Fotopletismografía laparoscópica: Nueva técnica mínimamente invasiva y estudios experimentales iniciales

In the endoscopic procedures there is not possible to use the sense of touch for the detection of weak palpitations as in open surgery, neither to directly evaluate the oxygenation and perfusion of intra-corporeal organs and tissues. Here, we present the initial results after the application of laparoscopic photoplethysmography, a novel technique developed by our group, which allows obtaining specific clinical parameters and overcome the cited drawbacks. From the photoplethysmograpic signals of different wavelengths recorded in intra-abdominal organs and territories of animal models, their pulse values and oxygenation related quotients have been derived. © Sociedad Española de Óptica.Este trabajo ha sido financiado por el proyecto PI 04/0715 del Fondo de Investigaciones Sanitarias. Agradecemos la colaboración prestada durante el estudio experimental por Dr. José Carlos Manuel Palazuelos, Dr. Juan Carlos González Cueli y las diplomadas en Enfermería del CENDOS. Parte de los resultados aquí expuestos han sido presentados oralmente en el Congreso de la Sociedad Española de Laparoscopia (SECLA 2009) celebrado en Santander en mayo de 2009. SMLS está contratada por el Programa I3P con financiación del Fondo Social Europeo.Peer Reviewe

Linear relationships between partition coefficients of different organic compounds and proteins in aqueous two-phase systems of various polymer and ionic compositions

Analysis of the partition coefficients of small organic compounds and proteins in different aqueous two-phase systems under widely varied ionic compositions shows that logarithms of partition coefficients for any three compounds or proteins or two organic compounds and one protein are linearly interrelated, although for protein(s) there are ionic compositions when the linear fit does not hold. It is suggested that the established interrelationships are due to cooperativity of different types of solute–solvent interactions in aqueous media. This assumption is confirmed by analysis of distribution coefficients of various drugs in octanol-buffer systems with varied ionic compositions of the buffer. Analysis of the partition coefficients characterizing distribution of variety of drugs between blood and different tissues of rats in vivo reported in the literature showed that the above assumption is correct and enabled us to identify the tissues with the components of which the drug(s) may engage in presumably direct interactions. It shows that the suggested assumption is valid for even complex biological systems.info:eu-repo/semantics/publishedVersio

Determination of tranexamic acid in human plasma by UHPLC coupled with tandem mass spectrometry targeting sub-microgram per milliliter levels

Tranexamic acid (TXA) is an antifibrinolytic drug, with the ability to inhibit lysine binding at plasminogen receptors, used in adult trauma patients with on-going or at risk of significant haemorrhage. To understand the pharmacokinetics and pharmacodynamics of this drug in variable age groups undergoing surgeries with high blood loss, effective methods for determination of TXA in biological samples at sub-μg mL−1 are still required. We describe herein the development and validation of a method based on ultra-high performance liquid chromatography coupled to triple quadrupole-tandem mass spectrometry to quantify TXA in human plasma. An inexpensive, simple and efficient sample clean-up was implemented, not requiring matrix-matching calibration. Sample preparation consisted in protein precipitation using acetonitrile containing 0.5% (v/v) formic acid, followed by hydrophilic interaction based chromatographic separation, with elution in isocratic mode using a combination of acetonitrile and water (75:25, v/v), with quantification of TXA based on selected reaction monitoring. Good linearity was achieved (r2 > 0.997) for TXA concentrations ranging from 30 to 600 ng mL−1, with LOD of 18 ng mL−1 in plasma. The developed method proved to be selective, sensitive, accurate (96.4–105.7% of nominal values) and precise (RSD ≤ 4.5%). TXA was found to be stable in plasma extracts standing 24 h at room temperature (20 °C) or in the autosampler, and after three freeze-thawing cycles. Mean recovery values of TXA spiked plasma samples were ≥91.9%. No significant matrix effects were observed. The proposed methodology was successfully applied to the clinical study of plasma samples recovered during scoliosis surgery of pediatric patients pretreatment with TXA.info:eu-repo/semantics/publishedVersio

Photocatalytic ozonation of urban wastewater and surface water using immobilized TiO2 with LEDs: Micropollutants, antibiotic resistance genes and estrogenic activity

Photocatalytic ozonation was employed for the first time in continuous mode with TiO2-coated glass Raschig rings and light emitting diodes (LEDs) to treat urban wastewater as well as surface water collected from the supply area of a drinking water treatment plant (DWTP). Different levels of contamination and types of contaminants were considered in this work, including chemical priority substances (PSs) and contaminants of emerging concern (CECs), as well as potential human opportunistic antibiotic resistant bacteria and their genes (ARB&ARG). Photocatalytic ozonation was more effective than single ozonation (or even than TiO2 catalytic ozonation) in the degradation of typical reaction by-products (such as oxalic acid), and more effective than photocatalysis to remove the parent micropollutants determined in urban wastewater. In fact, only fluoxetine, clarithromycin, erythromycin and 17-alpha-ethinylestradiol (EE2) were detected after photocatalytic ozonation, by using solid-phase extraction (SPE) pre-concentration and LC-MS/MS analysis. In surface water, this treatment allowed the removal of all determined micropollutants to levels below the limit of detection (0.01-0.20 ng L(-1)). The efficiency of this process was then assessed based on the capacity to remove different groups of cultivable microorganisms and housekeeping (16S rRNA) and antibiotic resistance or related genes (intI1, blaTEM, qnrS, sul1). Photocatalytic ozonation was observed to efficiently remove microorganisms and ARGs. Although after storage total heterotrophic and ARB (to ciprofloxacin, gentamicin, meropenem), fungi, and the genes 16S rRNA and intI1, increased to values close to the pre-treatment levels, the ARGs (blaTEM, qnrS and sul1) were reduced to levels below/close to the quantification limit even after 3-days storage of treated surface water or wastewater. Yeast estrogen screen (YES), thiazolyl blue tetrazolium reduction (MTT) and lactate dehydrogenase (LDH) assays were also performed before and after photocatalytic ozonation to evaluate the potential estrogenic activity, the cellular metabolic activity and the cell viability. Compounds with estrogenic effects and significant differences concerning cell viability were not observed in any case. A slight cytotoxicity was only detected for Caco-2 and hCMEC/D3 cell lines after treatment of the urban wastewater, but not for L929 fibroblasts.info:eu-repo/semantics/acceptedVersio

Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment

Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extra-cellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. in mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in DMD patients. Alterations in gastrointestinal tissues from DMD patients and mdx mice are not yet completely understood. Thus, we investigated the possible relationships between morphological (light and electron microscopy) and contractile function (by recording the isometric contractile response) with alterations in Ca2+ handling in the ileum of mdx mice. We evidenced a 27% reduction in the ileal muscular layer thickness, a partial damage to the mucosal layer, and a partial damage to mitochondria of the intestinal myocytes. Functionally, the ileum from mdx presented an enhanced responsiveness during stretch, a mild impairment in both the electromechanical and pharmacomechanical signaling associated with altered calcium influxinduced contraction, with no alterations in the sarcoplasmic reticulum Ca2+ storage (maintenance of the caffeine and thapsigargin-induced contraction) compared with control animals. Thus, it is evidenced that the protein dystrophin plays an important role in the preservation of both the microstructure and ultrastructure of mice intestine, while exerting a minor but important role concerning the intestinal contractile responsiveness and calcium handling.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Microscopia Eletron, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Microscopia Eletron, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04023062 São Paulo, BrazilFAPESP: 07/58132-9FAPESP: 12/15716-9FAPESP: 07/59976-6Web of Scienc

Pd and Pd-Cu supported on different carbon materials and immobilized as flow-through catalytic membranes for the chemical reduction of NO3, NO2-and BrO3- in drinking water treatment

Powdered catalysts are commonly used in lab-scale tests for the catalytic reduction of oxoanions in drinking water, but their powder nature limits their application at full scale. In this work, Pd and Pd-Cu catalysts (5% wt.) supported on carbon materials with different structural properties, in powder form, were used to prepare catalytic membranes that were tested in a reactor with flow-through configuration (FTCMR) to study their performance in the reduction of NO3-, NO2- and BrO3-. Pd catalytic membranes showed high activity in the reduction of NO2-, being the selectivity to NH4+ lower than 2% at 80% NO2- conversion in all cases. In BrO3- reduction, they exhibited a wide range of conversions being the catalyst supported on materials with high conductivity the most active ones, which may be ascribed to the charge distribution at the metal-carbon interface. NO3- reduction using Pd-Cu catalytic membranes showed that catalysts supported on materials with small nanoparticle size and low electrical conductivity exhibited higher selectivity to NH4+. FTCMR led to a good control of H2 transfer and availability in the active sites, facilitating the tuning of H2 availability conditions to preserve the activity, while maintaining/diminishing selectivity to NH4+. In simultaneous oxoanions reduction tests, NO3- reduction was inhibited by Br species, probably by affection of the Pd-Cu redox cycle. This fact could be crucial to the future development of drinking water treatment processes, as conditions the order of the disinfection and NO3- reduction stepsThe authors greatly appreciate the support from Spanish Agencia Estatal de Investigacion ´ (AEI, RTI2018–098431-BI00). Adrian ´ Marí thanks the Spanish AEI for a research grant (PRE-2019-088601). This work was also financially supported by: LA/P/0045/2020 (ALiCE), UIDB/50020/2020 and UIDP/50020/2020 (LSRE-LCM) and funded by national funds through FCT/MCTES (PIDDAC), and project NORTE01–0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund (ERDF), through North Portugal Regional Operational Program (NORTE2020), under the PORTUGAL 2020 Partnership Agreemen

Synthesis, biological evaluation, and molecular modeling of nitrile-containing compounds : exploring multiple activities as anti-Alzheimer agents

Funding: EC COST Actions D34 and CM1103 for Short-term Scientific Mission funding (EM, DS, MM); the School of Biology at the University of St. Andrews (EJS, RRR); the Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa (AN, ACJ, TR, MCC); FCT, the Portuguese Foundation for Science and Technology (Project PTDC/SAU-NEU/64151/2006 (MCC), and project grant (DS) Vega 2/0127/18 and the contract No. APVV-15-0455 of Slovak Research and Development Agency (MM).Based on the monoamine oxidase (MAO) inhibition properties of aminoheterocycles with a carbonitrile group we have carried out a systematic exploration to discover new classes of carbonitriles endowed with dual MAO and AChE inhibitory activities, and Aβ anti‐aggregating properties. Eighty‐three nitrile‐containing compounds, 13 of which are new, were synthesized and evaluated. in vitro screening revealed that 31 , a new compound, presented the best lead for trifunctional inhibition against MAO A (0.34 μM), MAO B (0.26 μM), and AChE (52 μM), while 32 exhibited a lead for selective MAO A (0.12 μM) inhibition coupled to AChE (48 μM) inhibition. Computational analysis revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped by an internal penalty caused by twisting of the ligand molecule and subsequent disruption of the conjugation ( 32 in MAO B compared to the conjugated 31 ). Conjugation is also important for AChE as well as the hydrophilic character of malononitrile that allows this group to be in close contact with the aqueous environment as seen for 83 . Although the effect of 31 and 32 against Aβ1–42, was very weak, the effect of 63 and 65 , and of the new compound 75 , indicated that these compounds were able to disaggregate Aβ1–42 fibrils. The most effective was 63 , a (phenylhydrazinylidene)propanedinitrile derivative that also inhibited MAO A (1.65 μM), making it a potential lead for Alzheimer's disease application.PostprintPeer reviewe

Improved syntheses of aromatase inhibitors and neuroactive steroids efficient oxidations and reductions at key positions for bioactivity

An Henbest reduction, followed by the preparation of a silyl enol ether and oxidation in situ with m-CPBA has led to the neurosteroids 3[alpha]-hydroxy- and 3[alpha],21-dihydroxy-5[alpha]-pregnanolones. Using testosterone as starting material, a new short synthesis of an aromatase inhibitor, 4-OHA, has been achieved through hydroboration/oxidation followed by a Swern type oxidation and epimerization. Another aromatase inhibitor, androst-4-ene-3,6-17-trione, has been efficiently prepared using PCC on montmorillonite K10, under ultrasonic irradiation.http://www.sciencedirect.com/science/article/B6THR-3WC46V7-8/1/5f915790e78df65f4c988ab78bf4f17