Design, Synthesis and biological evaluation of novel acridine-polyamine conjugates against prostate cancer

Prostate cancer is the most common cause of cancer death in men, aged 85 and over. Androgen receptor, a single polypeptide with three functional domains is very important during initiation and progression of the disease. In this study, a DNA intercalating agent, acridine is linked to the testosterone via a polyamine linker to obtain a compound with trifunctional characteristics, where the acridine intercalates the DNA, the polyamine linker binds the phosphoryl groups of the DNA backbone and the testosterone moiety binds into the AR ligand binding domain, with which its DNA binding domain is bound already to the DNA. This trifunctional compound and related derivatives have been synthesized and tested against androgen dependent- and androgen independent- prostate cancer cell lines and they have demonstrated to be cytotoxic at the micromolar concentrations

Experimental study of the dynamics of D+H2 reactive and inelastic collisions below 1.0 eV relative energy

We report the results of state-to-state dynamics experiments on the D + H2 → HD + H reaction as well as D + H2 → H 2 † + D energy transfer at relative energies of 0.67 and 0.79 eV. Both product state distributions and absolute partial cross sections have been determined, from coherent anti-Stokes Raman scattering (CARS) spectra of the HD and H2 † products recorded under single-collision conditions following pulsed-laser photolysis of DI to generate the D atom reactant. At both energies and for both reactive and inelastic collisions there is a strong dynamical bias against rotational and vibrational excitation of the product. However, at 0.67 eV there is an enhancement of both the relative and absolute yield of HD (v′ = 1), and to a lesser extent H2 (v′ = 1), the only energetically accessible vibrationally excited product states. This may be the result of a Feshbach resonance at ≈ 0.65 eV, just above the v′ = 1 threshold energy. Product quantum state distributions from quasiclassical trajectory calculations are in fairly good agreement with the experimental results, except that they do not show the v′ = 1 enhancement at 0.67 eV. However, the partial cross sections from the trajectory calculations are systematically larger than those measured. © 1989 American Institute of Physics.published_or_final_versio

Efficacy, pharmacokinetic and pharmacodynamic evaluation of Apaziquone in the treatment of non- muscle invasive bladder cancer

Introduction: Apaziquone (also known as EO9 and Qapzola) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 minutes or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers

Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

The Sphaleron Rate in SU(N) Gauge Theory

The sphaleron rate is defined as the diffusion constant for topological number NCS = int g^2 F Fdual/32 pi^2. It establishes the rate of equilibration of axial light quark number in QCD and is of interest both in electroweak baryogenesis and possibly in heavy ion collisions. We calculate the weak-coupling behavior of the SU(3) sphaleron rate, as well as making the most sensible extrapolation towards intermediate coupling which we can. We also study the behavior of the sphaleron rate at weak coupling at large Nc.Comment: 18 pages with 3 figure

Peripheral neural cell sensitivity to mTHPC-mediated photodynamic therapy in a 3D in vitro model

Background: The effect of photodynamic therapy (PDT) on neural cells is important when tumours are within or adjacent to the nervous system. The purpose of this study was to investigate PDT using the photosensitiser, meta tetrahydroxyphenyl chlorin (mTHPC), on rat neurons and satellite glia, compared with human adenocarcinoma cell (MCF-7).Methods: Fluorescence microscopy confirmed that mTHPC was incorporated into all three cell types. Sensitivity of cells exposed to mTHPC-PDT (0–10 µg ml–1) was determined in a novel 3-dimensional collagen gel culture system. Cell death was quantified using propidium iodide and cell types were distinguished using immunocytochemistry. In some cases, neuron survival was confirmed by measuring subsequent neurite growth in monolayer culture.Results: MCF-7s and satellite glia were significantly more sensitive to PDT than neurons. Importantly, 4 µg ml–1 mTHPC PDT caused no significant neuron death compared with untreated controls but was sufficient to elicit substantial cell death in the other cell types. Initially, treatment reduced neurite length; neurons then extended neurites equivalent to those of untreated controls. The protocol was validated using hypericin (0–3 µg ml–1), which caused neuron death equivalent to other cell types.Conclusion: Neurons in culture can survive mTHPC-PDT under conditions sufficient to kill tumour cells and other nervous system cells

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

The effectiveness of health coaching, home blood pressure monitoring, and home-titration in controlling hypertension among low-income patients: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Despite the many antihypertensive medications available, two-thirds of patients with hypertension do not achieve blood pressure control. This is thought to be due to a combination of poor patient education, poor medication adherence, and "clinical inertia." The present trial evaluates an intervention consisting of health coaching, home blood pressure monitoring, and home medication titration as a method to address these three causes of poor hypertension control.</p> <p>Methods/Design</p> <p>The randomized controlled trial will include 300 patients with poorly controlled hypertension. Participants will be recruited from a primary care clinic in a teaching hospital that primarily serves low-income populations.</p> <p>An intervention group of 150 participants will receive health coaching, home blood pressure monitoring, and home-titration of antihypertensive medications during 6 months. The control group (n = 150) will receive health coaching plus home blood pressure monitoring for the same duration. A passive control group will receive usual care. Blood pressure measurements will take place at baseline, and after 6 and 12 months. The primary outcome will be change in systolic blood pressure after 6 and 12 months. Secondary outcomes measured will be change in diastolic blood pressure, adverse events, and patient and provider satisfaction.</p> <p>Discussion</p> <p>The present study is designed to assess whether the 3-pronged approach of health coaching, home blood pressure monitoring, and home medication titration can successfully improve blood pressure, and if so, whether this effect persists beyond the period of the intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT01013857</p

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol