestrum associated to remodeling osteoplasty was performed under general anesthesia. The removable denture was rebased to drivehealing.DiscussionSurgical management of osseous bone dysplasia is legitimate only in the presence of complications not responding to medical treatment. In all other cases, therapeutic abstention and long term supervision are essential.
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Crystal structure of a polypeptide’s C-terminus in complex with the regulatory domain of ER aminopeptidase 1
Source:Molecular Immunology, Volume 80
Author(s): Lufei Sui, Amit Gandhi, Hwai-Chen Guo
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is involved in the final processing of peptide precursors to generate the N-termini of MHC class I-restricted epitopes. ERAP1 thus influences immunodominance and cytotoxic immune responses by controlling the peptide repertoire available for cell surface presentation by MHC molecules. To enable this critical role in antigen processing, ERAP1 trims peptides by a unique molecular ruler mechanism that turns on/off hydrolysis activity in a peptide-length and −sequence dependent manner. Thus unlike other aminopeptidases, ERAP1 could recognize both the N- and C-termini of peptides in order to read the substrate's length. To exemplify and validate this molecular ruler mechanism, we have carried out crystallographic studies on molecular recognition of antigenic peptide's C-terminus by ERAP1. In this report, we have determined a 2.8Å-resolution crystal structure of an intermolecular complex between the ERAP1 regulatory domain and a natural epitope's C-terminus displayed in a fusion protein. It reveals the structural details of peptide's C-termini recognition by ERAP1. ERAP1 uses specificity pockets on the regulatory domain to bind the peptide's carboxyl end and side chain of the C-terminal anchoring residue. At the same time, flexibility in length and sequence at the middle of peptides is accommodated by a kink with minimal interactions with ERAP1.
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Fever-range hyperthermia inhibits cells immune response to protein-bound polysaccharides derived from Coriolus versicolor extract
Source:Molecular Immunology, Volume 80
Author(s): Małgorzata Pawlikowska, Tomasz Jędrzejewski, Jakub Piotrowski, Wiesław Kozak
The aim of the study was to explore whether fever-range hyperthermia (FRH) might enhance the anticancer and immunoregulatory activities of protein-bound polysaccharides (PBP), a class of fungus derived immunomodifiers used in the cancer adjuvant therapy. Blood lymphocytes and breast cancer cells (MCF-7) were cultured at 39.5°C in humidified atmosphere containing 5% CO2 for 2h. After rested at 37°C for 6h, the cells were treated with PBP extract at 100- and 300μg/ml concentration. After indicated time, the proliferative response was analyzed and cytokine mRNA expression assessment was performed by qRT-PCR. In animal model, the FRH was induced by placing rats in the Homeothermic Controller with heating blanket. Animals were heated until Tb reached 39.5°C (±0.2°C) and were maintained at this temperature for 30min. The protein-bound polysaccharides solution was injected i.p. at a dose of 100 mg/kg 6h post FRH. Twenty four hours after treatment, the blood was collected and cytokines expression analysis were performed. The results have shown that fever-range hyperthermia has an inhibitory effect on PBP extract-induced proliferative response of blood lymphocytes, as well as IL-1β and IL-6 mRNA expression. Moreover, the temperature of 39.5°C blocks PBP-induced cytotoxicity against MCF-7 cells, which correlates with significant reduction in TNF-α level. Combined treatment of rats (FRH+PBP) results in decrease of IL-1β, IL-6 and TNF-α mRNA expression in peripheral blood mononuclear cells compared to cells derived from rats treated with protein-bound polysaccharides extract alone. This study demonstrates that fever-range temperature inhibits immunostimulatory as well as anticancer effects mediated by protein-bound polysaccharides.
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Progressive severe B cell deficiency in pediatric Rubinstein-Taybi syndrome
Publication date: Available online 5 November 2016
Source:Clinical Immunology
Author(s): Vassilios Lougaris, Elena Facchini, Manuela Baronio, Tiziana Lorenzini, Daniele Moratto, Fernando Specchia, Alessandro Plebani
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At the interface of medicine and dentistry: Shared decision making using decision aids and clinical decision support tools
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Lauren L. Patton
http://ift.tt/2fo3Pis
RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, STAB1, and IRF4
Abstract
Background
Asthma is a Th2 cell-driven inflammatory disease and a major public health concern. The cis-acting element Rad50 hypersensitive site 6 (RHS6) in the Th2 locus control region is essential for regulation of the Th2 cytokine genes; however, its role in allergic airway inflammation and underlying molecular mechanisms of the regulation by RHS6 are poorly understood.
Objective
We sought to understand the role of RHS6 in the development of allergic airway inflammation and its molecular mechanism for Th2 cytokine expression.
Methods
We used an ovalbumin-induced allergic inflammation model with RHS6-deficient mice to examine the role of RHS6 in this process. To examine molecular mechanism of RHS6 for Th2 cytokine expression, we used DNA-affinity chromatography and mass spectrometry, quantitative RT-PCR, ELISA, intracellular cytokine staining, chromatin immunoprecipitation and co-immunoprecipitation.
Results
Deletion of RHS6 caused a dramatic resistance to allergic airway inflammation. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes. RHS6 deficiency caused inhibition of transcription factor-induced Th2 cytokine gene expression.
Conclusion
RHS6 is a critical regulatory element for allergic airway inflammation and for coordinate regulation of Th2 cytokine genes by recruiting GATA3, SATB1 and IRF4.
This article is protected by copyright. All rights reserved.
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The clinical relationship between the slug-mediated PUMA/p53 signaling pathway and radiotherapy resistance in nasopharyngeal carcinoma
OBJECTIVE: To explore the clinical relationship between the Slug-mediated PUMA/p53 signaling pathway and radiotherapy resistance in nasopharyngeal carcinoma.
PATIENTS AND METHODS: Forty surgical specimens were collected from nasopharyngeal carcinoma patients treated at our hospital between February 2010 and February 2015. Twenty patients with poorly differentiated nasopharyngeal carcinoma with and without radiotherapy resistance were included in the experimental and control groups, respectively. Slug, PUMA, and p53 expression were quantified in all tissues using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry.
RESULTS: Slug and p53 mRNA levels were significantly higher in the experimental group than in the control group (p < 0.01). PUMA mRNA levels were significantly lower in the experimental group than in the control group (p < 0.01). Slug protein expression was significantly higher in the experimental group (6.07 ± 0.203 μg/L) than in the control group (1.24 ± 0.171 μg/L) (p < 0.01). p53 protein expression was significantly higher in the experimental group (4.28 ± 0.108 μg/L) than in the control group (0.63 ± 0.101 μg/L) (p < 0.01). PUMA protein expression was significantly lower in the experimental group (0.43 ± 0.11 μg/L) than in the control group (3.37 ± 0.112 μg/L) (v < 0.01). The number of Slug, PUMA, and p53-positive cells in the experimental group and the control group were quantified; these values confirmed the ELISA and Western blot findings.
CONCLUSIONS: Slug downregulated the PUMA protein expression signaling pathway and promoted radiotherapy resistance in poorly differentiated squamous cell carcinoma tissue, in a p53-independent manner.
L'articolo The clinical relationship between the slug-mediated PUMA/p53 signaling pathway and radiotherapy resistance in nasopharyngeal carcinoma sembra essere il primo su European Review.
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RT-PCR quantification of periodontal pathogens in crack users and nonusers
Abstract
Objective
Compare counts of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis and Fusobacterium nucleatum between crack users and nonusers.
Materials and methods
A cross-sectional study was conducted involving seventy-seven crack cocaine users and eighty-one nonusers matched for age, gender and tobacco use. Demographic and clinical variables were analysed. Subgingival bacterial samples were collected from four sites with the greatest probing depths and were analysed using real-time polymerase chain reaction.
Results
No significant difference was found in the prevalence of total counts for each bacterial species analyzed between groups. However, crack users had a 1.85 (95% CI: 1.03-3.31), 2.19 (95% CI 1.24-3.88), 2.53 (95% CI 1.27-5.04) and 2.40 (95% CI 1.22-4.75) greater probability of having the higher' rather counts (≥ 75th percentile) for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, respectively.
Conclusion
Although some crack users had higher (>75th percentile) bacterial counts for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, total counts did not differ between crack users and non users, leading the hypotheses that the higher occurrence of periodontitis on crack users may be related to other non bacterial factors.
This article is protected by copyright. All rights reserved.
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Errors in interpretation of neck levels in postoperative pathological specimens
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): I. Varley, T.E. Howe, K. Hunter, A.T. Smith
Accurate orientation of pathological specimens is of fundamental importance, and specimens that are divided postoperatively may be misinterpreted. We asked surgeons and pathologists to identify boundaries between nodal levels on a clinical photograph of a neck dissection specimen. Few participants were able to identify the boundaries between levels accurately, with several important errors where a marked level contained none of the relevant anatomical tissue. Most errors were in level I, and the number decreased towards level IV. Errors were made by both pathologists and surgeons. The boundaries of level IIA were consistently overestimated, which may have implications for previous studies that evaluated patterns of nodal spread.
http://ift.tt/2fpxV2U
New NICE referral guidance for oral cancer: does it risk delay in diagnosis?
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): D. Grimes, J. Patel, C. Avery
Changes to guidance about the two-week wait referrals for suspected cancer of the head and neck have created a new recommendation for a general medical practitioner to refer any patients to a dentist under certain criteria. The potential effect of this was assessed based on 91 referrals to an oral and maxillofacial unit. A total of 33 met the criteria for initial referral to a dentist; of these, one was later diagnosed with cancer. We outline the potential deleterious effects the new guidance might have on the rapid diagnosis of oral lesions.
http://ift.tt/2fpBHt2
The Right to Look Human-Head and Neck Surgery in Low- and Middle-Income Countries: The Chris O'Brien Memorial Lecture.
The Right to Look Human-Head and Neck Surgery in Low- and Middle-Income Countries: The Chris O'Brien Memorial Lecture.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 3;:
Authors: Shrime MG
PMID: 27812700 [PubMed - as supplied by publisher]
http://ift.tt/2fFaGoP
Appropriate Treatment of T3 Glottic Cancer.
Appropriate Treatment of T3 Glottic Cancer.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 3;:
Authors: D'Ascanio L, Pappacena M, Piazza F
PMID: 27812699 [PubMed - as supplied by publisher]
http://ift.tt/2frnk5P
Appropriate Treatment of T3 Glottic Cancer-Reply.
Appropriate Treatment of T3 Glottic Cancer-Reply.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 3;:
Authors: Al-Gilani M, Haughey B, Piccirillo JF
PMID: 27812697 [PubMed - as supplied by publisher]
http://ift.tt/2eyDzjP
Radiotherapy Characteristics and Outcomes for Head and Neck Carcinoma of Unknown Primary vs T1 Base-of-Tongue Carcinoma.
Radiotherapy Characteristics and Outcomes for Head and Neck Carcinoma of Unknown Primary vs T1 Base-of-Tongue Carcinoma.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 3;:
Authors: Hosni A, Dixon PR, Rishi A, Au M, Xu W, Song Y, Chepeha DB, Goldstein DP, Huang SH, Kim J, O'Sullivan B, Waldron J, Bratman SV, de Almeida JR
Abstract
Importance: Transoral robotic surgery- or transoral laser microsurgery-assisted lingual tonsillectomy may improve the identification rate of hidden base-of-tongue (BOT) carcinoma presenting as head or neck carcinoma of unknown primary (CUP) site.
Objective: To evaluate the potential impact of lingual tonsillectomy in CUP site by comparing differences in radiotherapy volumes, dosimetry, and clinical outcomes for CUP site and T1-category BOT carcinoma.
Design, Setting, and Participants: Retrospective study of 115 patients treated at a tertiary cancer center between January 1, 2005, and December 31, 2013, that included patients with BOT carcinoma (category T1N1-3M0) and CUP site (category T0N1-3M0) with known p16 status. Fifty-four patients with T1-category BOT carcinoma (50 [92.6%] p16-positive) were treated with definitive intensity-modulated radiotherapy (IMRT), including 34 (63%) who received concurrent chemotherapy. Sixty-one patients with CUP site (38 [62.3%] p16-positive) received definitive (42 [68.9%]) or postoperative (19 [31.1%]) IMRT, including 22 (36%) who received concurrent chemotherapy.
Interventions: Definitive or postoperative IMRT, with or without concurrent chemotherapy.
Main Outcomes and Measures: Characteristics of mucosal clinical target volume (CTV-T), nodal CTV, and organ-at-risk dosimetry; local, regional, and distant control; cause-specific and overall survival; and Radiation Therapy Oncology Group grade 3 or higher late toxic effects.
Results: Of 115 participants, 104 (90.4%) were male; mean (SD) age was 59 (10) years. High-dose CTV-T was prescribed in all 54 patients with BOT carcinoma and 23 (37.7%) with CUP site (effect size [Δ], 62%; 95% CI, 50%-74%). Low-dose CTV-T included mucosal pharyngeal sites outside the oropharynx in no patients with BOT carcinoma and 26 (42.6%) (95% CI, 30%-54%) with CUP site, with greater low-dose CTV-T volume in CUP site than BOT carcinoma (113 vs 84 cm3; Δ, 30 cm3; 95% CI, 10-49 cm3). Bilateral neck irradiation was used in 53 of 54 patients (98.1%) with BOT carcinoma and 46 of 61 (75.4%) with CUP site (Δ, 23%; 95% CI, 12% to 34%). Patients with BOT carcinoma received a higher maximum dose to the mandible (71 vs 67.2 Gy; Δ, 3.8 Gy; 95% CI, 1.6 to 6 Gy), with a nonsignificantly higher maximum dose (66.1 vs 62.8 Gy; 3.2 Gy; 95% CI, -0.1 to 6.5 Gy) and lower mean dose to the larynx (43.8 vs 47.1 Gy; 3.3 Gy; 95% CI, -0.3 to 6.9 Gy). There were no significant differences in local control, regional control, distant control, cause-specific survival, and overall survival between the BOT carcinoma and CUP site groups stratified by p16 status. Grade 3 Radiation Therapy Oncology Group late toxic effects occurred in 2 patients (3.3%) with CUP site (both neck fibrosis) and 5 (9.3%) with BOT carcinoma (2 neck fibrosis, 2 osteoradionecrosis, and 1 dysphagia).
Conclusions and Relevance: Intensity-modulated radiotherapy for CUP site or T1-category BOT carcinoma had similar clinical outcomes. Identifying hidden BOT primary carcinoma with novel approaches (eg, transoral robotic surgery and transoral laser microsurgery) may lead to changes in the radiotherapy target volume and dose prescription. Studies are needed to investigate the effect of these differences on quality of life and functional outcomes.
PMID: 27812692 [PubMed - as supplied by publisher]
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Identification of the Bacterial Reservoirs for the Middle Ear Using Phylogenic Analysis.
Identification of the Bacterial Reservoirs for the Middle Ear Using Phylogenic Analysis.
JAMA Otolaryngol Head Neck Surg. 2016 Nov 3;:
Authors: Chan CL, Wabnitz D, Bassiouni A, Wormald PJ, Vreugde S, Psaltis AJ
Abstract
Importance: The adenoid pad has long been considered a reservoir for bacteria in the pathogenesis of otitis media with effusion (OME). However, bacteria more reminiscent of external auditory canal (EAC) commensals are often demonstrated within middle ear aspirates.
Objective: To compare the microbiota of the EAC, the middle ear with OME, and the adenoid pad to further clarify the true source of middle ear bacteria.
Design, Setting, and Participants: Middle ear fluid (MEF) aspirates and EAC lavages were collected from 18 children with OME undergoing ventilation tube insertion from June 1, 2014, to August 31, 2015, at Women and Children's Hospital, Adelaide, Australia. Adenoid pad and MEF samples were included from a previous study. Samples were analyzed using sequencing of the 16S ribosomal RNA gene. Previously collected microbiota data from the adenoid pad were collated for analysis.
Main Outcome Measures: Mean relative abundance of top bacterial genera for the MEF, EAC, and adenoid pad samples.
Results: Eighteen pediatric patients with chronic OME (6 female; 12 male; mean [SD] age, 48 [36] months) were recruited prospectively, with 34 paired MEF and EAC samples. The MEF microbiota (mean relative abundance [SD]) consisted of Alloiococcus otitidis (37.5% [40.0%]), Haemophilus (14.4% [29.1%]), Moraxella (10.0% [26.4%]), Staphylococcus (8.2% [21.9%]), and Streptococcus (3.8% [13.1%]). The mean relative abundance (SD) microbiota of the EAC demonstrated a sparsity of classic otopathogens, including Haemophilus (0.3% [0.8%]), Moraxella (0.3% [0.7%]), and Streptococcus (0.2% [0.6%]), but had a high abundance of Alloiococcus (58.0% [44.1%]), Staphylococcus (20.8% [34.0%]), and Pseudomonas (3.2% [17.1%]). In contrast, based on previously collected data, the microbiota of the adenoid pad showed a high abundance of the classic otopathogens with a sparsity of EAC genera for Alloiococcus (0.1% vs 28.9%, respectively; P < .001), Haemophilus (25.2% vs 18.2%, respectively; P = .002), Staphylococcus (0.2% vs 10.8%, respectively; P = .02), Streptococcus (12.7% vs 4.2%, respectively; P < .001), and Pseudomonas (0 vs 2.1% respectively; P < .001). The microbiota of the MEF collected during 2 consecutive years were similar (Alloiococcus, 22.7% vs 37.5%; Haemophilus, 22.5% vs 14.0%; Staphylococcus, 10.9% vs 10.7%; Moraxella, 5.0% vs 9.7%; Corynebacteria, 6.2% vs 3.1%; Streptococcus, 4.8% vs 3.7%; and Pseudomonas, 1.1% vs 3.0%; P ≥ .05).
Conclusions and Relevance: The EAC and the nasopharynx could serve as reservoirs for microbiota of the middle ear. Furthermore, the microbiota of the middle ear with effusion appear to be relatively stable over time and between populations with OME.
PMID: 27812691 [PubMed - as supplied by publisher]
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Dysregulation of lipidomic profile and antiviral immunity in response to hyaluronan in severe asthma
Source:Journal of Allergy and Clinical Immunology
Author(s): Milena Sokolowska, Li-Yuan Chen, Yueqin Liu, Asuncion Martinez-Anton, Carolea Logun, Sara Alsaaty, Rosemarie A. Cuento, Rongman Cai, Junfeng Sun, Oswald Quehenberger, Aaron M. Armando, Edward A. Dennis, Stewart J. Levine, James H. Shelhamer
Teaser
Through lipidomics and transcriptomics, we demonstrated that fragmented hyaluronan increases production of several lipids in severe asthmatics, which correlates with decreases in antiviral gene and protein expression; effect partially reversed upon inhibition of lipid production.http://ift.tt/2fpm8l6
A Randomized, Multicenter Study Evaluating Xolair® Persistency Of Response After Long-Term Therapy (XPORT)
Source:Journal of Allergy and Clinical Immunology
Author(s): Dennis Ledford, William Busse, Benjamin Trzaskoma, Theodore A. Omachi, Karin Rosén, Bradley E. Chipps, Allan T. Luskin, Paul G. Solari
BackgroundFew data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab.ObjectiveTo evaluate the benefit and persistency of response in subjects continuing or withdrawing from long-term omalizumab treatment.MethodsEvaluating the Xolair® Persistency Of Response After Long-Term Therapy (XPORT) was a randomized, double-blind, placebo-controlled withdrawal study that included subjects with moderate-to-severe persistent asthma receiving long-term omalizumab. Subjects were randomized using a hierarchical dynamic randomization scheme, to continue their same dose of omalizumab or withdraw to placebo and were then followed every 4 weeks for 1 year. Primary outcome: any protocol-defined severe asthma exacerbation. Secondary outcome: time to first protocol-defined severe asthma exacerbation. Exploratory outcomes included changes in Asthma Control Questionnaire (ACQ) and Asthma Control Test (ACT) scores.ResultsSignificantly more subjects in the omalizumab group (67%) had no protocol-defined exacerbation than in the placebo group (47.7%); absolute difference of 19.3% (95% CI: 5.0%, 33.6%) represents a 40.1% relative difference. Time to first protocol-defined exacerbation analysis revealed a significantly different between-group exacerbation pattern that was consistent with the primary analysis. Subjects continuing omalizumab had significantly better asthma control (mean [SD] change from baseline to Week 52: ACT, –1.16 [4.14] vs placebo, –2.88 [5.38]; P = .0188 and ACQ, 0.22 [0.66] vs placebo, 0.63 [1.13]); P = .0039. Discontinuation of omalizumab was associated with an increase in free IgE and an increase in basophil expression of the high-affinity IgE receptor. No safety concerns were noted.ConclusionContinuation of omalizumab following long-term treatment results in continued benefit as evidenced by improved symptom control and reduced exacerbation risk.
Teaser
Continuation of omalizumab after long-term use results in improved symptom control and a reduced exacerbation risk. Use of biomarkers (FeNO and peripheral blood eosinophil counts) may further inform omalizumab treatment decisions.http://ift.tt/2f3XJTu
Cytokine and Estrogen Stimulation of Endothelial Cells Augment Activation of the Prekallikrein-High Molecular Weight Kininogen Complex: Implications for Hereditary Angioedema (HAE)
Source:Journal of Allergy and Clinical Immunology
Author(s): Kusumam Joseph, Baby G. Tholanikunnel, Allen P. Kaplan
BackgroundWhen the prekallikrein-high molecular weight kininogen complex is bound to endothelial cells, prekallikrein is stoichiometrically converted to kallikrein due to release of heat shock protein-90 (Hsp90). While bradykinin formation is typically initiated by factor XII autoactivation it is also possible to activate factor XII either by kallikrein, thus formed, or plasmin.RationaleSince attacks of hereditary angioedema can be related to infection and/or exposure to estrogen, we questioned whether estrogen or cytokine stimulation of endothelial cells could augment release of Hsp90 and prekallikrein activation. We also tested release of profibrinolytic enzymes, urokinase and tissue plasminogen activator (TPA) as a source for plasmin formation.MethodsCells were stimulated with agonists and secretion of Hsp90, urokinase, and TPA, were measured in the culture supernatants by ELISA. Activation of the prekallikrein-HK complex was measured employing pro-phe-arg-p-nitroanilide reflecting kallikrein formation.ResultsHsp90 release was stimulated with optimal doses of estradiol, IL-1, and TNFα (10ng/ml) from 15 min to 120 min. TPA release was not augmented by any of the agonists tested but urokinase was released by IL-1, TNFα and thrombin (positive control), but not estrogen. Augmented activation of the prekallikrein-HK complex to generate kallikrein was seen with each agonist that releases Hsp90. Addition of 0.1% factor XII relative to prekallikrein-HK leads to rapid formation of kallikrein; factor XII alone does not autoactivate.ConclusionsInterleukin-1, TNFα, and estrogen stimulate release of Hsp90 and augment activation of the prekallikrein-HK complex to generate kallikrein and bradykinin. IL-1 and TNFα stimulate release of urokinase, which can convert plasminogen to plasmin and represents a possible source for plasmin generation in all types of HAE, but particularly HAE with normal C1 inhibitor (HAE-N) with a factor XII mutation. Both kallikrein and plasmin activate factor XII; kallikrein is 20 times more potent on a molar basis.Clinical ImplicationAttacks of angioedema in patients with HAE may be initiated by estrogen (endogenous or exogenous) or by infection. Cytokine or estrogen stimulation of endothelial cells and augmented activation of the prekallikrein-HK complex could potentially initiate this process.
Teaser
Activation of endothelial cells by cytokines and estrogen augment secretion of Hsp90, which forms a zinc-dependent trimolecular complex with HK-prekallikrein and converts prekallikrein to kallikrein. Cytokines also stimulate release of urokinase. Novel mechanisms for initiation of bradykinin formation in hereditary angioedema by infection or estrogen are suggested.http://ift.tt/2fpjuvT
Oxidative stress drives CD8+T cells skin trafficking in vitiligo via CXCL16 upregulation by activating the unfolded protein response in keratinocytes
Source:Journal of Allergy and Clinical Immunology
Author(s): Shuli Li, Guannan Zhu, Yuqi Yang, Zhe Jian, Sen Guo, Wei Dai, Qiong Shi, Rui Ge, Jingjing Ma, Ling Liu, Kai Li, Qi Luan, Gang Wang, Tianwen Gao, Chunying Li
BackgroundIn vitiligo, elevated reactive oxygen species (ROS) have been proven as a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment e.g. keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and recently found to mediate homing of CD8+T cells in human skin.ObjectiveTo explicate the effect of oxidative stress on human keratinocyte and its capacity to drive CD8+T cell trafficking via CXCL16 regulation.MethodsWe first detected putative T cells skin homing chemokines and ROS level in vitiligo serum and lesions. The production of candidate chemokines was detected by qRT-PCR and ELISA in keratinocytes exposed to H2O2. Furthermore, mediators involved were analyzed by qRT-PCR, western blot, ELISA and immunofluorescence. Next, we tested the chemotactic migration of vitiligo CD8+T cells mediated by CXCL16–CXCR6 pair by transwell assay.ResultsCXCL16 expression increased and showed a positive correlation with oxidative stress level in vitiligo serum and lesions. The H2O2–induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways, PERK–eIF2α and IRE1α–XBP1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6+CD8+T cells derived from vitiligo patients. CXCR6+CD8+T cells skin infiltration is accompanied by melanocytes loss in vitiligo lesions.ConclusionOur study demonstrated that CXCL16–CXCR6 mediates CD8+T cell skin trafficking under oxidative stress in vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least partially, by UPR activation.
Teaser
Oxidative stress drives CD8+T cell trafficking via CXCL16–CXCR6 interaction in vitiligo, and the CXCL16 expression in stressed keratinocytes is mediated by UPR activation.http://ift.tt/2f41bhb
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