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Thyroid Eye Disease (TED) is an inflammatory autoimmune condition affecting the eyes, often associated with Graves’ disease. Inflammation is important in TED, involving immune cells and orbital tissues. While inflammatory markers have been studied in other diseases, their role in TED is unclear. We included 734 participants from 5 eligible studies investigated associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) and TED. Initial analysis found no significant differences in these markers between TED and control groups. However, sensitivity analysis excluding an outlier study revealed significant differences in NLR, PLR, and MLR between groups, suggesting the potential association between these inflammatory markers and TED. More research is needed, but these findings indicate complex TED pathogenesis and that inflammation may offer insights for TED diagnosis and management. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether patients with thyroid disease are at increased risk of uveitis.Methods: Data was collected from the Taiwan National Health Insurance system and included patients newly diagnosed with thyroid disease from 2000 to 2012. The endpoint of interest was a diagnosis of uveitis.Results: In analyzing 21,396 patients with thyroid disease, yielding 85,584 matched comparisons, patients with thyroid disease to have a significantly higher cumulative incidence of uveitis when compared to the control cohort with the Kaplan-Meier analysis. This result was further confirmed by Cox regression analysis. The increased risk was persistent in both genders. The association between thyroid disease and uveitis was stronger in patients without diabetes or hypertension.Conclusion: Patients with thyroid disease were found to have a higher risk for uveitis. For certain age groups or patients without diabetes or hypertension, the role of thyroid disease might be more crucial for uveitis development. [ABSTRACT FROM AUTHOR]

Abstract: An increase in cytosolic calcium concentration triggers intracellular signal transduction in vascular cells, which then regulates the vascular contraction. In the present study, the regulatory mechanism of carteolol on the intracellular free Ca2+ ([Ca2+] i ) mobilization was investigated in cultured A7r5 vascular smooth muscle cells. The A7r5 cells were cultured and loaded with fura-2-AM, which was used as a Ca2+ sensitive fluorescent probe. In both the presence and absence of external Ca2+, carteolol increased [Ca2+] i with a dose-dependent manner in A7r5 cells at concentrations between 608µM and 6.08µM. In a Ca2+-containing buffer, carteolol-induced [Ca2+] i showed an initial peak followed by a secondary and persistent plateau. Pretreatment of the cells with La3+, the plasma membrane Ca2+ pump inhibitor, and nifedipine, a L-type Ca2+ channel inhibitor, both partially restrained the carteolol-induced initial peak in [Ca2+] i by 92% and 86%, respectively. Pretreatment of the cells with adrenoceptor antagonists, prazosin inhibited the [Ca2+] i response by 80%, and propranolol enhanced the response by 61%. In the Ca2+−-free buffer, pretreatment of the cells with carteolol inhibited the endoplasmic reticulum Ca2+ pump inhibitor of thapsigargin-induced [Ca2+] i increase by 97%. Pretreatment of the cells with thapsigargin also inhibited the carteolol-induced [Ca2+] i rise by 98%. The internal Ca2+ release induced by the carteolol was partially inhibited by U73122 (phospholipase C inhibitor) and aristolochic acid, quinacrine (phospholipase A2 inhibitors). After incubation of carteolol in the Ca2+-free buffer, the addition of CaCl2 increased the Ca2+ influx, implying that the release of Ca2+ from internal stores further induced capacitative Ca2+ entry. These results suggest that carteolol-induced [Ca2+] i increase is mediated by the initial influx via the α1-adrenoceptor, L-type Ca2+ channel, nonselective calcium entry channels and release of Ca2+ from an intracellular store, which is mainly in the endoplasmic reticulum followed by capacitative Ca2+ entry but decrease via the β2-adrenoceptor. The intracellular Ca2+ release was also modulated by phospholipase A2, C-coupled events. [Copyright &y& Elsevier]

Background: Little is known of the pathogenetic mechanisms of enterovirus type 70 (EV70), a causative agent of acute hemorrhagic conjunctivitis. However, virus- or cytokine-induced perturbation of vascular endothelial cells are potential triggering events. Objective: To determine whether EV70 infection of human umbilical vascular endothelial cells (HUVECs) and human corneal epithelial cells (HCEs) causes the release of vasoactive cytokines, capable of triggering vascular endothelial cell activation. Study design: Susceptibility of cultured HUVECs and HCEs to EV70 was tested by observing the appearance of cytopathic effect or immunoprecipitation of viral protein in infected cells. The culture fluids from the virus-infected cells were tested for their ability to stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) on uninfected HUVECs. Anti-cytokine antibodies were used to identify ICAM-1-activating cytokine(s). Results: Both HUVECs and HCEs were susceptible to EV70 infection. Culture fluids from EV70-infected HUVECs and HCEs stimulated ICAM-l expression on uninfected HUVECs, which was completely blocked by anti-interleukin-1α (IL-1α) antibody but not by interleukin-1β (IL-1β) or anti-tumor necrosis factor α (TNFα) antibodies. Conclusion: This study provides the first evidence of EV70 infection of both HCEs and HUVECs, and furthermore, identifies IL-1α as the predominant endothelial cell-activating factor produced by EV70-infected cells. Since endothelial cell activation is often an initiating step towards vascular permeability and/or inflammation, the perturbation of endothelial cell function through EV70 induced IL-1α is thus a potential contributory factor in the pathogenesis of EV70-associated hemorrhagic conjunctivitis. [Copyright &y& Elsevier]

Although pulmonary inflammation is a serious, sometimes life-threatening, consequence of respiratory syncytial virus (RSV) infection, the mechanisms involved are not well understood. Since the process of inflammation is initiated by a complex series of events including the activation of specific adhesion molecules on vascular endothelium, we searched for endothelial cell-activating factors released from RSV-infected epithelial cells. We demonstrate here that vascular endothelial cells exposed to culture supernatants from RSV-infected pulmonary epithelial A549 cells are activated to express increased cell surface ICAM-1, and to a lesser extent, VCAM-1 and E-selectin. IL-1α was identified as the predominant endothelial cell-activating factor by pretreating epithelial cell supernatants with anti-IL-1α antibody. The preferential upregulation of endothelial ICAM-1 (relative to VCAM-1 and E-selectin) by RSV-infected epithelial cell supernatants was replicated by recombinant IL-1α thus confirming IL-1α as a major endothelial cell-activating cytokine released by RSV-infected epithelial cells. Il-1α mediated endothelial cell activation is thus a likely contributory event in the initiation of leukocyte inflammation associated with RSV infection. [Copyright &y& Elsevier]

Analyzes the effectiveness of antibiotics with bacterial susceptibility. Characteristics of the patients; Factors that led to orbital cellulitis; Bactericidal action of aminoglycosides; Comparison of the bactericidal actions between penicillins and cephalosporins.

To investigate whether patients with chronic kidney disease (CKD) are at increased risk of uveitis. Data was collected from the Taiwan National Health Insurance system and included patients newly diagnosed with CKD between 2000 and 2012. The endpoint of interest was a diagnosis of uveitis. 30,256 CKD patients and 121,024 matched comparisons were analyzed. CKD patients were found to have a significantly higher cumulative uveitis incidence. Through multivariate Cox regression analysis, the CKD group was found to have higher risk of developing uveitis (adjusted hazard ratio 1.51). After stratified by gender, age, and comorbidities (hypertension, diabetes, and hyperlipidemia), the increased risk of uveitis in CKD patients remained significant. Patients with CKD were found to have higher risk of developing uveitis. For patients over 18 years old and with hypertension, diabetes, or hyperlipidemia, the presence of CKD was demonstrated as an additional crucial factor for uveitis development. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epidemics of acute hemorrhagic conjunctivitis (AHC) caused by a coxsackievirus A24 variant (CA24v) appeared in Taiwan in 2000–2002 and again in 2006–2007. Objective: To analyze the molecular epidemiology of CA24v in recent outbreaks in Taiwan. Study design: A 510bp fragment of 3Cpro region was analyzed in 30 CA24v isolates during 2000–2007. Phylogenetic tree was constructed along with 130 CA24v isolates available from the GenBank. Moreover, the 235bp of 3′VP1 region was similarly analyzed in 15 randomly selected strains isolated during 1985–2007. Phylogenetic dendrogram was constructed for the 3′VP1 region in 105 CA24v strains worldwide. Genetic distances were calculated using Kimura 2-parameter model, and phylogenetic trees were constructed by neighbor-joining method. Results: The 3Cpro dendrogram depicted genotype IV (GIV), a new genotype that can be further divided into three clusters (C1–C3). The 2000–2002 outbreaks were caused by genotype IV-cluster 1 (GIV-C1) and GIV-C2. Strains isolated in the 2006–2007 outbreak belong to GIV-C3, also in the same cluster as Singapore strains from 2005. Analysis on 3′VP1 revealed only GI, GIII and GIV in line with the classification in 3Cpro dendrogram. All genotype IV strains were also divided into three clusters, though the GIV-C 2′ were isolated from broader geographic areas and over a longer period of time. Conclusions: Analysis of the 3Cpro region is more insightful than the 3′VP1 region in the molecular epidemiology of CA24v. The 3Cpro dendrogram accurately and chronologically identified all stains involved in the worldwide outbreaks. [Copyright &y& Elsevier]

We report the rescue effect of intravitreal aflibercept injections on retinal neovascularization and macular edema due to Eales disease. Case 1 was a 36-year-old female. Intravitreal aflibercept was administered as rescue therapy after persistent retinal neovascularization following retinal photocoagulation, periocular triamcinolone, and intravitreal ranibizumab injection. Retinal neovascularization initially regressed, but recurred after 5 months along with macular edema. Two more intravitreal aflibercept injections were given, and retinal neovascularization with macular edema regressed. Her vision improved to 20/25 and remained stable after 43 months. Case 2 was a 27-year-old female. Intravitreal aflibercept was administered after persistent retinal neovascularization and macular edema following periocular triamcinolone injection. The macular edema initially subsided but recurred after 3 months. Intravitreal aflibercept injections were then administered once every three months to maintain her vision 20/20. The patient has been followed up for 28 months. Intravitreal aflibercept was effective as a rescue therapy in the treatment of Eales disease to regress retinal neovascularization, though repeated injections were necessary in cases of recurrence. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy of micro-incision vitrectomy surgery using a non-contact wide-angle viewing system for fovea-attached type epiretinal membrane, and to report the factors influencing the outcome. Methods: A retrospective, comparative case series that included 50 patients with fovea-attached type epiretinal membrane who received micro-incision vitrectomy surgery using a non-contact wide-angle viewing system. Results: All patients were followed-up for a minimum of 12 months. Seven cases were classified as group 1A (mainly outer retinal thickening), 17 were group 1B (more tenting of outer retina and distorted inner retina), and 26 were group 1C (prominent inner retina thickening and inward tenting of outer retina). Outcome measures included operation time, recurrent rate, postoperative BCVA, and CRT. The mean operative time was 26.2 minutes. The mean change of BCVA (LogMAR) was − 0.43 (p< 0.001). The mean change of CRT was 135.3 μm (p< 0.001). The mean change of CRT was significantly higher in group 1C. Worse preoperative BCVA, male gender, and longer operative time can predict better postoperative BCVA found by multivariate logistic regression and multiple regression models. Conclusion: Significant improvement in BCVA and CRT is noted after micro-incision vitrectomy surgery to operate fovea-attached type epiretinal membranes. Worse preoperative BCVA, male, and longer operation time could predict better improvement. These findings may assist surgeons in better evaluating the potential of this method to help their patients with epiretinal membranes. [ABSTRACT FROM AUTHOR]

Clinical usage of botulinum neurotoxin (BoNT) in ophthalmology has dramatically increased since the 1980s and has become one of the most widely used agents for treating facial movement disorders, autonomic dysfunction and aesthetic wrinkles. Despite its high efficacy, there are some complications with periocular BoNT injections due to its chemodenervation effect. Among these, there is still controversy over the BoNT effect on tear film homeostasis and the ocular surface. A periocular BoNT injection could dry the eye by reducing tear production of the lacrimal gland and increase tear evaporation due to potential eyelid malposition and abnormal blinks. On the contrary, the injection of BoNT in the medial eyelids could treat dry eye disease by impairing lacrimal drainage. Regarding the ocular surface change, corneal astigmatism and high-order aberrations may decrease due to less eyelid tension. In conclusion, the entire awareness of the effect of BoNT and the patients' ocular condition is crucial for successful and safe results. [ABSTRACT FROM AUTHOR]

Purpose: This study surveyed the novel autoantigens expressed in the orbital fat tissue of patients with Graves’ orbitopathy (GO) and explored the possibility of the autoantibodies against novel autoantigens as biomarkers for GO.Methods: We used immuno-proteomic methods to survey novel autoantigens expressed in the orbit fat tissue of GO patients and confirmed by enzyme-linked immunosorbent assay (ELISA).Results: One protein spot (aldehyde dehydrogenase 2 (ALDH2)) revealed high reactivity with the GO serum than did the healthy control serum and was further verified by ELISA. We found that the plasma anti-ALDH2 antibody level was increased in GO patients compared to healthy control donors. In addition, anti-ALDH2 antibody level was correlated with GO activity classified by clinical activity score(r = 0.588, p < 0.001, using Pearson’s correlation).Conclusions: These increased levels of anti-ALDH2 antibody in GO serum suggested that ALDH2 could attribute target autoantigen in GO, and anti-ALDH2 autoantibody might serve as a biomarker for GO and help to predict disease activity. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection is a worldwide threat to public health. Toll-like receptor 8 (TLR8) is critical for eliminating RNA viruses, and variation within the TLR8 gene may alter the function of TLR8 in response to HCV infection. Our previous study demonstrated that the TLR8-129G>C (rs3764879) and TLR8+1G>A (rs3764880) variants were in complete linkage disequilibrium, and that the frequency of TLR8-129C/+1A was significantly higher in male patients with HCV infection compared with the healthy controls. In the present study, we found that the promoter activity of TLR8-129G was higher than that of TLR8-129C in THP-1 cells. Moreover, TLR8-129G mRNA stability and competitive DNA-binding ability were significantly lower than that of TLR8-129C. To investigate the functional effects of TLR8 polymorphisms, we compared the nuclear factor- κB (NF- κB)-driven luciferase activity in HEK293 cells transfected with the TLR8 variants. TLR8+1A plasmids induced less NF- κB signalling than did those transfected with TLR8+1G after 20 μ m CL075 ( P = 0·011) stimulation. We also analysed the mRNA expression and cytokine production in whole blood and monocytes from people of various genotypes stimulated ex vivo by the interferon- γ and TLR7/8 agonist CL075, R848. TLR8 expression in CD14+ cells derived from volunteers with TLR8-129G/+1G was significantly higher than that derived from TLR8-129C /+1A, and interleukin-12p40 production was higher in volunteers with TLR8-129G/+1G after stimulation. The data indicate that variations in TLR8 genes may modulate immune responses during HCV infection. [ABSTRACT FROM AUTHOR]

Background: Thyroid orbitopathy (TO) is a multi-system inflammatory disease characterized by orbital congestion, ocular surface disorders, restrictive myopathy, and skin lesions. The molecular and cellular processes of pathogenic formation of TO orbital fat tissues are not fully understood. In this study, a comparative proteomic analysis was conducted to investigate the importance of some differential proteins of orbital fat tissues in TO. Methods: The differential proteins were analyzed by comparing the two-dimensional gel electrophoresis (2-DE) maps of the orbital fat tissues of TO with those of normal orbital fat tissues. The 2-DE results were further verified by Western blot and immunohistochemistry. Results: Fifteen up-regulated and two down-regulated proteins in TO orbital fat tissues in comparison with the control were exhibited by 2-DE maps. The over-expressed proteins including guanine nucleotide-binding protein, isocitrate dehydrogenase (IDH), annexin A2, heat shock protein 60 (HSP 60), calreticulin (CALR), protein disulfide-isomerase A3 (PDIA3), spectrin, superoxide dismutase (SOD), and transitional endoplasmic reticulum ATPase (TER ATPase) may contribute to increased thyroid-stimulating hormone receptor (TSHR) expression and cell proliferation. The proteomic data of specific proteins are consistent with those determined by Western blot and immunohistochemistry. Conclusions: Comparison of orbital fat proteins from thyroid orbitopathy with age-matched controls shows significant differences in the proteome, and up-regulations of the specific proteins in orbital fat tissues from TO are associated with biochemical mechanisms or capacities against endoplasmic reticulum stress, mitochondria dysfunction, and cell proliferation as well as apoptosis in TO orbital fat tissues. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) 40: 684-692 Background: Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. Methods: To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. Results: A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibi-ted earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. Conclusions: Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms. [ABSTRACT FROM AUTHOR]