Publications by authors named "Ana-Maria Pereira"

67 Publications

Pharmacological characterisation of anticonvulsant effects elicited by erythrartine.

J Pharm Pharmacol 2021 Mar;73(1):93-97

Department of Biotechnology, University of Ribeirão Preto, Ribeirão Preto, SP, Brazil.

Objectives: The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants.

Methods: Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination.

Results: Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals.

Conclusion: Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.
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http://dx.doi.org/10.1093/jpp/rgaa024DOI Listing
March 2021

Precursor-directed Biosynthesis in Tabernaemontana catharinensis as a New Avenue for Alzheimer's Disease-modifying Agents.

Planta Med 2021 Feb 15;87(1-02):136-147. Epub 2020 Dec 15.

Biotechnology Unit, University of Ribeirão Preto (UNAERP), Ribeirão Preto, SP, Brazil.

Plants produce a high diversity of metabolites that can act as regulators of cholinergic dysfunction. Among plants, the potential of species of the genus to treat neurological disorders has been linked to iboga-type alkaloids that are biosynthesized by those species. In this context, precursor-directed biosynthesis approaches were carried out using plantlets to achieve new-to-nature molecules as promising agents against Alzheimer's disease. Aerial parts of , cultured in vitro, produced 7 unnatural alkaloids (5-fluoro-ibogamine, 5-fluoro-voachalotine, 5-fluoro-12-methoxy-Nb-methyl-voachalotine, 5-fluoro-isovoacangine, 5-fluoro-catharanthine, 5-fluoro-19-(S)-hydroxy-ibogamine, and 5-fluoro-coronaridine), while root extracts showed the presence of the same unnatural iboga-type alkaloids and 2 additional ones: 5-fluoro-voafinine and 5-fluoro-affinisine. Moreover, molecular docking approaches were carried out to evaluate the potential inhibition activity of ' natural and unnatural alkaloids against AChE and BChE enzymes. Fluorinated iboga alkaloids (5-fluoro-catharanthine, 5-fluoro-voachalotine, 5-fluoro-affinisine, 5-fluoro-isovoacangine, 5-fluoro-corinaridine) were more active than natural ones and controls against AchE, while 5-fluoro-19-(S)-hydroxy-ibogamine, 5-fluoro-catharanthine, 5-fluoro-isovoacangine, and 5-fluoro-corinaridine showed better activity than natural ones and controls against BChE. Our findings showed that precursor-directed biosynthesis strategies generated "new-to-nature" alkaloids that are promising Alzheimer's disease drug candidates. Furthermore, the isotopic experiments also allowed us to elucidate the initial steps of the biosynthetic pathway for iboga-type alkaloids, which are derived from the MEP and shikimate pathways.
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http://dx.doi.org/10.1055/a-1315-2282DOI Listing
February 2021

Development and characterization of microsatellite markers in (Leguminosae).

Physiol Mol Biol Plants 2020 Oct 16;26(10):2095-2101. Epub 2020 Sep 16.

Laboratório de Genética e Biodiversidade, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás Brazil.

In this study, we report the development and characterization of 15 new microsatellite markers for (Leguminosae) in order to support future analyses of genetic diversity in populations of this species. In screening with 48 individuals from three different populations of , we tested the amplification of 20 microsatellite loci, of which five are not useful for population genetic studies due to the lack of polymorphisms or amplification failures. For the final set of 15 loci, the number of alleles ranged from 2 to 15, with a total of 116 alleles. The expected heterozygosity ranged from 0.1219 to 0.8965, with an average of 0.6694 per locus. The combined probability of genetic identity ( = 8.12 × 10) and paternity exclusion ( = 0.99999) estimations showed that the loci may be useful to discriminate between individuals of Initial cross-amplification tests were satisfactory in three species of the genus : , and . This new set of markers will be a useful tool for population genetic studies, contributing to the knowledge about the evolutionary history of and, additionally, correlated species.
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http://dx.doi.org/10.1007/s12298-020-00876-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548263PMC
October 2020

The Effect of Rutin and Extracts of (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study.

Molecules 2020 Mar 13;25(6). Epub 2020 Mar 13.

Hospital Israelita Albert Einstein, Av. Albert Einstein 627, Morumbi 05651-901, São Paulo, SP, Brazil.

There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10-15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two- and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.
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http://dx.doi.org/10.3390/molecules25061325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144928PMC
March 2020

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-β-hydroxymaytenin Obtained from Cultivated Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p.

Molecules 2020 Feb 10;25(3). Epub 2020 Feb 10.

Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-β-hydroxymaytenin, obtained from roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-β-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.
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http://dx.doi.org/10.3390/molecules25030760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038027PMC
February 2020

Aqueous (Ker Gawl.) Miers extract attenuates allergen-induced asthma in a mouse model via an antioxidant mechanism.

J Asthma 2020 Feb 24:1-11. Epub 2020 Feb 24.

Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.

(Ker-Gawl.) Miers (Bignoniaceae) is a perennial invasive vine, distributed worldwide. In folk medicine, its parts are used for the treatment of inflammatory respiratory diseases. Extracts of have antioxidant, antimicrobial, and antinociceptive properties. The aim of this study was to evaluate the effects of two extracts (aqueous and hydroethanolic) of in the treatment of asthma in an animal model. Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally (ip), one week apart, and after one week, challenged with OVA intranasally on four alternate days. Mice were treated ip with 300 mg/kg of aqueous or hydroethanolic extracts for seven consecutive days. Control groups received saline on the same days. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, lung and airway inflammation, and antioxidant activity in lung tissue were assessed. Treatment with aqueous extract significantly decreased bronchial hyperresponsiveness, measured by total and tissue resistance and elastance. The administration of hydroethanolic extract did not reduce bronchial hyperresponsiveness. In addition, both extracts significantly reduced total cell and eosinophil counts in bronchoalveolar lavage. Both extracts did not change significantly IL-4, IL-5, IL-9, IL-13, IFN-gamma, and TGF-beta levels. Of note, only the aqueous extract significantly increased the total antioxidant activity and reduced lung inflammation. Aqueous extract of reduced bronchial hyperresponsiveness, lung and airway inflammation, probably via an antioxidant mechanism. These results demonstrate that may have potential for asthma treatment.
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http://dx.doi.org/10.1080/02770903.2020.1728768DOI Listing
February 2020

Can Enhanced Techniques Improve the Diagnostic Accuracy of Transvaginal Sonography and Magnetic Resonance Imaging for Rectosigmoid Endometriosis? A Systematic Review and Meta-analysis.

J Obstet Gynaecol Can 2020 Apr 23;42(4):488-499.e4. Epub 2019 Nov 23.

Department of Gynecology, Gynecology and Obstetrics Service, State Public's Servant Medical Assistant Institute, São Paulo, Brazil.

Objective: Our aim was to perform a systematic review and meta-analysis of the most commonly used examinations for rectosigmoid lesions of deeply infiltrating endometriosis, transvaginal sonography (TVS) and magnetic resonance imaging (MRI), to compare their diagnostic accuracy and enhanced or non-enhanced techniques.

Methods: A systematic search was performed until March 2018 without time or language restrictions. Eligibility criteria included studies that compared the accuracy of TVS and MRI for diagnosis of rectosigmoid endometriosis. The quality of the studies was assessed by means of Quality Assessment of Diagnostic Accuracy Studies-2 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Bivariate and hierarchical analysis were performed. The difference in the accuracy of TVS and MRI was tested, and heterogeneity was addressed by means of meta-regression, sensitivity, or subgroup analysis.

Results: A total of 1754 studies were screened; 105 studies were eligible, and 11 studies were included in the meta-analysis. Overall pooled sensitivity, specificity, and area under the receiver operating characteristic curve were 0.80, 0.94, and 0.95, respectively. The measures for MRI were 0.82, 0.94, and 0.95, respectively. There was no statistical difference between the accuracy values of TVS and MRI (P = 0.90). The use of bowel preparation and vaginal contrast could enhance the accuracy of MRI. Along with rectosigmoid prevalence, bowel and vaginal contrast explained a significant proportion of the statistical heterogeneity.

Conclusions: Both TVS and MRI showed high diagnostic accuracy for rectosigmoid deeply infiltrating endometriosis lesions. There is no strong evidence suggesting that the two diagnostic methods might differ in specificity or sensitivity, but enhanced techniques may increase the accuracy measures.
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http://dx.doi.org/10.1016/j.jogc.2019.07.016DOI Listing
April 2020

Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11α-hydroxy-erythravine against the pilocarpine model of epilepsy.

Life Sci 2020 Jan 18;240:117072. Epub 2019 Nov 18.

Department of Biotechnology, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil; School of Medicine, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil. Electronic address:

Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants.

Aims: The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance.

Main Methods: Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction.

Key Findings: Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement.

Significance: Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events.
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http://dx.doi.org/10.1016/j.lfs.2019.117072DOI Listing
January 2020

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.

Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.

Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

Quality of Life Assessment by the Endometriosis Health Profile (EHP-30) Questionnaire Prior to Treatment for Ovarian Endometriosis in Brazilian Women.

Rev Bras Ginecol Obstet 2019 Sep 3;41(9):548-554. Epub 2019 Sep 3.

Department of Gynecology, Division of Endometriosis, Hospital do Servidor Público Estadual, São Paulo, SP, Brazil.

Objective:  To evaluate the existence of an association between ultrasound findings and epidemiological and clinical factors using results obtained from the EHP-30 questionnaire in women with ovarian endometriosis.

Methods:  A cross-sectional observational study was performed between July 2012 and May 2015, in which patients with chronic pelvic pain suggestive of endometrioma, as indicated by the results from a transvaginal pelvic ultrasonography, completed the standardized Endometriosis Health Profile - 30 (EHP-30) questionnaire to access quality-of-life scores before beginning treatment for endometriosis. A total of 65 patients were included. The data was analyzed in the statistical program IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA) for the comparison of data through linear multiple regression.

Results:  The suitability of the linear regression model was confirmed by the histogram of the dependent variable and the residue distribution plot, confirming the trend of linearity as well as the homogeneous dispersion of the residues. The mean age of the patients was 39.7 ± 7.1 years old. The majority was Caucasian (64.5%), had completed higher education (56.5%) and was nulligravida (40.3%). Infertility was present in 48.4% of the patients studied. Out of the total sample, 80.6% of the cases were symptomatic and complained mainly of acyclic pain, 79% of dysmenorrhea, and 61.3% of dyspareunia. This reflects the negative influence of endometriosis on the quality of life of patients with this disease.

Conclusion:  Dyspareunia and acyclic pain were independent factors of correlation with high scores in the EHP-30 questionnaire, reflecting a worse quality of life.
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http://dx.doi.org/10.1055/s-0039-1693057DOI Listing
September 2019

Maytenin Plays a Special Role in the Regulation of the Endophytic Bacillus megaterium in Peritassa campestris Adventitious Roots.

J Chem Ecol 2019 Sep 17;45(9):789-797. Epub 2019 Aug 17.

Instituto de Química, Universidade Estadual Paulista - UNESP, Rua Prof. Francisco Degni, 55, Quitandinha, Araraquara, SP, 14800-060, Brazil.

Peritassa campestris (Celastraceae) root bark accumulates potent antitumor quinonemethide triterpenes (QMTs). When grown in their natural habitat, plants of the family Celastraceae produce different QMTs such as celastrol (3) and pristimerin (4). However, when they are inserted in in vitro culture systems, they accumulate maytenin (1) as the main compound. Recently, Bacillus megaterium was detected as an endophytic microorganism (EM) living inside P. campestris roots cultured in vitro. We hypothesized that compound (1) controls EM growth more efficiently, and that the presence of EMs in the root culture causes compound (1) to accumulate. For the first time, this work has explored plant-microorganism interaction in a species of the family Celastraceae by co-culture with an EM. Live endophytic bacteria were used, and QMT accumulation in P. campestris adventitious roots was our main focus. The antimicrobial activity of the main QMTs against endophytic B. megaterium was also evaluated. Our results showed that compound (1) and maytenol (5) were more effective than their precursors QMTs (3) and (4) in controlling the EM. Co-culture of B. megaterium with roots significantly reduced bacterial growth whereas root development remained unaffected. Compound (1) production was 24 times higher after 48 hr in the presence of the highest B. megaterium concentration as compared to the control. Therefore, P. campestris adventitious roots affect the development of the endophyte B. megaterium through production of QMTs, which in turn can modulate production of compound (1).
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http://dx.doi.org/10.1007/s10886-019-01096-yDOI Listing
September 2019

Unnatural spirocyclic oxindole alkaloids biosynthesis in Uncaria guianensis.

Sci Rep 2019 08 5;9(1):11349. Epub 2019 Aug 5.

Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Av. Costábile Romano, 2201, 14096-900, Ribeirão Preto, SP, Brazil.

Spiro-oxindole scaffolds have been studied due to their promising therapeutic potential. In the Amazon rainforest there are two important Uncaria species known as "cat's claw", which biosynthesize spirocyclic oxindole alkaloids; Uncaria tomentosa (Willd. ex Schult.) DC. and Uncaria guianensis (Aublet) Gmell. We carried out a precursor-directed biosynthesis approach with U. guianensis and successfully obtained oxindole alkaloid analogues with molecular mass corresponding to the addition of a methyl or fluorine group on the oxindole ring using tryptamine analogue precursors. Two of these novel oxindole alkaloid analogues (3b-7-methyl-isomitraphylline and 3c-6-fluoro-isomitraphylline) were isolated and characterized by NMR spectroscopy and ESI-QTOF-MS/MS. Having established a substrate feeding protocol for these plantlets, the biosynthetic route for mitraphylline (1), rhynchophylline (2), isomitraphylline (3) and isorhynchophylline (4) was also investigated using C-precursors (1-C-D-glucose, 2-C-tryptophan, 1-C-DL-glyceraldehyde, and methyl-C-D-methionine).
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http://dx.doi.org/10.1038/s41598-019-47706-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683290PMC
August 2019

Comparison of olive leaf, olive oil, palm oil, and omega-3 oil in acute kidney injury induced by sepsis in rats.

PeerJ 2019 9;7:e7219. Epub 2019 Jul 9.

Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Background: Hypotension, increased production of reactive oxygen species, and inflammation are all observed in experimental models of sepsis induced by lipopolysaccharide (LPS).

Purpose: The aim of this study was to evaluate the effects of an ethanolic extract of Brazilian olive leaf (Ex), Brazilian olive oil (Olv), Ex + Olv (ExOlv), and palm oil (Pal) in comparison to the effects of omega-3 fish oil (Omg) in a rat model of sepsis-induced acute kidney injury.

Materials: Wistar rats were divided into seven groups (seven per group), which were either untreated (control) or treated with LPS, LPS + Ex, LPS + ExOlv, LPS + Olv, LPS + Omg, or LPS + Pal.

Results: Lower values of creatinine clearance and blood pressure were observed in the LPS-treated group, and these values were not affected by Ex, Olv, ExOlv, Pal, or Omg treatment. Mortality rates were significantly lower in rats exposed to LPS when they were also treated with Ex, ExOlv, Olv, Pal, or Omg. These treatments also decreased oxidative stress and inflammation (Tumor necrosis factor alpha, interleukin-1 beta) and increased interleukin-10 levels and cell proliferation, which were associated with decreased apoptosis in kidney tissue.

Conclusion: Ex and Pal treatments were beneficial in septic rats, since they increased survival rate and did not aggravate inflammation. However, the most effective treatments for septic rats were Olv in comparison to Omg. These natural food substances could enable the development of effective therapeutic interventions to sepsis.
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http://dx.doi.org/10.7717/peerj.7219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625600PMC
July 2019

[Time-Trends in Cervical Cancer Mortality in Portugal].

Acta Med Port 2019 Jun;32(6):427-433

Instituto Politécnico de Bragança. Escola Superior de Saúde. Bragança. Portugal.

Introduction: The mortality rate due to cervical cancer is higher in Portugal compared to other European countries. This study aimed to evaluate the time-trends in cervical cancer mortality rates observed in Portugal over the last six decades.

Material And Methods: Age-standardized cervical cancer mortality rates reported in Portugal between 1955 and 2014, were collected from the International Agency for Research on Cancer (IARC). Joinpoint regression analysis was used to identify significant changes in mortality rates by assessing the percentage of annual variation (%AV) of the rate and respective 95% confidence interval (95%CI) according to the age groups.

Results: Among women with 30-39 years, cervical cancer mortality decreased 1.9% per year (95%CI: -2.3; -1.4) throughout the time-period, reaching 0.5/100 000 in 2014. Among women aged 40-49 years, CC mortality decreased between 1971 and 1981 (%AV = -11.6; IC 95%: -14.6; -8.6). Rates then increased by 2.4% per year (95%CI: 1.0; 3.8) until 2001 and such trend reverted from 2001 onwards (%AV = -5.2; IC 95%: -7.7; -2.6), reaching 3.0/100 000 in 2014. In women aged 50-64, 65-74 and 75 years or older, cervical cancer mortality rates decreased from 29.2 to 6.7/100 000, from 34.3 to 7.7/100 000 and from 24.7 to 9.2/100 000. The decline in mortality rates in these three age groups occurred mainly between 1970 and 1980, and there have been no significant changes in the last three decades.

Discussion: In Portugal, the most impressive decline in cervical cancer mortality rates occurred in the 1970s concurrently with changes in the National Healthcare System. The most important changes were the increased access to early diagnosis and the improvement in therapeutic approaches. The plateau that we observed among older women over the last three decades can be partially explained by factors with negative impact on adherence to cervical screening.

Conclusion: There was a marked decrease in mortality due to CC among all age groups. However, we observed a plateau of this indicator in more advanced age groups over the last three decades. These findings suggest the need of promoting adherence to cervical screening in Portugal.
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http://dx.doi.org/10.20344/amp.8921DOI Listing
June 2019

Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) powdered leaves are effective in treating anxiety symptoms: A phase-2, randomized, placebo-controlled clinical trial.

J Ethnopharmacol 2019 Oct 4;242:112060. Epub 2019 Jul 4.

Department of Plant Biotechnology, University of Ribeirão Preto, Ribeirão Preto, Brazil.

Ethnopharmacological Relevance: Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) is a plant traditionally used as medicine for anxiety symptoms. This activity was confirmed in preclinical studies. However, its efficacy was never studied in human clinical trials.

Aim Of The Study: We aimed to test the hypothesis that the herbal medicine of A. polystachya is superior to placebo for the treatment of anxiety-related symptoms in adults after 8 weeks.

Patients And Methods: This was a randomized, double-blind, placebo-controlled, phase-2 clinical trial. Fifty-four adults with self-reported anxiety symptoms were randomly allocated to receive either capsules containing A. polystachya powdered leaves (300 mg, twice a day) or placebo (maltodextrin), for 8 weeks. The intensity of anxiety symptoms was assessed by the Hamilton Anxiety Ranking Scale (HAM-A) at baseline and after 2, 4 and 8 weeks. All analyses were adjusted for physical activity (assessed by the International Physical Activity Questionnaire [IPAQ], short version) and gender.

Results: We confirmed the presence of acteoside (chromatographic analysis) and carvone and limonene (gas chromatography) as major constituents in our plant material. Only patients that received A. polystachya experienced a significant decrease in their HAM-A scores, with none or mild side-effects.

Conclusion: Administration of powdered leaves of A. polystachya, rich in acteoside, carvone and limonene, to adults with anxiety symptoms was significantly superior to placebo in decreasing HAM-A scores after 8 weeks. This finding confirms the ethnopharmacological use of this plant for anxiety symptoms.
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http://dx.doi.org/10.1016/j.jep.2019.112060DOI Listing
October 2019

Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial.

J Ethnopharmacol 2019 Jun 13;238:111882. Epub 2019 Apr 13.

Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address:

Ethnopharmacological Relevance: Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment.

Aim Of The Study: We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control.

Patients And Methods: We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests.

Results: Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months.

Conclusion: The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo.
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http://dx.doi.org/10.1016/j.jep.2019.111882DOI Listing
June 2019

Efficacy of a Homeopathic Medicine of Capsicum frutescens L. (Solanaceae) in the Treatment of Hot Flashes in Menopausal Women: A Phase-2 Randomized Controlled Trial.

Homeopathy 2019 05 8;108(2):102-107. Epub 2019 Feb 8.

Department of Plant Biotechnology, University of Ribeirão Preto (UNAERP), Ribeirão Preto, Brazil.

Background: Hot flashes are common in women during menopause, and are an important cause of discomfort, increasing the number of medical appointments. Hormone replacement therapy is an effective treatment, but it can bring undesirable consequences. Alternative treatments exist but they are not universally accepted or effective. The ingestion of malagueta peppers (popular name for fruits of L., Solanaceae) causes sensations similar to those experienced by women during hot flashes. Using the homeopathic law of similars (let like be cured by like), we hypothesized that a homeopathic remedy made of malagueta peppers can be effective in alleviating menopausal hot flashes. We named this remedy .

Methods: This randomized, placebo-controlled, double-blind, phase-2 clinical trial was designed to test the hypothesis that, in menopausal women, the homeopathic medicine (30 CH), compared with placebo, will significantly reduce the intensity of hot flashes, after 4 weeks of treatment. The primary outcome was the intensity of hot flashes, measured by the Measure Yourself Medical Outcome Profile (MYMOP) instrument. A total of 40 women were enrolled in the study, 20 in each group.

Results: The effect of on the primary outcome, the intensity of hot flashes, assessed by MYMOP, was superior to that of placebo over the 4 weeks of treatment, with worsening in both groups after treatment was interrupted (after week 4,  < 0.001 in ordinal logistic regression). The odds ratio for treatment response (reduction of at least three MYMOP categories) was 2.78 (95% confidence interval, 0.77 to 10.05). Treatment with , compared with placebo, also reduced the intensity of the secondary symptoms ( = 0.001) and improved level of activity ( = 0.025) and well-being ( = 0.008).

Conclusion: The homeopathic medicine of () was superior to placebo in reducing the intensity of hot flashes in menopausal women after 4 weeks of treatment.
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http://dx.doi.org/10.1055/s-0038-1676326DOI Listing
May 2019

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study.

Clin Exp Allergy 2019 04 12;49(4):442-460. Epub 2019 Mar 12.

MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France.

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries.

Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App.

Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach.

Results: A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users.

Conclusion And Clinical Relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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http://dx.doi.org/10.1111/cea.13333DOI Listing
April 2019

Effect of Costus spiralis (Jacq.) Roscoe Leaves, Methanolic Extract and Guaijaverin on Blood Glucose and Lipid Levels in a Type II Diabetic Rat Model.

Chem Biodivers 2019 Jan 11;16(1):e1800365. Epub 2019 Jan 11.

Unidade de Biotecnologia, Universidade de Ribeirão Preto (UNAERP), Av. Costábile Romano 2201, CEP14096-900, Ribeirão Preto, SP, Brazil.

This study aimed to isolate and identify flavonoids with hypoglycemic activity in Costus spiralis leaves. The methanolic extract (ME) was rich in flavonoids, while the powdered leaves (PL) contained considerable amounts of macro- and microelements. Oral acute treatment of streptozotocin (STZ)-induced diabetic rats for 18 h with the C. spiralis PL, ME and isolated guaijaverin (GUA) lowered glycemia, improved oral glucose tolerance and inhibited liver lipid peroxidation. GUA and ME lowered plasma levels of low-density and non-high density lipoproteins; GUA also lowered total cholesterol levels. PL, ME and GUA did not significantly alter the plasma levels of triglycerides, high-density lipoproteins, very low-density lipoproteins, creatinine and aspartate transaminase, and the total protein levels in the kidney and liver tissues. Therefore, C. spiralis leaves are promising raw materials and rich sources of bioactive flavonoids for the development of novel antidiabetic drugs due to their hypoglycemic, antidyslipidemic and antioxidant actions.
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http://dx.doi.org/10.1002/cbdv.201800365DOI Listing
January 2019

Genetic structure and chemical diversity in natural populations of Uncaria guianensis (Aubl.) J.F.Gmel. (Rubiaceae).

PLoS One 2018 26;13(10):e0205667. Epub 2018 Oct 26.

Universidade de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

Uncaria guianensis is native to the Amazon and is used traditionally as an anti-inflammatory. Natural populations of the species have declined markedly in recent times because of strong anthropic pressure brought about by deforestation and indiscriminate collection. The aim of the present study was to assess the genetic and chemical diversity among eight natural populations of U. guianensis located in the Brazilian states of Acre, Amapá and Amazonas. A set of four primer combinations was employed in sequence-related amplified polymorphism (SRAP) amplifications of leaf DNA, and the fragments were analyzed in an LI-COR model 4300 DNA Analyzer. Genetic variability within the populations (81%) was substantially greater than that detected between them (19%). The highest percentage of polymorphic loci (90.21%) and the largest genetic variability were observed in the population located in Mazagão, Amapá. Genetic differentiation between populations was high (Fst = 0.188) and the studied populations formed three distinct genetic groups (K = 3). The population located in Assis Brasil, Acre, presented the highest average content of the mitraphylline (0.60 mg/g dry weight,). However, mitraphylline and isomitraphylline not detected in most individuals in the studied populations, and it is questionable whether they should be considered as chemical markers of the species. The genetic data confirm the urgent need for conservation programs for U. guianensis, and for further studies aimed at ascertaining the genetic basis and heritability of alkaloid accumulation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205667PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203251PMC
April 2019

Oral administration of powdered dried rhizomes of Curcuma longa L. (turmeric, Zingiberaceae) is effective in the treatment of doxorubicin-induced kidney injury in rats.

Phytother Res 2018 Dec 15;32(12):2408-2416. Epub 2018 Aug 15.

Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.

Curcumin is a polyphenol present in the rhizomes of the species Curcuma longa L. ("turmeric," Zingiberaceae), which has been used for centuries as an anti-inflammatory. We aimed to evaluate the anti-inflammatory effects of C. longa in renal injury induced by doxorubicin (DOX, 3.5 mg.kg IV). We studied four groups of Wistar rats: two groups with DOX-induced kidney injury, one fed with standard food and another with standard food mixed with C. longa (5 mg.g ). Two other control groups without kidney injury were fed with the same foods. We measured albuminuria, body weight, and food intake every 2 weeks. After 8 weeks, treatment with C. longa did not change albuminuria, but it significantly attenuated the excretion of urinary inflammatory markers monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β (TGF-β) and significantly attenuated immunostaining for desmin, vimentin, and ED-1 cells in renal tissues of rats with DOX-induced kidney injury. In addition, treatment with C. longa resulted in significantly lower glomerular and tubule interstitial injury scores, compared with that in the DOX-STD group. In conclusion, administration of powdered rhizomes of C. longa for 8 weeks to rats with DOX-induced kidney injury did not reduce albuminuria but led to a significant decrease in urinary inflammatory markers MCP-1 and TGF-β and decreased histopathological alterations and immunostaining for desmin, vimentin, and ED-1 cells kidneys tissues.
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http://dx.doi.org/10.1002/ptr.6176DOI Listing
December 2018

The ethanolic extract from Erythrina mulungu Benth. flowers attenuates allergic airway inflammation and hyperresponsiveness in a murine model of asthma.

J Ethnopharmacol 2019 Oct 10;242:111467. Epub 2018 Aug 10.

Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes S/N, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil. Electronic address:

Ethnopharmacological Relevance: Erythrina mulungu Benth. ("mulungu", Fabaceae) is a Brazilian native species with ethnopharmacological use for respiratory diseases. However, the effects of E. mulungu on the respiratory were never studied.

Aims Of The Study: To evaluate the effects of an ethanolic extract from flowers of E. mulungu in ovalbumin (OVA)-induced asthma in mice, and to study the mechanisms involved.

Materials And Methods: OVA-sensitized mice were intraperitoneally (i.p.) treated with four doses (200, 400, 600, and 800 mg/kg) of the E. mulungu extract or dexamethasone (DEXA, 2 mg/kg) during seven consecutive days and simultaneously challenged with intranasal OVA. Bronchial hyperresponsiveness was evaluated in vivo, 24 h after the last OVA challenge. Bronchoalveolar lavage (BAL) was collected for counting the number of total and differential inflammatory cells. Blood was collected for measurement of anti-OVA IgE levels. Levels of cytokines interleukin (IL)- 4, IL-5, IL-10, IL-13, and interferon (INF)-γ were measured in pulmonary homogenate by ELISA. The recruitment of inflammatory cells to the lung tissue was determined using hematoxylin and eosin staining (H&E). The extract's chromatographic profile was evaluated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).

Results: The treatment with E. mulungu extract significantly reduced bronchial hyperresponsiveness, significantly reduced the number of leukocytes, eosinophils, and lymphocytes in BAL, and significantly decreased the levels of IL-4 and IL-5, while increased levels of IL-13 and INF-γ. In addition, E. mulungu significantly decreased the cellular inflammatory infiltration in the lung tissue. Erysotrine, erysotrine-N-oxide, and hypaphorine were the major constituents identified in the extract.

Conclusion: Collectively, these results confirm the potential of E. mulungu for asthma treatment, through modulation of inflammatory response, supporting its ethnopharmacological use for respiratory diseases.
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http://dx.doi.org/10.1016/j.jep.2018.08.009DOI Listing
October 2019

Surgical Treatment of Intestinal Endometriosis: Outcomes of Three Different Techniques.

Rev Bras Ginecol Obstet 2018 Jul 27;40(7):390-396. Epub 2018 Jun 27.

Ginecology Service, Hospital do Servidor Público Estadual, São Paulo, SP, Brazil.

Objective:  To outline the demographic and clinical characteristics of patients with deep intestinal endometriosis submitted to surgical treatment at a tertiary referral center with a multidisciplinary team, and correlate those characteristics with the surgical procedures performed and operative complications.

Methods:  A prospective cohort from February 2012 to November 2016 of 32 women with deep intestinal endometriosis operations. The variables analyzed were: age; obesity; preoperative symptoms (dysmenorrhea, dyspareunia, acyclic pain, dyschezia, infertility, urinary symptoms, constipation and intestinal bleeding); previous surgery for endometriosis; Enzian classification; size of the intestinal lesion; and surgical complications.

Results:  The mean age was 37.75 (±5.72) years. A total of 7 patients (22%) had a prior history of endometriosis. The mean of the largest diameter of the intestinal lesions identified intraoperatively was of 28.12 mm (±14.29 mm). In the Enzian classification, there was a predominance of lesions of the rectum and sigmoid, comprising 30 cases (94%). There were no statistically significant associations between the predictor variables and the outcome complications, even after the multiple logistic regression analysis. Regarding the size of the lesion, there was also no significant correlation with the outcome complications ( = 0.18; 95% confidence interval [95%CI]:0.94-1.44); however, there was a positive association between grade 3 of the Enzia classification and the more extensive surgical techniques: segmental intestinal resection and rectosigmoidectomy, with a prevalence risk of 4.4 ( < 0.001; 95%CI:1.60-12.09).

Conclusion:  The studied sample consisted of highly symptomatic women. A high prevalence of deep infiltrative endometriosis lesions was found located in the rectum and sigmoid region, and their size correlated directly with the extent of the surgical resection performed.
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http://dx.doi.org/10.1055/s-0038-1660827DOI Listing
July 2018

Female Sexual Function in Women with Suspected Deep Infiltrating Endometriosis.

Rev Bras Ginecol Obstet 2018 Mar 2;40(3):115-120. Epub 2018 Apr 2.

Hospital do Servidor Público Estadual, São Paulo, SP, Brazil.

Objective:  To evaluate the quality of the sexual function of women with suspected deep infiltrating endometriosis.

Methods:  A cross-sectional, observational and prospective study was conducted between May 2015 and August 2016, in which 67 patients with deep infiltrating endometriosis, suspected or diagnosed, were assessed for epidemiological and clinical characteristics, such as pain level through a visual analog scale (VAS), features of deep infiltrating endometriosis lesions and score on the Female Sexual Function Index (FSFI) before the onset of treatment. The statistical analysis was performed using the software STATA version 12.0 (StataCorp LLC, College Station, TX, USA) to compare the variables through multiple regression analysis.

Results:  The average age of the patients was 39.2 years old; most patients were symptomatic (92.5%); and the predominant location of the deep infiltrating lesions was on the rectosigmoid colon (50%), closely followed by the retrocervical region (48.3%). The median overall score on the FSFI was 23.4; in 67.2% of the cases the score was ≤ 26.5 (cutoff point for sexual dysfunction). Deep dyspareunia ( = 0.000, confidence interval [CI]: 0.64-0.83) and rectosigmoid endometriosis lesions ( = 0.008, CI: 0.72-0.95) showed significant correlation with lower FSFI scores, adjusted by bladder lesion, patients' age and size of lesions. Deep dyspareunia ( = 0.003, CI: 0.49-0.86) also exhibited significant correlation with FSFI pain domain, adjusted by cyclic bowel pain, vaginal lesion and use of gonadotropin-releasing hormone (GnRH) analog. These results reflect the influence of deep dyspareunia on the sexual dysfunction of the analyzed population.

Conclusion:  Most patients exhibited sexual dysfunction, and deep dyspareunia was the pelvic painful symptom that showed correlation with sexual dysfunction.
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http://dx.doi.org/10.1055/s-0038-1639593DOI Listing
March 2018

Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma.

J Ethnopharmacol 2018 May 10;218:76-89. Epub 2018 Feb 10.

Departamento de Biotecnologia em Plantas Medicinais, Universidade de Ribeirão Preto, Av. Costábile Romano 2201, 14096-900 Ribeirão Preto, SP, Brazil. Electronic address:

Ethnopharmacological Relevance: Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids.

Aims Of The Study: To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects.

Materials And Methods: Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined.

Results: Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200 mg kg, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg kg reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100 mg kg respectively.

Conclusion: The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma.
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http://dx.doi.org/10.1016/j.jep.2018.02.013DOI Listing
May 2018

Costus spiralis (Jacq.) Roscoe: A Novel Source of Flavones with α-Glycosidase Inhibitory Activity.

Chem Biodivers 2018 Jan 27;15(1). Epub 2017 Dec 27.

Unidade de Biotecnologia, Universidade de Ribeirão Preto, Ribeirão Preto, SP, CEP 14096-900, Brazil.

Costus spiralis, a plant used in traditional Brazilian medicine for the treatment of complications in diabetes, was investigated. Assay of hexane, ethyl acetate, methanol, and aqueous fractions obtained by partition of a crude methanol extract of dried leaves of C. spiralis revealed that AGI activity was confined to the ethyl acetate fraction. Purification of this fraction yielded schaftoside and isoschaftoside. The AGI activities of the two flavones were lower than, but comparable with, that of the anti-diabetic drug acarbose. In contrast, the IC value of the ethyl acetate fraction was 1.95-, 2.34-, and 2.22-fold higher than those of acarbose, schaftoside, and isoschaftoside, respectively. The results demonstrate for the first time that schaftoside and isoschaftoside are responsible, in part, for the AGI activity of C. spiralis. Our study suggests that further investigations into C. spiralis may lead to the discovery of additional compounds with antihyperglycemic activity.
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http://dx.doi.org/10.1002/cbdv.201700421DOI Listing
January 2018

Availability of herbal medicines and medicinal plants in the primary health facilities of the state of São Paulo, Southeast Brazil: results from the National Program for Access and Quality Improvement in Primary Care.

Cien Saude Colet 2017 May;22(5):1651-1659

Departamento de Medicina Social, Universidade de São Paulo. Av. Bandeirantes 3900, Monte Alegre. 14049-900 Ribeirão Preto SP Brasil.

This study aims to describe the availability of herbal medicines and medicinal plants in the primary care facilities in the state of São Paulo, Southeast Brazil, from the results of the first cycle of the National Program for Access and Quality Improvement in Primary Care (PMAQ). The PMAQ uses a national cross-sectional multicenter design, with data from 4,249 health facilities distributed among 645 municipalities of the state of São Paulo. Of these facilities, 467 (11%) had herbal medicines and/or medicinal plants. Among the 645 municipalities, 104 (16.1%) had at least one health facility that provided these drugs. We observed that the availability of herbal medicines is greater in larger cities with better social and economic conditions. Furthermore, we found that use of industrialized herbal medicines prevailed over that of vegetal drugs or compounded herbal medicines.
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http://dx.doi.org/10.1590/1413-81232017225.16722015DOI Listing
May 2017

Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.

Curr Genomics 2017 Feb;18(1):60-74

aAlbert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, Brazil; bDepartment of Biotechnology, Universidade de Ribeirão Preto, Ribeirão Preto, Brazil.

Squamous cell carcinoma of the head and neck is one of the most common cancer types worldwide. It initiates on the epithelial lining of the upper aerodigestive tract, at most instances as a consequence of tobacco and alcohol consumption. Treatment options based on conventional therapies or targeted therapies under development have limited efficacy due to multiple genetic alterations typically found in this cancer type. Natural products derived from plants often possess biological activities that may be valuable in the development of new therapeutic agents for cancer treatment. Several genera from the family Celastraceae have been studied in this context. This review reports studies on chemical constituents isolated from species from the Celastraceae family targeting cancer mechanisms studied to date. These results are then correlated with molecular characteristics of head and neck squamous cell carcinoma in an attempt to identify constituents with potential application in the treatment of this complex disease at the molecular level.
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http://dx.doi.org/10.2174/1389202917666160803160934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321769PMC
February 2017

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters.

An Acad Bras Cienc 2017 May 16;89(1 Suppl 0):445-456. Epub 2017 Apr 16.

Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.

This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 µL L-1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 µL L-1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.
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http://dx.doi.org/10.1590/0001-3765201720160457DOI Listing
May 2017

Genetic and chemical diversity of Uncaria tomentosa (Willd. ex. Schult.) DC. in the Brazilian Amazon.

PLoS One 2017 5;12(5):e0177103. Epub 2017 May 5.

Unidade de Biotecnologia, Universidade de Ribeirão Preto, Ribeirânia, Ribeirão Preto, São Paulo, Brazil.

Uncaria tomentosa (Willd. ex Schult.) DC., a plant native to the Amazon region, is used widely in popular medicine and by the pharmaceutical industry because of its anti-inflammatory activity. However, the survival of this species is endangered by deforestation and indiscriminate collection, and a preservation plan is urgently required. The objectives of this study were to determine the genetic and chemical variability between and within eight populations of U. tomentosa from the Brazilian states of Acre, Pará and Amapá, and to investigate possible correlations between genetic and geographical distances, and between geographical distances or altitude and the accumulation of bioactive oxindole alkaloids. Three sequence-related amplified polymorphism (SRAP) markers were employed to fingerprint genomic DNA, and the amounts of mitraphylline and isomitraphylline in leaf samples were established by high-performance liquid chromatography. Although significant divergence existed between the tested populations (FST = 0.246), the largest genetic diversity and the highest percentage of polymorphism (95.68%) was found within the population from Mâncio Lima, Acre. Gene flow was considered rather limited (Nm = 1.57), and no correlations between genetic and geographical distances were detected, suggesting that population structure followed an island model. Accumulations of mitraphylline and isomitraphylline varied in the range 32.94 to 0.57 and 3.75 to 0.36 mg g-1 dry weight, respectively. The concentration of isomitraphylline was positively influenced by altitude, such that the population collected at the site with the highest elevation (Tarauacá, Acre) exhibited the greatest alkaloid content. SRAP markers were very efficient in fingerprinting genomic DNA from U. tomentosa populations and clearly showed that genetic variability within populations was greater than between populations. A conservation and management plan should prioritize the creation of germplasm banks to prevent the loss of existing genetic variability, particularly within alkaloid-rich populations such as those of Tarauacá.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177103PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419575PMC
September 2017