Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats.

Alcohol Use Disorder (AUD) is a significant public health issue in the United States. It affects millions of individuals and their families and contributes to substantial societal and economic burdens. Despite the availability of some pharmacological treatments, there is still a pressing need to develop more effective therapeutic strategies to address the diverse range of symptoms and challenges associated with AUD. Catechol-O-methyltransferase (COMT) inhibition recently emerged as a promising new approach to treating AUD due to its potential to improve cognitive effects commonly associated with AUD. Tolcapone, an FDA-approved COMT inhibitor, has shown some promise for treating AUD; however, its ability to decrease drinking in ethanol-dependent rats has not been well-established. In this study, we evaluated the effects of tolcapone on operant, oral ethanol self-administration in non-dependent and dependent rats, and in rats that self-administered oral saccharin. To induce dependence, rats underwent the chronic intermittent exposure to vapor model, and their drinking levels were assessed during acute withdrawal from ethanol. Our results demonstrated that tolcapone attenuated responding for ethanol in dependent rats only, without affecting self-administration in non-dependent rats or rats self-administering saccharin. Moreover, we found that tolcapone was differentially effective in different estrous phases in female rats. These findings suggest that COMT inhibition, specifically using tolcapone, may be a valuable pharmacotherapy for treating AUD, particularly in individuals who are physically dependent on alcohol. Further research is needed to elucidate the precise mechanisms underlying the observed effects and to assess the potential of COMT inhibitors in a broader population of individuals with AUD.

Guttiferone E Displays Antineoplastic Activity Against Melanoma Cells.

Guttiferone E (GE) is a benzophenone found in Brazilian red propolis. In the present study, the effect of GE on human (A-375) and murine (B16-F10) melanoma cells was investigated. GE significantly reduced the cellular viability of melanoma cells in a time-dependent manner. In addition, GE demonstrated antiproliferative effect, with IC50 values equivalent to 9.0 and 6.6 µM for A-375 and B16-F10 cells, respectively. The treatment of A-375 cells with GE significantly increased cell populations in G0/G1 phase and decreased those in G2/M phase. Conversely, on B16-F10 cells, GE led to a significant decrease in the populations of cells in G0/G1 phase and concomitantly an increase in the population of cells in phase S. A significantly higher percentage of apoptotic cells was observed in A-375 (43.5%) and B16-F10 (49.9%) cultures after treatment with GE. Treatments with GE caused morphological changes and significant decrease to the melanoma cells' density. GE (10 µM) inhibited the migration of melanoma cells, with a higher rate of inhibition in B16-F10 cells (73.4%) observed. In addition, GE significantly reduced the adhesion of A375 cells, but showed no effect on B16-F10. Treatment with GE did not induce changes in P53 levels in A375 cultures. Molecular docking calculations showed that GE is stable in the active sites of the tubulin dimer with a similar energy to taxol chemotherapy. Taken together, the data suggest that GE has promising antineoplastic potential against melanoma.

Anti-glycemic potential of benzophenone thio/semicarbazone derivatives: synthesis, enzyme inhibition and ligand docking studies.

Inhibition of dipeptidyl peptidase-IV (DPP-IV) has been identified as a promising approach for the treatment of type 2 diabetes mellitus (T2DM). Therefore, development of DPP-IV inhibitors with new chemical scaffold is of utmost importance to medicinal chemistry. In the present study, we identified benzophenone thio- and semicarbazone scaffolds as novel DPP-IV inhibitors. For that purpose, benzophenone thio- and semicarbazone were synthesized through a 2-step reaction. These newly synthetic derivatives were characterized by different spectroscopic techniques, including HREI-MS and NMR. whereas stereochemistry of the iminic bond was predicted by NOESY experiments. Thio- and semicarbazones derivatives were evaluated for their DPP-IV inhibitory potential and found to exhibit a good to moderate enzyme inhibitory activity. Most active and non-cytotoxic derivatives were further evaluated for their DPP-IV inhibitory potential in in cellulo model. The binding sites as well as affinity of active compounds for DPP- IV enzyme were predicted by in silico studies, and compared to a standard drug, sitagliptin. Pharmacophore studies of thio- and semicarbazones derivatives 1-29 suggest that substitution of aryl group, particularly a lipophilic substituents at C-4″ of benzene ring, and a hydroxyl at C-4' strongly influenced the DPP-IV inhibitory activity. Compound 9 showed the highest inhibitory activity (IC50 = 15.0 ± 0.6 µM), whereas compounds 10, 17, 12, 14 and 23 showed a moderate activity with IC50 values in the range of 28.9-39.2 µM. This study identifies thio- and semicarbazones as new classes of DPP-IV inhibitors which may translate into safe and effective therapeutics for a better management of type 2 diabetes.Communicated by Ramaswamy H. Sarma.

Clinical effectiveness of posterior-only approach using polyetheretherketone cage combined with single-segment instrumentation for lumbar tuberculosis in children.

We sought to investigate the outcomes of posterior-only approach using polyetheretherketone (PEEK) cage combined with single-segment instrumentation (modified-approach) for mono-segment lumbar tuberculosis in children. Between February 2008 and August 2017 in our hospital, 18 children with single-segment lumbar tuberculosis enrolled in this study were treated by modified-approach. Medical records and radiographs were retrospectively analyzed. Mean follow-up time was 54.6 ± 12.1 months. No severe complications were noted to have occurred. Measures indicated there was satisfactory bone fusion for all patients. Mean Cobb angles were significantly decreased from preoperative angle (19.8° ± 13.1°) to those both postoperatively (- 4.9° ± 7.6°) and at final follow-up (- 3.5° ± 7.3°) (both P < 0.05), with a mean angle loss of 1.7° ± 0.9°. The erythrocyte sedimentation rate (ESR) returned to normal levels for all patients within 3 months postoperatively. All patients had significant postoperative improvement in neurological performance. The modified-approach was an effective and feasible treatment option for mono-segment children with lumbar tuberculosis. Such procedures can likely help patients by increasing retainment of lumbar mobility and reducing invasiveness.

High tibial osteotomy performed with PEEK implant demonstrated a failure rate of 28.

OBJECTIVES: Opening-wedge high tibia osteotomies (HTO) can be technically challenging. The HTO iBalance system was designed to reduce vascular complications and to avoid secondary plate removal. The purpose of the study was to evaluate the performance of the HTO iBalance system in patients with symptomatic medial osteoarthritis and varus malalignment. METHODS: The study was performed as a retrospective cohort study investigating a consecutive series of patients who underwent HTO with the iBalance system performed by a single surgeon from August 2013 to March 2016 at Zealand University Hospital, Koege, and Aleris-Hamlet Hospital. The primary outcome was the degree of realignment. The secondary outcome was Knee injury and Osteoarthritis Outcome Score (KOOS). Follow-up was performed at mean (SD) 25 (9.7) months. Weight-bearing long-leg standing radiographs were taken before surgery and at follow-up. Failure was defined as collapse of the HTO defined as a correction <50% of the intended correction at time of follow-up. Logistic regression was used to identify risk factors for failure. RESULTS: 44 patients and a total of 47 knees were included in this study. Preoperatively the mechanical axis was a mean (SD) 5.8° (2.9) varus and postoperatively 2.3° (3.7) varus . The HTO failed in 13 of 47 knees (28%). Patients with failure showed no statistically significant differences to non-failure in any KOOS subscore (p>0.05). American Society of Anesthesiologists (ASA) score (p=0.01) and body mass index (BMI) (p=0.05) were correlated with failure, whereas bone transplantation and smoking were not. CONCLUSION: In this study, the failure rate of HTO was 28%. High BMI and ASA-score were the only risk factors associated with failure while bone grafting and smoking were not. LEVEL OF EVIDENCE: Retrospective cohort study, level III.

Therapeutic targeting of FOS in mutant TERT cancers through removing TERT suppression of apoptosis via regulating survivin and TRAIL-R2.

The telomerase reverse transcriptase (TERT) has long been pursued as a direct therapeutic target in human cancer, which is currently hindered by the lack of effective specific inhibitors of TERT. The FOS/GABPB/(mutant) TERT cascade plays a critical role in the regulation of mutant TERT, in which FOS acts as a transcriptional factor for GABPB to up-regulate the expression of GABPB, which in turn activates mutant but not wild-type TERT promoter, driving TERT-promoted oncogenesis. In the present study, we demonstrated that inhibiting this cascade by targeting FOS using FOS inhibitor T-5224 suppressed mutant TERT cancer cells and tumors by inducing robust cell apoptosis; these did not occur in wild-type TERT cells and tumors. Mechanistically, among 35 apoptotic cascade-related proteins tested, the apoptosis induced in this process specifically involved the transcriptional activation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) and inactivation of survivin, two key players in the apoptotic cascade, which normally initiate and suppress the apoptotic cascade, respectively. These findings with suppression of FOS were reproduced by direct knockdown of TERT and prevented by prior knockdown of TRAIL-R2. Further experiments demonstrated that TERT acted as a direct transcriptional factor of survivin, up-regulating its expression. Thus, this study identifies a therapeutic strategy for TERT promoter mutation-driven cancers by targeting FOS in the FOS/GABPB/(mutant) TERT cascade, circumventing the current challenge in pharmacologically directly targeting TERT itself. This study also uncovers a mechanism through which TERT controls cell apoptosis by transcriptionally regulating two key players in the apoptotic cascade.

A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer.

Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m2) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m2. No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017).

Carbon-fiber reinforced PEEK instrumentation for spondylodiscitis: a single center experience on safety and efficacy.

Radiolucent carbon-fiber-reinforced (CFR) polyethyl-ether-ether-ketone (PEEK) has been established in spinal instrumentation for oncological reasons. Laboratory data reported comparable bacterial adhesion as titanium. Thus, using of CFR-PEEK spinal instrumentation for spondylodiscitis bases on artifact-free imaging to evaluate therapeutic success. Studies comparing the rate of pedicle screw loosening and relapse of spondylodiscitis following titanium versus CFR-PEEK instrumentation do not exist so far. This study evaluates the rate of pedicle screw loosening and recurrence of spondylodiscitis after CFR-PEEK instrumentation for spondylodiscitis compared to titanium. We conducted a prospective single center study between June 2018 and March 2019 on consecutive 23 patients with thoracolumbar spondylodiscitis. Imaging data was evaluated for screw loosening at a minimum of three months after surgery. A matched-pair analysis was performed using spondylodiscitis cases between 2014 and 2016 using titanium instrumentation for equal localization, surgery, and microorganism class. Among 17 cases with follow-up imaging, six cases (35%) showed screw loosening while only 14% (two patients) with titanium instrumentation were loosened (p = 0.004). In both groups the most frequent bacterium was Staphylococcus aureus, followed by Staphylococcus epidermidis. From the S. aureus cases, one infection in both groups was caused by methicillin resistant species (MRSA). No difference was found in the rate of 360° fusion in either group due to matching criteria. As opposed to other indications CFR-PEEK screws show more loosening than titanium in this series with two potentially underlying reasons: a probably stronger bacterial adhesion on CFR-PEEK in vivo as shown by a statistical trend in vitro and instrumentation of spondylytic vertebrae. Until these factors are validated, we advise caution when implanting CFR-PEEK screws in infectious cases.

Successful Clinical Outcome of Vancomycin-induced Hemorrhagic Occlusive Retinal Vasculitis.

We present a case of a patient that experienced severe hemorrhagic occlusive retinal vasculitis secondary to injection of 1.0 mg/0.1 ml of intracameral vancomycin for endophthalmitis prophylaxis after an uneventful cataract surgery. The case is especially unique in that our patient ended up maintaining 20/25 vision with an ocular disease that is typically visually threatening. This may be due to the aggressive administration of periocular and oral steroids combined with scheduled anti-VEGF injections that were later transitioned into a treat and extend regimen.

Guttiferone K Exerts the Anti-inflammatory Effect on Mycobacterium Tuberculosis- (H37Ra-) Infected Macrophages by Targeting the TLR/IRAK-1 Mediated Akt and NF-κB Pathway.

Mycobacterium tuberculosis (Mtb) remains a great threat to global health, killing more people than any other single infectious agent and causing uncontrollable inflammation in the host. Poorly controlled inflammatory processes can be deleterious and result in immune exhaustion. The current tuberculosis (TB) control is facing the challenge of drugs deficiency, especially in the context of increasingly multidrug resistant (MDR) TB. Under this circumstance, alternative host-directed therapy (HDT) emerges timely which can be exploited to improve the efficacy of TB treatment and disease prognosis by targeting the host. Here, we established the in vitro infection model of Mtb macrophages with H37Ra strain to seek effective anti-TB active agent. The present study showed that Guttiferone K, isolated from Garcinia yunnanensis, could significantly inhibit Mtb-induced inflammation in RAW264.7 and primary peritoneal macrophages. It was evidenced by the decreased production of inflammatory mediators, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Further studies with immunoblotting and immunofluorescence revealed that Guttiferone K obviously inhibits the nuclear factor-kappa B (NF-κB) both in RAW264.7 and primary peritoneal macrophages relying on the TLR/IRAK-1 pathway. Guttiferone K could also suppress the NLRP3 inflammasome activity and induce autophagy by inhibiting the protein kinase B (p-Akt) and mammalian target of rapamycin (mTOR) phosphorylation at Ser473 and Ser2448 in both cell lines. Thus, Guttiferone K possesses significant anti-inflammatory effect, alleviating Mtb-induced inflammation with an underlying mechanism that targeting on the TLR/IRAK-1 pathway and inhibiting the downstream NF-κB and Akt/mTOR signaling pathways. Together, Guttiferone K can be an anti-inflammatory agent candidate for the design of new adjunct HDT drugs fighting against tuberculosis.

Three-dimensional printed polyether-ether-ketone implant for extensive chest wall reconstruction: A case report.

Three-dimensional printed (3DP) implant offers a valid option with perfect anatomic fitting in individual and skeletal reconstruction of the chest wall. Herein, we present the case of a patient with a large chest wall tumor, where an extensive chest wall defect was repaired using 3DP polyether-ether-ketone (PEEK) implants. Surgical treatment planning was performed according to the computed tomography (CT) images in DICOM format. A 3DP implant was then design and fabricated. A wide excision of the chest wall tumor was performed, including the entire sternum, 2-6 costal cartilage and ribs, and parietal pleura. Furthermore, a skeletal reconstruction was carried out using a 3DP PEEK implant. The patient recovered well without surgical complications or tumor recurrence in the following year. In general, 3DP PEEK implant is an appropriate alternative for chest wall reconstruction. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Skeletal reconstruction after wide excision of the chest wall remains a challenging problem for clinicians. WHAT THIS STUDY ADDS: 3DP PEEK implant is an appropriate alternative for chest wall reconstruction.

Persistence of Inflammation After Uncomplicated Cataract Surgery: A 6-Month Laser Flare Photometry Analysis.

PURPOSE: To evaluate, by laser photometry, the persistency of anterior chamber flare after uneventful phacoemulsification in asymptomatic patients with no signs of inflammation on slit lamp examination. METHOD: Seventy-five patients previously enrolled in a randomized clinical trial that evaluated inflammation after uneventful phacoemulsification in eyes treated with dexamethasone 0.1% ophthalmic suspension (group 1) or bromfenac 0.09% ophthalmic solution (group 2) for 2 weeks. Anterior chamber inflammation was investigated by laser flare photometry. At 30 days after surgery, laser flare showed persistently elevated values. For this reason, patients were further analyzed at 3 and 6 months. Additionally, optical coherence tomography was used to measure the central macular thickness (CMT) and to assess for postoperative pseudophakic macular edema. RESULTS: When compared to preoperative values, laser flare photometry demonstrated persistent ocular inflammation at postoperative days 90 and 180 in group 1, but not in group 2. Laser flare values showed a significant reduction in group 2 compared to group 1 throughout all the follow-up (p < 0.001). The increase in mean CMT at days 90 and 180 with respect to baseline was statistically significant in group 1 but not in group 2, in which it decreased to levels similar to preoperative value. Group 1 showed a higher increase in mean CMT compared to group 2 throughout all the follow-up (p < 0.001). The proportion of patients that developed pseudophakic cystoid macular edema (CME) was 14% (n = 5) and 0% (n = 0) in group 1 and group 2, respectively (p = 0.02). The bivariate analysis demonstrated a positive correlation between laser flare and CMT values in group 1 but not in group 2. CONCLUSION: Anterior chamber inflammation persists for more than 30 days in a significant proportion of patients after uncomplicated cataract surgery and may be responsible for late onset of cystoid macular edema cases. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03317847.

Rate of pseudophakic cystoid macular edema using intraoperative and topical nonsteroidal antiinflammatory drugs alone without steroids.

PURPOSE: To determine the rate of postoperative cystoid macular edema (CME) in patients undergoing cataract surgery treated with intraoperative intracameral and postoperative topical nonsteroidal antiinflammatory drugs (NSAIDs) without steroids. SETTING: Academic outpatient surgery center Wake Forest Baptist Health in Bermuda Run, NC. DESIGN: Retrospective cohort study. METHODS: A retrospective chart review was performed. Patients were identified through a medical record search tool using criteria of the Current Procedural Terminology code (66984), a single surgeon, and a date range from January 1, 2016, through December 31, 2017. Medical records were reviewed to determine intraoperative and postoperative medication regimen, visual outcome, and development of postoperative CME. Patients with a history of uveitis, diabetic macular edema, retinal vein occlusions, epiretinal membranes, vitreomacular traction, or any prior macular edema were excluded. In addition, any patients with less than 6 weeks of postoperative follow-up were excluded. RESULTS: Overall, 824 patient records were reviewed, and the analysis included 504 eyes. Of these, 2 eyes developed postoperative CME (rate = 0.40%, 95% CI 0.0005 to 0.0143). CONCLUSIONS: The rate of CME in patients treated with intraoperative and postoperative NSAIDs without steroids was low and below the historical rates derived from a literature review of CME development with the use of steroids.

Incidence of cystoid macular edema following routine cataract surgery using NSAIDs alone or with corticosteroids / Incidência de edema macular cistóide após cirurgia de catarata de rotina com a utilização de AINEs isoladamente ou com corticosteroides

ABSTRACT Purpose: To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. Methods: The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. Results: The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). Conclusions: Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste­roidal anti-inflammatory drugs with corticosteroids.

RESUMO Objetivo: Avaliar a taxa de desenvolvimento do edema macular cistóide em pacientes submetidos à cirurgia de catarata em quatro esquemas terapêuticos diferentes. Métodos: O presente estudo é uma análise retrospectiva de 5.380 olhos após facoemulsificação não complicada na Wake Forest University. O período do estudo foi entre julho de 2007 e dezembro de 2012. Os pacientes receberam um dos quatro esquemas: cetorolaco genérico pós-operatório 0,4% e prednisolona 1%, cetorolaco 0,45% pós-operatório e prednisolona 1%, bromfenac 0,09% e a prednisolona 1% pós-operatório, bromfenaco 0,09% no pré-operatório e isoladamente no pós-operatório. Uma análise estatística foi realizada para avaliar as diferenças na taxa de desenvolvimento do edema macular cistóide entre os quatro diferentes regimes terapêuticos. O diagnóstico de edema macular cistóide exigiu uma piora da visão e uma evidência de aumento da espessura macular na tomografia de coerência óptica. Resultados: A taxa global de edema macular cistóide foi de 0,82%. O tratamento com cetorolaco genérico pós-operatório 0,45% e prednisolona 1% demonstrou a maior taxa de desenvolvimento de edema macular cistóide (2,20% dos casos). O cetorolaco 0,45% e a prednisolona 1% no pós-operatório exibiram taxas intermediárias de desenvolvimento de edema macular cistóide (0,90% dos casos). A administração de bromofenac 0,09% e de prednisolona 1% no pós-operatório apresentou taxas interme­diárias de desenvolvimento de edema macular cistóide (0,44% dos casos). O bromfenac 0,09% no pré e pós-operatório isoladamente resultou na menor taxa de desenvolvimento de edema macular cistóide (0,09% dos casos). A taxa de edema macular cistóide foi significativamente menor quando o bromfenac foi utilizado isoladamente em relação ao esquema onde cetorolaco e a prednisolona foram usados (OR 0,043, 95% CI 0,002 a 0,312; p<0,001). Conclusões: O edema macular cistóide pós-cirurgia de catarata desenvolveu-se com menor frequência após o tratamento tópico de medicamentos anti-inflamatórios não esteroidais, comparado às outras terapias avaliadas. Bromfenac, sem corticosteróides, alcançou taxas mais baixas de edema macular cistóide vs. Várias combinações em comparação com as várias combinações de drogas anti-inflamatórias não esteroidais com corticosteróides.

Incidence of cystoid macular edema following routine cataract surgery using NSAIDs alone or with corticosteroids.

PURPOSE: To evaluate the rate of cystoid macular edema development among cataract surgery patients on four different therapeutic regimens. METHODS: The present study is a retrospective analysis of 5,380 eyes following uncomplicated phacoemulsification at Wake Forest University. The study period went from July 2007 to December 2012. Patients received one of four regimens, as follows: postoperative generic ketorolac 0.4% and prednisolone 1%, postoperative name-brand ketorolac 0.45% and prednisolone 1%, postoperative bromfenac 0.09% and prednisolone 1%, preoperative and postoperative bromfenac 0.09% alone. A statistical analysis was performed to assess the differences in rate of cystoid macular edema development among the four different therapeutic regimens. The diagnosis of cystoid macular edema required worsening of vision and evidence of increased macular thickness on optical coherence tomography. RESULTS: The overall rate of cystoid macular edema was 0.82%. Treatment by postoperative generic ketorolac 0.45% and prednisolone 1% demonstrated the highest rate of cystoid macular edema development (2.20% of the cases). Postoperative name-brand ketorolac 0.45% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.90% of the cases). Postoperative administration of bromfenac 0.09% and prednisolone 1% exhibited intermediate rates of cystoid macular edema development (0.44% of the cases). Preoperative and postoperative bromfenac 0.09% alone resulted in the lowest rate of cystoid macular edema development (0.09% of the cases). The rate of cystoid macular edema was significantly lower when bromfenac was used alone vs. either regimen where ketorolac and prednisolone were used (OR 0.043, 95% CI 0.002 to 0.312; p<0.001). CONCLUSIONS: Post-cataract surgery cystoid macular edema developed less frequently following topical non-steroidal anti-inflammatory drugs regimen compared to the other therapies evaluated. Bromfenac, without corticosteroids, achieved lower rates of cystoid macular edema vs. various combinations of non-ste-roidal anti-inflammatory drugs with corticosteroids.

Update About the Effects of the Sunscreen Ingredients Oxybenzone and Octinoxate on Humans and the Environment.

As skin cancer prevalence continues to rise, the importance of sun protection, including sunscreen use, has become accepted in the public. Sunscreens are divided into two main categories based on the type of their active ingredient, organic and inorganic ultraviolet (UV) filters. It has been shown that inorganic filters are more effective at blocking forms of UV light, both UVA and UVB, as compared with organic filters because organic sunscreens absorb and convert radiation whereas inorganic sunscreens reflect radiation. The use of the two most common organic filters, oxybenzone and octinoxate, has recently been restricted in Hawaii due to their harmful effect on the coral reefs. Here, we discuss recent studies about these specific filters related to the adverse health risks they pose for humans and other organisms, as well as environmental repercussions.

T5224, RSPO2 and AZD5363 are novel drugs against functional pituitary adenoma.

We tested whether the drugs T5224, RSPO2, and AZD5363 exert therapeutic effects against functioning pituitary adenoma (FPA). We analysed the gene expression profiles of four FPA mRNA microarray datasets (GSE2175, GSE26966, GSE36314, and GSE37153) from the Gene Expression Omnibus database and identified genes differentially expressed in FPA vs control tissues. We then carried out Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network analyses. We also measured the difference in expression of hub genes between human normal pituitary cells and FPA cells using qRT-PCR. Our in vitro colony-formation and MTT assays showed that cell viability, number, and the size of clonogenicities were all lower in the presence of T5224, RSPO2, or AZD536 than in controls. Moreover, flow cytometry experiments showed that the incidence of apoptosis was higher in the presence of T5224, RSPO2, or AZD5363 than among controls, and was increased by increasing the doses of the drugs. This suggests these drugs could be used as therapeutic agents to treat FPA. Finally, we found that cFos, WNT5A, NCAM1, JUP, AKT3, and ADCY1 are abnormally expressed in FPA cells compared to controls, which highlights these genes as potential prognostic and/or therapeutic targets.

Anterior Chamber Inflammation After Cataract Surgery: A Randomized Clinical Trial Comparing Bromfenac 0.09% to Dexamethasone 0.1.

PURPOSE: To compare the efficacy of bromfenac 0.09% and dexamethasone 0.1% in the treatment of anterior chamber inflammation after uncomplicated cataract surgery. METHODS: Seventy-six patients with senile cataracts and no other ocular comorbidities who underwent uneventful phacoemulsification were randomized 1:1 to receive dexamethasone ophthalmic suspension 0.1% or bromfenac ophthalmic solution 0.09% for 2 weeks. All patients were examined on the day before surgery and postoperatively at day 1, 3, 7, 9, 11, 14 and 30. Laser flare photometry was used to quantify anterior chamber inflammation and optical coherence tomography to measure macular thickness. RESULTS: Bromfenac was as effective as dexamethasone in reducing inflammation in the anterior chamber of the eye. Laser flare increased the day after surgery and progressively decreased after starting the treatment with no statistically significant difference between dexamethasone and bromfenac at all time points. Visual acuity improved steadily after surgery in both groups. Mean macular thickness was similar in both the dexamethasone and bromfenac arms at 1 month. CONCLUSIONS: Short-term therapy with topical bromfenac alone is as effective as dexamethasone in low-risk cataract surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov # NCT03317847; EudraCT # 2016-004358-14. FUNDING: Santa Maria Nuova Hospital IRCCS, Reggio Emilia, Italy.

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery.

Introduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema. Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious. Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.

Update About the Effects of the Sunscreen Ingredients Oxybenzone and Octinoxate on Humans and the Environment.

As skin cancer prevalence continues to rise, the importance of sun protection, including sunscreen use, has become accepted in the public. Sunscreens are divided into two main categories based on the type of their active ingredient, organic and inorganic ultraviolet (UV) filters. It has been shown that inorganic filters are more effective at blocking forms of UV light, both UVA and UVB, as compared with organic filters because organic sunscreens absorb and convert radiation whereas inorganic sunscreens reflect radiation. The use of the two most common organic filters, oxybenzone and octinoxate, has recently been restricted in Hawaii due to their harmful effect on the coral reefs. Here, we discuss recent studies about these specific filters related to the adverse health risks they pose for humans and other organisms, as well as environmental repercussions.