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1.
Sci Rep ; 14(1): 12127, 2024 05 27.
Article in English | MEDLINE | ID: mdl-38802469

ABSTRACT

Antibiotic resistance is a paramount global health issue, with numerous bacterial strains continually fortifying their resistance against diverse antibiotics. This surge in resistance levels primarily stems from the overuse and misuse of antibiotics in human, animal, and environmental contexts. In this study, we advocate for exploring alternative molecules exhibiting antibacterial properties to counteract the escalating antibiotic resistance. We identified a synthetic antimicrobial peptide (AMP) by using computational search in AMP public databases and further engineering through molecular docking and dynamics. Microbiological evaluation, cytotoxicity, genotoycity, and hemolysis experiments were then performed. The designed AMP underwent rigorous testing for antibacterial and antibiofilm activities against Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), representing gram-positive and gram-negative bacteria, respectively. Subsequently, the safety profile of the AMP was assessed in vitro using human fibroblast cells and a human blood sample. The selected AMP demonstrated robust antibacterial and antibiofilm efficacy against MRSA and E. coli, with an added assurance of non-cytotoxicity and non-genotoxicity towards human fibroblasts. Also, the AMP did not demonstrate any hemolytic activity. Our findings emphasize the considerable promise of the AMP as a viable alternative antibacterial agent, showcasing its potential to combat antibiotic resistance effectively.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Peptides , Biofilms , Escherichia coli , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Biofilms/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Molecular Docking Simulation , Hemolysis/drug effects , Computer Simulation
2.
Front Genet ; 15: 1383452, 2024.
Article in English | MEDLINE | ID: mdl-38655054

ABSTRACT

MicroRNAs (miRNAs) play a crucial role in the early diagnosis of autoinflammatory diseases, with Hidradenitis Suppurativa (HS) being a notable example. HS, an autoinflammatory skin disease affecting the pilosebaceous unit, profoundly impacts patients' quality of life. Its hidden nature, with insidious initial symptoms and patient reluctance to seek medical consultation, often leads to a diagnostic delay of up to 7 years. Recognizing the urgency for early diagnostic tools, recent research identified significant differences in circulating miRNA expression, including miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p, between HS patients and healthy controls. These miRNAs serve as potential biomarkers for earlier disease detection. Traditional molecular biology techniques, like reverse transcription quantitative-polymerase chain reaction (RT-qPCR), are employed for their detection using specific primers and probes. Alternatively, short peptides offer a versatile and effective means for capturing miRNAs, providing specificity, ease of synthesis, stability, and multiplexing potential. In this context, we present a computational simulation pipeline designed for crafting peptide sequences that can capture circulating miRNAs in the blood of patients with autoinflammatory skin diseases, including HS. This innovative approach aims to expedite early diagnosis and enhance therapeutic follow-up, addressing the critical need for timely intervention in HS and similar conditions.

3.
Antibiotics (Basel) ; 12(5)2023 May 21.
Article in English | MEDLINE | ID: mdl-37237842

ABSTRACT

Non-specific lipid transfer proteins (nsLTPs) stand out among plant-specific peptide superfamilies due to their multifaceted roles in plant molecular physiology and development, including their protective functions against pathogens. These antimicrobial agents have demonstrated remarkable efficacy against bacterial and fungal pathogens. The discovery of plant-originated, cysteine-rich antimicrobial peptides such as nsLTPs has paved the way for exploring the mentioned organisms as potential biofactories for synthesizing antimicrobial compounds. Recently, nsLTPs have been the focus of a plethora of research and reviews, providing a functional overview of their potential activity. The present work compiles relevant information on nsLTP omics and evolution, and it adds meta-analysis of nsLTPs, including: (1) genome-wide mining in 12 plant genomes not studied before; (2) latest common ancestor analysis (LCA) and expansion mechanisms; (3) structural proteomics, scrutinizing nsLTPs' three-dimensional structure/physicochemical characteristics in the context of nsLTP classification; and (4) broad nsLTP spatiotemporal transcriptional analysis using soybean as a study case. Combining a critical review with original results, we aim to integrate high-quality information in a single source to clarify unexplored aspects of this important gene/peptide family.

4.
Front Immunol ; 13: 1060547, 2022.
Article in English | MEDLINE | ID: mdl-36544771

ABSTRACT

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin's physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.


Subject(s)
Anti-Infective Agents , Dermcidins , Hidradenitis Suppurativa , Child , Humans , Anti-Infective Agents/metabolism , Hidradenitis Suppurativa/genetics , Hidradenitis Suppurativa/metabolism , Mutation , Peptides/genetics , Peptides/metabolism , Skin/metabolism , Male , Female
5.
Microorganisms ; 10(8)2022 Aug 07.
Article in English | MEDLINE | ID: mdl-36014009

ABSTRACT

Zoonoses have recently become the center of attention of the general population and scientific community. Notably, more than 30 new human pathogens have been identified in the last 30 years, 75% of which can be classified as zoonosis. The complete eradication of such types of infections is far out of reach, considering the limited understanding of animal determinants in zoonoses and their causes of emergence. Therefore, efforts must be doubled in examining the spread, persistence, and pathogenicity of zoonosis and studying possible clinical interventions and antimicrobial drug development. The search for antimicrobial bioactive compounds has assumed great emphasis, considering the emergence of multi-drug-resistant microorganisms. Among the biomolecules of emerging scientific interest are antimicrobial peptides (AMPs), potent biomolecules that can potentially act as important weapons against infectious diseases. Moreover, synthetic AMPs are easily tailored (bioinformatically) to target specific features of the pathogens to hijack, inducing no or very low resistance. Although very promising, previous studies on SAMPs' efficacy are still at their early stages. Indeed, further studies and better characterization on their mechanism of action with in vitro and in vivo assays are needed so as to proceed to their clinical application on human beings.

6.
Saúde Redes ; 8(1)20220510.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1378216

ABSTRACT

Objetivo: analisar a produção nacional existente sobre educação e relações interprofissionais. Metodologia: constitui-se um estudo bibliográfico, semelhante à revisão integrativa, utilizando a Biblioteca Virtual em Saúde. Os critérios utilizados para inclusão foram trabalhos disponíveis de forma completa, produções brasileiras, no idioma português, espanhol e inglês publicados entre o ano de 2015 e 2020. Foram critérios de exclusão artigos duplicados e que a temática não estivesse relacionada ao interesse da pesquisa. Síntese dos dados: percebe-se que a educação interprofissional está em consonância com os princípios e diretrizes do Sistema Único de Saúde e vem sendo incorporada no Brasil há alguns anos. Destaca-se a importância das políticas e Instituições de Ensino Superior para o desenvolvimento de profissionais colaborativos interprofissionalmente. Ainda, identifica-se a positividade percebida em relação à integração da interprofissionalidade no ensino, bem como também desafios para sua efetiva incorporação, tanto no ensino, quanto nos ambientes de trabalho. Conclusões: este estudo (re)afirma a importância da temática pesquisada, tanto na formação em saúde, como na atuação profissional, contribuindo, sobremaneira, para a melhoria da atenção à saúde no contexto dos serviços de saúde, atualmente.

7.
Front Microbiol ; 12: 795217, 2021.
Article in English | MEDLINE | ID: mdl-34966375

ABSTRACT

Among chronic skin autoinflammatory diseases, Hidradenitis Suppurativa (HS) stands out for its chronicity, highly variable condition, and profound impact on the patients' quality of life. HS is characterized by suppurative skin lesions in diverse body areas, including deep-seated painful nodules, abscesses, draining sinus, and bridged scars, among others, with typical topography. To date, HS is considered a refractory disease and medical treatments aim to reduce the incidence, the infection, and the pain of the lesions. For this purpose, different classes of drugs, including anti-inflammatory molecules, antibiotics and biological drugs are being used. Antimicrobial peptides (AMPs), also called defense peptides, emerge as a new class of therapeutic compounds, with broad-spectrum antimicrobial action, in addition to reports on their anti-inflammatory, healing, and immunomodulating activity. Such peptides are present in prokaryotes and eukaryotes, as part of the innate eukaryotic immune system. It has been proposed that a deregulation in the expression of AMPs in human epithelial tissues of HS patients may be associated with the etiology of this skin disease. In this scenario, plant AMPs stand out for their richness, diversity of types, and broad antimicrobial effects, with potential application for topical systemic use in patients affected by HS.

8.
Antibiotics (Basel) ; 10(11)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34827219

ABSTRACT

Lipid transfer proteins (LTPs) are among the most promising plant-exclusive antimicrobial peptides (AMPs). They figure among the most challenging AMPs from the point of view of their structural diversity, functions and biotechnological applications. This review presents a current picture of the LTP research, addressing not only their structural, evolutionary and further predicted functional aspects. Traditionally, LTPs have been identified by their direct isolation by biochemical techniques, whereas omics data and bioinformatics deserve special attention for their potential to bring new insights. In this context, new possible functions have been identified revealing that LTPs are actually multipurpose, with many additional predicted roles. Despite some challenges due to the toxicity and allergenicity of LTPs, a systematic review and search in patent databases, indicate promising perspectives for the biotechnological use of LTPs in human health and also plant defense.

9.
Biochimie ; 186: 1-12, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33789147

ABSTRACT

Defensins are a prominent family of antimicrobial peptides. They play sophisticated roles in the defense against pathogens in all living organisms, but few works address their expression under different conditions and plant tissues. The present work prospected defensins of Manihot esculenta Crantz, popularly known as cassava. Five defensin candidates (MeDefs) were retrieved from the genome sequences and characterized. Considering chromosome distribution, only MeDef1 and 2 occupy adjacent positions in the same chromosome arm. All 3D structures had antiparallel ß-sheets, an α-helix, and amphipathic residues distributed throughout the peptides with a predominance of cationic surface charge. MeDefs expression was validated by RT-qPCR, including two stress types (biotic: fungus Macrophomina pseudophaseolina, and abiotic: mechanical injury) and a combination of both stresses (fungus+injury) in three different tissues (root, stem, and leaf). For this purpose, ten reference genes (RGs) were tested, and three were chosen to characterize MeDef expression. MeDef3 was up-regulated at roots in all stress situations tested. MeDef1 and MeDef5 were induced in leaves under biotic and abiotic stresses, but not in both stress types simultaneously. Only MeDef2 was down-regulated in the stem tissue also with biotic/abiotic combined stresses. These results indicate that although defensins are known to be responsive to pathogen infection, they may act as preformed defense or, still, have tissue or stress specificities. Aspects of their structure, stability and evolution are also discussed.


Subject(s)
Defensins , Gene Expression Regulation, Plant , Manihot , Plant Proteins , Stress, Physiological , Defensins/biosynthesis , Defensins/chemistry , Defensins/genetics , Gene Expression Profiling , Manihot/chemistry , Manihot/genetics , Manihot/metabolism , Plant Proteins/biosynthesis , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand
10.
J Clin Pathol ; 74(8): 528-532, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32759312

ABSTRACT

AIMS: Brazil is nowadays one of the epicentres of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and new therapies are needed to face it. In the context of specific immune response against the virus, a correlation between Major Histocompatibility Complex Class I (MHC-I) and the severity of the disease in patients with COVID-19 has been suggested. Aiming at better understanding the biology of the infection and the immune response against the virus in the Brazilian population, we analysed SARS-CoV-2 protein S peptides in order to identify epitopes able to elicit an immune response mediated by the most frequent MHC-I alleles using in silico methods. METHODS: Our analyses consisted in searching for the most frequent Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-C alleles in the Brazilian population, excluding the genetic isolates; then, we performed: molecular modelling for unsolved structures, MHC-I binding affinity and antigenicity prediction, peptide docking and molecular dynamics of the best fitted MHC-I/protein S complexes. RESULTS: We identified 24 immunogenic epitopes in the SARS-CoV-2 protein S that could interact with 17 different MHC-I alleles (namely, HLA-A*01:01; HLA-A*02:01; HLA-A*11:01; HLA-A*24:02; HLA-A*68:01; HLA-A*23:01; HLA-A*26:01; HLA-A*30:02; HLA-A*31:01; HLA-B*07:02; HLA-B*51:01; HLA-B*35:01; HLA-B*44:02; HLA-B*35:03; HLA-C*05:01; HLA-C*07:01 and HLA-C*15:02) in the Brazilian population. CONCLUSIONS: Being aware of the intrinsic limitations of in silico analysis (mainly the differences between the real and the Protein Data Bank (PDB) structure; and accuracy of the methods for simulate proteasome cleavage), we identified 24 epitopes able to interact with 17 MHC-I more frequent alleles in the Brazilian population that could be useful for the development of strategic methods for vaccines against SARS-CoV-2.


Subject(s)
Epitope Mapping , Epitopes , HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Brazil , Gene Frequency , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Host-Pathogen Interactions , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Protein Conformation , SARS-CoV-2/pathogenicity
11.
Bioinform Biol Insights ; 14: 1177932220952739, 2020.
Article in English | MEDLINE | ID: mdl-32952397

ABSTRACT

Even before the perception or interaction with pathogens, plants rely on constitutively guardian molecules, often specific to tissue or stage, with further expression after contact with the pathogen. These guardians include small molecules as antimicrobial peptides (AMPs), generally cysteine-rich, functioning to prevent pathogen establishment. Some of these AMPs are shared among eukaryotes (eg, defensins and cyclotides), others are plant specific (eg, snakins), while some are specific to certain plant families (such as heveins). When compared with other organisms, plants tend to present a higher amount of AMP isoforms due to gene duplications or polyploidy, an occurrence possibly also associated with the sessile habit of plants, which prevents them from evading biotic and environmental stresses. Therefore, plants arise as a rich resource for new AMPs. As these molecules are difficult to retrieve from databases using simple sequence alignments, a description of their characteristics and in silico (bioinformatics) approaches used to retrieve them is provided, considering resources and databases available. The possibilities and applications based on tools versus database approaches are considerable and have been so far underestimated.

12.
Arq. bras. oftalmol ; 83(2): 141-145, Mar.-Apr. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088976

ABSTRACT

ABSTRACT Purpose: To compare the postoperative refractive predictability of IOLMaster 500 and Pentacam HR on the basis of keratometry and anterior chamber depth values in eyes with an indication for multifocal intraocular lens (IOL) implantation. Methods: This was a retrospective study conducted on 118 eyes treated with phacoemulsification and multifocal intraocular lens implantation. Only the eyes that achieved emmetropia in the dynamic refraction performed on postoperative day 30 were included. Haigis' formula was used in each case to calculate the intraocular lens power, and the intraocular lens with the target refraction closest to emmetropia was implanted. Four lens calculation scenarios were tested by combining keratometry and anterior chamber depth measurements obtained using the two devices. Results: IOLMaster 500 and Pentacam HR differed with regard to mean keratometry (D 0.07 ± 0.03 D; p=0.0065) and anterior chamber depth (D 0.08 ± 0.01 mm; p<0.001). In the analysis of covariance, the following differences were obtained using the Haigis' formula when confronted with the biometric values obtained by inserting keratometry and anterior chamber depth values, respectively: Penta/IOL x IOL/Penta (0.13 ± 0.03; p<0.0001); Penta/Penta × IOL/Penta (0.13 ± 0.03; p<0.0001); Penta/IOL × IOL/IOL (0.11 ± 0.03; p=0.001); Penta/Penta × IOL/IOL (0.11 ± 0.03; p=0.002); IOL/IOL × IOL/Penta (0.02 ± 0.03; p=0.865); and Penta/IOL × Penta/Penta (0.002 ± 0.03; p=0.99). The difference was smaller when measuring the anterior chamber depth using the IOLMaster 500, regardless of which device was used to measure keratometry. Conclusions: Pentacam HR significantly differed from IOLMaster 500 when calculating keratometry. As regards the anterior chamber depth, the two devices were equally accurate.


RESUMO Objetivo: Comparar a previsibilidade refrativa pós-operatória do IOLMaster 500 e Pentacam HR com base nos valores de ceratometria e profundidade de câmara anterior nos olhos com indicação de implante de lentes intraoculares multifocais. Métodos: Estudo retrospectivo realizado em 118 olhos tratados com facoemulsificação e implante de lentes intraoculares multifocal. Apenas os olhos que atingiram a emetropia na refração dinâmica no 30º dia pós-operatório foram incluídos. A fórmula de Haigis foi usada em cada caso para calcular o poder das lentes intraoculares, e a lente intraocular com a refração alvo mais próxima da emetropia foi implantada. Cenários de cálculo de quatro lentes foram testados pela combinação de medidas de ceratometria e profundidade de câmara anterior obtidas usando os dois dispositivos. Resultados: IOLMaster 500 e Pentacam HR diferiram quanto à média de ceratometria (D 0,07 ± 0,03 D; p=0,0065) e profundidade de câmara anterior (D 0,08 ± 0,01 mm; p<0,001). Na análise da covariância, as seguintes diferenças foram obtidas usando a fórmula de Haigis quando confrontadas com os valores biométricos obtidos pela inserção dos valores de ceratometria e profundidade de câmara anterior, respectivamente: Penta/IOL x IOL/Penta (0,13 ± 0,03; p<0,0001); Penta/Penta x IOL/Penta (0,13 ± 0,03; p<0,0001); Penta/IOL x IOL/IOL (0,11 ± 0,03; p=0,001); Penta/Penta x IOL/IOL (0,11 ± 0,03; p=0,002); IOL/IOL x IOL/Penta (0,02 ± 0,03; p=0,865); Penta/IOL x Penta/Penta (0,002 ± 0,03; p=0,99). A diferença foi menor ao medir a profundidade da câmara anterior usando o IOLMaster 500, independentemente de qual dispositivo foi usado para medir a ceratometria. Conclusões: O Pentacam HR diferiu significativamente do IOLMaster 500 no cálculo de ceratometria. Quanto à profundidade da câmara anterior, os dois dispositivos foram igualmente precisos.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Phacoemulsification/methods , Cornea/pathology , Corneal Topography/instrumentation , Lens Implantation, Intraocular/methods , Multifocal Intraocular Lenses , Anterior Chamber/pathology , Postoperative Period , Reference Values , Refraction, Ocular/physiology , Time Factors , Visual Acuity/physiology , Predictive Value of Tests , Retrospective Studies , Biometry , Treatment Outcome , Cornea/diagnostic imaging , Interferometry/instrumentation , Interferometry/methods , Anterior Chamber/diagnostic imaging
13.
Arq Bras Oftalmol ; 83(2): 141-145, 2020.
Article in English | MEDLINE | ID: mdl-32159594

ABSTRACT

PURPOSE: To compare the postoperative refractive predictability of IOLMaster 500 and Pentacam HR on the basis of keratometry and anterior chamber depth values in eyes with an indication for multifocal intraocular lens (IOL) implantation. METHODS: This was a retrospective study conducted on 118 eyes treated with phacoemulsification and multifocal intraocular lens implantation. Only the eyes that achieved emmetropia in the dynamic refraction performed on postoperative day 30 were included. Haigis' formula was used in each case to calculate the intraocular lens power, and the intraocular lens with the target refraction closest to emmetropia was implanted. Four lens calculation scenarios were tested by combining keratometry and anterior chamber depth measurements obtained using the two devices. RESULTS: IOLMaster 500 and Pentacam HR differed with regard to mean keratometry (D 0.07 ± 0.03 D; p=0.0065) and anterior chamber depth (D 0.08 ± 0.01 mm; p<0.001). In the analysis of covariance, the following differences were obtained using the Haigis' formula when confronted with the biometric values obtained by inserting keratometry and anterior chamber depth values, respectively: Penta/IOL x IOL/Penta (0.13 ± 0.03; p<0.0001); Penta/Penta × IOL/Penta (0.13 ± 0.03; p<0.0001); Penta/IOL × IOL/IOL (0.11 ± 0.03; p=0.001); Penta/Penta × IOL/IOL (0.11 ± 0.03; p=0.002); IOL/IOL × IOL/Penta (0.02 ± 0.03; p=0.865); and Penta/IOL × Penta/Penta (0.002 ± 0.03; p=0.99). The difference was smaller when measuring the anterior chamber depth using the IOLMaster 500, regardless of which device was used to measure keratometry. CONCLUSIONS: Pentacam HR significantly differed from IOLMaster 500 when calculating keratometry. As regards the anterior chamber depth, the two devices were equally accurate.


Subject(s)
Anterior Chamber/pathology , Cornea/pathology , Corneal Topography/instrumentation , Lens Implantation, Intraocular/methods , Multifocal Intraocular Lenses , Phacoemulsification/methods , Aged , Anterior Chamber/diagnostic imaging , Biometry , Cornea/diagnostic imaging , Female , Humans , Interferometry/instrumentation , Interferometry/methods , Male , Middle Aged , Postoperative Period , Predictive Value of Tests , Reference Values , Refraction, Ocular/physiology , Retrospective Studies , Time Factors , Treatment Outcome , Visual Acuity/physiology
14.
C R Biol ; 340(6-7): 324-329, 2017.
Article in English | MEDLINE | ID: mdl-28734738

ABSTRACT

Production of antibiotics and enzymes by microorganisms is well recognized for its economic benefits. Searching potentially exploitable microorganisms, strains of heterotrophic bacteria were isolated from marine and estuarine waters in Niterói-RJ, Brazil, and tested for the production of enzymes and antimicrobial substances. From the 76 isolated colonies, 09.21% showed antimicrobial potential, 63.16% showed enzymatic activity for at least one of the substrates tested and 91% showed multidrug resistance. Strains that presented the better results were identified by sequencing. The species identified are widely distributed in many different types of environments, having been isolated previously from marine environment. Our results suggest that marine and estuarine waters can be a source for bioprospecting bacteria with potential biotechnological uses.

15.
Rio de Janeiro; s.n; 2015. xii,43 p. ilus, graf.
Thesis in Portuguese | LILACS | ID: lil-781850

ABSTRACT

A pneumonia é uma das principais causas de sepse, com alta mortalidade nas unidadesde terapia intensiva (UTI), mesmo com os recentes avanços da medicina. O estudo da sepse ede novas alternativas terapêuticas permanecem um desafio devido à complexidade destasíndrome, cujo principal componente é uma resposta inflamatória exacerbada. O PPARγ(receptor ativado por proliferadores de peroxissoma) é um fator de transcrição da família dereceptores nucleares, caracterizados por seu padrão de distribuição nos tecidos e por suafunção metabólica. Recentemente, vßrias populações de leucócitos, incluindomonócitos/macrófagos, linfócitos e células dendríticas, também têm sido evidenciadasexpressando PPARgama, sugerindo um importante papel para esta molécula na regulação derespostas imunes. O fßrmaco antidiabético rosiglitazona pertence à família dastiazolidinedionas. Este fßrmaco é agonista de PPARgama e apresenta além dos efeitos nometabolismo da glicose, uma potente ação anti-inflamatória, inclusive nas células do tratorespiratório. Nosso objetivo principal foi caracterizar o papel do PPARgama em um modelo depneumosepse em camundongos Swiss webster. Os animais foram desafiados com a bactériaKlebsiella pneumoniae, uma importante causadora de infecções relacionadas à assistência àsaúde, tanto no meio ambiente comunitßrio quanto hospitalar. Foram feitas anßlises desobrevida, parâmetros inflamatórios, produção de citocinas, migração celular e eliminaçãobacteriana no lavado broncoalveolar 24 horas após a instilação intratraqueal de K.pneumoniae...


Pneumonia is a leading cause of sepsis with high mortality in intensive care units(ICU), even with recent medical advances. The study of sepsis and new therapeutic optionsremain a challenge due to the complexity of this syndrome, whose main component is anexaggerated inflammatory response. The PPARγ (receptor peroxisome proliferator-activated)is a transcription factor of nuclear receptor family characterized by their pattern of tissuedistribution and its metabolic function. Recently, various leukocyte populations, includingmonocytes / macrophages, lymphocytes and dendritic cells, also have been evidencedexpressing PPARγ, suggesting a role for this molecule in regulation of immune responses.The antidiabetic drug rosiglitazone belongs to the family of thiazolidinediones. This drug isPPARγ agonist addition to the effects and features in the metabolism of glucose, potent antiinflammatoryaction, including the respiratory tract cells. Our main objective was tocharacterize the role of PPARγ in a pneumosepse model in mice Swiss webster. The animalswere challenged with Klebsiella pneumoniae bacteria, a major cause of infections related tohealth care, both through community and hospital environment. Survival analyzes wereperformed, inflammatory parameters, cytokine production, cell migration and bacterialelimination in the bronchoalveolar lavage fluid 24 hours after intratracheal instillation of K.pneumoniae...


Subject(s)
Mice , Klebsiella Infections , Klebsiella pneumoniae , Pneumonia , PPAR gamma , Sepsis/epidemiology , Sepsis/physiopathology
16.
Interaçöes estud. pesqui. psicol ; 11(21): 29-56, jan.-jun. 2006.
Article in Portuguese | LILACS | ID: lil-514944

ABSTRACT

Partindo da Reforma Psiquiátrica, investigamos a possibilidade de construção de enlaçamento social e simbólico por psicóticos, via criação artística, a fim de contribuir na elaboração de estratégias clínicas inclusivas e de reinserção social. Estudamos o caso do Profeta Gentileza, que pintou as pilastras do Viaduto do Caju-RJ com símbolos e grafias inéditas. Concluímos que a construção de seu processo de estabilização se deu via metáfora delirante, tendo sua obra funcionado enquanto contorno estético ao excesso de gozo que restou insignificantizável do trabalho com o delírio, permitindo uma saída que prescindiu do ato. Esse trabalho sustentou sua inserção social, tendo sua obra se tornado patrimônio cultural do Rio de Janeiro. Como efeito de aprendizado para os trabalhadores da saúde mental, se destacou a importância de acompanhar o estilo do sujeito na sua tentativa de cura, sustentando os movimentos deste diante do campo do Outro junto ao trabalho de reinserção social.


Subject(s)
Humans , Art Therapy , Social Adjustment , Psychotic Disorders/psychology , Health Care Reform
17.
Interaçöes estud. pesqui. psicol ; 11(21): 29-56, jan.-jun. 2006.
Article in Portuguese | Index Psychology - journals | ID: psi-36145

ABSTRACT

Partindo da Reforma Psiquiátrica, investigamos a possibilidade de construção de enlaçamento social e simbólico por psicóticos, via criação artística, a fim de contribuir na elaboração de estratégias clínicas inclusivas e de reinserção social. Estudamos o caso do Profeta Gentileza, que pintou as pilastras do Viaduto do Caju-RJ com símbolos e grafias inéditas. Concluímos que a construção de seu processo de estabilização se deu via metáfora delirante, tendo sua obra funcionado enquanto contorno estético ao excesso de gozo que restou insignificantizável do trabalho com o delírio, permitindo uma saída que prescindiu do ato. Esse trabalho sustentou sua inserção social, tendo sua obra se tornado patrimônio cultural do Rio de Janeiro. Como efeito de aprendizado para os trabalhadores da saúde mental, se destacou a importância de acompanhar o estilo do sujeito na sua tentativa de cura, sustentando os movimentos deste diante do campo do Outro junto ao trabalho de reinserção social.(AU)


Subject(s)
Humans , Art Therapy , Social Adjustment , Psychotic Disorders/psychology , Health Care Reform
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