Chemical and Biological Investigations of Pilocarpus spicatus essential oils [Estudios químicos y biológicos del aceite esencial de Pilocarpus spicatus]

El aceite esencial fue extraido por arraste de vapor de las partes aéreas de Pilocarpus spicatus Saint-Hilaire (Rutaceae) de la costa Norte del estado de Rio deJaneiro y examinado por GC-MS. Fueron identificados 17 componentes que corresponden al 96,06% de la composición quìmica del aceite. Los componentesmayoritarios fueron el limoneno (41,87%), 2 undecanona (11,0%) y sabineno (10,78%). El aceite esencial de P. spicatus tiene efecto inhibitorio sobre elcrecimiento bacteriano (Escherichia coli y Staphylococcus aureus) y presentando también actividad anticolinesterasa en ensayo de TLC. Adicionalmente elaceite volátil ha demostrado ser tóxico para las larvas de Artemia salina

Virulence potential of biofilm producing Staphylococcus pseudintermedius, Staphylococcus aureus and Staphylococcus coagulans causing skin infections in companion animals

publishersversioninpres

Role of the Rostral Ventrolateral Medulla in the Arterial Hypertension in Chronic Renal Failure

Sympathetic activation in chronic renal failure (CRF) is a major mechanism leading to the progression of renal disease and hypertension. In the present study, we tested the hypothesis that in CRF increased reactive oxygen species (ROS) production in the RVLM mediated by enhanced circulating Angiotensin II (Ang II) is an important mechanism leading to hypertension in CRF. In CRF rats we found an increase in the abundance of p47phox and gp91phox mRNA within the RVLM associated with a reduction of Ang II type 1 receptors (AT1) mRNA in the brainstem compared to controls (C). Tempol but not candesartan into the RVLM decreased MAP in CRF but not in C rats. GABA into the RVLM decreased MAP in CRF (63 ± 8 mmHg) more intensely than in C (33 ± 3 mmHg). The results suggest that increased oxidative stress within the RVLM has an important participation to maintain hypertension in CRF rats apparently independently of AT1 Ang II receptors

Sensitive bi-enzymatic biosensor based on polyphenoloxidases–gold nanoparticles–chitosan hybrid film–graphene doped carbon paste electrode for carbamates detection

A bi-enzymatic biosensor (LACC–TYR–AuNPs–CS/GPE) for carbamates was prepared in a single step by electrodeposition of a hybrid film onto a graphene doped carbon paste electrode (GPE). Graphene and the gold nanoparticles (AuNPs) were morphologically characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering and laser Doppler velocimetry. The electrodeposited hybrid film was composed of laccase (LACC), tyrosinase (TYR) and AuNPs entrapped in a chitosan (CS) polymeric matrix. Experimental parameters, namely graphene redox state, AuNPs:CS ratio, enzymes concentration, pH and inhibition time were evaluated. LACC–TYR–AuNPs–CS/GPE exhibited an improved Michaelis–Menten kinetic constant (26.9 ± 0.5 M) when compared with LACC–AuNPs–CS/GPE (37.8 ± 0.2 M) and TYR–AuNPs–CS/GPE (52.3 ± 0.4 M). Using 4-aminophenol as substrate at pH 5.5, the device presented wide linear ranges, low detection limits (1.68×10− 9 ± 1.18×10− 10 – 2.15×10− 7 ± 3.41×10− 9 M), high accuracy, sensitivity (1.13×106 ± 8.11×104 – 2.19×108 ± 2.51×107 %inhibition M− 1), repeatability (1.2–5.8% RSD), reproducibility (3.2–6.5% RSD) and stability (ca. twenty days) to determine carbaryl, formetanate hydrochloride, propoxur and ziram in citrus fruits based on their inhibitory capacity on the polyphenoloxidases activity. Recoveries at two fortified levels ranged from 93.8 ± 0.3% (lemon) to 97.8 ± 0.3% (orange). Glucose, citric acid and ascorbic acid do not interfere significantly in the electroanalysis. The proposed electroanalytical procedure can be a promising tool for food safety control

Estudio comparativo entre levobupivacaína a 0,5% y bupivacaína racémica a 0,5% asociadas al sufentanil en la anestesia peridural para cesáre

BACKGROUND AND OBJECTIVES: Although the widespread use of local anesthetics in surgery and obstetrics, racemic bupivacaine is associated to potentially fatal cardiotoxicity. Data suggest that levobupivacaine has local anesthetic effects similar to racemic bupivacaine with the advantage of less central nervous system and cardiovascular toxicity. Studies have shown that epidural anesthesia with racemic bupivacaine and sufentanil for cesarean sections results in a better quality of anesthesia. This study aimed at comparing the efficacy of 0.5% racemic bupivacaine and 0.5% levobupivacaine, both associated to sufentanil, for epidural anesthesia in parturients undergoing cesarean delivery. METHODS: Participated in this double-blind study 52 obstetric patients submitted to elective cesarean delivery under epidural anesthesia. Patients were randomized to receive 27 ml of 0.5% levobupivacaine and 30 µg sufentanil (Group I n=26) or 27 ml of 0.5% bupivacaine and 30 µg sufentanil (Group II n=26). Characteristics of sensory and motor block, time for analgesics request in the postoperative period and the incidence of side effects were investigated. RESULTS: Sensory and motor block, time for analgesics request and adverse effects did not differ between groups. However, motor block was significantly longer with levobupivacaine as compared to racemic bupivacaine (p < 0.05). CONCLUSIONS: Although a longer motor block duration with 0.5% epidural levobupivacaine associated to sufentanil, the efficacy of both local anesthetics associated to sufentanil for cesarean delivery was similar.JUSTIFICATIVA Y OBJETIVOS: A pesar del uso frecuente de anestésicos locales en procedimientos quirúrgicos y obstétricos, la bupivacaína racémica es asociada a la cardiotoxicidad potencialmente fatal. Estudios sugieren que la levobupivacaína presenta acción anestésica local semejante a la bupivacaína racémica, con la ventaja de menor toxicidad tanto en el sistema nervioso central como cardiovascular. Los trabajos han demostrado mejor calidad anestésica con el uso de bupivacaína racémica asociada al sufentanil, vía peridural para cesárea. El presente estudio compara la eficacia de la bupivacaína racémica 0,5% con levobupivacaína 0,5%, ambas asociadas al sufentanil, vía peridural, en parturientas sometidas a cesárea. MÉTODO: Fueron investigadas 52 mujeres embarazadas, sometidas a anestesia peridural para cesárea electiva. En este estudio duplamente encubierto, las pacientes fueron distribuidas aleatoriamente en dos grupos: Grupo I (n = 26): recibieron 27 ml de levobupivacaína 0,5% y 30 µg de sufentanil, Grupo II (n = 26) recibieran 27 ml de bupivacaína 0,5% y 30 µg de sufentanil. Fueron evaluadas las características de los bloqueos motor y sensorial, el tiempo necesario para solicitación de analgésicos y la incidencia de efectos adversos en el período pós-operatorio. RESULTADOS: Los bloqueos motor y sensorial, el tiempo para solicitación de analgésicos y los efectos adversos no divergieron entre los grupos. Entretanto, cuando se comparó la duración del bloqueo motor de la levobupivacaína con el de la bupivacaína racémica, se observó duración significantemente prolongada para levobupivacaína (p < 0,05). CONCLUSIONES: A pesar de la duración del bloqueo motor ser más prolongado para la levobupivacaína asociada al sufentanil, la eficacia anestésica de ambos anestésicos locales investigados, asociados al sufentanil en cesárea por vía peridural, fueron iguales.JUSTIFICATIVA E OBJETIVOS: Apesar do uso freqüente de anestésicos locais em procedimentos cirúrgicos e obstétricos, a bupivacaína racêmica é associada à cardiotoxicidade potencialmente fatal. Estudos sugerem que a levobupivacaína apresenta ação anestésica local semelhante à bupivacaína racêmica, com a vantagem de menor toxicidade tanto no sistema nervoso central como cardiovascular. Os trabalhos têm demonstrado melhor qualidade anestésica com uso de bupivacaína racêmica associada à sufentanil, via peridural para cesariana. O presente estudo compara a eficácia da bupivacaína racêmica 0,5% com levobupivacaína 0,5%, ambas associadas o sufentanil, via peridural, em parturientes submetidas a cesariana. MÉTODO: Foram investigadas 52 gestantes, submetidas à anestesia peridural para cesariana eletiva. Neste estudo duplamente encoberto, as pacientes foram distribuídas aleatoriamente em dois grupos: Grupo I (n = 26): receberam 27 ml de levobupivacaína 0,5% e 30 µg de sufentanil, Grupo II (n = 26) receberam 27 ml de bupivacaína 0,5% e 30 µg de sufentanil. Foram avaliados as características dos bloqueios motor e sensorial, o tempo necessário para solicitação de analgésicos e a incidência de efeitos adversos no período pós-operatório. RESULTADOS: Os bloqueios motor e sensorial, o tempo para solicitação de analgésicos e os efeitos adversos não diferiram entre os grupos. Entretanto, quando se comparou a duração do bloqueio motor da levobupivacaína com da bupivacaína racêmica, observou-se duração significantemente prolongada para levobupivacaína (p < 0,05). CONCLUSÕES: Apesar da duração do bloqueio motor ser mais prolongado para a levobupivacaína associada ao sufentanil, a eficácia anestésica de ambos os anestésicos locais investigados associados ao sufentanil em cesariana por via peridural, foram iguais.UFMAUFMA Hospital Universitário Materno InfantilUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

(Bio)Sensing Strategies Based on Ionic Liquid-Functionalized Carbon Nanocomposites for Pharmaceuticals: Towards Greener Electrochemical Tools

The interaction of carbon-based nanomaterials and ionic liquids (ILs) has been thoroughly exploited for diverse electroanalytical solutions since the first report in 2003. This combination, either through covalent or non-covalent functionalization, takes advantage of the unique characteristics inherent to each material, resulting in synergistic effects that are conferred to the electrochemical (bio)sensing system. From one side, carbon nanomaterials offer miniaturization capacity with enhanced electron transfer rates at a reduced cost, whereas from the other side, ILs contribute as ecological dispersing media for the nanostructures, improving conductivity and biocompatibility. The present review focuses on the use of this interesting type of nanocomposites for the development of (bio)sensors specifically for pharmaceutical detection, with emphasis on the analytical (bio)sensing features. The literature search displayed the conjugation of more than 20 different ILs and several carbon nanomaterials (MWCNT, SWCNT, graphene, carbon nanofibers, fullerene, and carbon quantum dots, among others) that were applied for a large set (about 60) of pharmaceutical compounds. This great variability causes a straightforward comparison between sensors to be a challenging task. Undoubtedly, electrochemical sensors based on the conjugation of carbon nanomaterials with ILs can potentially be established as sustainable analytical tools and viable alternatives to more traditional methods, especially concerning in situ environmental analysisThis work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of the project POCI-01-0145-FEDER-029547—PTDC/ASP-PES/29547/2017. This work received support by UIDB/50006/2020, UIDP/50006/ 2020 and LA/P/0008/2020 by the Fundação para a Ciência e a Tecnologia (FCT), Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through national funds. T.M.B.F. Oliveira thanks the Brazilian agencies CNPq (Proc. 420261/2018-4 and 308108/2020-5) and FUNCAP (Proc. BP4-0172-00111.01.00/20) for their financial support, and he is grateful to UFCA and CAPES (Finance code 001) for supporting his investigations. F.W.P. Ribeiro thanks all support provided by the UFCA’s Pro-Rectory of Research and Innovation and the funding provided by FUNCAP-BPI (Proc. BP4-0172-00150.01.00/20) and CNPq (Proc. 406135/2018-5). P. de Lima-Neto thanks the financial support received from CNPq projects 408626/2018-6 and 304152/2018-8 and FUNCAP project FCT-00141-00011.01.00/18. A. N. Correia thanks the financial support received from CNPq projects: 305136/2018-6 and 405596/2018-9info:eu-repo/semantics/publishedVersio

Characterization of thimet oligopeptidase and neurolysin activities in B16F10-Nex2 tumor cells and their involvement in angiogenesis and tumor growth

<p>Abstract</p> <p>Background</p> <p>Angiogenesis is a fundamental process that allows tumor growth by providing nutrients and oxygen to the tumor cells. Beyond the oxygen diffusion limit from a capillary blood vessel, tumor cells become apoptotic. Angiogenesis results from a balance of pro- and anti-angiogenic stimuli. Endogenous inhibitors regulate enzyme activities that promote angiogenesis. Tumor cells may express pro-angiogenic factors and hydrolytic enzymes but also kinin-degrading oligopeptidases which have been investigated.</p> <p>Results</p> <p>Angiogenesis induced by B16F10-Nex2 melanoma cells was studied in a co-culture with HUVEC on Matrigel. A stimulating effect on angiogenesis was observed in the presence of B16F10-Nex2 lysate and plasma membrane. In contrast, the B16F10-Nex2 culture supernatant inhibited angiogenesis in a dose-dependent manner. This effect was abolished by the endo-oligopeptidase inhibitor, JA-2. Thimet oligopeptidase (TOP) and neurolysin activities were then investigated in B16F10-Nex2 melanoma cells aiming at gene sequencing, enzyme distribution and activity, influence on tumor development, substrate specificity, hydrolytic products and susceptibility to inhibitors. Fluorescence resonance energy transfer (FRET) peptides as well as neurotensin and bradykinin were used as substrates. The hydrolytic activities in B16F10-Nex2 culture supernatant were totally inhibited by <it>o</it>-phenanthrolin, JA-2 and partially by Pro-Ile. Leupeptin, PMSF, E-64, Z-Pro-Prolinal and captopril failed to inhibit these hydrolytic activities. Genes encoding M3A enzymes in melanoma cells were cloned and sequenced being highly similar to mouse genes. A decreased proliferation of B16F10-Nex2 cells was observed in vitro with specific inhibitors of these oligopeptidases. Active rTOP but not the inactive protein inhibited melanoma cell development in vivo increasing significantly the survival of mice challenged with the tumor cells. On Matrigel, rTOP inhibited the bradykinin – induced angiogenesis. A possible regulation of the homologous tumor enzyme in the perivascular microenvironment is suggested based on the observed rTOP inhibition by an S-nitrosothiol NO donor.</p> <p>Conclusion</p> <p>Data show that melanoma cells secrete endo-oligopeptidases which have an important role in tumor proliferation in vitro and in vivo. rTOP inhibited growth of subcutaneously injected B16F10-Nex2 cells in mice. TOP from tumor cells and bradykinin in endothelial cells are two antagonist factors that may control angiogenesis essential for melanoma growth. A regulatory role of NO or S-nitrosothiols is suggested.</p

Metallochlorophylls of magnesium, copper and zinc: evaluation of the influence of the first coordination sphere on their solvatochromism and aggregation properties

In this study the role of different metal centers (magnesium, zinc and copper) on the enhancement of the hydrophilic character of metallochlorophylls, was evaluated. The solvatochromism as well as the aggregation process for these compounds in water/ethanol mixtures at different volume ratios were evaluated using Fluorescence, and Resonant Light Scattering (RLS) measurements, aiming to characterize the behavior of these compounds. Independently on the studied metallochlorophyll, the presence of at least 60% of water results in a considerable increase in the fluorescence emission, probably a direct consequence of a lower aggregation of these compounds, which is confirmed by the results from RLS measurements. Additionally, the results suggest that magnesium and zinc chlorophyll should be promising phototherapeutic agents for Photodynamic Therapy.No presente estudo, o papel de diferentes centros metálicos (magnésio, zinco e cobre) sobre o caráter hidrofílico de metaloclorofilas foi avaliado. O solvatocromismo, assim como o processo de agregação para esses compostos, em misturas água/etanol foram avaliados usando medidas de fluorescência e de espalhamento de luz ressonante (ELR), visando caracterizar o comportamento desses compostos. Independente da metaloclorofila estudada, a presença de ao menos 60% de água resulta em incremento considerável na emissão de fluorescência apresentada por esses compostos. Isso, provavelmente, é uma conseqüência direta de uma menor agregação, o que é confirmado pelos resultados de ELR. Adicionalmente, os resultados sugerem que as clorofilas de magnésio e de zinco devem ser promissores agentes fototerapêuticos para emprego em Terapia Fotodinâmica.FAPESPFundação AraucáriaFAPEMIGCNPqNanobra