Publications by authors named "Bruna Azevedo"

22 Publications

  • Page 1 of 1

Reviewing research on the synthesis of CALB-catalyzed sugar esters incorporating systematic mapping principles.

Crit Rev Biotechnol 2021 Feb 28:1-23. Epub 2021 Feb 28.

Chemical Engineering Department, Federal University of São Carlos (UFSCar), São Carlos, Brazil.

Rigorous evidence reviews must follow specific guidelines designed to improve transparency, reproducibility, and to minimize biases to which traditional reviews are susceptible. While evidence synthesis methods, such as systematic reviews and maps, have been used in several research fields, the majority of reviews published in the realm of chemical engineering are nonsystematic. In this study, we incorporated principles of systematic mapping to conduct a literature review covering research on the synthesis of sugar fatty acid esters (SFAE) with lipase B (CALB). Our results showed that the simple monosaccharides were the most cited sugars among studies we conducted. The direct use of renewable raw materials and frequently available resources to produce alternative sugar esters (SE) was scarcely reported in our data set. We found that free fatty acids (FFA) were the most commonly cited acyl donors amongst all publications, with lauric, oleic, and palmitic acids accounting for ∼43% of the occurrences. Tertiary alcohols (ter-butyl alcohol (T-but) and 2-methyl-2-butanol (2M2B)) and ionic liquids were the most used solvents to synthesize SE. The co-occurence analysis of keywords involving solvent terms showed that most of the papers evaluated different solvents as reaction media (mostly in the form of a bisolvent system), also investigating the impact of their choice on sugar ester productivities. Given the potential of reviews informing us of research decisions, this article reveals trends and spaces across CALB-catalyzed SE synthesis research, in addition to introducing a new methodological perspective for developing reviews in the field of chemical engineering.
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http://dx.doi.org/10.1080/07388551.2021.1888071DOI Listing
February 2021

Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

Front Physiol 2020 7;11:590308. Epub 2021 Jan 7.

Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Brazil.

Lead (Pb) exposure causes hazardous effects as hypertension and other cardiovascular diseases. We evaluated whether chronic Pb exposure alters the peripheral vascular resistance measuring the vascular reactivity of mesenteric resistance arteries in rats to identify the underlying mechanisms that are associated to the development of Pb-induced hypertension. Mesenteric resistance arteries from lead-treated and untreated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) were used. Contractile responses to phenylephrine increased, while acetylcholine and sodium nitroprusside-induced relaxation was not affected by lead treatment. Endothelium removal and inhibition of NO synthase by L-NAME similarly enhanced the response to phenylephrine in untreated and lead-treated rats. The antioxidants apocynin and superoxide dismutase (SOD) did not affect vasoconstriction in either group. The vascular expression of cyclooxygenase-2 (COX-2) protein increased after lead exposure. The respective non-specific or specific COX-2 inhibitors indomethacin and NS398 reduced more strongly the response to phenylephrine in treated rats. Antagonists of EP1 (SC19220), TP (SQ29548), IP (CAY10441) and angiotensin II type 1 (losartan) receptors reduced vasoconstriction only in treated rats. These conclusions present further evidence that lead, even in small concentration, produces cardiovascular hazards being an environmental contaminant that account for lead-induced hypertension.
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http://dx.doi.org/10.3389/fphys.2020.590308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818781PMC
January 2021

Measurement Properties of the Sedentary Behavior Questionnaire in Patients with Chronic Nonspecific Low Back Pain.

PM R 2020 Sep 11. Epub 2020 Sep 11.

Departamento de Fisioterapia, Faculdade de Ciências e Tecnologia, Universidade Estadual Paulista, Presidente Prudente, Brazil.

Background: The Sedentary Behavior Questionnaire (SBQ) is a brief and easy instrument to measure time spent on sedentary activities; however, no study has investigated the reliability and validity of this questionnaire in people with chronic low back pain (LBP).

Objective: To investigate the internal consistency, test-retest reliability, measurement error, construct validity, and interpretability of the SBQ against data derived from an accelerometer in patients with nonspecific chronic LBP.

Study Design: Cross-sectional study.

Setting: Outpatient physiotherapy clinic.

Patients: Seventy-five patients aged between 18 and 60 years (mean age, 42 years old) with nonspecific chronic LBP were recruited for this study.

Interventions: Not applicable.

Methods: The Cronbach's α was calculated to investigate the internal consistency of the SBQ and the intraclass correlation coefficient (ICC) was calculated to investigate the reliability of the SBQ between two administrations separated by a 1-week interval. Measurement error was assessed calculating the SEM and minimal detectable change (MDC). Spearman correlation (r) was calculated to investigate the construct validity using hypothesis testing. Interpretability was investigated using ceiling and floor effects.

Results: The Cronbach's α of the SBQ total score was 0.92, indicating homogeneity among the items of the instrument. The reliability of the SBQ was excellent (ICC > 0.75), without any evidence of ceiling and floor effects. Regarding measurement error, the total score of the SBQ showed an SEM and MDC of 109.8 minutes per day and 304.4 minutes per day, respectively. However, there were no correlations of the SBQ domains or the total score with the accelerometer-measured sedentary time (r < 0.25).

Conclusion: The SBQ is a reliable tool for quantifying time spent in sedentary activities of patients with chronic LBP. The SBQ showed poor construct validity compared to the accelerometer-measured sedentary time, which indicates that patients may underestimate their time spent in sedentary activities.
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http://dx.doi.org/10.1002/pmrj.12490DOI Listing
September 2020

Increased endothelial nitric oxide production after low level lead exposure in rats involves activation of angiotensin II receptors and PI3K/Akt pathway.

Toxicology 2020 10 11;443:152557. Epub 2020 Aug 11.

Centre of Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil; Health Science Center of Vitória-EMESCAM, Vitória, ES, Brazil.

Background: Lead induces endothelial dysfunction and hypertension in humans and animals. Seven-day exposure to a low dose in rats reduces vasocontractile responses and increases nitric oxide (NO) bioavailability. We hypothesized that this occurs by angiotensin II receptors (AT1/AT2) activation.

Materials And Results: Wistar rats were exposed to lead acetate (1 st dose 4 μg/100 g, subsequent dose 0.05 μg/100 g/day i.m., 7 days) or saline (control group). Lead acetate exposure reduced the phenylephrine vascular response. Pre-incubations with NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) increased the contractile response in aortas from lead-treated rats. Pre-incubation with AT2 antagonist (PD123319) restored normal vascular contraction, and both PD123319 or AT1 antagonist (losartan) impeded the potentiated effects of L-NAME and wortmannin. Reinforcing those findings, increased NO bioavailability was blunted by AT1 and AT2 antagonists without summative effect when co-incubated. Finally, to test whether activation of AT1 could upregulate AT2 to increase NO bioavailability rats were simultaneously exposed to lead acetate and treated with losartan (15 mg/kg/day, orally given). Losartan prevented changes on vascular reactivity and endothelial modulation in lead-exposed group. Moreover, incubation with PD123319 had no more effects in aortic from losartan-treated rats.

Conclusion: Our results suggest that low-dose lead acetate exposure induces an increase of NO involving mainly AT2 receptor activation and the PI3K/Protein Kinase B (PI3K/Akt) pathway. Additionally, we suggest that AT1 activation plays a role in AT2 upregulation, probably as a protective mechanism. Altogether, these effects might contribute to preserving endothelial function against the harmful effects by lead in the vascular system.
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http://dx.doi.org/10.1016/j.tox.2020.152557DOI Listing
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

Is There Equivalence Between the Electronic and Paper Version of the Questionnaires for Assessment of Patients With Chronic Low Back Pain?

Spine (Phila Pa 1976) 2020 Mar;45(6):E329-E335

Departamento de Educação Física, Faculdade de Ciências e Tecnologia, Universidade Estadual Paulista, Presidente Prudente, Brazil.

Study Design: Cross-sectional study.

Objective: To investigate the equivalence of electronic and paper version of self-report questionnaires for the assessment of disability, pain, fear of movement, depression, and physical activity of patients with chronic low back pain (LBP).

Summary Of Background Data: Paper and electronic versions of self-report questionnaires are commonly used for assessment of patients with LBP. However, the equivalence of self-report questionnaires commonly used for assessment of patients with chronic LBP remains unclear.

Methods: Seventy-nine individuals with chronic LBP seeking physiotherapy care were recruited. Participants attended the clinic twice with an interval of 1 week and completed the self-reported questionnaires in a random order. The following questionnaires were administered: Roland Morris Disability Questionnaire (RMDQ); 11-point numerical rating scale (NRS); Tampa Scale for Kinesiophobia (TSK); Center for Epidemiological Studies-Depression (CES-D), and Baecke Habitual Physical Activity Questionnaire (BPAQ). To investigate the equivalence between the two questionnaire versions, intraclass correlation coefficient with 95% confidence interval and Bland-Altman plotting was used.

Results: The paper and electronic versions of the RMDQ, TSK, and CES-D showed good reliability and the showed moderate reliability. In contrast, the NRS showed poor reliability between the electronic and paper versions.

Conclusion: Our findings support that the electronic version of the RMDQ, TSK, CES-D, and BPAQ can be administered in clinical and research settings for assessment of patients with chronic LBP. Nevertheless, electronic version of the NRS for assessment of pain intensity should not be used interchangeably in clinical practice in patients with chronic LBP.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003281DOI Listing
March 2020

Drought leads to reproductive quiescence in smooth-billed anis: Phenotypic evidence for opportunistic breeding and reproductive readiness.

J Morphol 2019 07 20;280(7):968-981. Epub 2019 May 20.

Department of Biosciences, Biological and Health Sciences Center, Federal Rural University of the Semi-Arid Region, Mossoró, Rio Grande do Norte, Brazil.

Previous studies have suggested that the smooth-billed ani (Crotophaga ani, Linnaeus, 1758) breeds opportunistically following unpredictable rainfall in drought areas. To obtain proof of this phenomenon, the present study described and compared reproductive morphology and cell proliferation in the gonads of free-living smooth-billed anis during a wet season (April to June 2012) and the following dry season (July to September 2012) in a semiarid area using light and electron microscopy (transmission and scanning) and the AgNOR method. The morphological findings indicated distinct levels of reproductive activity related to seasonal changes. Morphological and morphometric analyses of the gonads confirmed intense gametogenic activity during the wet season, whereas gonadal involution occurred after rainfall ceased. The sizes of the testes and ovaries were significantly reduced compared to those in the wet season. The volumetric fraction of the seminiferous tubules in the testis decreased considerably, and no preovulatory follicles were detected in the ovary in the dry season. Moreover, the AgNOR count in the gonads revealed a significant decline in cell recruitment for gametogenesis after rainfall ceased. The histological findings indicated partial gonadal activation throughout the dry season. The analysis of the seminiferous epithelium confirmed the early testicular recrudescence phase, and sporadic postovulatory follicles indicated random ovulation during this time. The excurrent ducts and the oviduct also underwent remarkable involution in the dry season. Taken together, these findings confirm opportunistic breeding by smooth-billed anis in a semiarid habitat and suggest that gonadal recrudescence has been established as a reproductive strategy to cope with unexpected precipitation events.
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http://dx.doi.org/10.1002/jmor.20995DOI Listing
July 2019

Analysis of Genetic VapC Profiles from the Toxin-Antitoxin Type II VapBC Modules among Pathogenic, Intermediate, and Non-Pathogenic .

Microorganisms 2019 Feb 20;7(2). Epub 2019 Feb 20.

Laboratório Especial de Desenvolvimento de Vacinas-Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900 São Paulo, Brazil.

Pathogenic spp. is the etiological agent of leptospirosis. The high diversity among species provides an array to look for important mediators involved in pathogenesis. Toxin-antitoxin (TA) systems represent an important survival mechanism on stress conditions. BC modules have been found in nearly one thousand genomes corresponding to about 40% of known TAs. In the present study, we investigated TA profiles of some strains of using a TA database and compared them through protein alignment of VapC toxin sequences among spp. genomes. Our analysis identified significant differences in the number of putative BC modules distributed in pathogenic, saprophytic, and intermediate strains: four in , three in , eight in , and 15 in . The VapC toxins show low identity among amino acid sequences within the species. Some VapC toxins appear to be exclusively conserved in unique species, others appear to be conserved among pathogenic or saprophytic strains, and some appear to be distributed randomly. The data shown here indicate that these modules evolved in a very complex manner, which highlights the strong need to identify and characterize new TAs as well as to understand their regulation networks and the possible roles of TA systems in pathogenic bacteria.
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http://dx.doi.org/10.3390/microorganisms7020056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406750PMC
February 2019

Effects of Chronic Exposure to Mercury on Angiotensin-Converting Enzyme Activity and Oxidative Stress in Normotensive and Hypertensive Rats.

Arq Bras Cardiol 2019 04 7;112(4):374-380. Epub 2019 Jan 7.

Departamento de Ciências Fisiológicas - Universidade Federal do Espírito Santo,Vitória, ES - Brazil.

Background: Mercury's deleterious effects are associated with increased cardiovascular risk.

Objective: To determine whether chronic exposure to inorganic mercury increases the activity of angiotensin-converting enzyme and its relationship with oxidative stress in several organs and tissues.

Methods: We studied male Wistar and spontaneously hypertensive rats (SHR) (3-month-old) exposed or not to HgCl2 for 30 days. At the end of treatment, we investigated the following: changes in body weight, hemodynamic parameters, angiotensin-converting enzyme (ACE) activity and oxidative stress in the heart, aorta, lung, brain and kidney in hypertensive compared to normotensive animals. A value of p < 0.05 was considered significant.

Results: Chronic exposure to HgCl2 did not affect weight gain in either group. Systolic blood pressure, measured weekly, did not increase in Wistar rats but showed a small increase in SHR rats. We also observed increases in left ventricular end-diastolic pressure and ACE activity in the plasma and hearts of normotensive rats. In the SHR+Hg group, ACE activity increased in plasma but decreased in kidney, lung, heart, brain and aorta. Oxidative stress was assessed indirectly by malondialdehyde (MDA) production, which increased in Hg-treated rats in both plasma and heart. In the SHR+Hg group, MDA increased in heart and aorta and decreased in lungs and brain.

Conclusion: These results suggest that chronic exposure to inorganic mercury aggravates hypertension and produces more expressive changes in ACE activity and oxidative stress in SHRs. Such exposure affects the cardiovascular system, representing a risk factor for the development of cardiovascular disorders in normotensive rats and worsening of pre-existing risks for hypertension.
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http://dx.doi.org/10.5935/abc.20180271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459440PMC
April 2019

New Isolates of Pandoraviruses: Contribution to the Study of Replication Cycle Steps.

J Virol 2019 03 19;93(5). Epub 2019 Feb 19.

Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Giant viruses are complex members of the virosphere, exhibiting outstanding structural and genomic features. Among these viruses, the pandoraviruses are some of the most intriguing members, exhibiting giant particles and genomes presenting at up to 2.5 Mb, with many genes having no known function. In this work, we analyzed, by virological and microscopic methods, the replication cycle steps of three new pandoravirus isolates from samples collected in different regions of Brazil. Our data indicate that all analyzed pandoravirus isolates can deeply modify the cytoplasmic environment, recruiting mitochondria and membranes into and around the electron-lucent viral factories. We also observed that the viral factories start forming before the complete degradation of the cellular nucleus. Various patterns of pandoravirus particle morphogenesis were observed, and the assembly of the particles seemed to be started either by the apex or by the opposite side. On the basis of the counting of viral particles during the infection time course, we observed that pandoravirus particles could undergo exocytosis after their morphogenesis in a process that involved intense recruitment of membranes that wrapped the just-formed particles. The treatment of infected cells with brefeldin affected particle exocytosis in two of the three analyzed strains, indicating biological variability among isolates. Despite such particle exocytosis, the lysis of host cells also contributed to viral release. This work reinforces knowledge of and reveals important steps in the replication cycle of pandoraviruses. The emerging Pandoraviridae family is composed of some of the most complex viruses known to date. Only a few pandoravirus isolates have been described until now, and many aspects of their life cycle remain to be elucidated. A comprehensive description of the replication cycle is pivotal to a better understanding of the biology of the virus. For this report, we describe new pandoraviruses and used different methods to better characterize the steps of the replication cycle of this new group of viruses. Our results provide new information about the diversity and biology of these giant viruses.
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http://dx.doi.org/10.1128/JVI.01942-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384056PMC
March 2019

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

Sensory Profile and Consumer Acceptability of Prebiotic White Chocolate with Sucrose Substitutes and the Addition of Goji Berry (Lycium barbarum).

J Food Sci 2017 Mar 9;82(3):818-824. Epub 2017 Feb 9.

Faculty of Food Engineering (FEA), Univ. of Campinas (UNICAMP), Monteiro Lobato, 80, 13083-862, Campinas, SP, Brazil.

Functional food is a product containing nutrients that provide health benefits beyond basic nutrition. The objective of the present study was to evaluate the descriptive sensory profile and consumers' acceptance of functional (prebiotic) white chocolates with and without the addition of an antioxidant source (goji berry [GB]) and sucrose replacement. The descriptive sensory profile was determined by quantitative descriptive analysis (QDA) with trained assessors (n = 12), and the acceptance test was performed with 120 consumers. The correlation of descriptive and hedonic data was determined by partial least squares (PLS). The results of QDA indicated that GB reduces the perception of most aroma and flavor attributes, and enhances the bitter taste, bitter aftertaste, astringency, and most of the texture attributes. The consumers' acceptance of the chocolates was positive for all sensory characteristics, with acceptance scores above 6 on a 9-point scale. According to the PLS regression analysis, the descriptors cream color and cocoa butter flavor contributed positively to the acceptance of functional white chocolates. Therefore, prebiotic white chocolate with or without the addition of GB is innovative and can attract consumers, due to its functional properties, being a promising alternative for the food industry.
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http://dx.doi.org/10.1111/1750-3841.13632DOI Listing
March 2017

A standardized methanol extract of Eclipta prostrata (L.) L. (Asteraceae) reduces bronchial hyperresponsiveness and production of Th2 cytokines in a murine model of asthma.

J Ethnopharmacol 2017 Feb 10;198:226-234. Epub 2016 Dec 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: Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses.

Aims Of The Study: To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma.

Materials And Methods: Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution. The standardized methanol extract of E. prostrata was administered in doses of 100, 250 and 500mgkg concomitantly with nasal instillation over seven consecutive days. Control animals were treated with dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, allergen sensitization, airway and lung inflammation, mucous secretion and airway remodeling were assessed.

Results: The concentrations of chemical markers in the standardized methanol extract were 0.02% oroboside, 1.69% demethylwedelolactone and 1.71% wedelolactone. Treatment with 250mgkg of extract, which provided 0.745, 4.22 and 4.30mgkgday of oroboside, demethylwedelolactone and wedelolactone, respectively, significantly reduced (P<0.05) respiratory resistance and elastance. Such effects were comparable with those produced by dexamethasone. The total number of inflammatory cells and eosinophils in the bronchoalveolar lavage and the concentrations of interleukin (IL)-4, IL-5 and IL-13 in lung homogenate were significantly reduced (P<0.05) by the methanol extract of E. prostrata.

Conclusion: The results presented herein demonstrate for the first time the anti-inflammatory activity of E. prostrata in a murine model of asthma, thereby supporting the ethnopharmacological uses of the plant.
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http://dx.doi.org/10.1016/j.jep.2016.12.008DOI Listing
February 2017

The Influence of the Rebaudioside A Content of Stevia (Stevia rebaudiana Bertoni) on the Determination of Sweetness Equivalence in Bittersweet Chocolates, Using the Time-Intensity Analysis.

J Food Sci 2016 Dec 3;81(12):S3006-S3014. Epub 2016 Nov 3.

Food and Nutrition Dept., Faculty of Food Engineering, Univ. of Campinas, UNICAMP, Campinas, 13083-862, São Paulo, Brazil.

The consumption of diet products has increased greatly in recent years. The objectives of the study were to develop a bittersweet chocolate added inulin and stevias with different rebaudioside A contents (60%, 80%, and 97%). Five chocolate samples were formulated with different sucrose concentrations to determine the ideal sucrose concentration for bittersweet chocolate. The use of just-about-right scale identified an ideal sucrose concentration of 47.5% (w/w). The sweetness equivalence in sugar-free bittersweet chocolates was determined by the time-intensity method by 14 selected and trained judges. The data collected during each session of sensory evaluation furnished the following parameters in relation to the sweet stimulus: Imax (maximum intensity recorded), Timax (time at which the maximum intensity was recorded), Area (area of time × intensity curve), and Ttot (total duration time of the stimulus). The time-intensity analysis indicated that the percentages of rebaudioside A did not interfere with the sweetness intensity of the sweetener stevia in bittersweet chocolate and there was no significant difference in the concentrations tested (0.16%, 0.22%, 0.27%) of each stevia, in relation to the parameters evaluated. In addition, the reduction in fat content did not alter the perception of the sweetness intensity of the samples. These results showed important information to research and development of chocolate products. Therefore, the use of the lowest stevia concentration tested (0.16%) is the most indicated for use, since this quantity was sufficient to reach the ideal sweetness of the product, so there was no point in adding more.
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http://dx.doi.org/10.1111/1750-3841.13546DOI Listing
December 2016

Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not Associated with Succinate Dehydrogenase Defects.

Eur Thyroid J 2016 Jul 10;5(2):94-9. Epub 2016 Mar 10.

Group for Advanced Molecular Investigation (NIMA), Graduate Program in Health Sciences (PPGCS), School of Medicine (EM), Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil; Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics (PDEGEN) and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Md., USA.

Background: Thyroid cancer is the most common endocrine gland malignancy. Advances in understanding the genetic basis for thyroid cancer revealed the potential involvement of several genes in the formation of thyroid tumors. Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH) is a heterotetrameric protein composed of four subunits, SDHA, SDHB, SDHC, and SDHD, and participates in both the electron transport chain and the tricarboxylic acid cycle. The aim of the study was to evaluate the association between variants in the SDHA, SDHB, SDHC, and SDHD genes and familiar PTC in a large Brazilian family.

Method: Four patients with PTC, 1 patient with PTC and gastrointestinal stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them with different thyroid problems - from a large Brazilian family were screened for genetic variations of SDHx genes with the use of polymerase chain reaction-single-stranded conformational polymorphism and direct sequencing.

Results: Only one rare variation in SDHA was found in some of the family members, but not segregating with the disease. No other genetic variants of these genes were detected in the family members that presented with PTC and/or GIST.

Conclusion: Familiar PTC and a GIST were not associated with SDHx mutations; additional genetic defects, yet unknown, may be responsible for the development of tumor.
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http://dx.doi.org/10.1159/000444522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949364PMC
July 2016

Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats.

Cardiovasc Toxicol 2017 04;17(2):190-199

Department of Physiological Sciences, Federal University of Espirito Santo, Avenida Marechal Campos, 1468, Maruípe, Vitoria, ES, 29043-900, Brazil.

Lead (Pb) induces adverse effects when it chronically accumulates in the body, including effects on the nervous and cardiovascular systems. Wistar rats were exposed to lead acetate for 30 days (first dose 4 µg/100 g followed by 0.05 µg/100 g/day, i.m.) to investigate the cardiovascular system impact on the autonomic control. The femoral artery and vein were catheterised to perform hemodynamic evaluations in awake rats: heart rate variability (HRV), baroreflex sensitivity, cardiopulmonary reflex and hemodynamic responses to vagal and sympathetic pharmacological blockade. Rats exposed to Pb exhibited a higher blood pressure and reduced HRV in the time domain when compared to the saline-injected group. Spectral analysis of the HRV in the frequency-domain showed an augmented low-frequency component of the spectrum. Methylatropine and atenolol administration suggest increased sympathetic tone and reduced vagal tone on the control of heart rate. Chronic Pb exposure decreased the sensitivity of the baroreflex without significantly changing the cardiopulmonary reflex. This study demonstrated for the first time in an animal model of a controlled, low-dose chronic lead exposure that cardiovascular changes, such as arterial hypertension, are accompanied by impaired autonomic control of the cardiovascular system, as characterised by reduced baroreflex sensitivity and a sympathovagal imbalance.
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http://dx.doi.org/10.1007/s12012-016-9374-yDOI Listing
April 2017

An effective and biocompatible antibiofilm coating for central venous catheter.

Can J Microbiol 2015 May 2;61(5):357-65. Epub 2015 Mar 2.

Center of Research and Innovation in Health Sciences (NUPICS), School of Pharmacy, Federal University of Juiz de Fora - Juiz de Fora, Minas Gerais, Brazil.

The aim of this study was to investigate the in vitro and in vivo efficacy and the tissue reaction of an antibiofilm coating composed of xylitol, triclosan, and polyhexamethylene biguanide. The antimicrobial activity was analyzed by a turbidimetric method. Scanning electron microscopy was used to evaluate the antiadherent property of central venous catheter (CVC) fragments impregnated with an antibiofilm coating (I-CVC) in comparison with noncoated CVC (NC-CVC) fragments. Two in vivo assays using subcutaneous implantation of NC-CVC and I-CVC fragments in the dorsal area of rats were performed. The first assay comprised hematological and microbiological analysis. The second assay evaluated tissue response by examining the inflammatory reactions after 7 and 21 days. The formulation displayed antimicrobial activity against all tested strains. A biofilm disaggregation with significant reduction of microorganism's adherence in I-CVC fragments was observed. In vivo antiadherence results demonstrated a reduction of early biofilm formation of Staphylococcus aureus ATCC 25923, mainly in an external surface of the I-CVC, in comparison with the NC-CVC. All animals displayed negative hemoculture. No significant tissue reaction was observed, indicating that the antibiofilm formulation could be considered biocompatible. The use of I-CVC could decrease the probability of development of localized or systemic infections.
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http://dx.doi.org/10.1139/cjm-2014-0783DOI Listing
May 2015

MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways.

Toxicol Appl Pharmacol 2015 Mar 14;283(2):127-38. Epub 2015 Jan 14.

Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain. Electronic address:

Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100g; subsequent doses: 0.125μg/100g, intramuscular, 30days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20μg/dL) were used. Lead blood levels of treated rats attained 21.7±2.38μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension.
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http://dx.doi.org/10.1016/j.taap.2015.01.005DOI Listing
March 2015

Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes mellitus: a non-controlled, pilot study.

Phytother Res 2014 Dec 6;28(12):1816-21. Epub 2014 Aug 6.

Ribeirão Preto Medical School, University of São Paulo, Avenida dos Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.

Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen patients were enrolled in a pilot, non-controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside, quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type-2 DM and deserve further investigation.
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http://dx.doi.org/10.1002/ptr.5206DOI Listing
December 2014

Mechanical analysis of femoral neck fracture fixation in synthetic bone.

Acta Ortop Bras 2014 ;22(3):155-8

1. Hospital Ortopédico e Medicina Especializada (HOME), Brasília, DF, Brazil, 1. Hospital Ortopédico e Medicina Especializada (HOME), Brasília, DF, Brazil, Hospital Ortopédico e Medicina Especializada (HOME), Brasília, DF, Brazil.

Objective: To analyze statistically results obtained between biomechanical assays on fixation of femoral neck fracture type Pauwels III, on synthetic bone, using 7.5 mm non parallel cannulated screws and control group.

Methods: Ten synthetic bones from a national brand were used. Test group: fixation of 70((o)) tilt femoral neck osteotomy was performed using three 7.5 mm non parallel cannulated screws. We analyzed the resistance of this fixation with 5 mm of displacement, and rotational deviation (phase 1) and with 10 mm offset (phase 2).

Control Group: the models were tested in their integrity until the femoral neck fracture occurred.

Results: the values of the test group in phase 1, in sample 1-5 had a mean of 517N and SD = 96N. Rotational deviations showed a mean of 3.79° e SD = 2. 03°. In phase 2, mean was 649N and SD = 94N. The values of the maximum load in the control group were: 1544N, 1110N, 1359N, 1194N, 1437N; respectively. Statistical analysis between the groups showed a statistically significant lower value in the test group.

Conclusion: the analysis of mechanical resistance between the groups has determined statistically significant value for the test group.
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http://dx.doi.org/10.1590/1413-78522014220300914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108699PMC
July 2014

Activation of K+ channels and Na+/K+ ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats.

Toxicol Appl Pharmacol 2012 Jul 23;262(1):22-31. Epub 2012 Apr 23.

Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.

Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K+ channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K+ channels and Na+/K+)-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O₂⁻ production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K+-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K+-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K+ channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress.
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http://dx.doi.org/10.1016/j.taap.2012.04.015DOI Listing
July 2012

Acute cardiorespiratory effects of intracisternal injections of mercuric chloride.

Neurotoxicology 2011 Jun 4;32(3):350-4. Epub 2011 Mar 4.

Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Espirito Santo, Espírito Santo, Brazil.

The present studies were conducted to changes arising from mercury poisoning in the central nervous system (CNS), with a focus on determining the receptors and neurotransmitters involved. Currently, little is known regarding the neurological basis of the cardiopulmonary effects of mercury poisoning. We evaluated changes in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), respiratory rate (RR) and heart rate (HR) following a 5 μl intracisternal (i.c) injection of mercuric chloride (HgCl(2)) and the participation of the autonomic nervous system in these responses. 58 animals were utilized and distributed randomly into 10 groups and administered a 5 μL intracisternal injection of 0.68 μg/kg HgCl(2) (n=7), 1.2 μg/kg HgCl(2) (n=7), 2.4 μg/kg HgCl(2) (n=7), 60 μg/kg HgCl(2) (n=7), 120 μg/kg HgCl(2) (n=3), saline (control) (n=7), 60 μg/kg HgCl(2) plus prazosin (n=6), saline plus prazosin (n=6), 60 μg/kg HgCl(2) plus metilatropina (n=4) or saline plus metilatropina (n=4)HgCl(2). Anesthesia was induced with halothane and maintained as needed with urethane (1.2 g/kg) administered intravenously (i.v.) through a cannula placed in the left femoral vein. The left femoral artery was also cannulated to record systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). A tracheotomy was performed to record respiratory rate. Animals were placed in a stereotaxic frame, and the cisterna magna was exposed. After a stabilization period, solutions (saline or HgCl(2)) were injected i.c., and cardiopulmonary responses were recorded for 50 min. Involvement of the autonomic nervous system was assessed through the i.v. injection of hexamethonium (20 mg/kg), prazosin (1 mg/kg) and methylatropine (1 mg/kg) 10 min before the i.c. injection of HgCl(2) or saline. Treatment with 0.68, 1.2, 2.4 μg/kg HgCl(2) or saline did not modify basal cardiorespiratory parameters, whereas the 120 μg/kg dose induced acute toxicity, provoking respiratory arrest and death. The administration of 60 μg/kg HgCl(2), however, induced significant increases (p<0.05) in SAP at the 30°, 40° and 50° min, timepoints and DAP at the 5°, 10°, 20°, 30°, 40° and 50° timepoints. RR was significantly decreased at the 5°, 10°, 20°, 40° and 50° min timepoints; however, there was no change in HR. Hexamethonium administration, which causes non-specific inhibition of the autonomic nervous system, abolished the observed cardiorespiratory effects. Similarly, prazosin, a α(1)-adrenoceptor blocker that specifically inhibits sympathetic nervous system function, abolished HgCl(2) induced increases in SAP and DAP without affecting HR and RR. Methylatropine (1 mg/Kg), a parasympathetic nervous system inhibitor, exacerbated the effects of HgCl(2) and caused slow-onset respiratory depression, culminating in respiratory arrest and death. Our results demonstrate that increases in SAP and DAP induced by the i.c. injection of mercuric chloride are mediated by activation of the sympathetic nervous system.
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http://dx.doi.org/10.1016/j.neuro.2011.02.006DOI Listing
June 2011