Disorganization of retinal inner layers correlates with ellipsoid zone disruption and retinal nerve fiber layer thinning in diabetic retinopathy.

PURPOSE: To study the correlation between disorganization of inner retinal layer (DRIL) and macular thickness parameters, ellipsoid zone (EZ) disruption and retinal nerve fiber layer (RNFL) thickness on spectral domain optical coherence tomography (SD-OCT) in diabetic retinopathy (DR), for the first time. METHODS: A tertiary care center-based cross-sectional study was undertaken. One hundred and four consecutive study subjects of type 2 diabetes mellitus were included: diabetes mellitus with no retinopathy (No DR) (n = 26); non-proliferative DR (NPDR) (n = 26); proliferative DR (PDR) (n = 26) and healthy controls (n = 26). Best Corrected Visual Acuity (BCVA) was measured on the logarithm of the minimum angle of resolution (logMAR) scale. Clinician-friendly, SD-OCT based, grading systems were created for DRIL and EZ disruption, within the macular cube. DRIL was graded as: grade 0, DRIL absent; and grade 1, DRIL present. EZ disruption was graded as; Grade 0: Intact EZ; Grade 1: Focal disruption and Grade 2: Global disruption. Every study subject underwent RNFL thickness analysis. RESULTS: DRIL was significantly associated with increase in severity of DR.Pearson correlation analysis showed significant positive correlation between DRIL and CST CAT and grades of EZ disruption . However, a significant negative correlation was found between DRIL and RNFL thickness . CONCLUSION: Presence of DRIL correlates with severity of DR, EZ disruption and RNFL thinning.

Anti-Cancer Agents in Proliferation and Cell Death: The Calcium Connection.

Calcium (Ca2+) signaling and the modulation of intracellular calcium ([Ca2+]i) levels play critical roles in several key processes that regulate cellular survival, growth, differentiation, metabolism, and death in normal cells. On the other hand, aberrant Ca2+-signaling and loss of [Ca2+]i homeostasis contributes to tumor initiation proliferation, angiogenesis, and other key processes that support tumor progression in several different cancers. Currently, chemically and functionally distinct drugs are used as chemotherapeutic agents in the treatment and management of cancer among which certain anti-cancer drugs reportedly suppress pro-survival signals and activate pro-apoptotic signaling through modulation of Ca2+-signaling-dependent mechanisms. Most importantly, the modulation of [Ca2+]i levels via the endoplasmic reticulum-mitochondrial axis and corresponding action of channels and pumps within the plasma membrane play an important role in the survival and death of cancer cells. The endoplasmic reticulum-mitochondrial axis is of prime importance when considering Ca2+-signaling-dependent anti-cancer drug targets. This review discusses how calcium signaling is targeted by anti-cancer drugs and highlights the role of calcium signaling in epigenetic modification and the Warburg effect in tumorigenesis.

Functional polymorphisms of the receptor for the advanced glycation end product promoter gene in inflammatory bowel disease: a case-control study.

The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn's disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy-Weinberg equilibrium was first assessed, and then, the Kruskal-Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients' characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy-Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.

The role of dietary phytochemicals in the carcinogenesis via the modulation of miRNA expression.

PURPOSE: Phytochemicals are naturally occurring plant-derived compounds and some of them have the potential to serve as anticancer drugs. Based on recent evidence, aberrantly regulated expression of microRNAs (miRNAs) is closely associated with malignancy. MicroRNAs are characterized as small non-coding RNAs functioning as posttranscriptional regulators of gene expression. Accordingly, miRNAs regulate various target genes, some of which are involved in the process of carcinogenesis. RESULTS: This comprehensive review emphasizes the anticancer potential of phytochemicals, either isolated or in combination, mediated by miRNAs. The ability to modulate the expression of miRNAs demonstrates their importance as regulators of tumorigenesis. Phytochemicals as anticancer agents targeting miRNAs are widely studied in preclinical in vitro and in vivo research. Unfortunately, their anticancer efficacy in targeting miRNAs is less investigated in clinical research. CONCLUSIONS: Significant anticancer properties of phytochemicals as regulators of miRNA expression have been proven, but more studies investigating their clinical relevance are needed.

Transthoracic Coronary Flow Data at Rest Predict High-Risk Stress Tests.

Background Several recent studies have reported the opportunity to diagnose significant narrowing of the coronary arteries without stress testing using local flow acceleration. Purpose To define how often patients with increased coronary flow velocities at rest (≥ 0.70 m/s) have a positive exercise echocardiography test. Material and Methods A total of 150 patients scheduled for exercise echocardiography were studied using transthoracic Doppler echocardiography in order to assess coronary artery flow velocity before exercise. Pulsed wave Doppler registered blood flow velocity placed on the color signal. The maximal diastolic velocity of coronary flow was measured. Results Of participants, 16% had a velocity of more than 0.70 m/s in the left main/proximal left anterior/proximal left circumflex arteries (LM/pLAD). A significant correlation was observed between the value of the maximal velocity in LM/pLAD and the ejection fraction at the peak of exercise ( r ≈ -0.39, P < 0.0001); between the value of the maximal velocity in LM/pLAD and index of wall motion abnormalities (IWMA) at the peak of exercise ( r ≈ 0.44, P < 0.0001); and between the value of the maximal velocity in LM/pLAD and dIWMA ( r ≈ 0.41, P < 0.0001). Afterwards, severe ischemia in stress echocardiography tests was observed in this group. The average IWMA of these tests was found to be 2.3. Sixty-two angiograms were available for comparison with Doppler data. Conclusion There is a significant correlation between the value of the maximal velocity in LM/pLAD/pLCx at rest and the severity of wall motion abnormalities during exercise tests.