Detection of Specific Immunoglobulins in the Saliva of Patients With Mild COVID-19.

Saliva has many advantages over blood as a biofluid, so using it for measuring and monitoring antibody responses in COVID-19 would be highly valuable. To assess the value of saliva-based IgG and IgM/IgA antibody testing in COVID-19, this cross-sectional pilot study evaluated the accuracy of salivary and serum IgG and IgM/IgA for detecting mild COVID-19 and their correlation. Fifty-one patients with mild COVID-19 (14-28 days post-symptom onset) were included in the study. Enzyme-linked immunosorbent assays (ELISA) were used to measure IgG and IgM/IgA responses to SARS-CoV-2 spike protein in both serum and saliva samples using a slightly modified protocol for saliva samples. Saliva-based IgG testing had 30% sensitivity and 100% specificity, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 50%. Saliva-based IgM/IgA testing had 13.2% sensitivity and 100% specificity, with a PPV of 100% and an NPV of 28.3%. Blood and saliva IgG values were positively correlated. Saliva currently has limited diagnostic value for COVID-19 testing, at least for mild disease. Nevertheless, the significant positive correlation between blood and saliva IgG titers indicates that saliva might be a complementary biofluid for assessing systemic antibody responses to the virus, especially if the assay is further optimized across the full disease spectrum.

Assessing Tele-Oral Medicine in Saudi Arabia: A Cross-Sectional Study on Specialists' Experiences and Effectiveness in Oral Healthcare.

INTRODUCTION: Teledentistry is an emerging tool to exchange medical information and clinical images to facilitate the diagnosis, prevention, and treatment of oral diseases and patient assurance and education. Considering the shortage of oral medicine specialists in Saudi Arabia, this study aims to assess the experiences of dental specialists with tele-oral medicine and its potential applicability in addressing this shortage. MATERIALS AND METHODS: This was a pilot, cross-sectional study conducted among specialists in the field of oral medicine from January 2020 to March 2020. A total of 16 preselected cases with oral lesions, including clinical history and images, were developed, validated, and shared via email with study participants. Each case included questions on differential diagnosis, provisional diagnosis, and management. The responses were recorded, analyzed, and presented as means and percentages. RESULTS: A total of 49 subjects participated in this study and more than half were under 40 years of age and two-thirds were women. A total of 23 participants had prior experience with tele-oral medicine, mainly via WhatsApp (95.7%), and these cases were received from patients, their families, friends, or other dentists. For all study cases, the correct diagnosis score ranged between 73.50 and 100%, and correct management ranged between 51 and 98%. CONCLUSIONS: Tele-oral medicine is an effective tool that may play an important role in patient management in rural regions with a shortage of oral medicine services. Further studies with larger sample sizes and in collaboration with international centers are warranted to confirm these findings.

Erythema multiforme-like lip presentation in pemphigus vulgaris patients: a multicenter case series.

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous blistering disease. Autoantibodies are directed against desmogleins, leading to the formation of intraepithelial bullae. PV, as with other autoimmune mucocutaneous disorders of the oral cavity, presents diagnostic and therapeutic challenges. Approximately 50-70% of cases present first with oral lesions. The lesions commonly start as vesicles or bullae that rapidly rupture, leading to erosions and ulcerations. The palatal, gingival, buccal, and labial mucosa are the most commonly affected sites. Oral PV can mimic several other diseases that cause mucosal erosions and/or ulcerations, including erythema multiforme (EM). EM is an acute, immune-mediated, self-limited hypersensitivity condition primarily associated with herpes simplex infection. Oral lesions can be variable, but a very characteristic presentation with labial hemorrhagic erosions, ulcerations and crusting is commonly seen. In this case series, we present six cases of PV: one male patient and five female patients whose ages ranged from 34 to 65 years old. All patients presented with hemorrhage and crusting of the lips in addition to multiple intraoral erosions and ulcerations. Three patients presented with oral and skin lesions. All patients underwent biopsies, and a diagnosis of PV was confirmed. All patients were treated with steroids (topical and systemic) and variable steroid-sparing agents. This case series emphasizes that oral PV may be misdiagnosed as EM in a subgroup of patients who present with persistent lip hemorrhage and crusting. Therefore, a comprehensive history, clinical examination and incisional biopsies should be considered in such patients.

Perineural Invasion Is a Significant Prognostic Factor in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

(1) Objectives: This systematic review and meta-analysis aimed to summarize current evidence regarding the prognostic role of perineural invasion (PNI) in patients with oral squamous cell carcinoma (OSCC). (2) Methods: We searched Cochrane Central, ProQuest, PubMed, Scopus, Science Direct, and Web of Science, using relevant keywords to identify eligible articles. Two independent reviewers conducted two-stage screening, data extraction, and quality assessment. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) criteria. All analyses were performed using comprehensive meta-analysis (CMA; version 3.3.070) software. (3) Results: The study included 101 published articles encompassing 26,062 patients. The pooled analyses showed that PNI was associated with significantly worse overall survival (OS; HR = 1.45, 95% CI: 1.32-1.58; p < 0.001), worse disease-specific survival (DSS; HR = 1.87, 95% CI: 1.65-2.12; p < 0.001), and worse disease-free survival (DFS; HR = 1.87, 95% CI: 1.65-2.12; p < 0.001). Similarly, both local recurrence-free survival (LRFS) and regional recurrence-free survival (RRFS) were worse in patients with PNI (HR = 2.31, 95% CI: 1.72-3.10, p < 0.001; and HR = 2.04, 95% CI: 1.51-2.74, p < 0.001), respectively. The random-effect estimate of three studies demonstrated that the presence of PNI was associated with worse failure-free survival (FFS; HR = 2.59, 95% CI: 1.12-5.98, p < 0.001). (4) Conclusions: The current evidence suggests that PNI can be used as an independent predictor of the prognosis for patients with OSCC. The presence of PNI was associated with worse OS, DFS, DSS, FFS, and with recurrence. Asian patients and patients with extra-tumoral or peripheral PNI invasion were associated with worse prognosis.

Osteolytic Lesion of the Maxilla in an Undiagnosed Multiple Myeloma Patient Identified Incidentally by Cone Beam Computed Tomography.

BACKGROUND Multiple myeloma is a hematological malignancy characterized by monoclonal plasma cell proliferation. Jaw lesions are found in nearly 35% of patients with symptomatic myeloma, and lesions occur in the mandible more often than in the maxilla. However, maxillary or mandibular lesions are rarely found as a primary manifestation of the disease. This report describes a case of a 65-year-old Palestinian woman with lytic lesions in the maxilla due to undiagnosed multiple myeloma identified incidentally on cone beam computed tomography (CBCT). CASE REPORT A 65-year-old Palestinian woman presented to the Oral Maxillofacial Surgery Clinic with an expansion of the maxilla which was initially thought of as an infection. CBCT imaging revealed diffuse osteolytic lesions involving multiple osseous structures. The patient was biopsied. Histopathological examination was suspicious for plasmacytic neoplasm. She was directly referred to the Hematology Department for further laboratory tests. These included complete blood count, liver function test, bone profile, protein electrophoresis, flow cytometry, and bone marrow biopsy, which were performed to confirm the diagnosis of multiple myeloma. The patient was treated with chemotherapy including zoledronic acid, dexamethasone, bortezomib, and cyclophosphamide. She went into remission for a year but unfortunately died 2 years later. CONCLUSIONS Primary myeloma of the maxilla is a rare presentation. The present report illustrates the role of CBCT imaging supported by a multidisciplinary approach to the diagnosis and management of myeloma. Consequently, it is recommended that dental practitioners be aware of radiographic features and possible oral manifestations to avoid any delay in medical intervention.

A 65-Year-Old Woman with an Enlarged Tongue Due to Amyloidosis.

BACKGROUND Amyloidosis is a clinical condition characterized by the extracellular deposition of insoluble, abnormal amyloid fibrils in various body tissues. It is generally categorized into 2 forms - localized and systemic - with a wide range of signs and symptoms. This case report discusses the localized amyloidosis involvement of the oral cavity and its treatment. CASE REPORT A 65-year-old woman presented to the oral medicine clinic reporting painless tongue enlargement, which has been slowly progressing over several years, leading to difficulty in tongue movement, eating, and swallowing. Extra-oral examination showed a prominent lower lip with rubbery consistency. Intra-oral examination revealed a significantly enlarged tongue almost filling the whole oral cavity with dental indentations evident on all tongue surfaces and multiple, deep ulcerative craters of various sizes ranging from 2 to 5 mm in diameter. Histopathological examination under light microscope using hematoxylin and eosinophil and Congo red stain were diagnostic for amyloidosis. Further investigation with the Rheumatology Department, including renal and liver function tests, as well as echocardiography, were conducted and ruled out systemic involvement of other body organs. The patient was treated with weekly intra-lesional triamcinolone injections, with significant improvement. CONCLUSIONS We report a rare case of localized amyloidosis presenting as macroglossia. Although the most effective management in tongue amyloidosis is surgical resection, conservative management in cases of localized oral amyloidosis presenting as macroglossia with weekly intra-lesional triamcinolone injections can be an effective approach, providing patients with better quality of life. Future studies exploring treatment modalities for similar cases with limited oral involvement are warranted.

A Case Report on Familial White Sponge Nevus in Saudi Arabia.

White sponge nevus (WSN) is an uncommon, benign, autosomal dominant disorder that usually appears at birth or in early childhood. It affects males and females equally and is caused by germ line mutations of the keratin genes leading to keratin instability and tonofilament aggregation. The condition causes painless, white, thickened, corrugated plaques to form on the oral mucosa, especially bilaterally on the buccal mucosa. Extra-orally, it occurs most often in the vaginal mucosa, as well as in the nasal and esophageal mucosa. In this report, we describe the case of a healthy 32-year-old Saudi male in Jizan in southern Saudi Arabia whose general dentist referred him to the oral medicine clinic at King Abdulaziz University Hospital, where he was diagnosed with white sponge nevus. The patient reported no medical problems and was a cigarette smoker for more than 10 years. An oral examination revealed white lesions affecting the buccal mucosa bilaterally and the labial mucosa. A biopsy of the buccal mucosa confirmed the diagnosis of white sponge nevus. Laser therapy was suggested for the aesthetic treatment of the lesions. Better awareness of this hereditary condition among dental professionals can help improve timely diagnoses early in life and thus avoid unnecessary or inadequate treatment for this benign condition.

Formulation, Optimization, and Evaluation of Oregano Oil Nanoemulsions for the Treatment of Infections Due to Oral Microbiota.

INTRODUCTION: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation's aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health. METHODS: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities. RESULTS: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats. CONCLUSION: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.

Why do students skip classroom lectures: A single dental school report.

BACKGROUND: Conventional classroom lectures continue to represent a major component of the dental education system to ensure optimum delivery of knowledge. Certain number of students are less compliant and likely to skip classes which may impact the overall academic performance. The aim of this study was to investigate dental students' attitude towards classroom attendance and potential reasons for absenteeism at King Abdulaziz University-Faculty of Dentistry (KAU-FD). METHODS: This was a cross-sectional survey of all dental students actively enrolled at KAU-FD from January to June 2019. The survey included questions on demographics, average travel time to school, current dental year, most recent GPA, student's perspective toward classroom lectures. The survey was validated and distributed to all students at a pre-selected time frame. Data were analysed and presented as frequencies and percentages; chi-square test was used to explore parameters association. RESULTS: A total of 678 students consented and completed the survey. Overall, 44.3% of students were more likely to skip two classes or less per month. Second year dental students were more likely to be absent from classroom lectures (31.3%), while 3rd year dental students were less likely to do so (15.4%). Reported students' justifications for missing classes included early morning classes (47.9%), exams preparation (42%), and lecturer's weak presentation skills (41.9%). CONCLUSION: Compliance of dental students with classroom attendance has been an ongoing challenge for most programs. The current data suggests a multifactorial module for students' attitude toward classroom attendance. Future studies focusing on reasons behind classroom attendance behavior and addressing students' concerns are needed.

The application of teledentistry for Saudi patients' care: A national survey study.

BACKGROUND/PURPOSE: Teledentistry has emerged as a new communication tool in various dental disciplines around the world. The aim of this study was to investigate the applicability and reliability of teledentistry in the field of diagnostic dentistry and explore the perception of Saudi dentists of its benefits and concerns. MATERIALS AND METHODS: An electronic survey with 40 questions was developed, validated and distributed electronically by email and social media channels to dentists from different specialty in Saudi Arabia. Collected data were analyzed for statistical significance. RESULTS: A total of 148 dentists completed the survey. The current data demonstrated that 50% of study participants have had applied teledentistry in their clinical practice. Out of all, 90% have computers in their dental offices and 72% have been using electronic medical records in which radiographs and clinical images are uploaded. Most participants had smart phones (91%), in which they were used more commonly (74.3%) than conventional cameras (54.1%) to capture and share patients' clinical images over communication applications (74.3%) and less likely through emails (62.2%). Overall, 83% were confident that teledentistry can improve daily dental practice, specifically in the fields of oral radiology followed by endodontics and oral medicine. CONCLUSION: Teledentistry is an emerging tool with potential to improve the delivery of diagnostic dental care for communities with limited or no access to dental specialists. As of today, teledentistry has not been truly implemented by the Saudi dental community. Development of national programs to educate the public and promote teledentistry among dental practitioners are warranted.

Medication-Induced Oral Hyperpigmentation: A Systematic Review.

BACKGROUND: Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact pathogenesis of tissue pigmentation varies greatly and is not completely known. This systematic review aimed to present data on the causal association between medications and the development of oral/mucosal pigmentation as an adverse drug reaction. METHODS: A systematic review and analysis of literature were conducted using the following databases: PubMed, Science Direct, ProQuest, Web of Science, and Scopus. The systematic review included original articles written in English and published between January 1982 and June 2020. Following the PRISMA statement, eligible articles were systematically reviewed, and data were extracted from eligible studies and analyzed. RESULTS: A total of 235 articles were identified, of which 57 met the inclusion criteria and were included in this review. The mean age of included patients was 46.2±16.38 years (range: 10-90 years) with a male to female ratio of 1:1.45. Oral mucosal hyperpigmentation was reported following the use of several classes of medications such as antiviral (eg, zidovudine), antibiotic (eg, minocycline), antimalarial (eg, chloroquine), anti-fungal (eg, ketoconazole), antileprotic (eg, clofazimine), antihypertensive (eg, amlodipine), chemotherapeutic, and antineoplastic drugs. The risk of developing oral pigmentation was significantly higher with antimalarial medications, antibiotics, antineoplastic and chemotherapeutic agents. Medication-induced oral hyperpigmentation was most frequent among women and in the hard palate. CONCLUSION: Future research is warranted to better understand the pathogenesis and risk factors for medication-induced oral hyperpigmentation in order to reassure patients during prescription and management.

Bone morphogenetic protein 2: a potential new player in the pathogenesis of diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus. Vision loss in DR principally occurs due to breakdown of the blood-retinal barrier (BRB), leading to macular edema, retinal detachment and inner retinal and vitreous hemorrhage. Several growth factors have been shown to play crucial role in the development of these vascular changes; however, the cellular and molecular mechanisms of DR are not yet fully revealed. In the current study we investigated the role of bone morphogenetic protein-2 (BMP2) in DR. We examined the changes in the protein levels of BMP2 in human vitreous and retina in addition to the mouse retina of streptozotocin-induced diabetes. To detect the source of BMP2 during diabetes, human retinal endothelial cells (hRECs) were subjected to high glucose (HG) for 5 days and levels of BMP2 protein were analyzed in conditioned media of these cells relative to control. We also evaluated the effect of BMP2 on the levels of VEGF in cultured rat Müller cells (rMC1). In addition, we tested the pro-inflammatory effects of BMP2 by examining its effect on leukocyte adhesion to cultured hRECs, and levels of adhesion molecules and cytokines production. Finally, the effect of different concentrations of BMP2 on permeability of confluent monolayer of hRECs was evaluated using FITC-Dextran flux permeability assay and by measuring Transcellular Electrical Resistance (TER) using Electric Cell-substrate Impedance Sensing (ECIS). Our results show, for the first time, the up-regulation of BMP2 in diabetic human and mouse retinas in addition to its detection in vitreous of patients with proliferative DR (72 ± 7 pg/ml). In vitro, hRECs showed upregulation of BMP2 in HG conditions suggesting that these cells are a potential source of BMP2 in diabetic conditions. Furthermore, BMP2 induced VEGF secretion by Müller cells in-vitro; and showed a dose response in increasing permeability of cultured hRECs. Meanwhile, BMP2 pro-inflammatory effects were recognized by its ability to induce leukocyte adhesion to the hRECs, intercellular adhesion molecule-1 (ICAM-1) and upregulation of interleukin-6 and 8 (IL-6 and IL-8). These results show that BMP2 could be a contributing growth factor to the development of microvascular dysfunction during DR via enhancing both pro-angiogenic and inflammatory pathways. Our findings suggest BMP2 as a potential therapeutic target to prevent/treat DR.

Difference in soft tissue response between immediate and delayed delivery suggests a new mechanism for recombinant human bone morphogenetic protein 2 action in large segmental bone defects.

The ability of recombinant human bone morphogenetic protein 2 on absorbable collagen sponge (rhBMP2/ACS) to regenerate bone in segmental defect has been well characterized. However, clinical results of rhBMP2/ACS constructs in secondary reconstruction of large mandibular and craniofacial defects have not been consistent. We hypothesized that rhBMP2 delivery triggers an endogenous response in the soft tissues surrounding the defect, in the form of expression of BMP2 and vascular endothelial growth factor (VEGF). Such osteogenic response will occur only after immediate, as opposed to delayed, rhBMP2 delivery, suggesting a new explanation to the difference in bone regeneration between the two settings. A 35-mm segmental bone and periosteum defect was created on one side of the mandible in 16 dogs divided in three groups. Group 1 (Gp1, n=6) ACS was loaded with 8 mL of rhBMP2 (0.2 mg/mL). In Gp2 (n=5) the same dose of rhBMP2/ACS was delivered into the defect 4 weeks after surgery. In Gp3 (control; n=5) the defect was reconstructed using ACS loaded with 8 mL of buffer only (devoid of rhBMP2). Tissues were collected after 12 weeks of reconstruction in all groups. Direct measurement of physical dimensions of regenerates and bone morphometry was performed to evaluate bone regeneration. The mRNA expression of both BMP2 and VEGF in the soft tissue surrounding the defect was evaluated using real-time quantitative PCR. Both BMP2 and VEGF proteins were quantified in immunostained sections. Immunoflurescence colocalization of BMP2 and acetylated low density lipoprotein (AcLDL) was done to detect the source of BMP2. Immediate delivery yielded better bone regeneration. Both BMP2 and VEGF mRNA expression was upregulated only in Gp1 (+7.3, p=0.001; +1.53, p=0.001, respectively). BMP2 protein was significantly higher in the immediate reconstruction group; however, VEGF protein was undetected in the examined sections. Immediate delivery of rhBMP2 seemed to induce endogenous release of BMP2 from the surrounding soft tissues, an effect that was lacking in delayed delivery and may explain the variability of clinical results associated with BMP2 use. Colocalization of BMP2 and endothelial cells (ECs) suggested that ECs could be the source of endogenous BMP2.

Recombinant bone morphogenetic protein-2 induces up-regulation of vascular endothelial growth factor and interleukin 6 in human pre-osteoblasts: role of reactive oxygen species.

OBJECTIVE: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). METHODS: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis genes were measured using angiogenic PCR array. VEGF and IL6 production were analysed using ELISA kit and real-time PCR. ROS production was assessed using dihydroethidine and dichlorofluorescein staining and lipid peroxidation. HIF-1α immunoreactivity was performed using immunofluorescence staining. RESULTS: There was an increase in the pro-angiogenic and -inflammatory genes as well as VEGF and IL6 protein expression in NHOst by rhBMP-2. This increase in VEGF and IL6 was blocked by the ROS scavenger N-acetyl cysteine (NAC). CONCLUSION: The regulatory effect of rhBMP-2 on angiogenesis and inflammation is mediated through a ROS-dependent mechanism, which involves upregulation of crucial angiogenic and inflammatory mediators such as VEGF and IL6. These findings highlight the need for future studies to identify new therapeutic targets downstream from rhBMP-2 to potentiate its beneficial effect or limit its complications such as seroma formation.

Reconstruction of canine mandibular bone defects using a bone transport reconstruction plate.

OBJECTIVES: Reconstruction of mandibular segmental bone defects is a challenging task. This study tests a new device used for reconstructing mandibular defects based on the principle of bone transport distraction osteogenesis. METHODS: Thirteen beagle dogs were divided into control and experimental groups. In all animals, a 3-cm defect was created on one side of the mandible. In 8 control animals, the defect was stabilized with a reconstruction plate without further reconstruction and the animals were killed 2 to 3 months after surgery. The remaining 5 animals were reconstructed with a bone transport reconstruction plate, comprising a reconstruction plate with attached intraoral transport unit, and were killed after 1 month of consolidation. RESULTS: Clinical evaluation, cone-beam CT densitometry, three-dimensional histomorphometry, and docking site histology revealed significant new bone formation within the defect in the distracted group. CONCLUSION: The physical dimensions and architectural parameters of the new bone were comparable to the contralateral normal bone. Bone union at the docking site remains a problem.

Suppression of retinal peroxisome proliferator-activated receptor gamma in experimental diabetes and oxygen-induced retinopathy: role of NADPH oxidase.

PURPOSE: Recently, the authors have shown that NADPH oxidase is positively correlated with increased leukocyte adhesion and vascular leakage in diabetes and neovascularization in oxygen-induced retinopathy (OIR). Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have been shown to prevent vascular inflammation and leakage in an experimental model of diabetes. The goal of this study was to investigate whether there is a link between NADPH oxidase and PPARgamma that leads to vascular dysfunction in diabetic retina or OIR. METHODS: Diabetes was induced with streptozotocin in wild-type mice or NOX2 knockout mice. One group of wild-type mice was treated with apocynin. Bovine retinal endothelial cells (BRECs) were treated with normal glucose (5 mM) or high glucose (25 mM) in the presence or absence of superoxide dismutase (SOD) or NADPH oxidase inhibitors (apocynin or diphenyleneiodonium [DPI]). Western blotting and immunofluorescence were used to evaluate PPARgamma expression. Activation of nuclear factor (NF)kappaB was measured using the transcription factor assay kit and Western blot analysis of phospho-NFkappaB. PPARgamma expression was also tested in OIR and lipopolysaccharide-induced retinal inflammation. RESULTS: Retinal expression of PPARgamma was suppressed in experimental models of diabetes, OIR, and retinal inflammation. This was associated with the activation of NFkappaB in the diabetic retina. These effects were prevented by apocynin or deletion of NOX2. PPARgamma expression was also suppressed in endothelial cells treated with high glucose, and this was prevented by apocynin, DPI, and SOD. CONCLUSIONS: Suppression of PPARgamma is involved in the pathogenesis of diabetic retinopathy and OIR. NADPH oxidase could be an upstream mediator of these changes.