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Made available in DSpace on 2021-06-25T11:01:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: Hepatitis C virus infection is a significant global health burden, which causes acute or chronic hepatitis. Acute hepatitis C is generally asymptomatic and progresses to cure, while persistent infection can progress to chronic liver disease and extrahepatic manifestations. Standard treatment is expensive, poorly tolerated, and has variable sustained virologic responses amongst the different viral genotypes. New therapies involve direct acting antivirals; however, it is also very expensive and may not be accessible for all patients worldwide. In order to provide a complementary approach to the already existing therapies, natural bioactive compounds are investigated as to their several biologic activities, such as direct antiviral properties against hepatitis C, and effects on mitigating chronic progression of the disease, which include hepatoprotective, antioxidant, anticarcinogenic and anti-inflammatory activities; additionally, these compounds present advantages, as chemical diversity, low cost of production and milder or inexistent side effects. Objective: To present a broad perspective on hepatitis C infection, the chronic disease, and natural compounds with promising anti-HCV activity. Methods: This review consists of a systematic review study about the natural bioactive compounds as a potential therapy for hepatitis C infection. Results: The quest for natural products has yielded compounds with biologic activity, including viral replication inhibition in vitro, demonstrating antiviral activity against hepatitis C. Conclusion: One of the greatest advantages of using natural molecules from plant extracts is the low cost of production, not requiring chemical synthesis, which can lead to less expensive therapies available to low and middle-income countries. Food and Nutrition Department School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Biotechnology Institute of Chemistry São Paulo State University (UNESP) Food and Nutrition Department School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Biotechnology Institute of Chemistry São Paulo State University (UNESP)

Systemic lupus erythematosus and ANCA-associated vasculitis overlap syndrome is rare and complex. Moreover, the mechanisms that explain the interaction between these two conditions are still unclear. The authors describe the case of a patient who had myeloperoxidase ANCA-associated vasculitis as the initial diagnosis, with biopsy-proven pauci immune crescentic glomerulonephritis, attaining complete remission after immunosuppression. Five years later, Systemic Lupus Erythematosus was diagnosed and a second kidney biopsy showed a pattern of lupus nephritis class III. While on immunosuppression treatment, the patient developed a progressive elevation of liver enzymes and was later diagnosed with primary biliary cholangitis. It seems that in this case, the overlap of Systemic Lupus Erythematosus and ANCA-associated vasculitis may be part of a poliautoimmune syndrome suggested by association with a third autoimmune disease.

OBJECTIVE: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years. STUDY DESIGN: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively. RESULTS: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1. CONCLUSIONS: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain. ispartof: JOURNAL OF PEDIATRICS vol:231 pages:148-156 ispartof: location:United States status: published

The electron-transfer flavoprotein dehydrogenase gene (ETFDH) encodes the ETF-ubiquinone oxidoreductase (ETF-QO) and has been reported to be the major cause of multiple acyl-CoA dehydrogenase deficiency (MADD). In this study, we present the clinical and molecular diagnostic challenges, at the DNA and RNA levels, involved in establishing the genotype of four MADD patients with novel ETFDH variants: a missense variant, two deep intronic variants and a gross deletion. RNA sequencing allowed the identification of the second causative allele in all studied patients. Simultaneous DNA and RNA investigation can increase the number of MADD patients that can be confirmed following the suggestive data results of an expanded newborn screening program. In clinical practice, accurate identification of pathogenic mutations is fundamental, particularly with regard to diagnostic, prognostic, therapeutic and ethical issues. Our study highlights the importance of RNA studies for a definitive molecular diagnosis of MADD patients, expands the background of ETFDH mutations and will be important in providing an accurate genetic counseling and a prenatal diagnosis for the affected families.

Background The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease. Methods In this report, the biochemical and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) are presented. Results Overall, the results show that a high overlap exists between different types of variants and phenylalanine levels. Molecular analyses reveal a wide mutational spectrum in our population with a total of 56 previously reported variants, most of them found in compound heterozygosity (74% of the patients). Intragenic polymorphic markers were used to assess the haplotypic structure of mutated chromosomes for the most frequent variants found in homozygosity in our population (p.Ile65Thr, p.Arg158Gln, p.Leu249Phe, p.Arg261Gln, p.Val388Met, and c.1066‐11G>A). Conclusion Our data reveal high heterogeneity at the biochemical and molecular levels and are expected to provide a better understanding of the molecular basis of this disease and to provide clues to elucidate genotype–phenotype correlations., The present study identify and characterize the variants underlying PKU in affected individuals in the Portuguese PKU/HPA cohort. Biochemical data, haplotic analysis and genetic findings performed in 223 patients diagnosed through the Portuguese Neonatal Screening Program (PNSP) is presented. The information obtained will improve the diagnostic applicability of mutational analysis and the capacity to predict the evolution of the disease.

Hemodialysis central venous catheter (CVC) insertion can be complicated in patients with anomalous vessel anatomy. In such cases detailed knowledge of thoracic vessel anatomy is necessary to identify the exact location of the catheter. Central venous placement under ultrasound control has significantly reduced the complications associated with blind puncture and allows an appropriate puncture of the desired vessel, but the CVC can still get misplaced if it follows an anomalous route. Herein, we report a case of dialysis catheter placed into a left sided superior vena cava, only diagnosed after CT scan study. Resumo A inserção do cateter venoso central (CVC) para hemodiálise pode ser complicada em pacientes com anatomia anômala dos vasos. Nesses casos, o conhecimento detalhado da anatomia do vaso torácico é necessário para identificar a localização exata do cateter. A colocação venosa central sob controle de ultrassom tem reduzido significativamente as complicações associadas à punção às cegas e permite uma punção apropriada do vaso desejado, mas o CVC ainda pode ficar mal posicionado se seguir uma rota anômala. Aqui, relatamos um caso de cateter de diálise colocado em uma veia cava superior esquerda, apenas diagnosticado após estudo de tomografia computadorizada.

Background and Aims Focal and segmental glomerulosclerosis (FSGS) is a histological pattern that is defined by the presence of segmental sclerosis of at least one glomerulus in the kidney biopsy. However, the etiological classification of this lesion remains challenging in clinical practice. FSGS can be divided into primary/idiopathic, genetic or secondary. Nowadays here is no biochemical marker that allows clinicians to distinguish between these categories nor a pathognomonic feature associated to a particular subtype of FSGS. Also, genetic testing is not suitable for all patients. Although it is crucial to determine the cause of FSGS, this is not easily done in clinical practice. Herein we present a series of patients with histologic diagnosis of FSGS in which clinical and histological criteria were applied in order to establish the etiologic classification of FSGS. Method A retrospective analysis of 359 patients who performed kidney biopsy from January 2010 to December 2018 was performed. Patients with histological features of FSGS were identified. Clinical, laboratorial and pathological data were collected, including treatment and outcome. Patients were classified as having genetic FSGS if they accomplished at least one of the following: a) nephrotic syndrome resistant to corticosteroids; b) non-nephrotic proteinuria or nephrotic syndrome with normal serum albumin; c) non-nephrotic proteinuria or nephrotic syndrome with focal foot process effacement or d) non-nephrotic proteinuria with diffuse foot process effacement. The remaining patients were classified as secondary FSGS (if they presented a disease known to be associated with FSGS) or primary FSGS. Each group was divided according to treatment with corticoid, other immunosuppressive agents or and RAAS blockage. Renal outcomes were assessed (progression to ESKD). Results A total of 359 kidney biopsies were performed between January 2010 to December 2018, 66 with a histological pattern of FSGS. 65% (N=43) were males, 71% (N=47) were Caucasian and 23% (N=15) were black. 74% (N=49) had past medical history of hypertension, 26% (N=17) diabetes mellitus and 5% (N=3) had HIV. The majority of patients were classified as having secondary FSGS (52%, N=34), 23% (N=15) were classified as primary and as 25% (N=17) genetic/idiopathic. From the genetic group 58.8% (N=10) were treated with corticoid, 12% (N=2) with other IS agents and 71% (N=12) with ACE/ARB. 29% (N=5) evolved to ESKD (median time to dialysis 11 IQR 1-30). In the primary FSGS group 40% (N=6) were treated with corticoid, 7% (N=1) with other IS agents and 80% (N=12) with ACE/ARB. 27% (N=4) evolved to ESKD (median time to dialysis 0 months, IQR 0-33). In the genetic group 59% (N=10) were treated with corticoid, 12% (N=2) with other IS agents and 71%(N=12) with ACE/ARB. 29% (N=5) evolved to ESKD (median time to dialysis 11 months, IQR 1-30). Conclusion FSGS is a very prevalent glomerular disease and its correct etiologic classification aids in better treatment choice. Although its etiology is not straightforward in most of the patients, some clinical and histological characteristics aid in FSGS classification.

The liver is primarily responsible for energy homeostasis and the regulation of lipid, carbohydrate and protein metabolism. Lipid metabolism consists of distributing lipids to peripheral tissues or ensuring their return to the liver to be reprocessed. Additionally, cellular metabolism is regulated by several molecules in different signaling pathways. Lipid homeostasis in the liver is mainly regulated by AKT, AMPK, SREBP, PPAR, and JNK. The PI3K/AKT/mTOR signaling pathway results in the biosynthesis of macromolecules and regulates lipogenesis and the expression of lipogenic genes. AMPK is an energy sensor that regulates metabolism and is activated when stored ATP is depleted, and it is responsible for the suppression of several key lipogenic factors in the liver related to cholesterol and fatty acid synthesis. SREBPs control lipogenic gene expression and cholesterol metabolism and act in the nutritional regulation of fatty acids and triglycerides. The continued activation of SREBPs is associated with cellular stress, inflammation and ultimately steatosis. PPARs are intrinsically important regulators of lipid metabolism. These genes are essential to various metabolic processes, especially lipid and glucose homeostasis, and can play a role in cell differentiation. JNK signaling is related to insulin resistance and its activation results in decreased mitochondrial activity and fat accumulation. Therefore, the study of cell signaling pathways related to lipid metabolism and liver function may help to identify abnormalities and develop strategies to manage and regulate metabolic disorders and resulting complications. The liver is primarily responsible for energy homeostasis and the regulation of lipid, carbohydrate and protein metabolism. Lipid metabolism consists of distributing lipids to peripheral tissues or ensuring their return to the liver to be reprocessed. Additionally, cellular metabolism is regulated by several molecules in different signaling pathways. Lipid homeostasis in the liver is mainly regulated by AKT, AMPK, SREBP, PPAR, and JNK. The PI3K/AKT/mTOR signaling pathway results in the biosynthesis of macromolecules and regulates lipogenesis and the expression of lipogenic genes. AMPK is an energy sensor that regulates metabolism and is activated when stored ATP is depleted, and it is responsible for the suppression of several key lipogenic factors in the liver related to cholesterol and fatty acid synthesis. SREBPs control lipogenic gene expression and cholesterol metabolism and act in the nutritional regulation of fatty acids and triglycerides. The continued activation of SREBPs is associated with cellular stress, inflammation and ultimately steatosis. PPARs are intrinsically important regulators of lipid metabolism. These genes are essential to various metabolic processes, especially lipid and glucose homeostasis, and can play a role in cell differentiation. JNK signaling is related to insulin resistance and its activation results in decreased mitochondrial activity and fat accumulation. Therefore, the study of cell signaling pathways related to lipid metabolism and liver function may help to identify abnormalities and develop strategies to manage and regulate metabolic disorders and resulting complications.

Purpose: The aim of this study is to characterize a Portuguese Intensive Care Unit experience in therapeutic plasma exchange in critically ill patients. Methods: We performed a retrospective analysis of the patients treated with therapeutic plasma exchange between 2000 and 2019. Data on patient characteristics, therapeutic plasma exchange prescription, adjuvant therapy used, adverse events and outcome under treatment were collected. Results: A total of 101 therapeutic plasma exchange procedures in 20 patients were studied. Mean number of therapeutic plasma exchange sessions per patient was 5.1±1.3. The most frequent indications to begin this treatment were myasthenia gravis (25.0%) and anti -neutrophil -cytoplasmic antibody -associated vasculitis (15.0%). There were 45.5% adverse events and the most frequent was hypotension (15.2%). 98% of the complications were mild -to -moderate. The outcome was favorable in 60.0% of patients. Conclusion: Therapeutic plasma exchange is an effective and safe therapy in many diseases that had high morbidity and mortality prior to the use of this technique. info:eu-repo/semantics/publishedVersion

Objective. To describe the development of the bacterial cellulose coating with anti-inflammatory Ibuprofen (BC/ Ibu) and to evaluate the cicatrization process with its use in patients with chronic wounds of venous and diabetic etiology. Methods. Longitudinal descriptive study. The cellulose membrane, cultivated with bacteria Gluconacetobacter xylinus and with incorporation of Ibuprofen, was used in the treatment of patients with chronic wounds in public health services in a Brazilian municipality. The ideal coverage characteristics were evaluated through physical, chemical and cell proliferation tests. Results. The sample consisted of 14 patients (10 women and 4 men), 8 with venous ulcer, 5with diabetic foot and one with mixed wound. There was reduction of area and pain in lesions; total healing of 3 wounds; and debridement of the devitalized tissue in 5 wounds with increased area. The use of the membrane was important in the reduction of pain, exudation and ease in the accomplishment of the curative. Conclusion. BC/Ibu favored the cicatrization process of patients with chronic vasculogenic wounds. How to cite this article : Zanoti MDU, Sonobe HM, Ribeiro SJL, Gaspar AMM. Development of coverage and its evaluation in the treatment of chronic wounds. Invest. Educ. Enferm. 2017; 35(3):330-339.

Mitochondrial diseases (MD) are a group of rare inherited disorders, characterized by phenotypic heterogeneity, with hitherto no effective therapeutic options. The aim of this study was to develop a next generation sequencing (NGS) strategy, by using a custom gene panel and whole mitochondrial genome, to identify the disease causing pathogenic variants in 146 patients suspicious of MD. The molecular analysis of this cohort revealed six novel and 15 described pathogenic variants, as well as 26 variants of unknown significance. Our findings are expanding the mutational landscape of these disorders and support the use of a NGS strategy for a higher diagnostic yield. This work was supported by FCT (PTDC/DTP-PIC/2220/2014) and NORTE2020 (NORTE-01-0246-FEDER-000014). Silvia Vilarinho is supported by the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number K08DK113109. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. info:eu-repo/semantics/publishedVersion

Fatty acid β-oxidation (FAO) disorders have a wide variety of symptoms, not usually evident between episodes of acute decompensations. Cardiac involvement is frequent, and severe ventricular arrhythmias are suspected of causing sudden death. Expanded newborn screening (ENS) for these disorders, hopefully, contribute to prevent potentially acute life-threatening events. In order to characterize acute decompensations observed in FAO-deficient cases identified by ENS, a retrospective analysis was performed, covering a period of 9 years. Demographic data, number/type of acute decompensations, treatment, and follow-up were considered. Eighty-three clinical charts, including 66 medium-chain acyl-CoA dehydrogenase deficiency (MCADD), 5 carnitine-uptake deficiency (CUD), 3 carnitine palmitoyltransferase I and II (CPT I/II) deficiency, 5 very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), and 4 multiple acyl-CoA dehydrogenase deficiency (MADD) cases were reviewed. Nineteen patients had acute decompensations (1 CPT I, 1 CPT II, 3 MADD, 14 MCADD). Six patients developed symptoms previously to ENS diagnosis. Severe clinical manifestations included multiple organ failure, liver failure, heart failure, and sudden death. Long-chain FAO disorders had the highest number of decompensations per patient. Conclusion: Despite earlier diagnosis by ENS, sudden deaths were not avoided and acute decompensations with severe clinical manifestations still occur as well. What is Known: Severe ventricular arrhythmias are suspected to cause unexpected death in FAO disorders; Neonatal screening intends to reduce the incidence of severe metabolic crisis and death. What is New: Acute severe decompensations occurred in FAO disorders diagnosed through neonatal screening; Sudden deaths were not avoided by starting treatment precociously. info:eu-repo/semantics/publishedVersion

Background: Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a congenital rare metabolic disease with broad clinical phenotypes and variable evolution. This inborn error of metabolism is caused by mutations in the ETFA, ETFB or ETFDH genes, which encode for the mitochondrial ETF and ETF:QO proteins. A considerable group of patients has been described to respond positively to riboflavin oral supplementation, which constitutes the prototypic treatment for the pathology. Objectives: To report mutations in ETFA, ETFB and ETFDH genes identified in Portuguese patients, correlating, whenever possible, biochemical and clinical outcomes with the effects of mutations on the structure and stability of the affected proteins, to better understand MADD pathogenesis at the molecular level. Methods: MADD patients were identified based on the characteristic urinary profile of organic acids and/or acylcarnitine profiles in blood spots during newborn screening. Genotypic, clinical and biochemical data were collected for all patients. In silico structural analysis was employed using bioinformatic tools carried out in an ETF:QO molecular model for the identified missense mutations. Results: A survey describing clinical and biochemical features of eight Portuguese MADD patients was made. Genotype analysis identified five ETFDH mutations, including one extension (p.X618QextX*14), two splice mutations (c.34+5G>C and c.405+3A>T) and two missense mutations (ETF:QO-p.Arg155Gly and ETF:QO-p.Pro534Leu), and one ETFB mutation (ETFβ- p.Arg191Cys). Homozygous patients containing the ETFDH mutations p.X618QextX*14, c.34+5G>C and ETF:QO-p.Arg155Gly, all presented severe (lethal) MADD phenotypes. However, when any of these mutations are in heterozygosity with the known ETF:QO-p.Pro534Leu mild variant, the severe clinical effects are partly and temporarily attenuated. Indeed, the latter destabilizes an ETF-interacting loop, with no major functional consequences. However, the position 155 in ETF:QO is localized at the ubiquinone binding and membrane interacting domain, and is thus expected to perturb protein structure and membrane insertion, with severe functional effects. Structural analysis of molecular models is therefore demonstrated to be a valuable tool to rationalize the effects of mutations in the context of the clinical phenotype severity. Conclusion: Advanced molecular diagnosis, structural analysis and clinical correlations reveal that MADD patients harboring a severe prognosis mutation in one allele can actually revert to a milder phenotype by complementation with a milder mutation in the other allele. However, such patients are nevertheless in a precarious metabolic balance which can revert to severe fatal outcomes during catabolic stress or secondary pathology, thus requiring strict clinical follow-up. This work was supported by the Fundação para a Ciência e Tecnologia (FCT/MCTES, Portugal) through fellowships to B.J.H. (SFRH/BPD/74475/2010) and T.G.L. (SFRH/BD/89690/2012) and a grant PTDC/ BBB-BQB/5366/2014 (to B.J.H.) and PTDC/NEUNMC/2138/2014 (to C.M.G.). The Gomes laboratory is partly supported by grant UID/MULTI/04046/2013 from FCT/MCTES/PIDDAC (to BioISI). info:eu-repo/semantics/publishedVersion

Healing is a complex process that involves cellular and biochemical events and several medicines have been used to shorten healing time and avoid aesthetic damage The development of an objective non invasive and in vivo examination method is urgently demanded towards helping the determination of the depth and degree of wound healing This manuscript reports on a comparison of two wound dressings based on bacterial cellulose phytoterapic Calendula officinalis and Jacaranda caroba hydrogel applied to rat dorsum with bacterial cellulose hydrogel and untreated wound The hydrogels were characterized by Scanning Electron Microscopy Thermogravimetric Analysis and Fourier transformed Infrared spectroscopy and the results showed they are biocompatible and easy to attach keep the site moist and do not damage the granulation tissue According to the in vivo test Bacterial Cellulose Calendula officinalis hydrogel promoted a better wound healing and statistically significant differences in the tissue repair between treatments on the rd and th days critical periods after surgery The results of the histological evaluation demonstrated a statistically significant difference for tissue inflammatory reaction between the treatments in the day period A statistically significant difference between the treatments in the evaluation of the quality quantity and orientation of the collagen fibers was verified in the day period The hydrogels especially bacterial cellulose with Calendula officinalis yielded satisfactory results and therefore can contribute to the tissue repair of rat skin wounds

This article presents a dataset proving the simultaneous presence of a 5′UTR-truncated PDHA1 mRNA and a full-length PDHA2 mRNA in the somatic cells of a PDC-deficient female patient and all members of her immediate family (parents and brother). We have designed a large set of primer pairs in order to perform detailed RT-PCR assays allowing the clear identification of both PDHA1 and PDHA2 mRNA species in somatic cells. In addition, two different experimental approaches were used to elucidate the copy number of PDHA1 gene in the patient and her mother. The interpretation and discussion of these data, along with further extensive experiments concerning the origin of this altered gene expression and its potential therapeutic consequences, can be found in “Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: null mutations in the PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells” (A. Pinheiro, M.J. Silva, C. Florindo, et al., 2016). This study was supported in part by grants from Fundação para a Ciência e a Tecnologia, Portugal (FCT): SFRH/BD/31264/2006 awarded to Ana Pinheiro, POCI/SAU-MMO/57052/2004 awarded to Isabel Rivera, and PEst-OE/SAU/UI4013/2013.

Human pyruvate dehydrogenase complex (PDC) catalyzes a key step in the generation of cellular energy and is composed by three catalytic elements (E1, E2, E3), one structural subunit (E3-binding protein), and specific regulatory elements, phosphatases and kinases (PDKs, PDPs). The E1α subunit exists as two isoforms encoded by different genes: PDHA1 located on Xp22.1 and expressed in somatic tissues, and the intronless PDHA2 located on chromosome 4 and only detected in human spermatocytes and spermatids. We report on a young adult female patient who has PDC deficiency associated with a compound heterozygosity in PDHX encoding the E3-binding protein. Additionally, in the patient and in all members of her immediate family, a full-length testis-specific PDHA2 mRNA and a 5′UTR-truncated PDHA1 mRNA were detected in circulating lymphocytes and cultured fibroblasts, being bothmRNAs translated into full-length PDHA2 and PDHA1 proteins, resulting in the co-existence of both PDHA isoforms in somatic cells.Moreover, we observed that DNA hypomethylation of a CpG island in the coding region of PDHA2 gene is associatedwith the somatic activation of this gene transcription in these individuals. This study represents the first natural model of the de-repression of the testis-specific PDHA2 gene in human somatic cells, and raises some questions related to the somatic activation of this gene as a potential therapeutic approach for most forms of PDC deficiency. This study was supported in part by grants from the Fundação para a Ciência e a Tecnologia (FCT), Portugal: SFRH/BD/31264/2006 awarded to Ana Pinheiro, POCI/SAU-MMO/57052/2004 awarded to Isabel Rivera, and PEst-OE/SAU/UI4013/2013.

Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that recognize lipid antigens presented on CD1d molecules at the surface of antigen-presenting cells. GM2 is a glycosphingolipid abundant in cellular membranes and known to bind CD1d molecules, but the functional consequences of this binding are not completely clarified. Herein, we analyzed the effect of GM2 in iNKT cell activation. We found that culturing antigen-presenting cells or total peripheral blood mononuclear cells with GM2 did not induce activation of human iNKT cells, implying that this lipid is not antigenic for human iNKT cells. To investigate if this lipid could inhibit iNKT cell activation, we simultaneously incubated antigen-presenting cells with GM2 and the iNKT cell antigen α-Galactosylceramide (α-GalCer) and used them to stimulate iNKT cells. We found that GM2 reduced human iNKT cell activation in a dose-dependent manner. An explanation for this effect could be a direct competition of GM2 with antigenic lipids for CD1d binding. This was demonstrated by the use of an antibody (L363) that stains mouse CD1d:α-GalCer complexes, as in the presence of GM2 the amount of CD1d:α-GalCer complexes are reduced. We further explored the consequences of chronic GM2 overload on human iNKT cells by analyzing iNKT cells in patients diagnosed with GM2 gangliosidoses. We found that pediatric patients present a higher frequency of circulating CD4+ iNKT cells and concomitant lower frequency of CD4−CD8− iNKTs. A lower percentage of iNKT cells expressing the NK marker CD161 was also observed in these patients. In contrast, in two adult patients studied, no differences on iNKT cell phenotype were observed. Altogether, this study uncovers a new role for GM2 in the modulation of iNKT cell activation, thus strengthening the central role of lipid metabolism in iNKT cell biology.

Made available in DSpace on 2018-12-11T17:36:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-03-14 Barrier membranes for guided bone regeneration (GBR) mainly promote mechanical maintenance of bone defect space and induce osteopromotion. Additionally, biopolymer-based membranes may provide greater bioactivity and biocompatibility due to their similarity to extracellular matrix (ECM). In this study, biopolymers-based membranes from bacterial cellulose (BC) and collagen (COL) associated with osteogenic growth peptide (OGP(10-14)) were evaluated to determine in vitro osteoinductive potential in early osteogenesis; moreover, histological study was performed to evaluate the BC-COL OGP(10-14) membranes on bone healing after GBR in noncritical defects in rat femur. The results showed that the BC-COL and BC-COL OGP(10-14) membranes promoted cell proliferation and alkaline phosphatase activity in osteoblastic cell cultures. However, ECM mineralization was similar between cultures grown on BC OGP(10-14) and BC-COL OGP(10-14) membranes. In vivo results showed that all the membranes tested, including the peptide-free BC membrane, promoted better bone regeneration than control group. Furthermore, the BC-COL OGP(10-14) membranes induced higher radiographic density in the repaired bone than the other groups at 1, 4 and 16 weeks. Histomorphometric analyses revealed that the BC-COL OGP(10-14) induced higher percentage of bone tissue in the repaired area at 2 and 4 weeks than others membranes. In general, these biopolymer-based membranes might be potential candidates for bone regeneration applications. São Paulo State University UNESP Institute of Chemistry São Paulo State University UNESP School of Dentistry Alfenas Federal University UNIFAL-MG School of Dentistry Faculty of Dentistry of Ribeirão Preto University of São Paulo - USP São Paulo State University UNESP Institute of Chemistry São Paulo State University UNESP School of Dentistry

Made available in DSpace on 2018-12-11T16:52:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-02-08 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Calcium phosphate cement has been widely investigated as a bone graft substitute due to its excellent self-setting ability, biocompatibility, osteoconductivity and moldability. In addition, mesoporous materials have been studied as potential materials for application in medical devices due to their large surface area, which is capable of loading numerous biological molecules, besides being bioactive. In this study, bone β-TCP-MCPM-based injectable cement with mesoporous silica particles was synthesized and characterized in terms of its mechanical properties, microstructure, porosity, injectability, in vitro bioactivity and degradability; together with toxicity effects in CHO-K1 cell culture. The results showed that the β-TCP-MCPM cement is bioactive after soaking in simulated body fluid solution, and mesoporous silica particles provided better physicochemical properties compared with silica-free cement. Toxicity assays showed low CHO-K1 cell viability after treatment with more concentrated extracts (200 mg ml-1). However, this behavior did not compromise the reproductive capacity and did not promote significant DNA damage in those cells. In conclusion, the β-TCP-MCPM cement associated with mesoporous silica might be considered as a potential bone substitute for the repair and regeneration of bone defects. São Paulo State University (Unesp) Institute of Chemistry São Paulo State University (Unesp) School of Dentistry Azurebio S.L. Instituto de Cerámica y Vidrio CSIC São Paulo State University (Unesp) Institute of Chemistry São Paulo State University (Unesp) School of Dentistry FAPESP: 2012/21735-6

Made available in DSpace on 2018-12-11T17:32:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-10-01 Despite advances in the field of biomaterials for bone repair/regeneration, some challenges for developing an ideal bone substitute need to be overcome. Herein, this study synthesized and evaluated in vitro a nanocomposite based on bacterial cellulose (BC), collagen (COL), apatite (Ap) and osteogenic growth peptide (OGP) or its C-terminal pentapeptide [OGP(10-14)] for bone regeneration purposes. The BC-COL nanocomposites were successfully obtained by carbodiimide-mediated coupling as demonstrated by spectroscopy analysis. SEM, FTIR and 31P NMR analyses revealed that in situ synthesis to apatite was an effective route for obtaining of bone-like apatite. The OGP-containing (BC-COL)-Ap stimulated the early development of the osteoblastic phenotype. Additionally, the association among collagen, apatite, and OGP peptides enhanced cell growth compared with OGP-containing BC-Ap. Furthermore, none of the nanocomposites showed cytotoxic, genotoxic or mutagenic effects. These promising results suggest that the (BC-COL)-Ap associated with OGP peptides might be considered a potential candidate for bone tissue engineering applications. São Paulo State University UNESP Institute of Chemistry Cell Culture Laboratory Faculty of Dentistry of Ribeirão Preto University of São Paulo USP São Paulo State University UNESP School of Dentistry at Araraquara Department of Genetics Faculty of Medicine of Ribeirão Preto University of São Paulo USP São Paulo State University UNESP Institute of Chemistry São Paulo State University UNESP School of Dentistry at Araraquara

Work supported by centregrant (toBioISI, Centre Reference: UID/MULTI/04046/2013), from FCT/MCTES/PIDDAC, Portugal

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid β-oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions-c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)-were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.

Classic galactosemia is an autosomal recessive disorder caused by deficient galactose-1-phosphate uridylyltransferase (GALT) activity. Patients develop symptoms in the neonatal period, which can be ameliorated by dietary restriction of galactose. Many patients develop long-term complications, with a broad range of clinical symptoms whose pathophysiology is poorly understood. The high allelic heterogeneity of GALT gene that characterizes this disorder is thought to play a determinant role in biochemical and clinical phenotypes. We aimed to characterize the mutational spectrum of GALT deficiency in Portugal and to assess potential genotype-phenotype correlations. Direct sequencing of the GALT gene and in silico analyses were employed to evaluate the impact of uncharacterized mutations upon GALT functionality. Molecular characterization of 42 galactosemic Portuguese patients revealed a mutational spectrum comprising 14 nucleotide substitutions: ten missense, two nonsense and two putative splicing mutations. Sixteen different genotypic combinations were detected, half of the patients being p.Q188R homozygotes. Notably, the second most frequent variation is a splicing mutation. In silico predictions complemented by a close-up on the mutations in the protein structure suggest that uncharacterized missense mutations have cumulative point effects on protein stability, oligomeric state, or substrate binding. One splicing mutation is predicted to cause an alternative splicing event. This study reinforces the difficulty in establishing a genotype-phenotype correlation in classic galactosemia, a monogenic disease whose complex pathogenesis and clinical features emphasize the need to expand the knowledge on this "cloudy" disorder.

Two types of polymer matrix composites were designed to use as bone replacement: PMMA+HA and PMMA+45S5® Blown Fibers. The materials were tested in vivo for 60 days and compared to two control groups: empty bone defect and porous PMMA. The histology results suggest that both materials provide a suitable scaffold for bone growth with the presence of newly formed bone tissue, blood vessels, osteocytes and osteoblasts cells. For a better understanding of the mechanical properties of scaffolds to bear physiological loads when implanted, compressive tests were carried out. The results showed difference in the compressive behaviour of the two composites, PMMA+HA specimens achieved higher values approaching 9.0 MPa of ultimate strength while PMMA+45S5® had values close to 8.0MPa. Both materials are suitable to bone replacement of small size areas.

Made available in DSpace on 2018-12-11T17:23:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-01-01. Added 1 bitstream(s) on 2019-10-09T18:32:00Z : No. of bitstreams: 1 S1516-14392016000100106.pdf: 4613088 bytes, checksum: 245d5ddc48747bc149d91e95ddbf0aee (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) This study compares a wound dressing based on bacterial cellulose/collagen (BC/COL) hydrogel in rat dorsum with commercial collagenase ointment and untreated wound. The hydrogel was characterized by Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA), Fourier transformed-Infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). According to the In vivo test and macroscopic evaluation, BC/COL hydrogel showed a better repair of wounds and promoted statistically significant differences of tissue repair between treatments on the 7th day after surgery. Better quality, quantity and orientation evaluation of collagen fibers (p=0.0001) were observed in the BC/COL hydrogel and collagenase ointment groups in relation to the control group. The BC/COL hydrogel promoted better wound healing than collagenase and the control group, therefore, it can be considered a potential wound dressing for skin regeneration. Programa de Pos Graduacao Interunidades Bioengenharia-EESC/FMRP/IQSC-USP, Av. Trabalhador Sao-carlense, 400 Laboratorio de Morfologia Universidade Estadual Paulista-UNESP, Rua Humaita, 1680 Instituto de Quimica Universidade Estadual Paulista-UNESP, Rua Prof. Francisco Degni, 55 Laboratorio de Biopolimeros e Biomateriais (BioPolMat) Centro Universitario de Araraquara-UNIARA, Rua Voluntarios da Patria, 1309 Instituto de Quimica de Sao Carlos/USP, Av. Trabalhador Sao-carlense, 400 Laboratorio de Morfologia Universidade Estadual Paulista-UNESP, Rua Humaita, 1680 Instituto de Quimica Universidade Estadual Paulista-UNESP, Rua Prof. Francisco Degni, 55

The aim of this study was to characterize the physicochemical properties of bacterial cellulose (BC) membranes functionalized with osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP[10-14], and to evaluate in vitro osteoinductive potential in early osteogenesis, besides, to evaluate cytotoxic, genotoxic and/or mutagenic effects. Peptide incorporation into the BC membranes did not change the morphology of BC nanofibers and BC crystallinity pattern. The characterization was complemented by Raman scattering, swelling ratio and mechanical tests. In vitro assays demonstrated no cytotoxic, genotoxic or mutagenic effects for any of the studied BC membranes. Culture with osteogenic cells revealed no difference in cell morphology among all the membranes tested. Cell viability/proliferation, total protein content, alkaline phosphatase activity and mineralization assays indicated that BC-OGP membranes enabled the highest development of the osteoblastic phenotype in vitro. In conclusion, the negative results of cytotoxicity, genotoxicity and mutagenicity indicated that all the membranes can be employed for medical supplies, mainly in bone tissue engineering/regeneration, due to their osteoinductive properties.

Hyperphenylalaninemia (HPA, OMIM #261600), which includes phenylketonuria (PKU), is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH), being already described more than 600 different mutations. Genotype-phenotype correlation is a useful tool to predict the metabolic phenotype, to establish the better tailored diet and, more recently, to assess the potential responsiveness to BH(4) therapy, a current theme on PKU field. The aim of this study was the molecular analysis of the PAH gene, evaluation of genotype-phenotype relationships and prediction of BH(4)-responsiveness in the HPA population living in South Portugal. We performed the molecular characterization of 83 HPA patients using genomic DNA extracted from peripheral blood samples or Guthrie cards. PAH mutations were scanned by PCR amplification of exons and related intronic boundaries, followed by direct sequence analysis. Intragenic polymorphisms were determined by PCR-RFLP analysis. The results allowed the full characterization of 67 patients. The mutational spectrum encompasses 34 distinct mutations, being the most frequent IVS10nt-11G>A (14.6%), V388M (10.8%), R261Q (8.2%) and R270K (7.6%), which account for 46% of all mutant alleles. Moreover, 12 different haplotypes were identified and most mutations were associated with a single one. Notably, more than half of the 34 mutations belong to the group of more than 70 mutations already identified in BH(4)-responsive patients, according to BIOPKU database. Fifty one different genotypic combinations were found, most of them in single patients and involving a BH(4)-responsive mutation. In conclusion, a significant number (30-35%) of South Portugal PKU patients may potentially benefit from BH(4) therapy which, combined with a less strict diet, or eventually in special cases as monotherapy, may contribute to reduce nutritional deficiencies and minimize neurological and psychological dysfunctions.

Bioceramics with different Ca/P ratio were prepared from a mechanical mixture of NaPO3, CaCO3, Ca(OH)2 and phosphate buffer solution and implanted in rats subcutaneous tissues. The cements were characterized by Thermogravimetric analysis (TG-TDA), X-ray diffraction and 31P-NMR. The implant sites were excised after 1, 4 and 16 weeks, fixed, dehydrated, included in paraffin wax for serial cutting and examined under the light transmitted microscope. They were biocompatible and biodegradable when implanted in rat subcutaneous. None of the materials induced ectopic osteogenesis. According to the results, the studied materials seem to be able for manufacturing reabsorbable bone implants.

The biological response following subcutaneous and bone implantation of β-wollastonite(β-W)-doped α-tricalcium phosphate bioceramics in rats was evaluated. Tested materials were: tricalcium phosphate (TCP), consisting of a mixture of α- and β-polymorphs; TCP doped with 5 wt. % of β-W (TCP5W), composed of α-TCP as only crystalline phase; and TCP doped with 15 wt. % of β-W (TCP15), containing crystalline α-TCP and β-W. Cylinders of 2x1 mm were implanted in tibiae and backs of adult male Rattus norvegicus, Holtzman rats. After 7, 30 and 120 days, animals were sacrificed and the tissue blocks containing the implants were excised, fixed and processed for histological examination. TCP, TCP5W and TCP15W implants were biocompatible but neither bioactive nor biodegradable in rat subcutaneous tissue. They were not osteoinductive in connective tissue either. However, in rat bone tissue β-W-doped α-TCP implants (TCP5W and TCP15W) were bioactive, biodegradable and osteoconductive. The rates of biodegradation and new bone formation observed for TCP5W and TCP15W implants in rat bone tissue were greater than for non-doped TCP.

Although bone autografts have been routinely used as “gold standard” for reconstruction/ replacement bone defects, because they have osteogenic, osteoinductive, osteoconductive properties, they have a high number of viable cells and are rich in growth factors. However, the use of autograft is limited by several factors, being one of them the insufficient amount of donor tissue. Therefore, bone substitute materials have been extensively studied in order to develop an ideal material for substitution of bone grafts, due to some disadvantages presented by autografts, allografts and xenografts, such as poor bone quality, an inadequate amount of bone and possible immunogenicity for allografts and xenografts, which limit the use of these grafts in specific surgical protocols. These disadvantages have led tissue engineering and biotechnology to develop new materials and promising methods for tissue repair, especially for bone tissue. Thus, bone substitutes, synthetic and/or biotechnologically processed have become potential materials for clinical applications in different areas of health.

Made available in DSpace on 2014-12-03T13:10:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-05-01Bitstream added on 2014-12-03T13:22:59Z : No. of bitstreams: 1 S1516-14392014000300015.pdf: 6453399 bytes, checksum: 356005a6eacb7c7f63967a22803dedeb (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) This study presents an innovative and original biomaterial designed to substitute for articular cartilage and mimic its mechanical behavior, including elastic cushioning and the characteristics of fiber-reinforced gel. The material was composed of polyurethane and bioglass microfiber 45S5. It was designed to present a tribological surface to the cartilage of the tibial plateau, and to convert over a functional gradient to an osteointegrable region for self-anchorage to the subchondral bone. The biomaterial samples showed no toxicity and promoted cell spreading. Subsequent in vivo studies in rabbits demonstrated the formation of a rigid structure similar to bone trabeculae in the distal region of the tribological surface of the implant. The tribological surface of the proximal region showed a fibrocartilaginous tissue with highly vascularized chondrocytes, thus validating the proposed concept for the design of the implant incorporating a functional gradient and auto-stability. Univ Sao Paulo, Dept Mech Engn, BR-13566590 Sao Carlos, SP, Brazil Univ ABC, Ctr Nat Sci & Humanities, BR-09210971 Santo Andre, SP, Brazil Univ Sao Paulo, Bioengn Interunits, BR-13566590 Sao Carlos, SP, Brazil Fed Univ Sao Carlos UFSCar, BR-13565905 Sao Carlos, SP, Brazil Univ Estadual Paulista Julio de Mesquita, UNESP, Lab Morfol, BR-14801903 Sao Paulo, Brazil Univ Estadual Paulista Julio de Mesquita, UNESP, Lab Morfol, BR-14801903 Sao Paulo, Brazil CAPES: PE 0652008481500/2007-3

Made available in DSpace on 2015-05-15T13:30:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2014Bitstream added on 2015-05-15T13:56:27Z : No. of bitstreams: 1 ISSN2347-212X-2014-02-01-001-008.pdf: 197916 bytes, checksum: f299ba30a47550ea8b7feb4002c2e44a (MD5) Made available in DSpace on 2015-05-15T13:30:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2014Bitstream added on 2015-05-15T13:56:27Z : No. of bitstreams: 1 ISSN2347-212X-2014-02-01-001-008.pdf: 197916 bytes, checksum: f299ba30a47550ea8b7feb4002c2e44a (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Bacterial cellulose membranes functionalized with hydroxyapatite or collagen with addition or not of osteogenic growth peptides (OGP) or its C-terminal pentapeptide OGP[10-14] were developed for improving bone repair. The aim of this study was to evaluate the potential cytotoxic, genotoxic and mutagenic effects of those nanocomposites in order to know whether they would be safe for biomedical applications. All nanocomposites (BC, BC-HA, BC-Col, BC-HA OGP, BC-Col-OGP, BC-HA OGP[10-14] and BC-Col-OGP[10-14]) were prepared as discs (5 mm in diameter) and submitted to in vitro tests in 24-well plates seeded with CHO-K1 cells. Cell viability was evaluated by the XTT assay and reproductive cell death was detected by the clonogenic assay. Genotoxicity was assessed by the comet assay and the cytokinesis-blocked micronucleus (CBMN) assay was used to detect mutagenicity. Only BC-HA OGP[10-14] showed a slight mutagenic effect, all other nanocomposites materials demonstrated no cytotoxic, genotoxic or mutagenic effects. In conclusion, the BC-HA OGP [10-14] promoted a slight mutagenic effect and future studies must be investigated for better understanding this result. The utilization of the investigated materials is promising for biomedical applications, such as bone repair and tissue engineering. Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Morfologia, Faculdade de Odontologia de Araraquara, Araraquara, Rua Humaitá, 1680, Centro, CEP 14801-903, SP, Brasil Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Morfologia, Faculdade de Odontologia de Araraquara, Araraquara, Rua Humaitá, 1680, Centro, CEP 14801-903, SP, Brasil School of Dentistry at Araraquara, São Paulo State University, UNESP, Department of Morphology. Rua Humaitá, 1680, Araraquara- SP, Brazil. Institute of Chemistry, São Paulo State University, UNESP. Rua Francisco Degni- Araraquara- SP, Brazil. Faculty of Medicine of Ribeirão Preto, São Paulo University, USP, Department of Genetic. Bloco G. Av. Bandeirantes, 3900, Ribeirão Preto, SP, Brazil. Faculty of Phylosophy, Sciences and Lyrics, São Paulo University, USP, Department of Biology. Av. Bandeirantes, 3900, Ribeirão Preto, SP, Brazil. University of Franca, UNIFRAN. Avenida Dr.Armando Salles Oliveira- Franca-SP, Brazil. FAPESP: 2008/58776-6 FAPESP: 2011/11810-8

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:29:58Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:48:41Z : No. of bitstreams: 1 2-s2.0-84880178217.pdf: 3560711 bytes, checksum: dab40a1a9ffafeed386100599fb00807 (MD5) Made available in DSpace on 2014-05-27T11:29:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-19 Among remarkable discoveries concerning propolis, such as antifungal, antiviral, and antioxidant activities, its anti-inflammatory, and mainly its antibacterial, properties deserve special attention when skin wound healing is concerned. Based on this and knowing the distinctive performance of bacterial (BC) membranes on wound healing, in this work it is proposed to demonstrate the potent antimicrobial activity and wound healing properties of a novel propolis containing biocellulose membrane. The obtained propolis/BC membrane was able to adsorb propolis not only on the surface, but also in its interstices demonstrated by scanning electron microscopy, X-ray diffraction, Fourier transform infrared (FT-IR) spectroscopy, and thermogravidimetric assays. Additionally, the polyphenolic compounds determination and the prominent antibacterial activity in the membrane are demonstrated to be dose dependent, supporting the possibility of obtaining propolis/BC membranes at the desired concentrations, taking into consideration its application and its skin residence time. Finally, it could be suggested that propolis/BC membrane may favor tissue repair in less time and more effectively in contaminated wounds. © 2013 Hernane da Silva Barud et al. Instituto de Química Universidade Estadual Paulista (UNESP), CP 355, 14800-900 Araraquara, SP Faculdade de Odontologia Universidade Estadual Paulista (UNESP), Rua Humaitá 1680, 14801-903 Araraquara, SP Laboratório de Pesquisa Desenvolvimento e Inovação (P, D and I) Apis Flora Industrial e Comercial Ltda, Rua Triunfo 945, 14020-670 Ribeirão Preto, SP Departamento de Ciências Farmacêuticas Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP Instituto de Química Universidade Estadual Paulista (UNESP), CP 355, 14800-900 Araraquara, SP Faculdade de Odontologia Universidade Estadual Paulista (UNESP), Rua Humaitá 1680, 14801-903 Araraquara, SP

Made available in DSpace on 2015-05-15T13:30:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2011 Diante da alta prevalência dos traumas buco-dentários na dentição decídua e das possíveis alterações que estas injúrias podem causar aos dentes permanentes em desenvolvimento, o diagnóstico precoce das sequelas e o estabelecimento de um plano de tratamento adequado são de extrema importância para que se possam minimizar os problemas decorrentes. As sequelas podem limitar-se à porção coronária (descolorações no esmalte associado ou não à hipoplasia, dilaceração da coroa), à porção radicular (dilaceração da raiz, duplicação ou paralisação da formação radicular), ou ao dente por completo (odontoma, sequestro do germe dentário, ou distúrbios de erupção). Portanto, este trabalho objetivou realizar uma revisão sobre os distúrbios de desenvolvimento da dentição permanente após injúria nos predecessores decíduos; apresentando alguns casos clínicos exemplificando algumas das alterações descritas para futuras orientações aos cirurgiões-dentistas, seus pacientes e responsáveis sobre os danos que os germes dos dentes em desenvolvimento possam vir a sofrer. In regarding to the high prevalence of traumatic dental injuries in primary teeth and the possible disturbances on developing permanent successor germs, an early diagnosis and an adequate establishment of treatment planning are very important to minimize the damage caused by the trauma. Sequelaes can affect the coronal portion (white or yellow-brown discoloration associated or not with enamel hipoplasia, dilacerations of the crown), the root portion (dilaceration, duplication or cessation of root formation) or the whole successor permanent tooth (odontoma sequestration or disturbances of permanent successor eruption). The aim of this study is to make a literature review of the developmental disturbances of permanent teeth followed by traumatic injuries to theirs primary predecessors and to present cases reports to advise the dentists, their patients and parents about the damage that developing permanents teeth can undergo. Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Morfologia, Faculdade de Odontologia de Araraquara, Araraquara, Rua Humaitá, 1680, Centro, CEP 14801-903, SP, Brasil Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Morfologia, Faculdade de Odontologia de Araraquara, Araraquara, Rua Humaitá, 1680, Centro, CEP 14801-903, SP, Brasil

Made available in DSpace on 2015-05-15T13:30:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2010Bitstream added on 2015-05-15T13:56:27Z : No. of bitstreams: 1 ISSN0103-6971-2010-58-04-451-455.pdf: 1605758 bytes, checksum: ef9da60c8e85f2860a3f4791b91c6ef7 (MD5) Made available in DSpace on 2015-05-15T13:30:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2010Bitstream added on 2015-05-15T13:56:27Z : No. of bitstreams: 1 ISSN0103-6971-2010-58-04-451-455.pdf: 1605758 bytes, checksum: ef9da60c8e85f2860a3f4791b91c6ef7 (MD5) Objetivo: Verificar as implicações do uso do piercing lingual em indivíduos da cidade de Araraquara, São Paulo. Métodos: O município de Araraquara, São Paulo possui cinco estabelecimentos para colocação de piercing, dos quais apenas dois autorizaram a realização da pesquisa e permitiram acesso a listagem dos usuários de piercing lingual. Os usuários foram contatados pelo telefone. Ao final do estudo a amostra esteve composta por 100 indivíduos de ambos os sexos, maiores de 18 anos, que fazem ou fizeram uso do piercing lingual. Para levantamento das informações utilizou-se um formulário, com seis questões objetivas. Os dados obtidos foram analisados por meio de estatística descritiva. Resultados: Dos participantes, 77 indivíduos usavam piercing lingual há mais de seis meses. O tempo de cicatrização após a colocação do adereço foi abaixo de quatro meses, sendo que, 68 pessoas utilizaram enxaguatórios bucais e 19, além deste, utilizaram analgésicos. Apenas 11 pessoas não apresentaram sintomas após as primeiras semanas decorrentes da colocação do piercing e 56 indivíduos relataram complicações como aumento da salivação, dificuldade na fala, fraturas dentárias, traumas na gengiva ou mucosa e dificuldades na alimentação. Conclusão: Frente às implicações apresentadas pelo uso do piercing lingual justifica-se o despendimento de esforços na orientação de jovens frente à opção de utilização de piercing na cavidade oral. Objective: Investigated the consequences of tongue piercing in individuals from the city of Araraquara, São Paulo, Brazil. Methods: In Araraquara there are five piercing shops, but only two agreed to help the research by providing the contact information of customers who had had their tongues pierced. These customers were contacted by telephone. By the end of the research, the sample consisted of 100 individuals from both genders aged 18 years or more. Not all of them still had their tongue piercing. A form with six objective questions was used to collect information. The information was then analyzed by descriptive statistics. Results: From the 100 participants, 77 had been using tongue piercing for more than 6 months. It took less than 4 months for the tongue to heal. Sixty–eight individuals used oral rinses and of these, 19 also used painkillers. Only 11 individuals did not present symptoms after the first weeks using the piercing. On the other hand, 56 individuals reported complications such as increased salivation, speaking difficulties, gingival or mucosal traumas, dental fractures and eating difficulties. Conclusion: All these tongue-piercing complications justify efforts to inform the youth about the use of piercing in the oral cavity. Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Morfologia, Faculdade de Odontologia de Araraquara, Araraquara, Rua Humaitá, 1680, Centro, CEP 14801-903, SP, Brasil Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Morfologia, Faculdade de Odontologia de Araraquara, Araraquara, Rua Humaitá, 1680, Centro, CEP 14801-903, SP, Brasil

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:02:32Z No. of bitstreams: 1 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) Made available in DSpace on 2013-08-22T19:02:32Z (GMT). No. of bitstreams: 1 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) Previous issue date: 2009-12-01 Made available in DSpace on 2013-09-30T18:32:11Z (GMT). No. of bitstreams: 2 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) S0365-05962009000600003.pdf.txt: 36608 bytes, checksum: 4430e16408525d140119682da155aa18 (MD5) Previous issue date: 2009-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:45:37Z No. of bitstreams: 2 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) S0365-05962009000600003.pdf.txt: 36608 bytes, checksum: 4430e16408525d140119682da155aa18 (MD5) Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:45:37Z No. of bitstreams: 2 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) S0365-05962009000600003.pdf.txt: 36608 bytes, checksum: 4430e16408525d140119682da155aa18 (MD5) Made available in DSpace on 2014-05-20T13:45:37Z (GMT). No. of bitstreams: 2 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) S0365-05962009000600003.pdf.txt: 36608 bytes, checksum: 4430e16408525d140119682da155aa18 (MD5) Previous issue date: 2009-12-01 Made available in DSpace on 2014-05-20T13:45:37Z (GMT). No. of bitstreams: 2 S0365-05962009000600003.pdf: 391380 bytes, checksum: 28257a58f040143dbfd9ba20ebefdc54 (MD5) S0365-05962009000600003.pdf.txt: 36608 bytes, checksum: 4430e16408525d140119682da155aa18 (MD5) Previous issue date: 2009-12-01 FUNDAMENTOS - Adesivos teciduais têm sido muito usados para síntese de ferida, em função de ser um método indolor, rápido e de fácil execução. OBJETIVOS -Analisar e comparar compatibilidade dos adesivos, etil- cianoacrilato (Super Bonder) e butilcianoacrilato (Histoacryl), e a reparação de incisões em dorso de ratos entre o fio de sutura e os respectivos adesivos. MÉTODOS - Foram usados 15 ratos. Realizaram-se duas lojas cirúrgicas no dorso. em cada uma, foi implantado um tubo de polietileno (10mm x 1mm), os quais foram preenchidos com os adesivos Super Bonder (lado direito) e Histoacryl (lado esquerdo). As incisões, do lado esquerdo, foram coaptadas com Super Bonder, e as do lado direito, com Histoacryl. Uma incisão mediana, entre as duas incisões,foi realizada e suturada com fio de seda. Os animais foram mortos, depois de 7(sete), 35(trinta) e 120 (cento e vinte dia) dias. RESULTADOS: Os adesivos usados, no presente estudo, não promoveram reação inflamatória, quando usados para síntese das incisões. Porém, estes adesivos, quando implantados no subcutâneo, promoveram reação inflamatória até 120 (cento e vinte dia) dias, no entanto, a reação é mais intensa com Histoacryl. CONCLUSÕES: Super Bonder e Histoacryl permitem o processo cicatricial dos tecidos incisados; facilitam a sutura das incisões. Desta forma, estes podem ser utilizados para sínteses de feridas, lacerações ou incisões cutâneas. BACKGROUND: Tissue adhesives have been used for the synthesis of wound due to their painless application and quick and easy handling. OBJECTIVES: The purpose of this study was to analyze and compare the compatibility of the adhesives ethylcyanoacrylate (Super Bonder) and butyl-cyanoacrylate (Histoacryl), and to compare the reparation of incisions in the dorsum of rats with suture and the respective adhesives. METHODS: Fifteen rats were used. Two surgical pockets were created in their dorsum. A polyethylene tube (10mm x 1mm) was implanted in each one. Each tube was filled with the adhesives Super Bonder(left side) and Histoacryl (right side). The incisions on the left side were closed with Super Bonder, and the incisions on the right side, with Histoacryl. A median incision between the two other incisions was made and closed with braided silk suture. The animals were killed after, 7, 35 and 120 days. RESULTS: The adhesives used in the present study did not promote inflammatory reaction when used for the synthesis of incisions. However, when implanted subcutaneously, they caused an inflammatory reaction within 120 days. Reaction is more severe with Histoacryl. CONCLUSIONS: Super Bonder and Histoacryl can be used effectively in the healing of incised tissues; they aid in the suture of incisions. However, these adhesives can be used for the synthesis of wounds, lacerations or cutaneous incisions. Universidade Estadual Paulista Instituto de Química de Araraquara Universidade Estadual Paulista Faculdade de Odontologia de Araraquara Departamento de Morfologia Universidade Estadual Paulista Faculdade de Odontologia de Araraquara Departamento de Diagnóstico e Cirurgia Universidade Estadual Paulista Instituto de Química de Araraquara Universidade Estadual Paulista Faculdade de Odontologia de Araraquara Departamento de Morfologia Universidade Estadual Paulista Faculdade de Odontologia de Araraquara Departamento de Diagnóstico e Cirurgia

Tissue adhesives have been used for the synthesis of wound due to their painless application and quick and easy handling.The purpose of this study was to analyze and compare the compatibility of the adhesives ethylcyanoacrylate (Super Bonder) and butyl-cyanoacrylate (Histoacryl), and to compare the reparation of incisions in the dorsum of rats with suture and the respective adhesives.Fifteen rats were used. Two surgical pockets were created in their dorsum. A polyethylene tube (10mm x 1mm) was implanted in each one. Each tube was filled with the adhesives Super Bonder(left side) and Histoacryl (right side). The incisions on the left side were closed with Super Bonder, and the incisions on the right side, with Histoacryl. A median incision between the two other incisions was made and closed with braided silk suture. The animals were killed after, 7, 35 and 120 days.The adhesives used in the present study did not promote inflammatory reaction when used for the synthesis of incisions. However, when implanted subcutaneously, they caused an inflammatory reaction within 120 days. Reaction is more severe with Histoacryl.Super Bonder and Histoacryl can be used effectively in the healing of incised tissues; they aid in the suture of incisions. However, these adhesives can be used for the synthesis of wounds, lacerations or cutaneous incisions.

Gelfoam® - a biologically resorbable gelatin sponge - has the function of restricting hemorrhage, providing platelet rupture, and supporting fibrin threads. Beriplast® - a fibrinogen-thrombin compound - is used to adhere tissues, to consolidate sutures and in hemostasis. The objective of this study was to perform a histological analysis of the effects of haemostatic agents on osseous repair. These materials were inserted into surgical sites in young rat right and left tibiae. After the observation periods of 7, 14, 30 and 45 days, according to the bioethic protocol, the animals were killed, the tibiae were removed and fixed in 10% formalin and decalcified in equal parts of formic acid and sodium citrate solutions. After routine processing, the specimens were embedded in paraffin for microtomy. Analysis of the results demonstrated that the haemostatic agents are effective in controlling hemorrhage; they stimulate osteogenesis, featuring a pattern of osseous tissue formation similar to the control pattern, although the amount of osseous trabeculae was superior, especially in the Gelfoam group in the periods of 7 and 14 days; 30 days after surgery, the delay in tissue healing in the control group in relation to the experimental groups started to decrease, and the control and experimental groups exhibited similar tissue repair after 45 days, when all the groups exhibited secondary osseous tissue. Gelfoam® - uma esponja de gelatina biologicamente reabsorvível - tem por função coibir as hemorragias, promover o rompimento de plaquetas e sustentar a rede de fibrina. Beriplast P® - um composto de fibrinogênio-trombina - é usado na adesão de tecidos, consolidação de suturas e hemostasia. O objetivo deste estudo foi verificar histologicamente os efeitos de agentes hemostáticos na reparação óssea, os quais foram colocados em lojas cirúrgicas nas tíbias direita e esquerda de ratos jovens. Após os períodos de observação de 7, 14, 30 e 45 dias, segundo o protocolo bioético, os animais foram sacrificados, as tíbias foram removidas e fixadas em formalina a 10% e descalcificadas em partes iguais de soluções de ácido fórmico e citrato de sódio, para inclusão em parafina e microtomia. A análise dos resultados demonstrou que os agentes hemostáticos têm eficácia no controle hemorrágico; eles estimulam a osteogênese, provocando um padrão de formação de tecido ósseo semelhante ao padrão do grupo controle, embora a quantidade de trabéculas ósseas tenha sido superior principalmente no grupo do Gelfoam, nos períodos de 7 e 14 dias; após os 30 dias da cirurgia, o retardo na reparação tecidual do grupo controle em relação aos grupos experimentais começou a decrescer, tornando-se a reparação tecidual daquele semelhante à destes aos 45 dias, quando todos os grupos apresentaram tecido ósseo secundário.