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1.
Article in Chinese | WPRIM | ID: wpr-928446

ABSTRACT

OBJECTIVE@#To characterize a novel HLA allele, A*24:191, its DNA sequence, MHC modeling structure, and the possible influence of the amino-acid residue variations on the molecule.@*METHODS@#The HLA sequence was determined by Luminex PCR-SSO and PCR-SBT. Its MHC molecular structure and the possible effects of the amino-acid residue variations were modeled and analyzed with Phyre2, RCSB PDB and HistoCheck software.@*RESULTS@#The PCR-SBT revealed the novel A*24:191 differs from A*24:02 in exon 2 at position 256, 265, 270 with G>C, G>C, A>T. The MHC molecular structure prediction showed that, compared with A*24:02, the 62nd residue of A*24:191 changed from the acidic E to a neutral Q, both with the side chain extending outside the α helix pointing forward the groove, (Risler's score, R=2), the 65th changed from the smaller neutral G extending inside the helix to a basic R with a long-chain extending upward outside the helix (R=52), and the 66th changed from the basic K to a neutral N both with a long side chain extending inside the groove (R=31). The above residues are located on the α helix of the α 1 domain which constituting the side wall of the peptide-binding groove. The DSS Score=3.85. From the surface image of the molecule, it can be clearly seen that the variations of the properties, sizes and configurations of the residues caused significant changes in the shape of the surface structure of the α helix.@*CONCLUSION@#It suggested that the residue variations are likely to change the peptide binding properties as well as the TCR and antibody binding characteristics of the molecule.


Subject(s)
Alleles , Amino Acid Sequence , HLA-A Antigens , Humans , Peptides , Protein Binding , Protein Conformation
2.
Chinese Journal of Biotechnology ; (12): 1490-1505, 2022.
Article in Chinese | WPRIM | ID: wpr-927795

ABSTRACT

Intrinsically disordered proteins (IDPs) are proteins or protein regions that fail to get folded into definite three-dimensional structures but participate in various biological processes and perform specific functions. Defying the traditional protein "sequence-structure-function" paradigm, they enrich the protein "structure-function" diversity. Ubiquitous in organisms, they show extreme hydrophilicity, charged amino acids, and highly repetitive amino acid sequences, with simple arrangement. As a result, they feature highly variable binding affinities and high coordination, which facilitate their functions. IDPs play an important role in cell stress response, which can improve the tolerance to a variety of stresses, such as freezing, high salt, heat shock, and desiccation. In this study, we briefed the characteristics, classifications, and identification of IDPs, summarized the molecular mechanism in improving cell stress resistance, and described the potential applications.


Subject(s)
Freezing , Intrinsically Disordered Proteins/metabolism , Protein Conformation
3.
Article in English | WPRIM | ID: wpr-776713

ABSTRACT

Proteins are dynamic, fluctuating between multiple conformational states. Protein dynamics, spanning orders of magnitude in time and space, allow proteins to perform specific functions. Moreover, under certain conditions, proteins can morph into a different set of conformations. Thus, a complete understanding of protein structural dynamics can provide mechanistic insights into protein function. Here, we review the latest developments in methods used to determine protein ensemble structures and to characterize protein dynamics. Techniques including X-ray crystallography, cryogenic electron microscopy, and small angle scattering can provide structural information on specific conformational states or on the averaged shape of the protein, whereas techniques including nuclear magnetic resonance, fluorescence resonance energy transfer (FRET), and chemical cross-linking coupled with mass spectrometry provide information on the fluctuation of the distances between protein domains, residues, and atoms for the multiple conformational states of the protein. In particular, FRET measurements at the single-molecule level allow rapid resolution of protein conformational states, where information is otherwise obscured in bulk measurements. Taken together, the different techniques complement each other and their integrated use can offer a clear picture of protein structure and dynamics.


Subject(s)
Fluorescence Resonance Energy Transfer , Magnetic Resonance Spectroscopy , Protein Conformation , Proteins , Chemistry , Physiology
4.
Braz. j. microbiol ; 49(2): 351-357, Apr.-June 2018. graf
Article in English | LILACS | ID: biblio-889245

ABSTRACT

Abstract Economic losses with high mortality rate associated with Porcine circovirus type 2 (PCV2) is reported worldwide. PCV2 commercial vaccine was introduced in 2006 in U.S. and in 2008 in Brazil. Although PCV2 vaccines have been widely used, cases of PCV2 systemic disease have been reported in the last years. Eleven nursery or fattening pigs suffering from PCV2 systemic disease were selected from eight PCV2-vaccinated farms with historical records of PCV2 systemic disease in Southern Brazil. PCV2 genomes were amplified and sequenced from lymph node samples of selected pigs. The comparison among the ORF2 amino acid sequences of PCV2 isolates revealed three amino acid substitutions in the positions F57I, N178S and A190T, respectively. Using molecular modeling, a structural model for the capsid protein of PCV2 was built. Afterwards, the mutated residues positions were identified in the model. The structural analysis of the mutated residues showed that the external residue 190 is close to an important predicted region for antibodies recognition. Therefore, changes in the viral protein conformation might lead to an inefficient antibody binding and this could be a relevant mechanism underlying the recent vaccine failures observed in swine farms in Brazil.


Subject(s)
Animals , Circovirus/chemistry , Capsid Proteins/chemistry , Protein Conformation , Swine , Swine Diseases/virology , Brazil , Models, Molecular , Circovirus/isolation & purification , Circovirus/genetics , Circoviridae Infections/veterinary , Circoviridae Infections/virology , Amino Acid Substitution , Capsid Proteins/genetics
5.
Article in English | WPRIM | ID: wpr-772963

ABSTRACT

Androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of many severe diseases such as prostate cancer, muscle atrophy, and osteoporosis. Binding of ligands to AR triggers the conformational changes in AR that may affect the recruitment of coactivators and downstream response of AR signaling pathway. Therefore, AR ligands have great potential to treat these diseases. In this study, we searched for novel AR ligands by performing a docking-based virtual screening (VS) on the basis of the crystal structure of the AR ligand binding domain (LBD) in complex with its agonist. A total of 58 structurally diverse compounds were selected and subjected to LBD affinity assay, with five of them (HBP1-3, HBP1-17, HBP1-38, HBP1-51, and HBP1-58) exhibiting strong binding to AR-LBD. The IC values of HBP1-51 and HBP1-58 are 3.96 µM and 4.92 µM, respectively, which are even lower than that of enzalutamide (Enz, IC = 13.87 µM), a marketed second-generation AR antagonist. Further bioactivity assays suggest that HBP1-51 is an AR agonist, whereas HBP1-58 is an AR antagonist. In addition, molecular dynamics (MD) simulations and principal components analysis (PCA) were carried out to reveal the binding principle of the newly-identified AR ligands toward AR. Our modeling results indicate that the conformational changes of helix 12 induced by the bindings of antagonist and agonist are visibly different. In summary, the current study provides a highly efficient way to discover novel AR ligands, which could serve as the starting point for development of new therapeutics for AR-related diseases.


Subject(s)
Androgen Receptor Antagonists , Pharmacology , Androgens , Metabolism , Pharmacology , Biological Assay , Cell Line, Tumor , Drug Discovery , Methods , Humans , Ligands , Male , Molecular Docking Simulation , Molecular Dynamics Simulation , Phenylthiohydantoin , Pharmacology , Principal Component Analysis , Prostatic Neoplasms , Drug Therapy , Protein Binding , Physiology , Protein Conformation , Receptors, Androgen , Metabolism
6.
Protein & Cell ; (12): 986-1003, 2018.
Article in English | WPRIM | ID: wpr-757992

ABSTRACT

Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures. However, protein-protein interactions often involve highly flexible elements that can assume many distinct conformations upon binding to different partners. Existing evidence suggests that arrestins are no exception to this rule: their flexibility is necessary for functional versatility. The data on arrestins and many other multi-functional proteins indicate that in many cases, "order" might be artificially imposed by highly non-physiological crystallization conditions and/or crystal packing forces. In contrast, conformational flexibility (and its extreme case, intrinsic disorder) is a more natural state of proteins, representing true biological order that underlies their physiologically relevant functions.


Subject(s)
Animals , Arrestins , Chemistry , Metabolism , Humans , Protein Conformation
7.
Protein & Cell ; (12): 568-579, 2018.
Article in English | WPRIM | ID: wpr-757988

ABSTRACT

Annexin A2, a multifunctional tumor associated protein, promotes nuclear factor-kappa B (NF-κB) activation by interacting with NF-κB p50 subunit and facilitating its nuclear translocation. Here we demonstrated that two ginsenosides Rg5 (G-Rg5) and Rk1 (G-Rk1), with similar structure, directly bound to Annexin A2 by molecular docking and cellular thermal shift assay. Both Rg5 and Rk1 inhibited the interaction between Annexin A2 and NF-κB p50 subunit, their translocation to nuclear and NF-κB activation. Inhibition of NF-κB by these two ginsenosides decreased the expression of inhibitor of apoptosis proteins (IAPs), leading to caspase activation and apoptosis. Over expression of K302A Annexin A2, a mutant version of Annexin A2, which fails to interact with G-Rg5 and G-Rk1, effectively reduced the NF-κB inhibitory effect and apoptosis induced by G-Rg5 and G-Rk1. In addition, the knockdown of Annexin A2 largely enhanced NF-κB activation and apoptosis induced by the two molecules, indicating that the effects of G-Rg5 and G-Rk1 on NF-κB were mainly mediated by Annexin A2. Taken together, this study for the first time demonstrated that G-Rg5 and G-Rk1 inhibit tumor cell growth by targeting Annexin A2 and NF-κB pathway, and G-Rg5 and G-Rk1 might be promising natural compounds for targeted cancer therapy.


Subject(s)
Active Transport, Cell Nucleus , Annexin A2 , Chemistry , Genetics , Metabolism , Antineoplastic Agents , Chemistry , Metabolism , Pharmacology , Apoptosis , Biological Products , Chemistry , Metabolism , Pharmacology , Cell Nucleus , Metabolism , Down-Regulation , Drug Discovery , Gene Knockdown Techniques , Ginsenosides , Chemistry , Hep G2 Cells , Humans , Molecular Docking Simulation , Molecular Targeted Therapy , NF-kappa B p50 Subunit , Metabolism , Protein Conformation
8.
Mem. Inst. Oswaldo Cruz ; 112(9): 617-625, Sept. 2017. tab, graf
Article in English | LILACS | ID: biblio-894879

ABSTRACT

BACKGROUND Leishmanolysins have been described as important parasite virulence factors because of their roles in the infection of promastigotes and resistance to host's defenses. Leishmania (Viannia) braziliensis contains several leishmanolysin genes in its genome, especially in chromosome 10. However, the functional impact of such diversity is not understood, but may be attributed partially to the lack of structural data for proteins from this parasite. OBJECTIVES This works aims to compare leishmanolysin sequences from L. (V.) braziliensis and to understand how the diversity impacts in their structural and dynamic features. METHODS Leishmanolysin sequences were retrieved from GeneDB. Subsequently, 3D models were built using comparative modeling methods and their dynamical behavior was studied using molecular dynamic simulations. FINDINGS We identified three subgroups of leishmanolysins according to sequence variations. These differences directly affect the electrostatic properties of leishmanolysins and the geometry of their active sites. We identified two levels of structural heterogeneity that might be related to the ability of promastigotes to interact with a broad range of substrates. MAIN CONCLUSION Altogether, the structural plasticity of leishmanolysins may constitute an important evolutionary adaptation rarely explored when considering the virulence of L. (V.) braziliensis parasites.


Subject(s)
Humans , Leishmania braziliensis/genetics , Metalloendopeptidases/genetics , Protein Conformation , Genetic Variation , Models, Molecular
9.
Electron. j. biotechnol ; 19(2): 9-13, Mar. 2016. ilus
Article in English | LILACS | ID: lil-782610

ABSTRACT

Background: Protein structural alignment is one of the most fundamental and crucial areas of research in the domain of computational structural biology. Comparison of a protein structure with known structures helps to classify it as a new or belonging to a known group of proteins. This, in turn, is useful to determine the function of protein, its evolutionary relationship with other protein molecules and grasping principles underlying protein architecture and folding. Results: A large number of protein structure alignment methods are available. Each protein structure alignment tool has its own strengths and weaknesses that need to be highlighted. We compared and presented results ofsix most popular and publically available servers for protein structure comparison. These web-based servers were compared with the respect to functionality (features provided by these servers) and accuracy (how well the structural comparison is performed). The CATH was used as a reference. The results showed that overall CE was top performer. DALI and PhyreStorm showed similar results whereas PDBeFold showed the lowest performance. In case of few secondary structural elements, CE, DALI and PhyreStorm gave 100% success rate. Conclusion: Overall none of the structural alignment servers showed 100% success rate. Studies of overall performance, effect of mainly alpha and effect of mainly beta showed consistent performance. CE, DALI, FatCat and PhyreStorm showed more than 90% success rate.


Subject(s)
Protein Conformation , Software , Sequence Alignment/methods
10.
Braz. j. microbiol ; 47(1): 251-258, Jan.-Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-775122

ABSTRACT

Abstract Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1–4) are antigenically and genetically distinct and each serotype is composed of multiple genotypes. In this study we isolated one Dengue virus 1 serotype, named BR/Alfenas/2012, from a patient with dengue hemorrhagic fever in Alfenas, South Minas Gerais, Brazil and molecular identification was performed based on the analysis of NS5 gene. Swiss mice were infected with this isolate to verify its potential to induce histopathological alterations characteristic of dengue. Liver histopathological analysis of infected animals showed the presence of inflammatory infiltrates, hepatic steatosis, as well as edema, hemorrhage and necrosis focal points. Phylogenetic and evolutionary analyses based on the envelope gene provided evidence that the isolate BR/Alfenas/2012 belongs to genotype V, lineage I and it is probably derived from isolates of Rio de Janeiro, Brazil. The isolate BR/Alfenas/2012 showed two unique amino acids substitutions (SER222THRE and PHE306SER) when compared to other Brazilian isolates from the same genotype/lineage. Molecular models were generated for the envelope protein indicating that the amino acid alteration PHE 306 SER could contribute to a different folding in this region located within the domain III. Further genetic and animal model studies using BR/Alfenas/2012 and other isolates belonging to the same lineage/genotype could help determine the relation of these genetic alterations and dengue hemorrhagic fever in a susceptible population.


Subject(s)
Animals , Humans , Mice , Dengue Virus/classification , Dengue Virus/genetics , Dengue/virology , Genetic Variation , Genotype , Phylogeny , Amino Acid Substitution , Animal Structures/pathology , Brazil , Disease Models, Animal , Dengue Virus/isolation & purification , Gene Products, env/chemistry , Gene Products, env/genetics , Histocytochemistry , Microscopy , Models, Molecular , Point Mutation , Protein Conformation , Viral Nonstructural Proteins/genetics
11.
Chinese Journal of Biotechnology ; (12): 355-364, 2016.
Article in Chinese | WPRIM | ID: wpr-337408

ABSTRACT

We constructed different N-terminal truncated variants based on Bacillus acidopullulyticus pullulanase 3D structure (PDB code 2WAN), and studied the effects of truncated mutation on soluble expression, enzymatic properties, and application in saccharification. Upon expression, the variants of X45 domain deletion existed as inclusion bodies, whereas deletion of CBM41 domain had an effective effect on soluble expression level. The variants that lack of CBM41 (M1), lack of X25 (M3), and lack both of CBM41 and X25 (M5) had the same optimal pH (5.0) and optimal temperature (60 degrees C) with the wild-type pullulanase (WT). The K(m) of M1 and M5 were 1.42 mg/mL and 1.85 mg/mL, respectively, 2.4- and 3.1-fold higher than that of the WT. k(cat)/K(m) value of M5 was 40% lower than that of the WT. Substrate specificity results show that the enzymes exhibited greater activity with the low-molecular-weight dextrin than with high-molecular-weight soluble starch. When pullulanases were added to the saccharification reaction system, the dextrose equivalent of the WT, M1, M3, and M5 were 93.6%, 94.7%, 94.5%, and93.1%, respectively. These results indicate that the deletion of CBM41 domain and/or X25 domain did not affect the practical application in starch saccharification process. Furthermore, low-molecular-weight variants facilitate the heterologous expression. Truncated variants may be more suitable for industrial production than the WT.


Subject(s)
Bacillus , Glycoside Hydrolases , Metabolism , Molecular Weight , Protein Conformation , Sequence Deletion , Substrate Specificity , Temperature
12.
Protein & Cell ; (12): 28-45, 2016.
Article in English | WPRIM | ID: wpr-757199

ABSTRACT

Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion.


Subject(s)
Animals , Cattle , Dogs , Hemagglutinins, Viral , Chemistry , Metabolism , Influenzavirus C , Physiology , Orthomyxoviridae Infections , Metabolism , Virology , Protein Conformation , Protein Folding , Protein Processing, Post-Translational , Viral Fusion Proteins , Chemistry , Metabolism
13.
Protein & Cell ; (12): 46-62, 2016.
Article in English | WPRIM | ID: wpr-757162

ABSTRACT

Single particle analysis, which can be regarded as an average of signals from thousands or even millions of particle projections, is an efficient method to study the three-dimensional structures of biological macromolecules. An intrinsic assumption in single particle analysis is that all the analyzed particles must have identical composition and conformation. Thus specimen heterogeneity in either composition or conformation has raised great challenges for high-resolution analysis. For particles with multiple conformations, inaccurate alignments and orientation parameters will yield an averaged map with diminished resolution and smeared density. Besides extensive classification approaches, here based on the assumption that the macromolecular complex is made up of multiple rigid modules whose relative orientations and positions are in slight fluctuation around equilibriums, we propose a new method called as local optimization refinement to address this conformational heterogeneity for an improved resolution. The key idea is to optimize the orientation and shift parameters of each rigid module and then reconstruct their three-dimensional structures individually. Using simulated data of 80S/70S ribosomes with relative fluctuations between the large (60S/50S) and the small (40S/30S) subunits, we tested this algorithm and found that the resolutions of both subunits are significantly improved. Our method provides a proof-of-principle solution for high-resolution single particle analysis of macromolecular complexes with dynamic conformations.


Subject(s)
Algorithms , Computer Simulation , Cryoelectron Microscopy , Methods , Crystallography, X-Ray , Humans , Macromolecular Substances , Chemistry , Models, Molecular , Protein Conformation , Ribosomes , Chemistry
14.
Article in Chinese | WPRIM | ID: wpr-345387

ABSTRACT

<p><b>OBJECTIVE</b>To explore the molecular mechanism for a boy suspected with 3-methylcrotonyl-CoA carboxylase deficiency by neonatal screening.</p><p><b>METHODS</b>PCR and Sanger sequencing were used to identify potential mutations of MCCC1 and MCCC2 genes. SIFT and Polyphen-2 software was used to predict the effect of variant on the protein function and conservation of the variant across various species. Human Splicing Finder and Swiss-PdbViewer4.1.0 were applied to analyze the possible mechanism of the variant.</p><p><b>RESULTS</b>For the proband, a compound heterozygous mutation was discovered in the MCCC1 gene, namely c.539G>T (p.G180V) and c.704_711del (p.A235Vfs*4), which were inherited from his father and mother, respectively. The two mutations have disrupted the protein conformation, which in turn may impact the function of MCC protein.</p><p><b>CONCLUSION</b>The compound heterozygous mutations of the MCCC1 gene may contribute to the 3-methylcrotonyl-CoA carboxylase deficiency manifested by the patient.</p>


Subject(s)
Amino Acid Sequence , Base Sequence , Carbon-Carbon Ligases , Chemistry , Genetics , DNA Mutational Analysis , Heterozygote , Humans , Infant, Newborn , Male , Models, Molecular , Mutation , Neonatal Screening , Methods , Protein Conformation , Sequence Homology, Amino Acid , Urea Cycle Disorders, Inborn , Diagnosis , Genetics
15.
Rev. panam. salud pública ; 38(6): 487-494, nov.-dic. 2015. tab
Article in English | LILACS | ID: lil-788107

ABSTRACT

OBJECTIVE:To assess the adequacy of energy and nutritional intakes compared to recommended daily intakes (RDIs) in schoolchildren from the Cochabamba region (Bolivia) and to determine micronutrient intake distributions across different ages and genders. METHODS: This nutritional study (n = 315) was part of a larger population-based crosssectional study (the "Bolkid" survey) that collected data on schoolchildren 5-16 years old in 2010 in the Cochabamba region. Information about food intake was gathered with a semiquan-titative, food-frequency, parent-administered questionnaire about l2 months before the study. Descriptive and bivariate analyses of energy and nutrient intakes were assessed. RESULTS: For all ages studied and both genders, the average energy and micronutrient intakes were acceptable but below the requirements. The diet included high amounts of fiber, some minerals (iron, magnesium, phosphorus, potassium, sodium), and vitamins (pantothenic acid, niacin, vitamins B2, B12, C, and E), but was low in calcium and vitamin D. However, more than half the children had insufficient energy intake, and low calcium, vitamin A, and vitamin D intakes, according to RDIs adjusted for age and gender; one-third of the children had insufficient folate and magnesium intakes; and adolescent girls had low iron intakes. CONCLUSIONS: Regardless of recommendations or demographic characteristics, the vast majority of children in Cochabamba consumed insufficient energy and too little calcium, folate, magnesium, and vitamin A and D. In addition, adolescent girls consumed insufficient iron. Higher energy intake for schoolchildren through increased food availability, frequency, and size portions in daily meals should be a priority for Bolivian public health institutions.


OBJETIVO:Evaluar la idoneidad del consumo energético y de nutrientes en escolares de la región de Cochabamba, Bolivia, por comparación con las cantidades diarias recomendadas (CDR), y determinar la distribución de la ingesta de micronutrientes en distintas edades y ambos sexos. MÉTODOS: Este estudio nutricional (n = 315) formó parte de un estudio transversal poblacional más amplio (la llamada encuesta Bolkid) en que se obtuvieron datos de escolares de 5 a 16 años de edad en la región de Cochabamba en el 2010. Se usó un cuestionario semicuantitativo, administrado por los padres, para obtener información acerca de la frecuencia del consumo de alimentos alrededor de 12 meses antes del estudio. Se evaluaron los resultados de análisis descriptivos y bivariados de la ingesta energética y de nutrientes. RESULTADOS: En todas las edades estudiadas y ambos sexos, las ingestas energética y de micronutrientes fueron aceptables pero inferiores a las cantidades necesarias. La alimentación tenía un alto contenido de fibra, de algunos minerales (hierro, magnesio, fósforo, potasio, sodio) y de vitaminas (ácido pantoténico, niacina, vitaminas B2, B12, C y E), pero poco contenido de calcio y vitamina D. No obstante, más de la mitad de los niños tenían una ingesta energética insuficiente e ingestas demasiado bajas de calcio, vitamina A y vitamina D, según las CDR ajustadas por edad y sexo; una tercera parte consumían cantidades insuficientes de folato y magnesio; y las adolescentes tenían ingestas de hierro demasiado bajas. CONCLUSIONES: Independientemente de las cantidades recomendadas o de las características demográficas, la gran mayoría de los niños en Cochabamba tenían un consumo energético insuficiente e ingestas demasiado bajas de calcio, folato, magnesio y vitaminas A y D. Además, las adolescentes consumían cantidades insuficientes de hierro. Las instituciones de salud pública bolivianas deberían dar prioridad a aumentar el consumo energético de los escolares propiciando una mayor disponibilidad de alimentos, un consumo más frecuente y porciones más grandes en las comidas diarias.


Subject(s)
Evolution, Molecular , Gene Expression Regulation , /chemistry , Transcription, Genetic , Crystallography, X-Ray , Enzyme Stability , Holoenzymes/chemistry , Protein Conformation , Protein Structure, Tertiary , /genetics
16.
Rev. bras. anestesiol ; 65(5): 384-394, Sept.-Oct. 2015. tab
Article in English | LILACS | ID: lil-763142

ABSTRACT

ABSTRACTBACKGROUND AND OBJECTIVES: Although many recognize that the first year of life and specifically the neonatal period are associated with increased risk of anesthetic morbidity and mortality, there are no studies directed to these pediatric subpopulations. This systematic review of the scientific literature including the last 15 years aimed to analyze the epidemiology of morbidity and mortality associated with general anesthesia and surgery in the first year of life and particularly in the neonatal (first month) period.CONTENT: The review was conducted by searching publications in Medline/PubMed databases, and the following outcomes were evaluated: early mortality in the first year of life (<1 year) and in subgroups of different vulnerability in this age group (0-30 days and 1-12 months) and the prevalence of cardiac arrest and perioperative critical/adverse events of various types in the same subgroups.CONCLUSIONS: The current literature indicates great variability in mortality and morbidity in the age group under consideration and in its subgroups. However, despite the obvious methodological heterogeneity and absence of specific studies, epidemiological profiles of morbidity and mortality related to anesthesia in children in the first year of life show higher frequency of morbidity and mortality in this age group, with the highest peaks of incidence in the neonates' anesthesia.


RESUMOJUSTIFICATIVA E OBJETIVOS: Embora muitos reconheçam que a idade inferior a um ano e especificamente o período neonatal estejam associados a maior risco de morbimortalidade anestésica, não existem estudos dirigidos a essas subpopulações pediátricas. Esta revisão sistemática das publicações científicas dos últimos 15 anos teve como objetivo analisar o perfil epidemiológico da morbimortalidade relacionada com a anestesia geral e cirurgia no primeiro ano de idade e em particular no período neonatal (primeiro mês de idade).CONTEúDO: A revisão foi conduzida por pesquisa de publicações nas bases de dados Medline/PubMed. Foram avaliados os seguintes desfechos: mortalidade precoce no primeiro ano de idade (< 1A) e em subgrupos de diferente vulnerabilidade nesta faixa etária (0-30 dias e 1-12 meses) e prevalência de parada cardíaca e eventos críticos/adversos perioperatórios de diversos tipos nos mesmos subgrupos.CONCLUSÕES: A literatura corrente indica grande variabilidade nos índices de mortalidade e morbidade na faixa etária em análise, bem como nos seus subgrupos. No entanto, apesar da óbvia heterogeneidade metodológica e da ausência de estudos específicos, os perfis epidemiológicos de morbimortalidade relacionada com a anestesia de crianças no primeiro ano de idade mostram frequência mais alta de morbimortalidade nessa faixa etária, com os maiores picos de incidência na anestesia de neonatos.


Subject(s)
Binding Sites , Protein Binding , Protein Conformation , Proteins/chemistry , Proteins/metabolism , Computational Biology , Databases, Protein , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular
17.
Rev. chil. pediatr ; 86(4): 283-286, ago. 2015.
Article in English | LILACS | ID: lil-764086

ABSTRACT

Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation.


El síndrome del cromosoma 22q11.2, también conocido como supresión o síndrome de DiGeorge o síndrome velocardiofacial, es uno de los síndromes más comunes de anomalías múltiples en los seres humanos. Este síndrome es comúnmente causado por una microdeleción del cromosoma 22 en q11.2 banda. Aunque este trastorno genético muestra varias anomalías clínicas y diferentes grados de compromiso orgánico, las características clínicas que han atraído la mayor atención son el comportamiento y el desarrollo, porque las personas con síndrome de deleción 22q11.2 tienen un riesgo 30 veces mayor de desarrollar esquizofrenia. Hay diferentes opiniones sobre el desarrollo cognitivo, y comúnmente se se ha observado un deterioro cognitivo en lugar de un inicio temprano de discapacidad intelectual. Presentamos un caso de síndrome de deleción 22q11.2 tanto con la evaluación temprana de discapacidades intelectuales leves como con la tetralogía de Fallot como única manifestación física.


Subject(s)
Fibrinogen/chemistry , Nanostructures/chemistry , Crystallization/methods , Freeze Drying/methods , Humidity , Protein Conformation , Scattering, Small Angle , Solubility , Thermodynamics , Water/chemistry , X-Ray Diffraction/methods , X-Rays
18.
Int. arch. otorhinolaryngol. (Impr.) ; 19(2): 171-175, Apr-Jun/2015.
Article in English | LILACS | ID: lil-747141

ABSTRACT

Introduction Analysis of the suppression effect is a simple method to evaluate cochlear status and central auditory mechanisms and, more specifically, the medial olivocochlear system. This structure may be involved in the generation of mechanisms that cause tinnitus and in the pathophysiology of tinnitus in patients with tinnitus and normal hearing. Objective To review the literature of the etiology of tinnitus on the lights of otoacoustic emissions in patients with normal hearing. Data Synthesis Individuals with tinnitus and normal hearing have a higher prevalence of alterations in transient-evoked otoacoustic emissions and distortion-product otoacoustic emissions than normal subjects. This fact suggests that dysfunctions of the outer hair cells (OHCs) might be important in the generation of the tinnitus; however, this feature is not always present in those who have the symptoms of tinnitus. Final Comments These findings suggest that OHC dysfunction is not necessary for tinnitus development—that is, there might be mechanisms other than OHC damage in the tinnitus development. On the other hand, OHC dysfunction alone is not sufficient to cause the symptom, because a great many individuals with OHC dysfunction did not complain about tinnitus. .


Subject(s)
Anti-Infective Agents/metabolism , Bacterial Outer Membrane Proteins/metabolism , Bacteriocins/metabolism , Receptors, Cell Surface/metabolism , Anti-Infective Agents/pharmacology , Endocytosis , Escherichia coli Proteins/metabolism , Escherichia coli/metabolism , Models, Molecular , Protein Conformation
19.
Arch. endocrinol. metab. (Online) ; 59(3): 245-251, 06/2015. tab, graf
Article in English | LILACS | ID: lil-751309

ABSTRACT

Objective Evaluate the effect of glycemic index (GI) on biochemical parameters, food intake, energy metabolism, anthropometric measures and body composition in overweight subjects.Materials and methods Simple blind study, in which nineteen subjects were randomly assigned to consume in the laboratory two daily low GI (n = 10) or high GI (n = 9) meals, for forty-five consecutive days. Habitual food intake was assessed at baseline. Food intake, anthropometric measures and body composition were assessed at each 15 days. Energy metabolism and biochemical parameters were evaluated at baseline and the end of the study.Results Low GI meals increased fat oxidation, and reduced waist circumference and HOMA-IR, while high GI meals increased daily dietary fiber and energy intake compared to baseline. There was a higher reduction on waist circumference and body fat, and a higher increase on postprandial fat oxidation in response to the LGI meals than after high GI meals. High GI meals increased fasting respiratory coefficient compared to baseline and low GI meals.Conclusion The results of the present study showed that the consumption of two daily low GI meals for forty-five consecutive days has a positive effect on obesity control, whereas, the consumption of high GI meals result has the opposite effect. Arch Endocrinol Metab. 2015;59(3):245-51.


Subject(s)
Bacterial Proteins/chemistry , Escherichia coli/enzymology , Membrane Proteins/chemistry , Phenylalanine/chemistry , Amino Acid Motifs , Amino Acid Sequence , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Chemotaxis , Conserved Sequence , Dimerization , Escherichia coli/chemistry , Escherichia coli/genetics , Escherichia coli/physiology , Molecular Sequence Data , Membrane Proteins/genetics , Membrane Proteins/metabolism , Protein Conformation , Phenylalanine/genetics , Phenylalanine/metabolism
20.
Rev. bras. anestesiol ; 65(3): 207-212, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-748922

ABSTRACT

BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50). Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50); in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37) of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50) of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out. .


JUSTIFICATIVA E OBJETIVO: O tratamento da dor pós-operatória em mastectomia continua sendo um grande desafio apesar da abordagem multimodal. O objetivo deste estudo foi investigar o efeito analgésico da lidocaína intravenosa em pacientes submetidas a mastectomia, como também, o consumo de opioide pós-operatório. MÉTODOS: Após aprovação pelo comitê de ética e pesquisa em seres humanos do Instituto de Medicina Integral Prof. Fernando Figueira em Recife - Pernambuco foi realizado ensaio clínico aleatório encoberto placebo controlado com lidocaína intravenosa na dose de 3 mg/kg infundida em uma hora, em 45 mulheres submetidas a mastectomia sob anestesia geral. Excluída uma paciente do grupo placebo. RESULTADOS: Os grupos foram semelhantes quanto à idade, índice de massa corpórea, tipo de intervenção cirúrgica e necessidade de opioide no pós-operatório. Solicitaram opioide 2/22 pacientes nos grupos da lidocaína e 3/22 placebo (p = 0,50). Identificada a dor ao despertar em 4/22 no grupo lidocaína e 5/22 (p = 0,50) no grupo placebo; na sala de recuperação pós-anestésica em 14/22 e 12/22 (p = 0,37) nos grupos lidocaína e placebo respectivamente. Ao avaliar a dor 24 horas após o procedimento cirúrgico 3/22 e 2/22 (p = 0,50) das pacientes relataram dor em ambos os grupos respectivamente. CONCLUSÃO: A lidocaína intravenosa na dose de 3mg/kg administrada em um período de uma hora no transoperatório de mastectomia não promoveu analgesia adicional em relação ao grupo placebo nas primeiras 24 horas e não diminuiu o consumo de opioide. Contudo, um efeito benéfico da lidocaína intravenosa em pacientes selecionadas e/ou em outros regimes terapêuticos não pode ser descartado. .


JUSTIFICACIÓN Y OBJETIVO: El tratamiento del dolor postoperatorio en la mastectomía continúa siendo un gran reto a pesar del abordaje multimodal. El objetivo de este estudio fue investigar el efecto analgésico de la lidocaína intravenosa en pacientes sometidas a mastectomía, así como el consumo postoperatorio de opiáceos. MÉTODOS: Después de la aprobación por el Comité de Ética e Investigación en seres humanos del Instituto de Medicina Integral Prof. Fernando Figueira, en Recife, Pernambuco, se realizó un ensayo clínico aleatorizado, encubierto, placebo controlado con lidocaína intravenosa en una dosis de 3 mg/kg infundida en una hora, en 45 mujeres sometidas a mastectomía bajo anestesia general. Una paciente del grupo placebo fue excluida. RESULTADOS: Los grupos fueron similares en cuanto a la edad, índice de masa corporal, tipo de intervención quirúrgica y necesidad de opiáceos en el postoperatorio. Solicitaron opiáceos 2/22 pacientes en los grupos de la lidocaína y 3/22 placebo (p = 0,50). Fue identificado el dolor al despertar en 4/22 en el grupo lidocaína y 5/22 (p = 0,50) en el grupo placebo; en la sala de recuperación postanestésica en 14/22 y 12/22 (p = 0,37) en los grupos lidocaína y placebo, respectivamente. Al calcular el dolor 24 h después del procedimiento quirúrgico 3/22 y 2/22 (p = 0,50) de las pacientes relataron dolor en ambos grupos respectivamente. CONCLUSIÓN: La lidocaína intravenosa en una dosis de 3 mg/kg administrada en un período de una hora en el transoperatorio de mastectomía no generó analgesia adicional con relación al grupo placebo en las primeras 24 h y no disminuyó el consumo de opiáceos. Sin embargo, no puede ser descartado un efecto beneficioso de la lidocaína intravenosa en pacientes seleccionadas y/o en otros regímenes terapéuticos. .


Subject(s)
Humans , Metapneumovirus/genetics , Transcription, Genetic , Viral Proteins/chemistry , Amino Acid Sequence , Adenosine Monophosphate/metabolism , Crystallography, X-Ray , DNA , Edetic Acid/pharmacology , Molecular Dynamics Simulation , Molecular Sequence Data , Protein Binding , Protein Conformation , Protein Multimerization , Protein Stability , Protein Subunits/chemistry , RNA, Viral/metabolism , RNA, Viral/ultrastructure , Scattering, Small Angle , Solutions , Solvents , Viral Proteins/metabolism , Viral Proteins/ultrastructure , Zinc Fingers
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