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1.
Int J Obes (Lond) ; 42(3): 384-390, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29381148

RESUMO

OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population. SUBJECTS: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans. Participants were genotyped on over 200 000 SNPs on the Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase I). Linear regression of the natural log of BMI, adjusting for age, sex, study site (if applicable), and ancestry principal components, was conducted for each race/ethnicity within each study cohort. Race/ethnicity-specific, and combined meta-analyses used fixed-effects models. RESULTS: We replicated 15 of 21 BMI loci included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436) and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 × 10-7). Bioinformatic functional investigation of SNPs at these loci suggests a possible impact on pathways that regulate metabolism and adipose tissue. CONCLUSION: Conducting studies in genetically diverse populations continues to be a valuable strategy for replicating known loci and uncovering novel BMI associations.


Assuntos
Índice de Massa Corporal , Grupos Raciais/genética , Grupos Raciais/estatística & dados numéricos , Estudo de Associação Genômica Ampla , Genômica , Humanos , Polimorfismo de Nucleotídeo Único/genética
2.
Int J Obes (Lond) ; 41(2): 324-331, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27867202

RESUMO

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.


Assuntos
Adiposidade/genética , População Negra/genética , Variação Genética , População Branca/genética , Adulto , Distribuição da Gordura Corporal , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Obesidade Abdominal/etnologia , Obesidade Abdominal/genética , Polimorfismo de Nucleotídeo Único/genética , Relação Cintura-Quadril
3.
Spinal Cord ; 49(12): 1198-202, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22006080

RESUMO

STUDY DESIGN: Prospective clinical study. OBJECTIVES: This study aimed to translate, adapting to Brazilian version in Portuguese, validate and measure inter and intra-examinator reliability and internal consistency of the Thoracic-Lumbar Control Scale instrument. SETTING: State University of Campinas, São Paulo, Brazil. METHODS: This instrument was translated to Brazilian Portuguese by a bilingual translator, and it was retranslated to English for conflict correction and cultural adaptation. Two physiotherapists were previously trained to standardize the scale administration. In all, 22 patients were selected and initially assessed through FIM and American Spinal Injury Association (ASIA) instruments. Furthermore, they were evaluated through the Thoracic-Lumbar Control Scale by two examiners and revaluated 1 week after by only one examinator. RESULTS: The Brazilian Portuguese version of Thoracic-Lumbar Control Scale showed excellent intra and inter-examinator reliability (0.961 and 0.986), high value of internal consistence (0.934) and significant correlation with ASIA sensory score (r=0.83, P=0.001). CONCLUSIONS: The Brazilian Portuguese version of Thoracic-Lumbar Control Scale is a valid and efficient instrument to assess trunk control of after-spinal cord injury patients, which certifies its replicability by other neurology professionals.


Assuntos
Índice de Gravidade de Doença , Traumatismos da Medula Espinal/complicações , Tronco/fisiopatologia , Traduções , Adolescente , Adulto , Idoso , Brasil , Feminino , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural/fisiologia , Postura/fisiologia , Reprodutibilidade dos Testes , Vértebras Torácicas , Adulto Jovem
4.
Eur J Clin Nutr ; 62(10): 1187-93, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17622257

RESUMO

OBJECTIVE: This study is to examine the relationship between dietary selenium intake and 24-h urinary selenium excretion in Japanese population samples participating in the INTERMAP Study. METHODS: Using highly standardized methods, we assessed individual dietary selenium intake from four 24-h dietary recalls and measured urinary selenium excretion in two timed 24-h urine collections in 1145 Japanese participants (574 men and 571 women) ages 40-59 years in four areas of Japan. RESULTS: The medians of dietary selenium intake were 177.5 microg/day in men and 139.8 microg/day in women; the medians of 24-h urinary selenium excretion were 127.9 microg/day in men and 109.4 microg/day in women, that is, urinary excretion was estimated to be 73% of dietary intake in men and 77% in women. Dietary selenium intake was significantly correlated with 24-h urinary selenium excretion (r=0.24 in men, r=0.18 in women; P<0.001). With dietary selenium intake and urinary selenium excretion expressed per kg of body weight, values were similar for men and women (dietary intake, 2.7 microg/kg body weight in men and 2.5 microg/kg body weight in women; urinary excretion, 2.0 microg/kg body weight in men and 2.0 microg/kg body weight in women). CONCLUSION: Dietary intake and 24-h urinary excretion of selenium are related in the Japanese adult population.


Assuntos
Dieta , Vigilância da População , Selênio/administração & dosagem , Selênio/urina , Adulto , Biomarcadores/urina , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Distribuição por Sexo , Fatores de Tempo
5.
Tsitol Genet ; 41(3): 13-22, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17649620

RESUMO

Overwintering crops such as winter wheat display significant increase in freezing tolerance during a period of cold acclimation (CA). To gain better understanding of molecular mechanisms of CA, it is important to unravel functions and regulations of CA-associated genes. Differential screening of a cDNA library constructed from cold acclimated crown tissue of winter wheat identified three novel CA-associated cDNA clones. Nucleotide sequence analysis showed that the clones encode a high mobility globular protein (HMGB1), a glycine-rich RNA-binding protein (TaGRP2), and a LEA D-11 dehydrin (DHN14). Accumulation of the three mRNAs during 14 days of CA was differentially regulated. In response to drought, and ABA, DHN14 mRNA rapidly accumulated while HMGB1 and TaGRP2 mRNA levels remained unchanged. The possible functions of each of these genes in cold acclimation are discussed.


Assuntos
Aclimatação/genética , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Triticum/genética , Sequência de Bases , Northern Blotting , Clonagem Molecular , DNA Complementar/genética , DNA de Plantas/genética , Genes de Plantas , Dados de Sequência Molecular , Proteínas de Plantas/genética , Alinhamento de Sequência
6.
Eur J Surg Oncol ; 33(10): 1191-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17314028

RESUMO

AIM: Historically, cancer therapy directly targeting tumor cells have yielded suboptimal clinical results, and therefore anti-angiogenic therapy that targets tumor cells indirectly through impairing tumor vasculature is now considered to be one of the novel approaches potentially effective against various types of cancer. In this study, we evaluated whether lysates of endothelium could be effectively pulsed in dendritic cells (DCs), to enhance their anti-tumor effects. METHODS: For this purpose, we prepared DCs of BALB/c mouse, incubated them with lysates of autologous or xenogeneic endothelium, and tested their anti-tumor effects in two syngeneic models of colon cancer. RESULTS: DCs pulsed with the respective endothelium lysates significantly inhibited the growth of subcutaneous tumors as well as pulmonary metastases in mice, and their anti-tumor effect was superior to that of unpulsed DCs. Immunohistopathological analysis showed significant decrease in the mean vascular density of tumors, correlating well with the extent of tumor inhibition. In vitro analysis of splenocytes isolated from immunized mice revealed an induction of cytotoxic T lymphocytes and activation of natural killer cells, with a lytic activity against activated endothelium but not tumor cells. In addition, antibodies reacting with activated endothelium, but not tumor cells, were detected in murine sera by ELISA, and their function was confirmed by complement-dependent cytotoxicity assay. CONCLUSIONS: Our present results suggest that lysates of endothelium can be effectively pulsed in DCs and enhance their anti-tumor effects through induction of anti-angiogenesis, and therefore should have important clinical implications for adjuvant cancer therapy.


Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasias do Colo/terapia , Células Dendríticas/imunologia , Células Endoteliais/imunologia , Neoplasias Pulmonares/terapia , Neovascularização Patológica/terapia , Animais , Antígenos de Neoplasias , Comunicação Celular/imunologia , Linhagem Celular Tumoral , Células Cultivadas , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Feminino , Tolerância Imunológica , Imunoterapia , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/imunologia , Linfócitos T Citotóxicos/imunologia
8.
Mol Genet Genomics ; 275(4): 399-408, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16614778

RESUMO

A perennial ryegrass cDNA clone encoding a putative glycine-rich RNA binding protein (LpGRP1) was isolated from a cDNA library constructed from crown tissues of cold-treated plants. The deduced polypeptide sequence consists of 107 amino acids with a single N-terminal RNA recognition motif (RRM) and a single C-terminal glycine-rich domain. The sequence showed extensive homology to glycine-rich RNA binding proteins previously identified in other plant species. LpGRP1-specific genomic DNA sequence was isolated by an inverse PCR amplification. A single intron which shows conserved locations in plant genes was detected between the sequence motifs encoding RNP-1 and RNP-2 consensus protein domains. A significant increase in the mRNA level of LpGRP1 was detected in root, crown and leaf tissues during the treatment of plants at 4 degrees C, through which freezing tolerance is attained. The increase in the mRNA level was prominent at least 2 h after the commencement of the cold treatment, and persisted for at least 1 week. Changes in mRNA level induced by cold treatment were more obvious than those due to treatments with abscisic acid (ABA) and drought. The LpGRP1 protein was found to localise in the nucleus in onion epidermal cells, suggesting that it may be involved in pre-mRNA processing. The LpGRP1 gene locus was mapped to linkage group 2. Possible roles for the LpGRP1 protein in adaptation to cold environments are discussed.


Assuntos
Aclimatação/genética , Lolium/genética , Proteínas de Plantas/genética , Proteínas de Ligação a RNA/genética , Ácido Abscísico/farmacologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Sequência de Bases , Núcleo Celular/metabolismo , Mapeamento Cromossômico , Clonagem Molecular , Temperatura Baixa , Citoplasma/metabolismo , Regulação da Expressão Gênica de Plantas , Ligação Genética , Lolium/efeitos dos fármacos , Dados de Sequência Molecular , Proteínas de Plantas/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo
9.
Eur J Surg Oncol ; 32(4): 363-70, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16520018

RESUMO

AIMS: To review the concept of tumour angiogenesis and anti-angiogenic therapy, limitations of recently used anti-angiogenic therapeutics; provide an up-to-date overview of the growing number of reports on vaccines targeting tumour angiogenesis; and finally discuss potential complications and future directions in the development of more potent and specific vaccines. METHODS: A literature search was carried out from PubMed for indexed articles. The most important articles were analysed and discussed. FINDINGS: The search yielded a large number of important indexed published articles that were reviewed, screened and tracked for other relevant publications. The most relevant articles, including those previously published by authors, were analysed and discussed. CONCLUSIONS: Recently, different vaccine strategies have been reported to inhibit tumour growth and metastasis by induction of specific cellular and/or humoral immunity against angiogenesis-associated antigens in pre-clinical models, suggesting effective combination of anti-angiogenesis and cancer immunotherapy. Evaluation of tumour endothelial cells and clinical phase I study of the vaccines are recently ongoing, and should give us better insight into the possibilities of this novel strategy for cancer immunotherapy.


Assuntos
Vacinas Anticâncer/uso terapêutico , Imunoterapia/métodos , Neoplasias/irrigação sanguínea , Neovascularização Patológica/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neovascularização Patológica/patologia , Resultado do Tratamento
10.
Conf Proc IEEE Eng Med Biol Soc ; 2006: 5101-4, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17946676

RESUMO

Near-infrared spectroscopy (NIRS) is a useful technique for noninvasive measurement of muscle oxygenation. However, analyses of the dynamic changes in muscle metabolism based only on experimental observations of NIRS are difficult. Therefore, we constructed a mathematical model of muscle metabolism, comprising of the ATP synthesizing systems and O2 diffusion system, to identify the mechanisms responsible for those observations. A customized NIRS instrument was used to measure the changes in muscle oxygenation of the forearm flexor muscles during intermittent and continuous isometric flexion exercises when healthy male subjects participated in exercises tests. The exercise-dependent difference in changes could be distinguished and the simulated results agreed well with that measured experimentally. Although the contraction intensity for both exercises was identical, the magnitude of energy needed to perform the respective exercises was different. This difference was reflected by the changes in the ATP synthesizing systems, in which the energy needed during the latter-half of continuous exercise was mostly supplied by anaerobic system, whereas that during intermittent exercise was supplied by the aerobic and anaerobic systems that operated synergistically. From the results, we conclude that the model could be a useful tool for the elucidation of the relationship between experimental observations of NIRS and muscle metabolism.


Assuntos
Exercício Físico , Metabolismo , Músculos/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Difosfato de Adenosina/química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Adulto , Simulação por Computador , Difusão , Humanos , Cinética , Masculino , Modelos Teóricos , Oxigênio/metabolismo , Consumo de Oxigênio , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação
11.
Plant Dis ; 89(10): 1132, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30791298

RESUMO

Root rot of cocoyam (Xanthosoma sagittifolium L. Schott) caused by Pythium myriotylum Drechsler is a major disease of this crop in Africa (1,2) but is unreported from other regions of the world. During September 1999, commercially grown cocoyam (cv. Ratu-kiri-ala) in Gampaha (7°05'N, 80°00'E), Sri Lanka suffered from severe root rot. Initial symptoms were water-soaked lesions at the root tips that gradually enlarged to rot the entire root system and tuber. Wilting and yellowing of leaves were observed in advanced stages of disease. A Pythium sp. was regularly isolated from the affected roots and an isolate, SC5, was identified as P. myriotylum on the basis of morphology and the internal transcribed spacer (ITS) rDNA sequence. Characteristics of isolate SC5, grown on a grass-leaf water culture (3) were main hyphae up to 8.5 µm wide, oogonia terminal or intercalary (22.5 to 33.8 µm in diameter), antheridia diclinous occasionally monoclinous, one to eight per oogonium, stalks branched, often more or less loosely enveloping the oogonium, antheridium clavate or crook-necked, making apical contact with the oogonium, breadth of antheridium 2.5 to 7.0 µm, oospores aplerotic (17.0 to 22.5 µm in diameter), oospore wall 0.8 to 2.0 µm in thickness, sporangia terminal or intercalary, filamentous, inflated lobulate, and digitate, of variable length, breadth of sporangia 7.0 to 17.5 µm, formed in water; zoospores formed at 25°C, and diameter of encysted zoospores 10.0 to 12.5 µm. Cardinal temperatures on potato carrot agar 8°C minimum, 34°C optimum, and 37°C maximum with daily radial growth rate for 34°C at 32.8 mm. The ITS rDNA sequence of the isolate matched the sequences of P. myriotylum in GenBank (Accession Nos. AB095051 and AF452156) and isolate CBS254.70 used for the species description by van der Plaats-Niterink (3). The sequence of SC5 has been deposited in GenBank, Accession No. DQ102701. Pathogenicity tests used potted cocoyam plants (20 cm high), planted in an autoclaved potting mix. Four agar disks (8 mm in diameter) of isolate SC5 grown at 25°C for 48 h on potato dextrose agar was mashed and injected at a depth of 2 to 3 cm in the soil around the roots. Inoculated plants were placed in transparent plastic bags and kept for 7 days in a growth chamber maintained at 24 to 26°C with continuous light (52 to 98 µmol m-2·s-1). The experiment was carried out twice with three replications for each test. Dark brown rotting on roots and wilting of leaves were observed in 7 days after the inoculation. P. myriotylum was reisolated from diseased tissues and found to be morphologically identical to the original isolate SC5. Noninoculated control plants remained healthy. On the basis of the symptoms, morphological and molecular characteristics and confirmation of pathogenicity, P. myriotylum is the causal agent of root rot of cocoyam. To our knowledge, this is the first report of P. myriotylum causing root rot of cocoyam in Sri Lanka. References: (1) S. Nzietchueng. L'agronomie Tropicale 38:321, 1983. (2) R. P. Pacumbaba et al. J. Phytopathol. 135:265, 1992. (3) A. J. Van Der Plaats-Niterink. Stud. Mycol. 21:1, 1981.

12.
Jpn Heart J ; 42(2): 249-54, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11384084

RESUMO

A 74-year-old Japanese male was referred to our hospital because of an abnormal electrocardiogram. The electrocardiogram revealed tall P waves in leads II, III, and aV(F). Echocardiography disclosed hypokinesis extending from the anteroseptal region to the apex. Iodine-123 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123-BMIPP) scintigraphy revealed reduced uptake from the anteroseptal region to the apex. Coronary arteriography demonstrated diffuse dilatation of the right and left coronary arteries without organic stenosis, and left ventriculography showed hypokinesis at the same area. Furthermore, the coronary flow reserve in the left anterior descending artery was decreased. He was treated with an antiplatelet agent. Ten months later, the left ventriculography, 123I-BMIPP scintigraphy findings and coronary flow reserve were normalized. These findings demonstrate that antiplatelet therapy may be useful in the preservation of left ventricular function in patients with coronary artery ectasia.


Assuntos
Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/patologia , Isquemia Miocárdica/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Angiografia Coronária , Circulação Coronária , Doença das Coronárias/fisiopatologia , Dilatação Patológica/tratamento farmacológico , Ácidos Graxos , Coração/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Iodobenzenos , Masculino , Contração Miocárdica , Cintilografia
13.
J Toxicol Sci ; 26 Suppl 1: 135-47, 2001 May.
Artigo em Japonês | MEDLINE | ID: mdl-11400309

RESUMO

To evaluate the repeated oral dose toxicity of Cefmatilen hydrochloride hydrate (S-1090) in juvenile dogs, S-1090 was administered to juvenile beagle dogs at dose levels of 50, 100, 200 and 400 mg potency/kg/day for 3 months. No deaths occurred. Urinalysis in the 400 mg potency/kg group revealed positive reactions of occult blood and protein, and erythrocytes in sediments. Cystitis was observed in the 200 and 400 mg potency/kg groups. In the thyroids, an increased weight in some animals in the groups dosed at 100 mg potency/kg or more and an increased follicular colloid in the 400 mg potency/kg group were observed. However, no related changes were noted in other examination items. Red to dark-red feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were observed in all treated groups. Plasma S-1090 concentrations increased in a manner less than dose-proportional. The lesions of urinary bladder were judged as S-1090-induced toxic changes and the NOAEL of S-1090 in this study was assessed to be 100 mg potency/kg/day.


Assuntos
Cefalosporinas/toxicidade , Administração Oral , Animais , Sedimentação Sanguínea , Cistite/induzido quimicamente , Cães , Esquema de Medicação , Feminino , Masculino , Sangue Oculto , Urinálise
14.
J Cardiol ; 37(4): 215-22, 2001 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-11337931

RESUMO

Iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single photon emission computed tomography(iodine-123 BMIPP myocardial SPECT) is useful for the diagnosis and evaluation of ischemic myocardial disease or cardiomyopathy. Changes in fatty acid metabolism in the post-myocardial ischemic state were evaluated using iodine-123 BMIPP myocardial SPECT. A 77-year-old woman was hospitalized for treatment of acute myocardial infarction. Emergency coronary angiography showed severe stenosis with delayed filling of contrast medium in the middle portion of the left anterior descending artery, so primary percutaneous transluminal coronary angioplasty was performed successfully. On the second day, iodine-123 BMIPP uptake was decreased slightly on the early imaging in the apico-anterior region, and increased slightly on the delayed imaging. On the seventh day, iodine-123 BMIPP uptake was decreased moderately or markedly in the apico-anterior region on the early imaging, and decreased markedly on the delayed imaging. Iodine-123 BMIPP myocardial SPECT subsequently became almost normalized. These unusual dynamic changes In iodine-123 BMIPP myocardial SPECT imaging may reflect metabolic changes of fatty acids in the ischemic state, the size of the triacylglycerol pool, and the degree of turnover in the triacylglycerol pool.


Assuntos
Ácidos Graxos , Radioisótopos do Iodo , Iodobenzenos , Infarto do Miocárdio/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Feminino , Humanos
15.
Ann Nucl Med ; 14(4): 303-9, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11023032

RESUMO

A 55-yr-old man underwent surgery. Soon after the procedure was finished, the patient complained of chest pain, and the electrocardiogram showed increase in the ST-segment in some leads. Emergency angiography showed normal coronary arteries, but there was asynergy in the left ventricle, and delayed filling of contrast medium was observed in the LCA. An intracoronary infusion of isosorbide dinitrate did not improve the delayed filling of contrast medium or ST segment increase in the electrocardiogram. Soon after nicorandil was injected into the LCA, the patient's symptoms, electrocardiogram, and delayed filling of contrast medium dramatically improved. On the second day, initial imaging by 123I-BMIPP myocardial SPECT showed a moderate increase in tracer uptake in the apico-anteroseptal region and a moderate decrease in tracer uptake in the lateral region, in which the first left ventriculography showed akinesis, and delayed imaging revealed a moderate increase in tracer uptake in the apical region and a high washout of 123I-BMIPP in the anteroseptal and lateral regions. On the sixth day, initial imaging by 123I-BMIPP myocardial SPECT showed a moderate decrease in tracer uptake in the apical and lateral regions and a mild decrease in tracer uptake in the anteroseptal region, and delayed imaging revealed a moderate increase in tracer uptake in the apical region and a high washout of 123I-BMIPP in the anteroseptal and lateral regions. By the 30th day, 123I-BMIPP myocardial SPECT had normalized. We consider that these dynamic changes in 123I-BMIPP myocardial SPECT imaging may reflect metabolic changes in fatty acids in the ischemic state, the size of the triacylglycerol pool, and the degree of turnover in the triacylglycerol pool.


Assuntos
Vasoespasmo Coronário/complicações , Ácidos Graxos , Radioisótopos do Iodo , Iodobenzenos , Miocárdio Atordoado/diagnóstico por imagem , Miocárdio Atordoado/etiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio Atordoado/metabolismo , Compostos Organofosforados , Compostos de Organotecnécio , Pirofosfato de Tecnécio Tc 99m , Triglicerídeos/metabolismo
16.
Eur J Pharmacol ; 404(1-2): 221-9, 2000 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10980282

RESUMO

The effects of 6,7,8, 9-tetrahydro-2-methyl-5H-cyclohepta[b]pyridine-3-carbonylguanidine maleate (TY-12533) on myocardial ischemia/reperfusion injury were evaluated in rats. Inhibitory effects of TY-12533, TY-50893 (the 9-chloro derivative of TY-12533) and cariporide on the platelet Na(+)/H(+) exchanger in vitro were almost equal at pH 6.2 and decreased at pH 6.7; but TY-12533 was four times more potent than TY-50893 and cariporide at pH 6.7. TY-12533, TY-50893 and cariporide administered before ischemia (0.01-1 mg/kg, i.v.) suppressed the ischemia/reperfusion-induced arrhythmias to the same extent in vivo; but TY-12533 was more effective than cariporide and TY-50893 when they were administered during ischemia (0.1-1 mg/kg). Similar results were obtained for the inhibitory effects of these drugs administered before ischemia (0.03-0.1 mg/kg, i.v.) and during ischemia (0.1-1 mg/kg) on the ischemia/reperfusion-induced myocardial infarction. These differences between TY-12533 and the other drugs in vitro and in vivo may be ascribed to the pK(a) values of the guanidinium moiety of TY-12533 (6.93), TY-50893 (6.35) and cariporide (6.28).


Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Guanidinas/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Piridinas/uso terapêutico , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Aconitina , Animais , Antiarrítmicos/farmacologia , Arritmias Cardíacas/etiologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Modelos Animais de Doenças , Guanidinas/farmacologia , Masculino , Infarto do Miocárdio/etiologia , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Trocadores de Sódio-Hidrogênio/metabolismo , Sulfonas/farmacologia , Sulfonas/uso terapêutico
17.
Hypertension ; 36(2): 215-9, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10948080

RESUMO

Although echocardiography is a useful diagnostic tool in hypertrophic cardiomyopathy (HCM), it is sometimes difficult to differentiate it from hypertensive heart disease (HHD): some patients with HCM show symmetrical hypertrophy, whereas patients with HHD sometimes show asymmetrical septal hypertrophy. We used a radioiodinated long-chain fatty acid tracer to visualize the altered myocardial fatty acid metabolism of HCM and HHD. Carnitine is the essential substance for the beta-oxidation of long-chain fatty acids. We recently reported that serum free carnitine levels in HCM were elevated and that they were significantly correlated with the severity of myocardial fatty acid metabolic disorder. Therefore, we investigated serum carnitine levels in patients with HCM and HHD, which can contribute to the differentiation of each other. We studied 56 patients with HCM and 20 patients with essential hypertension. Serum free carnitine levels were significantly higher in patients with HCM than those with HHD (HCM 52.5+/-9.5 nmol/mL, HHD 46.6+/-6.4 nmol/mL, P<0.01), but they showed no statistical difference between patients with HHD and normal subjects. Serum acylcarnitine levels were significantly lower in patients with HCM than those with HHD (HCM 10.1+/-4.0 nmol/mL, HHD 14.5+/-4.9 nmol/mL, P<0.0005), although they did not differ between patients with HHD and normal subjects. Scintigraphic analyses with a long-chain fatty acid analog revealed that myocardial tracer uptake was much reduced in patients with HCM compared with that in patients with HHD (quantitative analysis: HCM 2.11+/-0.12, HHD 2.22+/-0.17, P<0.05; semiquantitative analysis: HCM 13.6+/-6.3, HHD 2.0+/-1.5, P<0.0001). In conclusion, the differences in serum carnitine levels between HCM and HHD reflect altered myocardial fatty acid metabolic impairment, and the levels can help to distinguish these 2 diseases.


Assuntos
Cardiomiopatia Hipertrófica/sangue , Carnitina/sangue , Cardiopatias/sangue , Hipertensão/sangue , Adulto , Idoso , Análise de Variância , Cardiomiopatia Hipertrófica/patologia , Diagnóstico Diferencial , Ecocardiografia , Feminino , Cardiopatias/patologia , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único
18.
Biochim Biophys Acta ; 1467(1): 219-26, 2000 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-10930524

RESUMO

Liposomes have frequently been used as models of biomembranes or vehicles for drug delivery. However, the systematic characterization of lipid vesicles by right angle light scattering and turbidity has not been carried out despite the usefulness of such studies for size estimation. In this study, liposomes of various sizes were prepared by sonication and extrusion. The mean cumulant radii of the vesicles were determined by dynamic light scattering. The lamellarities were estimated based on fluorescence quenching of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)dipalmitoyl-L-alpha-phosph ati dylethanolamine by sodium dithionite. Right angle light scattering intensity and optical density at 436 nm per unit lipid concentration were measured as a function of vesicle radius. With a vesicle radius < or =100 nm, the optical parameters could be well explained by the Rayleigh-Gans-Debye theory in which the liposomes were modeled as homogeneous spheres with mean refractive indices determined by the volume fractions of lipids in vesicles.


Assuntos
Lipossomos/química , Ditionita , Corantes Fluorescentes , Modelos Teóricos , Nefelometria e Turbidimetria , Tamanho da Partícula , Fosfatidiletanolaminas , Refratometria , Espalhamento de Radiação , Espectrometria de Fluorescência/métodos
19.
Kaku Igaku ; 37(4): 327-32, 2000 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-10965653

RESUMO

This study was designed to evaluate the clinical usefulness of 123I-BMIPP myocardial SPECT for detecting cardiac involvement in patients with collagen disease. We studied 12 patients with systemic lupus erythematosus (SLE), 8 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM) and 3 with allergic granulomatosis and angiitis (AGA). A 111 MBq of 123I-BMIPP was intravenously injected at rest, and SPECT images were obtained at 15 min after the injection. Seven of 12 SLE, 6 of 8 PSS, 3 of 6 PM/DM and all 3 AGA patients showed an abnormal tracer uptake. The left ventricular ejection fraction was inversely correlated with a BMIPP abnormality. The regional wall motion abnormality was reduced in regions with reduced tracer uptake. These findings suggest that 123I-BMIPP imaging could be useful for assessment of cardiac involvement in patients with collagen disease.


Assuntos
Doenças do Colágeno/diagnóstico por imagem , Ácidos Graxos , Coração/diagnóstico por imagem , Radioisótopos do Iodo , Iodobenzenos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Kaku Igaku ; 37(3): 209-15, 2000 May.
Artigo em Japonês | MEDLINE | ID: mdl-10860351

RESUMO

This study was designed to evaluate the clinical usefulness of delayed exercise images in 99mTc-tetrofosmin (TF) myocardial SPECT in the diagnosis of vasospastic angina pectoris. We studied 30 patients with vasospastic angina, 10 of 30 patients (group A) had both effort and rest angina, 20 of 30 patients (group B) had rest angina. A 370 MBq of TF was intravenously injected at peak exercise, and initial (EX-I) and delayed exercise (EX-D) images were obtained at 30 min and 180 min after the injection. An additional 740 MBq of TF was intravenously reinjected after EX-D image acquisition, and rest images were obtained 30 min after the reinjection. The left ventricular wall was divided into 9 segments. Regional myocardial uptakes of TF were scored by 4-point defect score (0 = normal, 1 = mildly reduced, 2 = moderately reduced, and 3 = severely reduced). Total defect score (TDS) was calculated from the sum of defect scores in 9 segments. Reverse redistribution (RR) was defined as increase of more than 2 in TDS on EX-D images. In group A, 4 of 10 cases (40%) showed decreased uptake on EX-I images, 6 of 10 cases (60%) revealed RR on EX-D images, and none of the patients showed decreased uptake on rest images. In group B, no one showed decreased uptake on EX-I and rest images, 11 of 20 cases (55%) revealed RR on EX-D images. The mean +/- SD of TDS were 2.9 +/- 3.4, 5.1 +/- 4.5, 0.5 +/- 0.5 on EX-I, EX-D, rest images in group A, and serially 0.4 +/- 0.5, 3.3 +/- 3.6, 0.4 +/- 0.5 in group B. Regional wall motion abnormality was reduced in regions with RR. RR on EX-D images may reflect ischemic damaged but viable myocardium in vasospastic angina. The clinical usefulness of exercise-rest TF imaging in detection of organic coronary artery disease has been well established. Therefore, exercise-rest TF imaging with additional delayed exercise image could evaluate not only organic coronary artery disease but also coronary artery vasospasm.


Assuntos
Angina Pectoris/diagnóstico por imagem , Vasoespasmo Coronário/diagnóstico por imagem , Coração/diagnóstico por imagem , Compostos Organofosforados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Idoso , Angina Pectoris/etiologia , Vasoespasmo Coronário/complicações , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único
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