Síntesis y evaluación de compuestos heterocíclicos derivados de ?-hidroxiácidos con interés industrial potencial.

The reaction of 2-hydroxyheptadecanoyl chloride (2) and anthranilic acid gave 2-(1-hydroxyheptadecyl)-4H-3,1-benzoxazin-4-one (3) which was used as starting material to synthesize some condensed and non-condensed heterocyclic compounds by a reaction with nitrogen nucleophiles (e.g., hydrazine hydrate, and formamide). The subsequent reaction of the synthetic products with different amounts of propylene oxide gave a novel group of nonionic compounds having a double function as antibacterial and surface active agents which may serve in the manufacturing of drugs, cosmetics, pesticides or as antibacterial and/or antifungal products. The surface active properties such as surface and interfacial tensions, cloud point, foaming height, wetting time, and emulsification power were determined. Antimicrobial and biodegradability were also screened.La reacción de cloruro de 2-hidroxiheptadecanoilo (2) con ácido antranílico produjo 2-(1-hidroxiheptadecil)-4H-3,1-benzoxazin-4-ona (3) que fue usada como material de partida en la síntesis de compuestos heterocíclicos condensados y no condensados por reacción con nucleófilos nitrogenados (hidracina y formamida). La reacción de los productos sintetizados con distintas cantidades de óxido de propileno dio un grupo nuevo de compuestos no iónicos con una función doble como antibacterianos y agentes tensioactivos que pueden servir en la manufactura de medicamentos, cosméticos, pesticidas, o como productos antibacterianos y/o antifúngicos. Se determinaron las propiedades tensioactivas así como la capacidad antimicrobiana y la biodegrabilidad de los compuestos sintetizados

Electrical resistivity tomography array comparisons to detect cleared-wall foundations in brownfield sites

Electrical resistivity surveys are commonly used to detect and characterise near-surface buried objects in commercial developments of brownfield sites. 2D ERT profiles arrays predominate in such surveys due to their relatively rapid deployment, good penetration depths and fast data collection rates. However, there is a need to test the optimum array types in such surveys. A scaled-model was used to simulate a large cleared-building wall foundation at a test facility, before multiple 2D ERT profiles were acquired using different array configurations. Results were used to generate 2D resistivity models using both least-square smoothness-constraint and robust inversion. 2D profile array comparisons showed that the Wenner and dipole-dipole arrays were the best in detecting the cleared-wall foundation, although dipole-dipole arrays better delineated the top of the wall foundation. This study suggests that both Wenner and dipole-dipole array configurations should be utilised to detect buried wall foundations for 2D resistivity surveys

Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions

Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction

Glycosylated nanoparticles as efficient antimicrobial delivery agents

Synthetic polymer nanoparticles that can be tailored through multivalent ligand display on the surface, while at the same time allowing encapsulation of desired bioactive molecules, are especially useful in providing a versatile and robust platform in the design of specific delivery vehicles for various purposes. Glycosylated nanoparticles (glyco-NPs) of a poly(n-butyl acrylate) (pBA) core and poly(N-2-(β-d-glucosyloxy)ethyl acrylamide) (p(NβGlcEAM)) or poly(N-2-(β-D-galactosyloxy)ethyl acrylamide) (p(NβGalEAM)) corona were prepared via nanoprecipitation in aqueous solutions of preformed amphiphilic glycopolymers. Well-defined block copolymers of (poly(pentafluorophenyl acrylate) (pPFPA) and pBA were first prepared by RAFT polymerization followed by postpolymerization functionalization with aminoethyl glycosides to yield p(NβGlcEAM-b-BA) and p(NβGalEAM-b-BA), which were then used to form glyco-NPs (glucosylated and galactosylated NPs, Glc-NPs and Gal-NPs, respectively). The glyco-NPs were characterized by dynamic light scattering (DLS) and TEM. Encapsulation and release of ampicillin, leading to nanoparticles that we have termed “glyconanobiotics”, were studied. The ampicillin-loaded glyco-NPs were found to induce aggregation of Staphylococcus aureus and Escherichia coli and resulted in antibacterial activity approaching that of ampicillin itself. This glyconanobiotics strategy represents a potential new approach for the delivery of antibiotics close to the surface of bacteria by promoting bacterial aggregation. Defined release in the proximity of the bacterial envelope may thus enhance antibacterial efficiency and potentially reduce the quantities of agent required for potency

Understanding the reasons behind the low utilisation of thrombolysis in stroke

Background Thrombolysis remains the only approved therapy for acute ischaemic stroke (AIS); however, its utilisation is reported to be low. Aims This study aimed to determine the reasons for the low utilisation of thrombolysis in clinical practice. Method Five metropolitan hospitals comprising two tertiary referral centres and three district hospitals conducted a retrospective, cross-sectional study. Researchers identified patients discharged with a principal diagnosis of AIS over a 12-month time period (July 2009-July 2010), and reviewed the medical record of systematically chosen samples. Results The research team reviewed a total of 521 records (48.8% females, mean age 74.4 ±14 years, age range 5-102 years) from the 1261 AIS patients. Sixty-nine per cent of AIS patients failed to meet eligibility criteria to receive thrombolysis because individuals arrived at the hospital later than 4.5 hours after the onset of symptoms. The factors found to be positively associated with late arrival included confusion at onset, absence of a witness at onset and waiting for improvement of symptoms. However, factors negatively associated with late arrival encompassed facial droop, slurred speech and immediately calling an ambulance. Only 14.7% of the patients arriving within 4.5 hours received thrombolysis. The main reasons for exclusion included such factors as rapidly improving symptoms (28.2%), minor symptoms (17.2%), patient receiving therapeutic anticoagulation (6.7%) and severe stroke (5.5%). Conclusion A late patient presentation represents the most significant barrier to utilising thrombolysis in the acute stroke setting. Thrombolysis continues to be currently underutilised in potentially eligible patients, and additional research is needed to identify more precise criteria for selecting patients for thrombolysis

Evaluation of cytotoxic activity of live toxoplasma gondii tachyzoites and toxoplasma antigen on MCF-7 human breast cancer cell line

The aim of this study was to investigate the cytotoxic potency of live Toxoplasma gondii tachyzoites as well as Toxoplasma antigen on MCF-7 human breast cancer cell line. Cancer cell lines are considered an essential preliminary step towards in-vitro investigation of the potential antineoplastic impact of novel chemotherapeutic agents. Pathogens, including viruses, bacteria, and parasites are noticeably under investigation, considering their potential antineoplastic activity. Some have attained a steady position in the clinical field as hepatitis B virus, human papilloma virus and BCG immunization. Toxoplasma gondii is an apicomplexan parasite with promising antineoplastic activity. In this study, live Toxoplasma tachyzoites provoked a direct cytotoxic effect on MCF-7 in a dose dependent manner, while Toxoplasma antigen didn’t induce such impact. Skipping the direct cytotoxic effect of Toxoplasma antigen doesn’t totally divert the possible antineoplastic activity of Toxoplasma antigen. Potential alternative immune mediated mechanisms could be an alternative. Further in-vivo studies in different cancer models are mandatory to investigate the underlying mechanisms of antineoplastic activity of Toxoplasma gondi

Síntesis y evaluación de compuestos heterocíclicos derivados de ?-hidroxi ácidos grasos con interés industrial potencial

T2-Hydroxyheptadecanoic acid chloride (2) reacted with anthranilic acid to produce 2-substituted-3,1-benzoxazin-4-one (3) which was used as starting material to synthesize some condensed and non-condensed heterocyclic compounds by reaction with nitrogen nucleophiles e.g., hydrazine hydrate, and formamide. The products were subjected to reaction with different moles of propylene oxide (n = 5, 10, 15) to produce a novel group of nonionic compounds having a double function as antibacterial and surface active agents which can be used in the manufacturing of drugs, cosmetics, pesticides or can be used as antibacterial and/or antifungal additives. The surface active properties as surface and interfacial tension, cloud point, foaming height, wetting time, and emulsification power were determined, the antimicrobial and biodegradability were also screened.El cloruro del ácido 2-hidroxiheptadecanoico (2) reaccionó con el ácido antranílico para producir 3,1-benzoxazin-4-onas 2-sustituidas que fueron usadas como material de partida en la síntesis de compuestos heterocíclicos condensados y no condensados por reacción con nucleófilos nitrogenados, como la hidracina o la formamida. Los productos fueron hechos reaccionar con diferentes moles de óxido de propileno (n = 5, 10, 15) para producir un grupo nuevo de compuestos no-iónicos teniendo una doble función como antibacterianos y tensoactivos que pueden ser usados en la manufactura de medicamentos, cosméticos, pesticidas, o pueden ser usados como aditivos antibacterianos y/o antifúngicos. Se determinaron diversas propiedades físicas de los compuestos preparados así como sus efectos antimicrobianos y sus biodegrabilidad

The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study

Background Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women. Methods This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations. Results Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p  = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20 {12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14}days). Conclusions PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose