The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers

Publication date: Available online 1 October 2018

Source: Clinical Immunology

Author(s): Fernanda Guimarães Weiler, Pärt Peterson, Beatriz Tavares Costa-Carvalho, Mayra de Barros Dorna, Joya Emilie de Menezes Correia-Deur, Soraya Lopes Sader, Daniela Espíndola-Antunes, Gil Guerra-Junior, Magnus Régios Dias-da-Silva, Marise Lazaretti-Castro

Abstract

Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1 patients by clinical evaluation, searching mutation in the AIRE gene, measuring serum autoantibodies, and investigating correlations between findings. We recruited patients based on the clinical criteria and tested them for AIRE mutations, antibodies against interferon type I and interleukins 17A, 17F and 22. We identified 12 unrelated families (13 patients) with typical signs of APS1 in the proband, and the screening of relatives recognized an asymptomatic child. Candidiasis was present in all cases, and 19 other manifestations were observed. All patients carried one of 10 different mutations in AIRE, being 3 new ones, and were positive for anti-interferon type I serum antibody. Anti-interleukin-17A levels inversely correlated with the number of manifestations in each patient. This negative correlation may suggest a protective effect of anti-interleukin-17A with a potential therapeutic application.

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Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Zhaoheng Lin, Jing Jin, Weirong Bai, Jiao Li, Xiyun Shan

Abstract

Netrin-1 is best known for its function guiding axon growth and migration. Netrin-1 has been shown to be involved in regulating cardiovascular function. In this study, we aimed to understand the biological role of Netrin-1 and its receptor Unc5b in endothelial cells. Our results demonstrate that Unc5b was moderately expressed in human aortic endothelial cells (HAECs) and TNF-α had a dose-dependent inhibitory effect on Unc5b level. Netrin-1 potently suppressed TNF-α-induced vascular adhesion molecules VCAM-1, ICAM-1, E-selectin and blocked the adhesion of monocytes to endothelial cells. Netrin-1 also suppressed TNF-α-induced production of cytokines including MCP-1, IL-1β, and IL-6. Importantly, Netrin-1 suppressed toll like receptor 4 (TLR4) expression and prevented NF-κB activation. Mechanistically, Netrin-1 reduced TNF-α-induced IKK and IκBα activation and prevented degradation of IκBα. Netrin-1 reduced nuclear accumulation of p65 and strongly suppressed NF-κB promoter activation. Collectively, our data demonstrated that signaling of Netrin-1 and its receptor Unc5b had an anti-inflammatory effect in endothelial cells. Netrin-1 signaling could be imperative for normal endothelial function.

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The core promoter controls basal and inducible expression of duck retinoic acid inducible gene-I (RIG-I)

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Yanna Xiao, Matthew B. Reeves, Adam F. Caulfield, Danyel Evseev, Katharine E. Magor

Abstract

Retinoic acid inducible gene-I (RIG-I) is a cytoplasmic RNA sensor for detecting a variety of RNA viruses including influenza A viruses. Detection ultimately produces Type I interferon (IFN), which stimulates expression of interferon stimulated genes (ISGs), including RIG-I itself in a positive feedback loop. The structure and function of RIG-I is conserved across phylogeny, despite significant protein sequence divergence, however, the promoter sequences do not show the expected phylogenetic relationships and it is not known whether they are similarly regulated. We previously cloned duck RIG-I and showed it is highly induced during influenza A infection consistent with induction by the interferon produced. Here, we identified the Pekin duck RIG-I promoter and constructed promoter reporter vectors, which we transfected into duck embryonic fibroblasts or chicken DF-1 cells and tested in dual luciferase assays. We showed that activation of the Mitochondrial Antiviral Signalling (MAVS) pathway using the constitutively active N-terminal region of RIG-I or polyinosinic-polycytidylic acid (poly I:C) led to stimulation of duck RIG-I promoter activity. Using deletion constructs we showed the core promoter lies in the proximal 250 basepairs, and we identified essential cis-regulatory elements, a GC-box and an interferon-sensitive response element (ISRE), responsible for basal and inducible expression, respectively. Using mCherry-tagged interferon regulatory factors (IRFs) cloned from chickens and ducks, we show overexpression of chIRF7 induced the duck RIG-I promoter, and this required the ISRE site. Finally, we also demonstrated that overexpressed chIRF7 translocated to the nucleus, which was augmented by MAVS activation using RIG-I 2CARD. Our findings demonstrate that RIG-I expression is induced by chIRF7, in a positive regulatory loop. These studies show that the duck RIG-I promoter is appropriately regulated in chicken cells, necessary for the potential generation of transgenic chickens expressing RIG-I.

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Lipemia Retinalis, Macular Edema, and Vision Loss in a Diabetic Patient with a History of Type IV Hypertriglyceridemia and Pancreatitis

Background: Lipemia retinalis is a rare but known complication of elevated serum triglycerides. This case describes the clinical course of a diabetic patient who presented with lipemia retinalis and macular edema, which responded to systemic and local treatments. Case Report: A 40-year-old female with a history of type II diabetes mellitus, hypertriglyceridemia, and pancreatitis presented with decreased vision in the left eye. She had peripapillary and macular edema, intraretinal hemorrhages, and prominent exudates in the setting of lipemia retinalis due to type IV hypertriglyceridemia. She was treated with serial intravitreal bevacizumab injections for macular edema and systemic lipid lowering therapy, and her visual acuity improved back to baseline. Conclusions: In the setting of lipemia retinalis and hypertriglyceridemia, the current patient developed macular edema and vision loss. The macular edema was treated with intravitreal injections of bevacizumab, and the patient experienced a rapid recovery of visual acuity.
Case Rep Ophthalmol 2018;9:425–430

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Surgical treatments for a case of superior canal dehiscence syndrome associated with patulous Eustachian tube

Publication date: Available online 2 October 2018

Source: Auris Nasus Larynx

Author(s): Ryoukichi Ikeda, Hiromitsu Miyazaki, Masahiro Morita, Daisuke Yamauchi, Tetsuaki Kawase, Yukio Katori, Toshimitsu Kobayashi

Abstract

Objectives

The patulous Eustachian tube (PET) and superior semicircular canal dehiscence syndrome (SCDS) have similarity in their symptoms and similar effects caused by positional changes, causing difficulty in the differentiation between the two disorders. This report describes a case of both SCDS and PET that was eventually successfully treated.

Methods

A 68-year-old man presented with hyperacusis to his own footsteps and gait disturbance. He had been diagnosed as PET two years before and had been treated by insertion of a silicone plug (Kobayashi plug) at the other hospital. Clinical case records, audiological data, cervical vestibular-evoked myogenic potential (cVEMP), Eustachian tube function tests and computed tomography (CT) were taken in the sitting position.

Results

While the CT confirmed superior semicircular canal dehiscence, the results of cVEMP was not typical of SCD likely due to preexisting hearing impairment in the right ear with a history of middle ear surgeries for the treatment of PET. He received round window reinforcement (RWR) and achieved relief from his symptoms but six months after the surgery, he visited again with complaints of autophony of his own voice and breathing. The tympanic membrane was found to move synchronous with respiration, and Eustachian tube function tests and the sitting CT confirmed the recurrence of severe PET. He had his silicone plug exchanged (increase in size of the Kobayashi plug) and achieved relief from symptoms.

Conclusions

The present case was a rare instance showing that PET and SCDS can occur simultaneously in a patient. The patient achieved relief from symptoms after treatment with RWR and insertion of the Kobayashi plug.

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Simultaneous bilateral butterfly tympanoplasty using tragal cartilage from one ear

Publication date: Available online 2 October 2018

Source: Auris Nasus Larynx

Author(s): Mehmet Karataş, Emin Kaskalan

Abstract

Objective

To evaluate the outcomes of simultaneous bilateral inlay butterfly cartilage tympanoplasties (BIBCT) using tragal cartilage from one ear in patients with bilateral chronic otitis media (BCOM).

Methods

33 patients (66 ears) who underwent bilateral inlay butterfly cartilage tympanoplasties between June 2013 and September 2016 in Department of Otolaryngology–Head and Neck Surgery of Adiyaman University Education and Research Hospital, Adiyaman, Turkey — a tertiary care university teaching hospital. Anatomical success and functional success were assessed postoperatively. Air-bone gap (ABG), air-conduction thresholds, and bone-conduction thresholds were all assessed. The preoperative and postoperative averages of 0.5, 1, 2, and 3 kHz of pure-tone thresholds were used for the mean air- and bone-conduction thresholds according to the guidelines of the Committee on Hearing and Equilibrium.

Results

Anatomical success could be demonstrated in 57 of 66 ears (86.3%). The overall mean of ABG improved from 23.97 ± 8.63 dB preoperatively to 10.42 ± 4.82 dB postoperatively (p < 0.05). The ABG gain was 13.55 ± 8.17 dB. Postoperative percentages of patients with ABG less than 20 dB and 10 dB were excellently achieved to 98% (41% preoperatively) and 56% (10.6% preoperatively), respectively. The average length of operation time for both ears was 57.42 ± 9.39 min.

Conclusion

When compared with conventional two-staged tympanoplasty in patients with BCOM, simultaneous BIBCT using tragal cartilage from one ear is an advantageous approach for multiple reasons which include single hospital stay with resultant decreased risk of complications associated with anesthesia and surgery, less morbidity like cosmetic and hearing discomfort, time-savingness and cost-effectiveness.

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In situ effect of fluoride toothpaste supplemented with nano-sized sodium trimetaphosphate on enamel demineralization prevention and biofilm composition

Publication date: Available online 1 October 2018

Source: Archives of Oral Biology

Author(s): Nayara Gonçalves Emerenciano, Alberto Carlos Botazzo Delbem, Juliano Pelim Pessan, Gabriel Pereira Nunes, Francisco Nunes Souza Neto, Emerson Rodrigues de Camargo, Marcelle Danelon

Abstract

Objective

To evaluate the effect of a fluoride toothpaste containing nano-sized sodium trimetaphosphate (TMPnano) on enamel demineralization in situ and composition of the biofilm.

Design

This crossover double-blind study consisted of four phases (seven days each) and 12 volunteers who wore oral appliances containing four enamel bovine blocks. The cariogenic challenge was performed by 30% sucrose solution (6x/day). The toothpaste treatments (3x/day) were as follows: no F/TMP/TMPnano (Placebo), 1,100 ppm F (1100 F), 1100 F plus 3% micrometric or nano-sized TMP (1100 F/TMP; 1100 F/TMPnano). Percentage of surface hardness loss (%SH), and integrated loss of subsurface hardness (ΔKHN), as well as enamel calcium (Ca), phosphorus (P), and fluoride (F) were determined. Moreover, biofilm formed on the blocks were analyzed for F, Ca, P, and insoluble extracellular polysaccharide (EPS) concentrations. Data were analyzed using one-way ANOVA, repeated measures followed by Fisher LSD test (p < 0.001).

Results

1100 F/TMPnano promoted the lowest %SH and ΔKHN among all groups (p < 0.001). Regarding the F concentrations in the enamel and in the biofilm, there were no significant differences between 1100 F and 1100 F/TMPnano, but significantly increased enamel Ca concentrations (p < 0.001). 1100 F/TMPnano showed lower values of EPS concentration when compared with 1100 F (~80%) (p < 0.001).

Conclusion

1100 F/TMPnano promoted a greater protective effect against enamel demineralization and significantly affected the composition of biofilm formed in situ when compared to 1100 F toothpaste.

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