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1.
Sci Rep ; 10(1): 19377, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168851

RESUMO

The nematic phase in iron based superconductors (IBSs) has attracted attention with a notion that it may provide important clue to the superconductivity. A series of angle-resolved photoemission spectroscopy (ARPES) studies were performed to understand the origin of the nematic phase. However, there is lack of ARPES study on LaFeAsO nematic phase. Here, we report the results of ARPES studies of the nematic phase in LaFeAsO. Degeneracy breaking between the [Formula: see text] and [Formula: see text] hole bands near the [Formula: see text] and M point is observed in the nematic phase. Different temperature dependent band splitting behaviors are observed at the [Formula: see text] and M points. The energy of the band splitting near the M point decreases as the temperature decreases while it has little temperature dependence near the [Formula: see text] point. The nematic nature of the band shift near the M point is confirmed through a detwin experiment using a piezo device. Since a momentum dependent splitting behavior has been observed in other iron based superconductors, our observation confirms that the behavior is a universal one among iron based superconductors.

2.
Med Oral Patol Oral Cir Bucal ; 24(2): e231-e235, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30818316

RESUMO

BACKGROUND: Oral mucocele is the most common minor salivary gland lesion with good prognosis after surgical removal. However, its recurrence is not rare, sometimes bothersome. This study aimed to identify the possible predictive variables affecting the recurrence rate of oral mucocele. MATERIAL AND METHODS: The histoclinical data of 164 patients diagnosed with oral mucocele were retrospectively obtained by reviewing dental records. The predictive variables for its recurrence were identified by analyzing its recurrence rate according to clinical variables. RESULTS: The recurrence rate showed the significant differences according to location and age. Oral mucocele recurred with significantly higher frequency on the ventral mucosa of tongue (50.0%) than on the labial/buccal mucosa (8.8%). Its recurrence was significantly more common in the younger patients (aged < 30 years, 16.0%) than in the older patients (aged > 30 years, 4.4%). However, there was no significant difference in recurrence rates between surgical procedures using scalpels and those using lasers. CONCLUSIONS: Patients with oral mucocele should be more carefully informed of its possible recurrence, especially when it is found on the ventral surface of the tongue or in a younger population.


Assuntos
Mucocele/diagnóstico , Mucocele/patologia , Adolescente , Adulto , Biópsia , Criança , Feminino , Humanos , Terapia a Laser , Lábio/patologia , Masculino , Mucosa Bucal/patologia , Recidiva , Estudos Retrospectivos , Doenças das Glândulas Salivares/diagnóstico , Doenças das Glândulas Salivares/patologia , Doenças das Glândulas Salivares/cirurgia , Glândulas Salivares Menores/patologia , Língua/patologia , Doenças da Língua/patologia , Adulto Jovem
3.
J Intellect Disabil Res ; 61(7): 682-696, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28612475

RESUMO

OBJECTIVE(S): Although rates of human immunodeficiency virus (HIV) are similar for individuals with and without intellectual and developmental disabilities (IDD), very little is known about the health needs and service use of those with IDD and HIV. Among a population with IDD, we compared the physical and mental health profiles, as well as general and mental health service use for those with and without HIV. DESIGN: Retrospective cohort study in Ontario, Canada using linked administrative health and social service databases. METHODS: The prevalence of physical conditions and mental health disorders, and patterns of service use for any reason and service use for mental health issues were compared among Ontario adults with IDD and HIV (n = 107) and without HIV (n = 63 901) in log-binomial models adjusted for age, sex and neighbourhood income and rurality. RESULTS: Adults with IDD and HIV were more likely than those without HIV to have three types of mental health disorders: non-psychotic disorders [aRR: adjusted rate ratio (aRR): 1.22 (95% confidence interval (CI): 1.01-1.47)], psychotic disorders [aRR: 1.57 (1.09, 2.28)] and substance use disorders [aRR: 3.52 (2.53, 4.91)]. Adults with IDD and HIV were also more likely to have emergency department visits [aRR: 1.68 (1.42, 1.98)] and hospital admissions [aRR: 2.55 (1.74, 3.73)] for any reason, and to have mental health emergency department visits and/or admissions [aRR: 2.82 (1.90, 4.18)]. DISCUSSION: Adults with IDD and HIV have complex health profiles and greater health service use than HIV-negative adults with IDD. These findings call for closer integration of programs delivered by the HIV and disability sectors to optimise the health of this patient population.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Infecções por HIV/epidemiologia , Deficiência Intelectual/epidemiologia , Transtornos Mentais/epidemiologia , Avaliação das Necessidades/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Comores , Deficiências do Desenvolvimento/terapia , Feminino , Infecções por HIV/terapia , Humanos , Deficiência Intelectual/terapia , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Adulto Jovem
4.
Oral Dis ; 21(8): 987-93, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26389700

RESUMO

OBJECTIVE: Oral lichen planus is a chronic inflammatory oral mucosal disease whose exact cause is unclear and which requires efficient diagnostic and therapeutic strategies. Identification of disease-specific biomarkers in saliva is an easy, quick, and non-invasive approach for molecular diagnosis. This study was designed to examine salivary exosomal microRNAs (miRNAs) that could be candidates for diagnosing and elucidating the pathogenesis of oral lichen planus. SUBJECTS AND METHODS: We compared miRNA profiles of salivary exosomes of patients with oral lichen planus with those of healthy controls. Saliva samples from 16 patients with oral lichen planus and eight healthy controls were divided into two sets and examined using miRNA microarray analysis and TaqMan quantitative PCR. RESULTS: The three miRNAs identified (miR-4484, miR-1246, and miR-1290) were further validated. Of these, miR-4484 was significantly upregulated in the salivary exosomes of patients with oral lichen planus. CONCLUSIONS: This study thus identifies a potential miRNA biomarker for oral lichen planus and provides insight into the functions of miRNAs in the pathogenesis of oral inflammatory diseases.


Assuntos
Líquen Plano Bucal/diagnóstico , MicroRNAs/análise , Saliva/química , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Exossomos , Humanos , Pessoa de Meia-Idade
5.
Dentomaxillofac Radiol ; 44(2): 20140218, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25308829

RESUMO

Disc fracture of the temporomandibular joint (TMJ) is a little-known pathological condition owing to its extreme rarity. We report two cases of elderly patients who were diagnosed with disc fracture of the TMJ based on MRI, and we review related reports. On physical examination, an incomplete bite and mild joint pain were observed on the affected side in both patients. An MRI showed a complete fracture in the intermediate zone of the articular disc in the TMJ; the posterior fragment was displaced posteriorly, causing occlusal change in the closed position of the condyle and an incomplete bite. Conservative treatment including manual manipulation, physical therapy and oral appliance had no effect on the occlusal abnormality. Although the inciting cause of the disc fracture remained unclear, the degenerative changes in the joint may have been a factor by increasing the brittleness and reducing the elasticity of the disc.


Assuntos
Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia Panorâmica , Transtornos da Articulação Temporomandibular/terapia
6.
J Dent Res ; 93(1): 78-83, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24155265

RESUMO

In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig's epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.


Assuntos
Mesoderma/citologia , Dente Molar/crescimento & desenvolvimento , Morfogênese/fisiologia , Raiz Dentária/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Citocalasina D/farmacologia , Saco Dentário/citologia , Saco Dentário/crescimento & desenvolvimento , Órgão do Esmalte/citologia , Órgão do Esmalte/crescimento & desenvolvimento , Epitélio/efeitos dos fármacos , Epitélio/crescimento & desenvolvimento , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Antígeno Ki-67/análise , Mesoderma/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Dente Molar/citologia , Dente Molar/efeitos dos fármacos , Morfogênese/efeitos dos fármacos , Nocodazol/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Odontogênese/efeitos dos fármacos , Odontogênese/fisiologia , Técnicas de Cultura de Órgãos , Raiz Dentária/citologia , Raiz Dentária/efeitos dos fármacos , Moduladores de Tubulina/farmacologia
7.
Br J Pharmacol ; 168(5): 1133-45, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23043610

RESUMO

BACKGROUND AND PURPOSE: The effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, were investigated on human prostate cancer cells and its mechanism of action elucidated. EXPERIMENTAL APPROACH: The anti-cancer effects of MH were examined in prostate cancer and normal cells. The effects were validated in vivo using a mouse xenograft model. KEY RESULTS: MH increased the expression of PPARγ in prostate PC-3 and LNCap cells. The pull-down assay and molecular docking study indicated that MH directly binds to PPARγ. MH also increased transcriptional activity of PPARγ but decreased NF-κB activity. MH inhibited the growth of human prostate cancer cells, an effect attenuated by the PPARγ antagonist GW9662. MH induced apoptotic cell death and this was related to G(0) -G(1) phase cell cycle arrest. MH increased the expression of the cell cycle regulator p21, and apoptotic proteins, whereas it decreased phosphorylation of Rb and anti-apoptotic proteins. Transfection of PC3 cells with p21 siRNA or a p21 mutant plasmid on the cyclin D1/ cycline-dependent kinase 4 binding site abolished the effects of MH on cell growth, cell viability and related protein expression. In the animal studies, MH inhibited tumour growth, NF-κB activity and expression of anti-apoptotic proteins, whereas it increased the transcriptional activity and expression of PPARγ, and the expression of apoptotic proteins and p21 in tumour tissues. CONCLUSIONS AND IMPLICATION: MH inhibits growth of human prostate cancer cells through activation of PPARγ, suppression of NF-κB and arrest of the cell cycle. Thus, MH might be a useful tool for treatment of prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Compostos de Bifenilo/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Lignanas/farmacologia , NF-kappa B/metabolismo , PPAR gama/agonistas , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Lignanas/uso terapêutico , Masculino , Camundongos , Camundongos Nus , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Zoonoses Public Health ; 59(7): 482-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22958339

RESUMO

The purpose of this study was to determine the changing pattern of Salmonella serotypes causing acute diarrhoea in humans in Gwangju area, Korea, during 2000-2009. A total of 596 Salmonella isolated from culture of 29,896 faecal samples of patients with acute diarrhoea were included in this study. Faecal samples were collected from local hospitals and clinics in Gwangju area during January 2000-December 2009. The mean annual frequency of isolates for the 10 years was 2.0% (range, 0.9-6.0). The isolates were serologically classified into 43 different serotypes. The 10 most common serotypes were Salmonella Enteritidis (47.9%), S. Typhimurium (20.4%), S. Braenderup (3.2%), S. Montevideo (2.9%), S. Paratyphi B (2.9%), S. London (2.3%), S. Bardo (1.7%), S. Virchow (1.7%), S. Infantis (1.5%) and S. Typhi (1.5%), accounting for 86% of all the isolates. Temporal variations were observed in the distribution of different Salmonella serotypes over the years, and only S. Enteritidis and S. Typhimurium were persistent throughout the study period. Although age specificity varied with serotypes, Salmonella was isolated most frequently from children below 5 years of age (179/596, 30.0%). A seasonal trend was apparent, and the highest rates were found in the summer months. This is the first report of the annual frequency of isolation of Salmonella serotypes, and seasonal and age-specific patterns of salmonellosis in humans in Gwangju area, Korea, over a decade-long period.


Assuntos
Diarreia/microbiologia , Infecções por Salmonella/microbiologia , Salmonella/classificação , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Diarreia/epidemiologia , Fezes/microbiologia , Humanos , Pessoa de Meia-Idade , Antígenos O/imunologia , Prevalência , República da Coreia/epidemiologia , Infecções por Salmonella/epidemiologia , Salmonella enteritidis/classificação , Salmonella typhimurium/classificação , Estações do Ano , Sorotipagem , Adulto Jovem
9.
Br J Pharmacol ; 167(2): 356-67, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22462474

RESUMO

BACKGROUND AND PURPOSE: Although 5-HT(1B) receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons. EXPERIMENTAL APPROACH: Primary afferent-evoked EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices using a conventional whole-cell patch clamp technique under a voltage-clamp condition. KEY RESULTS: CP93129, a selective 5-HT(1B) receptor agonist, reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of spontaneous miniature EPSCs without affecting the current amplitude. The CP93129-induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT(1B/1D) receptor antagonist, but not LY310762, a 5-HT(1D) receptor antagonist. Sumatriptan, an anti-migraine drug, also decreased EPSC amplitude, and this effect was partially blocked by either GR55562 or LY310762. On the other hand, primary afferent-evoked EPSCs were mediated by the Ca(2+) influx passing through both presynaptic N-type and P/Q-type Ca(2+) channels. The CP93129-induced inhibition of EPSCs was significantly occluded by ω-conotoxin GVIA, an N-type Ca(2+) channel blocker. CONCLUSIONS AND IMPLICATIONS: The present results suggest that the activation of presynaptic 5-HT(1B) receptors reduces glutamate release from primary afferent terminals onto medullary dorsal horn neurons, and that 5-HT(1B) receptors could be, at the very least, a potential target for the treatment of pain from orofacial tissues.


Assuntos
Vias Aferentes/metabolismo , Ácido Glutâmico/metabolismo , Células do Corno Posterior/fisiologia , Receptor 5-HT1B de Serotonina/metabolismo , Potenciais de Ação , Animais , Fenômenos Eletrofisiológicos , Piridinas/farmacologia , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley
10.
Appl Microbiol Biotechnol ; 64(6): 833-9, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-14740195

RESUMO

The secretion of Bacillus stearothermophilus L1 lipase in Saccharomyces cerevisiae was investigated by employing a fusion partner, a cellulose-binding domain (CBD) from Trichoderma harzianum endoglucanase II (THEG). The CBD was connected to the N-terminal of L1 lipase through an endogenous linker peptide from THEG. The expression cassette for the fusion protein in S. cerevisiae was constructed using the alpha-amylase signal peptide and the galactose-inducible GAL10 promoter. Secretion of CBD-linker-L1 lipase by this fusion construct was dramatically 7-fold enhanced, compared with that of the mature L1 lipase without CBD-fusion. The fusion protein was secreted into the culture medium, reaching levels of approximately 1.3 g/l in high-cell-density fed-batch cultures. Insertion of a KEX2 cleavage site into the junction between CBD-linker and L1 lipase resulted in the same level of enhanced secretion, indicating that the CBD-linker fusion probably plays a critical role in secretion from endoplasmic reticulum to Golgi apparatus. Therefore, the CBD from THEG can be used both as an affinity tag and as a secretion enhancer for the secretory production of heterologous proteins in S. cerevisiae, since in vivo breakage at the linker was almost negligible.


Assuntos
Geobacillus stearothermophilus/enzimologia , Lipase/biossíntese , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Celulase/química , Celulase/metabolismo , Celulose/química , Celulose/metabolismo , Lipase/genética , Dados de Sequência Molecular , Mutagênese Insercional/métodos , Pró-Proteína Convertases/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Tempo , Trichoderma
12.
J Pharm Biomed Anal ; 25(3-4): 639-50, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11377045

RESUMO

A simple, reliable HPLC-UV detection method was developed for the simultaneous determination of loxoprofen and its metabolites (i.e. trans- and cis-alcohol metabolites), in human plasma and urine samples. The method involves the addition of a ketoprofen (internal standard) solution in methanol, zinc sulfate solution and acetonitrile to plasma and urine samples, followed by centrifugation. An aliquot of the supernatant was evaporated to dryness, and the residue reconstituted in a mobile phase (acetonitrile:water=35:65 v/v, pH 3.0). An aliquot of the solution was then directly injected into the HPLC system. Separations were performed on octadecylsilica column (250x4.5 mm, 5 microm) with a guard column (3.2x1.5 cm, 7 microm) at ambient temperature. Loxoprofen and the metabolites in the eluent were monitored at 220 nm (a.u.f.s. 0.005). Coefficients of variations (CV%) and recoveries for loxoprofen and its metabolites were below 10 and over 96%, respectively, in the 200 approximately 15000 ng ml(-1) range for plasma and 500 approximately 50000 ng ml(-1) range for urine. Calibration curves for all the compounds in the plasma and urine were linear over the above-mentioned concentration ranges with a common correlation coefficient of 0.999. The detection limit of the present method was 100 ng for all the compounds. These results indicate that the present method is very simple and readily applicable to routine bioavailability studies of these compounds with an acceptable sensitivity.


Assuntos
Anti-Inflamatórios não Esteroides/análise , Fenilpropionatos/análise , Álcoois/análise , Cromatografia Líquida de Alta Pressão , Humanos , Fenilpropionatos/sangue , Fenilpropionatos/urina , Estereoisomerismo , Raios Ultravioleta
13.
Bioorg Med Chem Lett ; 11(4): 559-62, 2001 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-11229771

RESUMO

The structure-activity relationship and molecular modelings of a novel pimarane COX-2 inhibitor are reported. Particularly, a series of linker extended analogues designed on the basis of these studies exhibited significantly enhanced COX-2 inhibitory activities and selectivities.


Assuntos
Inibidores de Ciclo-Oxigenase/síntese química , Diterpenos/síntese química , Isoenzimas/antagonistas & inibidores , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Diterpenos/farmacologia , Prostaglandina-Endoperóxido Sintases , Relação Estrutura-Atividade
14.
J Pharmacol Exp Ther ; 296(2): 364-71, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11160619

RESUMO

The pentacyclic palmarumycins are structurally unique natural products with both antifungal and antibacterial activities but their antineoplastic effects are not well established. We have examined their antiproliferative actions against tumor cells using a temperature-sensitive tsFT210 mouse mammary carcinoma cell line and found that a novel palmarumycin analog, [8-(furan-3-ylmethoxy)-1-oxo-1,4-dihydronaphthalene-4-spiro-2'-naphtho[1",8"-de][1',3'][dioxin] or SR-7, prominently blocked mammalian cell cycle transition in G2/M but not in G1 phase. We found no evidence for inhibition of the critical mitosis-controlling cyclin-dependent kinase Cdk1, or its regulator, the dual specificity phosphatase Cdc25. Moreover, Cdk1 was hypophosphorylated and not directly inhibited by SR-7. SR-7 also failed in vitro to hypernucleate bovine tubulin, did not compete with colchicine for tubulin binding, and only modestly blocked GTP-induced assembly. In addition, SR-7 caused almost equal inhibition of paclitaxel-sensitive and -resistant cell growth. Moreover, unlike benchmark tubulin-disrupting agents, SR-7 did not cause hyperphosphorylation of the antiapoptotic protein Bcl-2. Thus, SR-7 represents a novel chemical structure that can inhibit G2/M transition by a mechanism that appears to be independent of marked tubulin disruption.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Dioxanos/farmacologia , Compostos de Espiro/farmacologia , Animais , Ligação Competitiva/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/metabolismo , Divisão Celular/efeitos dos fármacos , Colchicina/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Citometria de Fluxo , Humanos , Camundongos , Naftalenos , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Estrogênio/efeitos dos fármacos , Tubulina (Proteína)/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo
15.
J Appl Microbiol ; 90(2): 216-22, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11168724

RESUMO

AIMS: To obtain an optimal combination of agitation speed and aeration rate for maximization of specific glucose oxidase (GOD) production in recombinant Saccharomyces cerevisiae, and to establish a correlation between kLa vis-à-vis oxygen transfer condition and specific glucose oxidase production. METHODS AND RESULTS: The oxygen transfer condition was manifested indirectly by manipulating the impeller speed and aeration rate in accordance with a Central Composite Rotatory Design (CCRD). The dissolved oxygen concentration and the volumetric oxygen transfer coefficient (kLa) were determined at corresponding combinations of impeller speed and aeration rate. The maximal specific extracellular glucose oxidase production (3.17 U mg-1 dry cell mass) was achieved when the initial dissolved oxygen concentration was 6.83 mg l-1 at the impeller speed of 420 rev min-1 and at the rate of aeration of 0.25 vvm. It was found out that while impeller speed had a direct effect on the production of enzyme, a correlation between kLa and specific GOD production could not be established. CONCLUSION: At the agitation speed of 420 rev min-1 and at 0.25 vvm aeration rate, the degree of turbulence and the dissolved oxygen concentration were thought to be optimal both for cellular growth and production of enzyme. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined effect of agitation and aeration on recombinant glucose oxidase production in batch cultivation has not yet been reported in the literature. Therefore, this study gives an insight into the effect of these two important physical parameters on recombinant protein production. It also suggests that since there is no correlation between kLa and specific production of GOD, kLa should not be used as one of the scale-up parameters.


Assuntos
Glucose Oxidase/metabolismo , Oxigênio , Recombinação Genética , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/crescimento & desenvolvimento , Reatores Biológicos , Meios de Cultura , Glucose Oxidase/genética , Oxigênio/farmacologia , Saccharomyces cerevisiae/genética
16.
J Org Chem ; 65(20): 6319-37, 2000 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-11052073

RESUMO

The highly oxygenated antifungal anticancer natural product (+/-)-diepoxin sigma was prepared in 10 steps and in 15% overall yield from O-methylnaphthazarin. Highlights of the synthetic work include an Ullmann coupling and a possibly biomimetic oxidative spirocyclization for the introduction of the naphthalene ketal as well as the use of a retro-Diels-Alder reaction to unmask the reactive enone moiety in the naphthoquinone bisepoxide ring system. A novel highly bulky chiral binaphthol ligand was developed for a boron-mediated Diels-Alder reaction that constitutes a formal asymmetric total synthesis of (+)-diepoxin sigma.


Assuntos
Compostos de Epóxi/síntese química , Plantas Medicinais/química , Compostos de Espiro/síntese química , África , Cristalografia por Raios X
17.
Gynecol Oncol ; 74(2): 170-80, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10419728

RESUMO

OBJECTIVE: The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp(6)) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent. METHODS: We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo. RESULTS: Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6% compared with control, 4-5%. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy. CONCLUSIONS: Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Pamoato de Triptorrelina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Proteína Quinase CDC2/biossíntese , Carcinoma/enzimologia , Carcinoma/patologia , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular , Feminino , Camundongos , Camundongos SCID , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas
18.
Solid State Nucl Magn Reson ; 13(4): 255-62, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10378434

RESUMO

Ag-impurity effects on the first- and second-order quadrupole interaction (QI) at 23Na site in an isomorphic mixed system, Na(1-x)Ag(x)NO2 (x = 0, 0.0084, 0.026, 0.079, 0.094, 0.16), have been investigated by employing 23Na (I = 3/2) magic angle spinning nuclear magnetic resonance (MAS NMR) technique. The central transition (CT) and satellite transition (ST) are simultaneously observed with this system. From the spectral analysis, the quadrupole parameter and its distribution width are obtained as a function of Ag concentration. From the intensity loss of CT MAS centerband and of the envelope function of ST MAS sidebands due to impurities, the range of their influence on the second- and first-order QI is estimated. The estimated ranges contain the second and first neighbouring Na sites from the resonating 23Na nucleus for the first- and second-order QI, respectively.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Prata , Isótopos de Sódio
20.
Int J Gynaecol Obstet ; 60 Suppl 1: S85-96, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9833620

RESUMO

UNLABELLED: A retrospective and comparative study of high-risk gestational trophoblastic tumor (GTT) treated with different chemoregimen from 1971 to 1995 was performed and to find most effective chemotherapy regimen and independent risk factors. Three hundred seven patients in scoring over 8 points in WHO classification were categorized into high-risk group among 802 GTT cases received chemotherapy in the 2,418 GTD patients registered at KRI-TRD (Korean Research Institute for Gestational Trophoblastic Disease), Catholic University Medical College in Korea. Study groups of multiagent combination chemotherapy in 227 patients of the high-risk GTT were divided such as 49 cases of combination chemotherapy with MTX + folinic acid and Act-D, 40 cases of MAC regimen, 42 cases of CHAMOCA regimen, and 96 cases of EMA/CO. Initial tumor response according to hCG titer decrease was found in good response (log fall) 69.8%, of EMA /CO regimen group. On the other hand, good response was shown in only 24.5% of MTX + ACT-D, 32.5% of MAC regimen, and 52.4%, of CHAMOCA regimen respectively. Remission rate of EMA/CO regimen was 90.6% (87/96) and courses of chemotherapy until remission was 8.5+/-2.2. However, remission rate of other regimens of MTX + Act-D, MAC, and CHAMOCA were 63.3%, (31/49) 67.5% (27/40) and 76.2% (32/45) respectively, with 10.0+/-4.0, 10.7+/-4.3, 9.1+/-3.9 chemotherapy courses respectively until remission. Therefore, EMA/CO regimen groups were found to have low drug toxicity, early remission and a low failure rate. In the study of independent risk factors in the 165 cases of high-risk gestational trophoblastic tumor patients received EMA/CO regimen, stepwise Coxs proportional hazard's regression of prognostic factors using multivariate analysis revealed tumor age, number of metastatic organs, metastatic site and inadequate previous chemotherapy. According to the performance of fitted logistic regression model, the prediction rate of death and survival was 80.5%. CONCLUSIONS: The most effective chemotherapy to high-risk GTT was EMA/CO regimen than other regimens. The following factors showed poor prognosis; 1) Tumor age is over 12 month, 2) more than 2 organs had metastatic lesion, 3) inadequate previous therapy that includes unplanned operation and inadequate previous chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Trofoblásticas/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Mola Hidatiforme/tratamento farmacológico , Coreia (Geográfico) , Metotrexato/administração & dosagem , Gravidez , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Trofoblásticas/mortalidade , Neoplasias Uterinas/mortalidade , Vincristina/administração & dosagem
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