RESUMO
STUDY QUESTION: Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo? SUMMARY ANSWER: Na+/K+ ATPase α1, ß1 and ß3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion. WHAT IS KNOWN ALREADY: In mouse embryos, Na+/K+ ATPase α1 and ß1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation). STUDY DESIGN, SIZE, DURATION: A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining. MAIN RESULTS AND THE ROLE OF CHANCE: RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, ß1 and ß3 isoforms in human blastocysts. Isoforms α1 and ß3 were localized to the basolateral membrane of TE cells, and ß1 was localized between TE cells. A high level of ß3 mRNA expression correlated with easier hatching (P = 0.0261). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis. WIDER IMPLICATIONS OF THE FINDINGS: Of the various Na+/K+ ATPase isoforms, expression levels of the α1, ß1 and ß3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and ß3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The ß1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.
Assuntos
Blastocisto , Embrião de Mamíferos , Animais , Blastocisto/metabolismo , Membrana Celular/metabolismo , Embrião de Mamíferos/metabolismo , Humanos , Camundongos , RNA Mensageiro/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismoAssuntos
Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Granulomatose com Poliangiite , Anticorpos Anticitoplasma de Neutrófilos , Glomerulonefrite/etiologia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , HumanosAssuntos
Doença de Depósito de Glicogênio Tipo V/diagnóstico , Espondiloartropatias/etiologia , Idoso , Diagnóstico Diferencial , Feminino , Doença de Depósito de Glicogênio Tipo V/complicações , Doença de Depósito de Glicogênio Tipo V/fisiopatologia , Antígeno HLA-B39/genética , Humanos , Músculo Esquelético/fisiopatologia , Polimiosite , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
OBJECTIVE: Cognitive impairment after intensive care unit (ICU) admission is becoming increasingly recognized. High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment. However, the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear. In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients. DESIGN: A prospective observational study was carried out. PATIENTS: A total of 17 surgical patients were studied. INTERVENTION: None. VARIABLES OF INTEREST: Cognitive function before and after ICU admission. RESULTS: Thirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study. Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl. Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery. Finally, a total of 17 patients were included in the analysis. Cognitive impairment (defined as a decline of >20% from the pre-admission cognitive evaluation scores in at least two of 6 tests) was observed in 5 of the 17 patients (29%). However, there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests. CONCLUSIONS: Middle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary-mandibular oral surgery with microvascular reconstruction.
Assuntos
Transtornos Cognitivos/prevenção & controle , Cognição/efeitos dos fármacos , Cuidados Críticos , Sedação Profunda/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Respiração Artificial , Idoso , Idoso de 80 Anos ou mais , Protocolos Clínicos , Transtornos Cognitivos/induzido quimicamente , Dexmedetomidina , Neoplasias Faciais/cirurgia , Feminino , Fentanila , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Unidades de Terapia Intensiva , Masculino , Neoplasias Maxilares/cirurgia , Microcirculação , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Testes Neuropsicológicos , Complicações Pós-Operatórias/induzido quimicamente , Propofol , Estudos Prospectivos , Procedimentos de Cirurgia Plástica , Fatores de TempoAssuntos
Eritrócitos Anormais , Oclusão da Artéria Retiniana/diagnóstico , Esferocitose Hereditária/diagnóstico , Diagnóstico Diferencial , Amarelo de Eosina-(YS)/análogos & derivados , Feminino , Humanos , Anamnese , Oclusão da Artéria Retiniana/sangue , Esferocitose Hereditária/sangue , Esferocitose Hereditária/complicações , Adulto JovemRESUMO
Balanced rates of mitochondrial division and fusion are required to maintain mitochondrial function, as well as cellular and organismal homeostasis. In mammals, the cellular machines that mediate these processes are dynamin-related GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2 and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are linked to varied pathologies, including cell death and neurodegeneration, raising the possibility that small molecules that target the division and fusion machines to restore balance may have therapeutic potential. Here we describe the discovery of novel small molecules that directly and selectively inhibit assembly-stimulated GTPase activity of the division dynamin, DRP1. In addition, these small molecules restore wild type mtDNA copy number in MFN1 knockout mouse embryonic fibroblast cells, a phenotype linked to deficient mitochondrial fusion activity. Thus, these compounds are unique tools to explore the roles of mitochondrial division in cells, and to assess the potential therapeutic efficacy of rebalancing mitochondrial dynamics in pathologies associated with excessive mitochondrial division.
Assuntos
Descoberta de Drogas , Dinaminas/antagonistas & inibidores , Mamíferos/metabolismo , Mitocôndrias/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , DNA Mitocondrial/genética , Dinaminas/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Hidrólise , Camundongos , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-AtividadeAssuntos
Músculo Esquelético/patologia , Miosite , Prednisolona/administração & dosagem , Partícula de Reconhecimento de Sinal/imunologia , Idoso de 80 Anos ou mais , Autoanticorpos/análise , Biópsia/métodos , Creatina Quinase/análise , Glucocorticoides/administração & dosagem , Humanos , Masculino , Miosite/diagnóstico , Miosite/tratamento farmacológico , Miosite/imunologia , Miosite/fisiopatologia , Necrose , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Resultado do TratamentoAssuntos
Condrocalcinose/diagnóstico , Joelho/diagnóstico por imagem , Lipoma/diagnóstico por imagem , Membrana Sinovial/diagnóstico por imagem , Idoso de 80 Anos ou mais , Humanos , Falência Renal Crônica/terapia , Lipoma/cirurgia , Imageamento por Ressonância Magnética , Masculino , Diálise Renal , SinovectomiaRESUMO
OBJECTIVE: Washing the hands using cleansers with antiseptic materials is the most popular method for hand hygiene and helps maintain health by preventing food poisoning and bacterial infections. However, repeated hand washing tends to induce eczema of the hand, such as dryness, cracking and erythema. Moreover, eczema on the hand leads to increased levels in Staphylococcus aureus (S. aureus) on the skin surface in contrast to expectations. Thus, mild hand cleansers which induce less eczema even with repeated washings are desired. Here, we evaluated the efficacy of a hand cleanser formulated with alkyl ether sulphate (AES), alkyl ether carboxylic acid (AEC) and alkyl glucoside (AG) that contains isopropyl methylphenol (IPMP) on skin symptoms and S. aureus levels. METHODS: Eczema of the hand and the presence of S. aureus on the skin surface were analysed prior to and following 4 weeks of usage of the hand cleanser. A soap-based hand cleanser with IPMP was used as a reference cleanser. Eczema and cutaneous conditions were evaluated by visual grading, transepidermal water loss (TEWL), stratum corneum moisture-retention ability (MRA) and skin surface pH. RESULTS: The repeated use of the soap-based hand cleanser significantly worsened the hand dryness, scaling and cracks on the tips of the fingers and significantly increased the TEWL and decreased the MRA. In contrast, usage of the test cleanser only induced a significant increase in skin dryness but did not induce skin scaling or cracking and did not increase TEWL or decrease the MRA. Corresponding to these changes in skin symptoms, the presence of S. aureus increased the following use of the reference cleanser but not the test cleanser. There was no significant difference in skin surface pH between the two cleansers. Moreover, the increase in S. aureus was significantly correlated to the worsening of skin dryness and scaling. CONCLUSION: These results suggest that not only antimicrobial activity but also the mildness, which minimizes cutaneous effects, are important for hand cleansers to prevent the growth of S. aureus. The cleanser formulated with AES, AEC and AG containing IPMP is mild and is effective to promote hand hygiene.