Generation of Oxygen Free Radicals by Proflavine: Implication in Protein Degradation

Proflavine, an acridine dye, is a known DNA intercalating agent. In the present study, we show that proflavine alone on photoillumination can generate reactive oxygen species (ROS). These proflavine-derived ROS cause damage to proteins, and this effect is enhanced when the divalent metal ion Cu (II) is included in the reaction. Bathocuproine, a specific Cu (I) sequestering agent, when present in the reaction mixture containing Cu (II), was found to inhibit the protein degradation, showing that Cu (I) is an essential intermediate in the reaction. The effect of several scavengers of ROS such as superoxide dismutase, sodium azide, potassium iodide, and thiourea were examined on the protein damaging reaction. Potassium iodide was found to be the most effective in inhibiting protein damage followed by sodium azide and thiourea. Our results indicate the involvement of superoxide, singlet oxygen, triplet oxygen, and hydroxyl radicals in proflavine-induced damage to proteins

A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes : role of dosing and glycaemic control

Background The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis. Methods A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period. Results Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time. Conclusions Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications. Trial registration EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26

Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi

The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments for thromboembolism, we sought to understand the structural and mechanical properties of blood clots and how this influences embolism in vivo. We developed a murine model in which fibrin γ-chain cross-linking by activated Factor XIII is eliminated (FGG3X) and applied methods to study thromboembolism at whole-body and organ levels. We show that FGG3X mice have a normal phenotype, with overall coagulation parameters and platelet aggregation and function largely unaffected, except for total inhibition of fibrin γ-chain cross-linking. Elimination of fibrin γ-chain cross-linking resulted in thrombi with reduced strength that were prone to fragmentation. Analysis of embolism in vivo using Xtreme optical imaging and light sheet microscopy demonstrated that the elimination of fibrin γ-chain cross-linking resulted in increased embolization without affecting clot size or lysis. Our findings point to a central previously unrecognized role for fibrin γ-chain cross-linking in clot stability. They also indirectly indicate mechanistic targets for the prevention of thrombosis through selective modulation of fibrin α-chain but not γ-chain cross-linking by activated Factor XIII to reduce thrombus size and burden, while maintaining clot stability and preventing embolism

Chemically processed CdTe thin films for potential applications in solar cells – Effect of Cu doping

Thin films of cadmium telluride (CdTe) have attained the attention of researchers due to the potential application in solar cells. However, cost-effective fabrication of solar cells based on thin films along with remarkable efficiency and control over optical properties is still a challenging task. This study presents an analysis of the structural, optical and electrical properties of undoped and Cu-doped CdTe thin films fabricated on ITO coated glass substrates using an electrodeposition process with a focus on practical applications. Electrolytes of cadmium (Cd), tellurium (Te) and copper (Cu) are prepared with a low molarity of 0.1 M. Thin films are deposited by keeping current density in the range of 0.12–0.3 mA/cm2. Copper doping is varied (2-10 wt%) for the optimized sample. X-ray diffraction crystallography indicates that both undoped CdTe and Cu-doped CdTe films crystallize into a dominant hexagonal lattice. Direct energy band gap is observed for both undoped and doped conditions. The study revealed a drop in the optical band gap energy to ∼1.46 eV with the increase in doping (Cu) concentration from 2 to 10 wt%. Increase in mobility and conductivity is observed with the increase in current density of the deposited undoped CdTe thin films. Whereas, Cu doping of 6 wt% produced thin films with acceptable mobility and conductivity for the doped samples. Furthermore, photoluminescence (PL) spectroscopy unveiled a multitude of emission peaks encompassing the visible spectrum, arising from the combination of electrons and holes through both direct and indirect recombination processes. Findings of this study suggest that chemically produced CdTe thin films would be suitable for use as low-cost applications pertaining to solar cells