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OBJECTIVES: To determine whether children advised by a pediatrician to take sports drinks consume them more frequently than do other children and whether these children have an increased risk of dental caries. METHODS: The subjects were 522 mother/child pairs who attended a dental checkup for 3-year-olds at one of ten community health centers in Nagasaki, Japan. Pearson's chi-square test was used to compare the prevalence of children with or without dental caries according to child-related variables. Multiple logistic regression was performed to assess the relationship between the presence of dental caries and child-related variables taken from a dental checkup and a questionnaire. RESULTS: A high frequency of sports drink consumption was strongly associated with dental caries in children. The highest proportion of mothers answered that they were advised by a pediatrician to give sports drinks to their children. However, these children consumed sports drinks significantly less frequently than did children who did so for reasons other than pediatrician recommendations. In addition, these children were significantly less likely to have dental caries than were children who consumed sports drinks for otherreasons. CONCLUSIONS: Pediatrician-recommended consumption of sports drinks does not lead to more frequent consumption of these beverages or to dental caries in 3-year-old children.
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Bebidas/efeitos adversos , Cárie Dentária/etiologia , Pediatria , Distribuição de Qui-Quadrado , Pré-Escolar , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Prevalência , Esportes , Inquéritos e QuestionáriosRESUMO
The radial electric field in a field-reversed configuration (FRC) plasma plays an important role in the global stability and confinement properties. Herein, we developed a new Langmuir probe array named "Skewered probe" employed in measuring the radial potential profile in the collisional merging formation of an FRC in the FAT-CM (FRC Amplification via Translation - Collisional Merging) device. Because an FRC has a strong toroidal flow, the skewered probe consists of alternately skewered ring electrodes and ceramic beads on a thin stainless-steel tube to neutralize the effect of plasma flow. The developed array has nine electrodes, one every 2 cm from r = 9-25 cm, and it measures the FRC boundary in the case when the radius of the excluded flux ranges from 10 to 20 cm. The skewered probe also has one additional electrode that measures the potential near the chamber wall as a reference for the other electrodes. The radial potential profile of the FRC formed by the collisional merging method in the FAT-CM device was measured using the probe, and the results showed that the region of negative potential gradually changed to a positive potential after merging the FRCs. It was also shown that a strong outward electric field is formed near the separatrix at n = 2 rotational instability.
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PURPOSE: This study aimed to determine the outcomes and prognostic factors associated with octogenarians who underwent pulmonary resection for lung cancer. METHODS/PATIENTS: From 2009 to 2018, 76 octogenarians underwent pulmonary surgery for lung cancer at the Kanazawa Medical University, Japan. They were divided into two groups (early and late octogenarians), and their clinicopathological characteristics and outcomes were investigated. Overall survival rates and recurrence-free survival rates were determined using Kaplan-Meier curves. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Limited surgery was performed more often in the late octogenarian group; however, most perioperative factors were not significantly different between the two groups. The 3-year overall survival and recurrence-free survival rates were 61.2% and 52.8%, respectively. The median observation period was 37.5 (8.9-112.3) months postoperatively. Kaplan-Meier curves showed that age ≥ 85 years (late octogenarian), smoking history, and squamous cell carcinoma on histology were associated with worse survival rates. Multivariate analysis identified age ≥ 85 years (late octogenarian) (p = 0.011) and cigarette smoking (p = 0.025) as unfavorable prognostic factors for overall survival and recurrence-free survival, respectively. CONCLUSIONS: Most octogenarians with an indication for surgery can tolerate pulmonary surgery. However, owing to the limitations of this retrospective, single-center study, future studies involving multiple-institutions are required to confirm our findings.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Fatores Etários , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fumar/efeitos adversos , Taxa de Sobrevida , Cirurgia Torácica Vídeoassistida , Resultado do TratamentoRESUMO
We investigated the effect of annealing in a hydrogen atmosphere on carbon nanocap formation during decomposition of a 6H-SiC(000-1) surface. It was determined that native oxides were reduced to below the detection limit of X-ray photoelectron spectroscopy after 30 min of annealing at 1200 degrees C in a hydrogen atomosphere at 10(-3) Pa. In addition, we found that the homogeneity of carbon nanocap size was improved on the SiC surface, compared with a sample annealed in ultra-high vacuum. This technique will be useful in the fabrication of homogeneous carbon nanotube layers by surface decomposition of SiC.
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The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.
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OBJECTIVES: To determine the aetiology, epidemiology and sanitary factors of carriage of enteropathogenic Escherichia coli (EPEC) and Shiga-toxin producing E. coli (STEC) in food-handlers working in tourist hotels in three popular tourist destinations in Kenya. DESIGN: Cross sectional laboratory based study. SETTING: Three tourist destinations of Nairobi, Malindi and Diani in Kenya. SUBJECTS: Food handlers who were working in hotels frequented by tourists in the three study sites. RESULTS: Overall, during the period of April 2003 to May 2004, a total of 1399 food handlers stool samples were collected and analysed. EPEC expressing the eaeA gene and STEC expressing the stx2 gene were detected in 11/1399 (0.8%) and 2/1399 (0.1%) of the study subjects respectively. The mean age of the subjects from whom EPEC and STEC were isolated was similar (32.6 years) to those from whom no EPEC and STEC were isolated (32.5 years). Prior use of antibiotics, water source and toilet types were not significantly associated with the isolation of EPEC and STEC (p>0.05). There were 11 resistance patterns with six isolates (6/13, 46.2%) showing multidrug resistance. High prevalence of resistance was observed to co-trimoxazole (55.6%), chloramphenicol (33.3%), ampicillin (22.2%) and tetracycline (22.2%). High concentrations of antibiotics were required to achieve MIC90 for tetracycline, (>64 mg ml(-1)) and ampicillin (>256 mg ml(-1)). Cluster analysis of the Pulse Field Gel Electrophoresis profiles revealed that the EPEC and STEC isolates belonged to two main genotypes with 11 distinct DNA fragment profiles. CONCLUSION: This is the first report in Africa on the isolation of STEC from food handlers working in tourist hotels. These food handlers who carry the STEC and EPEC could potentially infect tourists and other people through food or water contamination in the hotel settings and thus our findings are of great public health importance.
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Escherichia coli Enteropatogênica/isolamento & purificação , Manipulação de Alimentos , Escherichia coli Shiga Toxigênica/isolamento & purificação , Adolescente , Adulto , Portador Sadio/epidemiologia , Farmacorresistência Bacteriana , Eletroforese em Gel de Campo Pulsado , Escherichia coli Enteropatogênica/classificação , Escherichia coli Enteropatogênica/efeitos dos fármacos , Fezes/microbiologia , Feminino , Humanos , Quênia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Escherichia coli Shiga Toxigênica/classificação , Escherichia coli Shiga Toxigênica/efeitos dos fármacos , Adulto JovemRESUMO
The near-Earth carbonaceous asteroid 162173 Ryugu is thought to have been produced from a parent body that contained water ice and organic molecules. The Hayabusa2 spacecraft has obtained global multicolor images of Ryugu. Geomorphological features present include a circum-equatorial ridge, east-west dichotomy, high boulder abundances across the entire surface, and impact craters. Age estimates from the craters indicate a resurfacing age of [Formula: see text] years for the top 1-meter layer. Ryugu is among the darkest known bodies in the Solar System. The high abundance and spectral properties of boulders are consistent with moderately dehydrated materials, analogous to thermally metamorphosed meteorites found on Earth. The general uniformity in color across Ryugu's surface supports partial dehydration due to internal heating of the asteroid's parent body.
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BACKGROUND: In this paper, the characteristics of the early stage of dental caries are discussed and the methods we used to treat the early stage of dental caries to increase the number of caries-free patients are presented. Studies from in vitro to in situ experiments and a clinical study were carried out to support clinical remineralization therapy. METHODS AND RESULTS: To clarify the effect of time for remineralization, the degree of remineralization was assessed at 2 days, 6 days, and 10 days after 2-day demineralization in 0.01 M/L lactic acid buffer (pH 4.0 at 37 degrees ). The remineralization solution contained 3.0 mM/L Ca, 1.8 mM/L P, and 3 ppm fluoride adjusted to pH 7.0. A 10-day continuous remineralization with a 3 ppm fluoride resulted in a high fluoride concentration. To evaluate mineral loss from sound tooth structure and white spot lesions, thin sections (about 90 microm) including white spots (WS) were prepared and exposed to oral conditions for 2 weeks continuously. The mineral loss from sound tooth structure was found to be twice that from WS. In another experiment during the remineralization period, enamel samples were immersed in three different bicarbonate solutions; 0.5, 5.0 and 50 mM/L for 30 minutes, two times per day. Both the bicarbonate and fluoride applied groups showed higher improvement in acid resistance and the amount of remaining mineral was almost two times higher than the controls (p < 0.01). In a clinical study we demonstrated remineralization in patients who followed professional mechanical tooth cleaning and fluoride prophylaxis paste. Using this regime, in patients with deciduous caries present at baseline, over 80 per cent of permanent teeth were caries free at the age of 12 years. In these studies the digital camera with CasMaTCH and an image analysis system showed several advantages for monitoring in de- and remineralization. CONCLUSIONS: White spot lesions, rather than intact tooth surfaces, can be mineralized through the daily clinical procedures described in this paper.
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Cariostáticos/uso terapêutico , Cárie Dentária/tratamento farmacológico , Fluoretos/uso terapêutico , Fotografia Dentária , Bicarbonato de Sódio/uso terapêutico , Remineralização Dentária/métodos , Animais , Bovinos , Cárie Dentária/diagnóstico , Testes de Atividade de Cárie Dentária , Diagnóstico Precoce , Fluorescência , Humanos , Processamento de Imagem Assistida por Computador , LuzRESUMO
Sindbis virus can infect a broad range of insect and vertebrate cell types due to the widespread distribution of the cellular receptor for the virus. The development of Sindbis virus vectors that target specific cell types could have important implications for the design of gene therapy strategies. To achieve this goal we have designed and constructed Sindbis virus particles displaying the IgG-binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector has minimal infectivities against baby hamster kidney and human cell lines. When used in conjunction with monoclonal antibodies that react with cell-surface antigens, however, the protein A-envelope chimeric virus was able to infect human cell lines with high efficiency. Infection rates were 90% or higher for human lymphoblastoid cells. A variety of cells could be targeted by changing the monoclonal antibody without generating a new recombinant virus.
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Sistemas de Liberação de Medicamentos , Vetores Genéticos , Imunoglobulina G/metabolismo , Sindbis virus , Proteína Estafilocócica A/metabolismo , Animais , Anticorpos Monoclonais , Sítios de Ligação , Cricetinae , Ensaio de Imunoadsorção Enzimática , Técnicas de Transferência de Genes , Células HeLa , Humanos , Glicoproteínas de Membrana/genética , Camundongos , Proteínas Recombinantes de Fusão/metabolismo , Células Tumorais Cultivadas , Proteínas do Envelope Viral/genética , Vírion/metabolismo , beta-Galactosidase/genéticaRESUMO
Fimbriae are protein-based filamentous appendages that protrude from the bacterial cell surface and facilitate host adhesion. Two types of fimbriae, FimA and Mfa1, of the periodontal pathogen Porphyromonas gingivalis are responsible for adherence to other bacteria and to host cells in the oral cavity. Both fimbrial forms are composed of 5 proteins, but there is limited information about their polymerization mechanisms. Here, the authors evaluated the function of Mfa5, one of the Mfa1 fimbrial accessory proteins. Using mfa5 gene disruption and complementation studies, the authors revealed that Mfa5 affects the incorporation of other accessory proteins, Mfa3 and Mfa4, into fibers and the expression of fimbriae on the cell surface. Mfa5 is predicted to have a C-terminal domain (CTD) that uses the type IX secretion system (T9SS), which is limited to this organism and related Bacteroidetes species, for translocation across the outer membrane. To determine the relationship between the putative Mfa5 CTD and the T9SS, mutants were constructed with in-frame deletion of the CTD and deletion of porU, a C-terminal signal peptidase linked to T9SS-mediated secretion. The ∆CTD-expressing strain presented a similar phenotype to the mfa5 disruption mutant with reduced expression of fimbriae lacking all accessory proteins. The ∆porU mutants and the ∆CTD-expressing strain showed intracellular accumulation of Mfa5. These results indicate that Mfa5 function requires T9SS-mediated translocation across the outer membrane, which is dependent on the CTD, and subsequent incorporation into fibers. These findings suggest the presence of a novel polymerization mechanism of the P. gingivalis fimbriae.
Assuntos
Proteínas de Fímbrias/fisiologia , Porphyromonas gingivalis/fisiologia , Aderência Bacteriana/fisiologia , Western Blotting , Eletroforese em Gel de Poliacrilamida , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/isolamento & purificação , Regulação Bacteriana da Expressão Gênica/fisiologia , Mutação/genética , Porphyromonas gingivalis/genéticaRESUMO
Nasal growth after cleft lip surgery with or without primary nasal repair was evaluated using lateral cephalograms. In 14 patients who underwent simultaneous nasal repair with primary cleft lip repair and 12 patients without simultaneous nasal repair, lateral cephalograms were obtained at 5 and 10 years of age. Lateral cephalograms of normal Japanese children were used as a control. At 5 years of age, there were significant differences in the nasal height and columellar angle among the three groups. Children without simultaneous nasal repair had shorter noses with more upward tilt of the columella compared with the controls, while children with simultaneous nasal repair had much shorter noses and more upward tilt than those without repair. At 10 years of age, the children without simultaneous nasal repair showed no differences from the control group, while those with simultaneous repair still had shorter noses and more upward tilt of the columella. These findings suggest that performing nasal repair at the same time as primary cleft lip surgery has an adverse influence on the subsequent growth of the nose.
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Fenda Labial/cirurgia , Previsões , Septo Nasal/cirurgia , Nariz/crescimento & desenvolvimento , Rinoplastia/métodos , Retalhos Cirúrgicos , Cefalometria , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Most catalytic micro/nanomotors that have been developed so far use hydrogen peroxide as fuel, while some use hydrazine. These fuels are difficult to apply because they can cause skin irritation, and often form and store disruptive bubbles. In this paper, we demonstrate a novel catalytic Pt micromotor that does not produce bubbles, and is driven by the oxidation of stable, non-toxic primary alcohols and aldehydes with dissolved oxygen. This use of organic oxidation mirrors living systems, and lends this new motor essentially the same characteristics, including decreased motility in low oxygen environments and the direct isothermal conversion of chemical energy into mechanical energy. Interestingly, the motility direction is reversed by replacing the reducing fuels with hydrogen peroxide. Therefore, these micromotors not only provide a novel system in nanotechnology, but also help in further revealing the underlining mechanisms of motility of living organisms.
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Peróxido de Hidrogênio/química , Nanotecnologia , Oxigênio/química , Água/químicaRESUMO
Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1-naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta-isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta-isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity.
Assuntos
Aminoácidos/farmacologia , Dipeptídeos/farmacologia , Oligopeptídeos/farmacologia , Renina/antagonistas & inibidores , Animais , Sítios de Ligação , Catepsina D/antagonistas & inibidores , Cães , Humanos , Pepsina A/antagonistas & inibidores , Coelhos , Ratos , Especificidade da Espécie , Relação Estrutura-Atividade , SuínosRESUMO
Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors.
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Renina/antagonistas & inibidores , Angiotensina I/biossíntese , Angiotensinogênio/metabolismo , Animais , Reações Antígeno-Anticorpo , Catepsinas/metabolismo , Inibidores Enzimáticos , Humanos , Pepsina A/metabolismo , Pepstatinas/farmacologia , Peptidil Dipeptidase A/metabolismoRESUMO
An orally active renin inhibitor, ES 6864 (N-[(2R)-3-morpholinocarbonyl-2-(1-naphthylmethyl)propionyl]-(4- thiazolyl)-L-alanyl-cyclostatine-(2-morpholinoethyl)amide), was synthesized. ES 6864 was found to be a highly potent inhibitor of human renin with a Ki value of 7.3 x 10(-9) M. The compound competitively inhibited human renin. The inhibitor was also potent against monkey renin but was less effective against renins from pig, goat, dog, rabbit, and rat. ES 6864 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. ES 6864 was resistant to proteolytic actions of the enzymes in rat tissue homogenates (liver, kidney, pancreas, and small intestine). Oral administration of ES 6864 at 30 mg/kg to conscious, sodium-depleted marmosets produced a significant blood pressure reduction and almost complete inhibition of plasma renin activity, which persisted for 5 hours. Oral administration of ES 6864 also produced dose-related decreases of blood pressure in hog renin-infused rats, but the duration of action was much shorter than that in conscious marmosets. The parent compound in the blood following oral administration of ES 6864 to marmosets was confirmed directly by measuring the plasma concentration of ES 6864. These results enhance the possibility of developing renin inhibitors that can be used clinically.
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Dipeptídeos/farmacologia , Morfolinas/farmacologia , Renina/antagonistas & inibidores , Administração Oral , Animais , Callitrichinae , Cães , Cabras , Humanos , Masculino , Inibidores de Proteases/farmacologia , Coelhos , Ratos , Ratos Endogâmicos , Especificidade da Espécie , SuínosRESUMO
Griseolic acid inhibited cAMP phosphodiesterase (PDE) at low concentrations, the I50 being of the order of 0.01-0.1 microM. Administration of griseolic acid to rats increased the cAMP level in liver and plasma several-fold. It increased glycogen degradation in mouse liver and stimulated lipolysis in isolated rat fat cells. Griseolic acid did not block the adenosine-elicited accumulation of cAMP in guinea pig brain slices. It had no effect on cAMP-dependent protein kinase from rat liver nor on the adenyl cyclase from rat brain.
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3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Adenosina/análogos & derivados , Adenosina/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Encéfalo/enzimologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Cricetinae , AMP Cíclico , GMP Cíclico/metabolismo , Cobaias , Técnicas In Vitro , Cinética , Lipólise/efeitos dos fármacos , Fígado/metabolismo , Glicogênio Hepático/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Ratos , Ratos EndogâmicosRESUMO
We have studied metallothionein (MT) induction by three primary inducers; a heavy metal, a glucocorticoid and a cytokine, and by the combinations of these inducers in the cultured cells. MT-protein was synergistically induced by either a cytokine or a heavy metal with a glucocorticoid hormone and was additively induced by the combination of a cytokine and a heavy metal, but MT-mRNA levels were not completely correlated with MT-protein levels. These results suggest that posttranscriptional regulation may be involved in the synergistic induction of MT-protein. We propose a possible mechanism in which marked MT induction by stress in vivo is dependent on the combined effect of two or more inducers, because marked MT induction is not seen by an injection of a plausible dose of either a glucocorticoid hormone or a cytokine in vivo.
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Metalotioneína/biossíntese , Northern Blotting , Linhagem Celular , Dexametasona/farmacologia , Sinergismo Farmacológico , Fator de Crescimento Epidérmico/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado , Metalotioneína/genética , RNA Mensageiro/genética , Estresse Fisiológico/fisiopatologia , Zinco/farmacologiaRESUMO
The heterodimeric glycoprotein hormones, human chorionic gonadotrophin (hCG), LH, TSH and FSH, consist of two non-covalently linked subunits, the alpha and beta subunits. The beta subunit is specific for each hormone and is responsible for the biological specificity, but the beta subunits of different hormones show some degree of structural homology. The CAGY (cysteine-alanine-glycine-tyrosine) region is one of the amino acid sequences that is homologous in different beta subunits and is highly conserved between species. In the present study, site-specific in-vitro mutagenesis was used to change three individual nucleotides in the centre of the CAGY region of the hCG-beta subunit, and the effects of these mutations on hCG production was determined by in-vitro transcription and then translation in Xenopus laevis oocytes. The results indicate that the CAGY region, particularly the glycine residue at position 36 in the beta subunit, is essential for the production of hCG. This finding is consistent with previous studies showing that this region is necessary for the biological activity of human TSH.
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Gonadotropina Coriônica/genética , Fragmentos de Peptídeos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Gonadotropina Coriônica/biossíntese , Gonadotropina Coriônica Humana Subunidade beta , DNA/genética , DNA Recombinante , Feminino , Regulação da Expressão Gênica , Subunidade alfa de Hormônios Glicoproteicos/biossíntese , Subunidade alfa de Hormônios Glicoproteicos/genética , Humanos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Oócitos , Fragmentos de Peptídeos/biossíntese , RNA Mensageiro/biossíntese , Xenopus laevisRESUMO
Phomactins, natural products isolated from the culture broth of marine fungus Phoma sp., were found to be active as PAF antagonists. This unique carbon skeleton led us to investigate the structure-activity relationship demonstrating that the lipophilicity at C-(7-8), acetoxy, (methoxycarbonyl)oxy, and 3-isoxazolyloxy substitution at C-20, and 2-beta-OH configuration at C-2 are all required for the enhancement of inhibitor activity.
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Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Fator de Ativação de Plaquetas/antagonistas & inibidores , Espectroscopia de Ressonância Magnética , Ensaio Radioligante , Relação Estrutura-AtividadeRESUMO
alpha-[6-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-5-oxoperhydro -1,4-thiazepin-4-yl]acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity. The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity. The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally. The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.