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1.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360597

RESUMO

Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis and infects almost one-third of the global human population. A lack of effective drugs and vaccines and the emergence of drug resistant parasites highlight the need for the development of new drugs. The mitochondrial electron transport chain (ETC) is an essential pathway for energy metabolism and the survival of T. gondii. In apicomplexan parasites, malate:quinone oxidoreductase (MQO) is a monotopic membrane protein belonging to the ETC and a key member of the tricarboxylic acid cycle, and has recently been suggested to play a role in the fumarate cycle, which is required for the cytosolic purine salvage pathway. In T. gondii, a putative MQO (TgMQO) is expressed in tachyzoite and bradyzoite stages and is considered to be a potential drug target since its orthologue is not conserved in mammalian hosts. As a first step towards the evaluation of TgMQO as a drug target candidate, in this study, we developed a new expression system for TgMQO in FN102(DE3)TAO, a strain deficient in respiratory cytochromes and dependent on an alternative oxidase. This system allowed, for the first time, the expression and purification of a mitochondrial MQO family enzyme, which was used for steady-state kinetics and substrate specificity analyses. Ferulenol, the only known MQO inhibitor, also inhibited TgMQO at IC50 of 0.822 µM, and displayed different inhibition kinetics compared to Plasmodium falciparum MQO. Furthermore, our analysis indicated the presence of a third binding site for ferulenol that is distinct from the ubiquinone and malate sites.


Assuntos
Cumarínicos/metabolismo , Malatos/metabolismo , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/enzimologia , Ubiquinona/metabolismo , Animais , Humanos , Proteínas Mitocondriais/genética , Oxirredutases/genética , Proteínas de Protozoários/genética , Especificidade por Substrato
2.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281290

RESUMO

Plasmodium falciparum's resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.


Assuntos
Antimaláricos/farmacologia , Inibidores Enzimáticos/farmacologia , Iminas/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/antagonistas & inibidores , Pirimidinas/farmacologia , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Linhagem Celular , Di-Hidro-Orotato Desidrogenase , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/toxicidade , Humanos , Iminas/química , Iminas/toxicidade , Plasmodium falciparum/crescimento & desenvolvimento , Pirimidinas/química , Pirimidinas/toxicidade , Proteínas Recombinantes/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/farmacologia
3.
Int J Syst Evol Microbiol ; 70(5): 3069-3075, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32223833

RESUMO

A novel marine actinomycete, designated strain KJ-029T, was isolated from a marine sediment sample (water depth of 226 m) in Kagoshima, Japan. 16S rRNA gene sequence analysis revealed that the new isolate was most closely related to Micromonospora craniellae LHW 63014T (99.3 % similarity). Phylogenetic analyses of the genus Micromonospora based on 16S rRNA gene sequences showed that strain KJ-029T was clustered with Micromonospora craniellae LHW 63014T and Micromonospora endophytica 202201T. However, digital DNA-DNA hybridization analyses presented low levels of relatedness in the range of 24.8-32.9 % between strain KJ-029T and the above closely related strains. The novel strain contained meso-diaminopimelic acid and 3-OH-diaminopimelic acid, d-glutamic acid, glycine and d-alanine in the cell-wall peptidoglycan. The acyl type of the peptidoglycan was glycolyl and mycolic acids were absent. The major menaquinone was MK-9(H4). The whole-cell sugars consisted of glucose, mannose, xylose and ribose. Phosphatidylethanolamine was detected as the major phospholipid and corresponded to phospholipid type II. The predominant cellular fatty acid was iso-C16 : 0. The DNA G+C content of the genomic DNA was 71.5 mol%. Based on the present polyphasic study, strain KJ-029T represents a novel species of the genus Micromonospora, for which the name Micromonospora pelagivivens sp. nov. is proposed. The type strain is KJ-029T (=NBRC 113519T=TBRC 9233T).


Assuntos
Sedimentos Geológicos/microbiologia , Micromonospora/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Japão , Micromonospora/isolamento & purificação , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Água do Mar/microbiologia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados
4.
Int J Syst Evol Microbiol ; 69(5): 1299-1305, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30789325

RESUMO

A novel actinomycete, designated as strain H219T, was isolated from rhizosphere soil collected under an Elephant ear plant (Colocasiaesculenta) in Bangkok, Thailand. Strain H219T was characterised using a polyphasic approach. Phylogenetic analysis of the 16S rRNA gene sequences revealed that this isolate was most closely related to Saccharopolyspora tripterygii JCM 32123T (97.6 %), Saccharopolyspora dendranthemae NBRC 108675T (97.5 %) and Saccharopolyspora flava NBRC 16345T (97.5 %). However, DNA-DNA hybridization analyses showed a low relatedness in the range of 39-48 % between the novel isolate and the above closely related strains. The cell-wall peptidoglycan of strain H219T contained meso-diaminopimelic acid. The diagnostic whole-cell sugars consisted of arabinose and galactose. The cellular fatty acid profile mainly comprised iso-C16 : 0, anteiso-C17 : 0, iso-C15 : 0, and 10-methyl C17 : 0. The major menaquinone was MK-9(H4). The detected phospholipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylethanolamine-containing hydroxylated fatty acids and an unknown phospholipid. The DNA G+C content was 70.6 mol%. Strain H219T represented chemotaxonomic and morphological characteristics that were consistent with members of the genus Saccharopolyspora. However, strain H219T could be distinguished from closely related strains by several phenotypic properties. Based on the data from the polyphasic studies, we propose that strain H219T is a novel species within the genus Saccharopolyspora, Saccharopolysporarhizosphaerae sp. nov. The type strain is H219T (=TBRC 8564T=NBRC 113388T).


Assuntos
Colocasia/microbiologia , Filogenia , Rizosfera , Saccharopolyspora/classificação , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Saccharopolyspora/isolamento & purificação , Análise de Sequência de DNA , Tailândia , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Int Microbiol ; 22(4): 451-459, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30941598

RESUMO

An endophytic actinomycete strain SKH1-2 isolated from Musa (ABB) cv. 'Kluai Sao Kratuep Ho' collected in Suphan Buri province (14° 54' 22.5″ N/100° 04' 50″ E), Thailand, was identified as Streptomyces pseudovenezuelae based on phenotypic and chemotaxonomic characteristics, and 16S rRNA sequence analyses. A chemical investigation led to the isolation of two polyketide molecules from the n-butanol crude extract of the strain SKH1-2 culture broth. The compounds were purified using various chromatographic techniques and identified using spectroscopic methods compared with earlier published data. Compound 1, chartreusin, is known as an anti-Gram (+) bacterial compound and was active against Bacillus subtilis ATCC 6633, Kocuria rhizophila ATCC 9341 and Staphylococcus aureus ATCC 6538p with MIC values of 3.1, 1.6 and 12.5 µg/mL, respectively. Compound 2, lumichrome, did not show activity against all tested microbes. To our knowledge, this is the first report of chartreusin and lumichrome isolated from S. pseudovenezuelae. Taken together, it could be proved that Thai plant species are valuable reservoirs of interesting endophytic actinomycetes producing several interesting biologically active compounds.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Endófitos/metabolismo , Policetídeos/química , Policetídeos/farmacologia , Streptomyces/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Endófitos/química , Endófitos/genética , Endófitos/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Musa/microbiologia , Filogenia , Raízes de Plantas/microbiologia , Policetídeos/isolamento & purificação , Policetídeos/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptomyces/química , Streptomyces/genética , Streptomyces/isolamento & purificação , Tailândia
6.
Nihon Koshu Eisei Zasshi ; 66(8): 397-406, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31548448

RESUMO

Objectives The final evaluation of the Japanese government's Healthy Parents and Children 21 project in 2014 noted an increase in low birth weight infants as an aspect that worsened. In order to reduce the number of low birth weight infants, miscarriages, and stillbirths in Kurume City, we conducted a survey aimed at researching new measures, including the search for new risk factors of birth complications.Methods The participants of this study were 2,986 pregnant women who submitted a pregnancy notification form in 2014. We excluded women who moved away from Kurume city or for whom birth weight records could not be obtained. Information from the pregnancy notification form was linked to birth weight records to examine the relationships between low birth weight infants, miscarriages, stillbirths, and pregnancy attributes. Variables that were shown to be related in an initial univariate analysis were analyzed further in a multiple logistic regression analysis with low birth weight, miscarriage, or stillbirth as the response variables.Results A multiple logistic regression analysis showed that being 35 years or older (odds ratio [OR]: 1.41), height less than 158 cm (OR: 1.45), non-pregnant body mass index (BMI) less than 18.5 (OR: 1.48), and detection of physical abnormalities by a physician during the pregnancy (OR: 2.20) were independent maternal factors that were significantly associated with low birth weight. Being aged 35 years or older (OR: 2.05) and smoking (OR: 3.42) were independent factors that were significantly associated with miscarriage and stillbirth. In addition, the cessation of alcohol use (OR: 0.51) significantly reduced this risk.Conclusion Because some biological factors such as "age" and "non-pregnant BMI" are invariable, we encourage pregnant women to get checkups to detect abnormalities early or to attend birthing classes that offer mental support, especially for pregnant women over 35 years. We want to tell young generations that pregnant women over 35 are at an increased risk of having low birth weight infants, miscarriages, and stillbirths, and those pregnant women with a lower BMI have an increased risk of low birth weight infants. "Maintenance of appropriate body weight," "smoking," "alcohol," socioeconomic issues such as "lack of systems for seeking advice and support staff," and "financial concerns" can be improved with health education from public health nurses and multidisciplinary support interventions. At the Children Care Support Center in Kurume city, professionals work together to provide continuous support to families during pregnancy, childbirth, and parenting. As a result, we may be able to contribute to reducing the number of low birth weight infants, miscarriages, and stillbirths.


Assuntos
Aborto Espontâneo/epidemiologia , Aborto Espontâneo/prevenção & controle , Recém-Nascido de Baixo Peso , Tocologia , Enfermeiros de Saúde Pública , Educação de Pacientes como Assunto/métodos , Natimorto/epidemiologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Gravidez , Fatores de Risco , Apoio Social , Adulto Jovem
7.
Biochim Biophys Acta Bioenerg ; 1859(3): 191-200, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29269266

RESUMO

Plasmodium falciparum is an apicomplexan parasite that causes the most severe malaria in humans. Due to a lack of effective vaccines and emerging of drug resistance parasites, development of drugs with novel mechanisms of action and few side effects are imperative. To this end, ideal drug targets are those essential to parasite viability as well as absent in their mammalian hosts. The mitochondrial electron transport chain (ETC) of P. falciparum is one source of such potential targets because enzymes, such as L-malate:quinone oxidoreductase (PfMQO), in this pathway are absent humans. PfMQO catalyzes the oxidation of L-malate to oxaloacetate and the simultaneous reduction of ubiquinone to ubiquinol. It is a membrane protein, involved in three pathways (ETC, the tricarboxylic acid cycle and the fumarate cycle) and has been shown to be essential for parasite survival, at least, in the intra-erythrocytic asexual stage. These findings indicate that PfMQO would be a valuable drug target for development of antimalarial with novel mechanism of action. Up to this point in time, difficulty in producing active recombinant mitochondrial MQO has hampered biochemical characterization and targeted drug discovery with MQO. Here we report for the first time recombinant PfMQO overexpressed in bacterial membrane and the first biochemical study. Furthermore, about 113 compounds, consisting of ubiquinone binding site inhibitors and antiparasitic agents, were screened resulting in the discovery of ferulenol as a potent PfMQO inhibitor. Finally, ferulenol was shown to inhibit parasite growth and showed strong synergism in combination with atovaquone, a well-described anti-malarial and bc1 complex inhibitor.


Assuntos
Membranas Mitocondriais/enzimologia , Oxirredutases/metabolismo , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/metabolismo , Antimaláricos/farmacologia , Atovaquona/farmacologia , Biocatálise/efeitos dos fármacos , Cumarínicos/farmacologia , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Humanos , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Malatos/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Ácido Oxaloacético/metabolismo , Oxirredutases/antagonistas & inibidores , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/antagonistas & inibidores
8.
Nagoya J Med Sci ; 79(3): 279-290, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28878433

RESUMO

The aim of this study was to investigate the therapeutic effect of Sasa veitchii leaf extract (SE) on features of obesity induced by a high-fat diet (HFD), such as hyperglycemia, insulin resistance, and inflammatory response. Four-week-old male ddY mice were freely fed HFD or control normal diet for 12 weeks; half was given SE in addition twice per day in weeks 8-12. Glucose and insulin intolerance were estimated, and body weight measured, weekly throughout the study. Following the experiment, the mice were fasted for 16 h, euthanized, and plasma was collected. Liver and epididymal adipose tissue was collected and weighed. Treatment with SE significantly decreased body weight, adipose tissue weight, plasma glucose, insulin, leptin, and tumor necrosis factor α compared with HFD groups, and markedly reduced the impairment of glucose and insulin tolerance in obese mice. Furthermore, hepatic steatosis and hepatic insulin receptor substrate were improved by treatment with SE. Our findings demonstrate that SE may reduce obesity-induced glucose and insulin tolerance, not only by suppressing inflammatory responses but also by improving insulin signaling.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Resistência à Insulina/fisiologia , Obesidade/complicações , Extratos Vegetais/uso terapêutico , Sasa/química , Animais , Masculino , Camundongos
9.
Int J Syst Evol Microbiol ; 66(1): 468-473, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26552374

RESUMO

A novel species of the genus Actinoplanes, strain LDG1-22T, for which we propose the name Actinoplanes lichenis sp. nov., was isolated from a lichen sample collected from tree bark in Thailand. The taxonomic position of the species has been described based on a polyphasic approach. Strain LDG1-22T produced irregular sporangia on agar media. It contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The major menaquinone was MK-9(H4); the polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and phosphatidylglycerol. Whole-cell hydrolysates contained ribose, glucose, mannose and small amounts of arabinose and xylose. The major cellular fatty acids were anteiso-C15 : 0 (31.2 %) and iso-C16 : 0 (14.2 %). Mycolic acids were absent. The G+C content was 73.6 %. 16S rRNA gene sequence analysis of strain LDG1-22T showed highest similarity (98.8 %) to Actinoplanes friuliensis DSM 45797T and it clustered with Actinoplanes nipponensis JCM 3264T and Actinoplanes missouriensis JCM 3121T in phylogenetic tree analysis. On the basis of the phenotypic characteristics and DNA-DNA relatedness, strain LDG1-22T could be distinguished from related species of the genus Actinoplanes and so represents a novel species of this genus. The type strain of Actinoplanes lichenis sp. nov. is LDG1-22T ( = JCM 30485T = TISTR 2343T = PCU 344T).


Assuntos
Líquens/microbiologia , Micromonosporaceae/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Micromonosporaceae/genética , Micromonosporaceae/isolamento & purificação , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , Casca de Planta , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Tailândia , Vitamina K 2/análogos & derivados , Vitamina K 2/química
10.
Environ Health Prev Med ; 21(1): 34-41, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26498185

RESUMO

OBJECTIVES: This study aimed to evaluate students' subjective symptoms associated with exposure to low levels of formaldehyde (FA) during a gross anatomy course and to survey how the risk of subjective symptoms was affected by exposure to FA. METHODS: We conducted three questionnaire surveys of 125 students enrolled in an anatomy course (FA exposure group) and 124 students not enrolled in the course (FA nonexposure group) before, during, and 6 months after the course. The questionnaire included questions inquiring about subjective symptoms, sex, age, and allergies. We analyzed differences in the prevalence of subjective symptoms in distinct survey periods. Furthermore, we analyzed the relationship between the subjective symptoms and exposure to FA after adjusting for allergy, sex, and age using multiple logistic regression analysis. RESULTS: The prevalence of some of the ocular, nasal, and nonspecific symptoms in the FA exposure group was low before the course, increased during the course and decreased 6 months after the course. A significant positive relationship was observed between exposure to FA and some symptoms after adjusting for allergy, sex, and age. CONCLUSIONS: We identified some concrete symptoms associated with exposure to FA. We suggest that the exposure to low levels of FA influences students' subjective symptoms.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados , Formaldeído/toxicidade , Hipersensibilidade/epidemiologia , Exposição Ocupacional , Adolescente , Adulto , Feminino , Humanos , Hipersensibilidade/etiologia , Japão/epidemiologia , Masculino , Estudantes de Medicina , Adulto Jovem
11.
Angew Chem Int Ed Engl ; 55(12): 4049-53, 2016 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-26891236

RESUMO

Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, atpenin A5, are described. These analogues were selected on the basis of Cl→CH3 or H3 C→Cl exchanges in the side-chain of atpenin A5. The interchange of chloro and methyl substituents led to complex II inhibitors with equal IC50 values. This suggests that Cl↔Me bioisosteric exchange can be realized in aliphatic settings.


Assuntos
Piridonas/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Estrutura Molecular , Piridonas/química
12.
Int J Syst Evol Microbiol ; 65(12): 4417-4423, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26358439

RESUMO

The novel actinomycete strain PWB-003T, which produced fluostatins B and C antibiotics, was isolated from nearshore sediment collected from Panwa Cape, Phuket Province, Thailand. Data from the present polyphasic study indicated that strain PWB-003T represented a member of the genus Micromonospora. It produced single spores on substrate mycelia and contained meso-diaminopimelic acid in the cell-wall peptidoglycan. Whole-cell hydrolysate contained ribose, xylose, arabinose, mannose and glucose. The predominant menaquinone was MK-10 (H4). Cellular fatty acids comprised C18 : 1ω9c, iso-C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C17 : 0. On the basis of 16S rRNA gene sequence similarity analysis, the novel strain was closely related to Micromonospora eburnea LK2-10T (99.38 %), Micromonospora chaiyaphumensis MC5-1T (99.16 %), Micromonospora yangpuensis FXJ6.011T (98.97 %), Micromonospora echinaurantiaca DSM 43904T (98.97 %), Micromonospora pallida DSM 43817T (98.97 %), Micromonospora sagamiensis DSM 43912T and Micromonospora auratinigra JCM 12357T (both 98.97 %). The G+C content of the DNA was 74.5 mol%. DNA-DNA relatedness values among strain PWB-003T and related type strains ranged from 11.3 ± 1.3 to 38.8 ± 1.1 %. On the basis of these observations, strain PWB-003T could be distinguished from its closely related type strains and is considered to represent a novel species of the genus Micromonospora, for which the name Micromonospora fluostatini sp. nov. (type strain PWB-003T = JCM 30529T = PCU 341T = TISTR 2345T) is proposed.


Assuntos
Sedimentos Geológicos/microbiologia , Micromonospora/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Micromonospora/genética , Micromonospora/isolamento & purificação , Dados de Sequência Molecular , Peptidoglicano/química , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Tailândia , Vitamina K 2/química
14.
World J Microbiol Biotechnol ; 31(2): 391-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25543910

RESUMO

The rare actinomycetes strain 2EPS was isolated from soil and analysis of cultural, morphological characteristics, diaminopimelic acid content of its cell wall, and 16S rRNA gene sequence indicates that 2EPS belongs to genus Actinomadura. In addition, neighbor-joining phylogenetic tree also confirmed the relationships of this strain to other members of Actinomadura. A butanol extract with antibacterial activity was purified by reversed-phase chromatography to obtain three bioactive compounds, designated as compounds 1, 2 and 3. The structures of these compounds were determined using spectroscopic analysis ((1)H-NMR and (13)C-NMR) and mass spectrometric analysis (HR-TOF-MS). Compounds 1-3 were identified and found to be the same as those included in the Japanese patent number JP 09227587 for spirotetronate antibiotics and are BE-45722A (1), BE-45722B (2) and BE-45722C (3), respectively. All compounds were active against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, and B. subtilis ATCC 6633) with low MIC values between 0.08 and 5.0 µg/ml. Moreover, both 1 and 3 also exhibited strong activity, with similar MIC values, against Clostridium perfringens S107 at 0.63 µg/ml and C. difficile 630 at 0.08 µg/ml. These results suggest the identified spirotetronate compounds may have potential in the treatment of Clostridium infections. Overall, this analysis demonstrates that rare actinomycetes are a promising source for discovery of antimicrobial compounds.


Assuntos
Actinomycetales/química , Actinomycetales/isolamento & purificação , Antibacterianos/farmacologia , Butanóis/farmacologia , Clostridium/efeitos dos fármacos , Actinomycetales/classificação , Antibacterianos/química , Butanóis/química , Cromatografia de Fase Reversa , Testes de Sensibilidade Microbiana , Filogenia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Microbiologia do Solo
15.
Nihon Koshu Eisei Zasshi ; 62(9): 556-65, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-26608045

RESUMO

OBJECTIVES: Fatigue caused by high workload is often responsible for the high attrition among doctors, and has contributed to a disruption in community medicine. In order to address this problem, institutional mechanisms at the hospital level are required. Previous studies have shown that systemic measures at the hospital level and a change in the mindset of patients can help manage the problem. "Convenient visits" refer to emergency visits for non-emergency problems. It is an avoidable cause of high workload on doctors. Convenient visits also refer to emergency consultation for non-emergency symptoms. As this is a new phenomenon, its relationship with doctors' fatigue needs further research. We investigated the relationship between convenient visits and doctors' fatigue using burnout and work engagement scales. METHODS: We selected 44 hospitals, with >200 beds each, in provincial cities of prefectures with a doctor-population ratio lower than the national average. These cities were considered likely to manifest the phenomenon of 24-hour society and include overworked doctors. Ordinance-designated cities were excluded from this study owing to wide population variability. Three doctors from each hospital were randomly selected from among physicians, surgeons, and pediatricians. We distributed questionnaires (a questionnaire concerning convenient visits, Maslach Burnout Inventory-Human Services Survey, and Utrecht Work Engagement Scale) to 132 doctors. RESULTS: Forty-two doctors responded to the survey. The median proportion of convenient visits among emergency visits was 50%. Sixty percent of the doctors surveyed were annoyed by convenient visits. Other doctors indicated good collaboration between the hospitals and communities or that they were not currently annoyed by convenient visits, although they had been annoyed previously. The emotional exhaustion in doctors, who worked in hospitals that did not restrict convenient visits, was significantly higher than in those who worked in hospitals that restricted these visits. A significant risk of serious burnout was found via crude and multiple logistic regression analysis (adjusted for age and gender, or adjusted for age, gender, clinical department, frequency of work shifts, and sleep duration during work shifts). CONCLUSION: Doctors working in hospitals that do not protect them against convenient visits are more prone to burnout. Although the number of convenient visitors is increasing, many hospitals lack systemic measures to manage them. This contributes to doctors' burnout. We suggest that hospitals control convenient visits for preventing doctors' burnout. Collaboration between hospitals and communities is required to help alleviate this problem.


Assuntos
Agendamento de Consultas , Esgotamento Profissional , Tolerância ao Trabalho Programado , Adulto , Esgotamento Profissional/etiologia , Feminino , Humanos , Masculino
16.
Kurume Med J ; 69(3.4): 209-216, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38369339

RESUMO

To prevent unpleasant symptoms in medical students during systematic anatomy practice, we aimed to develop and validate a model that predicts the likelihood of these symptoms occurring during practice based on risk factors prior to the start of practice. A total of 452 medical students enrolled from 2014 to 2018 were surveyed before and during practice, with questions regarding their sex, psychological status, subjective symptoms, and allergies. The sum of the scores concerning three subjective symptoms related to the eyes and three subjective symptoms related to the nose and fatigue were defined as the "eye-score" and "mask-score," respectively, and a total score of 7 or more was considered symptomatic. A prediction model was developed based on a generalized linear mixed model; the outcome variable in the model was symptoms during practice, and the explanatory variables were indoor formaldehyde concentration during practice, sex, and pre-practice status, such as the students' psychological state, eye-score, mask-score, and the presence of allergies. Five-fold cross-validation was used to assess internal validity and the prediction model was applied to 110 medical students enrolled in 2021 to assess external validity. The sensitivity and specificity by five-fold cross-validation were 0.843 and 0.314 for eye symptoms and 0.847 and 0.432 for mask symptoms. In the external validity assessment, the sensitivity and specificity were 0.889 and 0.207 for eye symptoms and 0.879 and 0.532 for mask symptoms. The prediction model developed in this study can be used in future measures aimed at preventing symptoms in students.


Assuntos
Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Feminino , Masculino , Inquéritos e Questionários , Fatores de Risco , Adulto Jovem , Fadiga/psicologia , Hipersensibilidade/epidemiologia , Reprodutibilidade dos Testes
17.
Ind Health ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925930

RESUMO

To investigate factors contributing to the mental health of Vietnamese technical intern trainees in the food manufacturing industry, a questionnaire survey was conducted twice with a six-month interval. A total of 111 technical trainees who participated in two surveys were included in the analysis. We used a mixed-effects model, where items with statistically significant associations in the univariate analysis were fixed effects, factories were random effects, and the outcome was defined as the K6 score at follow-up. The mean K6 score increased from 3.13 (SD 3.5) at baseline to 3.86 (SD 4.1) at follow-up, with 26.1% and 34.2% exhibiting poor mental health (K6≥5) at baseline and follow-up, respectively. Insomnia and years of training experience were significantly associated with the K6 score at follow-up. Those with insomnia had significantly higher K6 score at follow-up. Compared to the first year of training, K6 score at follow-up increased significantly for training in their third year or more. It is important to understand the sleeping conditions of trainees and support them based on their years of training experience.

18.
Nat Commun ; 15(1): 568, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278791

RESUMO

Microbes can decompose biodegradable plastics on land, rivers and seashore. However, it is unclear whether deep-sea microbes can degrade biodegradable plastics in the extreme environmental conditions of the seafloor. Here, we report microbial decomposition of representative biodegradable plastics (polyhydroxyalkanoates, biodegradable polyesters, and polysaccharide esters) at diverse deep-sea floor locations ranging in depth from 757 to 5552 m. The degradation of samples was evaluated in terms of weight loss, reduction in material thickness, and surface morphological changes. Poly(L-lactic acid) did not degrade at either shore or deep-sea sites, while other biodegradable polyesters, polyhydroxyalkanoates, and polysaccharide esters were degraded. The rate of degradation slowed with water depth. We analysed the plastic-associated microbial communities by 16S rRNA gene amplicon sequencing and metagenomics. Several dominant microorganisms carried genes potentially encoding plastic-degrading enzymes such as polyhydroxyalkanoate depolymerases and cutinases/polyesterases. Analysis of available metagenomic datasets indicated that these microorganisms are present in other deep-sea locations. Our results confirm that biodegradable plastics can be degraded by the action of microorganisms on the deep-sea floor, although with much less efficiency than in coastal settings.


Assuntos
Plásticos Biodegradáveis , Poli-Hidroxialcanoatos , RNA Ribossômico 16S/genética , Biodegradação Ambiental , Poliésteres/metabolismo , Polissacarídeos
19.
Environ Health Prev Med ; 18(5): 386-93, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23588414

RESUMO

OBJECTIVES: Our purpose was to clarify whether subjective symptoms of low-level formaldehyde (FA) exposure in medical students were transient or persistent and to investigate whether the allergy state changed as a result of exposure. METHODS: We surveyed the prevalence of medical students' subjective symptoms and their allergy state before, during, and 6 months after completion of a gross anatomy dissection course by using two self-administrative questionnaires. Students completed the first survey at the end of the anatomy course to assess symptoms before and during the course. The second survey was completed 6 months after course completion. RESULTS: The prevalence of most subjective symptoms was lower 6 months after the course than during the course. The major symptoms experienced during the course were eye fatigue, runny nose, and dry eyes. The most common symptom 6 months after the course was eye fatigue. Four students continued to experience symptoms even after course completion. Three students developed symptoms only after course completion. Forty-eight students had allergies before the course began and the severity of the allergies did not change after the course. Additionally, the prevalence of most subjective symptoms 6 months after the course was lower than before the course. The patterns of subjective symptoms in the three periods differed between male and female students; the prevalence of most subjective symptoms tended to be higher in females. CONCLUSIONS: Subjective symptoms resulting from FA exposure during a gross anatomy course were transient and did not affect students' allergy states.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados , Formaldeído/toxicidade , Hipersensibilidade/epidemiologia , Exposição Ocupacional , Adulto , Feminino , Humanos , Hipersensibilidade/etiologia , Masculino , Estudantes de Medicina , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
20.
Kurume Med J ; 68(2): 69-74, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37005294

RESUMO

This study interviewed 39 mother-doctors from two university hospitals in Japan to investigate how certain stages in their lives influenced their working motivation. We conceptualized a Motivational Drive Chart to track changes of work motivation from enrollment in medical courses to the present day, recording changes in motivational values, age, and life events. It was found that the average value of motivation increased from the beginning of medical school enrollment until graduation; however, a sudden drop was noted in the age group 25 to 29 due to childcare and work-life conflicts. Motivational values were found to gradually increase in the 30 to 34 age group, owing to professional accomplishments, such as obtaining a specialist license. In Japanese society, social roles have traditionally been divided between men and women. The present study found that Japanese female doctors faced a decrease in work motivation during childrearing stages. The finding suggests that new avenues should be explored to support mother-doctors.


Assuntos
Motivação , Médicos , Masculino , Humanos , Feminino , Japão
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