Search

A rigorous high-quality sequencing strategy was used to sequence the entire mitochondrial genome in macrodissected prostate cancer tissue and distant benign cells and analyze frequency and nature of somatic mtDNA mutations and their suitability for monitoring malignant transformation, tumor progression and metastasis. The somatic mutations in transfer RNAs (tRNAs) was found to be associated with elevated prostate specific antigen (PSA) levels, and the degree of heteroplasmy increased with increasing tumor activity and hence somatic mutations in the mitochondrial genome are frequent events in prostate cancer.

Purpose: To analyse the effect of intravitreal aflibercept injections on systemic angiopoietin‐2 (Ang2) and vascular endothelial growth factor (VEGF)‐A levels in patients with neovascular age‐related macular degeneration (nAMD). Methods: In a prospective, randomized study, aflibercept (2.0 mg/50 µl) or ranibizumab (0.5 mg/50 µl) was administered intravitreally to 38 treatment‐naive patients. Blood samples were taken before, 7 days after, and 28 days after the first intravitreal therapy. Cytokine levels were measured by enzyme‐linked immunosorbent assay. Twenty‐two age‐ and sex‐matched individuals served as controls. Results: At baseline, there were no significant differences of systemic Ang2 and VEGF‐A levels among the treatment and control groups. After intravitreal aflibercept administration, median (interquartile range: IQR) systemic Ang2 was significantly upregulated from 1819 pg/ml (1262–3099) to 2123 pg/ml (1441–3769; p = 0.011) 7 days after the drug injection and remained non‐significantly elevated at 1944 pg/ml (1431–2546 pg/ml; p = 0.653) 28 days after the drug injection. Median (IQR) systemic VEGF‐A levels were significantly reduced from 43 pg/ml (30–57) to 8 pg/ml (8–8; p < 0.0001) 7 days and 16 pg/ml (8–26; p = 0.001) 28 days after the injection in the aflibercept group. There were no significant effects on systemic VEGF‐A and Ang2 levels in the ranibizumab group at any time point following the first injection. Conclusion: In this study, we report significant systemic upregulation of Ang2 after intravitreal aflibercept administration. This counterregulatory response may represent a potential escape mechanism from antiangiogenic therapy. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the interaction between aflibercept and galectin-1 and evaluate the plasma levels of galectin-1 and vascular endothelial growth factor (VEGF)-A after intravitreal injection of aflibercept in patients with diabetic retinopathy (DR). Methods: Interaction of galectin-1 with aflibercept was determined via immunoprecipitation. Seventeen patients with type 2 diabetes and diabetic macular edema (DME) were each treated with a single intravitreal injection of aflibercept (2.0 mg, 50 µL) monthly for three consecutive months. Plasma galectin-1 and VEGF-A levels were measured just before an injection was administered, 1 week after the first injection, and 2 months after the last injection. Nineteen age- and sex-matched healthy participants served as controls. Results: Irrespective of the tested galectin-1 concentration, 24% of added galectin-1 was precipitated by aflibercept. Baseline plasma concentrations of galectin-1 were 22.0 and 23.0 ng/mL in the control and aflibercept-treated groups, respectively. Systemic galectin-1 levels increased to 27.0 and 24.0 ng/mL at 7 days and 4 weeks, respectively, after treatment. At week 8, plasma galectin-1 levels significantly increased to 36.0 ng/mL. This level persisted for 20 weeks. Systemic VEGF-A levels significantly reduced to below the minimum detectable dose in 16 DME patients at 7 days after treatment. This level persisted for 4 weeks. Plasma VEGF-A levels were reduced at weeks 8 (p = 0.099) and 20 (p = 0.023). Decreased plasma VEGF-A levels were observed in all patients after treatment. Conclusion: We confirmed that physiological aflibercept levels precipitate galectin-1 inin vitroassays. Additionally, systemic upregulation of galectin-1 might be induced by intravitreal aflibercept, which may be relevant in the clinical outcomes of DR treatment. [ABSTRACT FROM PUBLISHER]

Aims To investigate the role of high-resolution anterior segment optical coherence tomography (HR-ASOCT) in the assessment of pterygia. Methods Single centre cross-sectional study. Patients with primary pterygium and/or pingueculae were included. Clinical assessment included HR-ASOCT, colour photography, keratometry followed by histology. Associations were tested between HR-ASOCT features of the pterygium and the degree of corneal scarring and elastotic degeneration, astigmatism and best-corrected visual acuity. Results 29 eyes of 26 patients with pterygium and 6 patients with pinguecula were included. Apical anterior stromal scarring was found in 23 cases (79.3%) reaching a mean depth of 68.8±21.7 µm (minimum: 33 µm, maximum: 126 µm). Increased stromal scarring and subepithelial elastotic degenerative tissue was significantly associated with HR-ASOCT features of flat bridging of the corneoscleral transition zone (p<0.01) reduced thickness of the pterygium head (p=0.01), and a greater degree of corneal astigmatism (p=0.04). Conclusions HR-ASOCT is a useful tool for the assessment and monitoring of pterygia in clinical practice. Features associated with increased stromal scarring and astigmatism are reduced thickness of the head of the pterygium and flat bridging of the corneoscleral transition zone. [ABSTRACT FROM AUTHOR]

In order to study the mechanisms of sperm competition and cryptic female choice we require an understanding of the patterns of sperm storage, sperm removal and sperm digestion. Current studies infer these patterns mainly from paternity data, which only reveal the ultimate outcomes of the interactions between male and female reproductive processes. However, only with a mechanistic understanding of the fate of received sperm, and the involved patterns of postcopulatory sexual selection, can we understand the evolution of male and female reproductive morphology and physiology. The currently available approaches for tracking donor sperm in a recipient are either very time consuming, spatially imprecise or limited to model organisms for which considerable genetic knowledge and molecular know-how is available. Using the free-living flatworm Macrostomum lignano we here present a novel sperm tracking approach that uses DNA-labelling with a halogenated pyrimidine and localisation of the label using immunocytochemistry. We first outline modifications to established protocols to allow visualisation of gametic cells, in addition to somatic cells, determine the duration and patterns of spermatogenesis, and then show that labelled sperm from labelled donors can be observed in unlabelled recipients. We further show that labelled worms have a mating behaviour that is comparable to that of unlabelled worms except in one parameter. We suggest ways in which this approach can be optimised, and that it should be readily transferable to other taxa. We conclude that this approach will be a valuable tool to study postcopulatory sexual selection. [ABSTRACT FROM AUTHOR]