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[PMID]:29295973
[Au] Autor:Blaskovich MAT; Hansford KA; Gong Y; Butler MS; Muldoon C; Huang JX; Ramu S; Silva AB; Cheng M; Kavanagh AM; Ziora Z; Premraj R; Lindahl F; Bradford TA; Lee JC; Karoli T; Pelingon R; Edwards DJ; Amado M; Elliott AG; Phetsang W; Daud NH; Deecke JE; Sidjabat HE; Ramaologa S; Zuegg J; Betley JR; Beevers APG; Smith RAG; Roberts JA; Paterson DL; Cooper MA
[Ad] Endereço:Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.blaskovich@uq.edu.au.
[Ti] Título:Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria.
[So] Source:Nat Commun;9(1):22, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature's control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes. Peptide libraries based on positively charged electrostatic effector sequences are ligated to N-terminal lipophilic membrane-insertive elements and then conjugated to vancomycin. These modified lipoglycopeptides, the 'vancapticins', possess enhanced membrane affinity and activity against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria, and retain activity against glycopeptide-resistant strains. Optimised antibiotics show in vivo efficacy in multiple models of bacterial infection. This membrane-targeting strategy has potential to 'revitalise' antibiotics that have lost effectiveness against recalcitrant bacteria, or enhance the activity of other intravenous-administered drugs that target membrane-associated receptors.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Bactérias/efeitos dos fármacos
Daptomicina/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Proteínas de Membrana/metabolismo
Vancomicina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/metabolismo
Antibacterianos/farmacocinética
Bactérias/classificação
Sobrevivência Celular/efeitos dos fármacos
Glicopeptídeos/metabolismo
Células HEK293
Células Hep G2
Seres Humanos
Masculino
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Camundongos
Testes de Sensibilidade Microbiana
Viabilidade Microbiana/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycopeptides); 0 (Membrane Proteins); 6Q205EH1VU (Vancomycin); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02123-w


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[PMID]:29348072
[Au] Autor:Liu C; Chen X; Zhi X; Weng W; Li Q; Li X; Zou Y; Su J; Hu HG
[Ad] Endereço:Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
[Ti] Título:Structure-based development of an osteoprotegerin-like glycopeptide that blocks RANKL/RANK interactions and reduces ovariectomy-induced bone loss in mice.
[So] Source:Eur J Med Chem;145:661-672, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis. Herein, we disclose the successful development of a novel glycopeptide (OM-2), the structure of which is based on the key interacting sites of the reported RANKL and OPG crystal structure. OM-2 exhibited potent binding affinity with RANKL and resistance to degradation by protease enzymes. It also blocked RANKL/RANK interactions, and inhibited osteoclastogenesis in vitro. In vivo studies confirmed that OM-2 could effectively reduce bone loss and inhibit osteoclast activation in ovariectomized (OVX) mice at a dosage of 20.0 mg/kg/day. Accordingly, OM-2 is suggested as a therapeutic candidate for postmenopausal osteoporosis (PMOP) and osteoclastogenesis-related diseases like rheumatoid arthritis (RA). More importantly, its identification validates our structure-based strategy for the development of drugs that target the RANKL/RANK/OPG system.
[Mh] Termos MeSH primário: Glicopeptídeos/farmacologia
Osteoporose/tratamento farmacológico
Osteoprotegerina/farmacologia
Ovariectomia
Ligante RANK/antagonistas & inibidores
Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Osso e Ossos/efeitos dos fármacos
Osso e Ossos/metabolismo
Osso e Ossos/patologia
Relação Dose-Resposta a Droga
Feminino
Glicopeptídeos/síntese química
Glicopeptídeos/química
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Simulação de Acoplamento Molecular
Estrutura Molecular
Osteoporose/metabolismo
Osteoprotegerina/química
Ligação Proteica/efeitos dos fármacos
Ligante RANK/metabolismo
Receptores Citoplasmáticos e Nucleares/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycopeptides); 0 (Osteoprotegerin); 0 (RANK Ligand); 0 (Receptors, Cytoplasmic and Nuclear)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE


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[PMID]:27776480
[Au] Autor:Hanson MA; Hamilton PT; Perlman SJ
[Ad] Endereço:Department of Biology, University of Victoria, Victoria, BC, Canada. markhans@uvic.ca.
[Ti] Título:Immune genes and divergent antimicrobial peptides in flies of the subgenus Drosophila.
[So] Source:BMC Evol Biol;16(1):228, 2016 10 24.
[Is] ISSN:1471-2148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Drosophila is an important model for studying the evolution of animal immunity, due to the powerful genetic tools developed for D. melanogaster. However, Drosophila is an incredibly speciose lineage with a wide range of ecologies, natural histories, and diverse natural enemies. Surprisingly little functional work has been done on immune systems of species other than D. melanogaster. In this study, we examine the evolution of immune genes in the speciose subgenus Drosophila, which diverged from the subgenus Sophophora (that includes D. melanogaster) approximately 25-40 Mya. We focus on D. neotestacea, a woodland species used to study interactions between insects and parasitic nematodes, and combine recent transcriptomic data with infection experiments to elucidate aspects of host immunity. RESULTS: We found that the vast majority of genes involved in the D. melanogaster immune response are conserved in D. neotestacea, with a few interesting exceptions, particularly in antimicrobial peptides (AMPs); until recently, AMPs were not thought to evolve rapidly in Drosophila. Unexpectedly, we found a distinct diptericin in subgenus Drosophila flies that appears to have evolved under diversifying (positive) selection. We also describe the presence of the AMP drosocin, which was previously thought to be restricted to the subgenus Sophophora, in the subgenus Drosophila. We challenged two subgenus Drosophila species, D. neotestacea and D. virilis with bacterial and fungal pathogens and quantified AMP expression. CONCLUSIONS: While diptericin in D. virilis was induced by exposure to gram-negative bacteria, it was not induced in D. neotestacea, showing that conservation of immune genes does not necessarily imply conservation of the realized immune response. Our study lends support to the idea that invertebrate AMPs evolve rapidly, and that Drosophila harbor a diverse repertoire of AMPs with potentially important functional consequences.
[Mh] Termos MeSH primário: Peptídeos Catiônicos Antimicrobianos/genética
Drosophila/genética
Drosophila/imunologia
Genes de Insetos
Imunidade/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Peptídeos Catiônicos Antimicrobianos/metabolismo
Evolução Biológica
Drosophila/microbiologia
Proteínas de Drosophila/química
Proteínas de Drosophila/genética
Fungos/imunologia
Regulação da Expressão Gênica
Variação Genética
Glicopeptídeos/química
Glicopeptídeos/genética
Filogenia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimicrobial Cationic Peptides); 0 (Drosophila Proteins); 0 (Glycopeptides); 149924-99-2 (drosocin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180128
[Lr] Data última revisão:
180128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29072130
[Au] Autor:Chugh M; Piskarev V; Galanina O; Khasbiullina N; Kadam P; Shilova N; Pazynina G; Dobrochaeva K; Bhanushali P; Kozlov N; Tupitsin N; Bovin N
[Ad] Endereço:1 Agappe Diagnostics Ltd, Kochi, India.
[Ti] Título:Glycoprotein CA19.9-specific monoclonal antibodies recognize sialic acid-independent glycotope.
[So] Source:Tumour Biol;39(10):1010428317725434, 2017 Oct.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A repertoire of monoclonal antibodies was generated by immunization of mice with cancer-associated glycoprotein CA19.9, and two of them were selected as optimal capture and detecting counterparts for sandwich test system for detection of CA19.9. Fine epitope specificity of the antibodies was determined using printed glycan array, enzyme-linked immunosorbent assay, and inhibitory enzyme-linked immunosorbent assay. Unexpectedly, both immunoglobulins did not bind key epitope of CA19.9 glycoprotein, tetrasaccharide SiaLe , as well as its defucosylated form sialyl Le (known as CA-50 epitope). The antibodies were found to have different glycan-binding profiles; however, they recognized similar glycotopes with common motif Galß1-3GlcNAcß (Le ), thus resembling specificity of human natural cancer-associated anti-Le antibodies. We propose that cancer-specific glycopeptide epitope includes Galß1-3GlcNAcß fragment of a glycoprotein O-chain in combination with proximal hydrophobic amino acid(s) of the polypeptide chain.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Antígeno CA-19-9/imunologia
Epitopos/imunologia
Neoplasias/imunologia
Trissacarídeos/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/genética
Antígeno CA-19-9/genética
Epitopos/genética
Glicopeptídeos/genética
Glicopeptídeos/imunologia
Seres Humanos
Camundongos
Ácido N-Acetilneuramínico/genética
Ácido N-Acetilneuramínico/imunologia
Neoplasias/genética
Trissacarídeos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (CA-19-9 Antigen); 0 (Epitopes); 0 (Glycopeptides); 0 (Trisaccharides); 0 (galactosyl-beta(1-3)-N-acetylglucosaminyl-beta(1-3)galactose); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171027
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317725434


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[PMID]:28931055
[Au] Autor:Kelen D; Andorka C; Szabó M; Alafuzoff A; Kaila K; Summanen M
[Ad] Endereço:First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
[Ti] Título:Serum copeptin and neuron specific enolase are markers of neonatal distress and long-term neurodevelopmental outcome.
[So] Source:PLoS One;12(9):e0184593, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The objective of this study was to evaluate the early changes in serial serum levels of copeptin and neuron-specific enolase (NSE) in neonates diagnosed with birth asphyxia, and to determine whether these biomarkers measured in the first 168 hours after birth are predictive of long-term neurodevelopmental outcome. Copeptin and NSE levels were measured from serum samples collected 6, 12, 24, 48, 72, and 168 hours after birth from 75 term neonates diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia for 72 hours. In addition, serum copeptin levels after birth were measured from 10 HIE diagnosed neonates, who were randomized to the normothermic arm of the TOBY cohort. All neonates underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development-II at two years of age. Copeptin levels were highest at 6 hours after birth and steadily decreased, whereas the highest NSE levels were measured at 24 hours after birth. The biomarker levels correlated with blood-gas parameters (base excess, pH and lactate) at 6 and 12 hours after birth. Copeptin and NSE levels in the early postnatal period were significantly higher in neonates with poor outcome compared to those with favorable outcome at two years of age. Furthermore, in the TOBY cohort, copeptin levels were significantly lower in hypothermic compared to normothermic neonates. To conclude, copeptin and NSE measured in the early postnatal period are potential prognostic biomarkers of long-term neurodevelopmental outcome in term neonates diagnosed with HIE and treated with therapeutic hypothermia.
[Mh] Termos MeSH primário: Asfixia Neonatal/sangue
Biomarcadores/sangue
Glicopeptídeos/sangue
Hipotermia Induzida
Hipóxia-Isquemia Encefálica/sangue
Fosfopiruvato Hidratase/sangue
[Mh] Termos MeSH secundário: Asfixia Neonatal/terapia
Pré-Escolar
Feminino
Idade Gestacional
Seres Humanos
Hipóxia-Isquemia Encefálica/terapia
Testes Imunológicos
Lactente
Recém-Nascido
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (Glycopeptides); 0 (copeptins); EC 4.2.1.11 (Phosphopyruvate Hydratase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184593


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[PMID]:28905441
[Au] Autor:Clark WF; Devuyst O; Roussel R
[Ad] Endereço:Division of Nephrology, Department of Medicine, London Health Sciences Centre, London, ON, Canada.
[Ti] Título:The vasopressin system: new insights for patients with kidney diseases: Epidemiological evidence and therapeutic perspectives.
[So] Source:J Intern Med;282(4):310-321, 2017 Oct.
[Is] ISSN:1365-2796
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:People with chronic kidney disease (CKD) are at risk of severe outcomes, such as end-stage renal disease or cardiovascular disease, and CKD is a globally increasing health burden with a high personal and economic cost. Despite major progresses in prevention and therapeutics in last decades, research is still needed to reverse this epidemic trend. The regulation of water balance and the state of activation of the vasopressin system have emerged as factors tightly associated with kidney health, in the general population but also in specific conditions; among them, various stages of CKD, diabetes and autosomal dominant polycystic kidney disease (ADPKD). Basic science findings and also epidemiological evidence have justified important efforts towards interventional studies supporting causality, and opening therapeutic avenues. On the basis of recent clinical data, the blockade of V2 vasopressin receptors using tolvaptan in patients with rapidly progressing ADPKD has been granted in several countries, and a long-term randomized trial evaluating the effect of an increase in water intake in patients with CKD is on-going.
[Mh] Termos MeSH primário: Nefropatias/fisiopatologia
Vasopressinas/fisiologia
[Mh] Termos MeSH secundário: Antagonistas de Receptores de Hormônios Antidiuréticos/uso terapêutico
Biomarcadores/sangue
Nefropatias Diabéticas/sangue
Nefropatias Diabéticas/fisiopatologia
Hidratação
Glicopeptídeos/sangue
Glicopeptídeos/fisiologia
Seres Humanos
Rim/fisiopatologia
Nefropatias/epidemiologia
Nefropatias/terapia
Rim Policístico Autossômico Dominante/tratamento farmacológico
Insuficiência Renal Crônica/epidemiologia
Insuficiência Renal Crônica/fisiopatologia
Insuficiência Renal Crônica/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antidiuretic Hormone Receptor Antagonists); 0 (Biomarkers); 0 (Glycopeptides); 0 (copeptins); 11000-17-2 (Vasopressins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1111/joim.12654


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[PMID]:28880909
[Au] Autor:Mastrangeli R; Satwekar A; Cutillo F; Ciampolillo C; Palinsky W; Longobardi S
[Ad] Endereço:Biotech Development Programme, Merck Serono S.p.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Guidonia Montecelio, Rome, Italy.
[Ti] Título:In-vivo biological activity and glycosylation analysis of a biosimilar recombinant human follicle-stimulating hormone product (Bemfola) compared with its reference medicinal product (GONAL-f).
[So] Source:PLoS One;12(9):e0184139, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recombinant human follicle-stimulating hormone (r-hFSH) is widely used in fertility treatment. Although biosimilar versions of r-hFSH (follitropin alfa) are currently on the market, given their structural complexity and manufacturing process, it is important to thoroughly evaluate them in comparison with the reference product. This evaluation should focus on how they differ (e.g., active component molecular characteristics, impurities and potency), as this could be associated with clinical outcome. This study compared the site-specific glycosylation profile and batch-to-batch variability of the in-vivo bioactivity of Bemfola, a biosimilar follitropin alfa, with its reference medicinal product GONAL-f. The focus of this analysis was the site-specific glycosylation at asparagine (Asn) 52 of the α-subunit of FSH, owing to the pivotal role of Asn52 glycosylation in FSH receptor (FSHR) activation/signalling. Overall, Bemfola had bulkier glycan structures and greater sialylation than GONAL-f. The nominal specific activity for both Bemfola and GONAL-f is 13,636 IU/mg. Taking into account both the determined potency and the nominal amount the average specific activity of Bemfola was 14,522 IU/mg (105.6% of the nominal value), which was greater than the average specific activity observed for GONAL-f (13,159 IU/mg; 97.3% of the nominal value; p = 0.0048), although this was within the range stated in the product label. A higher batch-to-batch variability was also observed for Bemfola versus GONAL-f (coefficient of variation: 8.3% vs 5.8%). A different glycan profile was observed at Asn52 in Bemfola compared with GONAL-f (a lower proportion of bi-antennary structures [~53% vs ~77%], and a higher proportion of tri-antennary [~41% vs ~23%] and tetra-antennary structures [~5% vs <1%]). These differences in the Asn52 glycan profile might potentially lead to differences in FSHR activation. This, together with the greater bioactivity and higher batch-to-batch variability of Bemfola, could partly explain the reported differences in clinical outcomes. The clinical relevance of the differences observed between GONAL-f and Bemfola should be further investigated.
[Mh] Termos MeSH primário: Medicamentos Biossimilares/farmacologia
Hormônio Foliculoestimulante Humano/farmacologia
Hormônio Foliculoestimulante/farmacologia
Proteínas Recombinantes/farmacologia
[Mh] Termos MeSH secundário: Asparagina/metabolismo
Fucose/metabolismo
Glicopeptídeos/química
Glicosilação/efeitos dos fármacos
Seres Humanos
Ácido N-Acetilneuramínico/metabolismo
Mapeamento de Peptídeos
Polissacarídeos/metabolismo
Subunidades Proteicas/metabolismo
Padrões de Referência
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biosimilar Pharmaceuticals); 0 (Follicle Stimulating Hormone, Human); 0 (Glycopeptides); 0 (Polysaccharides); 0 (Protein Subunits); 0 (Recombinant Proteins); 0 (follitropin alfa); 28RYY2IV3F (Fucose); 7006-34-0 (Asparagine); 9002-68-0 (Follicle Stimulating Hormone); GZP2782OP0 (N-Acetylneuraminic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184139


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[PMID]:28764642
[Au] Autor:Wu Q; Zhang J; Zhu P; Jiang W; Liu S; Ni M; Zhang M; Li W; Zhou Q; Cui Y; Xia X
[Ad] Endereço:Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, People's Republic of China.
[Ti] Título:The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis.
[So] Source:BMC Med Genet;18(1):81, 2017 Aug 01.
[Is] ISSN:1471-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Male infertility is a complex disorder caused by genetic, developmental, endocrine, or environmental factors as well as unknown etiology. Polymorphisms in the follicle stimulating hormone beta subunit (FSHB) (rs10835638, c.-211G > T) and follicle stimulating hormone receptor (FSHR) (rs1394205, c.-29G > A; rs6165, c.919A > G; rs6166, c.2039 A > G) genes might disturb normal spermatogenesis and affect male reproductive ability. METHODS: To further ascertain the aforementioned effects, we conducted a case-control study of 255 infertile men and 340 fertile controls from South China using the Mass ARRAY method, which was analyzed by the t-tests and logistic regression analysis using SPSS for Windows 14.0. In addition, a meta-analysis was performed by combining our results with previous reports using STATA 12.0. RESULTS: In the FSHB or FSHR gene single nucleotide polymorphism (SNP) evaluation, no statistically-significant difference was found in the frequency of allelic variants or in genotype distribution between cases and controls. However, a significant association for the comparison of GAA (P: 0.022, OR: 0.63, 95%CI: 0.43-0.94) was seen between the oligozoospermia and controls in haplotype analysis of rs1394205/rs6165/rs6166. In the meta-analysis, rs6165G allele and rs6166 GG genotype were associated with increased risk of the male infertility. CONCLUSIONS: This study suggested that FSHR GAA haplotype would exert protective effects against male sterility, which indicated that the combination of three SNP genotypes of FSHR was predicted to have a much stronger impact than either one alone. Then in the meta-analysis, a significant association was seen between FSHR rs6165, rs6166 polymorphisms and male infertility. In terms of male infertility with multifactorial etiology, further studies with larger sample sizes and different ethnic backgrounds or other risk factors are warranted to clarify the potential role of FSHB and FSHR polymorphisms in the pathogenesis of male infertility.
[Mh] Termos MeSH primário: Proteínas de Transporte/genética
Glicopeptídeos/genética
Infertilidade Masculina/genética
Polimorfismo de Nucleotídeo Único
Receptores do FSH/genética
[Mh] Termos MeSH secundário: Adulto
Grupo com Ancestrais do Continente Asiático/genética
Estudos de Casos e Controles
Predisposição Genética para Doença
Seres Humanos
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (FSH-BI protein, human); 0 (Glycopeptides); 0 (Receptors, FSH)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1186/s12881-017-0441-4


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[PMID]:28727741
[Au] Autor:Gladstone BP; Cona A; Shamsrizi P; Vilken T; Kern WV; Malek N; Tacconelli E
[Ad] Endereço:Infectious Diseases, Department of Internal Medicine I, DZIF Partner, Tübingen University Hospital, Tübingen, Germany.
[Ti] Título:Antimicrobial resistance rates in gram-positive bacteria do not drive glycopeptides use.
[So] Source:PLoS One;12(7):e0181358, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Surveillance data are considered essential to appropriate empiric antibiotic therapy and stewardship. The objective of this study was to determine if a change in the rates of antibiotic resistance impacts antibiotic use in European hospitals. Glycopeptides use was selected to study the correlation between resistance rates and antibiotic use because of the restricted spectrum against resistant gram positive bacteria. PubMed, ECDC databases and national/regional surveillance systems were searched to identify glycopeptides´ consumption in defined daily dose per 1000 inhabitant-days (DID) and rate of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase negative staphylococci (MRCoNS), and vancomycin-resistant enterococci (VRE) in bloodstream infections (BSIs) in European countries between 1997 and 2015. Time trends were studied and associations between DID and BSI resistance rates were tested using multi-level mixed effect models. To account for the gap in the publication and dissemination of the yearly resistance data, a 2-year lag in the resistance rates was applied. Data on glycopeptides´ DID and resistance rates of target microorganisms in blood cultures were identified among 31 countries over a 19-year period. Glycopeptides use significantly increased (p<0·0001) while rates of MRSA BSIs decreased in majority of the countries (p<0·0001) and MRCoNS and VRE BSIs remained stable. Variation in glycopeptides' DID was not associated with variation in BSIs due to MRSA (p = 0·136) and VRE (p = 0·613). After adjusting for MRCoNS and VRE resistance rates, among 21 countries, 11 (52%) had a concordant and 10 (48%) a discordant trend in yearly glycopeptides´ DID and MRSA BSI rates. No correlation was found between resistance rates and DID data even among 8 countries with more than 5% decrease in MRSA rates over time. (RC -0·009, p = 0·059). Resistance rate of MRSA, MRCoNS, and VRE BSIs does not impact DID of glycopeptides in European hospitals. This finding is key to redefining the role and structure of antimicrobial surveillance and stewardship programmes.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Farmacorresistência Bacteriana
Uso de Medicamentos
Glicopeptídeos/uso terapêutico
Bactérias Gram-Positivas/efeitos dos fármacos
Infecções por Bactérias Gram-Positivas/tratamento farmacológico
[Mh] Termos MeSH secundário: Monitoramento Epidemiológico
Europa (Continente)
Infecções por Bactérias Gram-Positivas/microbiologia
Hospitalização
Seres Humanos
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Enterococos Resistentes à Vancomicina/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycopeptides)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181358


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[PMID]:28719645
[Au] Autor:Bard F; Chia J
[Ad] Endereço:Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore, and Department of Biochemistry, National University of Singapore, Singapore, Singapore.
[Ti] Título:Comment on "The GalNAc-T Activation Pathway (GALA) is not a general mechanism for regulating mucin-type O-glycosylation".
[So] Source:PLoS One;12(7):e0180005, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Mucinas
N-Acetilgalactosaminiltransferases
[Mh] Termos MeSH secundário: Glicopeptídeos
Glicosilação
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Glycopeptides); 0 (Mucins); EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180005



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