Synthesis, Characterization and DNA Cleavage of Copper(II) Complex with D,L-Dithiothreitol

Purpose: To study deoxyribonucleic acid (DNA) shearing capability of copper(II) complex of dithiothreitol (DTT) and to fevaluate its potential application in cancer therapy.Methods: A parrot green complex was synthesized by grinding copper acetate monohydrate and DTT in 1:2 molar ratio in a mortar until no fumes of acetic acid were observed. The complex was characterized using attenuated total reflectance-Fourier transform infra-red (ATR-FTIR), and x-ray diffraction (XRD) techniques. Further information was also collected through Karl Fischer titration, thermogravimetric analysis (TGA) and (magnetic moment. Cleavage of DNA was determined by agarose gel electrophoresis. The gel was then stained, analyzed and photographed under ultraviolet (UV) light.Results: ATR-FTIR confirmed the formation of copper(II) complex with DTT by binding through thiol group based on the disappearance of the thiol (-SH) stretching peak at 2545 cm-1. The crystalline structure was elucidated by a sharp intense peak at 38.520 in XRD spectrum while the octahedral geometry of complex was inferred from a magnetic moment of 1.72 B.M. The results for water content obtained by Karl Fischer titration and TGA revealed that water molecules are not part of the coordination sphere of the complex. Cleavage study of DNA showed that the complex completely sheared the circular DNA compared to pure DTT.Conclusion: Solvent free synthesis of Copper(II)-DTT complex has been successfully achieved, and an anhydrous complex with octahedral geometry obtained. The complex has a greater potential to shear DNA molecule than pure DTT.Keywords: DNA shearing, Copper(II) complex, Dithiothreitol, Attenuated total reflectance-Fourier transform infra-red, Karl Fischer titration, Magnetic momen

Software agents and wireless E-commerce

Software agent technology will become a necessity to e-commerce (traditional or wireless) rather than luxury. We propose an agent-based environment, which we call E-Commerce through Wireless Devices (E-CWE), that allows users, stationary or mobile, to submit their requests for services offered by providers. The E-CWE environment consists of a reception platform including a repository of service descriptions. A supervisor-agent is in charge of this repository. Acting on behalf of their users, user-agents are dynamically created in this platform. In the E-CWE environment, security is achieved in two steps: securing service access and securing payment. A prototype of a Travel Planning Agent (TPA) system is proposed to evaluate the performance of the environment

Integrin CD11b activation drives anti-tumor innate immunity

Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, integrin CD11b does not regulate myeloid cell recruitment to tumors but instead controls myeloid cell polarization and tumor growth. CD11b activation promotes pro-inflammatory macrophage polarization by stimulating expression of microRNA Let7a. In contrast, inhibition of CD11b prevents Let7a expression and induces cMyc expression, leading to immune suppressive macrophage polarization, vascular maturation, and accelerated tumor growth. Pharmacological activation of CD11b with a small molecule agonist, Leukadherin 1 (LA1), promotes pro-inflammatory macrophage polarization and suppresses tumor growth in animal models of murine and human cancer. These studies identify CD11b as negative regulator of immune suppression and a target for cancer immune therapy

The preventive misconception: experiences from CAPRISA 004.

CAPRISA, 2014.Abstract available in pdf

Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial.

CAPRISA, 2014.Background: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. Methods/design: This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. Discussion: This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa. Trial registration: This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012

Monitoring microbicide gel use with real-time notification of the container’s opening events : results of the CAPRISA Wisebag study.

CAPRISA, 2014.Accurate estimation of the effectiveness of a microbicide for HIV prevention requires valid measurement of adherence to product use. A microbicide gel applicator container (Wisebag), fitted with cell phone technology to transmit opening events and text message reminders, was developed to monitor each opening event of the container as a proxy for gel use and adherence. Ten women were enrolled in a pilot study and followed for up to 4 months. Wisebag opening (WBO) dates and times were recorded and correlated with self-reported sex acts and gel applicator returns. During the 33 monthly follow-up visits, 47.8% (77/161) of the recorded number of WBO events were concordant with the number of empty (used) applicators returned. The discrepancies were likely due to removal of more than one applicator during a single opening event. When the date and time of the WBO event data was assessed in relation to three different self-report adherence measures, agreement was fairly modest. The Wisebag was found to be acceptable as a storage container and the cell phone reminders generated were useful in supporting the dosing strategy. We recommend that the Wisebag be considered for larger scale and lengthier testing in microbicide trials

Disclosure of microbicide gel use to sexual partners: influence on adherence in the CAPRISA 004 trial.

CAPRISA, 2014.Abstract available in pdf

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700