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1.
J Bone Miner Metab ; 33(1): 61-72, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24714934

RESUMO

This study examined whether the global clinical data for bazedoxifene could be extrapolated to a Japanese population by evaluating the results of a phase 2 study in postmenopausal Japanese women with osteoporosis as compared to those of a pivotal, phase 3 study. The efficacy of bazedoxifene 20 and 40 mg versus placebo on lumbar spine bone mineral density (BMD), bone turnover markers, lipid profile, incidence of fractures, and safety parameters was compared between the Japanese phase 2 study (N = 429) and the global phase 3 study (N = 7,492) during a 2-year period. In the primary population for assessment of bridging, differences in the mean percent change from baseline in lumbar spine BMD at 2 years relative to placebo were greater for women treated with bazedoxifene 20 and 40 mg in the phase 2 study than in the phase 3 study. BMD changes in the bazedoxifene groups were confirmed to be similar between the phase 2 study population and a subset of the phase 3 study population with similar baseline characteristics. The effects of bazedoxifene on incidence of fractures, bone turnover markers, and lipid metabolism were similar between studies. There were no major differences in safety parameters between studies. The greater improvement in lumbar spine BMD and similar results in bone turnover markers, fracture incidence, and safety profile observed with bazedoxifene in the phase 2 study compared with the phase 3 study confirmed the feasibility of extrapolating the global clinical data to a Japanese population.


Assuntos
Densidade Óssea/efeitos dos fármacos , Indóis/administração & dosagem , Vértebras Lombares/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/química , Estudos de Coortes , Método Duplo-Cego , Feminino , Consolidação da Fratura , Fraturas Ósseas/etiologia , Humanos , Japão , Lipídeos/química , Pessoa de Meia-Idade , Segurança do Paciente , Pós-Menopausa
2.
J Biosci Bioeng ; 137(2): 94-100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38092600

RESUMO

Dipeptidyl peptidase IV (DPP-IV) has become an important target in the prevention and treatment of diabetes. Although many DPP-IV inhibitory peptides have been identified by a general approach involving the repeated fractionation of food protein hydrolysates, the obtained results have been dependent on the content of each peptide and fractionation conditions. In the present study, a peptide array that provides comprehensive assays of peptide sequences was used to identify novel DPP-IV inhibitory peptides derived from bovine milk proteins; these peptides were then compared with those identified using the general approach. While the general approach identified only known peptides that were abundant in the hydrolysate, the peptide array-based approach identified 10 novel DPP-IV inhibitory peptides, all of which had proline at the second residue from the N-terminus. The proper or combined use of these two approaches, which have different advantages, will enable the efficient development of novel bioactive foods and drugs.


Assuntos
Inibidores da Dipeptidil Peptidase IV , Proteínas do Leite , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Peptídeos/química , Sequência de Aminoácidos
3.
Microorganisms ; 10(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36144321

RESUMO

Oral administration of a low dose of lactulose increases the abundance of genus Bifidobacterium in the large intestine; however, the details of the daily variation in Bifidobacterium have not been researched. To observe how the intestinal microbiota, including Bifidobacterium, change, especially immediately after the initiation of ingestion, we conducted a randomised, placebo-controlled, double-blind crossover study of ingestion of 4 g lactulose/day for 2 weeks in 36 healthy Japanese (including males and females). The primary outcome was the percentage of Bifidobacterium in the faecal bacteria. In the lactulose-treatment group, the percentage of Bifidobacterium was already significantly higher 2 days after starting lactulose ingestion than in the placebo group (20.5 ± 1.2% vs. 17.1 ± 1.2%, p = 0.021). Significant differences were maintained, gradually widening, until the end of the 2-week intervention period. There were significant increases in the percentage and the number of Bifidobacterium with ingestion of 4 g lactulose/day for 2 weeks, but no significant changes in the beta diversity of the intestinal microbiota between lactulose and placebo ingestion. The percentage of Bifidobacterium in the faecal bacteria returned to its original level within a week of the end of intervention with lactulose.

4.
Nutr Rev ; 80(12): 2288-2300, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-35640275

RESUMO

In the late 2010s, artificial intelligence (AI) technologies became complementary to the research areas of food science and nutrition. This review aims to summarize these technological advances by systematically describing the following: the use of AI in other fields (eg, engineering, pharmacy, and medicine); the history of AI in relation to food science and nutrition; the AI technologies currently used in the agricultural and food industries; and some of the important applications of AI in areas such as immunity-boosting foods, dietary assessment, gut microbiome profile analysis, and toxicity prediction of food ingredients. These applications are likely to be in great demand in the near future. This review can provide a starting point for brainstorming and for generating new AI applications in food science and nutrition that have yet to be imagined.


Assuntos
Inteligência Artificial , Atenção à Saúde , Humanos , Tecnologia de Alimentos
5.
J Cell Biochem ; 112(9): 2279-86, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21503962

RESUMO

ErbB2 has been proven to be an important target for breast cancer therapy. MP-412 is a dual ErbB2 and epidermal growth factor receptor tyrosine kinase inhibitor belonging to an irreversible-type anilinoquinazoline derivative. We demonstrate herein that along with the kinase inhibition, MP-412 has the ability to induce ubiquitination, internalization, and degradation of ErbB2 in several human breast cancer cell lines at concentrations relatively higher than those required for kinase inhibition. Another irreversible inhibitor, CI-1033, showed similar activity, while the reversible compounds were ineffective, suggesting a crucial role of covalent bonding functionality in these effects. In MCF7 cells, MP-412 depleted not only ErbB2 but also estrogen receptor (ER)-α, and to some extent, affected Raf-1, while MP-412 activated Hsp70 expression. Moreover, we observed that MP-412 increased immunocomplexing of Hsp70 with ErbB2 and ER-α, with simultaneous induction of ubiquitination of these client proteins. Furthermore, in combination with proteasome inhibitor, MP-412 resulted in the noticeable accumulation of ErbB2 and ER-α in the detergent insoluble fraction of cell lysates. These results suggest that MP-412 acts as an inhibitor of Hsp90 function, whereas MP-412 did not bind directly to ATP-binding site of Hsp90, unlike geldanamycin. We also found that new protein synthesis was involved in the activity of MP-412 on Hsp90 modulation. Since downregulation of ErbB2 and ER-α by accelerating the ubiquitin-proteolysis system will become an attractive approach for breast cancer therapy, we expect MP-412 to be a lead compound for the drug design and the development of such agents.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Receptor ErbB-2/metabolismo , Ubiquitinação/efeitos dos fármacos , Neoplasias da Mama , Linhagem Celular Tumoral , Ativação Enzimática , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Biossíntese de Proteínas , Receptor ErbB-2/antagonistas & inibidores , Estresse Fisiológico/efeitos dos fármacos
6.
J Biosci Bioeng ; 130(4): 374-381, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32713812

RESUMO

With increased awareness among consumers regarding food safety and security, food allergen control has become an indispensable requirement in the food industry. Although several methods for detecting allergens in food products are available, highly sensitive techniques are required. In this study, we developed a technique named as peptide array-based inhibition enzyme-linked immunosorbent assay (ELISA), Pep-iEIA, for evaluating antigenicity and detecting cow's milk antigen in infant formula products, using a peptide array consisting of a series of overlapping peptides found in allergenic milk proteins. Pep-iEIA was used to examine five cow's milk-based infant formulas with different degrees of hydrolyzation, and the assay offered both more sensitive detection and detailed analysis of remaining antigenic peptides in allergen compared to conventional ELISA. The antigenicity level of the allergenic peptides identified using Pep-iEIA was confirmed by surface plasmon resonance assay. We believe that Pep-iEIA will be highly useful for antigenicity evaluation of dairy products consumed by infants and patients with cow's milk allergy.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Fórmulas Infantis/efeitos adversos , Análise Serial de Proteínas , Alérgenos/imunologia , Animais , Bovinos , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas do Leite/imunologia , Peptídeos/imunologia
7.
Biochem Biophys Res Commun ; 390(4): 1214-20, 2009 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-19878660

RESUMO

Methamphetamine induces several cardiac dysfunctions, which leads to arrhythmia, cardiac failure and sudden cardiac death. Although these cardiac alterations elicited by methamphetamine were thought to be due to an indirect action of methamphetamine, namely, an excessive catecholamine release from synaptic terminals, while it seems likely that methamphetamine directly modulates the functioning of cardiomyocytes independent of neurotransmitters. However, the direct effects of methamphetamine on cardiomyocytes are still not clear. We show that methamphetamine directly accelerates the beating rate and alters Ca(2+) oscillation pattern in cultured neonatal rat cardiomyocytes. Adrenergic receptor antagonists did not block the methamphetamine-induced alterations in cardiomyocytes. Treatment with a ryanodine receptor type 2 inhibitor and a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor did not affect these responses, either. In contrast, the L-type Ca(2+) channel inhibitor nifedipine eradicated these responses. Furthermore, methamphetamine elevated the internal free Ca(2+) concentration in HEK-293T cells stably transfected with the L-type Ca(2+) channel alpha1C subunit. In neonatal rat cardiomyocytes, methamphetamine accelerates beating rate and alters Ca(2+) oscillation pattern by increasing Ca(2+) entry via the L-type Ca(2+) channels independent of any neurotransmitters.


Assuntos
Canais de Cálcio Tipo L/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Metanfetamina/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Linhagem Celular , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Ratos , Receptores Adrenérgicos/metabolismo
8.
J Biosci Bioeng ; 128(2): 156-161, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30862433

RESUMO

Food processing technology such as protein hydrolysis using proteases has been receiving a lot of attention, and it is important to accurately understand the cleavage specificity of each protease for selecting a protease suited to aims. Although numerous methods have been reported to reveal the substrate specificity of proteases, there is no method to evaluate simply, quickly, reasonably, and accurately. This study set out to devise Pep-MS assay, a novel assay system that can be used to comprehensively clarify positions at which proteases cleave, by combining a mass spectrometer and a photo-cleavable peptide array. First, we evaluated peptide array corresponding to the primary sequences of αS1-casein, αS2-casein and ß-casein with trypsin to verify the accuracy of the Pep-MS assay. The evaluation of cleavage positions by the trypsin protease reagent using the Pep-MS assay resulted in a matching rate of about 96.8% to rational cleavage positions. Next, we confirmed the cleavage positions in αS2-casein or ß-lactoglobulin by an industrial bacterial protease from Bacillus subtilis at some protease reaction temperatures or reaction times. The Pep-MS assay clarified the differences in the cleavage patterns due to the reaction temperature, and the change in the cleavage strength with the reaction time. Pep-MS assay is a promising method for evaluating the substrate specificity of proteases, which will be useful to find effective production conditions for functional peptide from foods and effective hydrolysis conditions for decreasing allergen of food proteins.


Assuntos
Caseínas/metabolismo , Lactoglobulinas/metabolismo , Espectrometria de Massas , Processos Fotoquímicos , Análise Serial de Proteínas , Tripsina/metabolismo , Bacillus subtilis/enzimologia , Manipulação de Alimentos , Hidrólise , Cinética , Proteólise , Especificidade por Substrato , Temperatura
9.
Biosci Microbiota Food Health ; 38(2): 69-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31106110

RESUMO

To investigate the prebiotic effect of lactulose at low dosages, we assessed changes in defaecation frequency following ingestion of 1, 2, or 3 g/day of lactulose for 2 weeks. Each test was carried out after a 2-week washout period. This was an open-label, before-after trial that enrolled 26 healthy Japanese women. The defaecation frequency, number of defaecation days, and number of faecal bifidobacteria increased significantly compared with before ingestion of 1, 2, and 3 g/day of lactulose. These results suggest that even 1 g/day of lactulose could have a prebiotic effect.

10.
Anim Sci J ; 89(9): 1348-1354, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29943396

RESUMO

Whey protein hydrolysates (WPH) were prepared from whey protein concentrate (WPC) by partial or extensive hydrolysis. WPC and two WPH types were characterized by a descriptive sensory analysis. WPC exhibited a "milky", "sweet", and "mild milk fat" odor, whereas extensively hydrolyzed whey protein (E-WPH) demonstrated "cheese-like", "acrid odor", and "sour" olfactory characteristics. In E-WPH, 3-(methylthio)-propanal, phenylacetaldehyde, and 3-methylbutanoic acid were specifically detected with high flavor dilution factors upon aroma extract dilution analysis. These odor-active compounds likely contributed to the olfactory characteristics of E-WPH, and their concentration increased together with that of their respective putative precursors: free methionine, phenylalanine, and leucine.


Assuntos
Odorantes/análise , Proteínas do Soro do Leite , Acetaldeído/análogos & derivados , Acetaldeído/análise , Adulto , Aldeídos/análise , Ácido Butírico/análise , Feminino , Humanos , Hidrólise , Leucina/análise , Masculino , Metionina/análise , Fenilalanina/análise , Adulto Jovem
11.
Orthop J Sports Med ; 5(9): 2325967117726740, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28932752

RESUMO

BACKGROUND: The high failure rate of rotator cuff repairs requires the development of methods to enhance healing at the tendon-bone junction of the repair site. PURPOSE: To assess functional recovery and structural outcomes in detail after implanting recombinant human bone morphogenetic protein-12 (rhBMP-12)/absorbable collagen sponge (ACS) as adjuvant treatment during open rotator cuff repair in patients over a 1-year postoperative follow-up. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 20 patients were randomized into 2 groups, rhBMP-12/ACS and standard-of-care (SOC) control, with 16 and 4 patients, respectively. The patients underwent open repair of a rotator cuff tear at least 2 to 4 cm wide; in the rhBMP-12/ACS group, this was augmented with a bioscaffold containing rhBMP-12. Follow-up assessments were conducted with a 100-mm visual analog scale (VAS) for pain and active and passive ranges of motion (ROMs) including forward flexion, elevation in the scapular plane, abduction, and external rotation at 12, 16, 26, 39, and 52 weeks after surgery; isometric strength in scapular abduction and external rotation at 16, 26, 39, and 52 weeks; and magnetic resonance imaging (MRI) at 12 and 52 weeks. RESULTS: The mean VAS score decreased from 37.9 mm preoperatively to 13.8 mm at week 52, and ROM and isometric strength recovered at week 52 in the rhBMP-12/ACS group. The mean VAS score decreased from 48.3 mm preoperatively to 1.5 mm at week 52, and ROM (excluding external rotation) and isometric strength recovered by week 52 in the SOC control group. Of the 16 patients in the rhBMP-12/ACS group, 14 showed an intact repair at week 12; the MRI scans of the other 2 patients could not be evaluated because of artifacts. In the SOC control group, 1 patient showed repair failure. At week 52, 14 repairs in the rhBMP-12/ACS group and 2 repairs with available MRI scans in the SOC control group remained intact. CONCLUSION: Functional recovery and structural outcomes in patients in whom rhBMP-12/ACS was used as adjuvant therapy in rotator cuff repair justify conducting future, larger, multicenter, prospective studies. REGISTRATION: NCT00936559, NCT01122498 (ClinicalTrials.gov identifier).

12.
Cardiovasc Res ; 65(1): 263-71, 2005 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-15621055

RESUMO

OBJECTIVE: Lysophosphatidylcholine (lysoPC) is abundant in atherosclerotic lesions and has potential immunomodulatory activities. This study is aimed to investigate effects of lysoPC on the interferon (IFN)-gamma-induced gene expression, focusing on T cell-directed CXC chemokines relevant to atherosclerosis. METHODS AND RESULTS: Effects of lysoPC on the IFN gamma-induced gene expression of IFN-inducible protein of 10 kDa (IP-10), IFN-inducible T cell alpha chemoattractant (I-Tac), and monokine induced by IFN gamma (Mig) were evaluated in cultured endothelial cells. Northern blotting showed that lysoPC transiently and dose-dependently inhibited the IFN gamma-induced accumulation of IP-10, Mig and I-Tac but not p48, interferon regulatory factor-1 and guanidine binding protein-1. Nuclear run-off assays showed that lysoPC did not inhibit IP-10, Mig and I-Tac gene transcription. An analysis of the degradation of IP-10, Mig and I-Tac mRNA revealed it to be enhanced by lysoPC. CONCLUSION: LysoPC selectively inhibits IFN gamma-induced IP-10, I-Tac and Mig expression in endothelial cells, at least in part, by reducing mRNA stability. Thus, lysoPC might regulate T cell-mediated immunity by affecting IFN gamma-mediated activation of endothelial cells in atherosclerotic lesions.


Assuntos
Quimiocina CXCL10/antagonistas & inibidores , Quimiocinas/metabolismo , Células Endoteliais/imunologia , Endotélio Vascular/imunologia , Lisofosfatidilcolinas/farmacologia , Arteriosclerose/imunologia , Northern Blotting/métodos , Western Blotting/métodos , Células Cultivadas , Quimiocina CXCL11 , Quimiocina CXCL9 , Quimiocinas CXC/metabolismo , Depressão Química , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferon gama/metabolismo
13.
Am J Sports Med ; 43(8): 1994-2004, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26033972

RESUMO

BACKGROUND: Recombinant human bone morphogenetic protein-12 (rhBMP-12) has been shown to induce tendon and ligament formation in rats and to improve tendon healing; however, the safety and feasibility of implanting rhBMP-12/absorbable collagen sponge (ACS) in humans are not known. PURPOSE: To investigate the safety and feasibility of rhBMP-12 on an ACS as an adjuvant therapy in open rotator cuff repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: This study consisted of 20 patients with full-thickness rotator cuff tears. Patients were randomized either to standard of care (SOC) treatment (open rotator cuff repair) or to receive 0.015 mg/mL rhBMP-12/ACS and SOC treatment during their open rotator cuff repair (rhBMP-12/ACS group) at a rate of 1/4 SOC/rhBMP-12/ACS. The feasibility of implanting the product and the safety of the product were evaluated during the 1-year follow-up period. The evaluation involved up to 10 postoperative visits, which included physical examinations, radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans with an emphasis on heterotopic ossification (HO), pharmacokinetics, immunogenicity, laboratory evaluations, and local and systemic adverse events at specified time points. RESULTS: Small amounts of HO were seen on follow-up CT scans in 10 of 16 patients in the rhBMP-12/ACS group and in 2 of 3 patients in the SOC group. HO did not increase at 26 weeks and was not associated with any adverse events or unsatisfactory clinical outcomes. Pharmacokinetics demonstrated that circulating levels of rhBMP-12 were not detectable after administration. Five of 16 patients showed a postoperative immunogenic response but did not show any correlating adverse events. Complete healing of the rotator cuff was observed in 14 of 16 patients; 2 of 16 imaging results could not be analyzed because of artifacts in the rhBMP-12 group on MRI scans. In the SOC group, 1 of 4 patients showed a retear at 12 weeks after surgery. CONCLUSION: The use of rhBMP-12/ACS has been shown to be feasible and safe in a concentration of 0.015 mg/mL when used in open rotator cuff repair. Higher dose concentrations of rhBMP-12 should be evaluated in the future to evaluate their safety and potential to increase rotator cuff healing after open surgical repair.


Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Fatores de Diferenciação de Crescimento/administração & dosagem , Lesões do Manguito Rotador , Manguito Rotador/cirurgia , Animais , Proteínas Morfogenéticas Ósseas/efeitos adversos , Proteínas Morfogenéticas Ósseas/farmacocinética , Colágeno , Estudos de Viabilidade , Fatores de Diferenciação de Crescimento/efeitos adversos , Fatores de Diferenciação de Crescimento/farmacocinética , Humanos , Masculino , Ossificação Heterotópica , Período Pós-Operatório , Ratos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Manguito Rotador/patologia , Padrão de Cuidado , Tampões de Gaze Cirúrgicos , Cicatrização
14.
Am J Hypertens ; 16(12): 993-9, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14643571

RESUMO

OBJECTIVE: The normal suppression of vascular sensitivity to angiotensin II (Ang II) in pregnancy is lost in pregnancy-induced hypertension (PIH). To examine the mechanism, we investigated Ang II receptor subtype 1 (AT1R) and 2 (AT2R) expression in human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC). METHODS: The HUVEC and VSMC were incubated with serum from normal pregnant women and PIH patients for 0 to 12 h. The AT1R and AT2R mRNA were semiquantified as the ratio to glyceraldehyde-3-phosphate dehydrogenase mRNA, using multiplex reverse transcription-polymerase chain reaction. The AT1R expression was also evaluated by immunocytochemistry. RESULTS: Serum from PIH patients significantly increased AT1R mRNA of HUVEC (1.48 +/- 0.44) after a 12-h incubation compared with that from normal pregnant women (0.25 +/- 0.14). On the other hand, AT2R mRNA of HUVEC incubated with serum from PIH patients (0.14 +/- 0.02) was significantly decreased compared with HUVEC incubated with serum from normal pregnant women (0.31 +/- 0.08). The AT1R mRNA of VSMC was significantly increased by serum from both PIH patients and normal pregnant women. The AT1R-to-AT2R mRNA ratio increased by serum from PIH patients was significantly reduced by anti-tumor necrosis factor-alpha (TNF-alpha) antibody (20 microg/mL). Valsartan (an AT1R antagonist, at 1 to 10 nmol/L) significantly increased AT2R mRNA of HUVEC. Also, immunocytochemistry demonstrated that endothelial AT1R expression was strongly increased by PIH sera and reduced by anti-TNF-alpha antibody. CONCLUSIONS: Endothelial AT1R expression is increased and AT2R expression is decreased in PIH. The TNF-alpha is related to the pathogenesis of PIH by reduced AT2R mRNA through an increase of AT1R mRNA.


Assuntos
Endotélio Vascular/metabolismo , Hipertensão/metabolismo , Complicações Cardiovasculares na Gravidez/metabolismo , RNA Mensageiro/biossíntese , Receptores de Angiotensina/biossíntese , Adulto , Feminino , Humanos , Músculo Liso Vascular/metabolismo , Gravidez , Veias Umbilicais/metabolismo
15.
Hypertens Pregnancy ; 22(1): 31-43, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12648441

RESUMO

OBJECTIVE: Our purpose was to elucidate the role of adhesion molecules in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: Sera, peripheral lymphocytes, and polymorphonuclear cells (PMN) from PIH patients, normal pregnant women, and nonpregnant women were collected. Soluble intercellular adhesion molecule-1 (sICAM-1) in sera was measured by ELISA. ICAM-1 expression on endothelial cells (EC) incubated with sera was analyzed by flow cytometry and RT-PCR. CD11a, CD11b, and CD18 expression on lymphocytes and PMN were also measured by flow cytometory. RESULTS: CD11a and CD18 expression levels on PMN and lymphocytes of PIH patients were significantly higher than those of normal pregnant women (p<0.05). The expression of CD11b was significantly increased in normal pregnancy compared with that in nonpregnant women (p<0.05). Serum sICAM-1 in PIH patients was higher than that in normal pregnant women (p<0.05). ICAM-1 expression level on EC incubated with PIH serum for 24 hr was significantly higher than that with normal pregnant serum (p<0.0005). ICAM-1 mRNA expression after 12-hr incubation with PIH serum was also significantly increased compared with serum from normal pregnant women (p<0.05). CONCLUSION: Adhesion molecules may play an important role in the pathogenesis of PIH.


Assuntos
Moléculas de Adesão Celular/metabolismo , Hipertensão/imunologia , Complicações Cardiovasculares na Gravidez/imunologia , Adulto , Estudos de Casos e Controles , Endotélio Vascular , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Hipertensão/sangue , Cadeias alfa de Integrinas/metabolismo , Cadeias beta de Integrinas/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Linfócitos/imunologia , Antígeno de Macrófago 1/metabolismo , Neutrófilos/imunologia , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , RNA Mensageiro , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Asia Pac J Clin Nutr ; 22(4): 557-64, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24231016

RESUMO

BACKGROUND: It has been reported that adequate calcium intake decreases body fat and appropriate intakes of magnesium suppress the development of the metabolic syndrome. Furthermore, lactulose increases the absorption of calcium and magnesium. An optimal combination of calcium, magnesium and lactulose may therefore reduce body fat mass. METHODS: An open-label randomized controlled trial was conducted to investigate the body fat-reducing effects of a test food containing 300 mg calcium, 150 mg magnesium, and 4.0 g lactulose. Body composition parameters and blood hormone and urine mineral concentrations were measured at baseline and at 6 and 12 months thereafter. Whole-body fat mass was measured with dual-energy x-ray absorptiometry. RESULTS: Seventy-six middle-aged Japanese women (47.5±4.7 years) were randomized to the intake group (n=48) or the non-intake control group (n=28). At 12 months the difference in body fat mass change between the two groups (intake group - control group) was -0.8 kg (95% CI: -1.5 - 0.0 kg, p=0.046), although there were no differences in anthropometric data between the two groups. Body fat percentage at 12 months tended to be lower in the intake group, but the difference was not significant (p=0.09). CONCLUSIONS: These findings may suggest that calcium in combination with magnesium and lactulose can reduce body fat mass in middle-aged Japanese women. However, the contribution of magnesium and lactulose are unclear in this study. Further studies are needed to clarify these contributions.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Cálcio da Dieta/administração & dosagem , Lactulose/administração & dosagem , Magnésio/administração & dosagem , Absorciometria de Fóton , Adulto , Cálcio/sangue , Cálcio/urina , Cálcio da Dieta/efeitos adversos , Feminino , Humanos , Japão , Lactulose/efeitos adversos , Magnésio/efeitos adversos , Magnésio/sangue , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue
17.
J Biosci Bioeng ; 113(6): 751-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22386562

RESUMO

Gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS) was used to analyze hydrophilic low molecular weight components, including amino acids, fatty acids, amines, organic acids, and saccharides, in cheese, and the sensometric application for practical metabolomic studies in the food industry is described. Derivatization of target analytes was conducted prior to the GC/TOF-MS analysis. Data on 13 cheeses, six Cheddar cheeses, six Gouda cheeses and one Parmigiano-Reggiano cheese, were analyzed by multivariate analysis. The uniqueness of the Parmigiano-Reggiano cheese metabolome was revealed. Principal component analysis (PCA) showed no grouping of the Cheddar cheeses and Gouda cheeses according to production method or country of origin. The PCA loading plot confirms that many amino acids contribute positively to PC1, suggesting that PC1 is closely related to degradation of proteins, and that lactic acid contributed positively to PC2, whereas glycerol contributed negatively to PC2, suggesting that factors regarding degradation of carbohydrates and fats were expressed in PC2. Partial least squares (PLS) regression models were constructed to predict the relationship between the metabolite profile and two sensory attributes, "Rich flavor" and "Sour flavor", which were related to maturation. The compounds that play an important role in constructing each sensory prediction model were identified as 12 amino acids and lactose for "Rich flavor", and 4-aminobutyric acid, ornithine, succinic acid, lactic acid, proline and lactose for "Sour flavor". The present study revealed that metabolomics-based component profiling, focusing on hydrophilic low molecular weight components, was able to predict the sensory characteristics related to ripening.


Assuntos
Queijo/microbiologia , Metabolômica , Paladar , Aminoácidos/análise , Queijo/análise , Gorduras/análise , Cromatografia Gasosa-Espectrometria de Massas , Ácido Láctico/análise , Lactose/análise , Modelos Químicos
18.
J Biosci Bioeng ; 114(5): 506-11, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22824260

RESUMO

Metabolic fingerprinting using gas chromatography with flame ionization detector (GC/FID) was used to generate a practical metabolomics-based tool for quality evaluation of natural cheese. Hydrophilic low molecular weight components, relating to sensory characteristics, including amino acids, fatty acids, amines, organic acids, and saccharides, were extracted and derivatized prior to the analysis. Data on 12 cheeses, six Cheddar cheeses and six Gouda cheeses, were analyzed by multivariate analysis. Prediction models for two sensory attributes relating to maturation, "Rich flavor" and "Sour flavor", were constructed with 4199 data points from GC/FID, and excellent predictability was validated. Chromatograms from GC/FID and gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) were comparable when the same column was used. Although GC/FID alone cannot identify peaks, the mutually complementary relationship between GC/FID and GC/MS does allow peak identification. Compounds contributing significantly to the sensory predictive models included lactose, succinic acid, L-lactic acid, and aspartic acid for "Rich flavor", and lactose, L-lactic acid, and succinic acid for "Sour flavor". Since similar model precision was obtained using GC/FID and GC/TOF-MS, metabolic fingerprinting using GC/FID, which is a relatively inexpensive instrument compared with GC/MS, is easy to maintain and operate, and is a valid alternative when metabolomics (especially using GC/MS) is to be used in a practical setting as a novel quality evaluation tool for manufacturing processes or final products.


Assuntos
Queijo/análise , Ionização de Chama/métodos , Aminoácidos/análise , Ácidos Graxos/análise , Ionização de Chama/instrumentação , Cromatografia Gasosa-Espectrometria de Massas , Lactose/análise , Metabolômica/métodos , Modelos Biológicos
19.
J Food Sci ; 77(12): H254-61, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23106349

RESUMO

Polyphenols, retained in black tea wastes following the commercial production of tea beverages, represent an underutilized resource. The purpose of this study was to investigate the potential use of hot-compressed water (HCW) for the extraction of pancreatic lipase-inhibiting polyphenols from black tea residues. Black tea residues were treated with HCW at 10 °C intervals, from 100 to 200 °C. The resulting extracts were analyzed using high-performance liquid chromatography-mass spectrometry and assayed to determine their inhibitory effect on pancreatic lipase activity in vitro. Four theaflavins (TF), 5 catechins, 2 quercetin glycosides, quinic acid, gallic acid, and caffeine were identified. The total polyphenol content of extracts increased with increasing temperature but lipase inhibitors (TF, theaflavin 3-O-gallate, theaflavin 3'-O-gallate, theaflavin 3,3'-O-gallate, epigallocatechin gallate, and epicatechin gallate) decreased over 150 °C. All extracts inhibited pancreatic lipase but extracts obtained at 100 to 140 °C showed the greatest lipase inhibition (IC(50) s of 0.9 to 1.3 µg/mL), consistent with the optimal extraction of TFs and catechins except catechin by HCW between 130 and 150 °C. HCW can be used to extract pancreatic lipase-inhibiting polyphenols from black tea waste. These extracts have potential uses, as dietary supplements and medications, for the prevention and treatment of obesity.


Assuntos
Inibidores Enzimáticos/química , Lipase/metabolismo , Extratos Vegetais/química , Polifenóis/química , Chá/química , Biflavonoides/química , Cafeína/química , Catequina/análogos & derivados , Catequina/química , Cromatografia Líquida de Alta Pressão , Manipulação de Alimentos , Ácido Gálico/química , Temperatura Alta , Concentração Inibidora 50 , Lipase/antagonistas & inibidores , Espectrometria de Massas , Extratos Vegetais/análise
20.
Intern Med ; 51(24): 3317-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23257514

RESUMO

OBJECTIVE: The purpose of this study was to clarify the clinical features and hepatitis B virus (HBV) genotypes in pregnant women chronically infected with HBV. METHODS: Among 1,489 pregnant women who visited our hospital in 2010, 26 were positive for hepatitis B surface antigens (HBsAg). Of these subjects, 21 from whom informed consent was obtained were included in this study. The clinical features and HBV markers, including genotypes, were investigated. RESULTS: No adverse events were observed in the subjects or the neonates during pregnancy or the perinatal period. The HBV genotypes were C in 14 cases, D in six cases, and undetermined in one case. Hepatitis B e antigens and a high viral load (>7.0 log copies/mL) were found in four and six subjects with genotype C, respectively, and in none of subjects with genotype D. The alanine aminotransferase (ALT) levels and platelet counts were within the normal ranges during pregnancy in all subjects except two and three subjects with genotype C, respectively. Three subjects with genotype C showed transient elevations of ALT after delivery. CONCLUSION: The majority of subjects were anti-HBe-positive with normal ALT levels; however, some subjects with genotype C showed a high viral load, elevated ALT levels and/or low platelet counts. The pregnancies and deliveries were safe; however, transient elevations of ALT after delivery were observed in some subjects with genotype C.


Assuntos
Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Adulto , Feminino , Genótipo , Humanos , Gravidez , Estudos Prospectivos
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