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1.
Bioscience ; 72(10): 999-1006, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36196220

ABSTRACT

Native peoples (Native American, Alaskan Native, Native Hawaiian) are underrepresented in academia; they represent 2% of the US population but 0.01% of enrolled undergraduate students. Native peoples share the experiences of colonization and forced assimilation, resulting in the loss of ancestral knowledge, language, and cultural identity. Recognizing history and the literature on social integration and mentorship, we followed 100 Native science and engineering scholars across a year of participation in the hybrid American Indian Science and Engineering Society mentorship program. The results showed that high-quality faculty mentorship predicted persistence a year later. Furthermore, mentors who shared knowledge of Native culture-through experience or shared heritage-uniquely contributed to the Native scholars' social integration and persistence through scientific community values in particular. Therefore, Native scholars may benefit from mentorship supporting the integration of their Native culture and discipline rather than assimilation into the dominant disciplinary culture.

2.
AJNR Am J Neuroradiol ; 43(8): 1124-1130, 2022 08.
Article in English | MEDLINE | ID: mdl-35835591

ABSTRACT

BACKGROUND AND PURPOSE: ICA-selective MRA using a pencil beam presaturation pulse can accurately visualize anterior communicating artery flow. We evaluated the impact of anterior communicating artery flow on the perioperative hemodynamic status and new ischemic lesions after carotid revascularization. MATERIALS AND METHODS: Eighty-three patients with carotid artery stenosis were included. We assessed anterior communicating artery flow using ICA-selective MRA. The preoperative hemodynamic status was measured using SPECT. We also measured the change in regional cerebral oxygen saturation after temporary ICA occlusion. New ischemic lesions were evaluated by DWI on the day after treatment. RESULTS: Anterior communicating artery flow was detected in 61 patients, but it was not detected in 22 patients. Preoperative cerebrovascular reactivity was significantly higher in patients with (versus without) anterior communicating artery flow with a mean peak systolic velocity of ≥200 cm/s (39.6% [SD, 23.8%] versus 25.2% [SD, 16.4%]; P = .030). The decrease in mean regional cerebral oxygen saturation was significantly greater in patients without (versus with) anterior communicating artery flow (8.5% [SD, 5.6%] versus 3.7% [SD, 3.8%]; P = .002). New ischemic lesions after the procedure were observed in 23 patients. The multivariate logistic regression analysis revealed that anterior communicating artery flow (OR, 0.07; 95% CI, 0.012-0.45; P = .005) was associated with new ischemic lesions. CONCLUSIONS: The absence of anterior communicating artery flow influenced the perioperative hemodynamic status in patients with carotid stenosis and was associated with an increased incidence of new ischemic lesions after carotid revascularization.


Subject(s)
Carotid Artery, Internal , Carotid Stenosis , Humans , Carotid Artery, Internal/pathology , Carotid Arteries , Magnetic Resonance Imaging , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Carotid Stenosis/pathology , Anterior Cerebral Artery , Cerebrovascular Circulation
4.
Diabet Med ; 36(12): 1621-1628, 2019 12.
Article in English | MEDLINE | ID: mdl-31335979

ABSTRACT

AIM: To test the hypothesis that the addition of a glucagon-like peptide-1 receptor agonist that can decrease glucose levels without increasing the hypoglycaemia risk will achieve appropriate glycaemic control during the peri-operative period. METHODS: We studied 70 people with Type 2 diabetes who underwent elective cardiac surgery. Participants were randomized to either an insulin-alone or an insulin plus liraglutide 0.6 mg/day group. We evaluated average M values, which indicated the proximity index of the target glucose level from day 1 to day 10. RESULTS: The average M value in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (liraglutide plus insulin 5.8 vs insulin-alone 12.3; P < 0.001). The frequency of insulin dose modification in the liraglutide plus insulin group was significantly lower than that in the insulin-alone group (odds ratio 0.19, 95% CI 0.08-0.49; P < 0.001). The frequency of hypoglycaemia in the liraglutide plus insulin group tended to be lower than that in the insulin-alone group (odds ratio 0.57, 95% CI 0.15-2.23; P = 0.21). CONCLUSIONS: The results of this study showed that the addition of low-dose liraglutide to insulin achieved lower M values than insulin alone, suggesting that the addition of low-dose liraglutide may achieve better glycaemic control during the peri-operative period. (Clinical trials registry no.: UMIN 000008003).


Subject(s)
Cardiac Surgical Procedures/methods , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Insulin/administration & dosage , Liraglutide/administration & dosage , Perioperative Period/methods , Aged , Aged, 80 and over , Blood Glucose/analysis , Cardiac Surgical Procedures/mortality , Diabetes Mellitus, Type 2/blood , Drug Therapy, Combination , Female , Glycated Hemoglobin/analysis , Humans , Hyperglycemia/complications , Hypoglycemia/complications , Hypoglycemia/epidemiology , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Male , Middle Aged , Postoperative Complications/prevention & control , Risk Factors
5.
Obes Sci Pract ; 3(4): 407-416, 2017 12.
Article in English | MEDLINE | ID: mdl-29259799

ABSTRACT

Objective: To investigate the effects of monthly feedback of changes in visceral fat area (VFA) as measured by dual bioelectrical impedance analysis method and the importance of VFA in individuals with obesity. Methods: Thirty-eight Japanese patients with obesity underwent VFA measurements. The feedback group was given feedback on VFA measurements each month for 4 months. The control group underwent VFA measurements at the beginning and end of the study but was not informed of the results. All the study participants completed eating behaviour and weight efficacy lifestyle questionnaires. Results: Mean age was 53.9 (14.3) years; mean body mass index was 30.6 (4.3) kg m-2. At the 4-month follow-up, there was no significant difference in VFA reduction between the control and feedback groups (-4.4% vs. -3.0%; 95% CI, -3.8 to 5.5). In post-hoc analysis using the overall group irrespective of allocation, changes of eating style were significantly associated with a reduction in VFA at 4 months (p = 0.034). Conclusions: Monthly feedback on changes in VFA does not reduce VFA. More frequent feedback may be required. In post-hoc analysis, changes of eating style were associated with a reduction in VFA.

6.
Dis Esophagus ; 30(3): 1-9, 2017 03 01.
Article in English | MEDLINE | ID: mdl-28184414

ABSTRACT

Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patient's specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.


Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/genetics , Cysteine Dioxygenase/genetics , DNA Methylation/genetics , Esophageal Neoplasms/genetics , Genetic Predisposition to Disease/epidemiology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Barrett Esophagus/pathology , Barrett Esophagus/surgery , Cell Transformation, Neoplastic/genetics , Cohort Studies , Disease-Free Survival , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagectomy/mortality , Esophagoscopy/methods , Female , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Polymerase Chain Reaction/methods , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis
7.
Eur J Surg Oncol ; 42(9): 1253-60, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27017273

ABSTRACT

TNM staging is no doubt the most critical prognostic factors, representing tumor (T)/lymph node metastasis (N)/distant metastasis (M) in gastric cancer. Lymph node ratio-based N system (Nr) has been repeatedly reported to be of prognostic relevance in advanced gastric cancer independent of stage in the multivariate analysis world-wide, and proposed as more sophisticated than N with regard to predicting accurate prognosis. As a result, proposed TNrM system may predict survival more accurately than the present TNM staging system for patients undergoing limited lymph node analysis. It could adjust stage migration when the lymph node number was used as staging factor. Although correlation of the number of metastatic lymph nodes and lymph node ratio is obvious, biological characteristics other than that could also have been reflected on. It may indicate how successful the operation of lymph node dissection was, or it may be revealing the potential of the patient's lymph node immune-reaction. Recently, high lymph node ratio is closely associated with EGFR expression in advanced gastric cancer. When efficiency of applying lymph node ratio as a biomarker is verified and confirmed in an expansive research, and when cancer causing molecules are identified, as well as the competence as a treatment target is studied, the new biomarker, namely, lymph node ratio, could find itself in a limelight in gastric cancer treatment in the future.


Subject(s)
Carcinoma/pathology , Lymph Nodes/pathology , Stomach Neoplasms/pathology , Carcinoma/therapy , Humans , Lymph Node Excision , Lymphatic Metastasis , Multivariate Analysis , Neoplasm Staging , Prognosis , Stomach Neoplasms/therapy
8.
Eur J Surg Oncol ; 41(10): 1324-32, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26251341

ABSTRACT

BACKGROUND: Peritoneal lavage cytology cancer-positive (CY1) is a critical prognostic factor and is taken as representing stage IV in gastric cancer. There is no consensus treatment strategy for CY1-gastric cancer, and the detailed clinicopathological features remain obscure. PATIENTS AND METHODS: Among 790 gastric cancer patients between 2005 and 2009, 52 cases of CY1 were identified (6.6%). A multivariate prognostic model was applied to the univariate prognostic factors to identify independent prognostic factors and factors associated with long-term survival in CY1-gastric cancer. RESULTS: (1) Five-year overall survival (OS) was 17.6% in CY1-gastric cancer as compared with 93.9% in CYX and 77.7% in CY0 (77.7%), where tumors with pT2 or beyond were included in 11% of CYX, 73% of CY0, and 98% of CY1 cases. (2) On univariate analysis, factors associated with a negative prognosis were the presence of peritoneal dissemination (p = 0.029) and high preoperative serum albumin (p = 0.011) in CY1-gastric cancer. The multivariate Cox proportional hazards and logistic regression model using propensity score identified preoperative albumin as a critical independent prognostic indicator. (3) Long-term survivors were identified and, were often characterized by long-term postoperative adjuvant treatment. CONCLUSION: Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival in patients with advanced gastric cancer with positive cytology test. Long-term postoperative adjuvant therapy might improve survival of patients with CY1.


Subject(s)
Hypoalbuminemia/blood , Peritoneal Neoplasms/secondary , Serum Albumin/metabolism , Stomach Neoplasms/blood , Stomach Neoplasms/mortality , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Disease-Free Survival , Docetaxel , Drug Combinations , Female , Gastrectomy , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Oxonic Acid/administration & dosage , Peritoneal Lavage , Peritoneal Neoplasms/mortality , Preoperative Period , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Taxoids/administration & dosage , Tegafur/administration & dosage
9.
Horm Metab Res ; 47(3): 168-75, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25415231

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of the metabolic syndrome. Although NAFLD is a major cause of cirrhosis and cancer of the liver of unknown cause, no established pharmacological treatment for NAFLD has been established yet. It has been reported that leptin treatment improved fatty liver dramatically as well as insulin resistance and hyperphagia in patients with lipodystrophy. However, it is unclear whether leptin improves fatty liver independently of these metabolic improvements. We investigated the liver effect of leptin independently of insulin sensitization and appetite suppression using hepatocyte-specific Pten-deficient (AlbCrePtenff) mouse, a model of severe fatty liver with insulin hypersensitivity. Male AlbCrePtenff mice were infused subcutaneously with leptin (20 ng/g/h) for 2 weeks using osmotic minipumps. Leptin infusion effectively reduced liver weight, liver triglyceride content, and glutamate pyruvate transaminase (GPT) concentrations as well as food intake and body weight without the change of plasma insulin concentration in AlbCrePtenff mice. Pair-feeding also reduced body weight but not liver triglyceride content. Pair feeding reduced α1 and α2 AMP-activated protein kinase (AMPK) activities and PGC1α gene expression in the liver, while leptin infusion unchanged them. The present study clearly demonstrated that leptin improve fatty liver independently of insulin sensitization and suppression of food intake. It was suggested that leptin improves fatty liver by stimulation of ß-oxidation in the liver. The present study might provide a further understanding on the mechanism of metabolic effect of leptin.


Subject(s)
Hepatocytes/metabolism , Insulin/metabolism , Leptin/administration & dosage , Non-alcoholic Fatty Liver Disease/drug therapy , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Animals , Appetite/drug effects , Hepatocytes/drug effects , Humans , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Knockout , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/physiopathology , PTEN Phosphohydrolase/deficiency , PTEN Phosphohydrolase/genetics , Triglycerides/metabolism
10.
J Dairy Sci ; 97(2): 952-60, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24342688

ABSTRACT

The effects of the substitution of brown rice (Oryza sativa L.; BR) for corn (Zea mays L.) in ensiled total mixed ration (TMR) that had a high proportion of grain on feed intake, lactation performance, ruminal fermentation, digestion, and N utilization were evaluated. Nine multiparous Holstein cows (51 ± 9 d in milk) were used in a replicated 3 × 3 Latin square design with 3 dietary treatments: a diet containing 0, 20, or 40% steam-flaked BR and 40, 20, or 0% steam-flaked corn (dry matter basis). Cows were fed ad libitum an ensiled TMR consisting of 40.7% alfalfa silage, 11.8% grass silage, 7.1% soybean meal, and 40.0% steam-flaked grain (dry matter basis). The ensiled TMR was prepared by baling fresh TMR, and then sealed by a bale wrapper and stored outdoors at 5 to 30 °C for over 6 mo. Dry matter intake and milk yield were lower for cows fed 40% BR than for cows fed 40% corn. The ruminal pH and total volatile fatty acid concentrations were not affected by dietary treatment. The ruminal ammonia-N concentration decreased as the percentage of BR in the diets was elevated. The proportion of acetate decreased, and that of propionate and butyrate increased with the increasing levels of BR. Plasma urea-N concentrations was lower and glucose and insulin concentrations were higher for cows fed 40% BR than for cows fed 40% corn. The whole-tract apparent digestibility of dry matter, organic matter, and starch increased, and the digestibility of neutral detergent fiber and acid detergent fiber decreased with the increasing BR level in the diet, with no dietary effect on crude protein digestion. As a proportion of N intake, the urinary N excretion was lower and the retention of N was higher for cows fed 40% BR than for cows fed 40% corn, with no dietary effect observed on N secretion in milk and fecal N excretion. These results show that substituting BR for corn decreases urinary N losses and improves N utilization, but causes adverse effects on milk production when cows are fed high-grain diets at 40% of dietary dry matter.


Subject(s)
Cattle/physiology , Oryza/chemistry , Silage/analysis , Zea mays/chemistry , Ammonia/metabolism , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Dietary Fiber/metabolism , Digestion/drug effects , Female , Fermentation , Lactation , Medicago sativa/metabolism , Milk/metabolism , Starch/metabolism
11.
J Neuroendocrinol ; 24(8): 1120-5, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22487415

ABSTRACT

Recent epidemiological studies demonstrate that obesity is related to a high incidence of cognitive impairment. In the present study, cognitive behaviours in diet-induced obese (DIO) mice fed 60% high-fat diet for 16 weeks were compared with those in mice fed a control diet (CD) in fear-conditioning tests including both contextual and cued elements that preferentially depend on the hippocampus and amygdala, respectively. Furthermore, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) content in the brain areas was examined in both CD and DIO mice. In fear-conditioning tests, the freezing percentages of both contextual fear and cued fear responses in DIO mice were significantly lower than in CD mice. BDNF content in the cerebral cortex and hippocampus of DIO mice was significantly lower than that in CD mice. Its receptor, full-length TrkB, in the amygdala of DIO mice was significantly decreased compared to that in CD mice, although not in the cerebral cortex, hippocampus and hypothalamus. By contrast, NT-3 content in the hippocampus, amygdala and hypothalamus of DIO mice was significantly higher than that in CD mice. Its receptor, full-length TrkC, was not significantly different between CD and DIO mice. The present study demonstrates that DIO mice show impairment of both hippocampus-dependent contextual and amygdala-dependent cued responses in the fear-conditioning tests, as well as an imbalance in the interaction between the BDNF and NT-3 systems in the cerebral cortex, hippocampus and amygdala related to cognition and fear.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Conditioning, Classical , Diet , Fear , Nerve Growth Factors/metabolism , Obesity/metabolism , Animals , Behavior, Animal , Blotting, Western , Brain/metabolism , Male , Mice , Mice, Inbred C57BL , Obesity/etiology
12.
AJNR Am J Neuroradiol ; 33(8): 1557-64, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22403782

ABSTRACT

BACKGROUND AND PURPOSE: Findings on MR imaging of carotid plaques correlate with histologic findings and may be useful in identifying vulnerable plaques. The objective of this study was to show how MR imaging findings and clinical factors could be used to construct a preliminary model and a nomogram for predicting the risk of new ischemic lesions on DWI following CEA or CAS. MATERIALS AND METHODS: One hundred four patients with carotid stenosis undergoing treatment (63 CEA, 41 CAS) were prospectively enrolled (mean age, 71.7 ± 7.0 years; 11 women). T1-SIR and T2-SIR of carotid plaque were measured on MR imaging. Associations among carotid MR imaging findings, treatment procedures, degree of stenosis, cardiovascular risk factors, and occurrence of new ischemic lesions on DWI 1 day after treatment were studied by multivariate logistic regression. RESULTS: One stroke occurred after CAS (2.4%), and none after CEA. New DWI lesions after treatment were observed in 25 patients (24%). Our preliminary prediction model demonstrated that T1-SIR (OR [per 0.5 increase], 3.99; 95% CI, 2.18-7.31; P < .0001) and CAS (OR, 2.06; 95% CI, 1.01-4.24; P = .048 compared with CEA) were positively associated with new DWI lesions on posttreatment DWI scans. T2-SIR (OR [per 0.5 increase], 0.74; 95% CI, 0.55-0.98; P = .037) was negatively associated. The C-index of this model was 0.79 (95% CI, 0.69-0.89), which indicated some utility in predicting the response. CONCLUSIONS: Our preliminary prediction model and nomogram may provide an individualized risk estimate of new ischemic lesions after CEA or CAS and useful information for decision-making regarding treatment strategy.


Subject(s)
Brain Ischemia/etiology , Carotid Artery, Internal/pathology , Carotid Stenosis/surgery , Diffusion Magnetic Resonance Imaging , Endarterectomy, Carotid , Plaque, Atherosclerotic/diagnosis , Stents , Aged , Carotid Artery, Internal/surgery , Carotid Stenosis/pathology , Endarterectomy, Carotid/adverse effects , Female , Humans , Image Processing, Computer-Assisted , Male , Models, Statistical , Nomograms , Risk Assessment , Stents/adverse effects
13.
Diabetologia ; 55(6): 1689-98, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22396012

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to generate induced pluripotent stem (iPS) cells from patients with mitochondrial DNA (mtDNA) mutation. METHODS: Skin biopsies were obtained from two diabetic patients with mtDNA A3243G mutation. The fibroblasts thus obtained were infected with retroviruses encoding OCT4 (also known as POU5F1), SOX2, c-MYC (also known as MYC) and KLF4. The stem cell characteristics were investigated and the mtDNA mutation frequencies evaluated by Invader assay. RESULTS: From the two diabetic patients we isolated four and ten putative mitochondrial disease-specific iPS (Mt-iPS) clones, respectively. Mt-iPS cells were cytogenetically normal and positive for alkaline phosphatase activity, with the pluripotent stem cell markers being detectable by immunocytochemistry. The cytosine guanine dinucleotide islands in the promoter regions of OCT4 and NANOG were highly unmethylated, indicating epigenetic reprogramming to pluripotency. Mt-iPS clones were able to differentiate into derivatives of all three germ layers in vitro and in vivo. The Mt-iPS cells exhibited a bimodal degree of mutation heteroplasmy. The mutation frequencies decreased to an undetectable level in six of 14 clones, while the others showed several-fold increases in mutation frequencies (51-87%) compared with those in the original fibroblasts (18-24%). During serial cell culture passage and after differentiation, no recurrence of the mutation or no significant changes in the levels of heteroplasmy were seen. CONCLUSIONS/INTERPRETATION: iPS cells were successfully generated from patients with the mtDNA A3243G mutation. Mutation-rich, stable Mt-iPS cells may be a suitable source of cells for human mitochondrial disease modelling in vitro. Mutation-free iPS cells could provide an unlimited, disease-free supply of cells for autologous transplantation therapy.


Subject(s)
DNA, Mitochondrial/genetics , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Alkaline Phosphatase/metabolism , Cell Culture Techniques , Cell Differentiation/genetics , Cell Differentiation/physiology , Embryoid Bodies/cytology , Fibroblasts/cytology , Humans , Immunohistochemistry , Karyotype , Kruppel-Like Factor 4 , Microsatellite Repeats/genetics , Mutation
14.
Diabetes Obes Metab ; 13(12): 1123-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21749604

ABSTRACT

AIM: Hypertension often coexists with insulin resistance. However, most metabolic effects of the antihypertensive agents have been investigated in nomotensive animals, in which different conclusions may arise. We investigated the metabolic effects of the new angiotensin II type 1 receptor blocker azilsartan using the obese Koletsky rats superimposed on the background of the spontaneously hypertensive rats. METHODS: Male Koletsky rats were treated with azilsartan (2 mg/kg/day) over 3 weeks. Blood pressure was measured by tail-cuff. Blood biochemical and hormonal parameters were determined by enzymatic or ELISA methods. Gene expression was assessed by RT-PCR. RESULTS: In Koletsky rats, azilsartan treatment lowered blood pressure, basal plasma insulin concentration and the homeostasis model assessment of insulin resistance index, and inhibited over-increase of plasma glucose and insulin concentrations during oral glucose tolerance test. These effects were accompanied by decreases in both food intake and body weight (BW) increase. Although two treatments showed the same effect on BW gain, insulin sensitivity was higher after azilsartan treatment than pair-feeding. Azilsartan neither affected plasma concentrations of triglyceride and free fatty acids, nor increased adipose mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and its target genes such as adiponectin, aP2. In addition, azilsartan downregulated 11ß-hydroxysteroid dehydrogenase type 1 expression. CONCLUSIONS: These results show the insulin-sensitizing effect of azilsartan in obese Koletsky rats. This effect is independent of decreases in food intake and BW increase or of the activation of adipose PPARγ. Our findings indicate the possible usefulness of azilsartan in the treatment of metabolic syndrome.


Subject(s)
Antihypertensive Agents/pharmacology , Benzimidazoles/pharmacology , Blood Glucose/drug effects , Hypertension/drug therapy , Insulin Resistance , Insulin/metabolism , Obesity/metabolism , Oxadiazoles/pharmacology , Animals , Blood Pressure , Enzyme-Linked Immunosorbent Assay , Hypertension/complications , Male , Obesity/complications , PPAR gamma/metabolism , Polymerase Chain Reaction/methods , Rats , Rats, Inbred SHR
15.
AJNR Am J Neuroradiol ; 32(8): 1545-51, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21757531

ABSTRACT

BACKGROUND AND PURPOSE: Arterial spin-labeling is an emerging technique for noninvasive measurement of cerebral perfusion, but concerns remain regarding the reliability of CBF quantification and clinical applications. Recently, an ASL implementation called QUASAR was proposed, and it was shown to have good reproducibility of CBF assessment in healthy volunteers. This study aimed to determine the utility of QUASAR for CBF assessment in patients with cerebrovascular diseases. MATERIALS AND METHODS: Twenty patients with carotid stenosis underwent CBF quantification by ASL (QUASAR) within 3 days of performance of (123)I-iodoamphetamine-SPECT. CVR to acetazolamide also was assessed by ASL and SPECT. In surgically treated patients, the respective scans before and after the procedures were compared. RESULTS: Regional CBF and CVR values measured by ASL were significantly correlated and agreed with those measured by SPECT (r(s) = 0.92 and 0.88, respectively). A Bland-Altman plot demonstrated good agreement between 2 methods in terms of CBF quantification. Furthermore, ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion, equivalent to SPECT. However, ASL tended to overestimate CBF values especially in high-perfusion regions. CONCLUSIONS: ASL perfusion MR imaging is clinically applicable and can be an alternative method for CBF assessment in patients with cerebrovascular diseases.


Subject(s)
Carotid Stenosis/diagnosis , Magnetic Resonance Imaging/methods , Tomography, Emission-Computed, Single-Photon , Aged , Carotid Stenosis/diagnostic imaging , Evaluation Studies as Topic , Female , Humans , Male , Spin Labels
16.
Diabetologia ; 52(4): 675-83, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19169663

ABSTRACT

AIMS/HYPOTHESIS: We have previously demonstrated the therapeutic usefulness of leptin in lipoatrophic diabetes and insulin-deficient diabetes in mouse models and could also demonstrate its dramatic effects on lipoatrophic diabetes in humans. The aim of the present study was to explore the therapeutic usefulness of leptin in a mouse model of type 2 diabetes with increased adiposity. METHODS: To generate a mouse model mimicking human type 2 diabetes with increased adiposity, we used a combination of low-dose streptozotocin (STZ, 120 microg/g body weight) and high-fat diet (HFD, 45% of energy as fat). Recombinant mouse leptin was infused chronically (20 ng [g body weight](-1) h(-1)) for 14 days using a mini-osmotic pump. The effects of leptin on food intake, body weight, metabolic variables, tissue triacylglycerol content and AMP-activated protein kinase (AMPK) activity were examined. RESULTS: Low-dose STZ injection led to a substantial reduction of plasma insulin levels and hyperglycaemia. Subsequent HFD feeding increased adiposity and induced insulin resistance and further augmentation of hyperglycaemia. In this model mouse mimicking human type 2 diabetes (STZ/HFD), continuous leptin infusion reduced food intake and body weight and improved glucose and lipid metabolism with enhancement of insulin sensitivity. Leptin also decreased liver and skeletal muscle triacylglycerol content accompanied by an increase of alpha2 AMPK activity in skeletal muscle. Pair-feeding experiments demonstrated that leptin improved glucose and lipid metabolism independently of the food intake reduction. CONCLUSIONS/INTERPRETATION: This study demonstrates the beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity, indicating the possible clinical usefulness of leptin as a new glucose-lowering drug in humans.


Subject(s)
Adipose Tissue/metabolism , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Dietary Fats/pharmacology , Energy Intake/drug effects , Leptin/therapeutic use , Streptozocin/pharmacology , Weight Loss/drug effects , Adipose Tissue/drug effects , Adipose Tissue/pathology , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Male , Mice , Mice, Inbred C57BL
17.
Endocrinology ; 148(11): 5268-77, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17702848

ABSTRACT

Increased activity of intracellular glucocorticoid reactivating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in obese adipose tissue contributes to adipose dysfunction. As recent studies have highlighted a potential role of preadipocytes in adipose dysfunction, we tested the hypothesis that a variety of metabolic stress mediated by ceramide or AMP-activated protein kinase (AMPK) would regulate 11beta-HSD1 in preadipocytes. The present study is the first to show that 1) expression of 11beta-HSD1 in 3T3-L1 preadipocytes was robustly induced when cells were treated with cell-permeable ceramide analogue C(2) ceramide, bacterial sphingomyelinase, and sphingosine 1-phosphate, 2) 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced activation of AMPK augmented the expression and enzyme activity of 11beta-HSD1, and 3) these results were reproduced in human preadipocytes. We demonstrate for the first time that C(2) ceramide and AICAR markedly induced the expression of CCAAT/enhancer-binding protein (C/EBP) beta and its binding to 11beta-HSD1 promoter. Transient knockdown of C/EBPbeta protein by small interfering RNA markedly attenuated the expression of 11beta-HSD1 induced by C(2) ceramide or AICAR. The present study provides novel evidence that ceramide- and AMPK-mediated signaling pathways augment the expression and activity of 11beta-HSD1 in preadipocytes by way of C/EBPbeta, thereby highlighting a novel, metabolic stress-related regulation of 11beta-HSD1 in a cell-specific manner.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , Adipocytes/metabolism , Ceramides/physiology , Multienzyme Complexes/physiology , Protein Serine-Threonine Kinases/physiology , 3T3-L1 Cells , AMP-Activated Protein Kinases , Adipocytes/cytology , Adipocytes/drug effects , Adipocytes/enzymology , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Animals , CCAAT-Enhancer-Binding Protein-beta/genetics , Cell Differentiation/drug effects , Ceramides/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Mice , Ribonucleotides/pharmacology , Signal Transduction/drug effects
18.
Reprod Domest Anim ; 42(3): 225-9, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17506798

ABSTRACT

The present study was conducted to investigate the effects of bovine follicular fluid (bFF) fractions or epidermal growth factor (EGF) on cumulus cell expansion in bovine cumulus-oocyte complexes (COCs) in vitro. bFF derived from large follicles (15-20 mm) and its fractions (>100, 10-100 and <100 kDa) were added to the medium. Cumulus cell expansion was stimulated when COCs were incubated with the 10-100 and <100 kDa fractions or bFF; in contrast, the culture of COCs with the >100 kDa fraction resulted in the suppression of cumulus cell expansion. Although the >100 kDa fraction prohibited the expansion of cumulus cells in the medium with or without low concentration EGF, cumulus expansion was promoted when COCs were cultured with the >100 kDa fraction and high-concentration EGF. In conclusion, the results suggest that bFF contains promoting and inhibiting effect for expansion of cumulus cells in COCs in vitro. The inhibiting effect of bFF may act antagonistically against the effect of EGF for the event of expanding cumulus cells.


Subject(s)
Epidermal Growth Factor/pharmacology , Follicular Fluid/physiology , Oocytes/drug effects , Ovarian Follicle/cytology , Animals , Cattle , Cells, Cultured , Dose-Response Relationship, Drug , Female , In Vitro Techniques , Oocytes/physiology
19.
Eur J Clin Nutr ; 60(11): 1330-6, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16804556

ABSTRACT

OBJECTIVE: To assess possibility of polyphenol-enriched oolong tea to reduce dietary lipid absorption in humans. DESIGN: Twelve healthy adult subjects, three males and nine females, aged (mean+/-s.d.) 22.0+/-1.8 years, respectively, were randomly divided into two groups. The participants were followed a double-blind placebo-controlled crossover design, including 7-day washout periods and 10-day treatment periods. During the treatment periods, subjects were given about 38 g of lipids from potato chips (19 g each within 30 min after lunch and dinner) and total 750 ml beverages (placebo- or polyphenol-enriched oolong tea) at three meals. Blood samples were collected for biochemical examination at days 8, 18, 25 and 35 of the study period. On the last 3 days of each treatment period, feces were collected to measure the excretion of lipids. RESULTS: Lipid excretion into feces was significantly higher in the polyphenol-enriched oolong tea period (19.3+/-12.9 g/3 day) than in the placebo period (9.4+/-7.3 g/3 day) (P < 0.01). Cholesterol excretion tended to increase in polyphenol-enriched oolong tea period (1.8+/-1.2 g/3 day) compared with that of placebo (1.2+/-0.6 g/3 day) (P = 0.056). CONCLUSIONS: The results of this study indicated that polyphenol-enriched oolong tea could increase lipid excretion into feces when subjects took high-lipid diet.


Subject(s)
Dietary Fats/pharmacokinetics , Feces/chemistry , Flavonoids/pharmacology , Intestinal Absorption/drug effects , Lipids/analysis , Phenols/pharmacology , Tea , Adult , Cholesterol/analysis , Cholesterol/metabolism , Cross-Over Studies , Dietary Fats/administration & dosage , Double-Blind Method , Female , Food, Fortified , Humans , Hypercholesterolemia/diet therapy , Male , Obesity/diet therapy , Polyphenols
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