ITF2357 regulates NF-κB signaling pathway to protect barrier integrity in retinal pigment epithelial cells.

The robust integrity of the retinal pigment epithelium (RPE), which contributes to the outer brain retina barrier (oBRB), is compromised in several retinal degenerative and vascular disorders, including diabetic macular edema (DME). This study evaluates the role of a new generation of histone deacetylase inhibitor (HDACi), ITF2357, in regulating outer blood-retinal barrier function and investigates the underlying mechanism of action in inhibiting TNFα-induced damage to RPE integrity. Using the immortalized RPE cell line (ARPE-19), ITF2357 was found to be non-toxic between 50 nM and 5 µM concentrations. When applied as a pre-treatment in conjunction with an inflammatory cytokine, TNFα, the HDACi was safe and effective in preventing epithelial permeability by fortifying tight junction (ZO-1, -2, -3, occludin, claudin-1, -2, -3, -5, -19) and adherens junction (E-cadherin, Nectin-1) protein expression post-TNFα stress. Mechanistically, ITF2357 depicted a late action at 24 h via attenuating IKK, IκBα, and p65 phosphorylation and ameliorated the expression of IL-1ß, IL-6, and MCP-1. Also, ITF2357 delayed IκBα synthesis and turnover. The use of Bay 11-7082 and MG132 further uncovered a possible role for ITF2357 in non-canonical NF-κB activation. Overall, this study revealed the protection effects of ITF2357 by regulating the turnover of tight and adherens junction proteins and modulating NF-κB signaling pathway in the presence of an inflammatory stressor, making it a potential therapeutic application for retinal vascular diseases such as DME with compromised outer blood-retinal barrier.

To Compare the Effectiveness of Granisetron Versus Ondansetron to Control Nausea and Vomiting During Lower Segment Cesarean Section Under Subarachnoid Block.

Background: Nausea and vomiting (NV) seen during and after lower segment cesarean section (LSCS) are due to increased intragastric pressure, hypotension, stretching the peritoneum (exteriorization of the uterus), excessive surgical manipulation and visceral stimulation, using opioids, using uterotonic agents, and the patient's mental status. Ondansetron and granisetron intravenous (i.v.) are useful for avoiding bradycardia and hypotension. Objectives: The objective of this study is to study the effectiveness of granisetron versus ondansetron to control NV during LSCS under subarachnoid block. Materials and Methods: Eighty patients undergoing elective cesarean section under spinal anesthesia by intrathecal bupivacaine were randomly divided into two groups (40 pregnant females of the American Society of Anesthesiologists physical status Classes I and II in each Group). Group 1 received granisetron 40 mg.kg-1 i.v. stat after clamping the cord and Group 2 given i.v. ondansetron 8 mg stat after clamping the cord. NV were observed at the "early postoperative period (0-3 h)" and "late postoperative period (4-24 h)." Statistical Analysis Used: Student's t-test and Chi-square test were used to find out the statistical significance, P < 0.05 was considered statistically significant. Results: The mean age was 29.3 years with 4.15 standard deviation (SD) and 28.3 years with 4.41 SD in Groups 1 and 2, respectively. The mean duration of surgery was 53.1 min with 6.67 min SD and 57.7 min with 10.26 SD in Groups 1 and 2, respectively. In the "early postoperative period," NV observed in 7.5% and 10.0% participants in Groups 1 and 2, respectively (P > 0.05), and in "late postoperative period," NV observed in 0.0% and 22.5% participants in Groups 1 and 2, respectively (P < 0.05). Conclusion: Granisetron reduces the severity of spinal-induced hypotension, need for rescue vasopressor, and incidence of nausea.

Characterization of Fatty Acid Binding Protein 7 (FABP7) in the Murine Retina.

PURPOSE: To characterize the mouse retina lacking fatty acid binding protein (FABP7-/-). METHODS: Immunohistochemistry (IHC) was performed in 8-week-old mice to localize FABP7 in the retina. Retinal thickness was measured using image-guided spectral-domain optical coherence topography images. Electroretinography was carried out to assess retinal function. Fundus photography and fundus fluorescein angiography were performed on FABP7-/- and littermate wild-type (WT) mice, and retinal vascular changes were calculated using Singapore I Vessel Assessment (SIVA) analysis. Blood glucose levels were measured in the 8-week-old WT and FABP7-/- mice. In addition, retina was processed for trypsin digestion and retinal flat mounts for isolectin staining. Transcript levels of FABP7, VEGF, GFAP, and Na+K+ATPase were quantified using real-time PCR, and protein expression was analyzed by IHC and Western blot. RESULTS: Fatty acid binding protein 7 is expressed in the inner nuclear layer, outer plexiform layer, and photoreceptor inner segments. No significant difference in retinal thickness and ERG responses was observed between FABP7-deficient and WT retinas. FABP7-/- mice have significantly decreased retinal venular caliber retinal arteriolar fractal dimension compared with WT littermates. FABP7-/- mice showed significant increased areas of fluorescein leakage in the retina. FABP7-/- mice exhibited elevated high blood glucose levels compared with WT mice. Trypsin digested FABP7-/- mice retina showed increased acellular strands and endothelial cell drop outs, and reduced microvasculature branching compared with WT retina. FABP7-/- mice retina also have increased GFAP and VEGF expression. CONCLUSIONS: Fatty acid binding protein 7 is expressed in the retina and might play an important role in maintaining retinal vasculature.

Alcohol misuse in older people: heavy consumption and protean presentations.

BACKGROUND: Alcohol misuse, especially binge drinking in young people, and alcoholic liver disease are major public health concerns. However, alcohol misuse in older people is underestimated and often goes undetected. OBJECTIVE: To document alcohol consumption and clinical presentation of alcohol misuse in hospital inpatients aged >or=60 years. METHODS: 208 inpatients aged >or=60 years, referred to the alcohol liaison nurse between 1998 and 2003 at the Royal Bolton Hospital, Bolton, UK, were assessed for sex, alcohol intake, primary and secondary reasons for admission, and other concurrent health problems and death. RESULTS: 90% of men drank >21 units weekly and 93% of women drank >14 units weekly. Median weekly alcohol intake was 78.5 units for men and 47 units for women. Acute intoxication, falls, circulatory problems and alcoholic liver disease were the main primary reasons for admission. Neglect or malnutrition, alcoholic liver disease and hypertension were the main secondary reasons and concurrent health problems. 30% of patients died between 1998 and 2003. CONCLUSION: In inpatients aged >or=60 years who were referred to the alcohol liaison nurse in a district general hospital, heavy alcohol consumption, often to very high levels, was characteristic in both men and women and was associated with a wide variety of primary and secondary clinical presentations, including death.

Quantifying DNA concentrations using fluorometry: a comparison of fluorophores.

Detection of low concentrations of DNA is important in vision research because many animal models only provide scant samples of ocular tissue. Quantitative analysis of low concentrations of double stranded DNA is now feasible using fluorometry with newer fluorophores. This technique offers a rapid way to evaluate the DNA content of samples based on the measurement of fluorescence enhancement emitted by fluorophore-bound DNA and is more sensitive than absorption spectrometry. The purpose of this study was to compare the sensitivity of several different fluorophores for measuring DNA concentrations by fluorometry. Based on our studies, we conclude that SYBR Green I and PicoGreen are substantially more sensitive for quantifying DNA concentrations than ethidium bromide and Hoechst 33258.