Publications by authors named "Luís Freitas"

51 Publications

[Pregnancy and Hemodialysis: About a Successful Twin Pregnancy].

Acta Med Port 2021 Jan 4;34(1):56-58. Epub 2021 Jan 4.

Departamento de Obstetrícia A. Maternidade Doutor Daniel de Matos. Centro Hospitalar e Universitário de Coimbra. Coimbra. Portugal.

Pregnancy is a rare condition in women with chronic kidney disease on hemodialysis, but its incidence has increased in recent years. Despite being a high-risk condition for both mother and fetus, there has been an improvement in care due to the increased number of cases described and the experience gained in dialysis therapy. We report the case of a multiparous 32-years-old women with chronic hypertension and chronic kidney disease with 10 years of evolution and difficult control, with a diagnosis of dichorionic/diamniotic twin pregnancy, 4 months after beginning hemodialysis. Pregnancy was managed by a multidisciplinary team, hemodialysis sessions were clinically and hemodynamically well tolerated, with good blood pressure and analytical control, as well as adequate development of both fetuses. She went into labor at 34 weeks and 6 days, so a caesarean section was performed, with 2 boys born with adequate weight for gestational age.
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http://dx.doi.org/10.20344/amp.11377DOI Listing
January 2021

Predictive factors for long-term survival in patients with advanced hepatocellular carcinoma treated with sorafenib.

Eur J Gastroenterol Hepatol 2020 Nov 10. Epub 2020 Nov 10.

Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte EPE.

Background And Aims: Sorafenib, used for advanced-stage hepatocellular carcinoma (HCC), has an overall survival (OS) of 10 months. However, some patients have better response and long-term survival (LTS). Aims to assess predictive factors for LTS.

Methods: Retrospectively reviewed 77 advanced HCC patients, starting sorafenib treatment between 2007 and 2016, with LTS (OS ≥24 months) as primary endpoint. Univariate and multivariable analysis of clinical variables were performed in order to identify predictive factors for LTS.

Results: Patients: seventy (90.9%) males; median age: 65 years (39-82). All had cirrhosis mostly HCV infection (n = 32, 41.6%). Majority were Child-Pugh class A (n = 50, 64.9%); median MELD-Na: 11 (6-30). Multinodular HCC: 74% (n = 57); portal vein invasion (PVI): 50.6% (n = 39); extrahepatic spread: 18.2% (n = 14). Median time between HCC diagnosis and sorafenib start: 3.3 months (0-37.6). Median OS: 13 months [95% confidence interval (CI) 8.2-17.8]. Twenty-five (32.5%) patients were considered LTS, with amedian OS: 52.3 months (95% CI 17.1-87.4). Multivariable analysis identified Child-Pugh class A [odds ratio (OR) 11.1, 95% CI 1.78-69.54] and absence of PVI (OR 7.88, 95% CI 1.56-39.8) as independent predictors of LTS. Sub-analysis of Child-Pugh class A: absence of PVI (OR 7.13, 95% CI 1.69-30.2) and alpha-fetoprotein <400 ng/ml (OR 5.82, 95% CI 1.18-28.75) independently related to LTS.

Conclusion: Despite global short median OS, sorafenib treatment is associated with longer than 2-year survival in a sub-group, more likely in compensated liver disease and absence of PVI.
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http://dx.doi.org/10.1097/MEG.0000000000001974DOI Listing
November 2020

Spray-dried bacterial cellulose nanofibers: A new generation of pharmaceutical excipient intended for intestinal drug delivery.

Carbohydr Polym 2020 Dec 11;249:116838. Epub 2020 Aug 11.

School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, 14800-903, Brazil.

Defibrillation of bacterial cellulose by ultra-refining was efficient to release nanofibers (BCNF) which were spray dried with the matrices formers mannitol (MN), maltodextrin or hydroxypropylmethylcellulose. The best microsystem comprised the association of BCNF and MN, so the selected microparticles were loaded with diclofenac sodium or caffeine. Depending on the proportion of BCNF, the nanofibers collapse promoted by spray drying can occur onto surface or into microparticles core, leading to different release behaviors. Samples showed pH-dependent drug release, so the microsystem developed with the lowest BCNF concentration showed important trend to gastroresistance. Caffeine was spray dried as a free drug and for this reason it was devoid of any control over release rates. The set of results showed BCNF can be considered an interesting and potential pharmaceutical excipient for lipophilic drugs. Beyond that, BCNF association with MN can lead to novel enteric drug delivery systems based on natural polymers.
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http://dx.doi.org/10.1016/j.carbpol.2020.116838DOI Listing
December 2020

New species of Myrmicium Westwood (Psedosiricidae = Myrmiciidae: Hymenoptera, Insecta) from the Early Cretaceous (Aptian) of the Araripe Basin, Brazil.

An Acad Bras Cienc 2020 28;92(3):e20200479. Epub 2020 Aug 28.

Departamento de Geologia, Universidade Federal do Ceará/UFC, Fortaleza, CE, Brazil.

This paper records the first occurrence of the genus Myrmicium Westwood, 1854 in the Cretaceous of Gondwana and describes it as a new species Myrmicium araripterum sp. nov, based on the most complete specimen of this genus yet known, which represents the largest specimen of the grade "Symphyta" ever found in the Crato Formation.
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http://dx.doi.org/10.1590/0001-3765202020200479DOI Listing
October 2020

From sea monsters to charismatic megafauna: Changes in perception and use of large marine animals.

PLoS One 2019 31;14(12):e0226810. Epub 2019 Dec 31.

NIWA, Wellington, New Zealand.

Marine megafauna has always elicited contrasting feelings. In the past, large marine animals were often depicted as fantastic mythological creatures and dangerous monsters, while also arousing human curiosity. Marine megafauna has been a valuable resource to exploit, leading to the collapse of populations and local extinctions. In addition, some species have been perceived as competitors of fishers for marine resources and were often actively culled. Since the 1970s, there has been a change in the perception and use of megafauna. The growth of marine tourism, increasingly oriented towards the observation of wildlife, has driven a shift from extractive to non-extractive use, supporting the conservation of at least some species of marine megafauna. In this paper, we review and compare the changes in the perception and use of three megafaunal groups, cetaceans, elasmobranchs and groupers, with a special focus on European cultures. We highlight the main drivers and the timing of these changes, compare different taxonomic groups and species, and highlight the implications for management and conservation. One of the main drivers of the shift in perception, shared by all the three groups of megafauna, has been a general increase in curiosity towards wildlife, stimulated inter alia by documentaries (from the early 1970s onwards), and also promoted by easy access to scuba diving. At the same time, environmental campaigns have been developed to raise public awareness regarding marine wildlife, especially cetaceans, a process greatly facilitated by the rise of Internet and the World Wide Web. Currently, all the three groups (cetaceans, elasmobranchs and groupers) may represent valuable resources for ecotourism. Strikingly, the economic value of live specimens may exceed their value for human consumption. A further change in perception involving all the three groups is related to a growing understanding and appreciation of their key ecological role. The shift from extractive to non-extractive use has the potential for promoting species conservation and local economic growth. However, the change in use may not benefit the original stakeholders (e.g. fishers or whalers) and there may therefore be a case for providing compensation for disadvantaged stakeholders. Moreover, it is increasingly clear that even non-extractive use may have a negative impact on marine megafauna, therefore regulations are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938407PMC
April 2020

LS-SVR as a Bayesian RBF Network.

IEEE Trans Neural Netw Learn Syst 2020 Oct 11;31(10):4389-4393. Epub 2019 Dec 11.

We show theoretical similarities between the least squares support vector regression (LS-SVR) model with a radial basis functions (RBFs) kernel and maximum a posteriori (MAP) inference on Bayesian RBF networks with a specific Gaussian prior on the regression weights. Although previous articles have pointed out similar expressions between those learning approaches, we explicitly and formally state the existing correspondences. We empirically demonstrate our result by performing computational experiments with standard regression benchmarks. Our findings open a range of possibilities to improve LS-SVR by borrowing strength from well-established developments in Bayesian methodology.
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http://dx.doi.org/10.1109/TNNLS.2019.2952000DOI Listing
October 2020

Different levels of selenomethionine on the meat quality and selenium deposition in tissue of finishing pigs.

J Anim Physiol Anim Nutr (Berl) 2019 Nov 22;103(6):1866-1874. Epub 2019 Aug 22.

Department of Food Science, Federal University of Lavras, Lavras, Brazil.

The aim of the study was to verify the influence of selenomethionine (SM) supplementation on performance, carcass yield, characteristics of meat quality and Se tissue deposition of finishing pigs. A total of 128 hybrid pigs with an average weight of 76 kg were distributed in randomized blocks according to body weight in eight treatments and eight replicates. The experimental treatments were two Se levels from sodium selenite-SS (0.3 and 0.6 ppm), four Se levels from SM (0.3, 0.4, 0.5 and 0.6 ppm) and two combinations of SS with SM (SS 0.15 + SM 0.15 ppm and SS 0.3 + SM 0.3 ppm) providing 0.3 and 0.6 ppm Se in the diet respectively. The feeds were based on corn and soya bean meal. After 30 days on test, were analysed the performance indices and the pigs were slaughtered at commercial slaughterhouse. The cold carcass yield, the physicochemical characteristics of the loin meat and the Se content in muscle and liver were evaluated. There was no significant difference in performance indices (p > .05); however, there was a linear effect on the increase in pig carcass yield by increasing SM (p < .05). The use of SM solely or combined with SS provided higher Se deposition in muscle compared to SS (p < .05). The highest Se deposition in muscle occurred for SM at 0.4 ppm (p < .05). The SS provided higher Se deposition in liver (p < .05). The SM presented best results for meat quality compared to other sources (p < .05). The level of 0.4 ppm Se promoted the best results for the indices of yellow, luminosity, cooking loss and pH (p < .05). The use of SM at any level promotes higher oxidation stability of pig meat (p < .05). The supplementation of SM at a level of 0.4 ppm promotes better physicochemical characteristics and higher Se deposition on swine meat.
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http://dx.doi.org/10.1111/jpn.13179DOI Listing
November 2019

Risk factors associated with recurrent venous thromboembolism after a first cerebral venous thrombosis event: A cohort study.

Thromb Res 2019 Jun 10;178:85-90. Epub 2019 Apr 10.

Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais State, Brazil; Hematology Unit, University Hospital, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais State, Brazil. Electronic address:

Background: Cerebral venous thrombosis (CVT), although rare, is potentially fatal. Few studies have investigated risk factors associated with recurrent venous thromboembolism (VTE) after a first CVT event of which most are from Caucasian populations. The aim of this study was to evaluate risk factors associated with recurrent VTE after a first CVT event in a South American-population.

Patients/methods: In this cohort, multicenter study, patients aged >18 years and objectively-diagnosed with CVT were included, with follow-up starting after discontinuing anticoagulant therapy. The primary outcome was symptomatic VTE recurrence at any venous site.

Results: We included 203 patients with a median age of 30.8 (interquartile range [IQR], 24.7-40.9) years and a follow-up of 3.0 (IQR, 1.2-5.6) years. Most patients (86.2%) were women, and among those of reproductive age (n = 162), 65.4% developed CVT during oral contraceptive use, and 9.2% during pregnancy/puerperium. Thirteen patients (6.9%) developed VTE recurrence after a first CVT, yielding an overall rate of 1.6/100 patient-years (95% confidence interval [CI], 0.8-2.8). Recurrence rate was higher in males (4.6/100 patient-years; 95% CI, 1.2-11.7) than in females (1.2/100 patient-years; 95% CI, 0.6-2.4), and in patients with factor V Leiden mutation (9.2/100 patient-years; 95% CI, 1.1-33.1) than in those without it (1.2/100 patient-years; 95% CI, 0.5-2.4).

Conclusions: VTE recurrence after a first CVT was low. In spite of the limitation of small sample size, male sex and factor V Leiden mutation were the only factors associated with a significant higher risk of recurrent VTE after a first CVT in a multivariate analysis.
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http://dx.doi.org/10.1016/j.thromres.2019.04.008DOI Listing
June 2019

Effects of walk training with self-selected intensity on biochemical markers and anthropometric variables in women with obesity.

Obes Res Clin Pract 2019 Mar - Apr;13(2):211-213. Epub 2019 Mar 1.

Universidade Estadual de Maringá (UEM), Maringá, Brazil.

To evaluate the effects of 12-weeks of walk training with self-selected intensity on lipid profile and anthropometric variables in women with obesity. Forty-eight women volunteers with obesity were randomly assigned into two training groups: self-selected walking group (SSWG; n=25) and control group (CG; n=23). There was improvement in biochemical markers only in the SSWG post-intervention (p<0.05), however no changes were verified in anthropometric variables (p>0.05). This study demonstrates that walking at self-selected intensity improved the lipid profile in women with obesity.
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http://dx.doi.org/10.1016/j.orcp.2019.02.004DOI Listing
May 2020

Supplementation of selenomethionine at different ages and levels on meat quality, tissue deposition, and selenium retention in broiler chickens.

Poult Sci 2019 May;98(5):2150-2159

Department of Animal Science, Federal University of Lavras, Lavras, CEP 37200-000, Minas Gerais, Brazil.

The aim of the present study was to verify the effect of selenomethionine (SM) supplementation in the diet of chickens on performance, carcass yield, apparent retention, meat quality, and selenium (Se) deposition in tissues. In the first experiment, 2,100 day-old male chicks from the Hubbard Flex strain were randomly distributed in 84 plots with 12 treatments and 7 replicates. The treatments consisted of SM (1,600 ppm) supplementation at levels of 0.3 and 0.5 ppm in substitution of sodium selenite (45.7%) in different preslaughter phases. In the second experiment, 224 day-old male chicks from Hubbard Flex strain were randomly distributed in 28 metabolic cages. Poultry were distributed in 4 treatments with 7 replicates (8 poultry) in the experimental period from 1 to 21 D and experimental plot with 4 poultry aged from 22 to 42 D. Treatments consisted of 4 SM addition levels (0.3, 0.4, 0.5, and 0.6 ppm). In both experiments, the performance (1 to 21 and 1 to 42 D), carcass yield and cuts, apparent retention of Se (33 to 35 D), physical and chemical characteristics of the breast meat were evaluated: objective color, drip loss (DL), cooking loss (CL), pH, peroxide value, and Se deposition in tissues. In experiment I, it was found that SM at 0.3 ppm improved the weight gain and feed conversion of 1 to 42 D. The use of SM at 0.5 ppm resulted in lower DL and CL. The highest Se deposition in muscles was obtained using the SM at 0.5 ppm of 1 to 42 D. Using the SM at 0.5 ppm, only in the last week there was a deposition similar to the use of SM at 0.3 ppm of 1 to 42 D. In experiment II, it can be observed that increased SM levels provided lower DL and lower pH values. Se deposition in tissues of broiler chickens increased linearly at the SM level from 0.3 to 0.6 ppm.
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http://dx.doi.org/10.3382/ps/pey569DOI Listing
May 2019

Safety of a formulation containing chitosan microparticles with chamomile: blind controlled clinical trial.

Rev Lat Am Enfermagem 2018 Nov 29;26:e3075. Epub 2018 Nov 29.

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

Objective: to evaluate the safety of a topical formulation containing chamomile microparticles coated with chitosan in the skin of healthy participants.

Method: phase I blind, controlled, non-randomized, single-dose clinical trial with control for skin, base formulation, and formulation with microparticles. The variables analyzed were irritation and hydration by the Wilcoxon and Kruskall-Wallis tests.

Results: the study started with 35 participants with a mean age of 26.3 years. Of these, 30 (85.71%) were female, 29 (82.90%) were white skinned and 32 (91.40%) had no previous pathologies. One participant was removed from the study reporting erythema at the site of application, and four other participants for not attending the last evaluation. In the 30 participants who completed the study, the tested formulation did not cause erythema, peeling, burning, pruritus or pain; there was an improvement in cutaneous hydration in the site of application of the formulation with microparticles. In the evaluation of the barrier function, there was an increase in transepidermal water loss in all sites.

Conclusion: the formulation with chamomile microparticles is safe for topical use, not causing irritation and improving skin hydration over four weeks of use. Its effects on barrier function need further investigation. No. RBR-3h78kz in the Brazilian Registry of Clinical Trials (ReBEC).
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http://dx.doi.org/10.1590/1518-8345.2648.3075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280169PMC
November 2018

Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion.

Int J Pharm 2018 Apr 16;541(1-2):1-10. Epub 2018 Feb 16.

Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil. Electronic address:

Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ± 7.22 nm, 0.219 ± 0.011 and -9.77 ± 0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets.
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http://dx.doi.org/10.1016/j.ijpharm.2018.02.020DOI Listing
April 2018

Fluidized Bed Hot-Melt Granulation as a Tool to Improve Curcuminoid Solubility.

AAPS PharmSciTech 2018 Apr 16;19(3):1061-1071. Epub 2017 Nov 16.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Instituto Nacional de Ciência e Tecnologia-INCT-Nanotecnologia Farmacêutica, Universidade de São Paulo, Via do Café s/n, Campus USP, Ribeirão Preto, SP, 14040-903, Brazil.

Curcumin is the main bioactive component of Curcuma longa L. and has recently aroused growing interest from the scientific community. Unfortunately, the medicinal properties attributed to curcuminoids are impaired by their low oral bioavailability or low solubility in aqueous solutions. Many strategies have been studied to improve curcumin solubility; however, the preparation of granules using hydrophilic materials has never been attempted. The aim of this work was to develop curcumin granules by fluidized bed hot-melt granulation using the hydrophilic carrier Gelucire® 50:13. A two-level factorial design was used to verify the influence of Gelucire® 50:13 and lactose contents found in the granules on their size, morphology, bulk and tapped densities, flow, moisture content, and water activity. The granules obtained were also evaluated by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and infrared spectrometry. The curcumin solubility and dissolution rates in water were determined by liquid chromatography. The best formulation provides an increase of curcumin solubility of 4642-fold and 3.8-fold compared to the physical mixture. The dissolution tests showed a maximum drug release from granules after 45 min of 70% at pH 1.2 and 80% at pH 5.8 and 7.4, while for non-granulated curcumin, the release was below 20% in all pH. The solid-state characterization and solubility measurement showed good stability of granules over 9 months. The results attest that the fluidized bed hot-melt granulation with hydrophilic binders is an attractive and promising alternative to obtain solid forms of curcumin with enhanced bioavailability.
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http://dx.doi.org/10.1208/s12249-017-0909-8DOI Listing
April 2018

Triterpene saponins from Billia rosea.

Phytochemistry 2017 Sep 7;141:105-113. Epub 2017 Jun 7.

Laboratoire de Pharmacognosie, PEPITE EA 4267, UFR des Sciences de Santé, Université de Bourgogne Franche-Comté, 7, Bd. Jeanne d'Arc, BP 87900, F-21079 Dijon Cedex, France. Electronic address:

Five previously undescribed triterpene saponins, billiosides A-E, and a known analogue, were isolated from the seeds of Billia rosea (Planch. & Linden) C. Ulloa & P. Jørg. Their structures were elucidated on the basis of extensive 1D and 2D NMR experiments (H, C, DEPT, COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC) and mass spectrometry as (3β,21β,22α)-3-[(2-O-β-D-glucopyranosyl-O-[α-L-arabinopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-21-[((2E,6S)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl)oxy]-22-(acetyloxy)-24-hydroxyolean-12-en-28-oic acid, (3β,21β,22α)-3-[(2-O-β-D-galactopyranosyl-β-D-glucopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-α-L-arabinopyranosyl-(1 → 4)-β-D-glucopyranoside, (3β,21β,22α)-3-[(2-O-β-D-galactopyranosyl-O-[α-L-arabinopyranosyl-(1 → 4)]-β-D-xylopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-β-D-glucopyranoside, (3β,21β,22α)-3-[(2-O-β-D-galactopyranosyl-O-[α-L-arabinopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-β-D-glucopyranoside, (3β,21β,22α)-3-[(2-O-β-D-galactopyranosyl-O-[α-L-arabinopyranosyl-(1 → 4)]-β-D-glucopyranosyl)oxy]-21,22-dihydroxyolean-12-en-28-yl O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside, and dipteroside A. Billiosides B and C exhibited moderate effects when tested as hepatic glucose-6-phosphatase inhibitors and as glucose intestinal absorption inhibitors, using in situ rat intestinal segments.
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http://dx.doi.org/10.1016/j.phytochem.2017.04.023DOI Listing
September 2017

Box-Behnken analysis and storage of spray-dried collagenolytic proteases from Myceliophthora thermophila submerged bioprocess.

Prep Biochem Biotechnol 2017 May 10;47(5):473-480. Epub 2017 Feb 10.

a Faculdade de Ciências Farmacêuticas de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , SP , Brazil.

Enzymes do not have long-term storage stability in soluble forms, thus drying methods could minimize the loss of enzymatic activity, the spray dryer removes water under high temperatures and little time. The aims of this study were to improve the stability of enzymatic extract from Myceliophthora thermophila for potential applications in industry and to evaluate the best conditions to remove the water by spray drying technique. The parameters were tested according to Box-Behnken and evaluated by analysis of variance (ANOVA), all the parameters measured were found to influence the final enzyme activity and spray drying process yield ranged from 38.65 to 63.75%. Enzyme powders showed increased storage stability than extract and maintained about 100% of collagenolytic activity after 180 days of storage at 30°C. The results showed that the microbial enzymes maintained activity during the spray drying process and were stable during long-term storage; these are promising characteristics for industrial applications.
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http://dx.doi.org/10.1080/10826068.2017.1292289DOI Listing
May 2017

Topical Formulation Containing Beeswax-Based Nanoparticles Improved In Vivo Skin Barrier Function.

AAPS PharmSciTech 2017 Oct 17;18(7):2505-2516. Epub 2017 Feb 17.

School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Campus USP, 14040-903, Ribeirão Preto, São Paulo, Brazil.

Lipid nanoparticles have shown many advantages for treatment/prevention of skin disorders with damaged skin barrier function. Beeswax is a favorable candidate for the development of nanosystems in the cosmetic and dermatological fields because of its advantages for the development of products for topical application. In the present study, beeswax-based nanoparticles (BNs) were prepared using the hot melt microemulsion technique and incorporated to a gel-cream formulation. The formulation was subsequently evaluated for its rheological stability and effect on stratum corneum water content (SCWC) and transepidermal water loss (TEWL) using in vivo biophysical techniques. BNs resulted in mean particle size of 95.72 ± 9.63 nm and zeta potential of -9.85 ± 0.57 mV. BN-loaded formulation showed shear thinning behavior, well adjusted by the Herschel-Bulkley model, and a small thixotropy index that were stable for 28 days at different temperatures. BN-loaded formulation was also able to simultaneously decrease the TEWL and increase the SCWC values 28 days after treatment. In conclusion, the novel beeswax-based nanoparticles showed potential for barrier recovery and open the perspective for its commercial use as a novel natural active as yet unexplored in the field of dermatology and cosmetics for treatment of skin diseases with damaged skin barrier function.
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http://dx.doi.org/10.1208/s12249-017-0737-xDOI Listing
October 2017

Adenoid bacterial colonization in a paediatric population.

Eur Arch Otorhinolaryngol 2017 Apr 18;274(4):1933-1938. Epub 2017 Feb 18.

Departamento de Saúde Ambiental, Unidade de Investigação e Desenvolvimento, INSA, Avenida Padre Cruz, 1649-016, Lisbon, Portugal.

Adenoids play a key role in both respiratory and ear infection in children. It has also been shown that adenoidectomy improves these symptoms in this population. The main goal of the present study was to evaluate adenoid bacterial colonization and document a possible relation with infectious respiratory disease. A prospective observational study was designed to evaluate the proposed hypothesis in a paediatric population submitted to adenoidectomy by either infectious or non-infectious indications and compare these two cohorts. A total of 62 patients with ages ranging from 1 to 12 years old were enrolled in the study. Adenoid surface, adenoid core and middle meatus microbiota were compared. A close association between adenoid colonization and nasal infection was found, supporting that adenoids may function as bacterial reservoir for upper airway infection. The obtained results also contribute to explain the success of adenoidectomy in patients with infectious indications.
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http://dx.doi.org/10.1007/s00405-017-4493-zDOI Listing
April 2017

First Occurrence and Paleo-Ecological Implications of Insects (Orthoptera: Ensifera Gryllidae) in the Romualdo Member of the Santana Formation, Eo-Cretaceous of the Araripe Basin.

An Acad Bras Cienc 2016 Oct-Dec;88(4):2113-2120. Epub 2016 Nov 10.

Universidade Regional do Cariri, Laboratório de Paleontologia da URCA - L.P.U., Rua Cel. Antônio Luiz, 1161E, Pimenta, 63100-000 Crato, CE, Brazil.

The Romualdo Member of the Santana Formation, a lithostatigraphic unit attributed to a marine intrusion, is famous for its preserved fossils in calcareous concretions, which stand out for their diversity and excellent preservation levels. This paper aims to record the first occurrence of the Class Insecta in the Romualdo Member of the Santana Formation of the Araripe Basin, as well as to describe and discuss the paleo-ecological implications of such finding. The first occurrence of the order Orthoptera (family Gryllidae) is presented for this unit. This new species is attributed to the genus Araripegryllus, that lasted throughout the deposition of the Crato Member, which is under the Romualdo Member. In reference to its statigraphic origin, the specimens was named Araripegryllus romualdoi sp. nov.
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http://dx.doi.org/10.1590/0001-3765201620150375DOI Listing
February 2018

Curcumin suppresses inflammatory cytokines and heat shock protein 70 release and improves metabolic parameters during experimental sepsis.

Pharm Biol 2017 Dec;55(1):269-276

a Department of Morphology, Physiology and Basic Pathology , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , São Paulo, Brazil.

Context: Curcumin has been reported to have anti-inflammatory, antioxidant and hypoglycaemic properties, besides reducing mortality in sepsis.

Objective: This study evaluates the biological activities of a curcumin dispersion formulated by spray-drying in experimental sepsis.

Materials And Methods: Male Wistar rats were subjected to sepsis by caecal ligation and puncture (CLP), controls were sham operated. The animals were treated with curcumin dispersion (100 mg/kg, p.o.) or water for 7 days prior to CLP and at 2 h after surgery. One group was used to analyze curcumin absorption through HPLC; another had the survival rate assessed during 48 h; and from a third group, blood was collected by decapitation to analyze metabolic and inflammatory parameters.

Results: The plasma curcumin levels reached 2.5 ng/mL at 4 h, dropped significantly (p < 0.001) at 6 h (1.2 ng/mL), and were undetectable at 24 h in both groups. Curcumin temporarily increased the survival rate of the septic rats by 20%. Moreover, it attenuated glycaemia (p < 0.05) and volemia (p < 0.05) alterations typically observed during sepsis, and decreased the levels of the proinflammatory cytokines IL-1β and IL-6 in plasma (p < 0.001) and peritoneal lavage fluid (p < 0.05) of septic rats. Serum HSP70 levels were decreased (p < 0.01) at 24 h after CLP.

Discussion And Conclusion: Our results show that the curcumin dispersion dose employed was not detrimental to the septic rats. In fact, it temporarily increased their survival rate, improved important metabolic parameters, reduced proinflammatory cytokines and HSP70 production.
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http://dx.doi.org/10.1080/13880209.2016.1260598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130593PMC
December 2017

Upper gastrointestinal bleeding in a patient with Sjögren syndrome.

Rev Esp Enferm Dig 2016 Sep;108(9):576

Serviço de Gastrenterologia e Hepatologia, Hospital Santa Maria, Portugal.

A 68-year-old female patient with Sjögren syndrome was admitted with asthenia, anorexia and weight loss. On the third day of admission, she developed severe hematemesis. Urgent upper gastrointestinal endoscopy (UGE) showed multiple gastric and duodenal ulcers, some with active bleeding requiring endoscopic therapy. The anatomopathologic examination was compatible with gastric and duodenal infiltration by a diffuse CD20+ large B cell lymphoma with germinal center B cell-like morphology. And the patient was referred for chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone. Although seldom observed, the risk of lymphoma in Sjögren syndrome is up to 44 times higher than the general population and rises 7 years after diagnosis. We present a brief case report with interesting iconography.
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September 2016

Fluidized Bed Hot Melt Granulation with Hydrophilic Materials Improves Enalapril Maleate Stability.

AAPS PharmSciTech 2017 May 3;18(4):1302-1310. Epub 2016 Aug 3.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil.

This work aimed at developing enalapril maleate granules in order to improve its stability in solid dosage form. Granules were prepared by hot melt granulation using a fluidized bed apparatus. Gelucire 50/13®, polyethylene glycol 6000 e Poloxamer 407® were studied and compared as binders in 2 × 2 factorial designs where the proportions of enalapril maleate, binders and spray dried lactose were varied. The granulation process resulted in high yields and granule sizes that indicated the prevalence of particles coating. Furthermore, the granules obtained showed adequate flowability and a fast dissolution rate of enalapril maleate with almost 100% of the drug released in 10 min. The stability of enalapril maleate in hard gelatin capsules showed that the drug stability was greatly increased in granules, since for raw drug, the remaining content of enalapril maleate after 91 days was 68.4% and, for granules, the content was always above 93%. This result was confirmed by the quantification of the degradation products, enalaprilat and diketopiperazine, which were found in very low content in granules samples. The results demonstrate that fluidized bed hot melt granulation with hydrophilic binders is a suitable alternative for improving the chemical stability of enalapril maleate.
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http://dx.doi.org/10.1208/s12249-016-0593-0DOI Listing
May 2017

Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug.

Ultrason Sonochem 2016 Mar 31;29:461-9. Epub 2015 Oct 31.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Núcleo de Pesquisa em Produtos Naturais e Sintéticos - Universidade de São Paulo, Via do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil. Electronic address:

Solid dispersions have been successfully used to enhance the solubility of several poorly water soluble drugs. Solid dispersions are produced by melting hydrophilic carriers and mixing in the poorly water soluble drug. Supersaturation is obtained by quickly cooling the mixture until it solidifies, thereby entrapping the drug. The effects of using ultrasound to homogenize the molten carrier and drug mixture were studied. In particular, the increase in drug solubility for the resulting solid dispersions was analyzed. Piroxicam, which has very low water solubility, was used as a model drug. A full factorial design was used to analyze how sonication parameters affected the solubility and in vitro release of the drug. The results show that the use of ultrasound can significantly increase the solubility and dissolution rate of the piroxicam solid dispersion. Pure piroxicam presented a solubility of 13.3 μg/mL. A maximum fourfold increase in solubility, reaching 53.8 μg/mL, was observed for a solid dispersion sonicated at 19 kHz for 10 min and 475 W. The in vitro dissolution rate test showed the sonicated solid dispersion reached a maximum rate of 18%/min, a sixfold increase over the piroxicam rate of 2.9%/min. Further solid state characterization by thermal, X-ray diffraction and Fourier transform infrared analyses also showed that the sonication process, in the described conditions, did not adversely alter the drug or significantly change its polymorphic form. Ultrasound is therefore an interesting technique to homogenize drug/carrier mixtures with the objective of increasing the solubility of drugs with poor water solubility.
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http://dx.doi.org/10.1016/j.ultsonch.2015.10.022DOI Listing
March 2016

Comparative study of curcumin and curcumin formulated in a solid dispersion: Evaluation of their antigenotoxic effects.

Genet Mol Biol 2015 Dec 3;38(4):490-8. Epub 2015 Nov 3.

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Curcumin (CMN) is the principal active component derived from the rhizome of Curcuma longa (Curcuma longa L.). It is a liposoluble polyphenolic compound that possesses great therapeutic potential. Its clinical application is, however, limited by the low concentrations detected following oral administration. One key strategy for improving the solubility and bioavailability of poorly water-soluble drugs is solid dispersion, though it is not known whether this technique might influence the pharmacological effects of CMN. Thus, in this study, we aimed to evaluate the antioxidant and antigenotoxic effects of CMN formulated in a solid dispersion (CMN SD) compared to unmodified CMN delivered to Wistar rats. Cisplatin (cDDP) was used as the damage-inducing agent in these evaluations. The comet assay results showed that CMN SD was not able to reduce the formation of cDDP-DNA crosslinks, but it decreased the formation of micronuclei induced by cDDP and attenuated cDDP-induced oxidative stress. Furthermore, at a dose of 50 mg/kg b.w. both CMN SD and unmodified CMN increased the expression of Tp53 mRNA. Our results showed that CMN SD did not alter the antigenotoxic effects observed for unmodified CMN and showed effects similar to those of unmodified CMN for all of the parameters evaluated. In conclusion, CMN SD maintained the protective effects of unmodified CMN with the advantage of being chemically water soluble, with maximization of absorption in the gastrointestinal tract. Thus, the optimization of the physical and chemical properties of CMN SD may increase the potential for the therapeutic use of curcumin.
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http://dx.doi.org/10.1590/S1415-475738420150046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763312PMC
December 2015

MOLECULAR CHARACTERIZATION OF AMERICAN CUTANEOUS LEISHMANIASIS IN THE TRI‑BORDER AREA OF ASSIS BRASIL, ACRE STATE, BRAZIL.

Rev Inst Med Trop Sao Paulo 2015 Jul-Aug;57(4):343-7

Departamento de Parasitologia, Instituto de Ciências Biomédicas, São Paulo, SP, BR,

In this study, Leishmania species were identified by Polymerase Chain Reaction (PCR). The epidemiology of patients suspected of having American Cutaneous Leishmaniasis in the municipality of Assis Brasil, Acre State, located in the Brazil/Peru/Bolivia tri-border was also investigated. By PCR, the DNA of Leishmania was detected in 100% of the cases (37 samples) and a PCR-Restriction Fragment Length Polymorphism (RFLP) of the hsp 70 gene identified the species in 32 samples: Leishmania (Viannia) braziliensis (65.6%) , L. (V.) shawi (28.1%) , L. (V.) guyanensis (3.1%) and mixed infection L. (V.) guyanensis and L. (Leishmania) amazonensis(3.1%)This is the first report of L. (V.) shawi and L. (L.) amazonensis in Acre. The two predominant species were found in patients living in urban and rural areas. Most cases were found in males living in rural areas for at least three years and involved in rural work. This suggests, in most cases, a possible transmission of the disease from a rural/forest source, although some patients had not engaged in activities associated with permanence in forestall areas, which indicate a possible sandflies adaptation to the periurban setting.
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http://dx.doi.org/10.1590/S0036-46652015000400012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616921PMC
May 2016

Effect of a 12-week aerobic training program on perceptual and affective responses in obese women.

J Phys Ther Sci 2015 Jul 22;27(7):2221-4. Epub 2015 Jul 22.

Department of Physical Education, Federal University of Parana, Brazil.

[Purpose] The aim of this study was to observe the effect of self-selected intensity or imposed intensity during aerobic training on perceptual and affective responses in obese women. [Subjects] The study included 26 obese women aged 30-60 years. [Methods] The subjects were randomly divided into two groups, with 13 subjects in each group: self-selected intensity and imposed intensity (10% above ventilatory threshold) groups. All subjects completed an intervention program that lasted 12 weeks, with three exercise sessions a week. The rating of perceived exertion and affective responses (Feeling Scale and Felt Arousal Scale) were monitored in the first, sixth, and twelfth weeks. [Results] Significant differences were observed between groups in heart rate and rating of perceived exertion. The affective responses during exercise were more negative in the imposed intensity group. [Conclusion] Use of a self-selected exercise intensity can promote smaller negative affective responses during exercise and provide a sufficient stimulus for improvement in cardiorespiratory fitness.
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http://dx.doi.org/10.1589/jpts.27.2221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540853PMC
July 2015

Improvement of enalapril maleate chemical stability by high shear melting granulation.

Pharm Dev Technol 2015 Dec 18;20(8):1002-1008. Epub 2014 Sep 18.

b Laboratory of Pharmaceutical Processing , University of São Paulo , Ribeirão Preto , SP , Brazil.

Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.
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http://dx.doi.org/10.3109/10837450.2014.959178DOI Listing
December 2015

Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique.

J Microencapsul 2014 25;31(7):644-53. Epub 2014 Apr 25.

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo , Ribeirão Preto , Brazil.

Purpose: Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen's photoprotection were impaired by the microencapsulation process.

Methods: The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique.

Results: The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53-102.2%), average particle sizes between 28.5 and 60.0 µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation.

Conclusion: The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.
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http://dx.doi.org/10.3109/02652048.2014.911378DOI Listing
June 2015

Impact of cross-linking and drying method on drug delivery performance of casein-pectin microparticles.

AAPS PharmSciTech 2013 Sep 9;14(3):1227-35. Epub 2013 Aug 9.

Faculdade de Farmácia, Universidade Federal de Goiás, Av. Universitária esq. com 1ª Avenida, Setor Universitário, 74605-220, Goiânia, GO, Brazil.

Pectin is a heteropolysaccharide which has been investigated for the development of colon-specific drug delivery systems. Polymers have been associated with pectin to reduce its aqueous solubility and improve the performance of drug delivery systems. Pectin-casein interaction is widely known in food research, but it has not been fully considered by pharmaceutical scientists. Thus, this study investigated the potential of casein-pectin microparticles as a drug delivery system and clarified the impact of cross-linking and drying methods on the in vitro release of indomethacin (IND) or acetaminophen (PCT) from microparticles. Microparticles were prepared by coacervation and dried by spray or spouted bed methods. Drug recovery, in vitro drug release, size, morphology, and the thermal and diffractometric properties of dried microparticles were determined. Spray-dried non-cross-linked microparticles were able to prolong IND release, and pectin was still degraded by pectinolytic enzymes. On the other hand, glutaraldehyde cross-linking prevented the enzymatic breakdown of pectin without improving IND release. Spouted bed drying reduced IND recovery from all microparticles when compared with spray drying, thus the successful spouted bed drying of microparticles depends on the chemical characteristics of both the drug and the polymer. Release data from PCT microparticles suggested that the microparticle formulation should be improved to bring about a more efficient delivery of water-soluble drugs. In conclusion, casein-pectin microparticles show great potential as a drug delivery system because casein reduces the water solubility of pectin. The drying method and cross-linking process had significant effects on the in vitro performance of these microparticles.
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http://dx.doi.org/10.1208/s12249-013-0012-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755150PMC
September 2013