Transcriptomic footprints disclose specificity of reactive oxygen species signaling in Arabidopsis

Reactive oxygen species ( ROS) are key players in the regulation of plant development, stress responses, and programmed cell death. Previous studies indicated that depending on the type of ROS ( hydrogen peroxide, superoxide, or singlet oxygen) or its subcellular production site ( plastidic, cytosolic, peroxisomal, or apoplastic), a different physiological, biochemical, and molecular response is provoked. We used transcriptome data generated from ROS-related microarray experiments to assess the specificity of ROS-driven transcript expression. Data sets obtained by exogenous application of oxidative stress-causing agents ( methyl viologen, Alternaria alternata toxin, 3-aminotriazole, and ozone) and from a mutant ( fluorescent) and transgenic plants, in which the activity of an individual antioxidant enzyme was perturbed ( catalase, cytosolic ascorbate peroxidase, and copper/zinc superoxide dismutase), were compared. In total, the abundance of nearly 26,000 transcripts of Arabidopsis ( Arabidopsis thaliana) was monitored in response to different ROS. Overall, 8,056, 5,312, and 3,925 transcripts showed at least a 3-, 4-, or 5- fold change in expression, respectively. In addition to marker transcripts that were specifically regulated by hydrogen peroxide, superoxide, or singlet oxygen, several transcripts were identified as general oxidative stress response markers because their steady-state levels were at least 5- fold elevated in most experiments. We also assessed the expression characteristics of all annotated transcription factors and inferred new candidate regulatory transcripts that could be responsible for orchestrating the specific transcriptomic signatures triggered by different ROS. Our analysis provides a framework that will assist future efforts to address the impact of ROS signals within environmental stress conditions and elucidate the molecular mechanisms of the oxidative stress response in plants

The effect of intravitreal bevacizumab (Avastin®) on ocular pulse amplitude in neovascular age-related macular degeneration

PURPOSE: To evaluate the effect of intravitreal (IVT) bevacizumab in neovascular age-related macular degeneration (AMD) on global choroidal hemodynamics, as measured by ocular pulse amplitude (OPA). METHODS: This was a two-center prospective study (Sheba Medical Center, Israel, and University Hospitals Leuven, Belgium). AMD patients who required IVT bevacizumab (1.25 mg/0.05 mL; first or repeated) were examined three times: at days 0 (prior to injection), 7 (±3), and 28 (±7) postinjection. At each visit, OPAs of both eyes were measured using the Pascal dynamic contour tonometer (DCT). A paired t-test between preoperative and postoperative OPA was conducted. Pearson correlation was used to evaluate the influence of various measured parameters on DCT-OPA. RESULTS: A total of 38 neovascular AMD patients were recruited, and 30 patients were included in the final analysis (18 females and 12 males; age 78.8 ± 5.82 years [mean ± standard deviation]). A good correlation was found throughout the study between the DCT-intraocular pressure (IOP) and Goldmann IOP and between DCT-IOP and DCT-OPA. No change in OPA of bevacizumab-treated eyes was found between the visits (2.24 ± 0.73, 2.2 ± 0.86, and 2.23 ± 0.73 mm Hg at visits 1, 2, and 3, respectively; paired t-test: P = 0.77 between visits 1 and 2, P = 0.98 between visits 1 and 3). No correlations were found between DCT-OPA and age, heart rate, systemic blood pressure, axial length, keratometry readings, and central corneal thickness. CONCLUSIONS: OPA, an indirect measure of global choroidal hemodynamics, remains unchanged following IVT off-label bevacizumab. This finding adds to the growing evidence regarding the safety profile of bevacizumab in AMD treatment.status: publishe

Agreement and Accuracy of Non-Expert Ophthalmologists in Assessing Glaucomatous Changes in Serial Stereo Optic Disc Photographs

PURPOSE:: To compare the interobserver agreement in detecting glaucomatous optic disc changes using serial stereophotography between a large group of non-expert ophthalmologists and glaucoma specialists; to assess the accuracy of non-experts; to investigate whether the interobserver agreement and the accuracy of non-experts changed after a training session. DESIGN:: Masked interobserver agreement study. PARTICIPANTS:: Serial optic disc stereophotos from 40 patients with glaucoma. METHODS:: Three independent experienced glaucoma specialists (readers of the European Glaucoma Prevention Study) evaluated a set of 2 serial optic disc color stereo-slides for glaucomatous change, obtained with a delay varying from 2 to 7 years of 40 patients, masked from the temporal sequence of the slides. Each patient was graded as changed or stable by agreement of 2 of 3 of the experts (the reference standard). Thirty-seven non-expert ophthalmologists independently evaluated the same set of serial optic disc stereo-slides twice, with the second evaluation on the same day, masked from the results of the previous evaluation, after a training session on a separate slide set. MAIN OUTCOME MEASURES:: Interobserver agreement of non-experts and experts in detecting glaucomatous optic disc changes (expressed as kappa coefficient); agreement of non-experts with the reference standard (accuracy) before and after a training session. RESULTS:: The interobserver kappa coefficient (κ) of the non-experts and experts was 0.20 (95% confidence interval [CI], 0.19-0.21) and 0.51 (95% CI, 0.33-0.69), respectively (P<0.0001). The mean κ of the non-experts with the reference standard was 0.33 (95% CI, 0.27-0.39). After a training session, the interobserver agreement of the non-experts increased from 0.20 to 0.27 (95% CI, 0.26-0.28) (P<0.0001). The percentage agreement of the non-experts with the reference standard improved from 68.5% before to 71.4% after the training session (Wilcoxon signed-rank test, P=0.034). CONCLUSIONS:: The interobserver agreement of non-expert ophthalmologists in detecting glaucomatous optic disc changes using serial stereophotos was significantly lower than that of experts, which was moderate. After a training session, the interobserver agreement and the accuracy of the non-experts showed a small but statistically significant improvement. FINANCIAL DISCLOSURE(S):: The author(s) have no proprietary or commercial interest in any materials discussed in this article.status: publishe

Variability of the Standard Reference Height and its Influence on the Stereometric Parameters of the Heidelberg Retina Tomograph 3

Purpose: To investigate the variability of the standard reference height (SRH) in consecutive Heidelberg Retina Tomograph 3 (HRT3) examinations and its influence on 5 main stereometric parameters. Methods: The HRT3 results of all patients attending our glaucoma center from August to October 2007 were retrospectively reviewed. Only one eye per patient with at least 3 consecutive HRT's with a quality control label of acceptable or better was selected. A SRH difference >/=10% compared to baseline was considered as excess SRH variability. Results: A review of 641 patients yielded 150 patients (150 eyes) who met the inclusion criteria representing a total of 556 examinations. The mean total number of HRT's per patient was 3.7 (range 3-7), and the mean follow-up time was 3.5 years (range 1.4-6.7). The mean proportion of consecutive HRT3 examinations with intra-individual excess SRH variability was 46% (95%CI [40;52]), while the mean intra-individual excess SRH variability was 24% (95%CI [20;28]). The median absolute SRH difference was 8.6% (interquartile range [IQR] 3.9%-16.2%). Furthermore, 55.5%, 75.3%, 74.7%, 0.0% and 19.4% of the variability in Rim Area (RA), Rim Volume (RV), Retinal Nerve Fiber Layer (RNFL) thickness, Cup Shape Measure (CSM), and Height Variation Contour (HVC), respectively, could be attributed to SRH variability. Conclusions: There is considerable SRH variability between HRT3 examinations of the same eye and this could explain more than half of the variability of the parameters RA, RV, and RNFL. These findings indicate that changes of HRT3 parameters should be considered with caution when excess SRH variability is present.status: publishe

Reactive oxygen species as signals that modulate plant stress responses and programmed cell death

International audienc

Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis

Background: Cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma. Methods: Following complete cytoreduction, HIPEC was performed using 460 mg/m(2) oxaliplatin in 5% dextrose for 30 min at a temperature of 41-42 degrees C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival. Results: From July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year. Conclusion: Cytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival

Ectopic meningioma anterior to the lacrimal gland fossa

A 66-year-old man reported a slowly growing tumor on the lateral edge of his left upper eyelid. This lesion was hard but movable on palpation. A neoplasm of the lacrimal gland was suspected. CT showed a highly calcified lesion at the left upper eyelid. Resection of the tumor was performed, which was located just behind the orbital septum and in front of the lacrimal gland. Anatomopathologic investigation of the excised specimen with immunohistochemistry revealed a benign meningioma of a meningotheliomatous type, containing multiple bone elements. An ectopic orbital meningioma is rare, and this is the first case of a unique lateral localization of this lesion. Therefore, it should be included in the differential diagnosis of a lacrimal gland tumor