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1.
J Neurosurg ; : 1-7, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386017

RESUMO

OBJECTIVE: A primary cause of cognitive decline after carotid endarterectomy (CEA) is cerebral injury due to cerebral hyperperfusion. However, the mechanisms of how cerebral hyperperfusion induces cerebral cortex and white matter injury are not known. The presence of cerebral microbleeds (CMBs) on susceptibility-weighted imaging (SWI) is independently associated with a decline in global cognitive function. The purpose of this prospective observational study was to determine whether cerebral hyperperfusion following CEA leads to the development of CMBs and if postoperative cognitive decline is related to these developed CMBs. METHODS: During the 27-month study period, patients who underwent CEA for ipsilateral internal carotid artery stenosis (≥ 70%) also underwent SWI and neuropsychological testing before and 2 months after surgery, as well as quantitative brain perfusion SPECT prior to and immediately after surgery. RESULTS: According to quantitative brain perfusion SPECT and SWI before and after surgery, 12 (16%) and 7 (9%) of 75 patients exhibited postoperative cerebral hyperperfusion and increased CMBs in the cerebral hemisphere ipsilateral to surgery, respectively. Cerebral hyperperfusion was associated with an increase in CMBs after surgery (logistic regression analysis, 95% CI 5.08-31.25, p < 0.0001). According to neuropsychological assessments before and after surgery, 10 patients (13%) showed postoperative cognitive decline. Increased CMBs were associated with cognitive decline after surgery (logistic regression analysis, 95% CI 6.80-66.67, p < 0.0001). Among the patients with cerebral hyperperfusion after surgery, the incidence of postoperative cognitive decline was higher in those with increased CMBs (100%) than in those without (20%; p = 0.0101). CONCLUSIONS: Cerebral hyperperfusion following CEA leads to the development of CMBs, and postoperative cognitive decline is related to these developed CMBs.

2.
J Med Food ; 24(1): 10-17, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33370165

RESUMO

The number of diabetes mellitus and borderline diabetes cases is increasing and poses a serious problem worldwide. Plants of the genus Salacia are known to have α-glucosidase inhibitory activity and to lower postprandial hyperglycemia. Two randomized, double-blind, placebo-controlled clinical trials were conducted to evaluate the efficacy of Salacia chinensis extract. Study 1 was a single-dose crossover study of 150, 300, or 600 mg of Salacia extract or placebo to determine the dose dependency of the effect on postprandial hyperglycemia. The duration of the washout period between each experimental day was a minimum of 6 days. Study 2 was a 12-week, multiple-dose, parallel-group study to evaluate the effects of 600 mg/day of Salacia extract on blood glucose parameters. In Study 1, Salacia induced significant dose-dependent suppression of postprandial blood glucose, insulin, and their incremental area under the curve values. The dose of 600 mg appeared to have the most significant effect. In Study 2, Salacia significantly improved several blood glucose-related parameters, such as hemoglobin A1c, and glucose tolerance after glucose challenge. These results suggest that S. chinensis extract may have beneficial effects in patients with diabetes.

3.
Sensors (Basel) ; 20(22)2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218023

RESUMO

The purpose of the present study was to determine whether objective gait test scores obtained using a tri-axial accelerometer can detect subjective improvement in gait as determined by the patient after carotid endarterectomy (CEA). Each patient undergoing CEA for ipsilateral internal carotid artery stenosis determined whether their gait was subjectively improved at six months after CEA when compared with preoperatively. Gait testing using a tri-axial accelerometer was also performed preoperatively and six months postoperatively. Twelve (15%) of 79 patients reported subjectively improved gait. Areas under the receiver operating characteristic curve for differences between pre- and postoperative test values in stride time, cadence, and ground floor reaction for detecting subjectively improved gait were 0.995 (95% confidence interval (CI), 0.945-1.000), 0.958 (95%CI, 0.887-0.990), and 0.851 (95%CI, 0.753-0.921), respectively. Cut-off points for value differences in detecting subjectively improved gait were identical to mean -1.7 standard deviation (SD) for stride time, mean +1.6 SD for cadence, and mean +0.4 SD for ground floor reaction of control values from normal subjects. Objective gait test scores obtained using the tri-axial accelerometer can detect subjective gait improvements after CEA. When determining significant postoperative improvements in gait using a tri-axial accelerometer, optimal cut-off points for each test value can be defined.

4.
Case Rep Nephrol Dial ; 10(3): 130-138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33251250

RESUMO

A male hepatitis B virus (HBV) carrier in his 40s under hemodialysis treatment exhibited chronic hepatitis (alanine aminotransferase: 41 IU/L, HBV-DNA: >9.1 log copies/mL). Following discontinuation of the initial treatment with pegylated interferon-α-2a at 24 weeks due to adverse effects, the administration of tenofovir disoproxil fumarate (TDF) (300 mg/week) led to a rapid improvement in hepatitis markers: HBV DNA became undetectable at month 34, and seroconversion of hepatitis B envelope antigen was confirmed at 45 months. No side effects were recorded during TDF treatment. TDF is a newly approved nucleoside analogue that may cause severe side effects via proximal tubular injury in patients with renal dysfunction. However, few reports have described its use in hemodialysis patients, whose anuric state may render them less susceptible to side effects including kidney injury. Hepatitis improved remarkably without any adverse drug reactions in the present case. TDF may therefore be considered for chronic hepatitis B patients receiving hemodialysis.

5.
J Biomol NMR ; 74(10-11): 521-529, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32901320

RESUMO

No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation.

6.
Medicine (Baltimore) ; 99(37): e22202, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925796

RESUMO

Metabolic syndrome (MetS), mainly caused by intra-abdominal fat (IAF) accumulation, is an important risk factor for cardiovascular disease. The prevalence of MetS increases rapidly after the age of 40 years, and it is presumed that there is a substantial proportion of MetS in younger age groups. However, the association of IAF with MetS in adults aged 20 to 30 years has not been fully investigated.This study aimed to determine the prevalence of MetS and to verify whether IAF accumulation is associated with other MetS-related metabolic disorders including dyslipidemia, high blood pressure, and high blood glucose among the Japanese population in their 20s.In this cross-sectional study, IAF area (IAFA) and MetS-related metabolic parameters were evaluated in university students in their 20s (n = 1822, 21.5 ±â€Š1.5 years). IAFA was measured using a non-invasive device, DUALSCAN, which can be readily measured through the dual impedance method. The participants were divided into four groups according to IAFA: 0-49.9, 50-74.9, 75-99.9, and ≥100 cm.MetS was prevalent in 3.3% and 0.0% of the males and females, respectively, according to the Japanese criteria of MetS. The sex- and lifestyle-adjusted odds ratios (ORs) for the three metabolic component levels of Mets were elevated in the larger IAFA groups compared to the smallest IAFA group, according to the level of IAFA. The levels particularly increased in participants with abdominal obesity, defined by both, IAFA and waist circumference rather than by waist circumference alone.IAF accumulation was significantly associated with MetS-related metabolic disorders in young adults. An evaluation of IAFA may contribute to the early prediction of the risk of developing MetS in the future.


Assuntos
Síndrome Metabólica/epidemiologia , Obesidade Abdominal/epidemiologia , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Pesos e Medidas Corporais , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Gordura Intra-Abdominal/fisiopatologia , Estilo de Vida , Lipídeos/sangue , Masculino , Fatores Sexuais , Circunferência da Cintura , Adulto Jovem
7.
Nucl Med Commun ; 41(11): 1161-1168, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32815897

RESUMO

OBJECTIVE: Carotid endarterectomy (CEA) often restores cerebral perfusion and neurotransmitter receptor function, which is seen on early and late images, respectively, on brain I-iomazenil single-photon emission computed tomography (SPECT). The reliability of gait-related parameters obtained using a triaxial accelerometer, a portable device for gait assessment, has been confirmed with test-retest measurements. The purpose of the present prospective cohort study was to determine whether improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex. METHODS: Gait testing using a triaxial accelerometer was performed preoperatively and 6 months postoperatively in 64 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%). I-iomazenil SPECT was also performed with scanning within 30 min (early images) and at 180 min (late images) after tracer administration before and after surgery. SPECT data were analyzed using a three-dimensional stereotactic surface projection, and motor (Brodmann 4) and premotor (Brodmann 6) cortexes in each hemisphere were combined and defined as the motor-related cortex. RESULTS: Based on preoperative and postoperative gait testing, seven patients (11%) showed postoperative improved gait. Logistic regression analysis revealed that postoperative increase in I-iomazenil uptake in the motor-related cortex ipsilateral to surgery on early [95% confidence interval (CI), 4.32-365.21; P = 0.0477) or late (95% CI, 9.45-1572.57; P = 0.0173) images was an independent predictor of postoperative improved gait. CONCLUSIONS: Improvement in gait function after CEA is associated with postoperative recovery in perfusion and neurotransmitter receptor function in the motor-related cerebral cortex.

8.
J Stroke Cerebrovasc Dis ; 29(9): 105081, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807478

RESUMO

BACKGROUND: Cerebrovascular reactivity (CVR) to acetazolamide (ACZ) on single-photon emission computed tomography (SPECT) can be used to assess the severity of chronic cerebral ischemia; however, this is an invasive method. We examined whether whole-brain magnetic resonance angiography (MRA) at 7T could non-invasively detect impaired CVR in patients with chronic cerebral ischemia by demonstrating the leptomeningeal collaterals (LMCs). METHODS: Fifty-seven patients with symptomatic unilateral cervical stenosis underwent whole-brain time-of-flight MRA at 7T and cerebral perfusion SPECT before/after the ACZ challenge. MRA images were visually assessed based on 6-point grading systems to evaluate the development of LMCs toward the middle cerebral artery (MCA) and antegrade flow of MCA. CVR of the affected side was calculated from the SPECT data. Subsequently, we compared the LMC grades on MRA with CVR on SPECT. RESULTS: CVR was significantly lower in grades ≥ 2 of LMCs than in grades 0-1 (P < 0.05) when applying LMCs from the anterior cerebral artery (ACA) and/or posterior cerebral artery (PCA). These differences were more evident than those in the grading of the antegrade MCA flow. The LMC grades from ACA/PCA readily detected reduced CVR (< 18.4%) with a sensitivity/specificity of 0.79/0.82. CONCLUSION: The development of LMCs on whole-brain MRA at 7T can non-invasively detect reduced CVR with a high sensitivity/specificity in patients with unilateral cervical stenosis.


Assuntos
Angiografia Cerebral/métodos , Circulação Cerebrovascular , Circulação Colateral , Angiografia por Ressonância Magnética , Meninges/irrigação sanguínea , Artéria Cerebral Média/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Imagem de Perfusão , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton Único , Insuficiência Vertebrobasilar/fisiopatologia
9.
Food Sci Nutr ; 8(6): 2773-2779, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32566194

RESUMO

Fish paste product, "Hanpen," is a traditional type of Japanese food made from minced fish as well as imitation crab and kamaboko, and a marshmallow-like soft texture is characteristic of hanpen. Hanpen is known as a high-protein and low-fat food. However, there is a lack of evidence on its health benefits. The aim of this study was to investigate the effects of hanpen intake on organ weight and biomarker levels in Sprague-Dawley rats with diets consisting of hanpen for 84 days as an initial study. Male, 6-week-old Sprague-Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5% dried hanpen. Throughout the 84-day treatment period, we checked body weight and food intake, and after 84 days, we performed organ weight and blood biochemical analyses. No significant differences were seen in body weight, food intake, organ weight, and most biochemical parameters between group I and group II. Interestingly, total cholesterol (T-CHO) and high-density lipoprotein cholesterol (HDL-C) levels of group II were significantly higher than those of group I after administration for 84 days. Moreover, lactate dehydrogenase (LDH) level of group II was marked lower than that of group I, and other liver function parameters of group II tended to be lower than those of group I. As conclusion, "Hanpen," a Japanese traditional food, could be effective as a functional food for human health management worldwide.

10.
Biomedicines ; 8(4)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260271

RESUMO

Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical features and outcomes between first treatment (n = 159) and retreatment (n = 23) G/P groups. Overall, 77 patients (42.3%) were male, the median age was 68 years, and 86/66/1/4 cases had genotype 1/2/1+2/3, respectively. An SVR was achieved in 97.8% (178/182) of cases by intention-to-treat analysis and 99.4% (178/179) of cases by per-protocol analysis. There were no remarkable differences between the first treatment and retreatment groups for male (42.8% vs. 39.1%, p = 0.70), median age (68 vs. 68 years, p = 0.36), prior hepatocellular carcinoma (5.8% vs. 8.7%, p = 0.59), or the fibrosis markers AST-to-platelet ratio index (APRI) (0.5 vs. 0.5, p = 0.80) and fibrosis-4 (FIB-4) index (2.2 vs. 2.6, p = 0.59). The retreatment group had a significantly more frequent history of interferon treatment (12.3% vs. 52.2%, p < 0.01) and the Y93H mutation (25.0% vs. 64.7%, p = 0.02). The number of retreatment patients who had experienced 3, 2, and 1 DAA treatment failures was 1, 3, and 19, respectively, all of whom ultimately achieved an SVR by G/P treatment. In conclusion, G/P was effective and safe for both HCV first treatment and retreatment cases despite the retreatment group having specific resistance mutations for other prior DAAs. As G/P treatment failure has been reported for P32 deletions, clinicians should consider resistance mutations during DAA selection.

11.
J Stroke Cerebrovasc Dis ; 29(4): 104680, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32057651

RESUMO

BACKGROUND: Complete removal of the distal end of the plaque is an important requirement in carotid endarterectomy (CEA) to avoid postoperative complication. Preoperative identification of the distal end of plaque contributes to complete plaque removal. Three-dimensional (3D) magnetic resonance (MR) plaque imaging has been widely used to evaluate carotid plaque characterization. The purpose of the present study was to determine whether preoperative 3D fast spin echo (FSE) T1-weighted MR plaque imaging could identify the distal end of carotid plaque. METHODS: This study was designed as a prospective cohort study. We examined 50 patients with cervical internal carotid artery (ICA) stenosis who underwent CEA. 3D-FSE T1-weighted MR plaque imaging of the affected carotid bifurcation was preoperatively performed using a 1.5-T scanner. Identification of the distal end of plaque (DEMRI) on MR plaque imaging was performed and the distance from the baseline (DistanceMRI) was measured. Intraoperatively, the superimposed distal end of carotid plaque (Esim) was marked on the ICA according to the measurement on MR plaque imaging. The actual distal end of plaque (DECEA) was then identified after arteriotomy and the difference (DifferenceCEA-MRI) between Esim and DECEA was measured. Contrast ratio of carotid plaque and tortuosity of the ICA were calculated using MR plaque imaging. RESULTS: Interobserver agreements in measurement of DistanceMRI were excellent (intraclass correlation coefficient, .955; 95% confidence interval, .922-.974). In 28 patients (56%), Esim was identical to DECEA. Mean DifferenceCEA-MRI was 1.32 ± 1.77 mm. DifferenceCEA-MRI was significantly greater with fibrotic plaque (4.14 ± 1.21 mm) than with lipid-rich or necrotic plaque (.43 ± .87 mm; P < .05) or hemorrhagic plaque (1.27 ± 1.64 mm; P < .05). Mean DifferenceCEA-MRI was significantly greater in the group with tortuosity of the ICA less than 120° (3.86 ± 1.77 mm) than in the group with greater than or equal to 120° but less than or equal to 150° (1.15 ± 1.51 mm; P < .05) or greater than150° (0.50 ± 1.10 mm; P < .05). No patients showed residual stenosis after surgery on postoperative MR angiography. CONCLUSIONS: Using 3D-FSE T1-weighted MR plaque imaging allowed identification of the distal end of carotid plaque and contributed to complete removal of the plaque, although it may be reduced for cases with low-signal-intensity plaque or severe tortuosity of the ICA.


Assuntos
Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Placa Aterosclerótica , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes
12.
Int J Stroke ; 15(6): 657-665, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31500554

RESUMO

BACKGROUND: Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. AIMS: The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. METHODS: Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. RESULTS: Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74-3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01-0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. CONCLUSION: Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

13.
Clin Nucl Med ; 45(2): e115-e116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31524676

RESUMO

A 67-year-old man had a slowly progressing impairment of recent memory. Cerebral angiography showed atherosclerotic occlusion of the right internal carotid artery with insufficient collateral circulation. Positron emission tomography (PET) using O2 gas showed reduced cerebral blood flow, reduced cerebral metabolic rate of oxygen, and elevated oxygen extraction fraction in the precentral region of the right cerebral hemisphere. Use of F-florbetapir PET depicted amyloid ß deposition as decreased tracer uptake in the precentral region in the right cerebral hemisphere when compared with the contralateral hemisphere.


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Arteriosclerose Intracraniana/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Idoso , Compostos de Anilina , Etilenoglicóis , Feminino , Humanos , Masculino , Compostos Radiofarmacêuticos
15.
JACC Cardiovasc Interv ; 12(7): 637-647, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30947938

RESUMO

OBJECTIVES: The aim of this study was to compare 7-year outcomes between the first-generation sirolimus-eluting stent (SES) and the new-generation everolimus-eluting stent (EES) in a randomized clinical trial. BACKGROUND: There is a scarcity of very long-term (beyond 5 years) data from clinical trials investigating whether new-generation drug-eluting stents have clear clinical advantages over first-generation drug-eluting stents. METHODS: RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) is the largest randomized trial comparing EES with SES (NCT01035450). Among a total of 3,197 patients in the original RESET population from 100 centers, the present extended 7-year follow-up study was conducted in 2,667 patients from 75 centers after excluding those patients enrolled from centers that denied participation. Complete 7-year follow-up was achieved in 91.5% of patients. RESULTS: The cumulative 7-year incidence of the primary efficacy endpoint of target lesion revascularization was not significantly different between EES and SES (10.2% vs. 11.7%; hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.10; p = 0.24). The risk for the primary safety endpoint of death or myocardial infarction trended lower with EES than with SES (20.6% vs. 23.6%; hazard ratio: 0.85; 95% confidence interval: 0.72 to 1.005; p = 0.06). The cumulative 7-year incidence of definite stent thrombosis was very low and similar between EES and SES (0.9% vs. 1.0%; p = 0.82). The lower risk of EES relative to SES was significant for the composite secondary endpoint of target lesion failure (13.3% vs. 18.1%; hazard ratio: 0.72; 95% confidence interval: 0.59 to 0.88; p = 0.001). CONCLUSIONS: During 7 years of follow-up, the risk for target lesion revascularization was not significantly different between the new-generation EES and the first-generation SES.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Everolimo/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Sirolimo/administração & dosagem , Idoso , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Everolimo/efeitos adversos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Desenho de Prótese , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
J Nat Med ; 73(3): 584-588, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028661

RESUMO

The antidiabetic effects of a hot water extract of the stems of Salacia chinensis (SCE) were evaluated in vivo in ob/ob mice (genetically obese hyperglycemic mice). Administration of dietary feed containing 0.20 and 0.50% of SCE for 23 days to ob/ob mice significantly suppressed the elevation of both blood glucose and HbA1c levels, without significantly changing body weight and food intake. To characterize the antidiabetic effects of the thiosugar sulfonium constituent neokotalanol (1), which has potent α-glucosidase inhibitory activity, we performed a similar in vivo study. HbA1c levels were significantly suppressed in ob/ob mice after the administration of dietary feed containing 0.0003% of neokotalanol (1) for 20 days. These results indicate that SCE and neokotalanol (1) are potential leads for the development of novel antidiabetic agents.


Assuntos
Hemoglobina A Glicada/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Salacia/química , Tioaçúcares/farmacologia , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Peso Corporal , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos Obesos , Obesidade , Tioaçúcares/química
17.
Cerebrovasc Dis ; 47(1-2): 57-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30783065

RESUMO

BACKGROUND: Hypoxic but viable neural tissue is seen on 1-(2-18F-fluoro-1-[hydroxymethyl]ethoxy) methyl-2-nitroimidazole (18F-FRP170) positron emission tomography (PET) in patients with chronic cerebral ischemia with a combination of misery perfusion and moderately reduced oxygen metabolism. Cognitive function sometimes improves after revascularization surgery in patients with chronic cerebral ischemia. OBJECTIVES: We used brain perfusion single-photon emission computed tomography (SPECT) and 18F-FRP170 PET to determine whether hypoxic tissue was reduced following the restoration of cerebral perfusion after carotid endarterectomy (CEA) in patients with severe stenosis of the cervical internal carotid artery (ICA) and whether the reduction in hypoxic tissue was associated with cognitive improvement. METHOD: Eighteen patients with abnormally reduced cerebral blood flow (CBF) in the affected cerebral hemispheres on preoperative brain perfusion SPECT -underwent CEA. They underwent 18F-FRP170 PET and neuropsychological tests preoperatively and 6 months postoperatively. Brain perfusion SPECT was also performed 6 months postoperatively. Regions of interest were placed in the bilateral middle cerebral artery territories on SPECT and PET images, and the ratio of values in the affected versus contralateral hemispheres was calculated. RESULTS: The CBF ratio (p = 0.0006) and 18F-FRP170 ratio (p = 0.0084) were significantly increased and reduced, respectively, after surgery compared to the corresponding ratios before surgery. The difference in the 18F-FRP170 ratio (postoperative - preoperative value) was negatively correlated with the difference in the CBF ratio (ρ = -0.695; p = 0.0009). The difference in the 18F-FRP170 ratio was significantly lower in patients with postoperative improved cognition compared to that in those without (p = 0.0007). The area under the receiver operating characteristics curve for the difference in the 18F-FRP170 ratio for detecting postoperative improved cognition was significantly greater than that for the difference in the CBF ratio (difference between areas, 0.278; p = 0.0248). CONCLUSIONS: Hypoxic tissue is reduced following the restoration of cerebral perfusion with revascularization surgery in patients with severe atherosclerotic stenosis of the cervical ICA. The reduction in hypoxic tissue is associated with cognitive improvement in such patients.


Assuntos
Isquemia Encefálica/cirurgia , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Transtornos Cognitivos/psicologia , Cognição , Endarterectomia das Carótidas , Hipóxia Encefálica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Animais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/psicologia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/psicologia , Circulação Cerebrovascular , Doença Crônica , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Hipóxia Encefálica/diagnóstico por imagem , Hipóxia Encefálica/fisiopatologia , Hipóxia Encefálica/psicologia , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Imagem de Perfusão/métodos , Animais de Estimação , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento
18.
Neurol Res ; 41(5): 480-487, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30774013

RESUMO

OBJECTIVE: Adult patients with ischemic moyamoya disease (MMD) who receive treatment with antiplatelet drugs reportedly show improvements in neuropsychological test scores after around 2 years. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, results in better improvement of cognitive function among non-surgical adult patients showing ischemic MMD without severe hemodynamic compromise. METHODS: Sixty-six patients without cerebral misery perfusion on 15O gas positron emission tomography were treated with pharmacotherapy alone. Patients ≥50 years old and <50 years old initially received clopidogrel and cilostazol, respectively. Any patient suffering side effects of the antiplatelet drug switched to the other antiplatelet drug. Neuropsychological tests were performed at study entry and at the end of the 2-year follow-up, and differences in each neuropsychological test score between the two time points (second test score - first test score) were calculated and defined as Δ scores. RESULTS: Among the five neuropsychological tests, Δ scores for two tests were significantly greater in patients treated with cilostazol (n = 36) than in those treated with clopidogrel (n = 30), and Δ scores of the remaining three tests did not differ between patient groups. Based on Δ scores, 15 patients (23%) were defined as showing interval cognitive improvement. On multivariate analysis, cilostazol administration (95% confidence interval, 1.19-193.98; P = 0.0361) represented an independent predictor of interval cognitive improvement. CONCLUSIONS: Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic MMD.


Assuntos
Cilostazol/farmacologia , Clopidogrel/farmacologia , Cognição/efeitos dos fármacos , Doença de Moyamoya/tratamento farmacológico , Doença de Moyamoya/psicologia , Nootrópicos/uso terapêutico , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
19.
Clin Nucl Med ; 44(4): 295-296, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30688740

RESUMO

A 48-year-old man experienced recurrent vertigo refractory to antiplatelet medications. Cerebral angiography showed occlusion of bilateral vertebral arteries with poor collateral circulation. PET using O2 gas showed reduced blood flow and metabolic rate of oxygen and elevated oxygen extraction fraction in bilateral cerebellar hemispheres. Subsequent F-FRP170 (1-(2-F-fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole) PET, which depicts hypoxic but viable tissue, revealed elevated tracer uptake in the same regions. After superficial temporal artery-posterior cerebral artery anastomosis, O-gas PET showed normalization of blood flow, metabolic rate of oxygen, and oxygen extraction fraction in bilateral cerebellar hemispheres. Abnormally elevated F-FRP-170 uptake was also resolved in those regions.


Assuntos
Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/patologia , Cerebelo/patologia , Nitroimidazóis , Tomografia por Emissão de Pósitrons , Enxerto Vascular , Artéria Vertebral/cirurgia , Arteriopatias Oclusivas/cirurgia , Hipóxia Celular , Angiografia Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/patologia
20.
Org Biomol Chem ; 17(5): 1058-1061, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30637418

RESUMO

SurE is a new, stand-alone thioesterase (TE) offloading the non-ribosomal peptide (NRP) assembly line found in surugamide biosynthesis. It is homologous to penicillin binding protein (PBP) and capable of cyclizing two structurally unrelated substrates derived from two different NRP assembly lines, highlighting the broad substrate tolerance of the SurE offloading cyclase.


Assuntos
Esterases/química , Oligopeptídeos/química , Peptídeos Cíclicos/química , Compostos de Sulfidrila/química , Vias Biossintéticas , Cromatografia Líquida/métodos , Ciclização , Genes Bacterianos , Espectrometria de Massas/métodos , Estrutura Molecular , Espectrofotometria Ultravioleta , Streptomyces/química , Streptomyces/genética , Especificidade por Substrato
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