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1.
BMC Genomics ; 25(1): 487, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755557

RESUMO

BACKGROUND: The identification of low-frequency haplotypes, never observed in homozygous state in a population, is considered informative on the presence of potentially harmful alleles (candidate alleles), putatively involved in inbreeding depression. Although identification of candidate alleles is challenging, studies analyzing the dynamics of potentially harmful alleles are lacking. A pedigree of the highly endangered Gochu Asturcelta pig breed, including 471 individuals belonging to 51 different families with at least 5 offspring each, was genotyped using the Axiom PigHDv1 Array (658,692 SNPs). Analyses were carried out on four different cohorts defined according to pedigree depth and at the whole population (WP) level. RESULTS: The 4,470 Linkage Blocks (LB) identified in the Base Population (10 individuals), gathered a total of 16,981 alleles in the WP. Up to 5,466 (32%) haplotypes were statistically considered candidate alleles, 3,995 of them (73%) having one copy only. The number of alleles and candidate alleles varied across cohorts according to sample size. Up to 4,610 of the alleles identified in the WP (27% of the total) were present in one cohort only. Parentage analysis identified a total of 67,742 parent-offspring incompatibilities. The number of mismatches varied according to family size. Parent-offspring inconsistencies were identified in 98.2% of the candidate alleles and 100% of the LB in which they were located. Segregation analyses informed that most potential candidate alleles appeared de novo in the pedigree. Only 17 candidate alleles were identified in the boar, sow, and paternal and maternal grandparents and were considered segregants. CONCLUSIONS: Our results suggest that neither mutation nor recombination are the major forces causing the apparition of candidate alleles. Their occurrence is more likely caused by Allele-Drop-In events due to SNP calling errors. New alleles appear when wrongly called SNPs are used to construct haplotypes. The presence of candidate alleles in either parents or grandparents of the carrier individuals does not ensure that they are true alleles. Minimum Allele Frequency thresholds may remove informative alleles. Only fully segregant candidate alleles should be considered potentially harmful alleles. A set of 16 candidate genes, potentially involved in inbreeding depression, is described.


Assuntos
Alelos , Haplótipos , Linhagem , Polimorfismo de Nucleotídeo Único , Animais , Suínos/genética , Dinâmica Populacional , Feminino , Masculino , Frequência do Gene
2.
Genet Sel Evol ; 55(1): 74, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880572

RESUMO

BACKGROUND: In spite of the availability of single nucleotide polymorphism (SNP) array data, differentiation between observed homozygosity and that caused by mating between relatives (autozygosity) introduces major difficulties. Homozygosity estimators show large variation due to different causes, namely, Mendelian sampling, population structure, and differences among chromosomes. Therefore, the ascertainment of how inbreeding is reflected in the genome is still an issue. The aim of this research was to study the usefulness of genomic information for the assessment of genetic diversity in the highly endangered Gochu Asturcelta pig breed. Pedigree depth varied from 0 (founders) to 4 equivalent discrete generations (t). Four homozygosity parameters (runs of homozygosity, FROH; heterozygosity-rich regions, FHRR; Li and Horvitz's, FLH; and Yang and colleague's FYAN) were computed for each individual, adjusted for the variability in the base population (BP; six individuals) and further jackknifed over autosomes. Individual increases in homozygosity (depending on t) and increases in pairwise homozygosity (i.e., increase in the parents' mean) were computed for each individual in the pedigree, and effective population size (Ne) was computed for five subpopulations (cohorts). Genealogical parameters (individual inbreeding, individual increase in inbreeding, and Ne) were used for comparisons. RESULTS: The mean F was 0.120 ± 0.074 and the mean BP-adjusted homozygosity ranged from 0.099 ± 0.081 (FLH) to 0.152 ± 0.075 (FYAN). After jackknifing, the mean values were slightly lower. The increase in pairwise homozygosity tended to be twofold higher than the corresponding individual increase in homozygosity values. When compared with genealogical estimates, estimates of Ne obtained using FYAN tended to have low root-mean-squared errors. However, Ne estimates based on increases in pairwise homozygosity using both FROH and FHRR estimates of genomic inbreeding had lower root-mean-squared errors. CONCLUSIONS: Parameters characterizing homozygosity may not accurately depict losses of variability in small populations in which breeding policy prohibits matings between close relatives. After BP adjustment, the performance of FROH and FHRR was highly consistent. Assuming that an increase in homozygosity depends only on pedigree depth can lead to underestimating it in populations with shallow pedigrees. An increase in pairwise homozygosity computed from either FROH or FHRR is a promising approach for characterizing autozygosity.


Assuntos
Endogamia , Polimorfismo de Nucleotídeo Único , Humanos , Suínos , Animais , Linhagem , Homozigoto , Genoma , Genótipo
3.
Animals (Basel) ; 13(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37508128

RESUMO

Copy number variations regions (CNVRs) can be classified either as segregating, when found in both parents, and offspring, or non-segregating. A total of 65 segregating and 31 non-segregating CNVRs identified in at least 10 individuals within a dense pedigree of the Gochu Asturcelta pig breed was subjected to enrichment and functional annotation analyses to ascertain their functional independence and importance. Enrichment analyses allowed us to annotate 1018 and 351 candidate genes within the bounds of the segregating and non-segregating CNVRs, respectively. The information retrieved suggested that the candidate genes spanned by segregating and non-segregating CNVRs were functionally independent. Functional annotation analyses allowed us to identify nine different significantly enriched functional annotation clusters (ACs) in segregating CNVR candidate genes mainly involved in immunity and regulation of the cell cycle. Up to five significantly enriched ACs, mainly involved in reproduction and meat quality, were identified in non-segregating CNVRs. The current analysis fits with previous reports suggesting that segregating CNVRs would explain performance at the population level, whereas non-segregating CNVRs could explain between-individuals differences in performance.

4.
Gene ; 854: 147111, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36509293

RESUMO

Copy Number Variation Regions (CNVR) were subjected to pedigree analysis to contribute to the understanding of their segregation patterns. Up to 492 Gochu Asturcelta pig individuals forming 478 different parents-offspring trios (61 different families) were genotyped using the Axiom_PigHDv1 Array (658,692 SNPs). CNVR calling, performed using two different platforms (PennCNV and QuantiSNP), allowed to identify a total of 344 candidate CNVR on the 18 porcine autosomes covering about 106.8 Mb of the pig genome. Sixty-nine CNVR were identified, to some extent, in both the parents and the offspring and were classified as segregating CNVR. The other candidate CNVR were called in one or more progeny but in neither parent and classified either as singleton or recurrent de novo CNVR. Segregating CNVR were, on average, larger and more frequent than the recurrent de novo CNVR (444.8 kb vs 287.9 kb long and 34 vs 5 individuals, respectively). In any case, segregating CNVR did not conform to strict Mendelian inheritance patterns: estimates of average paternal and maternal transmission rates ranged from 11.0 % to 13.4 % and mean inheritance rate was below 21 %. This issue should be carefully considered when interpreting the results of CNV studies. Segregating CNVR, present across generations, are unlikely to be artifacts or false positives and can be hypothesized to be important at the population level.


Assuntos
Variações do Número de Cópias de DNA , Genoma , Animais , Suínos , Linhagem , Genótipo , Padrões de Herança , Polimorfismo de Nucleotídeo Único
5.
Sci Rep ; 12(1): 19686, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385499

RESUMO

Up to 478 Gochu Asturcelta pig parents-offspring trios (61 different families) were genotyped using the Axiom_PigHDv1 Array to identify the causes of Mendelian errors (ME). Up to 545,364 SNPs were retained. Up to 40,540 SNPs gathering 292,297 allelic mismatches were identified and were overlapped with SINEs and LINEs (Sscrofa genome 11.1). Copy number variations (CNV) were called using PennCNV. ME were classified into eight different classes according to the trio member ("Trio" meaning no assignment) and the allele on which ME was identified: TrioA/B, FatherA/B, MotherA/B, OffspringA/B. Most ME occurred due to systematic causes: (a) those assigned to the Father, Mother or Offspring occurred by null or partial null alleles characterized by heterozygote deficiency, varied with family size, involved a low number of loci (6506), and gathered most mismatches (228,145); (b) TrioB errors varied with family size, covaried with SINEs, LINEs and CNV, and involved most ME loci (33,483) and mismatches (65,682); and (c) TrioA errors were non-systematic ME with no sampling bias involving 1.2% of mismatches only and a low number of loci (1939). The influence of TrioB errors on the overall genotyping quality may be low and, since CNV vary among populations, their removal should be considered in each particular dataset. ME assignable to the Father, Mother or Offspring may be consistent within technological platforms and may bias severely linkage or association studies. Most ME caused by null or partial null alleles can be removed using heterozygote deficiency without affecting the size of the datasets.


Assuntos
Variações do Número de Cópias de DNA , Genômica , Suínos , Animais , Linhagem , Genótipo , Características da Família
6.
Molecules ; 27(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364359

RESUMO

The chemical composition and biological capacities of berries depend on environmental parameters, maturity, and location. The Andean blueberry (Vaccinium floribundum Kunth), also known as mortiño, presents a unique combination of several phytochemicals, which play a synergistic role in its characterization as a functional food. We aimed to expose the possible variations that exist in the profile of the phenolic compounds as well as the antioxidant and antimicrobial capacity of the wild Andean blueberry with respect to three ripeness stages and two different altitudes. We found that polyphenols are the predominant compounds in the berry during the early ripeness stage and are the main bioactive compounds that give rise to the antioxidant capacity and inhibition effect on the growth of gram-positive and gram-negative bacteria. Moreover, the accumulation of ascorbic acid, free amino acids, and anthocyanins increases as the ripening process progresses, and they were the main bioactive compounds in the ripe berry. The latter compounds influence the production of the typical bluish or reddish coloration of ripe blueberries. In addition, it was determined that environmental conditions at high altitudes could have a positive influence in all cases. Overall, our data provide evidence regarding the high functional value of the wild Andean blueberry.


Assuntos
Anti-Infecciosos , Mirtilos Azuis (Planta) , Vaccinium , Mirtilos Azuis (Planta)/química , Vaccinium/química , Antioxidantes/química , Antocianinas/química , Altitude , Antibacterianos/análise , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Frutas/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/análise
7.
Animals (Basel) ; 12(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36009719

RESUMO

A total of 106 West African taurine cattle belonging to the Lagunaire breed of Benin (33), the N'Dama population of Burkina Faso (48), and N'Dama cattle sampled in Congo (25) were analyzed for Copy Number Variations (CNVs) using the BovineHDBeadChip of Illumina and two different CNV calling programs: PennCNV and QuantiSNP. Furthermore, 89 West African zebu samples (Bororo cattle of Mali and Zebu Peul sampled in Benin and Burkina Faso) were used as an outgroup to ensure that analyses reflect the taurine cattle genomic background. Analyses identified 307 taurine-specific CNV regions (CNVRs), covering about 56 Mb on all bovine autosomes. Gene annotation enrichment analysis identified a total of 840 candidate genes on 168 taurine-specific CNVRs. Three different statistically significant functional term annotation clusters (from ACt1 to ACt3) involved in the immune function were identified: ACt1 includes genes encoding lipocalins, proteins involved in the modulation of immune response and allergy; ACt2 includes genes encoding coding B-box-type zinc finger proteins and butyrophilins, involved in innate immune processes; and Act3 includes genes encoding lectin receptors, involved in the inflammatory responses to pathogens and B- and T-cell differentiation. The overlap between taurine-specific CNVRs and QTL regions associated with trypanotolerant response and tick-resistance was relatively low, suggesting that the mechanisms underlying such traits may not be determined by CNV alterations. However, four taurine-specific CNVRs overlapped with QTL regions associated with both traits on BTA23, therefore suggesting that CNV alterations in major histocompatibility complex (MHC) genes can partially explain the existence of genetic mechanisms shared between trypanotolerance and tick resistance in cattle. This research contributes to the understanding of the genomic features of West African taurine cattle.

8.
J Anim Breed Genet ; 139(1): 13-25, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34494688

RESUMO

In genetic evaluation of horses, the genetic trend does not correspond into a phenotypic trend when using ranking as a phenotype due to its uniform distribution, and some other effects might be absorbing that trend. From a founder population, a further four discrete generations of 100 individuals were simulated under random mating. Then, ten additional discrete generations were simulated by selecting the best 10% of the animals. Likewise, an underlying variable with heritability 0.1 or 0.2, affected by an event environmental influence, generation and permanent environment, was simulated to establish the ranking assignment of 10 random participants or according to the competitive level for each event, in 10 or 100 structured or unstructured events. The ranking trait genetic evaluation model was tested to include or exclude the event effect and the permanent environment effect, depending on the scenario. The results showed that the event effect fitted the different competitive level of each event, leading to a 5% to 23% of selection response improvement for structured competitions. Therefore, the event effect should be included in the genetic evaluation models of horses. The permanent environment fitted or simulated did not significantly improve the selection response. The event effect explained the competition genetic level, by compensating the genetic trend obtained by selection.


Assuntos
Modelos Genéticos , Reprodução , Animais , Cavalos/genética , Fenótipo
9.
Biociencias ; 15(2)2020. tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1247685

RESUMO

Introducción: La aterosclerosis es un factor de riesgo para la enfermedad cardiovascular (ECV), la cuallidera anualmente los más altos índices de mortalidad,afectando principalmente apersonasmayores de 45 años. Sin embargo, la población infantil se está exponiendo afactores de riesgo que desencadenan la enfermedad a futuro; esta alteración patológica de las arterias coronarias se caracterizapor el depósito anormal de grasas;surgecomo consecuencia de las dislipidemias o anomalías en el metabolismo de los lípidos presentes en el plasma sanguíneo.Objetivo: Describir la caracterización de dislipidemias y riesgo aterogénico en escolares de la Institución Educativa Policarpa Salavarrieta, Bogotá D.C., 2015, con el fin de promover hábitos de vida saludables que permitan prevenir la enfermedad y disminuir a futuro la prevalencia de la Enfermedad Cardiovascular.Métodos: Estudio descriptivo, transversal. La muestra por conveniencia fue de88 niños y niñas con edades comprendidas entre los 6 a los 12 añosdela Institución Educativa Policarpa Salavarrieta, Bogotá D.C. Resultados: Los 88 escolares se distribuyeron en 62% (55) en niñas y un 38% (33) en niños. Se encontró que un 11% de los estudiantes presentaron hipercolesterolemia, un 19% hipertrigliceridemia y un 4% dislipidemia mixta. Adicionalmente 5 estudiantes sobrepasan el índice de Castelli (>4).Conclusión: Es importante realizar el perfil lipídico en la población infantil controlando los valores de lípidos plasmáticos, evitando así el desarrollo de arterosclerosis, el cual inicia desde edades tempranas, siendo éste un factor de riesgo para enfermedad cardiovascular, y dando relevancia al cambio de estilo de vida.


Introduction:Atherosclerosis is a risk factor for cardiovascular disease, which annually leads the highest mortality rates, mainly affecting people over 45 years of age. However, the child population is being exposed to risk factors that will trigger the disease in the future; this pathological alterationof the coronary arteries is characterized by abnormal fat deposition; it arises as a consequence of dyslipidemias or abnormalities in the lipid metabolism present in the blood plasma.Objective:Describe the characterization of dyslipidemias and atherogenic risk in schoolchildren from the Policarpa Salavarrieta Educational Institution, Bogotá D.C., 2015, in order to promote healthy lifestyle habits that prevent the disease and decrease the prevalence of Cardiovascular Disease in the future.Methods:Descriptive, cross-sectional study. The sample of convenience was 88 boys and girls aged 6 to 12 years at the Policarpa Salavarrieta Educational Institution, Bogotá D.C.Results:The 88 schoolchildren were distributed at 62% (55) in girls and 38% (33) in boys. It was found that 11% of the students presented hypercholesterolemia, 19% hypertriglyceridemia and 4% mixed dyslipidemia. Additionally, 5 students surpass the Castell index (> 4).Conclusion: It is important to carry out the lipid profile in the child population, controlling the plasma lipid values, thus avoiding the development of atherosclerosis, which begins from an early age, this being a risk factor for cardiovascular disease and giving relevance to lifestyle change.Keywords:Atherosclerosis; Risk factor; Cardiovascular Disease; Dyslipidemias; Lipid;Castell index.


Assuntos
Índice de Massa Triponderal , Análise de Mediação , Proteínas de Checkpoint Imunológico , Neoplasias
10.
Artigo em Inglês | MEDLINE | ID: mdl-28194191

RESUMO

BACKGROUND: Peanut sensitization does not necessarily indicate clinical peanut allergy, and uncertainty as to whether or not there is true peanut allergy can lead to increased anxiety and decreased quality of life for patients and their families. The gold standard for diagnosing clinical peanut allergy is the oral food challenge, but this method is time-consuming and can cause severe allergic reactions. It would therefore be beneficial to develop a tool for predicting clinical peanut allergy in peanut-sensitized individuals whose peanut allergy status is unknown so as to better determine who requires an oral food challenge for diagnosis. METHODS: Two separate studies were conducted. In Study 1, we recruited 100 participants from the allergy clinic at McMaster University and community allergy outpatient clinics in the greater Hamilton area. We examined 18 different variables from participants and used univariate and multivariable logistic regression analysis to determine how well these variables, singly and in combination, were able to predict clinical peanut allergy status. In Study 2, we conducted a retrospective chart review of a second cohort of 194 participants to investigate the reproducibility of our findings. This was a matched case-control study where 97 peanut-allergic participants were gender- and age-matched to 97 non-allergic control participants. RESULTS: Peanut skin prick test wheal size was the best predictor of clinical peanut allergy in both study cohorts. For every 1 mm increase in wheal size, the odds ratio of an individual having clinical peanut allergy was 2.36 in our first cohort and 4.85 in our second cohort. No other variable approached the predictive power of wheal size. CONCLUSIONS: Peanut skin prick test wheal size is a robust predictor of clinical peanut reactivity. The findings of this study may be useful in guiding clinician decision-making regarding peanut allergy diagnostics.

11.
J Allergy Clin Immunol ; 127(6): 1552-61.e1, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21624619

RESUMO

BACKGROUND: Food-induced anaphylaxis is often a severe allergic reaction characterized by multiorgan dysfunction and a potentially fatal outcome. OBJECTIVES: We sought to investigate the relative contribution of immunoglobulin-dependent effector pathways to anaphylactic responses to food (ie, peanut). METHODS: Wild-type and various mutant mice were sensitized with peanut protein and cholera toxin by means of oral gavage weekly for 4 weeks. Mice were subjected to different cellular depletion and Fc receptor blocking strategies before challenge with peanut 1 week after the last sensitization. RESULTS: Our data indicate that pathways other than the classical mast cell (MC)-IgE pathway contribute to the full spectrum of anaphylactic reactions to peanut. We show that the single deletion of MCs, basophils, or phagocytes (ie, macrophages) prevents the most significant clinical outcome: death. Remarkably, the combined deficiency of MCs and phagocytes, but not MCs and basophils, averted nearly all clinical and physiological signs of anaphylaxis. Furthermore, blockade of both IgE and IgG1 signaling was necessary to abolish anaphylactic responses to peanut. Although MC responses occurred through IgE and IgG1, phagocyte responses were fully mediated through IgG1. CONCLUSIONS: Peanut-induced anaphylaxis is a process that involves the concerted action of multiple immune effector pathways, and thus interventions targeting a single pathway (eg, MC-IgE) might not be sufficient to fully prevent anaphylactic responses.


Assuntos
Anafilaxia/imunologia , Hipersensibilidade a Amendoim/imunologia , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Animais , Basófilos/imunologia , Feminino , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Macrófagos/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Hipersensibilidade a Amendoim/etiologia , Receptores de IgG/metabolismo , Transdução de Sinais/imunologia
12.
Am J Respir Crit Care Med ; 183(2): 179-88, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20732990

RESUMO

RATIONALE: Current thinking accredits eosinophils with preeminent contributions to allergic airway responses, including a major role in the development of airway remodeling, a process thought to significantly contribute to airway dysfunction. However, direct evidence in support of this notion is limited and often controversial. OBJECTIVES: We elucidated the requirement for eosinophils in the generation of allergic sensitization, airway inflammation, and remodeling in a model involving chronic respiratory exposure to house dust mite (HDM). METHODS: We used three methods to selectively eliminate eosinophils, a depleting antibody (anti-CCR3), and two strains of eosinophil-deficient mice (ΔdblGATA and the transgenic line PHIL). MEASUREMENTS AND MAIN RESULTS: Anti-CCR3 treatment markedly reduced pulmonary eosinophilia (> 80%) over the course of HDM exposure but had no effect on the remaining inflammatory response, the extent of lung Th2 cells, or the development of remodeling-associated changes, including subepithelial collagen deposition and smooth muscle thickening. In addition, we observed that, despite the absence of eosinophils, HDM-exposed GATA mice mounted robust airway and lung inflammation and hyperresponsiveness and showed a remodeling response equivalent to that observed in wild-type mice. Moreover, these mice had similar serum HDM-specific IgE levels and Th2-associated splenocyte cytokine production as HDM-exposed wild-type control mice. Similar observations were made in PHIL eosinophil-deficient mice subjected to chronic HDM exposure, although slight decreases in airway mononuclear cells, but not lung Th2 cells, and remodeling were noted. CONCLUSIONS: Collectively, these data demonstrate that, at variance with the prevailing paradigm, eosinophils play negligible roles in the generation of HDM-induced allergic immunity and airway remodeling.


Assuntos
Eosinófilos/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Colágeno/imunologia , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/etiologia , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/metabolismo , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo
13.
J Allergy Clin Immunol ; 124(2): 307-14, 314.e1-2, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19409603

RESUMO

BACKGROUND: Food anaphylaxis is an acute and life-threatening systemic allergic reaction. Fatality registries place peanut as the most common culprit of fatal and near-fatal reactions in North America. Because prophylaxis and treatment have advanced little in recent years, it is imperative to evaluate novel therapies. OBJECTIVE: To investigate the impact of blocking mast cell mediators in a mouse model of peanut-induced anaphylaxis. METHODS: Mice were sensitized with peanut protein and cholera toxin via oral gavage weekly for 4 weeks. One week after the last sensitization, separate groups of mice were treated with either a (1) 5-lypoxygenase inhibitor, (2) a platelet-activating factor (PAF) receptor antagonist, (3) histamine receptor antagonists, or (4) a PAF receptor antagonist along with histamine receptor antagonists before peanut challenge. RESULTS: Treatment targeting either leukotrienes or histamine alone had no beneficial effects. In contrast, PAF antagonism significantly attenuated the magnitude and duration of the anaphylactic reactions. Particularly, it prevented severe reactions. Moreover, 83% of PAF-treated versus 43% of untreated mice reached recovery within 120 minutes after peanut challenge. Notably, combined blockade of PAF and histamine had a clearly greater beneficial effect. In fact, all but 1 mouse developed mild, if any, anaphylactic reactions. In addition, combination therapy was associated with a significant decrease in vascular leakage and release of vasoactive mediators after peanut challenge. CONCLUSION: Combination therapy blocking both PAF and histamine markedly reduces the severity of peanut-induced anaphylaxis, and thus it may be a potential life-saving therapeutic approach in peanut and, likely, other food-induced anaphylaxis.


Assuntos
Anafilaxia/prevenção & controle , Arachis/imunologia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Histamina/metabolismo , Hipersensibilidade a Amendoim/complicações , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Alérgenos/imunologia , Anafilaxia/imunologia , Animais , Toxina da Cólera/imunologia , Cimetidina/administração & dosagem , Cimetidina/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Feminino , Histamina/imunologia , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/farmacologia , Hidroxiureia/administração & dosagem , Hidroxiureia/análogos & derivados , Hidroxiureia/farmacologia , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Inibidores de Lipoxigenase/administração & dosagem , Inibidores de Lipoxigenase/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Pirilamina/administração & dosagem , Pirilamina/farmacologia , Receptores Histamínicos/imunologia , Receptores Histamínicos/metabolismo
14.
Curr Clin Pharmacol ; 4(2): 113-25, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19442076

RESUMO

Anaphylaxis is an acute and often severe systemic allergic reaction. The prevalence of food allergy has been increasing and is currently estimated at approximately 3.5%. Food allergic reactions account for one-third to one-half of anaphylaxis cases worldwide. It is estimated that approximately 30,000 food-related anaphylactic reactions are treated in United States emergency departments (ED) every year resulting in approximately 2000 hospitalizations and 150 deaths. The increasing rate of food-induced anaphylactic episodes in the last few decades underlines the existence of major challenges. This review will critically appraise current guidelines for the diagnosis as well as the acute and long-term management of food-induced anaphylaxis (FIA). Importantly, it will outline existing challenges and suggest measures to improve outcomes in patients with FIA. We propose that the discovery of novel diagnostic (i.e. biomarkers and predictors) and therapeutic approaches is a major challenge that may be overcome as the mechanisms underlying FIA are better delineated. We further propose that better dissemination, implementation and compliance with the consensus management guidelines are urgently needed. This will require education of ED personnel, patient empowerment as well as effective multilateral communication among patients, emergency and family physicians, allergists and specialized volunteer organizations.


Assuntos
Anafilaxia/terapia , Hipersensibilidade Alimentar/terapia , Guias de Prática Clínica como Assunto , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Animais , Biomarcadores/metabolismo , Serviços Médicos de Emergência/métodos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/etiologia , Fidelidade a Diretrizes , Humanos , Disseminação de Informação/métodos , Prevalência , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Regul Toxicol Pharmacol ; 54(3 Suppl): S37-40, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19047008

RESUMO

Many commodity crops are grown for human consumption, and the resulting food products usually contain proteins, some of which may be allergenic. The legumes, peanut and soybean, as well as tree nuts and some cereal grains are well recognized sources of food allergens. In peanut, there are 11 documented allergenic proteins, although the major allergens are considered to be Ara h 1 and Ara h 2, both of which are seed storage proteins. Methods to reduce or eliminate these proteins from seeds are available and allow the feasibility of this approach to be tested. Greatly reduced amounts of Ara h 2 can be achieved by RNA silencing in transgenic peanut; however, mutagenesis is a more viable and socially acceptable approach to allergen elimination. Although the techniques for mutagenesis are not new, methods for mutant detection at the molecular level have recently been developed. However, these methods are dependent on genome sequence. These methods will facilitate discovery of spontaneous and induced mutations that may be useful over the long term to eliminate certain allergens from peanut.


Assuntos
Albuminas 2S de Plantas/genética , Alérgenos/genética , Produtos Agrícolas/imunologia , Glicoproteínas/genética , Mutação , Antígenos de Plantas , Splicing de RNA
16.
Hacia promoc. salud ; 13: 131-142, ene.-dic. 2008. graf
Artigo em Espanhol | LILACS | ID: lil-539794

RESUMO

Este estudio descriptivo tiene como principal objetivo determinar algunos aspectos de la calidad del control prenatal realizado por el profesional de enfermería en una IPS pública de Manizales en el año 2007, basados en el grado de adherencia a la Norma técnica de detección temprana de las alteraciones del embarazo contenida en la Resolución 412 de 2000; con la información obtenida a partir de las historias clínicas, se evaluó la calificación obtenida en cada ítem de acuerdo a los criterios obtenidos en el Anexo 1. La población fue de 613 gestantes inscritas en el programa de control prenatal de dicha IPS, y 120 mujeres escogidas para la muestra por medio de la técnica de distribución de frecuencia; para la graficación de los resultados se utilizaron diagramas de barras mostrados de manera comparativa. Los resultados muestran que algunas variables tales como: temperatura, educación a la gestante, solicitud y análisis de paraclínicos, remisión al curso de preparación para el parto, remisión al odontólogo, y la adopción de una conducta en caso de alteraciones del peso materno o de la altura uterina, se registraron entre un 25% y un 70%. Las variables evaluadas en cuanto a la satisfacción de las usuarias fueron: percepción del beneficio obtenido, preferencia por el control con la enfermera(o), satisfacción con la prestación del servicio; fueron calificadas por las usuarias con niveles superiores al 80%. Además se realizó una evaluación de la infraestructura y dotación de los consultorios, comparando la información recolectada con el formato de evaluación contenido en la Resolución 1043 del Sistema Obligatorio de Garantía de Calidad del Sistema General de Seguridad Social en Salud, para la habilitación de los servicios de salud. En cuanto a esta evaluación no se encontraron camillas con estribos, espéculos y portaobjetos dentro de los consultorios. En conclusión, este estudio...


The main objective of this descriptive study is to identify some aspects regarding the quality of prenatal care conducted by the nursing professionals in a public Health Service Provider (IPS by its initial in Spanish) in Manizales in 2007, based on the degree of adherence to the technical norm for early detection of changes in the pregnancy included in Resolution 412 of 2000. The study was done using information obtained from medical records, evaluating the points earned in each item according to the criteria in Annex 1. The population included 613 pregnant women enrolled in the prenatal control program of said IPS, and 120 women selected for the sample using the frequency distribution technique. For diagramming the results, bar charts were used displayed in a comparative manner. The results show that some variables such as temperature, education to pregnant women, application and analysis of paraclinical exams, referral to the childbirth preparation course, dentist referral, and the adoption of conducts in case of maternal weight and uterine height alterations, were in a 25% and 70%. The variables evaluated regarding the users’ satisfaction included the perception of the benefit obtained, preference for a particular nurse during the check-ups, service satisfaction, were described by the users with levels above 80%. In addition, an evaluation of the infrastructure and provision of the doctors’ offices was also made, comparing the information collected in the assessment form, included in Resolution 1043 of the Quality Mandatory System for the General Social Welfare Health System, for enabling health services. This evaluation found lack of stretchers with stirrups, speculums and slides within the doctors’ offices. In conclusion this study shows that the adhesion of nursing professionals to Resolution 412 of 2000 is between 70 and 90%.


Esta pesquisa descritiva tem como principal objetivo determinar alguns aspectos da qualidade do control pré-natal realizado por o profissional de enfermaria numa IPS publica de Manizales no ano 2007, baseados no grau de aderência à Norma técnica de detecção prematura das alterações da gestação conteúda na Resolução 412 de 2000; com a informação obtida a partir das historias clinicas, se avaliou a qualificação obtida em cada item de acordo a los critérios obtidos em o Anexo 1. A povoação foi de 613 gestantes inscritas no programa do control pré-natal de dita IPS, e 120 mulheres escolhidas para a mostra por médio da técnica de distribuição de freqüência, para a gratificação dos resultados se utilizaram diagramas de barras mostrados de maneira comparativa. Os resultados mostram que algumas variáveis como: temperatura, educação à gestante, solicitude e análise de paraclinicos, remissão ao curso de preparação para o parto, remissão ao dentista, e a adoção de uma conduta em caso de alterações do peso materna o da altura uterina, se registraram entre 25% e um 70%. As variáveis avaliadas em quanto à satisfação das usuárias foram: percepção do beneficio obtido, preferência por o control com a enfermeira(o), satisfação com a prestação do serviço; foram qualificadas pelas usuárias com niveles superiores ao 80%. Alias se realizou uma avaliação da infra-estrutura e dotação dos consultórios, comparando a informação recolhida com o formato de evacuação conteúda na Resolução 1043 do Sistema Obrigatório de Garantia de Qualidade do Sistema Geral de Seguridade Social em Saúde, para a habilitação dos serviços de saúde. Em quanto a esta evacuação não encontraram se macas com estribo, especulas um logo apropriado para guardar instrumentos médicos dentro dos consultórios. Em conclusão, este estudo demonstra que a aderência dos profissionais de enfermaria à Resolução 412 de 2000, esta entre o 70 e o 90%.


Assuntos
Humanos , Feminino , Gravidez , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/normas , Qualidade da Assistência à Saúde , Enfermagem/instrumentação , Enfermagem/métodos , Enfermagem/normas , Enfermagem , Satisfação do Paciente
17.
Am J Respir Crit Care Med ; 177(6): 593-603, 2008 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18174546

RESUMO

RATIONALE: It is now believed that both chronic airway inflammation and remodeling contribute significantly to airway dysfunction and clinical symptoms in allergic asthma. Transforming growth factor (TGF)-beta is a powerful regulator of both the tissue repair and inflammatory responses, and numerous experimental and clinical studies suggest that it may play an integral role in the pathogenesis of asthma. OBJECTIVES: We investigated the role of TGF-beta in the regulation of allergic airway inflammation and remodeling using a mouse model of house dust mite (HDM)-induced chronic allergic airway disease. METHODS: We have previously shown that intranasal administration of an HDM extract (5 d/wk for 5 wk) elicits robust Th2-polarized airway inflammation and remodeling that is associated with increased airway hyperreactivity. Here, Balb/c mice were similarly exposed to HDM and concurrently treated with a pan-specific TGF-beta neutralizing antibody. MEASUREMENTS AND MAIN RESULTS: We observed that anti-TGF-beta treatment in the context of either continuous or intermittent HDM exposure had no effect on the development of HDM-induced airway remodeling. To further confirm these findings, we also subjected SMAD3 knockout mice to 5 weeks of HDM and observed that knockout mice developed airway remodeling to the same extent as HDM-exposed littermate controls. Notably, TGF-beta neutralization exacerbated the eosinophilic infiltrate and led to increased airway hyperreactivity. CONCLUSIONS: Collectively, these data suggest that TGF-beta regulates HDM-induced chronic airway inflammation but not remodeling, and furthermore, caution against the use of therapeutic strategies aimed at interfering with TGF-beta activity in the treatment of this disease.


Assuntos
Asma/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Hipersensibilidade/imunologia , Pyroglyphidae/imunologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Asma/imunologia , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Eosinófilos , Feminino , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteína Smad3/genética , Proteína Smad3/imunologia
18.
J Immunol ; 179(10): 6696-703, 2007 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17982059

RESUMO

The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and FcepsilonRI in the elicitation of anaphylaxis in a murine model. Assessment of peanut hypersensitivity reactions was performed clinically and biologically. Our data show that wild-type (WT; C57BL/6 strain) mice consistently developed severe anaphylaxis (median clinical score: 3.5/5), an approximately 8 degrees C drop in core body temperature, and significantly increased plasma levels of histamine and leukotrienes. CD40 ligand- and B cell-deficient mice presented evidence of allergic sensitization as demonstrated by production of Th2-associated cytokines by splenocytes and a late-phase inflammatory response that were both indistinguishable to those detected in WT mice. However, CD40 ligand- and B cell-deficient mice did not exhibit any evidence of anaphylaxis. Our data also show that MC-deficient (Kit(W)/Kit(W-v)) mice did not suffer, unlike their littermate controls, anaphylactic reactions despite the fact that serum levels of peanut-specific Igs were similarly elevated. Finally, FcepsilonRI-deficient mice experienced anaphylactic responses although to a significantly lesser degree than those observed in WT mice. Thus, these data demonstrate that the presence of peanut-specific Abs along with functional MCs comprise a necessary and sufficient condition for the elicitation of peanut-induced anaphylaxis. That the absence of FcepsilonRI prevented the development of anaphylaxis only partially insinuates the contribution of an IgE-independent pathway, and suggests that strategies to impair MC degranulation may be necessary to improve the efficacy of anti-IgE therapy.


Assuntos
Anafilaxia/imunologia , Linfócitos B/imunologia , Ligante de CD40/imunologia , Mastócitos/imunologia , Hipersensibilidade a Amendoim/imunologia , Anafilaxia/sangue , Anafilaxia/induzido quimicamente , Anafilaxia/genética , Animais , Anticorpos/sangue , Anticorpos/imunologia , Linfócitos B/metabolismo , Temperatura Corporal/efeitos dos fármacos , Ligante de CD40/genética , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Histamina/sangue , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Leucotrienos/sangue , Mastócitos/metabolismo , Camundongos , Camundongos Knockout , Hipersensibilidade a Amendoim/sangue , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/terapia , Receptores de IgE/genética , Receptores de IgE/imunologia , Células Th2/imunologia , Células Th2/metabolismo
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