RESUMO
The aim of this study was to evaluate the antimicrobial activity and toxicity of glass ionomer cement (GIC) modified with 5-methyl-2-(1-methylethyl)phenol (thymol) against Streptococcus mutans in silico and in vitro. The antimicrobial activity of thymol on GIC modified with concentrations of 2% (GIC-2) and 4% (GIC-4) was evaluated in a model of planktonic cell biofilm using agar diffusion test, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), dynamic biofilm (continuous flow cell parallel), and bacterial kinetics. Conventional GIC (GIC-0) was used as a control. Thymol toxicity was evaluated in Artemia salina and in silico using Osiris® software. Differences between groups were estimated by analysis of variance, followed by Tukey post hoc test, with a 5% significance level. The results of the agar diffusion test between groups were not significantly different (P≥0.05). Thymol had potential bacteriostatic and bactericidal activity against Streptococcus mutans with respect to planktonic growth, with MIC of 100 µg/mL and MBC of 400 µg/mL. The groups GIC-0, GIC-2, and GIC-4 reduced the biofilm by approximately 10, 85, and 95%, respectively. Bacterial kinetics showed efficiency of the modified GICs for up to 96 h. GIC with thymol was effective against S. mutans, with significant inhibition of the biofilms. Analyses in silico and using Artemia salina resulted in no relevant toxicity, suggesting potential for use in humans. GIC-2 was effective against S. mutans biofilm, with decreased cell viability.
Assuntos
Anti-Infecciosos/farmacologia , Biofilmes , Cimentos de Ionômeros de Vidro/toxicidade , Humanos , Teste de Materiais , Óleos Voláteis/farmacologia , Streptococcus mutansRESUMO
The aim of this study was to evaluate the antimicrobial activity and toxicity of glass ionomer cement (GIC) modified with 5-methyl-2-(1-methylethyl)phenol (thymol) against Streptococcus mutans in silico and in vitro. The antimicrobial activity of thymol on GIC modified with concentrations of 2% (GIC-2) and 4% (GIC-4) was evaluated in a model of planktonic cell biofilm using agar diffusion test, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), dynamic biofilm (continuous flow cell parallel), and bacterial kinetics. Conventional GIC (GIC-0) was used as a control. Thymol toxicity was evaluated in Artemia salina and in silico using Osiris® software. Differences between groups were estimated by analysis of variance, followed by Tukey post hoc test, with a 5% significance level. The results of the agar diffusion test between groups were not significantly different (P≥0.05). Thymol had potential bacteriostatic and bactericidal activity against Streptococcus mutans with respect to planktonic growth, with MIC of 100 µg/mL and MBC of 400 µg/mL. The groups GIC-0, GIC-2, and GIC-4 reduced the biofilm by approximately 10, 85, and 95%, respectively. Bacterial kinetics showed efficiency of the modified GICs for up to 96 h. GIC with thymol was effective against S. mutans, with significant inhibition of the biofilms. Analyses in silico and using Artemia salina resulted in no relevant toxicity, suggesting potential for use in humans. GIC-2 was effective against S. mutans biofilm, with decreased cell viability.
Assuntos
Humanos , Anti-Infecciosos/farmacologia , Streptococcus mutans , Teste de Materiais , Óleos Voláteis/farmacologia , Biofilmes , Cimentos de Ionômeros de Vidro/toxicidadeRESUMO
This study compares the fertility effects of inducing ovulation using the GnRH analogue, dephereline, versus natural GnRH at the end of a 5-day progesterone(P4)-based protocol for fixed-time artificial insemination (FTAI) in in heat-stressed and non-heat stressed lactating dairy cows. Cows were given GnRH (GnRH group, nâ¯=â¯369) or dephereline (DEPH group, nâ¯=â¯379) and were inseminated 14-20â¯h later. Dephereline treatment increased corpus luteum (CL) size on Day 7 post-AI compared with GnRH (Pâ¯<â¯.0001) while a one-mm increase in CL size was found to give rise to a 1.1-fold increase in the pregnancy rate at FTAI (Pâ¯=â¯.001). Based on odds ratios, the interaction between treatment and heat stress had a significant effect on the ovulation failure rate (Pâ¯<â¯.01). This meant that relative to non-heat-stressed GnRH-treated cows, ovulation failure was 2.9 times more likely in heat-stressed GnRH-treated cows (Pâ¯=â¯.001), 0.3 times less likely in non-heat-stressed DEPH-treated cows (Pâ¯=â¯.04) and was similar in heat-stressed DEPH-treated cows. Further, non-heat-stressed DEPH-treated cows were more likely to conceive by a factor of 1.6 than the remaining cows (Pâ¯=â¯.03). Finally, GnRH-treated multiparous cows were 9.9 times more likely to suffer pregnancy loss than the remaining cows (Pâ¯=â¯.03). Our results indicate that, compared to treatment with GnRH, dephereline reduced the risk of ovulation failure and consequently increased the pregnancy rate under heat stress conditions. In multiparous cows, dephereline treatment also reduced the negative age effect on pregnancy maintenance.
Assuntos
Bovinos , Sincronização do Estro/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Inseminação Artificial/veterinária , Ovulação/efeitos dos fármacos , Animais , Corpo Lúteo , Feminino , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/farmacologia , Lactação/efeitos dos fármacos , Gravidez , Taxa de Gravidez , Progesterona/farmacologiaRESUMO
From a biogeographic perspective, Africa is subdivided into distinct horizontal belts. Human populations living along the Sahel/Savannah belt south of the Sahara desert have often been overshadowed by extensive studies focusing on other African populations such as hunter-gatherers or Bantu in particular. However, the Sahel together with the Savannah bordering it in the south is a challenging region where people had and still have to cope with harsh climatic conditions and show resilient behaviours. Besides exponentially growing urban populations, several local groups leading various lifestyles and speaking languages belonging to three main linguistic families still live in rural localities across that region today. Thanks to several years of consistent population sampling throughout this area, the genetic history of the African Sahelian populations has been largely reconstructed and a deeper knowledge has been acquired regarding their adaptation to peculiar environments and/or subsistence modes. Distinct exposures to pathogens-in particular, malaria-likely contributed to their genetic differentiation for HLA genes. In addition, although food-producing strategies spread within the Sahel/Savannah belt relatively recently, during the last five millennia according to recent archaeological and archaeobotanical studies, remarkable amounts of genetic differences are also observed between sedentary farmers and more mobile pastoralists at multiple neutral and selected loci, reflecting both demographic effects and genetic adaptations to distinct cultural traits, such as dietary habits.
Assuntos
População Negra/genética , Etnicidade/genética , Genética Populacional , DNA Mitocondrial/genética , Haplótipos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
With the aim to understand how next-generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well-documented population from sub-Saharan Africa (Mandenka). The results of full-gene NGS-MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity. A comprehensive analysis of exons 2, 3, 4 and 5 nucleotide diversity at the 8 HLA loci revealed remarkable differences among these gene regions, notably a greater variation concentrated in the antigen recognition sites of class I exons 3 and some class II exons 2, likely associated with their peptide-presentation function, a lower diversity of HLA-C exon 3, possibly related to its role as a KIR ligand, and a peculiar molecular diversity of HLA-A exon 2, revealing demographic signals. Based on full-length HLA sequences, we also propose that the most frequent DRB1 allele in the studied population, DRB1*13:04, emerged from an allelic conversion involving 3 potential alleles as donors and DRB1*11:02:01 as recipient. Finally, our analysis revealed a high occurrence of the DRB1*13:04-DQA1*05:05:01-DQB1*03:19 haplotype, possibly resulting from a selective sweep due to protection to Onchorcerca volvulus, a prevalent pathogen in West Africa. This study unveils highly relevant information on the molecular evolution of HLA genes in relation to their immune function, calling for similar analyses in other populations living in contrasting environments.
Assuntos
Antígenos HLA-A/genética , Antígenos HLA-C/genética , Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Adulto , África Subsaariana , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: A catalogue of common and well-documented (CWD) human leukocyte antigen (HLA), previously established by the American Society for Histocompatibility and Immunogenetics (ASHI), is widely used as indicator for typing ambiguities to be resolved in tissue transplantation or for checking the universality of any HLA allele in the world. However, European population samples, which are characterized by a substantial level of genetic variation, are underrepresented in the ASHI catalogue. Therefore, the Population Genetics Working Group of the European Federation for Immunogenetics (EFI) has facilitated data collection for an European CWD catalogue. MATERIALS AND METHODS: To this end, 2nd-field HLA-A, -B, -C,- DRB1,- DQA1,- DQB1 and -DPB1 data of 77 to 121 European population samples (21 571-3 966 984 individuals) from 3 large databases, HLA-net/Gene[VA], allelefrequencies.net and DKMS, were analysed. RESULTS: The total number of CWD alleles is similar in the EFI (N = 1048) and ASHI (N = 1031) catalogues, but the former counts less common (N = 236 vs 377) and more well-documented (N = 812 vs 654) alleles than the latter, possibly reflecting differences in sample numbers and sizes. Interestingly, approximately half of the CWD alleles reported by EFI were not reported by ASHI and vice-versa, underlining the distinct features of the two catalogues. Also, although 78 common alleles are widely distributed across Europe, some alleles are only common within specific sub-regions, showing regional variability. CONCLUSION: Although the definition of CWD alleles itself is affected by different parameters, calling for current updates of the list, the EFI CWD catalogue provides new insights into European population genetics and will be a very useful tool for tissue-typing laboratories in and beyond Europe.
Assuntos
Alelos , Variação Genética , Antígenos HLA/genética , Haplótipos , Imunogenética/métodos , Bases de Dados Factuais , Europa (Continente) , Expressão Gênica , Frequência do Gene , Genética Populacional , Antígenos HLA/classificação , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Terminologia como Assunto , População BrancaRESUMO
Human leukocyte antigen (HLA) genes are very informative in population genetics studies and their variability has been widely used to reconstruct the history of geographic and/or demographic expansions of human populations. The characterization of HLA diversity at the population level is also fundamental in clinical studies, particularly for bone marrow transplantation programs. In this study, we investigated the HLA molecular variation in Rio Grande do Sul, South Brazil, in order to identify possible regional differences across this state. More than 97,000 bone marrow donors were typed at the HLA- A, -B and -DRB1 loci and analyzed by considering two kinds of subdivisions based on both self-identified ethnicity and place of residence: (a) the official geographic subdivision defined by the Brazilian Institute of Geography and Statistics and (b) known information about the colonization history of the state. HLA allele and haplotype frequencies were estimated and compared among the defined subgroups. The results indicate a lack of correlation between genetic variation and geography and thus no clear HLA genetic structure based on geographic criteria. On the other hand, major differences were observed regarding ethnicity. In addition, local populations from Rio Grande do Sul were found to be genetically similar to their corresponding parental European populations from Germany, Italy and Portugal, as documented by historical data. Overall, this study provides a thorough characterization of the HLA genetic variation in Rio Grande do Sul and a better understanding of its demographic history, being most useful for the development of more efficient strategies in bone marrow donors' recruitment.
RESUMO
The simultaneous typing of five-HLA loci at high resolution and the availability of pedigree data allowed us to characterize extended five-locus phased haplotypes in 124 Nigerian families and to compare the observed frequencies with those expected by an expectation-maximization algorithm for unphased data. Despite the occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed to protect against Plasmodium falciparum), as many as 82% of the sampled individuals carry two unique five-locus haplotypes and only three extended haplotypes with frequency above 1% exhibit significant linkage disequilibrium. Although preliminary, these results reveal an extreme level of HLA diversity in the Nigerian population, which reflects both its multi-ethnic composition and the very ancient demographic history of African populations.
Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Desequilíbrio de Ligação , Alelos , Família , Expressão Gênica , Frequência do Gene , Variação Genética , Genética Populacional , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DQ/imunologia , Cadeias HLA-DRB1/imunologia , Teste de Histocompatibilidade , Humanos , Nigéria , LinhagemRESUMO
Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.
Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Polimorfismo Genético , Roma (Grupo Étnico) , População Branca , Adolescente , Adulto , Alelos , Transplante de Medula Óssea , Feminino , Efeito Fundador , Deriva Genética , Haplótipos , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Filogeografia , Doadores de TecidosRESUMO
Recent studies have shown that under specific conditions such as high sample sizes and Hardy-Weinberg equilibrium, bone marrow donor registry data can be used to describe HLA molecular variation across a specific geographic area, thus providing excellent data sets to infer human migrations history. The province of Quebec is known to have experienced a complex history of settlement, characterized by multiple migrations and demographic changes. We thus analysed the data of more than 13 000 unrelated individuals acting as volunteer bone marrow donors who were molecularly typed for HLA-A, B and DRB1 polymorphisms in the Héma-Quebec registry. HLA allelic and haplotypic frequencies were estimated and compared among regions. The results indicate that, despite an overall low genetic diversity in Quebec, genetic variation is correlated with geography, compatible with isolation-by-distance across the province. However, some localities also harbour contrasting genetic profiles, that is a highly diversified genetic pool in the two main urban centres (Montréal and Laval) and a more pronounced genetic divergence of two specific regions characterized by a peculiar peopling history (Saguenay-Lac-St-Jean and Gaspésie-Îles-De-La-Madeleine). In agreement with other independent molecular markers, the observations based on HLA data thus account for the main demographic mechanisms that shaped the genetic structure of the present day Quebecer population. In addition, the detailed analysis of the Héma-Quebec registry provides key genetic information on which an efficient bone marrow transplantation recruitment strategy can be settled.
Assuntos
Heterogeneidade Genética , Genética Populacional , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Alelos , Transplante de Medula Óssea , Frequência do Gene , Variação Genética , Geografia , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Cadeias HLA-DRB1/imunologia , Haplótipos , Teste de Histocompatibilidade , Humanos , Desequilíbrio de Ligação , Tipagem Molecular , Quebeque , Sistema de Registros , Doadores de TecidosRESUMO
Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B*44:02:01G, DRB1*14:01:01G and DQB1*03:01:01G, was undertaken in 12 European populations. Ambiguities were resolved by polymerase chain reaction-sequence-specific amplification (PCR-SSP) or PCR-sequence-based typing (PCR-SBT) in a total of 5095 individuals. The results of the DRB1*14:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB1*14:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the B*44:02/44:27 ambiguity showed that B*44:27 had a high relative ratio in Slovenians (25.5%) and Bulgarians (37%) and low in French and Swiss (0.02-1%), and was not observed in Greeks and Italians. The highest relative ratio of DQB1*03:19 was found in Portuguese (11%), by contrast with low ratios (0-3%) in the other five populations. Analysis of the A, B, DRB1 phenotypes and family-derived haplotypes in 1719 and 403 individuals positive for either HLA-B*44:02G or DRB1*14:01G ambiguities, respectively, showed some preferential associations, such as A*26â¼DRB1*14:01, B*35â¼DRB1*14:01, B*38â¼DRB1*14:01 and B*44:27â¼DRB1*16. Because these ambiguities are located outside the peptide-binding site, they may not be recognized by alloreactive T-cells. However, because of strong linkage disequilibrium (LD), the DRB1*14:01 vs DRB1*14:54 and the B*44:02 vs B*44:27 mismatches are associated to DRB3-, and C-mismatches, respectively. These results are informative for algorithms searching unrelated hematopoietic stem cell donors. For B*44:27-positive patients, searches are expected to be more successful when requesting donors from Southeastern-European ancestry. Furthermore, the introduction of human leukocyte antigen (HLA)-typing strategies that allow resolving exon 4 (for class I) and exon 3 (for class II) polymorphisms can be expected to contribute significantly to population genetics studies.
Assuntos
Alelos , Frequência do Gene , Variação Genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Seleção do Doador , Europa (Continente) , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Doadores Vivos , MasculinoRESUMO
In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics, transplantation and epidemiological studies.
Assuntos
Alelos , Biologia Computacional/métodos , Antígenos HLA/genética , Software , África do Norte , Ásia Ocidental , Biologia Computacional/instrumentação , Bases de Dados Genéticas , Europa (Continente) , Frequência do Gene , Ligação Genética , Variação Genética , Antígenos HLA/classificação , Antígenos HLA/imunologia , Haplótipos , Teste de Histocompatibilidade , Humanos , FilogeografiaRESUMO
We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.
Assuntos
Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1/genética , Ásia , Etnicidade , Europa (Continente) , Frequência do Gene , Variação Genética , Genética Populacional , Genótipo , Haplótipos , Humanos , Oceania , Grupos PopulacionaisRESUMO
HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling strategies for population genetics' analyses) recommends avoiding outdated racial classifications and population names (e.g. 'Caucasian') and using instead geographic and/or cultural (e.g. linguistic) criteria to describe human populations (e.g. 'pan-European'). A standard 'HLA-NET POPULATION DATA QUESTIONNAIRE' has been finalized and is available for the whole HLA community. WG2 (HLA typing standards for population genetics analyses) recommends retaining maximal information when reporting HLA typing results. Rather than using the National Marrow Donor Program coding system, all ambiguities should be provided by listing all allele pairs required to explain each genotype, according to the formats proposed in 'HLA-NET GUIDELINES FOR REPORTING HLA TYPINGS'. The group also suggests taking into account a preliminary list of alleles defined by polymorphisms outside the peptide-binding sites that may affect population genetic statistics because of significant frequencies. WG3 (Bioinformatic strategies for HLA population data storage and analysis) recommends the use of programs capable of dealing with ambiguous data, such as the 'gene[rate]' computer tools to estimate frequencies, test for Hardy-Weinberg equilibrium and selective neutrality on data containing any number and kind of ambiguities. WG4 (Ethical issues) proposes to adopt thorough general principles for any HLA population study to ensure that it conforms to (inter)national legislation or recommendations/guidelines. All HLA-NET guidelines and tools are available through its website http://hla-net.eu.
Assuntos
Epidemiologia , Genética Populacional , Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Histocompatibilidade/genética , Transplante , Alelos , Biologia Computacional , Frequência do Gene/genética , Guias como Assunto , Teste de Histocompatibilidade/normas , Humanos , Estatística como AssuntoRESUMO
OBJECTIVE: To evaluate glycosaminoglycans (GAGs) in the parametrium, paraurethral tissue and vaginal apex in postmenopausal women with uterine prolapse and to evaluate the effect of 30-day estrogen therapy in these patients. MATERIAL AND METHODS: Double-blind trial of estrogen and placebo in 40 women with a control group of 20 premenopausal women without uterine prolapse. Twenty postmenopausal women with prolapse formed a second group and were treated with placebo for 30 days before vaginal hysterectomy. The third group included 20 postmenopausal women with prolapse who received 0.625 mg oral conjugated estrogens for 30 days before vaginal hysterectomy. Samples of the parametrium, vaginal apex and paraurethral tissue were obtained during surgery. RESULTS: Hyaluronic acid was the predominant GAG detected, followed by dermatan sulfate, chondroitin sulfate and heparan sulfate. In postmenopausal women with prolapse, we did not observe significant differences in total GAGs compared to the control group. However, hyaluronic acid was increased in the parametrium of women receiving estrogen compared to those treated with the placebo (2033.39â±â3037.90 mg/g vs. 587.87â±â697.89 mg/g, respectively; pâ=â0.041). CONCLUSIONS: There are differences in GAGs in the parametrium, paraurethral tissue and vaginal apex between women in premenopause and those in the postmenopause period. Therefore, 30-day estrogen therapy produces significant differences in levels of hyaluronic acid, dermatan sulfate and chondroitin sulfate.
Assuntos
Tecido Conjuntivo/metabolismo , Terapia de Reposição de Estrogênios , Glicosaminoglicanos/metabolismo , Uretra/metabolismo , Prolapso Uterino/terapia , Vagina/metabolismo , Método Duplo-Cego , Estrogênios/administração & dosagem , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Histerectomia Vaginal , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.
Assuntos
Genética Populacional/métodos , Antígenos HLA/genética , Imunogenética , Grupos Populacionais/genética , Software , Frequência do Gene , HumanosRESUMO
A five-year field study was conducted to evaluate the potential use of oiled and de-oiled two-phase olive mill waste (TPOMW and DTPOMW, respectively) as soil amendment on a representative olive grove soil: a Cutanic Luvisol. Treatments included a non-amended control, TPOMW1, TPOMW2, DTPOMW1 and DTPOMW2 (30, 60, 27 and 54Mgha(-1) dry weight equivalent). Significant increases (P<0.05) in organic carbon, total N, available P and K, and aggregate stability were observed in the amended soils. Leaf analysis showed significant increases in N, P, and K concentrations in treated plots after the two first years of TPOMW or DTPOMW amendments. Also, a general increase in olive production was observed in the treated plots, this increase being higher in the TPOMW1 and DTPOMW1 treated soils. After five years of repeated TPOMW and DTPOMW application, the increase in yield was 29%, 9.8%, 30%, and 19% for TPOMW1, TPOMW2, DTPOMW1, and DTPOMW2, respectively. Raw TPOMW and DTPOMW have the potential to be valuable soil amendments and source of organic matter, with a positive effect on olive yield, and closing the cycle of residues-resources.