Photochemical reactions of cobalt(III)-amine complexes innon-aqueous solvents: Mechanistic details of oxygenation reaction of cobalt(III) systems-II]

1-5Flash photolysis and steady-state photolysis studies of a series [Co(Am)(NO2)2- (Am = 2 en, trien) of complexes have been carried out in acetonitrile. Photolysis of the complexes in air-equilibrated acetonitrile medium produces mononuclear superoxo, dinuclear superoxo and dinuclear peroxo complexes sequentially. Transient absorptions are observed for the formation of mononuclear and dinuclear superoxo complexes at 400 and 700 nm respectively during flash photolysis. Steady state photolysis results in the dinuclear peroxo complex as the final product

Photochemical reactions of cobalt(III)-amine complexes innon-aqueous solvents: Mechanistic details of oxygenation reaction of cobalt(III) systems-II]

1-5Flash photolysis and steady-state photolysis studies of a series [Co(Am)(NO2)2- (Am = 2 en, trien) of complexes have been carried out in acetonitrile. Photolysis of the complexes in air-equilibrated acetonitrile medium produces mononuclear superoxo, dinuclear superoxo and dinuclear peroxo complexes sequentially. Transient absorptions are observed for the formation of mononuclear and dinuclear superoxo complexes at 400 and 700 nm respectively during flash photolysis. Steady state photolysis results in the dinuclear peroxo complex as the final product

Magnetism in amorphous Ru<SUB>x</SUB>Fe<SUB>80-x</SUB>B<SUB>20</SUB> alloys: magnetization and Mossbauer study

Amorphous alloys of RuxFe80-xB20, 0 &#8804; x &#8804; 22 have been investigated using low field ac susceptibility, dc magnetization and 57Fe Mossbauer spectroscopy. The magnetic phase diagram of RuxFe80-xB20 is confirmed. Mossbauer measurements reveal a low temperature transition in Ru18Fe62B20 below Tc at which the average Fe hyperfine field rises anomalously and magnetization measurements indicate a non-collinear magnetic structure. The effect of substitution of Ru on distribution in exchange is discussed

Differential Mechanisms of Cell Death Induced by HDAC Inhibitor SAHA and MDM2 Inhibitor RG7388 in MCF-7 Cells

Gene expression is often altered by epigenetic modifications that can significantly influence the growth ability and progression of cancers. SAHA (Suberoylanilide hydroxamic acid, also known as Vorinostat), a well-known Histone deacetylase (HDAC) inhibitor, can stop cancer growth and metastatic processes through epigenetic alterations. On the other hand, Letrozole is an aromatase inhibitor that can elicit strong anti-cancer effects on breast cancer through direct and indirect mechanisms. A newly developed inhibitor, RG7388 specific for an oncogene-derived protein called MDM2, is in clinical trials for the treatment of various cancers. In this paper, we performed assays to measure the effects of cell cycle arrest resulting from individual drug treatments or combination treatments with SAHA + letrozole and SAHA + RG7388, using the MCF-7 breast cancer cells. When SAHA was used individually, or in combination treatments with RG7388, a significant increase in the cytotoxic effect was obtained. Induction of cell cycle arrest by SAHA in cancer cells was evidenced by elevated p21 protein levels. In addition, SAHA treatment in MCF-7 cells showed significant up-regulation in phospho-RIP3 and MLKL levels. Our results confirmed that cell death caused by SAHA treatment was primarily through the induction of necroptosis. On the other hand, the RG7388 treatment was able to induce apoptosis by elevating BAX levels. It appears that, during combination treatments, with SAHA and RG7388, two parallel pathways might be induced simultaneously, that could lead to increased cancer cell death. SAHA appears to induce cell necroptosis in a p21-dependent manner, and RG7388 seems to induce apoptosis in a p21-independent manner, outlining differential mechanisms of cell death induction. However, further studies are needed to fully understand the intracellular mechanisms that are triggered by these two anti-cancer agents

Cell Cycle Arrest and Cytotoxic Effects of SAHA and RG7388 Mediated through p21^WAF1/CIP1 and p27^KIP1 in Cancer Cells

Background and Objective: Alterations in gene expressions are often due to epigenetic modifications that can have a significant influence on cancer development, growth, and progression. Lately, histone deacetylase inhibitors (HDACi) such as suberoylanilide hydroxamic acid (SAHA, or vorinostat, MK0683) have been emerging as a new class of drugs with promising therapeutic benefits in controlling cancer growth and metastasis. The small molecule RG7388 (idasanutlin, R05503781) is a newly developed inhibitor that is specific for an oncogene-derived protein called MDM2, which is also in clinical trials for the treatment of various types of cancers. These two drugs have shown the ability to induce p21 expression through distinct mechanisms in MCF-7 and LNCaP cells, which are reported to have wild-type TP53. Our understanding of the molecular mechanism whereby SAHA and RG7388 can induce cell cycle arrest and trigger cell death is still evolving. In this study, we performed experiments to measure the cell cycle arrest effects of SAHA and RG7388 using MCF-7 and LNCaP cells. Materials and Methods: The cytotoxicity, cell cycle arrest, and apoptosis/necroptosis effects of the SAHA and RG7388 treatments were assessed using the Trypan Blue dye exclusion (TBDE) method, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence assay with DEVD-amc substrate, and immunoblotting methods. Results: The RG7388 treatment was able to induce cell death by elevating p21WAF1/CIP1 through inhibition of MDM2 in LNCaP, but not in MCF-7 cells, even though there was evidence of p53 elevation. Hence, we suspect that there is some level of uncoupling of p53-mediated transcriptional induction of p21WAF1/CIP1 in MCF-7 cells. Conclusion: Our results from MCF-7 and LNCaP cells confirmed that SAHA and RG7388 treatments were able to induce cell death via a combination of cell cycle arrest and cytotoxic mechanisms. We speculate that our findings could lead to the development of newer treatments for breast and prostate cancers with drug combinations including HDACi

Accuracy of the smartphone-based nonmydriatic retinal camera in the detection of sight-threatening diabetic retinopathy.

Purpose: To evaluate the sensitivity and specificity of smartphone-based nonmydriatic (NM) retinal camera in the detection of diabetic retinopathy (DR) and sight-threatening DR (STDR) in a tertiary eye care facility. Methods: Patients with diabetes underwent retinal photography with a smartphone-based NM fundus camera before mydriasis and standard 7-field fundus photography with a desktop mydriatic fundus camera after mydriasis. DR was graded using the international clinical classification of diabetic retinopathy system by two retinal expert ophthalmologists masked to each other and to the patient's identity. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to detect DR and STDR by NM retinal imaging were assessed. Results: 245 people had gradable images in one or both eyes. DR and STDR were detected in 45.3% and 24.5%, respectively using NM camera, and in 57.6% and 28.6%, respectively using mydriatic camera. The sensitivity and specificity to detect any DR by NM camera was 75.2% (95% confidence interval (CI) 68.1-82.3) and 95.2% (95%CI 91.1-99.3). For STDR the values were 82.9% (95% CI 74.0-91.7) and 98.9% (95% CI 97.3-100), respectively. The PPV to detect any DR was 95.5% (95% CI 89.8-98.5) and NPV was 73.9% (95% CI 66.4-81.3); PPV for STDR detection was 96.7% (95% CI 92.1-100)) and NPV was 93.5% (95% CI 90.0-97.1). Conclusion: Smartphone-based NM retinal camera had fairly high sensitivity and specificity for detection of DR and STDR in this clinic-based study. Further studies are warranted in other settings

Positron-lifetime studies in YNi<SUB>2</SUB>B<SUB>2</SUB>C

Positron-lifetime measurements have been carried out in the temperature range of 300 to 5 K in the borocarbide superconductor, YNi2B2C. The positron lifetime 189 ps at 300 K is observed to decrease to 179 ps at 5 K. No change in lifetime is seen across the superconducting transition at ~16 K. The observed magnitude of lifetime and its temperature variation are discussed with support from theoretical computations of positron density distribution and annihilation characteristics for a perfect crystal of tetragonal YNi2B2C and for various plausible defect configurations. On the basis of these calculations, it is inferred that the lifetime and its temperature dependence are governed by positron annihilation from carbon vacancies

Positron lifetime studies in borocarbides

Positron lifetime measurements have been carried out in RNi<SUB>2</SUB>B<SUB>2</SUB>C, with R = Y, Lu, Ho, Er, Tb and Ce, at room temperature. A systematic increase in the bulk lifetime from 130 ps to 145 ps is observed with increase in unit cell volume. Theoretical computations of the positron lifetime, also carried out on these systems show a trend in agreement with the experiment. Positron lifetime measurements in YNi<SUB>2</SUB>B<SUB>2</SUB>C, done in the temperature range of 300-5 K, across the superconducting transition, shows a monotonic decrease in lifetime with the lowering of temperature. This variation in lifetime is related to the trapping behaviour of positrons at carbon vacancies and their clusters

Upper critical field in borocarbides

Resistive measurement of superconducting transitions under externally applied magnetic fields in polycrystalline samples of YPd<SUB>5</SUB>B<SUB>3</SUB>C<SUB>0.3</SUB> and YNi<SUB>2</SUB>B<SUB>2</SUB>C has revealed a marked positive curvature in the temperature dependence of H<SUB>c2</SUB>, with the slope - dH<SUB>c2</SUB>/dT increasing monotonically from T<SUB>c</SUB> to 4.2 K. This observed positive curvature is in marked contrast with the predictions of the conventional theories of upper critical field. It is possible that a compensation mechanism may have to be invoked to account for the observed results