RESUMO
OBJECTIVE: Sesamin is a major lignan constituent of sesame and possesses various health-promoting effects. Previous studies have demonstrated that sesamin extends the lifespan of Drosophila and Caenorhabditis elegans and corrects oxidative damage-related tissue dysfunction in mammals. To understand its anti-aging effects, we aimed to determine whether sesamin restores tissue function hampered by oxidative damage and suppresses several aging-related phenotypes using Drosophila senescence-accelerated models. MATERIALS AND METHODS: We elucidated the anti-aging effects of sesamin on several aging-related phenotypes in the muscle, brain and midgut using the senescence-accelerated models (Sod1n1 mutant and Sod1-depleted flies) by immunostaining experiments. We determined the expression levels of several anti-oxidative and DNA repair genes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We also identified the metabolite of sesamin in Drosophila by LC-MS/MS. RESULTS: We confirmed that sesamin (0.35 and 2 mg/ml) extended the lifespan of the fly models. As observed in mammals, it can be absorbed and metabolized by Drosophila adults. The sesamin feeding suppressed the age-dependent impairment of locomotor activity and inhibited the accumulation of reactive oxygen species (ROS) in their bodies. Sesamin delayed the age-dependent accumulation of damaged proteins in the muscle, partially suppressed the loss of dopaminergic neurons in adult brains displaying ROS accumulation, and suppressed the accumulation of DNA damage and hyperproliferation of intestinal stem cells. Four antioxidative genes and two DNA repair genes were simultaneously upregulated in sesamin-fed adults. CONCLUSIONS: These observations represent the first direct evidence of the anti-aging effects of sesamin at the individual level. We propose that sesamin exerts anti-aging effects in the muscles, brain and midgut by inducing antioxidative and DNA repair genes, resulting in extended lifespan in flies.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Dioxóis/farmacologia , Modelos Animais de Doenças , Drosophila melanogaster , Intestinos , Lignanas/farmacologia , Longevidade , Envelhecimento/genética , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Células Cultivadas , Cromatografia Líquida , Dioxóis/análise , Dioxóis/metabolismo , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Intestinos/efeitos dos fármacos , Lignanas/análise , Lignanas/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/metabolismo , Fenótipo , Superóxido Dismutase/deficiência , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Espectrometria de Massas em TandemRESUMO
The use of antibiotics in poultry is being heavily scrutinized, therefore alternatives such as probiotics are being investigated. Lactobacilli spp. are a commonly used bacteria in formulating probiotics, and the addition of Lactobacilli to broiler diets has demonstrated increased growth rates, stimulated immune systems, and reduced pathogen loads in the gastro-intestinal tract ( GI: ) tract. However, previous research has shown that when rooster semen is directly exposed to Lactobacillus acidophilus (L. acidophilus) sperm quality is reduced. Therefore, the objective of the current study was to determine if oral administration of L. acidophilus increases the concentration of Lactobacilli in semen as well as the cloaca. A total of 30 roosters were used: 15 roosters were gavaged with 1X PBS (Control) and 15 roosters were gavaged with 10(7) cfu/mL of L. acidophilus (Treated). All roosters were gavaged for 14 consecutive days. Semen was collected on a 3 d interval, and cloacal swabs were collected on a 2 d interval, beginning on the first day prior to oral administration. Semen and cloacal swabs were serial diluted, and 100 µL of each dilution was then plated on Man, Rogosa, Sharpe ( MRS: ) agar plates. All plates were incubated for 48 h at 37°C under anaerobic conditions and counted. All Lactobacilli counts were first log transformed, then log transformed (day 0) pre-counts were subtracted from the log transformed day counts providing log differences for the analysis. Seminal Lactobacilli counts were not altered by treatments. However, the main effect of treatment (P = 0.026) for cloacal counts indicated that roosters gavaged with Lactobacilli yielded higher counts than the controls. Additionally, cloaca samples also demonstrated a treatment by day interaction trend (P = 0.082), where Lactobacilli was higher in the L. acidophilus gavaged roosters than the controls only on days 3, 5, 13, and 15. In conclusion, the addition of L. acidophilus to the male breeder diet over extended periods may increase concentrations of Lactobacilli in the cloaca even higher than the concentrations observed in this study. If Lactobacilli reaches high enough concentrations in the cloaca, then sperm quality may be impacted which could lead to poor fertility within the breeder flock.
Assuntos
Galinhas/microbiologia , Cloaca/microbiologia , Lactobacillus acidophilus/metabolismo , Probióticos/farmacologia , Sêmen/microbiologia , Animais , Carga Bacteriana/veterinária , MasculinoRESUMO
Marine planktonic copepods are an ecologically important group with high species richness and abundance. Here, we propose a new metagenetic approach for revealing the community structure of marine planktonic copepods using 454 pyrosequencing of nuclear large subunit ribosomal DNA. We determined an appropriate similarity threshold for clustering pyrosequencing data into molecular operational taxonomic units (MOTUs) using an artificial community containing 33 morphologically identified species. The 99% similarity threshold had high species-level resolution for MOTU clustering but overestimated species richness. The artificial community was appropriately clustered into MOTUs at 97% similarity, with little inflation in MOTU numbers and with relatively high species-level resolution. The number of sequence reads of each MOTU was correlated with dry weight of that taxon, suggesting that sequence reads could be used as a proxy for biomass. Next, we applied the method to field-collected samples, and the results corresponded reasonably well with morphological analysis of these communities. Numbers of MOTUs were well correlated with species richness at 97% similarity, and large numbers of sequence reads were generally observed in MOTUs derived from species with large biomass. Further, MOTUs were successfully classified into taxonomic groups at the family level at 97% similarity; similar patterns of species richness and biomass were revealed within families with metagenetic and morphological analyses. At the 99% similarity threshold, MOTUs with high proportions of sequence reads were identified as biomass-dominant species in each field-collected sample. The metagenetic approach reported here can be an effective tool for rapid and comprehensive assessment of copepod community structure.
Assuntos
Biota , Copépodes/classificação , Copépodes/genética , Metagenômica , Animais , Análise por Conglomerados , Copépodes/anatomia & histologia , DNA Ribossômico/química , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , RNA Ribossômico/genética , Água do Mar , Análise de Sequência de DNARESUMO
BACKGROUND: Epidemiological studies suggest that apolipoprotein E (apoE) polymorphism influences plasma lipoprotein levels and the development of cardiovascular disease. OBJECTIVE: To clarify the role of apoE polymorphism as a risk factor for early atherosclerosis. DESIGN: Using a high-resolution ultrasound method, we investigated the association between apoE phenotypes, carotid intima-media thickness (CCA-IMT), and flow-mediated dilation in the brachial artery (brachial-FMD) in 96 healthy asymptomatic Japanese men (mean +/- SD age, 50 +/- 8 years). RESULTS: Serum cholesterol and LDL-cholesterol levels in subjects with E3E4 were highest and those with E2E3 were lowest (P < 0.05 and P < 0.05, respectively). The CCA-IMT in E3E4 subjects (0.76 +/- 0.17 mm) was greater than that in E2E3 and E3E3 (0.61 +/- 0.15 and 0.64 +/- 0.14 mm, respectively; P < 0.01). In contrast, there was no difference between brachial-FMD and apoE phenotypes (P=0.15). By univariate analysis, CCA-IMT was positively correlated with age (r=0.51, P < 0.01), LDL-chol/HDL-chol ratio (r=0.37, P < 0.01), triglycerides (r=0.23, P < 0.05), and negatively correlated with HDL-cholesterol (r=-0.31, P < 0.01). An association between CCA-IMT and the presence of E4 allele was also found (P < 0.05). Logistic regression analysis revealed that the presence of E4 allele was a higher risk for increased IMT (relative risk of 4.4, 95% CI 1.5-12.5), even after adjustment for age, LDL-cholesterol, blood pressure and other known risk factors. A negative correlation between brachial-FMD and CCA-IMT was also found in all subjects (r=-0.21, P < 0.05), being most apparent in the E3E4 subjects (r=-0.53, P < 0.02). CONCLUSION: ApoE4 phenotype was independently associated with an increased risk of carotid atherosclerosis and elevated LDL-cholesterol levels in asymptomatic middle-aged Japanese men.
Assuntos
Apolipoproteínas E/genética , Povo Asiático/genética , Artéria Braquial/fisiopatologia , Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Estenose das Carótidas/fisiopatologia , Túnica Íntima/patologia , Túnica Média/patologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Artéria Braquial/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/genética , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fenótipo , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia , VasodilataçãoRESUMO
BACKGROUND: Patients with end-stage renal disease (ESRD) have high mortality from atherosclerotic/atherothrombotic vascular disease (AVD). However, the role of an elevated plasma total homocysteine (tHcy) level as a risk factor is uncertain in ESRD. METHODS: We enrolled 55 ESRD patients in a prospective follow-up study in order to evaluate the prognostic significance of their tHcy levels, common methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and other atherosclerotic risk factors, in combination with the results of B mode ultrasound for carotid arteries. RESULTS: Mean intima-media thickness of the common carotid artery (CCA-IMT) in ESRD patients was thicker than that in 102 age- and sex-matched healthy controls. Carotid plaque was more frequently present in patients compared with controls, as was calcified plaque more common in patients (p < 0.001). Plasma tHcy levels (mean +/- SD) in patients (39.1 +/- 27.2 nmol/ml) were higher than that (8.8 +/- 2.7 nmol/ml) in controls (p < 0.001). Folic acid was the major determinant of elevated tHcy levels in ESRD patients. During the follow-up period of 31 +/- 3 months, 14 patients had one or more AVD complications, and 10 consequently died from AVD causes. Proportional hazards modeling showed that 5-year intervals of age (relative risk of 2.95, 95% CI 1.62 - 5.37), 10 nmol/ml intervals of tHcy levels (relative risk of 2.31, 95% CI 1.31 - 4.08), and presence of diabetes mellitus (relative risk of 6.62, 95% CI 1.07 +/- 40.8) were independent predictors of future AVD events, and tHcy levels (relative risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% CI 1.15 - 3.83) were those of AVD mortality. We also found a significant association between carotid plaque prevalence and AVD events (X(2) = 11.6, p = 0.001). CONCLUSION: Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis appeared to contribute independently to increase the risk of AVD outcome in Japanese patients with ESRD.
Assuntos
Arteriosclerose/etiologia , Doenças das Artérias Carótidas/complicações , Complicações do Diabetes , Hiper-Homocisteinemia/complicações , Falência Renal Crônica/complicações , Adulto , Idoso , Arteriosclerose/mortalidade , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Homocisteína/sangue , Humanos , Japão/epidemiologia , Falência Renal Crônica/genética , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Polimorfismo Genético , Estudos Prospectivos , Fatores de Risco , UltrassonografiaRESUMO
We examined the inhibitory effect of sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam: ND2001) upon liver metastases of the LMFS tumor. A permanent cell line, LMFS, was established from a spontaneously occurring murine retroperitoneal tumor of BALB/c mouse origin, and after a subcutaneous injection, the LMFS cells proliferated at the inoculation site (100% take) with liver metastases. ND2001 had little effect on the cell growth, cell cycle and phagokinesis of the LMFS cells in vitro. However, when the invasive activity was measured by the Boydem chamber method, the number of LMFS cells was reduced, with inhibition rates of 98.0%. After the LMFS cells treated with ND2001 in vitro, the numbers of hepatic metastases of subcutaneous inoculation of treated cells were reduced dose-dependently, and those of intravenous inoculation were not found by microscopical study. When the LMFS tumor-bearing mice were treated with ND2001 (0, 30, 100 mg/kg/d) from day 1, ND2001 (30 mg/kg) inhibited the liver metastases with a rate of 56.4%, and when given from day 15, ND2001 (100 mg/kg) inhibited with a rate of 47.5%. But ND2001 showed neither cytocidal nor anti-tumor activity. Combination therapy of primary tumor resection and ND2001 administration revealed that preoperative use of ND2001 was more effective in preventing liver metastases. These results suggested that ND2001 might have a potential use as an anti-metastatic agent for operative patients without metastasis.
Assuntos
Antineoplásicos/uso terapêutico , Ácido Glucárico/análogos & derivados , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/secundário , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Contagem de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Ácido Glucárico/administração & dosagem , Ácido Glucárico/farmacocinética , Ácido Glucárico/uso terapêutico , Infusões Intravenosas , Injeções Subcutâneas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica/prevenção & controle , Transplante de Neoplasias , Células Tumorais CultivadasRESUMO
Combination therapy using HCFU and TNP 470, which inhibits angiogenesis, was examined for effectiveness against the footpad injection model of LMFS tumor. This LMFS, a retroperitoneal sarcoma of BALB/c mice, proliferated at the inoculation site (100% take) and all mice operated on after day 15 had spontaneous metastatic nodules in the liver. Mice with the LMFS tumor were given HCFU and 5-FU (5 days/week), and/or TNP 470 (3 days/week) from day 3 for 3 weeks and sacrified at day 28 under anesthesia. Seven of 10 mice receiving 5-FU and TNP 470 died from the side effects of the drugs. Mean tumor weight and liver metastatic nodules were determined and compared with a control group. The results were as follows: HCFU group: 94.6%, 11.8%, 5 FU group: 73.9%, 28.8%, TNP 470 group: 67.6%, 44%, HCFU and TNP 470 group: 33.3%, 6.4%. Mice with LMFS were given HCFU and/or TNP 470 from day 3 for 4 weeks. The foot on the injected side was amputated on day 15, and the animals were sacrified on day 35. Liver metastatic nodules compared with those of the operation (OP) group as follows: OP + HCFU group: 14.4%, OP + TNP group: 39.1%, and OP + HCFU + TNP 470 group: 5.4%. Histologically, 5 of 5 mice of the OP group, 3 of 5 of the OP + HCFU group, 4 of 5 of the OP + TNP 470 group and 1 of 5 of the OP + HCFU + TNP 470 group had liver metastases. These results show that while either HCFU or TNP 470 is effective by itself, a combination of these drugs is more effective against liver metastasis.
Assuntos
Inibidores da Angiogênese/farmacologia , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos/farmacologia , Fluoruracila/análogos & derivados , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/secundário , Neoplasias Retroperitoneais/patologia , Sarcoma Experimental/secundário , Sesquiterpenos/farmacologia , Inibidores da Angiogênese/administração & dosagem , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Cicloexanos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , O-(Cloroacetilcarbamoil)fumagilol , Sesquiterpenos/administração & dosagem , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
A 68-year-old man suffering from chronic heart failure due to coronary artery disease (CAD) underwent rest technetium-99m (99mTc)-tetrofosmin and thallium-201 (201Tl) with reinjection studies, but died thereafter. The heart was removed and sectioned into short-axis slices and examined by gross and microscopic pathologic methods. A close correlation between the amount of residual cardiomyocytes and the level of regional tracer activity in the left ventricular wall was obtained for redistribution 201Tl, reinjection 201Tl and rest 99mTc tetrofosmin images. The correlation coefficients were r=0.901 for the 201Tl redistribution images, r=0.913 for the 201Tl reinjection images and r=0.917 for the rest 99mTc-tetrofosmin images. This case report provides further evidence of the validity of SPECT tetrofosmin imaging for the determination of myocardial viability in CAD.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/patologia , Coração/diagnóstico por imagem , Miocárdio/patologia , Compostos Organofosforados , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão , Idoso , Sobrevivência Celular , Humanos , MasculinoRESUMO
A new catheter for retrograde cerebral perfusion (RCP) was developed that can be used to deliver blood directly into the internal jugular vein (IJV) beyond the venous valves at the jugular-subclavian junction and prevent blood from draining into the lower half of the body. This catheter can be inserted into the IJV via a standard puncture technique by use of a 14 Fr sheath. The catheter shaft has two channels for balloon inflation and blood perfusion, respectively. A balloon for occlusion of drainage veins (superior vena cava and azygos vein) is installed at the catheter tip. Side holes, through which oxygenated cold blood is delivered into the IJV, are located 95 mm from the catheter tip. In a mock circulatory study, the pressure at the perfusion line (16-118 mmHg) increased with the increasing flow rate (0-400 ml/min). In clinical application, under circulatory arrest with profound hypothermia, inflation of the balloon effectively reduced blood drainage into the lower half of the body and, consequently, RCP was successfully performed (flow rate, 300-350 ml/min; pressure at the IJV, 15 mmHg). Because all of these procedures were controlled from outside the operative field, RCP by use of this catheter could be useful in distal arch replacement via left lateral thoracotomy.
Assuntos
Circulação Assistida , Cateterismo/instrumentação , Circulação Cerebrovascular , Animais , Aorta Torácica/cirurgia , Lesões Encefálicas/prevenção & controle , Cateterismo/métodos , Cães , Estudos de Avaliação como Assunto , Humanos , Técnicas In Vitro , Veias Jugulares , PerfusãoRESUMO
UNLABELLED: The aim of this study was to determine whether late redistribution imaging after rest injection of 201Tl would provide further information on myocardial viability over conventional rest-early redistribution 201Tl imaging. METHODS: Twenty-nine patients with coronary artery disease and left ventricular dysfunction underwent rest, early (3-4 hr) and late (20-24 hr) redistribution 201Tl and gated blood pool studies. In 14 patients with successful revascularization, gated blood pool study was repeated after the coronary intervention. RESULTS: Nine of 29 patients showed early redistribution, and six additional patients showed further redistribution on the late images. Of 136 segments with initial 201Tl defects, 18 showed early redistribution, and 10 showed late redistribution. When a threshold of 60% of peak activity was used as an index of myocardial viability, only a small fraction (3%) of the initial 201Tl defects were additionally considered viable by the late images. In 14 patients who underwent revascularization, the positive (69%) and negative (87%) predictive values of the early redistribution images for functional recovery were similar to those obtained by the late images (68% and 86%, respectively). CONCLUSION: Although late redistribution after rest injection of 201Tl occasionally occurs, most of the clinically relevant information on myocardial viability may be obtained by conventional rest-early redistribution 201Tl imaging when the defect severity is considered an index of tissue viability.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Coração/diagnóstico por imagem , Radioisótopos de Tálio , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Doença das Coronárias/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Cintilográfica , Descanso , Sobrevivência de Tecidos , Disfunção Ventricular Esquerda/terapiaRESUMO
OBJECTIVES: This study was undertaken to 1) compare the regional myocardial tracer distributions between rest technetium (Tc)-99m tetrofosmin and rest-redistribution thallium (Tl)-201 images in patients with coronary artery disease and left ventricular dysfunction; and 2) assess the comparative values of these agents for predicting functional recovery after revascularization. BACKGROUND: Tc-99m tetrofosmin is a new myocardial perfusion imaging agent, but its role for detecting viable myocardium is still unclear. METHODS: Thirty-six patients with coronary artery disease and left ventricular dysfunction underwent rest Tc-99m tetrofosmin, rest-redistribution Tl-201 and gated blood pool scintigraphy. In 21 patients with successful revascularization confirmed by follow-up angiography, gated blood pool scintigraphy was repeated after revascularization. Optimal threshold cutoffs to separate reversible from irreversible dysfunction were determined by receive operating characteristic analysis. RESULTS: Regional Tc-99m tetrofosimin activity highly correlated with redistribution Tl-201 activity (r = 0.93). The diagnostic performance for predicting functional recovery, as measured by the area under the receiver operating characteristic curves, measured 0.66 +/- 0.07 (mean +/- SD) for Tc-99m tetrofosmin and 0.67 +/- 0.07 for Tl-201 (p = 0.60, 96.7% power to detect difference in area of 0.10). The optimal threshold cutoffs for viability were considered to be 50% of peak activity for Tc-99m tetrofosmin and 55% of peak activity for Tl-201. The positive and negative predictive values for reversible dysfunction were, respectively, 69% and 82% for Tc-99m tetrofosmin and 69% (p = 0.99 vs. Tc-99m tetrofosmin) and 71% (p = 0.66 vs. Tc-99m tetrofosmin) by Tl-201. CONCLUSIONS: The diagnostic performance of quantitative rest Tc-99m tetrofosmin imaging in predicting functional recovery after revascularization is comparable to that of rest-redistribution Tl-201.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/terapia , Coração/diagnóstico por imagem , Compostos Organofosforados , Compostos de Organotecnécio , Radioisótopos de Tálio , Idoso , Angioplastia Coronária com Balão , Estudos de Casos e Controles , Ponte de Artéria Coronária , Feminino , Imagem do Acúmulo Cardíaco de Comporta , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/terapiaRESUMO
Iodine 123-labeled 15-iodophenyl-3-methyl-pentadecanoic acid (BMIPP) has been proposed as a potential myocardial fatty acid probe. We studied BMIPP uptake in ischemic myocardium identified by thallium reinjection. Fifty-five patients with coronary artery disease who had persistent defects on standard exercise-redistribution thallium imaging were investigated. Patients underwent exercise-redistribution-reinjection thallium and resting BMIPP imaging. BMIPP uptake less than that seen with thallium on reinjection imaging was observed in 105 (82%) of 128 myocardial segments with new fill-in after thallium reinjection and 87 (37%) of 238 segments with reversible thallium defects. In contrast, only 32 (19%) of 166 segments with no fill-in showed discordantly decreased BMIPP uptake. Quantitative analysis showed reduction in BMIPP activity compared with differential uptake of thallium, an index of resting myocardial perfusion, especially in the area of fill-in (53.5% +/- 15.0% vs 76% +/- 12.1% of peak; p<0.01). These observations are consistent with impaired fatty acid uptake in ischemic myocardium, particularly in the area of fill-in after thallium reinjection.
Assuntos
Ácidos Graxos/metabolismo , Coração/diagnóstico por imagem , Isquemia Miocárdica/metabolismo , Radioisótopos de Tálio , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço , Feminino , Humanos , Radioisótopos do Iodo , Iodobenzenos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Miocárdio/metabolismo , Sobrevivência de Tecidos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Defect size on exercise-rest technetium (Tc)-99m tetrofosmin myocardial perfusion imaging was compared with that on exercise-reinjection thallium-201 imaging with 20 patients with 1-vessel coronary artery disease. In each patient, exercise-reinjection thallium-201 single-photon emission computed tomography (SPECT) and exercise-rest Tc-99m tetrofosmin SPECT imaging were performed. For visual analysis of the obtained SPECT images, the left ventricular myocardium was divided into 20 segments based on 3 short-axis slices from the apical, middle, and basal ventricular levels. For quantitative analysis, a square region of interest was placed on the center of each segment which was used for visual analysis, and relative regional activity to the normal reference region was calculated for each segment. By visual interpretation of the images, exercise Tc-99m tetrofosmin imaging showed a smaller defect size than exercise thallium-201 imaging (6.9 +/- 3.9 vs 8.8 +/- 3.0 segments, p <0.01). In contrast, rest Tc-99m tetrofosmin imaging showed a defect size similar to that on reinjection thallium-201 imaging (5.9 +/- 3.6 vs 5.6 +/- 3.9 segments, p = NS). Similarly, the mean defect sizes during exercise determined by quantitative analysis were smaller on Tc-99m tetrofosmin SPECT than those on thallium-201 SPECT at all tested threshold cutoff points ranging from 50% to 70%, whereas there were no significant differences in defect sizes between rest Tc-99m tetrofosmin and reinjection thallium-201 imaging. These data indicate that exercise Tc-99m tetrofosmin SPECT defect size determined either by visual analysis or by quantitative analysis may be smaller than on exercise thallium-201 SPECT.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Coração/diagnóstico por imagem , Compostos Organofosforados , Compostos de Organotecnécio , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Constrição Patológica , Doença das Coronárias/patologia , Vasos Coronários/patologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de TálioRESUMO
Three patients with ascending aortic aneurysms underwent graft replacement using deep hypothermic circulatory arrest with continuous retrograde cerebral perfusion. In all three cases, preoperative radiographic examination revealed that the aneurysm was large, thin, and adherent to the back of the sternum. For this reason, left ventricular venting was performed through a left thoracotomy before median sternotomy, to decrease both the risk of rupture of the aneurysm and the difficulty of cannulation. This new method, called transthoracic left ventricular venting, was very useful for performing a median sternotomy under hypotensive and hypothermic conditions adequate to reduce the risk of rupture and to manage any rupture immediately through deep hypothermic circulatory arrest.
Assuntos
Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Cateterismo Cardíaco/métodos , Coração Auxiliar , Idoso , Prótese Vascular , Feminino , Humanos , Hipotermia Induzida , Pessoa de Meia-IdadeRESUMO
In this study, a tubular hybrid vascular tissue composed of vascular cells and collagen was implanted as a venous substitute, and its remodeling process was histologically investigated. First, a hybrid medial tissue was prepared by pouring a cold mixed solution of canine jugular smooth muscle cells (SMCs) and Type I collagen into a tubular glass mold and subsequent incubation at 37 degrees C. Culture in medium for 10 days produced a dense tubular tissue. Seeding of jugular endothelial cells (ECs) onto the luminal surface of the tissue produced a hybrid vascular tissue with a hierarchical structure. These vascular tissues (inner diameter, 7 mm; length, 3 cm; wall thickness, 1 mm; n = 14) were implanted autologously in the canine posterior vena cava wrapped in Dacron mesh for up to 24 wk. Nine of 14 grafts were patent throughout implantation. In patent grafts, monolayered ECs were oriented in the direction of blood flow at 1 wk. Circumferentially oriented SMCs accumulated at the subendothelial layer and ingrown fibroblasts were sparsely distributed throughout the wall at 12 wk. Contractile phenotype of SMCs was evident at 24 wk. Collagen fibrils, which were sparsely distributed at an early period of implantation, gradually assembled to form fibrous meshes at 24 wk. Sheet-like elastic lamellae were also observed at this time. Marked wall thinning was observed at 12 and 24 wk. The resultant tissues became highly dense. The specific gravity of tissues increased with time, and reached those of natural vessels at 24 wk. Tissue remodeling progressed in a time-dependent manner and appeared to be almost complete within 6 mo of implantation.
Assuntos
Colágeno , Sobrevivência de Enxerto , Músculo Liso Vascular/transplante , Anastomose Cirúrgica , Animais , Membrana Basal/ultraestrutura , Cães , Endotélio Vascular/fisiologia , Endotélio Vascular/transplante , Endotélio Vascular/ultraestrutura , Veias Jugulares , Microscopia Eletrônica de Varredura , Músculo Liso Vascular/fisiologia , Músculo Liso Vascular/ultraestrutura , Regeneração , Fatores de Tempo , Procedimentos Cirúrgicos Vasculares/instrumentação , Procedimentos Cirúrgicos Vasculares/métodosRESUMO
Dictyostelium discoideum makes multiple developmentally regulated lysosomal cysteine proteinases. One of these, a lysosomal enzyme called proteinase I, contains a cluster of GlcNAc-alpha-1-P-Ser residues. We call this phosphoglycosylation. To study its function, a cDNA library from vegetative cells was screened, and two novel cysteine proteinase clones were characterized (cprD and cprE). Each of them has highly conserved regions expected for cysteine proteinases, but unlike any other, each has a serine-rich domain containing three distinct motifs, poly-S, SGSQ, and SGSG. cprD and cprE cDNAs were overexpressed in Dictyostelium and the active enzymes identified. cprD codes for a protein of approximately 36 kDa (CP4), which is recognized by monoclonal antibodies against GlcNAc-1-P and fucose. cprE corresponds to a 29-kDa protein, which is recognized by antibodies against GlcNAc-1-P. mRNA for both enzymes is present in the vegetative phase and increases during growth on bacteria but decreases throughout development. When the formation of the fruiting body is complete the mRNA for both messages is detected again but in very low levels. Having cloned cDNAs for proteins that carry GlcNAc-1-P should allow us to probe the function of the carbohydrate in these putative lysosomal enzymes.
Assuntos
Acetilglucosamina/análogos & derivados , Cisteína Endopeptidases/genética , Dictyostelium/enzimologia , Proteínas de Protozoários/genética , Acetilglucosamina/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Cisteína Endopeptidases/química , DNA Complementar , Dictyostelium/crescimento & desenvolvimento , Humanos , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/química , Proteínas de Protozoários/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Homologia de Sequência de AminoácidosRESUMO
UNLABELLED: Exercise-rest 99mTc-tetrofosmin myocardial perfusion images with a 2-day protocol was compared to exercise-redistribution-reinjection 201Tl images to assess the ability of 99mTc-tetrofosmin to detect viable myocardium. METHODS: We studied 25 patients with coronary artery disease and regional or global left ventricular dysfunction. Myocardial SPECT images with 99mTc-tetrofosmin were obtained 10 min after injection during exercise and 1 and 3 hr after rest injection. Within 1 wk of the 99mTc-tetrofosmin study, exercise-redistribution-reinjection 201Tl SPECT imaging was performed. RESULTS: Visual analysis demonstrated concordance between 201Tl and 99mTc-tetrofosmin imaging for defect reversibility in 126 of 209 segments (60%), with initial defects on both exercise 201Tl and 99mTc-tetrofosmin images. In the remaining discordant 83 segments (40%), 73 (88%) appeared nonreversible on 99mTc-tetrofosmin imaging but were reversible on 201Tl imaging. CONCLUSION: On the basis of defect reversibility by visual analysis, exercise-rest 99mTc-tetrofosmin imaging underestimates myocardial viability compared to 201Tl reinjection imaging. The identification of viable myocardium with both 99mTc-tetrofosmin and 201Tl can be greatly enhanced to a similar degree if the severity of reduction in activity within nonreversible defects is considered. These two agents may provide comparable information about myocardial viability by quantitative analysis of defect severity.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Coração/diagnóstico por imagem , Compostos Organofosforados , Compostos de Organotecnécio , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Teste de Esforço , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
A tubular, hierarchically structured hybrid vascular tissue composed of vascular cells and collagen was prepared. First, a cold mixed solution of bovine aortic smooth muscle cells (SMCs) and Type I collagen was poured into a tubular glass mold composed of a mandrel and a sheath (example of dimensions: inner diameter, 1.5 mm; outer diameter, 7 mm; length, 7 cm). Upon incubation at 37 degrees C, an SMC-incorporated collagenous gel was formed. After the sheath was removed, the resulting fragile tissue, when cultured in medium, thinned in a time-dependent manner to form an opaque, dense tissue. Higher SMC seeding density and lower initial collagen concentration induced more rapid and prominent shrinkage of the tissue. Morphologic investigation showed that over time, bipolarly elongated SMCs and collagen fiber bundles became positioned around the mandrel. Both components became circumferentially oriented. When the mandrel was removed, a tubular hybrid medial tissue was formed. A hybrid vascular tissue with a hierarchical structure was constructed by seeding endothelial cells onto the inner surface of the hybrid medial tissue. Prepared tissues tolerated luminal pressures as great as 100 mmHg and mechanical stress applied during an anastomotic procedure. This method allowed us to prepare a tubular hybrid medial tissue of predetermined size (inner diameter, wall thickness, and length) by selecting appropriate mold design, initial collagen concentration, and SMC seeding density. Such hybrid vascular tissues may provide physiological functions when implanted into the venous system.
Assuntos
Prótese Vascular , Colágeno/farmacologia , Músculo Liso Vascular/citologia , Animais , Aorta/citologia , Fenômenos Biomecânicos , Bovinos , Endotélio Vascular/citologia , Matriz Extracelular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Pressão , Veias/fisiologia , Veias/cirurgia , Veias/ultraestruturaRESUMO
Exercise-reinjection 201Tl imaging and resting 20-min and 3-hr BMIPP imaging were performed before and 4 mo after percutaneous transluminal coronary angioplasty (PTCA) in a patient with effort angina. Before PTCA, exercise 201Tl imaging showed decreased 201Tl activity in the septal wall, with significant fill-in on the reinjection 201Tl image. The resting 20-min BMIPP image showed decreased activity in the septal wall, with a slight redistribution on the 3-hr BMIPP image. The 201Tl and BMIPP images 4 mo after PTCA showed significant improvement in the 201Tl pattern and BMIPP uptake in the septal wall with no abnormally decreased activities.
Assuntos
Angioplastia Coronária com Balão , Ácidos Graxos/metabolismo , Miocárdio/metabolismo , Idoso , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/metabolismo , Doença das Coronárias/terapia , Ácidos Decanoicos , Teste de Esforço , Coração/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Iodobenzenos , Masculino , Cintilografia , Radioisótopos de TálioRESUMO
A woven fabric graft made of ultrafine polyester fibers (UFPF) (Toray Graft, water porosity: 100 ml/min/cm2:120 mm Hg H2O) was clinically applied in 81 cases (28 thoracic aortic aneurysms, 6 thoracoabdominal aortic aneurysms, 42 abdominal aortic aneurysms, and 5 atherosclerotic obstructions of the peripheral arteries). Eight patients died after surgery due to causes unrelated to the graft. The other 73 patients were in good condition after surgery. For operations requiring extracorporeal circulation, the graft was presealed with human albumin. For the abdominal aortic aneurysms, the graft was preclotted in situ with nonheparinized autoblood after the completion of the proximal anastomosis. It took about 2 min to complete the preclotting. A nonsealed graft was used for the reconstruction of peripheral arteries for the intraaortic balloon pumping procedure. The graft was easy to handle. There was no cut edge fraying problem with the graft in any direction of cutting. Even after presealing, the graft was soft and pliable enough to enable easy adaptation and anastomosis. Just after implantation, bleeding was minimal from the graft wall, anastomotic sites, and suture pores, and it stopped spontaneously. These clinical data showed that the woven UFPF graft exhibited both easy handling despite in spite of low porosity and safe application in the reconstruction of arterial systems even under totally heparinized conditions during extracorporeal circulation.