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Sample records for improves oral glucose

  1. Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion.

    PubMed

    Mizokami, Akiko; Yasutake, Yu; Higashi, Sen; Kawakubo-Yasukochi, Tomoyo; Chishaki, Sakura; Takahashi, Ichiro; Takeuchi, Hiroshi; Hirata, Masato

    2014-12-01

    Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion and pancreatic β-cell proliferation. We previously showed that the effect of GluOC on insulin secretion is mediated largely by glucagon-like peptide-1 (GLP-1) secreted from the intestine in response to GluOC exposure. We have now examined the effect of oral administration of GluOC on glucose utilization as well as the fate of such administered GluOC in mice. Long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level and improved glucose tolerance in mice without affecting insulin sensitivity. It also increased the fasting serum insulin concentration as well as the β-cell area in the pancreas. A small proportion of orally administered GluOC reached the small intestine and remained there for at least 24h. GluOC also entered the general circulation, and the serum GLP-1 concentration was increased in association with the presence of GluOC in the intestine and systemic circulation. The putative GluOC receptor, GPRC6A was detected in intestinal cells, and was colocalized with GLP-1 in some of these cells. Our results suggest that orally administered GluOC improved glucose handling likely by acting from both the intestinal lumen and the general circulation, with this effect being mediated in part by stimulation of GLP-1 secretion. Oral administration of GluOC warrants further study as a safe and convenient option for the treatment or prevention of metabolic disorders. PMID:25230237

  2. Oral Administration of Collagen Hydrolysates Improves Glucose Tolerance in Normal Mice Through GLP-1-Dependent and GLP-1-Independent Mechanisms.

    PubMed

    Iba, Yoshinori; Yokoi, Koji; Eitoku, Itsuka; Goto, Masaki; Koizumi, Seiko; Sugihara, Fumihito; Oyama, Hiroshi; Yoshimoto, Tadashi

    2016-09-01

    The aim of this study was to evaluate the antidiabetic properties of collagen hydrolysates (CHs). CHs exhibited dipeptidyl peptidase-IV inhibitory activity and stimulated glucagon-like-peptide-1 (GLP-1) secretion in vitro. We also determined whether CHs improve glucose tolerance in normal mice. Oral administration of CHs suppressed the glycemic response during the oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT), but the effects were weaker in IPGTT than in OGTT. CHs had no effect on the gastric emptying rate. A pretreatment with the GLP-1 receptor antagonist, exendin 9-39 (Ex9), partially reversed the glucose-lowering effects of CHs, but only when coadministered with glucose. CHs administered 45 min before the glucose load potentiated the glucose-stimulated insulin secretion. This potentiating effect on insulin secretion was not reversed by the pretreatment with Ex9, it appeared to be enhanced. These results suggest that CHs improve glucose tolerance by inhibiting intestinal glucose uptake and enhancing insulin secretion, and also demonstrated that GLP-1 was partially involved in the inhibition of glucose uptake, but not essential for the enhancement of insulin secretion. PMID:27540823

  3. Monitoring breath during oral glucose tolerance tests.

    PubMed

    Ghimenti, S; Tabucchi, S; Lomonaco, T; Di Francesco, F; Fuoco, R; Onor, M; Lenzi, S; Trivella, M G

    2013-03-01

    The evolution of breath composition during oral glucose tolerance tests (OGTTs) was analysed by thermal desorption/gas chromatography/mass spectrometry in 16 subjects and correlated to blood glucose levels. The glucose tolerance tests classified five of the subjects as diabetics, eight as affected by impaired glucose tolerance and three as normoglycaemic. Acetone levels were generally higher in diabetics (average concentration values: diabetics, 300 ± 40 ppbv; impaired glucose tolerance, 350 ± 30 ppbv; normoglycaemic, 230 ± 20 ppbv) but the large inter-individual variability did not allow us to identify the three groups by this parameter alone. The exhalation of 3-hydroxy-butan-2-one and butane-2,3-dione, likely due to the metabolization of glucose by bacteria in the mouth, was also observed. Future work will involve the extension of the analyses to other volatile compounds by attempting to improve the level of discrimination between the various classes of subjects. PMID:23446273

  4. Oral vanadate and Tiron in treatment of diabetes mellitus in rats: improvement of glucose homeostasis and negative side-effects.

    PubMed

    Domingo, J L; Sanchez, D J; Gomez, M; Llobet, J M; Corbella, J

    1993-12-01

    It has been shown that improvement of glucose homeostasis by oral vanadate or vanadyl treatment in streptozotocin-induced diabetic rats is accompanied by severe negative side effects (some deaths, decreased weight gain, alteration in renal function as well as tissue vanadium accumulation) which argue against the use of vanadium compounds in diabetes treatment. The present study was undertaken to assess the effectiveness in alleviating some signs of diabetes in streptozotocin-treated rats with oral therapy with sodium metavanadate (NaVO3) and sodium 4,5 dihydroxybenzene-1,3-disulfonate (Tiron), a chelating agent effective in mobilizing vanadium. In a preliminary experiment, diabetic rats were given aqueous solutions of 0.20 mg NaVO3/ml for 4 days. Vanadium-treated rats which showed blood glucose levels significantly lower (p < 0.001) than vanadate-untreated diabetic rats were selected for subsequent experiments. These animals were given 0.20 mg NaVO3/ml in drinking water and 0, 125.6, 314 or 628 mg Tiron/kg/d by gavage for 2 w. Although most of the animals did not become normoglycemic, several characteristic signs of diabetes (hyperglycemia, hyperphagia and polydipsia) were alleviated by the NaVO3 treatment. The administration of 314 mg Tiron/kg/d (approximately 1 NaVO3: 5 Tiron, mole ratio) did not diminish the ameliorative effects of NaVO3 with respect to diabetes, but significantly decreased the level of vanadium accumulation in target organs. These results show that some of the beneficial effects of NaVO3 are maintained in diabetic animals given Tiron, while the administration of the chelator results in a significant decrease in tissue vanadium accumulation. Accordingly, this would diminish the possibility of toxic side effects derived from prolonged oral vanadium administration.

  5. A Randomized Clinical Trial of an Intensive Behavior Education Program in Gestational Diabetes Mellitus Women Designed to Improve Glucose Levels on the 2-Hour Oral Glucose Tolerance Test.

    PubMed

    Durnwald, Celeste P; Kallan, Michael J; Allison, Kelly C; Sammel, Mary D; Wisch, Susan; Elovitz, Michal; Parry, Samuel

    2016-10-01

    Objective To evaluate whether women with gestational diabetes mellitus (GDM) enrolled in an intensive behavior education program (IBEP) demonstrate lower mean fasting glucose levels on the 2-hour 75 g oral glucose tolerance test (2-hour OGTT) at 6 to 12 weeks postpartum compared with women who undergo routine GDM management. Study Design A prospective randomized controlled trial of women diagnosed with GDM was conducted. Exclusion criteria were GDM diagnosis ≥ 33 weeks or < 20 weeks. Women were randomly assigned to one of two treatment arms: (1) routine GDM management or (2) an IBEP. Women underwent a 2-hour OGTT at 6 to 12 weeks postpartum. Fisher exact test, t-test, and Wilcoxon rank sum test were used as appropriate. Results Of the 101 women randomized, 49 were assigned to IBEP and 52 received routine GDM management. There was no difference in mean fasting and 2-hour glucose levels on the postpartum 2-hour OGTT between the IBEP and routine management group (88.5 ± 22.9 mg/dL vs. 85.2 ± 13.3 mg/dL, p = 0.49 and 109.8 ± 38.5 mg/dL vs. 109.4 ± 40.8 mg/dL, p = 0.97, respectively). Conclusion GDM women enrolled in a healthy lifestyle intervention program did not demonstrate lower glucose values on the postpartum 2-hour OGTT.

  6. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    PubMed

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P < 0.05 or 0.001). These results suggested that RRDY and yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models. PMID:27499387

  7. Analgesic Effect of Oral Glucose in Neonates.

    PubMed

    Jatana, S K; Dalal, S S; Wilson, C G

    2003-04-01

    The International Association for the Study of Pain, has defined pain as "an unpleasant sensory and emotional experience connected with actual or potential tissue damage or described in terms of such damage". It was thought that the newborn baby does not experience pain because of incompletely developed nervous system. However, it has been shown that neurological system known to be associated with pain transmission and modulation, is intact and functional. A study was conducted in our center to study the analgesic effect of administration of oral glucose in various concentrations, in neonates undergoing heel punctures, for collection of blood for investigations. This was compared with the analgesic effects of breast milk (which contains lactose). 125 full term normal neonates with no history of birth asphyxia or underlying neurological abnormality, requiring heel punctures for collection of blood for various investigations were selected for the study. They were matched for gestational age, birth weight and sex distribution and divided into 5 groups of 25 each. One group comprised control subjects and was administered sterile water. 3 groups were administered 1 ml of varying strengths of glucose solutions i.e. 10%, 25% and 50% respectively. The last group was given 1 ml of expressed breast milk (EBM). Prior to heel pricks, state of arousal, baseline heart rate (HR) and transcutaneous oxygen saturation (SpO2) were recorded by pulse oximeter in each neonate. Autolet, a mechanical device for capillary sampling, was used for heel pricks to give equal strength of painful stimulus in each procedure. Audio tape recorder was used to record the cry. The oral solution was administered slowly over 30 seconds by means of a syringe placed in the mouth. Heel puncture was done after 2 minutes, taking all aseptic precautions. HR and SpO2 were monitored using pulse oximeter. Pain response was assessed, by recording duration of crying, change in HR, change in SpO2 and facial action

  8. Evaluation of a Self-Administered Oral Glucose Tolerance Test

    PubMed Central

    Bethel, M. Angelyn; Price, Hermione C.; Sourij, Harald; White, Sarah; Coleman, Ruth L.; Ring, Arne; Kennedy, Irene E.C.; Tucker, Lynne; Holman, Rury R.

    2013-01-01

    OBJECTIVE To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes. PMID:23321216

  9. Diagnostic value of fasting capillary glucose, fructosamine and glycosylated haemoglobin in detecting diabetes and other glucose tolerance abnormalities compared to oral glucose tolerance test.

    PubMed

    Herdzik, E; Safranow, K; Ciechanowski, K

    2002-04-01

    New diagnostic criteria for diabetes mellitus recommend lowering of the fasting plasma glucose to 7.0 mmol/l. In contrast to recommendations of the American Diabetes Association (ADA), WHO recommends using the oral glucose tolerance test (OGTT) in clinical practice. In this study. based on OGTT results and WHO 1998 criteria, we determined if measuring fasting capillary glycaemia (FCG) along with fructosamine and/or glycosylated haemoglobin allows the detection of glucose tolerance abnormalities better than FCG alone. OGTT was performed in 538 patients. Serum fructosamine was determined in 480 of the patients, and glycosylated haemoglobin in 234 of the patients. According to WHO 1998 criteria, the patients were divided into groups due to glucose tolerance abnormalities. Fructosamine correlated stronger with 2-h post-load glucose concentrations than with FCG. HbAlc correlated stronger with FCG than with 2-h post-load glucose. Combined use of fructosamine and FCG predicted 2-h post-load glucose better than combined use of FCG and HbA1c. Receiver operating characteristic curve analyses showed that FCG was the best criterion in discriminating diabetes. Combined use of FCG and fructosamine slightly improved the ability to discriminate glucose tolerance abnormalities from normal glucose tolerance. FCG is the most effective predictor of 2-h post-load glucose and the best criterion for discriminating diabetes and other glucose tolerance abnormalities from normal glucose tolerance. Fructosamine is a potentially useful post-load glycaemia index. OGTT is irreplaceable in identification of patients with high post-load glycaemia.

  10. Prediabetes Phenotype Influences Improvements in Glucose Homeostasis with Resistance Training

    PubMed Central

    Eikenberg, Joshua D.; Savla, Jyoti; Marinik, Elaina L.; Davy, Kevin P.; Pownall, John; Baugh, Mary E.; Flack, Kyle D.; Boshra, Soheir; Winett, Richard A.; Davy, Brenda M.

    2016-01-01

    Purpose To determine if prediabetes phenotype influences improvements in glucose homeostasis with resistance training (RT). Methods Older, overweight individuals with prediabetes (n = 159; aged 60±5 yrs; BMI 33±4 kg/m2) completed a supervised RT program twice per week for 12 weeks. Body weight and composition, strength, fasting plasma glucose, 2-hr oral glucose tolerance, and Matsuda-Defronza estimated insulin sensitivity index (ISI) were assessed before and after the intervention. Participants were categorized according to their baseline prediabetes phenotype as impaired fasting glucose only (IFG) (n = 73), impaired glucose tolerance only (IGT) (n = 21), or combined IFG and IGT (IFG/IGT) (n = 65). Results Chest press and leg press strength increased 27% and 18%, respectively, following the 12-week RT program (both p<0.05). Waist circumference (-1.0%; pre 109.3±10.3 cm, post 108.2±10.6 cm) and body fat (-0.6%; pre 43.7±6.8%, post 43.1±6.8%) declined, and lean body mass (+1.3%; pre 52.0±10.4 kg, post 52.7±10.7 kg) increased following the intervention. Fasting glucose concentrations did not change (p>0.05) following the intervention. However, 2-hr oral glucose tolerance improved in those with IGT (pre 8.94±0.72 mmol/l, post 7.83±1.11 mmol/l, p<0.05) and IFG/IGT (pre 9.66±1.11mmol/l, post 8.60±2.00 mmol/l) but not in those with IFG (pre 6.27±1.28mmol/l, post 6.33± 1.55 mmol/l). There were no significant changes in ISI or glucose area under the curve following the RT program. Conclusions RT without dietary intervention improves 2-hr oral glucose tolerance in individuals with prediabetes. However, the improvements in glucose homeostasis with RT appear limited to those with IGT or combined IFG and IGT. Trial Registration ClinicalTrials.gov: NCT01112709 PMID:26840904

  11. Effect of oral glucose on serum zinc in the elderly

    SciTech Connect

    Lopez, A.L.; Kohrs, M.B.; Horwitz, D.L.; Cyborski, C.K.; Czajka-Narins, D.M.; Kamath, S.

    1986-03-05

    To determine the effect of glucose loading on serum zinc concentrations, 34 elderly subjects aged 60-86 y were studied. Anthropometric data, medical and dietary histories were obtained. Serum zinc and glucose concentrations were obtained fasting and 1/2, 1, 1 1/2, 2 and 3 h after 75 g oral glucose load; glycohemoglobin and fasting serum lipids were also determined. For comparison, the subjects were categorized as: normal or low serum zinc concentrations; normal or high body mass index BMI; normal or high sum of skinfolds and normal or high serum cholesterol. Results showed that low serum zinc concentrations increased significantly over baseline values after the glucose load and did not return to fasting levels. On the other hand, mean serum zinc concentrations significantly declined without recovery for those with normal zinc values. For the total group, no significant differences were noted between fasting values and subsequent time periods. No correlations were noted between fasting serum zinc and area under the curve for zinc except in the high BMI group (positive correlation observed). For the high BMI group, fasting serum zinc differed significantly from the succeeding measurements except for 30 min. For the group as a whole, mean serum zinc concentration was within normal limits (76.9 +/- 2.8 mcg/ml): mean zinc intake was less than 2/3rds the RDA. They conclude that glucose ingestion may alter serum zinc and should be considered in interpreting these levels.

  12. Improvements in glucose tolerance with Bikram Yoga in older obese adults: a pilot study.

    PubMed

    Hunter, Stacy D; Dhindsa, Mandeep; Cunningham, Emily; Tarumi, Takashi; Alkatan, Mohammed; Tanaka, Hirofumi

    2013-10-01

    Bikram yoga is an exotic form of physical activity combining hatha yoga and thermal therapy that could positively impact metabolic health. Although this increasingly popular alternative exercise may be ideal for obese adults due to its low impact nature, few studies have elucidated the health benefits associated with it. As an initial step, we determined the effect of Bikram yoga on glucose tolerance. Fourteen young lean and 15 older obese subjects completed an 8-week Bikram yoga intervention in which classes were completed 3 times per week. Glucose tolerance was assessed using a 75 g oral glucose tolerance test. The area under the glucose curve following the oral glucose tolerance test was significantly reduced as a result of the Bikram Yoga intervention in older obese (P < 0.05) but not in young lean subjects. We concluded that a short-term Bikram yoga intervention improved glucose tolerance in older obese, but not in young lean adults. PMID:24138995

  13. Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

    PubMed

    Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

    1995-05-01

    A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects. PMID:7587920

  14. Nanoemulsion: for improved oral delivery of repaglinide.

    PubMed

    Akhtar, Juber; Siddiqui, Hefazat Hussain; Fareed, Sheeba; Badruddeen; Khalid, Mohammad; Aqil, Mohammed

    2016-07-01

    Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic β-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months. PMID:27187792

  15. Quality Improvement Efforts in Pediatric Oral Health.

    PubMed

    Ng, Man Wai

    2016-04-01

    Quality improvement (QI) and measurement are increasingly used in health care to improve patient care and outcomes. Despite current barriers in oral health measurement, there are nascent QI and measurement efforts emerging. This paper describes the role that QI and measurement can play in improving oral health care delivery in clinical practice by presenting a QI initiative that aimed to test and implement a chronic disease management approach to address early childhood caries. PMID:27265978

  16. Serum progranulin concentrations are not responsive during oral lipid tolerance test and oral glucose tolerance test.

    PubMed

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2015-07-01

    The postprandial regulation of progranulin by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of progranulin in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 hours (h) (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. A novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of progranulin were measured by enzyme-linked immunosorbent assay (ELISA). Circulating progranulin levels remained unchanged during OLTT and OGTT. Fasting progranulin levels ranged between 31.3±8.7 and 40.6±7.7 ng/ml and were not different in subgroups addressing BMI, gender, family history, smoking habits, and hormonal contraception. There was a reciprocal correlation of progranulin with HDL (negative) and LDL cholesterol levels (positive). In healthy adults, fasting and postprandial circulating progranulin levels are not different in BMI subgroups. Oral uptake of carbohydrates and lipids does not influence circulating progranulin levels in a short-term manner. A postprandial and short-term regulation of this adipokine is absent, at least in healthy subjects. There is a negative correlation of progranulin with HDL cholesterol, but a positive correlation with LDL cholesterol. This reciprocal association might be of physiological importance for an individual's atherosclerotic risk. PMID:25565096

  17. A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin.

    PubMed

    Li, Lei; Jiang, Guohua; Yu, Weijiang; Liu, Depeng; Chen, Hua; Liu, Yongkun; Huang, Qin; Tong, Zaizai; Yao, Juming; Kong, Xiangdong

    2016-12-01

    Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers. PMID:27612686

  18. [Role of classical oral glucose-lowering medications in current treatment].

    PubMed

    Carramiñana Barrera, F C

    2014-07-01

    Classical oral glucose were discovered in the mid twentieth century. Despite the time elapsed since then and the lack of large studies to support the use of some of these drugs, they continue to be employed, are indicated in all clinical practice guidelines and consensus documents and, overall, remain among the most widely prescribed drugs in the national health system. The main arguments for their continued use are their widespread and prolonged prescription, their effectiveness, and cost. Their main disadvantages have always been and continue to be their adverse gastrointestinal effects, weight gain, the risk of hypoglycemia and other adverse effects, which have encouraged the development of new glucose-lowering drugs with an improved pharmacological profile that would cover the various mechanisms of hyperglycemia. Currently, deep knowledge of glucose-lowering drugs is required in the patient-centered management of diabetes. Furthermore, this knowledge should be adapted to each individual patient to acquire the experience necessary to achieve effective metabolic control, delay the development of chronic complications, and improve the quality of life and life expectancy of patients with diabetes.

  19. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    PubMed

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. PMID:26472183

  20. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    PubMed

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice.

  1. Improving Children’s Oral Health

    PubMed Central

    Casamassimo, P.S.; Lee, J.Y.; Marazita, M.L.; Milgrom, P.; Chi, D.L.; Divaris, K.

    2014-01-01

    Despite the concerted efforts of research and professional and advocacy stakeholders, recent evidence suggests that improvements in the oral health of young children in the United States has not followed the prevailing trend of oral health improvement in other age groups. In fact, oral health disparities in the youngest children may be widening, yet efforts to translate advances in science and technology into meaningful improvements in populations’ health have had limited success. Nevertheless, the great strides in genomics, biological, behavioral, social, and health services research in the past decade have strengthened the evidence base available to support initiatives and translational efforts. Concerted actions to accelerate this translation and implementation process are warranted; at the same time, policies that can help tackle the upstream determinants of oral health disparities are imperative. This article summarizes the proceedings from the symposium on the interdisciplinary continuum of pediatric oral health that was held during the 43rd annual meeting of the American Association for Dental Research, Charlotte, North Carolina, USA. This report showcases the latest contributions across the interdisciplinary continuum of pediatric oral health research and provides insights into future research priorities and necessary intersectoral synergies. Issues are discussed as related to the overwhelming dominance of social determinants on oral disease and the difficulty of translating science into action. PMID:25122218

  2. Conversion of oral glucose to lactate in dogs. Primary site and relative contribution to blood lactate

    SciTech Connect

    Youn, J.H.; Bergman, R.N. )

    1991-06-01

    The authors evaluated the relative contribution of oral glucose to arterial lactate and the relative role of the splanchnic bed in converting glucose to lactate in dogs. After an oral glucose load (1.2 g/kg) spiked with (U-14C)glucose (16.9 muCi/kg; protocol 1, n = 7), arterial blood lactate increased from 0.43 {plus minus} 0.03 mM at basal to a peak of 1.04 {plus minus} 0.07 mM at 45 min and then slowly decreased to 0.47 {plus minus} 0.07 mM at 240 min. Arterial blood {sup 14}Clactate peaked at 60 min and then decreased to {approximately} 35% of the peak at 4 h. When arterial blood lactate peaked at 45 min, the proportion of arterial lactate that was derived from oral glucose was 34 {plus minus} 3%. The integrated area under the curve of lactate derived from exogenous glucose was 40 {plus minus} 2% of that of total lactate. The splanchnic bed released lactate and {sup 14}Clactate during the initial 2 h after oral {sup 14}Cglucose. Thus, the splanchnic bed apparently contributed to the conversion of exogenous glucose to lactate. In the matched experiments (protocol 2, n = 5), dogs were given the same amount of oral glucose but no {sup 14}Cglucose, and (U-14C)lactate was infused into the right atrium to match the splanchnic {sup 14}Clactate release from the first experiment. Despite a well-matched splanchnic {sup 14}Clactate contribution, arterial concentrations of {sup 14}Clactate were markedly lower in protocol 2 compared with protocol 1. The integrated area under the {sup 14}Clactate profile in protocol 2 was only 11 {plus minus} 1% of that in protocol 1. These results indicate that the splanchnic bed is responsible for only 11% of arterial blood lactate that was derived from oral glucose. They concluded that (1) after oral glucose loading, a major portion of circulating lactate has its origin not in exogenous glucose but in endogenous sources, and (2) the splanchnic bed is not the major site of oral glucose conversion to lactate after glucose ingestion.

  3. Pancreatic islet hormone response to oral glucose in morbidly obese patients.

    PubMed Central

    Sirinek, K R; O'Dorisio, T M; Howe, B; McFee, A S

    1985-01-01

    Pancreatic islet peptides, as well as other gastrointestinal hormones, have been implicated in both the pathogenesis of obesity and the etiology of associated metabolic derangements. This study evaluated the pancreatic islet and gastrointestinal (GI) hormone response to oral glucose in 20 morbidly obese (151% above ideal body weight) patients. Glucose intolerance, hyperinsulinism, and exaggerated gastric inhibitory polypeptide (GIP) release occurred following glucose ingestion. Significant release of PP occurred in 14 patients, while only six patients had release of somatostatin. No significant changes in plasma concentrations of glucagon occurred. Since GIP is insulinotropic in the presence of hyperglycemia, the hyperinsulinism of morbid obesity may be secondary to the abnormally high glucose-stimulated GIP levels in these patients. Failure of glucagon suppression in response to oral glucose many contribute to the hyperglycemia noted. Somatostatin and pancreatic polypeptide may be responsible for some of the metabolic derangements of morbid obesity. PMID:2860876

  4. Failure of Hyperglycemia and Hyperinsulinemia to Compensate for Impaired Metabolic Response to an Oral Glucose Load

    PubMed Central

    Hussain, M; Janghorbani, M; Schuette, S; Considine, RV; Chisholm, RL; Mather, KJ

    2014-01-01

    Objective To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Methods Non-obese, obese normoglycemic and obese Type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. Results Breath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. Conclusions Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes. PMID:25511878

  5. Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

    PubMed Central

    Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

    2014-01-01

    Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

  6. Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

    SciTech Connect

    Radziuk, J. )

    1989-08-01

    The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or (3-{sup 3}H)glucose and a marker for gluconeogenesis, (U-{sup 14}C)lactate or sodium ({sup 14}C)bicarbonate ({sup 14}C)bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ((6-{sup 3}H)glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of ({sup 14}C)glucose production or for dilution of {sup 14}C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from (U-{sup 14}C)-lactate incorporation and 7.4 +/- 1.3 g calculated using ({sup 14}C)bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for (U-{sup 14}C)lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with ({sup 14}C)bicarbonate as tracer (P less than 0.05, vs. ({sup 14}C)-lactate as tracer). When (2-{sup 14}C)acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that {sup 14}CO{sub 2} is a potentially useful marker for the gluconeogenetic process in vivo.

  7. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load.

    PubMed

    Walsh, Lauren K; Restaino, Robert M; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

    2016-11-01

    Postprandial hyperglycaemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. In the present study, we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500 mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycaemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, and at 60 and 120 min after an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized cross-over design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycaemia under the placebo condition (-32% at 60 min and -28% at 120 min post oral glucose load; P<0.05 from baseline) but not under the TUDCA condition (-4% at 60 min and +0.3% at 120 min post oral glucose load; P>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and thiobarbituric acid reactive substance (TBARS) remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycaemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycaemia.

  8. Novel Glucagon-Like Peptide-1 Analog Delivered Orally Reduces Postprandial Glucose Excursions in Porcine and Canine Models

    PubMed Central

    Eldor, Roy; Kidron, Miriam; Greenberg-Shushlav, Yael; Arbit, Ehud

    2010-01-01

    Background Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, β-cell function preservation, improved lipid profiles, and increased insulin sensitivity. Thus, GLP-1 harbors significant therapeutic potential for regulating type 2 diabetes mellitus, where its physiological impact is markedly impaired. To date, GLP-1 analogs are only available as injectable dosage forms, and its oral delivery is expected to provide physiological portal/peripheral concentration ratios while fostering patient compliance and adherence. Methods Healthy, fasting, enterically cannulated pigs and beagle canines were administered a single dose of the exenatide-based ORMD-0901 formulation 30 min before oral glucose challenges. Blood samples were collected every 15 min for evaluation of ORMD-0901 safety and efficacy in regulating postchallenge glucose excursions. Results Enterically delivered ORMD-0901 was well tolerated by all animals. ORMD-0901 formulations RG3 and AG2 led to reduced glucose excursions in pigs when delivered prior to a 5 g/kg glucose challenge, where area under the curve (AUC)0–120 values were up to 43% lower than in control sessions. All canines challenged with a glucose load with no prior exposure to exenatide, demonstrated higher AUC0–150 values than in their exenatide-treated sessions. Subcutaneous exenatide delivery amounted to a 51% reduction in mean glucose AUC0–150, while formulations AG4 and AG3 prompted 43% and 29% reductions, respectively. Conclusions When delivered enterically, GLP-1 (ORMD-0901) is absorbed from the canine and porcine gastrointestinal tracts and retains its biological activity. Further development of this drug class in an oral dosage form is expected to enhance diabetes control and patient compliance. PMID:21129350

  9. Policies for Improving Oral Health in Europe

    ERIC Educational Resources Information Center

    Blinkhorn, Anthony S.; Downer, Martin C.; Drugan, Caroline S.

    2005-01-01

    Background and Objective: The main purpose of this review was to rehearse the available evidence of good practice in dental public health in order to define policies that could improve oral health in the enlarged European Union and associated countries. Secondary objectives were to describe the basic principles of health service organisation and…

  10. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

    PubMed

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-03-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation.

  11. Colestimide improves glycemic control via hepatic glucose production in db/db mice.

    PubMed

    Yamakawa, Tadashi; Ogihara, Kikumi; Utsunomiya, Hirotoshi; Muraoka, Tomonori; Kadonosono, Kazuaki; Terauchi, Yasuo

    2014-01-01

    The objective of this study was to assess the chronic effects of a bile acid sequestrant, colestimide, on glucose metabolism. After db/db mice were fed a diet containing colestimide or cholic acid (CA) for 12 weeks, we investigated the impact of these agents on glucose and lipid metabolism. Colestimide significantly reduced the elevated fasting blood glucose level (p<0.01), and CA even more markedly reduced fasting blood glucose. The blood glucose level after an oral glucose load was significantly lower in the CA group than in the control group, but the colestimide group showed no significant difference. The insulin response to a glucose load was abolished in the control and colestimide groups. A hyperinsulinemic-euglycemic clamp study revealed that colestimide significantly improved the GIR (p=0.013). Hepatic EGP and Rd were also improved by colestimide, suggesting that it alleviated insulin resistance by suppressing hepatic glucose production and increasing peripheral glucose usage. CA significantly increased both the weight and cholesterol content of the liver, while colestimide reduced these parameters. Colestimide suppressed hepatic gene expression of SHP, but enhanced SREBP2 expression. On the other hand, CA increased the expression of SHP and lipogenic enzymes such as ACC and SCD-1, but had no effect on SREBP2. The present study demonstrated that colestimide improves hyperglycemia and hyperlipidemia, as well as reducing the hepatic lipid content. In contrast, CA exacerbates hyperlipidemia and increases the hepatic lipid content, although it improves glycemic control. Thus, colestimide is a well-balanced drug for the treatment of diabetes mellitus.

  12. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  13. Selenium-enriched exopolysaccharides improve skeletal muscle glucose uptake of diabetic KKAy mice via AMPK pathway.

    PubMed

    Zhou, Xihong; Chen, Jingqing; Wang, Fengqin; Yang, Hangxian; Yang, Ren; Wang, Xinxia; Wang, Yizhen

    2014-06-01

    Selenium-enriched exopolysaccharides (EPS) produced by Enterobacter cloacae Z0206 have been proven to possess effect on reducing blood glucose level in diabetic mice. To investigate the specific mechanism, we studied the effects of oral supply with EPS on skeletal muscle glucose transportation and consumption in high-fat-diet-induced diabetic KKAy mice. We found that EPS supplementation increased expressions of glucose transporter 4 (Glut4), hexokinase 2 (hk2), phosphorylation of AMP-activated kinase subunit α2 (pAMPKα2), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and increased expression of characteristic protein of oxidative fibers such as troponin I and cytochrome c (Cytc). Furthermore, we found that EPS increased glucose uptake and expressions of pAMPKα2 and PGC-1α in palmitic acid (PA)-induced C2C12 cells. However, while EPS inhibited AMPKα2 with interference RNA (iRNA), effects of EPS on the improvement of glucose uptake diminished. These results indicated that EPS may improve skeletal muscle glucose uptake of diabetic KKAy mice through AMPKα2-PGC-1α pathway. PMID:24729044

  14. In search of a super solution: controlled trial of glycine-glucose oral rehydration solution in infantile diarrhoea.

    PubMed

    Patra, F C; Mahalanabis, D; Jalan, K N; Sen, A; Banerjee, P

    1984-01-01

    In a double blind trial a glycine fortified oral glucose electrolyte solution was evaluated in a group of infants and small children (n=25) with moderate to severe dehydration due to acute diarrhoea, and was compared with a matched control group (n=26) receiving only glucose based oral rehydration solution. It is seen that the diarrhoea stool output, duration of diarrhoea, and volume of oral rehydration fluid required to achieve and maintain hydration are significantly lower in the group receiving glycine fortified glucose electrolyte solution. The possibility of developing an oral rehydration solution which could also act as an absorption promoting drug is discussed.

  15. Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

    PubMed

    Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

    2015-02-15

    Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro.

  16. Oral glucose for pain relief during examination for retinopathy of prematurity: a masked randomized clinical trial

    PubMed Central

    da Costa, Marlene Coelho; Eckert, Gabriela Unchalo; Fortes, Bárbara Gastal Borges; Filho, João Borges Fortes; Silveira, Rita C.; Procianoy, Renato S

    2013-01-01

    OBJECTIVE: Ophthalmologic examination for retinopathy of prematurity is a painful procedure. Pharmacological and non-pharmacological interventions have been proposed to reduce pain during eye examinations. This study aims to evaluate the analgesic effect of 25% glucose using a validated pain scale during the first eye examination for retinopathy of prematurity in preterm infants with birth weight ≤1,500 g and/or gestational age ≤32 weeks. METHODS: A masked, randomized clinical trial for one dose of 1 ml of oral 25% glucose solution 2 minutes before the first ophthalmologic examination for retinopathy of prematurity was conducted between March 2008 and April 2010. The results were compared to those of a control group that did not receive oral glucose solution. Pain was evaluated using a Neonatal Infant Pain Scale immediately before and immediately after the ophthalmologic examination in both groups. Clinicaltrials.gov: NCT00648687 RESULTS: One hundred and twenty-four patients who were examined for the first time for retinopathy of prematurity were included. Seventy were included in the intervention group and 54 in the control group. The number of patients with pain immediately before the procedure was similar in both groups. The number of patients with pain after ophthalmologic examination was 15.7% in the intervention group and 68.5% in the control group (p<0.001). CONCLUSIONS: One ml of oral 25% glucose solution given 2 minutes before an ophthalmologic examination for retinopathy of prematurity was an effective measure for pain relief. PMID:23525316

  17. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients

    PubMed Central

    Handisurya, Ammon; Kerscher, Corinna; Tura, Andrea; Herkner, Harald; Payer, Berit Anna; Mandorfer, Mattias; Werzowa, Johannes; Winnicki, Wolfgang; Reiberger, Thomas; Kautzky-Willer, Alexandra; Pacini, Giovanni; Säemann, Marcus; Schmidt, Alice

    2016-01-01

    Background Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. Methods In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). Results After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82–441.92) vs. 468.80 (414.27–488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032–0.106) vs. 0.083 (0.054–0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. Conclusions HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV

  18. Oral rehydration in infantile diarrhoea. Controlled trial of a low sodium glucose electrolyte solution.

    PubMed Central

    Chatterjee, A; Mahalanabis, D; Jalan, K N; Maitra, T K; Agarwal, S K; Dutta, B; Khatua, S P; Bagchi, D K

    1978-01-01

    The paper describes the first controlled trial of an oral glucose electrolyte solution designed on the basis of the optimum pathophysiological needs for rehydration in infantile diarrahoea. The solution, having a sodium concentration of 50 mmol/l, was tried in a group of 20 infants with moderate to severe dehydration due to acute diarrhoea and was compared with a matched group of 19 infants predominantly under 2 years of age taking a 'standard' oral solution with a sodium concentration of 90 mmol/l. They could be hydrated as well with a low sodium oral solution alone as with the standard solution. Intravenous fluid was not required in either group. The group treated with the high soldium 'standard' solution appeared to develop hypernatraemia and/or periorbital oedema more frequently than the other group. Also, the low sodium solution eliminated the need for additional free water orally. PMID:348125

  19. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

    PubMed

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine; Duchampt, Adeline; Bäckhed, Fredrik; Mithieux, Gilles

    2016-07-12

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. PMID:27411015

  20. Combined glucose ingestion and mouth rinsing improves sprint cycling performance.

    PubMed

    Chong, Edwin; Guelfi, Kym J; Fournier, Paul A

    2014-12-01

    This study investigated whether combined ingestion and mouth rinsing with a carbohydrate solution could improve maximal sprint cycling performance. Twelve competitive male cyclists ingested 100 ml of one of the following solutions 20 min before exercise in a randomized double-blinded counterbalanced order (a) 10% glucose solution, (b) 0.05% aspartame solution, (c) 9.0% maltodextrin solution, or (d) water as a control. Fifteen min after ingestion, repeated mouth rinsing was carried out with 11 × 15 ml bolus doses of the same solution at 30-s intervals. Each participant then performed a 45-s maximal sprint effort on a cycle ergometer. Peak power output was significantly higher in response to the glucose trial (1188 ± 166 W) compared with the water (1036 ± 177 W), aspartame (1088 ± 128 W) and maltodextrin (1024 ± 202 W) trials by 14.7 ± 10.6, 9.2 ± 4.6 and 16.0 ± 6.0% respectively (p < .05). Mean power output during the sprint was significantly higher in the glucose trial compared with maltodextrin (p < .05) and also tended to be higher than the water trial (p = .075). Glucose and maltodextrin resulted in a similar increase in blood glucose, and the responses of blood lactate and pH to sprinting did not differ significantly between treatments (p > .05). These findings suggest that combining the ingestion of glucose with glucose mouth rinsing improves maximal sprint performance. This ergogenic effect is unlikely to be related to changes in blood glucose, sweetness, or energy sensing mechanisms in the gastrointestinal tract.

  1. The long term oral regulation of blood glucose in diabetic patients by using of Escherichia coli Nissle 1917 expressing CTB-IGF-1 hybrid protein.

    PubMed

    Bazi, Zahra; Jalili, Mahsa; Hekmatdoost, Azita

    2013-11-01

    Regarding to the high prevalence and comorbidities of chronic high blood glucose in diabetic patients and the limited efficacy and current painful treatments. It is necessary to improve new treatments that are non-invasive and long-term for controlling blood glucose. Recent studies have shown that the healthy microflora in different body organs can perform as the gene vectors for expressing different types of gene therapies in situ. We have proposed that by constructing a recombinant Escherichia coli Nissle 1917 that expresses CTB-IGF-1 hybrid gene under control of ompC glucose sensitive promoter, the intestinal glucose level can be regulated. This method in comparison with other methods is a non-invasive way to control the blood glucose orally and it can be used for all types of diabetes. PMID:24074833

  2. Improvement in glucose biosensing response of electrochemically grown polypyrrole nanotubes by incorporating crosslinked glucose oxidase.

    PubMed

    Palod, Pragya Agar; Singh, Vipul

    2015-10-01

    In this paper a novel enzymatic glucose biosensor has been reported in which platinum coated alumina membranes (Anodisc™s) have been employed as templates for the growth of polypyrrole (PPy) nanotube arrays using electrochemical polymerization. The PPy nanotube arrays were grown on Anodisc™s of pore diameter 100 nm using potentiostatic electropolymerization. In order to optimize the polymerization time, immobilization of glucose oxidase (GOx) was first performed using physical adsorption followed by measuring its biosensing response which was examined amperometrically for increasing concentrations of glucose. In order to further improve the sensing performance of the biosensor fabricated for optimum polymerization duration, enzyme immobilization was carried out using cross-linking with glutaraldehyde and bovine serum albumin (BSA). Approximately six fold enhancement in the sensitivity was observed in the fabricated electrodes. The biosensors also showed a wide range of linear operation (0.2-13 mM), limit of detection of 50 μM glucose concentration, excellent selectivity for glucose, notable reliability for real sample detection and substantially improved shelf life. PMID:26117773

  3. Improvement in glucose biosensing response of electrochemically grown polypyrrole nanotubes by incorporating crosslinked glucose oxidase.

    PubMed

    Palod, Pragya Agar; Singh, Vipul

    2015-10-01

    In this paper a novel enzymatic glucose biosensor has been reported in which platinum coated alumina membranes (Anodisc™s) have been employed as templates for the growth of polypyrrole (PPy) nanotube arrays using electrochemical polymerization. The PPy nanotube arrays were grown on Anodisc™s of pore diameter 100 nm using potentiostatic electropolymerization. In order to optimize the polymerization time, immobilization of glucose oxidase (GOx) was first performed using physical adsorption followed by measuring its biosensing response which was examined amperometrically for increasing concentrations of glucose. In order to further improve the sensing performance of the biosensor fabricated for optimum polymerization duration, enzyme immobilization was carried out using cross-linking with glutaraldehyde and bovine serum albumin (BSA). Approximately six fold enhancement in the sensitivity was observed in the fabricated electrodes. The biosensors also showed a wide range of linear operation (0.2-13 mM), limit of detection of 50 μM glucose concentration, excellent selectivity for glucose, notable reliability for real sample detection and substantially improved shelf life.

  4. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    PubMed

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C

  5. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss.

    PubMed

    Esler, William P; Rudolph, Joachim; Claus, Thomas H; Tang, Weifeng; Barucci, Nicole; Brown, Su-Ellen; Bullock, William; Daly, Michelle; Decarr, Lynn; Li, Yaxin; Milardo, Lucinda; Molstad, David; Zhu, Jian; Gardell, Stephen J; Livingston, James N; Sweet, Laurel J

    2007-11-01

    Ghrelin, through action on its receptor, GH secretagogue receptor type 1a (GHS-R1a), exerts a variety of metabolic functions including stimulation of appetite and weight gain and suppression of insulin secretion. In the present study, we examined the effects of novel small-molecule GHS-R1a antagonists on insulin secretion, glucose tolerance, and weight loss. Ghrelin dose-dependently suppressed insulin secretion from dispersed rat islets. This effect was fully blocked by a GHS-R1a antagonist. Consistent with this observation, a single oral dose of a GHS-R1a antagonist improved glucose homeostasis in an ip glucose tolerance test in rat. Improvement in glucose tolerance was attributed to increased insulin secretion. Daily oral administration of a GHS-R1a antagonist to diet-induced obese mice led to reduced food intake and weight loss (up to 15%) due to selective loss of fat mass. Pair-feeding experiments indicated that weight loss was largely a consequence of reduced food intake. The impact of a GHS-R1a antagonist on gastric emptying was also examined. Although the GHS-R1a antagonist modestly delayed gastric emptying at the highest dose tested (10 mg/kg), delayed gastric emptying does not appear to be a requirement for weight loss because lower doses produced weight loss without an effect on gastric emptying. Consistent with the hypothesis that ghrelin regulates feeding centrally, the anorexigenic effects of potent GHS-R1a antagonists in mice appeared to correspond with their brain exposure. These observations demonstrate that GHS-R1a antagonists have the potential to improve the diabetic condition by promoting glucose-dependent insulin secretion and promoting weight loss.

  6. Return for Postpartum Oral Glucose Tolerance Test Following Gestational Diabetes Mellitus.

    PubMed

    Mohd Suan, Mohd Azri

    2015-09-01

    A cross-sectional study was conducted to assess the prevalence and characteristics of women who received a postpartum oral glucose tolerance test and to examine barriers as reported by women who failed to return for the test. Data were collected using a mobile phone-based short messaging service. Only 352 (81.9%) women returned for the test. Women who failed to return for the test were younger (30.1 vs 32.1, P = .003) and did not have a previous history of gestational diabetes (93.6% vs 84.9%, P = .043) compared to women who returned for the test. The commonest reasons given for not returning for the test was "Still waiting for the appointment date for the test" (37.2%), "had family/health problems" (11.5%), and "busy/no time" (10.3%). Flexible time for the test, active involvement from health care staff, and strengthening continuous care system were among the interventions needed to improve the return rate for this screening test.

  7. Return for Postpartum Oral Glucose Tolerance Test Following Gestational Diabetes Mellitus.

    PubMed

    Mohd Suan, Mohd Azri

    2015-09-01

    A cross-sectional study was conducted to assess the prevalence and characteristics of women who received a postpartum oral glucose tolerance test and to examine barriers as reported by women who failed to return for the test. Data were collected using a mobile phone-based short messaging service. Only 352 (81.9%) women returned for the test. Women who failed to return for the test were younger (30.1 vs 32.1, P = .003) and did not have a previous history of gestational diabetes (93.6% vs 84.9%, P = .043) compared to women who returned for the test. The commonest reasons given for not returning for the test was "Still waiting for the appointment date for the test" (37.2%), "had family/health problems" (11.5%), and "busy/no time" (10.3%). Flexible time for the test, active involvement from health care staff, and strengthening continuous care system were among the interventions needed to improve the return rate for this screening test. PMID:26041835

  8. SGLT1 sugar transporter/sensor is required for post-oral glucose appetition.

    PubMed

    Sclafani, Anthony; Koepsell, Hermann; Ackroff, Karen

    2016-04-01

    Recent findings suggest that the intestinal sodium-glucose transporter 1 (SGLT1) glucose transporter and sensor mediates, in part, the appetite-stimulation actions of intragastric (IG) glucose and nonmetabolizable α-methyl-d-glucopyranoside (MDG) infusions in mice. Here, we investigated the role of SGLT1 in sugar conditioning using SGLT1 knockout (KO) and C57BL/6J wild-type (WT) mice. An initial experiment revealed that both KO and WT mice maintained on a very low-carbohydrate diet display normal preferences for saccharin, which was used in the flavored conditioned stimulus (CS) solutions. In experiment 2, mice were trained to drink one flavored solution (CS+) paired with an IG MDG infusion and a different flavored solution (CS-) paired with IG water infusion. In contrast to WT mice, KO mice decreased rather than increased the intake of the CS+ during training and failed to prefer the CS+ over the CS- in a choice test. In experiment 3, the KO mice also decreased their intake of a CS+ paired with IG glucose and avoided the CS+ in a choice test, unlike WT mice, which preferred the CS+ to CS-. In experiment 4, KO mice, like WT mice preferred a glucose + saccharin solution to a saccharin solution. These findings support the involvement of SGLT1 in post-oral glucose and MDG conditioning. The results also indicate that sugar malabsorption in KO mice has inhibitory effects on sugar intake but does not block their natural preference for sweet taste.

  9. Diurnal Variation in Oral Glucose Tolerance: Blood Sugar and Plasma Insulin Levels Morning, Afternoon, and Evening

    PubMed Central

    Jarrett, R. J.; Baker, I. A.; Keen, H.; Oakley, N. W.

    1972-01-01

    Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes. PMID:5058728

  10. Improving Oral Reports: A Heuristic Approach.

    ERIC Educational Resources Information Center

    Glossner, Alan J.

    A student's fear of giving oral reports and the instructor's objection to using too much class time on oral reports are often seen as the major barriers that prevent an oral communication unit from being included in a business or management communications course. One approach to easing both concerns is the use of videotaping as a self-discovery…

  11. The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from Pterospartum tridentatum, on oral glucose tolerance in rats.

    PubMed

    Paulo, Alexandra; Martins, Sofia; Branco, Pedro; Dias, Teresa; Borges, Carlos; Rodrigues, Ana Isabel; Costa, Maria do Céu; Teixeira, Adriano; Mota-Filipe, Hélder

    2008-04-01

    The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin.

  12. Glucose-fructose likely improves gastrointestinal comfort and endurance running performance relative to glucose-only.

    PubMed

    Wilson, P B; Ingraham, S J

    2015-12-01

    This study aimed to determine whether glucose-fructose (GF) ingestion, relative to glucose-only, would alter performance, metabolism, gastrointestinal (GI) symptoms, and psychological affect during prolonged running. On two occasions, 20 runners (14 men) completed a 120-min submaximal run followed by a 4-mile time trial (TT). Participants consumed glucose-only (G) or GF (1.2:1 ratio) beverages, which supplied ∼ 1.3 g/min of carbohydrate. Substrate use, blood lactate, psychological affect [Feeling Scale (FS)], and GI distress were measured. Differences between conditions were assessed using magnitude-based inferential statistics. Participants completed the TT 1.9% (-1.9; -4.2, 0.4) faster with GF, representing a likely benefit. FS ratings were possibly higher and GI symptoms were possibly-to-likely lower with GF during the submaximal period and TT. Effect sizes for GI distress and FS ratings were relatively small (Cohen's d = ∼0.2 to 0.4). GF resulted in possibly higher fat oxidation during the submaximal period. No clear differences in lactate were observed. In conclusion, GF ingestion - compared with glucose-only - likely improves TT performance after 2 h of submaximal running, and GI distress and psychological affect are likely mechanisms. These results apply to runners consuming fluid at 500-600 mL/h and carbohydrate at 1.0-1.3 g/min during running at 60-70% VO2peak .

  13. Plasma glucose and insulin response to two oral nutrition supplements in adults with type 2 diabetes mellitus

    PubMed Central

    Huhmann, Maureen B; Smith, Kristen N; Schwartz, Sherwyn L; Haller, Stacie K; Irvin, Sarah; Cohen, Sarah S

    2016-01-01

    Objective The purpose of this clinical trial was to compare the glucose usage of two oral nutritional supplement (ONS) products and to assess whether a diabetes-specific formulation provides improved glucose stabilization and management compared with a standard formula. Research design and methods A total of 12 subjects with type 2 diabetes (7 males and 5 females) completed a randomized, cross-over design trial. Each subject consumed isocaloric amounts of either the standard ONS or the diabetes-specific formula ONS on different dates, 1 week apart. Glucose and insulin measures were recorded at baseline, and 10, 20, 30, 60, 90, 120, 150, 180, 210 and 240 min after the beverage was consumed and then used to calculate area under the curve (AUC) for each subject. Results The mean glucose AUC was lower in the diabetes-specific ONS group than in the standard group (p<0.0001), but there was not a significant difference observed for mean insulin AUC (p=0.068). A sensitivity analysis of the mean insulin AUC measures was performed by removing a potential outlier from the analysis, and this resulted in a significant difference between the groups (p=0.012). First-phase insulin measures and an insulinogenic index calculated for the beverages showed no significant differences. Conclusions On the basis of the results of this trial of 12 subjects, the diabetes-specific ONS appears to provide better glucose maintenance in persons with type 2 diabetes when compared to the standard formula ONS. Trial registration number NCT02612675. PMID:27648290

  14. Plasma glucose and insulin response to two oral nutrition supplements in adults with type 2 diabetes mellitus

    PubMed Central

    Huhmann, Maureen B; Smith, Kristen N; Schwartz, Sherwyn L; Haller, Stacie K; Irvin, Sarah; Cohen, Sarah S

    2016-01-01

    Objective The purpose of this clinical trial was to compare the glucose usage of two oral nutritional supplement (ONS) products and to assess whether a diabetes-specific formulation provides improved glucose stabilization and management compared with a standard formula. Research design and methods A total of 12 subjects with type 2 diabetes (7 males and 5 females) completed a randomized, cross-over design trial. Each subject consumed isocaloric amounts of either the standard ONS or the diabetes-specific formula ONS on different dates, 1 week apart. Glucose and insulin measures were recorded at baseline, and 10, 20, 30, 60, 90, 120, 150, 180, 210 and 240 min after the beverage was consumed and then used to calculate area under the curve (AUC) for each subject. Results The mean glucose AUC was lower in the diabetes-specific ONS group than in the standard group (p<0.0001), but there was not a significant difference observed for mean insulin AUC (p=0.068). A sensitivity analysis of the mean insulin AUC measures was performed by removing a potential outlier from the analysis, and this resulted in a significant difference between the groups (p=0.012). First-phase insulin measures and an insulinogenic index calculated for the beverages showed no significant differences. Conclusions On the basis of the results of this trial of 12 subjects, the diabetes-specific ONS appears to provide better glucose maintenance in persons with type 2 diabetes when compared to the standard formula ONS. Trial registration number NCT02612675.

  15. Nitrogenous compounds stimulate glucose-derived acid production by oral Streptococcus and Actinomyces.

    PubMed

    Norimatsu, Yuka; Kawashima, Junko; Takano-Yamamoto, Teruko; Takahashi, Nobuhiro

    2015-09-01

    Both Streptococcus and Actinomyces can produce acids from dietary sugars and are frequently found in caries lesions. In the oral cavity, nitrogenous compounds, such as peptides and amino acids, are provided continuously by saliva and crevicular gingival fluid. Given that these bacteria can also utilize nitrogen compounds for their growth, it was hypothesized that nitrogenous compounds may influence their acid production; however, no previous studies have examined this topic. Therefore, the present study aimed to assess the effects of nitrogenous compounds (tryptone and glutamate) on glucose-derived acid production by Streptococcus and Actinomyces. Acid production was evaluated using a pH-stat method under anaerobic conditions, whereas the amounts of metabolic end-products were quantified using high performance liquid chromatography. Tryptone enhanced glucose-derived acid production by up to 2.68-fold, whereas glutamate enhanced Streptococcus species only. However, neither tryptone nor glutamate altered the end-product profiles, indicating that the nitrogenous compounds stimulate the whole metabolic pathways involving in acid production from glucose, but are not actively metabolized, nor do they alter metabolic pathways. These results suggest that nitrogenous compounds in the oral cavity promote acid production by Streptococcus and Actinomyces in vivo.

  16. Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight.

    PubMed

    Sisley, Stephanie R; Arble, Deanna M; Chambers, Adam P; Gutierrez-Aguilar, Ruth; He, Yanlin; Xu, Yong; Gardner, David; Moore, David D; Seeley, Randy J; Sandoval, Darleen A

    2016-09-01

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei. PMID:27217488

  17. Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight.

    PubMed

    Sisley, Stephanie R; Arble, Deanna M; Chambers, Adam P; Gutierrez-Aguilar, Ruth; He, Yanlin; Xu, Yong; Gardner, David; Moore, David D; Seeley, Randy J; Sandoval, Darleen A

    2016-09-01

    Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei.

  18. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice.

    PubMed

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-06-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice. PMID:27255361

  19. β-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy.

    PubMed

    Garibay, Darline; McGavigan, Anne K; Lee, Seon A; Ficorilli, James V; Cox, Amy L; Michael, M Dodson; Sloop, Kyle W; Cummings, Bethany P

    2016-09-01

    Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible for this remain incompletely defined. Glucagon-like peptide-1 (GLP-1) is a gut hormone that contributes to the maintenance of glucose homeostasis and is elevated after VSG. VSG-induced increases in postprandial GLP-1 secretion have been proposed to contribute to the glucoregulatory benefits of VSG; however, previous work has been equivocal. In order to test the contribution of enhanced β-cell GLP-1 receptor (GLP-1R) signaling we used a β-cell-specific tamoxifen-inducible GLP-1R knockout mouse model. Male β-cell-specific Glp-1r(β-cell+/+) wild type (WT) and Glp-1r(β-cell-/-) knockout (KO) littermates were placed on a high-fat diet for 6 weeks and then switched to high-fat diet supplemented with tamoxifen for the rest of the study. Mice underwent sham or VSG surgery after 2 weeks of tamoxifen diet and were fed ad libitum postoperatively. Mice underwent oral glucose tolerance testing at 3 weeks and were euthanized at 6 weeks after surgery. VSG reduced body weight and food intake independent of genotype. However, glucose tolerance was only improved in VSG WT compared with sham WT, whereas VSG KO had impaired glucose tolerance relative to VSG WT. Augmentation of glucose-stimulated insulin secretion during the oral glucose tolerance test was blunted in VSG KO compared with VSG WT. Therefore, our data suggest that enhanced β-cell GLP-1R signaling contributes to improved glucose regulation after VSG by promoting increased glucose-stimulated insulin secretion. PMID:27501183

  20. Valine Pyrrolidide Preserves Intact Glucose-Dependent Insulinotropic Peptide and Improves Abnormal Glucose Tolerance in Minipigs With Reduced β-Cell Mass

    PubMed Central

    Rolin, Bidda; Ribel, Ulla; Wilken, Michael; Deacon, Carolyn F.; Svendsen, Ove; Gotfredsen, Carsten F.; Carr, Richard David

    2003-01-01

    The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation.However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced β-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)–treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg).VP did not significantly affect levels of intact GLP-1 but increased levels of intact GIP (from 4543 ± 1880 to 9208 ± 3267 pM × min; P<.01), thus improving glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 ± 480 to 1582 ± 353 mM × min;P = .05).VP did not increase insulin levels during the oral glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 ± 42 to 192 ± 108; P < .05), but not after NIA + STZ, possibly because of less residual insulin secretory capacity in these animals. GIP seems to contribute to the antihyperglycemic effect of VP in this model; however, additional mechanisms for the effect of DPPIV inhibition cannot be excluded. The authors conclude that DPPIV inhibitors may be useful to treat type 2 diabetes, even when this is due to reduced β-cell mass. PMID:14630571

  1. Partnerships to Improve Oral Hygiene Practices: Two Complementary Approaches.

    PubMed

    Dale, Craig M; Wiechula, Rick; Lewis, Adrienne; McArthur, Alexa; Breen, Helen; Scarborough, Alan; Rose, Louise

    2016-01-01

    The omission of oral care is linked to increased nurse workload and may contribute to serious patient infection and growing healthcare costs. Therefore, ineffective oral care comprises a significant patient safety issue across healthcare settings internationally. As studies have demonstrated a positive relationship between Nurs Leadersh (Tor Ont) and improved patient outcomes, it is imperative that leaders seek effective approaches to facilitate contextual exploration of barriers and facilitators for resolution of oral care delivery problems. One approach to improved processes of oral care is the creative engagement of front-line clinicians in the problems they confront in everyday practice. By drawing upon the role and process of facilitation, we outline two projects, located in Australia and Canada, that engaged front-line nurses, health leaders, and researchers as partners to identify a path to improved oral care delivery. In this paper, we summarize key learnings for nursing leaders about strategies to facilitate delivery of fundamental oral care. We found that facilitation, contextual knowledge and academic-clinician partnerships were essential to the detection and evaluation of oral care delivery problems and the identification of priorities for practice improvement. As collaboration is imperative for sustainable innovation, we summarize strategies of effective leadership for improving oral care delivery. PMID:27309641

  2. Improved Oxygen-Beam Texturing of Glucose-Monitoring Optics

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A.

    2006-01-01

    An improved method has been devised for using directed, hyperthermal beams of oxygen atoms and ions to impart desired textures to the tips of polymethylmethacrylate [PMMA] optical fibers to be used in monitoring the glucose content of blood. The improved method incorporates, but goes beyond, the method described in Texturing Blood-Glucose- Monitoring Optics Using Oxygen Beams (LEW-17642-1), NASA Tech Briefs, Vol. 29, No. 4 (April 2005), page 11a. The basic principle of operation of such a glucose-monitoring sensor is as follows: The textured surface of the optical fiber is coated with chemicals that interact with glucose in such a manner as to change the reflectance of the surface. Light is sent down the optical fiber and is reflected from, the textured surface. The resulting change in reflectance of the light is measured as an indication of the concentration of glucose. The required texture on the ends of the optical fibers is a landscape of microscopic cones or pillars having high aspect ratios (microscopic structures being taller than they are wide). The average distance between hills must be no more than about 5 mso that blood cells (which are wider) cannot enter the valleys between the hills, where they would interfere with optical sensing of glucose in the blood plasma. On the other hand, the plasma is required to enter the valleys, and high aspect ratio structures are needed to maximize the surface area in contact with the plasma, thereby making it possible to obtain a given level of optical glucose-measurement sensitivity with a relatively small volume of blood. There is an additional requirement that the hills be wide enough that a sufficient amount of light can propagate into them and, after reflection, can propagate out of them. The method described in the cited prior article produces a texture comprising cones and pillars that conform to the average-distance and aspect-ratio requirements. However, a significant fraction of the cones and pillars are so

  3. Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

    SciTech Connect

    Kang, Seong-Il; Jin, Young-Jun; Ko, Hee-Chul; Choi, Soo-Youn; Hwang, Joon-Ho; Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok; Kim, Se-Jae

    2008-08-22

    The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPAR{gamma} luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.

  4. A new route to improved glucose yields in cellulose hydrolysis

    SciTech Connect

    Zhao, Haibo; Holladay, John E.; Kwak, Ja Hun; Zhang, Z. Conrad

    2007-08-01

    An unusual inverse temperature-dependent pathway was discovered for cellulose decrystallization in trifluoroacetic acid (TFA). Cellulose was completely decrystallized by TFA at 0 °C in less than 2 hours, a result not achieved in 48 hours at 25°C in the same medium. The majority of TFA used in cellulose decrystallization was recycled via a vacuum process. The small remaining amount of TFA was diluted with water to make a 0.5% TFA solution and used as a catalyst in dilute acid hydrolysis. After one minute, under batch conditions at 185 °C, the glucose yield reached 63.5% without production of levulinic acid. In comparison, only 15.0% glucose yield was achieved in the hydrolysis of untreated cellulose by 0.5% H2SO4 under the same condition. Further improvement of glucose yield is possible by optimizing reaction conditions. Alternatively, the remaining TFA can be completely removed by water while keeping the regenerated cellulose in a highly amorphous state. This regenerated cellulose is much more reactive than untreated cellulose in hydrolysis reactions, but still less reactive than corn starch. The lower temperatures and shorter reaction times with this activated cellulose makes it possible to reduce operating costs and decrease byproduct yields such as HMF and levulinic acid.

  5. Co-immobilization of gold nanoparticles with glucose oxidase to improve bioelectrocatalytic glucose oxidation

    NASA Astrophysics Data System (ADS)

    Aquino Neto, Sidney; Milton, Ross D.; Crepaldi, Laís B.; Hickey, David P.; de Andrade, Adalgisa R.; Minteer, Shelley D.

    2015-07-01

    Recently, there has been much effort in developing metal nanoparticle catalysts for fuel oxidation, as well as the development of enzymatic bioelectrocatalysts for fuel oxidation. However, there has been little study of the synergy of hybrid electrocatalytic systems. We report the preparation of hybrid bioanodes based on Au nanoparticles supported on multi-walled carbon nanotubes (MWCNTs) co-immobilized with glucose oxidase (GOx). Mediated electron transfer was achieved by two strategies: ferrocene entrapped within polypyrrole and a ferrocene-modified linear poly(ethylenimine) (Fc-LPEI) redox polymer. Electrochemical characterization of the Au nanoparticles supported on MWCNTs indicate that this catalyst exhibits an electrocatalytic response for glucose even in acidic conditions. Using the redox polymer Fc-LPEI as the mediator, voltammetric and amperometric data demonstrated that these bioanodes can efficiently achieve mediated electron transfer and also indicated higher catalytic currents with the hybrid bioelectrode. From the amperometry, the maximum current density (Jmax) achieved with the hybrid bioelectrode was 615 ± 39 μA cm-2, whereas the bioanode employing GOx only achieved a Jmax of 409 ± 26 μA cm-2. Biofuel cell tests are consistent with the electrochemical characterization, thus confirming that the addition of the metallic species into the bioanode structure can improve fuel oxidation and consequently, improve the power generated by the system.

  6. Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.

    PubMed

    Berhane, Feven; Fite, Alemu; Daboul, Nour; Al-Janabi, Wissam; Msallaty, Zaher; Caruso, Michael; Lewis, Monique K; Yi, Zhengping; Diamond, Michael P; Abou-Samra, Abdul-Badi; Seyoum, Berhane

    2015-01-01

    Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D. PMID:25961050

  7. Oral Assessments: Improving Retention, Grades, and Understanding

    ERIC Educational Resources Information Center

    Nelson, Mary A.

    2011-01-01

    This article reports on an innovative approach to teaching Calculus I which was initiated in a two-semester course designed for students at risk of failing Calculus I. The treatment consisted of voluntary oral assessments offered before every written examination. Analyses showed that the treatment students did significantly better than the control…

  8. Improving Oral Performance through Interactions Flashcards

    ERIC Educational Resources Information Center

    Urquijo, Jasson

    2012-01-01

    This paper describes an action research project that addressed the issue of low oral performance in English among third grade learners at a public girls' school in Bogota, Colombia. The issue was identified via content analysis of ten field logs compiled over the third and fourth quarter of the second semester, 2010. To address the problem of…

  9. Phloretin promotes adipocyte differentiation in vitro and improves glucose homeostasis in vivo.

    PubMed

    Shu, Gang; Lu, Nai-Sheng; Zhu, Xiao-Tong; Xu, Yong; Du, Min-Qing; Xie, Qiu-Ping; Zhu, Can-Jun; Xu, Qi; Wang, Song-Bo; Wang, Li-Na; Gao, Ping; Xi, Qian-Yun; Zhang, Yong-Liang; Jiang, Qing-Yan

    2014-12-01

    Adipocyte dysfunction is associated with many metabolic diseases such as obesity, insulin resistance and diabetes. Previous studies found that phloretin promotes 3T3-L1 cells differentiation, but the underlying mechanisms for phloretin's effects on adipogenesis remain unclear. In this study, we demonstrated that phloretin enhanced the lipid accumulation in porcine primary adipocytes in a time-dependent manner. Furthermore, phloretin increased the utilization of glucose and nonesterified fatty acid, while it decreased the lactate output. Microarray analysis revealed that genes associated with peroxisome proliferator-activated receptor-γ (PPARγ), mitogen-activated protein kinase and insulin signaling pathways were altered in response to phloretin. We further confirmed that phloretin enhanced expression of PPARγ, CAAT enhancer binding protein-α (C/EBPα) and adipose-related genes, such as fatty acids translocase and fatty acid synthase. In addition, phloretin activated the Akt (Thr308) and extracellular signal-regulated kinase, and therefore, inactivated Akt targets protein. Wortmannin effectively blocked the effect of phloretin on Akt activity and the protein levels of PPARγ, C/EBPα and fatty acid binding protein-4 (FABP4/aP2). Oral administration of 5 or 10 mg/kg phloretin to C57BL BKS-DB mice significantly decreased the serum glucose level and improved glucose tolerance. In conclusion, phloretin promotes the adipogenesis of porcine primary preadipocytes through Akt-associated signaling pathway. These findings suggested that phloretin might be able to increase insulin sensitivity and alleviate the metabolic diseases. PMID:25283330

  10. The effect of endurance training and subsequent physical inactivity on glycaemic control after oral glucose load and physical exercise in healthy men

    NASA Astrophysics Data System (ADS)

    Radikova, Zofia; Ksinantova, Lucia; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Vigas, Milan; Koska, Juraj

    2007-02-01

    Physical inactivity during space flight has a profound effect on glucose metabolism. The aim of this study was to test whether endurance training (ET) may improve a negative effect of subsequent -6∘ head-down bed rest (HDBR) on glucose metabolism. Fourteen healthy males completed the study consisting of 6 weeks lasting ET followed by 6 days HDBR. Treadmill exercise at 80% of pre-training VO2max and 75 g oral glucose tolerance test (OGTT) were performed before and after ET as well as after HDBR. ET increased VO2max by 11%. ET significantly lowered while HDBR had no effect on fasting and OGTT plasma glucose levels. ET had no effect while HDBR was followed by an augmentation of insulin and C-peptide response to OGTT. Insulin sensitivity tended to increase after ET and to decrease during HDBR, however, mostly without statistical significance. Plasma glucose, insulin and C-peptide response to exercise were elevated after HDBR only. Our study shows that antecedent physical training could ameliorate a negative effect of simulated microgravity on insulin-mediated glucose metabolism.

  11. Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

    PubMed

    Van Proeyen, Karen; Ramaekers, Monique; Pischel, Ivo; Hespel, Peter

    2012-08-01

    The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t₀) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t₆₀. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t₃₀ and t₆₀ (p < .05). Furthermore, a higher serum insulin concentration was noted after OFI intake at baseline and at t₃₀ (p < .05). In OGTT(EX), blood glucose at t₆₀ was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p < .05). However, insulin values and AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

  12. Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice

    PubMed Central

    Membrez, M; Chou, C J; Raymond, F; Mansourian, R; Moser, M; Monnard, I; Ammon-Zufferey, C; Mace, K; Mingrone, G; Binnert, C

    2010-01-01

    Aim: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D). Methods: Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA1.5% and SA15%, respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results: After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA15% group compared with the other groups showing a beneficial effect of SA on hyperglycaemia. During OGTT, plasma glucose area under the curve was reduced after SA15% compared with the other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared with Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusion: Dietary supplementation of SA largely improves glycaemic control in a mouse model of T2D. This beneficial effect may be due to (i) an improved glucose-induced insulin secretion and (ii) a reduced hepatic glucose output. PMID:20977585

  13. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  14. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Pillai, Subramanian Iyyam; Subramanian, Sorimuthu Pillai

    2014-10-01

    Liver plays a vital role in blood glucose homeostasis. Recent studies have provided considerable evidence that hepatic glucose production (HGP) plays an important role in the development of fasting hyperglycemia in diabetes. From this perspective, diminution of HGP has certainly been considered for the treatment of diabetes. In the present study, we have analyzed the modulatory effects of fisetin, a flavonoid of strawberries, on the expression of key enzymes of carbohydrate metabolism in STZ induced experimental diabetic rats. The physiological criterions such as food and fluid intake were regularly monitored. The levels of blood glucose, plasma insulin, hemoglobin and glycosylated hemoglobin were analyzed. The mRNA and protein expression levels of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined by immunoblot as well as PCR analysis. Diabetic group of rats showed significant increase in food and water intake when compared with control group of rats. Upon oral administration of fisetin as well as gliclazide to diabetic group of rats, the levels were found to be decreased. Oral administration of fisetin (10 mg/kg body weight) to diabetic rats for 30 days established a significant decline in blood glucose and glycosylated hemoglobin levels and a significant increase in plasma insulin level. The mRNA and protein expression levels of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), were decreased in liver tissues upon treatment with fisetin. The results of the present study suggest that fisetin improves glucose homeostasis by direct inhibition of gluconeogenesis in liver.

  15. Insulin resistance in the oral glucose tolerance test--a link with hypertension.

    PubMed

    Cederholm, J; Wibell, L

    1991-03-01

    Insulin resistance was evaluated in 807 middle-aged subjects at a health survey, with use of an index measured in 75 g oral glucose tolerance tests. The mean value of insulin resistance was higher in a hypertensive group than among the normotensives, independent of body mass index, physical activity, smoking sex, age, and thiazide treatment. One-third of the hypertensives had a high resistance value. Another third of the hypertensives, and also about one-third of the normotensives, had a slightly increased resistance. The remaining third of the hypertensives had a normal-low resistance. A high resistance was also independently related to obesity, low physical leisure time activity, and a family history of NIDDM, but not to a family history of hypertension. The statistical analysis implied a sequence of events: low physical activity might cause high resistance, which in turn might cause high blood pressure.

  16. Sugarcane transgenics expressing MYB transcription factors show improved glucose release

    DOE PAGES

    Poovaiah, Charleson R.; Bewg, William P.; Lan, Wu; Ralph, John; Coleman, Heather D.

    2016-07-15

    In this study, sugarcane, a tropical C4 perennial crop, is capable of producing 30-100 tons or more of biomass per hectare annually. The lignocellulosic residue remaining after sugar extraction is currently underutilized and can provide a significant source of biomass for the production of second-generation bioethanol. As a result, MYB31 and MYB42 were cloned from maize and expressed in sugarcane with and without the UTR sequences. The cloned sequences were 98 and 99 % identical to the published nucleotide sequences. The inclusion of the UTR sequences did not affect any of the parameters tested. There was little difference in plantmore » height and the number of internodes of the MYB-overexpressing sugarcane plants when compared with controls. MYB transgene expression determined by qPCR exhibited continued expression in young and maturing internodes. MYB31 downregulated more genes within the lignin biosynthetic pathway than MYB42. MYB31 and MYB42 expression resulted in decreased lignin content in some lines. All MYB42 plants further analyzed showed significant increases in glucose release by enzymatic hydrolysis in 72 h, whereas only two MYB31 plants released more glucose than control plants. This correlated directly with a significant decrease in acid-insoluble lignin. Soluble sucrose content of the MYB42 transgenic plants did not vary compared to control plants. In conclusion, this study demonstrates the use of MYB transcription factors to improve the production of bioethanol from sugarcane bagasse remaining after sugar extraction.« less

  17. Effects of oral glucose on exercise thermoregulation in men after water immersion

    NASA Technical Reports Server (NTRS)

    Dearborn, Alan S.; Ertl, Andrew C.; Greenleaf, John E.; Barnes, Paul R.; Jackson, Catherine G. R.; Breckler, Jennifer L.

    1994-01-01

    To test the hypothesis elevated blood glucose would attenuate the rise in exercise rectal temperature, six men age 35 plus or minus S.D. 7 years participated in each of three trials by 4-hr water immersion to the neck: (1) 2.0 g/kg body wt of oral glucose (33.8 percent wt./vol.) was consumed followed by 80 min controlled rest (Glu/Rest), and 70 min horizontal supine cycle exercise at 62.8 percent plus or minus S.E. 0.5 percent (1.97 plus or minus 0.02 L/min) of peak O2 uptake followed by 10 min recovery (2) with (Glu/Ex) and (3) without prior flucose (No Glu/Ex). Blood samples were taken at -25, 0, 15, 45, and 68 min of exercise and after plus 10 min of recovery for measurement of hemoglobin, hematocrit, and blood glucose. Both mean skin (T sub sk) (from six sites) and rectal temperatures (T sub re) were monitored continuously. Sweat rate was measured by resistanc hygrometry. The mean of delta PV for the exercise trials was -12.2 plus or minus 2.1 percent. Mean blood glucose for the Glu/Ex trial was higher than that of the No Glu/Ex trial was (108.4 equal or minus 3.9 and 85.6 plus or minus 1.6 mg/dl, respectively, P less than 0.05. At the end of exercise T(sub sk) for the Glu/Ex trial was lower than for No Glu/Ex(32.0 plus or minus 0.3 and 32.4 equals or minus 0.2 C, respectively, P less than 0.05); T(sub re) for the Glu/Ex trial was lower than for No Glu/Es (38.22 plus or minus 0.17 and 38.60 plus or minus 0.11 C, respectively, P less than 0.05); and forearm sweat rate for the Glu/Ex trial (0.34 plus or minus 0.04 and 0.43 plus or minus g/sq cm, respectively, P less than 0.05). These data suggest that elevation of blood glucose prior to horizontal exercise following hypohydration attenuates the increase in body temperature without altering heat production or exercise hypovolemia.

  18. Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition.

    PubMed

    Sclafani, Anthony; Zukerman, Steven; Ackroff, Karen

    2014-12-15

    Recent studies indicate that, unlike glucose, fructose has little or no post-oral preference conditioning actions in C57BL/6J (B6) mice. The present study determined whether this is also the case for FVB mice, which overconsume fructose relative to B6 mice. In experiment 1, FVB mice strongly preferred a noncaloric 0.1% sucralose + 0.1% saccharin (S+S) solution to 8% fructose in a 2-day choice test but switched their preference to fructose after separate experience with the two sweeteners. Other FVB mice displayed a stronger preference for 8% glucose over S+S. In a second experiment, ad libitum-fed FVB mice trained 24 h/day acquired a significant preference for a flavor (CS+) paired with intragastric (IG) self-infusions of 16% fructose over a different flavor (CS-) paired with IG water infusions. IG fructose infusions also conditioned flavor preferences in food-restricted FVB mice trained 1 h/day. IG infusions of 16% glucose conditioned stronger preferences in FVB mice trained 24- or 1 h/day. Thus, fructose has post-oral flavor conditioning effects in FVB mice, but these effects are less pronounced than those produced by glucose. Further studies of the differential post-oral conditioning effects of fructose and glucose in B6 and FVB mice should enhance our understanding of the physiological processes involved in sugar reward.

  19. Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

    PubMed

    Wapnir, R A; Litov, R E; Zdanowicz, M M; Lifshitz, F

    1991-04-01

    Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will

  20. Identification of Differential Responses to an Oral Glucose Tolerance Test in Healthy Adults

    PubMed Central

    Morris, Ciara; O’Grada, Colm; Ryan, Miriam; Roche, Helen M.; Gibney, Michael J.; Gibney, Eileen R.; Brennan, Lorraine

    2013-01-01

    Background In recent years an individual’s ability to respond to an acute dietary challenge has emerged as a measure of their biological flexibility. Analysis of such responses has been proposed to be an indicator of health status. However, for this to be fully realised further work on differential responses to nutritional challenge is needed. This study examined whether metabolic phenotyping could identify differential responders to an oral glucose tolerance test (OGTT) and examined the phenotypic basis of the response. Methods and Results A total of 214 individuals were recruited and underwent challenge tests in the form of an OGTT and an oral lipid tolerance test (OLTT). Detailed biochemical parameters, body composition and fitness tests were recorded. Mixed model clustering was employed to define 4 metabotypes consisting of 4 different responses to an OGTT. Cluster 1 was of particular interest, with this metabotype having the highest BMI, triacylglycerol, hsCRP, c-peptide, insulin and HOMA- IR score and lowest VO2max. Cluster 1 had a reduced beta cell function and a differential response to insulin and c-peptide during an OGTT. Additionally, cluster 1 displayed a differential response to the OLTT. Conclusions This work demonstrated that there were four distinct metabolic responses to the OGTT. Classification of subjects based on their response curves revealed an “at risk” metabolic phenotype. PMID:23991163

  1. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance

    PubMed Central

    Sayers, Sophie R.; Reimann, Frank; Gribble, Fiona M.; Parker, Helen; Zac-Varghese, Sagen; Bloom, Stephen R.; Foretz, Marc; Viollet, Benoit; Rutter, Guy A.

    2016-01-01

    Background Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1) in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK) in these cells. Method Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre) to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay. Results Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01) in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01) and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01) GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01). Conclusion AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes. PMID:27010458

  2. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis. PMID:24656388

  3. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis.

  4. Probiotics: can they be used to improve oral health?

    PubMed

    Gungor, O E; Kirzioglu, Z; Kivanc, M

    2015-01-01

    The role of probiotic bacteria in improving human health has been an attractive subject for researchers since the beginning of the 20(th) century. They have been used to control gastro-intestinal infections, to promote immunity and to prevent various diseases (allergies, urogenital infections, etc.). However, the use of beneficial bacteria in the field of dentistry has only recently gained interest. Investigation of the effects of probiotic bacteria on oral health has become an important research subject. These studies are still in the early stages, however results show that probiotic bacteria are effective against tooth caries, periodontal disease, oral mucosal lesions and oral malodour. This review provides information on the effects of probiotics--well-known for their effects on general health, and therefore more widely used in healthcare--on oral and dental health, in order to promote their use/prescription by physicians and patients.

  5. Effects of three day bed-rest on circulatory, metabolic and hormonal responses to oral glucose load in endurance trained athletes and untrained subjects

    NASA Technical Reports Server (NTRS)

    Smorawinski, J.; Kubala, P.; Kaciuba-Uociako, H.; Nazar, K.; Titow-Stupnicka, E.; Greenleaf, J. E.

    1996-01-01

    Endurance trained long distance runners and untrained individuals underwent three days of bed rest and oral glucose loading. Before and after bed rest, individuals were given glucose tolerance tests, and their heart rates, blood pressure, blood glucose levels, insulin levels, and catecholamine interactions were measured. Results indicated that glucose tolerance is more affected by bed rest-induced deconditioning in untrained individuals than in trained individuals.

  6. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice.

    PubMed

    Gunnarsson, P Thomas; Winzell, Maria Sörhede; Deacon, Carolyn F; Larsen, Marianne O; Jelic, Katarina; Carr, Richard D; Ahrén, Bo

    2006-07-01

    Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P < 0.01), which was associated with enhanced oral glucose tolerance (P < 0.01). The insulin response to glucose was also augmented by addition of OA (34 mg; P < 0.05) although only 1.5-fold and with no associated increase in glucose elimination. The slope of the glucose-insulin curve was increased by OA (1.7-fold; P < 0.05) and by WP (4-fold; P < 0.01) compared with glucose alone, suggesting potentiation of glucose-stimulated insulin release. WP increased GLP-1 secretion (P < 0.01), whereas GIP secretion was unaffected. OA did not affect GIP or GLP-1 secretion. Nevertheless, WP increased the levels of both intact GIP and intact GLP-1 (both P < 0.01), and OA increased the levels of intact GLP-1 (P < 0.05). WP inhibited dipeptidyl peptidase IV activity in the proximal small intestine by 50% (P < 0.05), suggesting that luminal degradation of WP generates small fragments, which are substrates for dipeptidyl peptidase IV and act as competitive inhibitors. We therefore conclude that fat and protein may serve as exogenous regulators of secretion and inactivation of the incretin hormones with beneficial influences on glucose metabolism.

  7. Mild insulin resistance during oral glucose tolerance test (OGTT) in women with acne.

    PubMed

    Aizawa, H; Niimura, M

    1996-08-01

    The purpose of this study was to evaluate serum levels of basal insulin and glucose-stimulated insulin, and to evaluate their correlations with androgen levels in women with acne. Serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IFG-1), and immunoreactive insulin (IRI) were measured and compared in thirty women with moderate or severe acne and thirteen healthy controls. Serum FT, DHT and DHEA-S levels in the acne group were significantly higher than those in the control group. In the acne group, there were no significant correlations between insulin or IGF-1 levels and T, FT, DHT and SHBG, despite the positive correlation between insulin and IGF-1. In order to determine the effects of insulin secretion as a dynamic response to an oral glucose tolerance test (OGTT) on serum androgen levels in acne patients, we examined the responses of serum insulin and androgen levels to a 75 g, 2 hour OGTT in the acne group and in the control group. Basal insulin levels were not significantly higher than those in the control group, but the summed insulin levels during the OGTT in the acne group were significantly higher than those in the control group. Serum T and FT levels in the acne group decreased during the OGTT, but these changes were not so significant when compared to normal controls. In conclusion, we tried to demonstrate mild insulin resistance during the OGTT in acne patients. However, postmeal transient hyperinsulinemia does not seem to play an important role in determining hyperandrogenemia in acne patients. PMID:8854583

  8. Improved operational stability of peroxidases by coimmobilization with glucose oxidase.

    PubMed

    van de Velde, F; Lourenço, N D; Bakker, M; van Rantwijk, F; Sheldon, R A

    2000-08-01

    The operational stability of peroxidases was considerably enhanced by generating hydrogen peroxide in situ from glucose and oxygen. For example, the total turnover number of microperoxidase-11 in the oxidation of thioanisole was increased sevenfold compared with that obtained with continuous addition of H(2)O(2). Coimmobilization of peroxidases with glucose oxidase into polyurethane foams afforded heterogeneous biocatalysts in which the hydrogen peroxide is formed inside the polymeric matrix from glucose and oxygen. The total turnover number of chloroperoxidase in the oxidation of thioanisole and cis-2-heptene was increased to new maxima of 250. 10(3) and 10. 10(3), respectively, upon coimmobilization with glucose oxidase. Soybean peroxidase, which normally shows only classical peroxidase activity, was transformed into an oxygen-transfer catalyst when coimmobilized with glucose oxidase. The combination catalyst mediated the enantioselective oxidation of thioanisole [50% ee (S)] with 210 catalyst turnovers. PMID:10861408

  9. Pre-Type 1 Diabetes Dysmetabolism: Maximal sensitivity achieved with Both Oral and Intravenous Glucose Tolerance Testing

    PubMed Central

    Barker, Jennifer M.; McFann, Kim; Harrison, Leonard C.; Fourlanos, Spiros; Krischer, Jeffrey; Cuthbertson, David; Chase, H. Peter; Eisenbarth, George S.; Group, the DPT-1 Study

    2007-01-01

    Objective To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and identify an optimal testing strategy for detecting pre-clinical diabetes. Study design Diabetes Prevention Trial Type 1 randomized subjects to oral (n=372) and parenteral (n=339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. Results Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of FPIR at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline BMI, FPIR and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal first phase insulin response (FPIR) and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs. 73%). Conclusions Most (97%) subjects had abnormal IVGTTs and/or OGTTs prior to the development of diabetes. The highest sensitivity is achieved using both tests. PMID:17188609

  10. ARA290 Improves Insulin Release and Glucose Tolerance in Type 2 Diabetic Goto-Kakizaki Rats

    PubMed Central

    Muller, Carole; Yassin, Kamal; Li, Luo-Sheng; Palmblad, Magnus; Efendic, Suad; Berggren, Per-Olof; Cerami, Anthony; Brines, Michael; Östenson, Claes-Göran

    2015-01-01

    Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats. In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity. Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats. Additionally, in response to glucose, carbachol and KCl, islet cytoplasmic free Ca2+ concentrations, [Ca2+]i, were higher and the frequency of [Ca2+]i oscillations enhanced compared with placebo. ARA290 also improved stimulus–secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion. ARA290 also exerted an effect distal to the ATP-sensitive potassium (KATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when KATP channels were kept open by diazoxide. Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion. In conclusion, ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats. This effect appears to be due to improved β-cell glucose metabolism and [Ca2+]i handling, and thereby enhanced glucose-induced insulin release. PMID:26736179

  11. Lead, cadmium and aluminum in Canadian infant formulae, oral electrolytes and glucose solutions

    PubMed Central

    Dabeka, Robert; Fouquet, Andre; Belisle, Stephane; Turcotte, Stephane

    2011-01-01

    Lead (Pb), cadmium (Cd) and aluminum (Al) were determined in 437 individual samples of infant formulae, oral electrolytes and 5% glucose solutions available in Canada. In the electrolytes, Cd and Pb concentrations were all below 0.01 and 0.041 ng g−1, respectively. In the 5% glucose solutions, Pb and Cd levels averaged 0.01 and 0.09 ng g−1, respectively. Reported on an as-consumed basis, Pb levels in milk- and soya-based formulae averaged 0.90 and 1.45 ng g−1, respectively, while Cd levels averaged 0.23 and 1.18 ng g−1, respectively Average Al levels on an as-consumed basis were 440 ng g−1 (range 10–3400 ng g−1) in milk-based formulae and 730 ng g−1 (range 230–1100 ng g−1) in soy-based formulae. Al concentrations increased in the following order: plain formula < low-iron formula < iron-supplemented formula < casein hydrolysate formula ≈ premature formula ≤ soy formula. For example, in the powdered formulae, average Al concentrations were 18 ng g−1 for plain milk-based, 37 ng g−1 for low-iron, 128 ng g−1 for iron supplemented, 462 ng g−1 for lactose-free, 518 ng g−1 for hypoallergenic and 619 ng g−1 for soy-based formula. Al concentrations, as-consumed, increased with decreasing levels of concentration: powder < concentrated liquid < ready-to-use. Formulae stored in glass bottles contained between 100 and 300 ng g−1 more Al than the same formulae stored in cans. The source of the increased Al did not appear to be the glass itself, because most electrolytes and glucose solutions, also stored in glass, contained less than 8 ng g−1 Al. Corresponding differences in Pb and Cd levels were not observed. Al concentrations varied substantially among manufacturers; however, all manufacturers were able to produce plain milk-based formulae containing less than 50 ng g−1 Al, i.e. within the range of Al concentrations found in human milk. Next to soya-based and hypoallergenic formulae, premature formulae contained among the highest

  12. Nighttime Administration of Nicotine Improves Hepatic Glucose Metabolism via the Hypothalamic Orexin System in Mice.

    PubMed

    Tsuneki, Hiroshi; Nagata, Takashi; Fujita, Mikio; Kon, Kanta; Wu, Naizhen; Takatsuki, Mayumi; Yamaguchi, Kaoru; Wada, Tsutomu; Nishijo, Hisao; Yanagisawa, Masashi; Sakurai, Takeshi; Sasaoka, Toshiyasu

    2016-01-01

    Nicotine is known to affect the metabolism of glucose; however, the underlying mechanism remains unclear. Therefore, we here investigated whether nicotine promoted the central regulation of glucose metabolism, which is closely linked to the circadian system. The oral intake of nicotine in drinking water, which mainly occurred during the nighttime active period, enhanced daily hypothalamic prepro-orexin gene expression and reduced hyperglycemia in type 2 diabetic db/db mice without affecting body weight, body fat content, and serum levels of insulin. Nicotine administered at the active period appears to be responsible for the effect on blood glucose, because nighttime but not daytime injections of nicotine lowered blood glucose levels in db/db mice. The chronic oral treatment with nicotine suppressed the mRNA levels of glucose-6-phosphatase, the rate-limiting enzyme of gluconeogenesis, in the liver of db/db and wild-type control mice. In the pyruvate tolerance test to evaluate hepatic gluconeogenic activity, the oral nicotine treatment moderately suppressed glucose elevations in normal mice and mice lacking dopamine receptors, whereas this effect was abolished in orexin-deficient mice and hepatic parasympathectomized mice. Under high-fat diet conditions, the oral intake of nicotine lowered blood glucose levels at the daytime resting period in wild-type, but not orexin-deficient, mice. These results indicated that the chronic daily administration of nicotine suppressed hepatic gluconeogenesis via the hypothalamic orexin-parasympathetic nervous system. Thus, the results of the present study may provide an insight into novel chronotherapy for type 2 diabetes that targets the central cholinergic and orexinergic systems. PMID:26492471

  13. Nighttime Administration of Nicotine Improves Hepatic Glucose Metabolism via the Hypothalamic Orexin System in Mice.

    PubMed

    Tsuneki, Hiroshi; Nagata, Takashi; Fujita, Mikio; Kon, Kanta; Wu, Naizhen; Takatsuki, Mayumi; Yamaguchi, Kaoru; Wada, Tsutomu; Nishijo, Hisao; Yanagisawa, Masashi; Sakurai, Takeshi; Sasaoka, Toshiyasu

    2016-01-01

    Nicotine is known to affect the metabolism of glucose; however, the underlying mechanism remains unclear. Therefore, we here investigated whether nicotine promoted the central regulation of glucose metabolism, which is closely linked to the circadian system. The oral intake of nicotine in drinking water, which mainly occurred during the nighttime active period, enhanced daily hypothalamic prepro-orexin gene expression and reduced hyperglycemia in type 2 diabetic db/db mice without affecting body weight, body fat content, and serum levels of insulin. Nicotine administered at the active period appears to be responsible for the effect on blood glucose, because nighttime but not daytime injections of nicotine lowered blood glucose levels in db/db mice. The chronic oral treatment with nicotine suppressed the mRNA levels of glucose-6-phosphatase, the rate-limiting enzyme of gluconeogenesis, in the liver of db/db and wild-type control mice. In the pyruvate tolerance test to evaluate hepatic gluconeogenic activity, the oral nicotine treatment moderately suppressed glucose elevations in normal mice and mice lacking dopamine receptors, whereas this effect was abolished in orexin-deficient mice and hepatic parasympathectomized mice. Under high-fat diet conditions, the oral intake of nicotine lowered blood glucose levels at the daytime resting period in wild-type, but not orexin-deficient, mice. These results indicated that the chronic daily administration of nicotine suppressed hepatic gluconeogenesis via the hypothalamic orexin-parasympathetic nervous system. Thus, the results of the present study may provide an insight into novel chronotherapy for type 2 diabetes that targets the central cholinergic and orexinergic systems.

  14. Oral green tea catechins transiently lower plasma glucose concentrations in female db/db mice.

    PubMed

    Wein, Silvia; Schrader, Eva; Rimbach, Gerald; Wolffram, Siegfried

    2013-04-01

    Polyphenols, including green tea catechins, are secondary plant compounds often discussed in the context of health-promoting potential. Evidence for such effects is mainly derived from epidemiological and cell culture studies. The aim of the present study was to investigate antidiabetic, antiadipogenic, and anti-inflammatory effects at nonpharmacological doses in an obese diabetic mouse model that exerts early relevant clinical signs of non-insulin-dependent diabetes mellitus. Female db/db mice received a flavonoid-poor diet either without additive, with rosiglitazone (RSG, 0.02 g/kg diet), or with green tea extract (low-dose green tea extract [LGTE] and high-dose green tea extract [HGTE], 0.1 and 1 g/kg diet). Food and water were freely available. The body weight was monitored weekly. Blood was sampled (12-h fasted) from the tail vein on day 28 and analyzed for glucose, cholesterol, triacylglycerol, nonesterified fatty acids, insulin, adiponectin, and soluble intercellular adhesion molecule-1 (sICAM-1). Blood glucose was also analyzed on day 14. Furthermore, sICAM-1 release was investigated in tumor necrosis factor alpha-stimulated EAhy926 cells. After 14 days, fasting glycemia was improved by RSG or HGTE supplementation compared to controls. However, at the end of the study (day 28), only RSG exhibited glucose-lowering effects and induced plasma adiponectin concentrations, paralleled by higher body weight gain and reduced periuterine fat pads compared to controls. However, only GTE treatment reduced sICAM-1 release in vitro and in vivo. Nonpharmacological HGTE supplementation in db/db mice caused (1) no adiponectin-inducing or antiadipogenic effects, (2) reduced sICAM-1 release, thereby potentially exerting anti-inflammatory effects in the progressive diabetic state, and (3) a transient improvement in glycemia.

  15. Oral green tea catechins transiently lower plasma glucose concentrations in female db/db mice.

    PubMed

    Wein, Silvia; Schrader, Eva; Rimbach, Gerald; Wolffram, Siegfried

    2013-04-01

    Polyphenols, including green tea catechins, are secondary plant compounds often discussed in the context of health-promoting potential. Evidence for such effects is mainly derived from epidemiological and cell culture studies. The aim of the present study was to investigate antidiabetic, antiadipogenic, and anti-inflammatory effects at nonpharmacological doses in an obese diabetic mouse model that exerts early relevant clinical signs of non-insulin-dependent diabetes mellitus. Female db/db mice received a flavonoid-poor diet either without additive, with rosiglitazone (RSG, 0.02 g/kg diet), or with green tea extract (low-dose green tea extract [LGTE] and high-dose green tea extract [HGTE], 0.1 and 1 g/kg diet). Food and water were freely available. The body weight was monitored weekly. Blood was sampled (12-h fasted) from the tail vein on day 28 and analyzed for glucose, cholesterol, triacylglycerol, nonesterified fatty acids, insulin, adiponectin, and soluble intercellular adhesion molecule-1 (sICAM-1). Blood glucose was also analyzed on day 14. Furthermore, sICAM-1 release was investigated in tumor necrosis factor alpha-stimulated EAhy926 cells. After 14 days, fasting glycemia was improved by RSG or HGTE supplementation compared to controls. However, at the end of the study (day 28), only RSG exhibited glucose-lowering effects and induced plasma adiponectin concentrations, paralleled by higher body weight gain and reduced periuterine fat pads compared to controls. However, only GTE treatment reduced sICAM-1 release in vitro and in vivo. Nonpharmacological HGTE supplementation in db/db mice caused (1) no adiponectin-inducing or antiadipogenic effects, (2) reduced sICAM-1 release, thereby potentially exerting anti-inflammatory effects in the progressive diabetic state, and (3) a transient improvement in glycemia. PMID:23514230

  16. [An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

    PubMed

    Hideo, Sakaguchi

    2014-06-01

    Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

  17. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    PubMed Central

    Aekplakorn, Wichai; Tantayotai, Valla; Numsangkul, Sakawduan; Sripho, Wilarwan; Tatsato, Nutchanat; Burapasiriwat, Tuanjai; Pipatsart, Rachada; Sansom, Premsuree; Luckanajantachote, Pranee; Chawarokorn, Pongpat; Thanonghan, Anek; Lakhamkaew, Watchira; Mungkung, Aungsumalin; Boonkean, Rungnapa; Chantapoon, Chanidsa; Kungsri, Mayuree; Luanseng, Kasetsak; Chaiyajit, Kornsinun

    2015-01-01

    Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. PMID:26347060

  18. Relation between Delayed Superfluous Insulin Secretion during An Oral Glucose Tolerance Test and Metabolic Disorders in Obese Japanese Children.

    PubMed

    Sato, Hidetoshi; Kikuchi, Toru; Harada, Waka; Yoshida, Hiroshi; Ito, Sueshi; Uchiyama, Makoto

    2011-04-01

    The aim of this study was to clarify the relation between postprandial hyperinsulinemia and metabolic disorders in obese children. Twenty-eight obese Japanese children (8.8-16.2 yr) were divided into four groups: without impaired liver function and dyslipidemia (Group A), with impaired liver function (Group B), with dyslipidemia (Group C), and with impaired liver function and dyslipidemia (Group D). The levels of PG, serum immunoreactive insulin (IRI) and serum C-peptide (CPR) were measured during an oral glucose tolerance test (OGTT). The subjects had delayed superfluous insulin and CPR secretion during the OGTT compared with healthy references. In regard to the insulin secretion pattern, Group A's response peaked at 60 min and then decreased gradually until 120 min, Group B's response peaked at 60 min, remained at the peak until 120 min and then decreased gradually until 180 min, Group C's response peaked at 120 min and then decreased gradually until 180 min, and Group D's response peaked at 120 min and remained at the peak until 180 min. These results suggest that delayed superfluous insulin secretion during an OGTT is related to metabolic disorders in obese Japanese children and that these patients will experience a vicious cycle of postprandial hyperinsulinemia and metabolic disorders. It is important to prevent healthy children from becoming obese and to improve management of childhood obesity.

  19. Interstitial lactate levels in human skin at rest and during an oral glucose load: a microdialysis study.

    PubMed

    Petersen, L J

    1999-05-01

    In vitro data have suggested that the skin is a significant lactate source. The purpose of the present study was to measure lactate and glucose concentrations in intact human skin in vivo using the microdialysis technique. Microdialysis fibres of 216 microns were inserted intradermally and perfused at a rate of 3 microliters min-1. In the first experimental protocol, dialysis fibres were calibrated by the method of no net flux in eight subjects. Skin lactate concentrations of 2.48 +/- 0.17 mmol l-1 were significantly greater than lactate concentrations of 0.84 +/- 0.15 mmol l-1 in venous plasma (P < 0.01). Glucose concentrations in skin and venous plasma were similar (5.49 +/- 0.18 vs. 5.26 +/- 0.24 mmol l-1). In the second experimental protocol, changes in lactate and glucose levels were studied in 10 subjects after an oral glucose tolerance test (OGTT). After the OGTT, plasma glucose and lactate levels increased by 54% and 39% to peak levels at 30 and 60 min respectively. In comparison, skin glucose and lactate increased by 41% and 18% at 60 and 90 min. No changes in skin blood flow were observed during the OGTT. The data suggest that resting skin is a significant lactate source with no significant lactate production during OGTT. The cellular source of lactate in the skin remains undetermined to date.

  20. Improving oral medication management in home health agencies.

    PubMed

    Shearer, Janelle

    2009-03-01

    This study focused on home health agency characteristics and evidence-based practices that could have an impact on the ability to improve the home health outcome-based quality improvement measure: improvement in the management of oral medications. The findings of this Quality Improvement Organization-approved study suggest that there are organizational characteristics and evidence-based practices associated with better rates for this outcome measure. Organizational characteristics include belonging to a healthcare system that is hospital based, not-for-profit part of a network focused on quality, and intentionally working on the oral medications outcome. Evidence-based practices include use of reminder strategies, phone follow-up interventions, repeat patient education about medications at subsequent home care visits, and use of medication simplification strategies for patients receiving multiple medications.

  1. Polyphenol-Rich Rutgers Scarlet Lettuce Improves Glucose Metabolism and Liver Lipid Accumulation in Diet Induced Obese C57BL/6 Mice

    PubMed Central

    Cheng, Diana M.; Pogrebnyak, Natalia; Kuhn, Peter; Poulev, Alexander; Waterman, Carrie; Rojas-Silva, Patricio; Johnson, William D.

    2014-01-01

    Objective The aims of the following experiments were to characterize anti-diabetic in vitro and in vivo activity of the polyphenol-rich aqueous extract of Rutgers Scarlet Lettuce. Materials / Methods Rutgers Scarlet Lettuce (RSL) extract (RSLE) and isolated compounds were evaluated for inhibitory effects on glucose production as well as tumor necrosis factor alpha (TNFα)-dependent inhibition of insulin activity in H4IIE rat hepatoma cells. Additionally, high fat diet-induced obese mice were treated with RSLE (100 or 300 mg/kg), Metformin (250 mg/kg) or vehicle (water) for 28 days by oral administration and insulin and oral glucose tolerance tests were conducted. Tissues were harvested at the end of the study and evaluated for biochemical and physiological improvements in metabolic syndrome conditions. Results A polyphenol-rich RSLE, containing chlorogenic acid, cyanidin malonyl-glucoside and quercetin malonyl-glucoside, was produced by simple boiling water extraction at pH 2. In vitro, RSLE and chlorogenic acid demonstrated dose-dependent inhibition of glucose production. In vivo, RSLE treatment improved glucose metabolism measured by oral glucose tolerance tests, but not insulin tolerance tests. RSLE treated groups had a lower ratio of liver weight to body weight as well as decreased total liver lipids compared to control group after 28 days of treatment. No significant differences in plasma glucose, insulin, cholesterol, and triglycerides were observed with RSLE treated groups compared to vehicle control. Conclusion RSLE demonstrated anti-diabetic effects in vitro and in vivo and may improve metabolic syndrome conditions of fatty liver and glucose metabolism. PMID:24985107

  2. Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status.

    PubMed

    Santos, J L; Yévenes, I; Cataldo, L R; Morales, M; Galgani, J; Arancibia, C; Vega, J; Olmos, P; Flores, M; Valderas, J P; Pollak, F

    2016-06-01

    Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.

  3. Are the WHO (1980) criteria for the 75 g oral glucose tolerance test appropriate for pregnant women?

    PubMed

    Cheng, L C; Salmon, Y M

    1993-07-01

    To assess the normal response to the 75 gm oral glucose tolerance test (OGTT) in normal pregnant women, healthy Chinese and Malay women who had been referred to the antenatal clinic of the Department of Reproductive Medicine, Kandang Kerbau Hospital, Singapore, were evaluated. The women were selected on the basis of having none of the generally accepted risk factors for diabetes mellitus: their age was 35 years, they weighed 80 kg, they did not have a personal history of diabetes or a family history of diabetes or a family history of diabetes in first degree relatives, nor did they have a history of babies weighing 4000 gm at birth, still-births, neonatal deaths, congenital malformations, or recurrent miscarriages. All OGTTs were performed after 28 weeks of gestation. The fasting blood sample was taken from the antecubital vein. Further samples were taken 1 and 2 hours after the glucose drink. A glucose analyzer using 5 mcl of plasma was employed. The analytical method was based on the glucose oxidase/peroxidase/aminophenazone process. There was no significant difference in mean glucose levels at corresponding points of the OGTT in Chinese and Malay women. correlation calculations confirmed the absence of any influence of gestational age after 28 weeks on glucose tolerance. Of the 64 women, 47 were Chinese and 17 Malays; 20 wee nulliparous, and 44 were parous. Their mean age was 27.2 years (range 18-35). The mean birthweight of the infants was 3140 gm (range 2094-4240 gm). There were 33 female and 31 male infants. The mean apgar scores at 1 and 5 min were 8.8 (range 7-9) and 9.0 (range 6-10). The mean values and the proposed upper limits of normality for the 75 gm OGTT were 3.9 and 4.9 mmol/1, respectively. 6 women had abnormal OGTT results according to the WHO criteria (fasting glucose 6 mmol/1; 2 hour glucose 8 mmol/1).

  4. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes.

  5. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  6. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    PubMed

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin

  7. Rosiglitazone fails to improve hypertriglyceridemia and glucose tolerance in CD36-deficient BN.SHR4 congenic rat strain.

    PubMed

    Seda, Ondrej; Kazdova, Ludmila; Krenova, Drahomira; Kren, Vladimir

    2003-01-15

    The favorable metabolic effects of thiazolidinediones are supposedly related to the peroxisome proliferator-activated receptor-gamma (PPARgamma)-driven changes in lipid metabolism, particularly in free fatty acid (FFA) trafficking. The fatty acid translocase CD36 is one of the proposed PPARgamma targets to mediate this action. We assessed the effect of rosiglitazone (RSG, Avandia) administration in two inbred rat strains, BN/Cub and BN.SHR4 congenic strain, differing in 10 cM proximal segment of chromosome 4. Rats were fed high-sucrose diet with or without RSG for 1 wk. In BN.SHR4, which carries defective Cd36 allele of SHR origin, RSG failed to improve glucose tolerance (assessed by the oral glucose tolerance test), did not lower triglyceridemia, nor induced increases in epididymal and retroperitoneal adipose tissue weights and adipose tissue glucose utilization, effects observed in BN/Cub. On the other hand, the RSG-treated BN.SHR4 showed lower concentrations of FFA and substantial increase in glycogen synthesis and glucose oxidation in skeletal muscle. Altogether, these results support involvement of CD36 in RSG action, suggesting this pharmacogenetic interaction may be of particular importance in CD36-deficient humans.

  8. Glycemic variability in relation to oral disposition index in the subjects with different stages of glucose tolerance

    PubMed Central

    2013-01-01

    Background Glucose variability could be an independent risk factor for diabetes complications in addition to average glucose. The deficiency in islet β cell secretion and insulin sensitivity, the two important pathophysiological mechanisms of diabetes, are responsible for glycemic disorders. The oral disposition index evaluated by product of insulin secretion and sensitivity is a useful marker of islet β cell function. The aim of the study is to investigate glycemic variability in relation to oral disposition index in the subjects across a range of glucose tolerance from the normal to overt type 2 diabetes. Methods 75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47 with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8 with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin secretion index (ΔI30/ΔG30), and integrated β cell function measured by the oral disposition index (ΔI30/ΔG30 multiplied by the ISI) were derived from OGTT. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SD), mean of blood glucose (MBG), high blood glucose index (HBGI), continuous overlapping net glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE). Results From the NGR to IGM to DM2h to DM group, the respective values of SD (mean ± SD) (0.9 ± 0.3, 1.5 ± 0.5, 1.9 ± 0.6 and 2.2 ± 0.6 mmol/), MBG (5.9 ± 0.5, 6.7 ± 0.7, 7.7 ± 1.0 and 8.7 ± 1.5 mmol/L), HGBI [median(Q1–Q3)][0.8(0.2–1.2), 2.0(1.2–3.7), 3

  9. Berberine improves glucose metabolism through induction of glycolysis.

    PubMed

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2008-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for > or =16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.

  10. Chromium improves insulin response to glucose in rats.

    PubMed

    Striffler, J S; Law, J S; Polansky, M M; Bhathena, S J; Anderson, R A

    1995-10-01

    The effects of chromium (Cr) supplementation on insulin secretion and glucose clearance (KG) during intravenous glucose tolerance tests (IVGTTS) were assessed in rats with impaired glucose tolerance due to dietary Cr deficiency. Male Wistar rats were maintained after weaning on a basal low-Cr diet containing 55% sucrose, 15% lard, 25% casein. American Institute of Nutrition (AIN)-recommended levels of vitamins, no added Cr, and an altered mineral content as required to produce Cr deficiency and impaired glucose tolerance. The Cr-supplemented group ([+Cr] n = 6) were provided with 5 ppm Cr as CrCl3 in the drinking water, and the Cr-deficient group ([-Cr]n = 5) received purified drinking water. At 12 weeks on the diet, both groups of rats were hyperinsulinemic (+Cr, 103 +/- 13; -Cr, 59 +/- 12 microU/mL) and normoglycemic (+Cr, 127 +/- 7; -Cr, 130 +/- 4 mg/dL), indicating insulin resistance. After 24 weeks, insulin levels were normal (+Cr, 19 +/- 5; -Cr, 21 +/- 3 microU/mL) and all rats remained normoglycemic (+Cr, 124 +/- 8; -Cr, 131 +/- 6 mg/dL). KG values during IVGTTS were lower in -Cr rats (KG = 3.58%/min) than in +Cr rats (KG = 5.29%/min), correlating with significantly greater 40-minute glucose areas in the -Cr group (P < .01). Comparisons of 40-minute insulin areas indicated marked insulin hyperresponsiveness in the -Cr group, with insulin-secretory responses increased nearly twofold in -Cr animals (P < .05). Chromium deficiency also led to significant decreases in cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (PDE) activity in spleen and testis (P < .01). In these studies, Cr deficiency was characterized by both beta-cell hypersecretion of insulin and tissue insulin resistance that were associated with decreased tissue levels of cAMP PDE activity.

  11. An Improved Method for Studying the Enzyme-Catalyzed Oxidation of Glucose Using Luminescent Probes

    ERIC Educational Resources Information Center

    Bare, William D.; Pham, Chi V.; Cuber, Matthew; Demas, J. N.

    2007-01-01

    A new method is presented for measuring the rate of the oxidation of glucose in the presence of glucose oxidase. The improved method employs luminescence measurements to directly determine the concentration of oxygen in real time, thus obviating complicated reaction schemes employed in previous methods. Our method has been used to determine…

  12. Comparison of glycosylated hemoglobin with the oral glucose tolerance test. A study in subjects with normoglycemia, glucose intolerance and non-insulin-dependent diabetes mellitus.

    PubMed

    Cederholm, J; Ronquist, G; Wibell, L

    1984-10-01

    At a health survey of 819 subjects, 47-54 years old, the rate of glucose intolerance (GI) was 6.2% (51 subjects) according to 75 g oral glucose tolerance tests (OGTT) and WHO criteria. In GI-subjects, the mean HbA1 was 7.3% (10th-90th percentile range 6.2-8.3%), and significantly higher than the mean HbA1 in 150 subjects with normal OGTT, which was 6.5% (10th-90th percentile range 5.7-7.4%). With an upper normal limit of 7.8% (mean + 2 SD) only 20% of all GI-subjects had a raised HbA1. The differences between 31 GI-subjects, with low HbA1 (mean 6.9%), and 20 GI-subjects, with relatively high HbA1 (mean 7.9%), were not significant with respect to fasting and 2-hour blood glucose, area under glucose curve, body mass index, index of physical activity, rate of hypertension or rate of first degree relatives with diabetes. In an unselected group of 157 subjects, sampled consecutively during the first part of the survey, the mean HbA1 was 6.6% (10th-90th percentile range 5.8-7.5 %) 150 subjects were those with normal OGTT, 6 subjects had GI and only one subject had previously unknown diabetes. No distinct correlations between HbA1 and OGTT fasting or 2 hour values were found in this sample. No correlation was found within the separate groups of 51 GI-subjects and 150 normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Short-Term Regulation of Lipocalin-2 but not RBP-4 During Oral Lipid Tolerance Test and Oral Glucose Tolerance Test.

    PubMed

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2016-02-01

    The postprandial regulation of lipocalin-2 and retinol binding protein-4 (RBP-4) by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of lipocalin-2 and RBP-4 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn after 0, 2, 4, and 6 h in OLTT and after 0, 1, and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of lipocalin-2 and RBP-4 were measured by enzyme-linked immunosorbent assay (ELISA). Whereas RBP-4 levels remained unchanged during OGTT, lipocalin-2 concentrations significantly decreased during OGTT. During OLTT, RBP-4 levels were not influenced, whereas lipocalin-2 levels decreased significantly and stepwise. Fasting concentrations of RBP-4 were negatively correlated with BMI and waist-hip ratio, whereas lipocalin-2 levels were positively associated with BMI and waist-hip ratio. Female users of hormonal contraception had higher RBP-4 levels than females not on contraceptives. There is no significant short-term regulation of RBP-4 by orally ingested lipids or carbohydrates. Lipocalin-2 is downregulated after lipid and carbohydrate ingestion and this kind of regulation was not predicted by age, sex, triglycerides, glucose, or insulin levels. PMID:26069091

  14. Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats

    PubMed Central

    Lin, Wenting; Wang, Wenxiang; Liao, Dongdong; Chen, Damiao; Zhu, Pingping; Cai, Guoxi; Kiyoshi, Aoyagi

    2015-01-01

    This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. PMID:26347892

  15. Breed differences in insulin sensitivity and insulinemic responses to oral glucose in horses and ponies of moderate body condition score.

    PubMed

    Bamford, N J; Potter, S J; Harris, P A; Bailey, S R

    2014-04-01

    Breed-related differences may occur in the innate insulin sensitivity (SI) of horses and ponies, an important factor believed to be associated with the risk of laminitis. The aim of this study was to measure the glucose and insulin responses of different breeds of horses and ponies in moderate body condition to a glucose-containing meal and to compare these responses with the indices of SI as determined by a frequently sampled intravenous glucose tolerance test (FSIGT). Eight Standardbred horses, 8 mixed-breed ponies, and 7 Andalusian-cross horses with a mean ± SEM BCS 5.0 ± 0.3 of 9 were used in this study. Each animal underwent an oral glucose tolerance test (OGTT) in which they were fed a fiber-based ration (2.0 g/kg BW) containing 1.5 g/kg BW added glucose, as well as a standard FSIGT with minimal model analysis. The glucose response variables from the OGTT were similar between groups; however, the peak insulin concentration was higher in ponies (94.1 ± 29.1 μIU/mL; P = 0.003) and Andalusians (85.3 ± 18.6; P = 0.004) than in Standardbreds (21.2 ± 3.5). The insulin area under the curve was also higher in ponies (13.5 ± 3.6 IU · min · L(-1); P = 0.009) and Andalusians (15.0 ± 2.7; P = 0.004) than in Standardbreds (3.1 ± 0.6). Insulin sensitivity, as determined by the FSIGT, was lower in Andalusians (0.99 ± 0.18 × 10(-4)/[mIU · min]) than in Standardbreds (5.43 ± 0.94; P < 0.001) and in ponies (2.12 ± 0.44; P = 0.003) than in Standardbreds. Peak insulin concentrations from the OGTT were negatively correlated with SI (P < 0.001; rs = -0.75). These results indicate that there are clear breed-related differences in the insulin responses of horses and ponies to oral and intravenous glucose. All animals were in moderate body condition, indicating that breed-related differences in insulin dynamics occurred independent of obesity. PMID:24308928

  16. Sourdough-leavened bread improves postprandial glucose and insulin plasma levels in subjects with impaired glucose tolerance.

    PubMed

    Maioli, Mario; Pes, Giovanni Mario; Sanna, Manuela; Cherchi, Sara; Dettori, Mariella; Manca, Elena; Farris, Giovanni Antonio

    2008-06-01

    Sourdough bread has been reported to improve glucose metabolism in healthy subjects. In this study postprandial glycaemic and insulinaemic responses were evaluated in subjects with impaired glucose tolerance (IGT) who had a meal containing sourdough bread leavened with lactobacilli, in comparison to a reference meal containing bread leavened with baker yeast. Sixteen IGT subjects (age range 52-75, average BMI 29.9 +/- 4.2 kg/ m2) were randomly given a meal containing sourdough bread (A) and a meal containing the reference bread (B) in two separate occasions at the beginning of the study and after 7 days. Sourdough bread was leavened for 8 h using a starter containing autochthonous Saccharomyces cerevisiae and several bacilli able to produce a significant amount of D-and L-lactic acid, whereas the reference bread was leavened for 2 h with commercial baker yeast containing Saccharomyces cerevisiae. Plasma glucose and insulin levels were measured at time 0, 30, 60, 120, and 180 min. In IGT subjects sourdough bread induced a significantly lower plasma glucose response at 30 minutes (p = 0.048) and a smaller incremental area under curve (AUC) delta 0-30 and delta 0-60 min (p = 0.020 and 0.018 respectively) in comparison to the bread leavened with baker yeast. Plasma insulin response to this type of bread showed lower values at 30 min (p = 0.045) and a smaller AUC delta 0-30 min (p = 0.018). This study shows that in subjects with IGT glycaemic and insulinaemic responses after the consumption of sourdough bread are lower than after the bread leavened with baker yeast. This effect is likely due to the lactic acid produced during dough leavening as well as the reduced availability of simple carbohydrates. Thus, sour-dough bread may potentially be of benefit in subjects with impaired glucose metabolism.

  17. Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion

    PubMed Central

    Wang, Fei; Kohan, Alison B.; Kindel, Tammy L.; Corbin, Kathryn L.; Nunemaker, Craig S.; Obici, Silvana; Woods, Stephen C.; Davidson, W. Sean; Tso, Patrick

    2012-01-01

    Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV–treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca2+ influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV−/− mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV−/− mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes. PMID:22619326

  18. Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

    PubMed Central

    Li, Haiying; Pan, Tingting; Cui, Ying; Li, Xiaxia; Gao, Jiefang; Yang, Wenzhi; Shen, Shigang

    2016-01-01

    The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM. PMID:27540291

  19. Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique.

    PubMed

    Li, Haiying; Pan, Tingting; Cui, Ying; Li, Xiaxia; Gao, Jiefang; Yang, Wenzhi; Shen, Shigang

    2016-01-01

    The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box-Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM. PMID:27540291

  20. Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults.

    PubMed

    Ochiai, Ryuji; Sugiura, Yoko; Shioya, Yasushi; Otsuka, Kazuhiro; Katsuragi, Yoshihisa; Hashiguchi, Teruto

    2014-02-01

    Brewed coffee is a widely consumed beverage, and many studies have examined its effects on human health. We investigated the vascular effects of coffee polyphenols (CPPs), hypothesizing that a single ingestion of CPP during glucose loading would improve endothelial function. To test this hypothesis, we conducted a randomized acute clinical intervention study with crossover design and measured reactive hyperemia index (RHI) to assess the acute effects of a 75-g glucose load with CPP in healthy, nondiabetic adult men. Blood glucose and insulin levels were elevated after glucose loading with and without CPP, with no significant differences between treatments. The RHI did not significantly decrease after glucose loading without CPP. With CPP, however, RHI significantly (P < .05) increased over baseline after glucose loading. The difference between treatments was statistically significant (P < .05). No significant changes were observed in an oxidative stress marker after glucose loading with or without CPP. These findings suggest that a single ingestion of CPP improves peripheral endothelial function after glucose loading in healthy subjects.

  1. Mango Supplementation Improves Blood Glucose in Obese Individuals

    PubMed Central

    Evans, Shirley F; Meister, Maureen; Mahmood, Maryam; Eldoumi, Heba; Peterson, Sandra; Perkins-Veazie, Penelope; Clarke, Stephen L; Payton, Mark; Smith, Brenda J; Lucas, Edralin A

    2014-01-01

    This pilot study examined the effects of freeze-dried mango (Mangifera indica L.) supplementation on anthropometrics, body composition, and biochemical parameters in obese individuals. Twenty obese adults (11 males and 9 females) ages 20- to 50-years old, received 10 g/day of ground freeze-dried mango pulp for 12 weeks. Anthropometrics, biochemical parameters, and body composition were assessed at baseline and final visits of the study. After 12 weeks, mango supplementation significantly reduced blood glucose in both male (−4.45 mg/dL, P = 0.018) and female (−3.56 mg/dL, P = 0.003) participants. In addition, hip circumference was reduced in male (−3.3 cm, P = 0.048) but not in female participants. However, there were no significant changes in body weight or composition in either gender. Our findings indicate that regular consumption of freeze-dried mango by obese individuals does not negatively impact body weight but provides a positive effect on fasting blood glucose. PMID:25210462

  2. Optimized zein nanospheres for improved oral bioavailability of atorvastatin

    PubMed Central

    Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama AA

    2015-01-01

    Background This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. Methods Twelve experimental runs of atorvastatin–zein nanosphere formula were formulated by a liquid–liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X1), pH (X2), and stirring time (X3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y1), zeta potential (Y2), drug loading efficiency (Y3), drug encapsulation efficiency (Y4), and yield (Y5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin–zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. Results The optimized atorvastatin–zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin–zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. Conclusion The atorvastatin–zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability. PMID:26150716

  3. Electroacupuncture improves glucose tolerance through cholinergic nerve and nitric oxide synthase effects in rats.

    PubMed

    Lin, Rong-Tsung; Chen, Ching-Yuan; Tzeng, Chung-Yuh; Lee, Yu-Chen; Cheng, Yu-Wen; Chen, Ying-I; Ho, Wai-Jane; Cheng, Juei-Tang; Lin, Jaung-Geng; Chang, Shih-Liang

    2011-04-25

    The purpose of this investigation was to evaluate the effect and mechanisms of electroacupuncture (EA) at the bilateral Zusanli acupoints (ST-36) on glucose tolerance in normal rats. Intravenous glucose tolerance test (IVGTT) was performed to examine the effects of electroacupuncture (EA) on glucose tolerance in rats. The EA group underwent EA at the ST-36, with settings of 15 Hz, 10 mA, and 60 min; the control group underwent the same treatments, but without EA. Atropine, hemicholinium-3 (HC-3) or NG-nitro-L-arginine methyl ester (L-NAME) were injected into the rats alone or simultaneously and EA was performed to investigate differences in plasma glucose levels compared to the control group. Plasma samples were obtained for assaying plasma glucose and free fatty acid (FFA) levels. Western blot was done to determine the insulin signal protein and nNOS to exam the correlation between EA and improvement in glucose tolerance. The EA group had significantly lower plasma glucose levels compared to the control group. Plasma glucose levels differed significantly between the EA and control groups after the administration of L-NAME, atropine, or HC-3 treatments alone, but there were no significant differences in plasma glucose with combined treatment of L-NAME and atropine or L-NAME and HC-3. EA decreased FFA levels and enhanced insulin signal protein (IRS1) and nNOS activities in skeletal muscle during IVGTT. In summary, EA stimulated cholinergic nerves and nitric oxide synthase for lowering plasma FFA levels to improve glucose tolerance. PMID:21376780

  4. An inverse U-shaped association of late and peak insulin levels during an oral glucose load with glucose intolerance in a Japanese population: a cross-sectional study.

    PubMed

    Takahara, Mitsuyoshi; Katakami, Naoto; Matsuoka, Taka-Aki; Noguchi, Midori; Shimomura, Iichiro

    2015-01-01

    The current study investigated the association of post-load insulin levels with glucose tolerance in a Japanese population. A total of 1450 Japanese employees who underwent a 75-g oral glucose tolerance test (OGTT) were included. Glucose tolerance was assessed by 120-min glucose levels during a 75-g OGTT. A penalized cubic regression spline model analysis revealed that the 60- and 120-min insulin levels, but not 0- or 30-min insulin levels, had an inverse U-shaped relationship to the 120-min glucose level. Furthermore, peak insulin level followed an inverse U shape in relation to the 120-min glucose level, whereas the peak of insulin appeared at a later point in time as the 120-min glucose level increased. These associations were similarly observed in both obese and non-obese subgroups, although obesity was associated with higher insulin levels. Peak insulin levels also demonstrated an inverse U shape in association with 0-min glucose levels and indices of β cell function, assessed by the disposition index and the β-cell function index. In conclusion, peak insulin levels followed an inverse U shape in relation to glucose intolerance in a Japanese population, whereas the impairment of glucose tolerance was associated with a delay in the time to reach peak insulin levels.

  5. Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle

    PubMed Central

    Amitani, Haruka; Asakawa, Akihiro; Cheng, Kaichun; Amitani, Marie; Kaimoto, Kaori; Nakano, Masako; Ushikai, Miharu; Li, Yingxiao; Tsai, Minglun; Li, Jiang-Bo; Terashi, Mutsumi; Chaolu, Huhe; Kamimura, Ryozo; Inui, Akio

    2013-01-01

    Hydrogen (H2) acts as a therapeutic antioxidant. However, there are few reports on H2 function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H2 promoted 2-[14C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally. PMID:23326534

  6. Improving adherence to oral cancer therapy in clinical practice.

    PubMed

    McCue, Debbie A; Lohr, Lisa K; Pick, Amy M

    2014-05-01

    Adherence to oral chemotherapy regimens maximizes their effectiveness and minimizes any potential toxicities. Factors specifically related to the treatment, patient, and health care provider may influence medication adherence. Treatment-related factors include the complexity of the regimen, the cost of therapy, the possibility of side effects, and the delay in treatment benefits. Meanwhile, patients may not have an adequate support system or an understanding of the need for the medication, and providers may not fully succeed in communicating the importance of adherence and the types of side effects that may occur. Nonadherence may lead to an increased risk of toxicity, decreased effectiveness, and increased utilization of health care resources. Although various methods for measuring adherence are available, self-reporting is the most widely used. Studies describing adherence in a broad range of cancers are reviewed. Treatment of chronic myeloid leukemia has been revolutionized by the development of oral tyrosine kinase inhibitors that are highly effective in managing the disease when taken consistently. However, nonadherence is relatively common and can lead to reduced rates of response and increased medical costs. Similar effects of nonadherence on outcome and cost have also been observed in patients with various other hematologic malignancies and solid tumors. Interventions to improve adherence to oral chemotherapy regimens include communication about the importance of adherence and the potential consequences of nonadherence, simplification of the patient's medication schedule (if possible), and inclusion of a caregiver or family member in the conversation. Written materials should always be provided to accompany verbal instructions. This review summarizes factors influencing medication adherence, impact of nonadherence on patient outcomes, methods for measuring adherence, previous studies of nonadherence in patients with cancer, common barriers to access, and

  7. Longterm oral cisapride improves interdigestive antroduodenal motility in dyspeptic patients.

    PubMed Central

    Testoni, P A; Bagnolo, F; Fanti, L; Passaretti, S; Tittobello, A

    1990-01-01

    We have evaluated the effect of cisapride on interdigestive antroduodenal motility during a prolonged oral therapy in 20 consecutive dyspeptic subjects. Individuals with less than two migrating motor complexes (MMCs) starting from the antral region in 240 minutes and without evidence of upper gastrointestinal tract diseases were randomly treated with either cisapride (10 cases), or placebo (10 cases) for 15 days. Computerised manometry of antroduodenal region was performed for 240 minutes, in basal conditions and on the 15th day of therapy. Symptomatic evaluation of patients was also performed before and after treatment. After cisapride administration, a significant increase in the incidence of antral migrating motor complexes was noticed (p = 0.022); likewise, the motility index, calculated for phase-2 periods, appeared to be significantly higher both in the antrum and in the duodenum (p less than 0.001). Symptomatic improvement was observed in both groups, with a hardly significant (p = 0.049) reduction of dyspeptic symptoms severity only but not of frequency in cisapride treated patients v controls. We conclude that longterm oral therapy with cisapride improves interdigestive antroduodenal motor activity. PMID:2323591

  8. Modeling insulin kinetics: responses to a single oral glucose administration or ambulatory-fed conditions.

    PubMed

    Lenbury, Y; Ruktamatakul, S; Amornsamarnkul, S

    2001-01-01

    This paper presents a nonlinear mathematical model of the glucose-insulin feedback system, which has been extended to incorporate the beta-cells' function on maintaining and regulating plasma insulin level in man. Initially, a gastrointestinal absorption term for glucose is utilized to effect the glucose absorption by the intestine and the subsequent release of glucose into the bloodstream, taking place at a given initial rate and falling off exponentially with time. An analysis of the model is carried out by the singular perturbation technique in order to derive boundary conditions on the system parameters which identify, in particular, the existence of limit cycles in our model system consistent with the oscillatory patterns often observed in clinical data. We then utilize a sinusoidal term to incorporate the temporal absorption of glucose in order to study the responses in the patients under ambulatory-fed conditions. A numerical investigation is carried out in this case to construct a bifurcation diagram to identify the ranges of parametric values for which chaotic behavior can be expected, leading to interesting biological interpretations. PMID:11226623

  9. Rare sugar D-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

    PubMed

    Hossain, Mohammad A; Kitagaki, Shigeru; Nakano, Daisuke; Nishiyama, Akira; Funamoto, Yasunobu; Matsunaga, Toru; Tsukamoto, Ikuko; Yamaguchi, Fuminori; Kamitori, Kazuyo; Dong, Youyi; Hirata, Yuko; Murao, Koji; Toyoda, Yukiyasu; Tokuda, Masaaki

    2011-02-01

    A rare sugar, D-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of D-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% D-psicose or 5% D-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, D-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that D-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed D-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. D-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that D-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.

  10. Sensor Monitoring of Physical Activity to Improve Glucose Management in Diabetic Patients: A Review

    PubMed Central

    Ding, Sandrine; Schumacher, Michael

    2016-01-01

    Diabetic individuals need to tightly control their blood glucose concentration. Several methods have been developed for this purpose, such as the finger-prick or continuous glucose monitoring systems (CGMs). However, these methods present the disadvantage of being invasive. Moreover, CGMs have limited accuracy, notably to detect hypoglycemia. It is also known that physical exercise, and even daily activity, disrupt glucose dynamics and can generate problems with blood glucose regulation during and after exercise. In order to deal with these challenges, devices for monitoring patients’ physical activity are currently under development. This review focuses on non-invasive sensors using physiological parameters related to physical exercise that were used to improve glucose monitoring in type 1 diabetes (T1DM) patients. These devices are promising for diabetes management. Indeed they permit to estimate glucose concentration either based solely on physical activity parameters or in conjunction with CGM or non-invasive CGM (NI-CGM) systems. In these last cases, the vital signals are used to modulate glucose estimations provided by the CGM and NI-CGM devices. Finally, this review indicates possible limitations of these new biosensors and outlines directions for future technologic developments. PMID:27120602

  11. Efficacy of standard glucose-based and reduced-osmolarity maltodextrin-based oral rehydration solutions: effect of sugar malabsorption.

    PubMed Central

    el-Mougi, M.; Hendawi, A.; Koura, H.; Hegazi, E.; Fontaine, O.; Pierce, N. F.

    1996-01-01

    Previously we reported that standard oral rehydration salts (ORS) solution is not as effective as a reduced-osmolarity glucose-based ORS for the treatment of children with acute noncholera diarrhoea: with standard ORS the diarrhoea lasts longer, stool output is greater, serum sodium is higher, and there is more need for supplemental intravenous infusion. We studied a reduced-osmolarity maltodextrin (MD)-based ORS to determine whether it had similar benefits, and also the effect of sugar malabsorption on the efficacy of standard and MD-based ORS. A total of 90 boys aged 3-24 months with acute noncholera diarrhoea and moderate dehydration were randomly assigned to either standard ORS (glucose 20 g/l, osmolarity 311 mmol/l) or MD-ORS (MD 50 g/l, osmolarity 227 mmol/l). There were no differences in treatment results. Some 46% of subjects had a high total stool output (> 300 g/kg), which was unrelated to the type of ORS given. High stool output was significantly associated with a longer duration of diarrhoea (33 vs. 15 hours; P < 0.001), a persistently elevated serum sodium (149 vs. 144 mmol/l at 24 h; P < 0.02), the need for intravenous infusion (11/41 vs. 0/48; P < 0.002), and an increase in faecal reducing substances (10.8 vs. 3.4 g/l at 24 h; P < 0.001). We conclude that some children given standard ORS develop osmotic diarrhoea owing to the combined effect of transient sugar malabsorption and slight hypertonicity of the ORS. Earlier studies show that this adverse outcome can largely be avoided when extra water is given in reduced-osmolarity glucose-based ORS. Reduced osmolarity has no benefit, however, when glucose is replaced by maltodextrin, probably because the sugars released by hydrolysis of MD, when malabsorbed, raise the intraluminal osmolarity to equal or exceed that of standard ORS. Thus, reduced-osmolarity glucose-based ORS is superior to both standard ORS and reduced-osmolarity solutions based on maltodextrin and probably other complex carbohydrates

  12. Germinated Pigmented Rice (Oryza Sativa L. cv. Superhongmi) Improves Glucose and Bone Metabolisms in Ovariectomized Rats

    PubMed Central

    Chung, Soo Im; Ryu, Su Noh; Kang, Mi Young

    2016-01-01

    The effect of germinated Superhongmi, a reddish brown pigmented rice cultivar, on the glucose profile and bone turnover in the postmenopausal-like model of ovariectomized rats was determined. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n = 10): normal control diet (NC) and normal diet supplemented with non-germinated Superhongmi (SH) or germinated Superhongmi (GSH) rice powder. After eight weeks, the SH and GSH groups showed significantly lower body weight, glucose and insulin concentrations, levels of bone resorption markers and higher glycogen and 17-β-estradiol contents than the NC group. The glucose metabolism improved through modulation of adipokine production and glucose-regulating enzyme activities. The GSH rats exhibited a greater hypoglycemic effect and lower bone resorption than SH rats. These results demonstrate that germinated Superhongmi rice may potentially be useful in the prevention and management of postmenopausal hyperglycemia and bone turnover imbalance. PMID:27775654

  13. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism.

    PubMed

    Kopf, S R; Baratti, C M

    1994-11-01

    Post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) facilitated 24-h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. Glucose did not increase the retention latencies of mice that had not received a footshock during training. The effect of glucose (30 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by glucose (30 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to glucose treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training glucose on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and glucose (10 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of glucose (10 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the memory facilitation induced by post-training administration of glucose could result from an enhancement of brain acetylcholine synthesis and/or its release that, in turn, might modulate the activity of muscarinic cholinergic mechanisms that are critically involved in memory storage. PMID:7857246

  14. Memory-improving actions of glucose: involvement of a central cholinergic muscarinic mechanism.

    PubMed

    Kopf, S R; Baratti, C M

    1994-11-01

    Post-training intraperitoneal administration of alpha-D[+]-glucose (10-300 mg/kg) facilitated 24-h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. Glucose did not increase the retention latencies of mice that had not received a footshock during training. The effect of glucose (30 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by glucose (30 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to glucose treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training glucose on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and glucose (10 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of glucose (10 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the memory facilitation induced by post-training administration of glucose could result from an enhancement of brain acetylcholine synthesis and/or its release that, in turn, might modulate the activity of muscarinic cholinergic mechanisms that are critically involved in memory storage.

  15. Improving Oral Communication Skills of Students in Food Science Courses

    ERIC Educational Resources Information Center

    Reitmeier, C. A.; Svendsen, L. K.; Vrchota, D. A.

    2004-01-01

    Communication activities about food evaluation were incorporated into food preparation courses. Oral reports replaced quizzes and an oral presentation replaced the final exam. A rubric was developed to help students evaluate ingredient functions, procedures, techniques, temperatures, and sensory evaluation. Oral report scores, self-evaluations,…

  16. Effect of long-term oral administration of green tea extract on weight gain and glucose tolerance in Zucker diabetic (ZDF) rats.

    PubMed

    Janle, Elsa M; Portocarrero, Carla; Zhu, Yongxin; Zhou, Qin

    2005-01-01

    There have been some claims that green tea reduces weight and lowers blood glucose in diabetes. Intraperitoneal injections of green tea catechins in diabetic rats have shown beneficial effects. To determine if oral administration of green tea would prevent development of diabetes, young Zucker diabetic rats were dosed with green tea extract containing 50-125 mg/kg of Epigallocatechin gallate (EGCG) starting at 7 weeks of age, before the appearance of excessive weight gain and glucose elevation. While there was a trend toward lower weight gain and average daily glucose, there was no statistically significant difference.

  17. Aqueous extract of tamarind seeds selectively increases glucose transporter-2, glucose transporter-4, and islets' intracellular calcium levels and stimulates β-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes mellitus.

    PubMed

    Sole, Sushant Shivdas; Srinivasan, B P

    2012-08-01

    Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)-induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin (A1c)) and tumor necrosis factor α (TNF-α) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased β-cell neogenesis, indicating its effect on islets and β-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of β-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy.

  18. Aqueous extract of tamarind seeds selectively increases glucose transporter-2, glucose transporter-4, and islets' intracellular calcium levels and stimulates β-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes mellitus.

    PubMed

    Sole, Sushant Shivdas; Srinivasan, B P

    2012-08-01

    Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)-induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin (A1c)) and tumor necrosis factor α (TNF-α) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased β-cell neogenesis, indicating its effect on islets and β-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of β-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy. PMID:22935346

  19. Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet

    PubMed Central

    Carter, Lindsay G; Ngo Tenlep, Sara Y; Woollett, Laura A; Pearson, Kevin J

    2016-01-01

    Objective Physical activity has been suggested as a non-pharmacological intervention that can be used to improve glucose homeostasis in women with gestational diabetes mellitus. The purpose of this study was to determine the effects of voluntary exercise on glucose tolerance and body composition in pregnant high fat diet fed mice. Methods Female mice were put on a standard diet or high fat diet for two weeks. The mice were then split into 4 groups; control standard diet fed, exercise standard diet fed, control high fat diet fed, and exercise high fat diet fed. Exercise mice had voluntary access to a running wheel in their home cage one week prior to mating, during mating, and throughout pregnancy. Glucose tolerance and body composition were measured during pregnancy. Akt levels were quantified in skeletal muscle and adipose tissue isolated from saline or insulin injected pregnant dams as a marker for insulin signaling. Results Consumption of the high fat diet led to significantly increased body weight, fat mass, and impaired glucose tolerance in control mice. However, voluntary running in the high fat diet fed dams significantly reduced weight gain and fat mass and ultimately improved glucose tolerance compared to control high fat diet fed dams. Further, body weight, fat mass, and glucose disposal in exercise high fat diet dams were indistinguishable from control dams fed the standard diet. High fat diet fed exercise dams also had significantly increased insulin stimulated phosphorylated Akt expression in adipose tissue, but not skeletal muscle, compared to control dams on high fat diet. Conclusion The use of voluntary exercise improves glucose homeostasis and body composition in pregnant female mice. Thus, future studies could investigate potential long-term health benefits in offspring born to obese exercising dams. PMID:26966635

  20. Glucose tolerance factor extracted from yeast: oral insulin-mimetic and insulin-potentiating agent: in vivo and in vitro studies.

    PubMed

    Weksler-Zangen, Sarah; Mizrahi, Tal; Raz, Itamar; Mirsky, Nitsa

    2012-09-01

    In search for an effective oral treatment for diabetes, we examined the capacity of glucose tolerance factor (GTF) extracted from yeast and administered orally to reduce hyperglycaemia in rat models exhibiting insulin deficiency. The cellular effect of GTF on the insulin signalling pathway was investigated in vitro. GTF (oral bolus), insulin (intraperitoneal) or their combination was administered to streptozotocin-diabetic (STZ) or hyperglycaemic Cohen diabetic-sensitive (hyp-CDs) rats. Blood glucose (BG) and insulin levels were measured in the postprandial (PP) state and during an oral glucose tolerance test. Deoxy-glucose transport and insulin signal transduction were assessed in 3T3-L1 adipocytes and myoblasts incubated with the GTF. Low dose of insulin produced a 34 and 12·5 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. GTF induced a 33 and 17 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. When combined with insulin, a respective decrease (58 and 42 %) in BG levels was observed, suggesting a partially additive (hyp-CDs) or synergistic (STZ rats) effect of the GTF and insulin. GTF did not induce insulin secretion in hyp-CDs rats, yet it lowered their BG levels, proposing an effect on glucose clearance by peripheral tissues. GTF induced a dose-dependent increase in deoxy-glucose transport into myoblasts and fat cells similar to insulin, while the combined treatment resulted in augmented transport rate. GTF induced a dose- and time-dependent phosphorylation of insulin receptor substrate 1, Akt and mitogen-activated protein kinase independent of insulin receptor phosphorylation. GTF exerts remarkable insulin-mimetic and insulin-potentiating effects, both in vivo and in vitro. It produces an insulin-like effect by acting on cellular signals downstream of the insulin receptor. These results demonstrate a potential source for a novel oral medication for diabetes.

  1. Oral nitrite therapy improves vascular function in diabetic mice

    PubMed Central

    Sindler, Amy L; Cox-York, Kimberly; Reese, Lauren; Bryan, Nathan S; Seals, Douglas R; Gentile, Christopher L

    2016-01-01

    Aim We tested the hypothesis that short-term oral sodium nitrite supplementation would improve vascular dysfunction in obese, diabetic mice. Methods and results Vascular function was determined in control mice and in db/db mice receiving drinking water with or without sodium nitrite (50 mg/L) for 5 weeks. Nitrite supplementation increased plasma nitrite concentrations in db/db mice (0.19±0.02 μM vs 0.80±0.26μM; p < 0.05). Db/db mice had lower endothelium-dependent dilation (EDD) in response to increasing doses of acetylcholine versus heterozygous control mice (71.2% ± 14.3% vs 93% ± 7.0%; p < 0.05), and sodium nitrite supplementation restored endothelium-dependent dilation to control levels (92.9% ± 2.3% vs 93% ± 7.0%; p < 0.05). The improvement in endothelial function was accompanied by a reduction in intrinsic stiffness, but not by alterations in plasma or vascular markers of inflammation. Conclusion These data suggest that sodium nitrite may be a novel therapy for treating diabetes-related vascular dysfunction; however, the mechanisms of improvement are unknown. PMID:25696116

  2. Glucose screening tests during pregnancy

    MedlinePlus

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... first step, you will have a glucose screening test: You DO NOT need to prepare or change ...

  3. GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism

    PubMed Central

    Efanov, Alexander M.; Fang, Xiankang; Beavers, Lisa S.; Wang, Xuesong; Wang, Jingru; Gonzalez Valcarcel, Isabel C.; Ma, Tianwei

    2016-01-01

    GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes. PMID:27322810

  4. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    SciTech Connect

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  5. Improving the safety of oral immunotherapy for food allergy.

    PubMed

    Vazquez-Ortiz, Marta; Turner, Paul J

    2016-03-01

    Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health-related quality of life. In the last decade, research into disease-modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks-months. OIT has proven effective to induce immune modulation and 'desensitization' - that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short- and long-term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long-term adherence is unclear, which rises concerns given the low rates of long-term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti-IgE, pre-/probiotics). Biomarkers of safe/successful OIT are also under investigation. PMID:26593873

  6. Improving the safety of oral immunotherapy for food allergy.

    PubMed

    Vazquez-Ortiz, Marta; Turner, Paul J

    2016-03-01

    Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health-related quality of life. In the last decade, research into disease-modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks-months. OIT has proven effective to induce immune modulation and 'desensitization' - that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short- and long-term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long-term adherence is unclear, which rises concerns given the low rates of long-term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti-IgE, pre-/probiotics). Biomarkers of safe/successful OIT are also under investigation.

  7. Nrf2 Deficiency Improves Glucose Tolerance in Mice Fed a High-Fat Diet

    PubMed Central

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-01-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. PMID:23017736

  8. HIF prolyl 4-hydroxylase-2 inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction.

    PubMed

    Rahtu-Korpela, Lea; Karsikas, Sara; Hörkkö, Sohvi; Blanco Sequeiros, Roberto; Lammentausta, Eveliina; Mäkelä, Kari A; Herzig, Karl-Heinz; Walkinshaw, Gail; Kivirikko, Kari I; Myllyharju, Johanna; Serpi, Raisa; Koivunen, Peppi

    2014-10-01

    Obesity is a major public health problem, predisposing subjects to metabolic syndrome, type 2 diabetes, and cardiovascular diseases. Specific prolyl 4-hydroxylases (P4Hs) regulate the stability of the hypoxia-inducible factor (HIF), a potent governor of metabolism, with isoenzyme 2 being the main regulator. We investigated whether HIF-P4H-2 inhibition could be used to treat obesity and its consequences. Hif-p4h-2-deficient mice, whether fed normal chow or a high-fat diet, had less adipose tissue, smaller adipocytes, and less adipose tissue inflammation than their littermates. They also had improved glucose tolerance and insulin sensitivity. Furthermore, the mRNA levels of the HIF-1 targets glucose transporters, glycolytic enzymes, and pyruvate dehydrogenase kinase-1 were increased in their tissues, whereas acetyl-CoA concentration was decreased. The hepatic mRNA level of the HIF-2 target insulin receptor substrate-2 was higher, whereas that of two key enzymes of fatty acid synthesis was lower. Serum cholesterol levels and de novo lipid synthesis were decreased, and the mice were protected against hepatic steatosis. Oral administration of an HIF-P4H inhibitor, FG-4497, to wild-type mice with metabolic dysfunction phenocopied these beneficial effects. HIF-P4H-2 inhibition may be a novel therapy that not only protects against the development of obesity and its consequences but also reverses these conditions.

  9. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.

    PubMed

    Miranda, Cristobal L; Elias, Valerie D; Hay, Joshua J; Choi, Jaewoo; Reed, Ralph L; Stevens, Jan F

    2016-06-01

    Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice. PMID:26976708

  10. Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

    PubMed

    Hirata, Ayumu; Funato, Hiroki; Nakai, Megumi; Iizuka, Michiro; Abe, Noriaki; Yagi, Yusuke; Shiraishi, Hisashi; Jobu, Kohei; Yokota, Junko; Hirose, Kahori; Hyodo, Masamitsu; Miyamura, Mitsuhiko

    2016-01-01

    We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function. PMID:27374286

  11. Detection of Abnormal Glucose Tolerance in Africans Is Improved by Combining A1C With Fasting Glucose: The Africans in America Study

    PubMed Central

    Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.; Tulloch-Reid, Marshall K.; Lozier, Jay N.; Sacks, David B.

    2015-01-01

    OBJECTIVE Abnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A1c by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG ≥5.6 mmol/L, 2) A1C ≥ 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG ≥5.6 mmol/L and/or A1C ≥5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance. RESEARCH DESIGN AND METHODS An oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 ± 10 years [mean ± SD], range 20–64 years). Abnormal glucose tolerance was defined as 2-h glucose ≥7.8 mmol/L. RESULTS Variant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose ≥7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P > 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values ≤ 0.01). CONCLUSIONS No significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone. PMID:25338926

  12. Potentiation of insulin secretion and improvement of glucose intolerance by combining a novel G protein-coupled receptor 40 agonist DS-1558 with glucagon-like peptide-1 receptor agonists.

    PubMed

    Nakashima, Ryutaro; Yano, Tatsuya; Ogawa, Junko; Tanaka, Naomi; Toda, Narihiro; Yoshida, Masao; Takano, Rieko; Inoue, Masahiro; Honda, Takeshi; Kume, Shoen; Matsumoto, Koji

    2014-08-15

    G protein-coupled receptor 40 (GPR40) is a Gq-coupled receptor for free fatty acids predominantly expressed in pancreatic β-cells. In recent years, GPR40 agonists have been investigated for use as novel therapeutic agents in the treatment of type 2 diabetes. We discovered a novel small molecule GPR40 agonist, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid (DS-1558). The GPR40-mediated effects of DS-1558 on glucose-stimulated insulin secretion were evaluated in isolated islets from GPR40 knock-out and wild-type (littermate) mice. The GPR40-mediated effects on glucose tolerance and insulin secretion were also confirmed by an oral glucose tolerance test in these mice. Furthermore, oral administration of DS-1558 (0.03, 0.1 and 0.3mg/kg) significantly and dose-dependently improved hyperglycemia and increased insulin secretion during the oral glucose tolerance test in Zucker fatty rats, the model of insulin resistance and glucose intolerance. Next, we examined the combination effects of DS-1558 with glucagon like peptide-1 (GLP-1). DS-1558 not only increased the glucose-stimulated insulin secretion by GLP-1 but also potentiated the maximum insulinogenic effects of GLP-1 after an intravenous glucose injection in normal Sprague Dawley rats. Furthermore, the glucose lowering effects of exendin-4, a GLP-1 receptor agonist, were markedly potentiated by the DS-1558 (3mg/kg) add-on in diabetic db/db mice during an intraperitoneal glucose tolerance test. In conclusion, our results indicate that add-on GPR40 agonists to GLP-1 related agents might be a potential treatment compared to single administration of these compounds. Therefore the combinations of these agents are a novel therapeutic option for type 2 diabetes.

  13. Using Reading and Writing to Improve Oral Language Skills.

    ERIC Educational Resources Information Center

    Johnson, Doris J.

    1985-01-01

    Use of reading and writing to enhance oral communication skills requires analysis of the individual's performance; understanding of the interaction among auditory, oral, and written language disorders; integration of speech-language and educational services; and attention to skills of phonemic discrimination, auditory verbal comprehension, word…

  14. Pain reduction and financial incentives to improve glucose monitoring adherence in a community health center.

    PubMed

    Huntsman, Mary Ann H; Olivares, Faith J; Tran, Christina P; Billimek, John; Hui, Elliot E

    2014-01-01

    Self-monitoring of blood glucose is a critical component of diabetes management. However, patients often do not maintain the testing schedule recommended by their healthcare provider. Many barriers to testing have been cited, including cost and pain. We present a small pilot study to explore whether the use of financial incentives and pain-free lancets could improve adherence to glucose testing in a community health center patient population consisting largely of non-English speaking ethnic minorities with low health literacy. The proportion of patients lost to follow-up was 17%, suggesting that a larger scale study is feasible in this type of setting, but we found no preliminary evidence suggesting a positive effect on adherence by either financial incentives or pain-free lancets. Results from this pilot study will guide the design of larger-scale studies to evaluate approaches to overcome the variety of barriers to glucose testing that are present in disadvantaged patient populations. PMID:25486531

  15. Methylene blue protects astrocytes against glucose oxygen deprivation by improving cellular respiration.

    PubMed

    Roy Choudhury, Gourav; Winters, Ali; Rich, Ryan M; Ryou, Myoung-Gwi; Gryczynski, Zygmunt; Yuan, Fang; Yang, Shao-Hua; Liu, Ran

    2015-01-01

    Astrocytes outnumber neurons and serve many metabolic and trophic functions in the mammalian brain. Preserving astrocytes is critical for normal brain function as well as for protecting the brain against various insults. Our previous studies have indicated that methylene blue (MB) functions as an alternative electron carrier and enhances brain metabolism. In addition, MB has been shown to be protective against neurodegeneration and brain injury. In the current study, we investigated the protective role of MB in astrocytes. Cell viability assays showed that MB treatment significantly protected primary astrocytes from oxygen-glucose deprivation (OGD) & reoxygenation induced cell death. We also studied the effect of MB on cellular oxygen and glucose metabolism in primary astrocytes following OGD-reoxygenation injury. MB treatment significantly increased cellular oxygen consumption, glucose uptake and ATP production in primary astrocytes. In conclusion our study demonstrated that MB protects astrocytes against OGD-reoxygenation injury by improving astrocyte cellular respiration.

  16. Improved CEEMDAN and PSO-SVR Modeling for Near-Infrared Noninvasive Glucose Detection

    PubMed Central

    Li, Xiaoli

    2016-01-01

    Diabetes is a serious threat to human health. Thus, research on noninvasive blood glucose detection has become crucial locally and abroad. Near-infrared transmission spectroscopy has important applications in noninvasive glucose detection. Extracting useful information and selecting appropriate modeling methods can improve the robustness and accuracy of models for predicting blood glucose concentrations. Therefore, an improved signal reconstruction and calibration modeling method is proposed in this study. On the basis of improved complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and correlative coefficient, the sensitive intrinsic mode functions are selected to reconstruct spectroscopy signals for developing the calibration model using the support vector regression (SVR) method. The radial basis function kernel is selected for SVR, and three parameters, namely, insensitive loss coefficient ε, penalty parameter C, and width coefficient γ, are identified beforehand for the corresponding model. Particle swarm optimization (PSO) is employed to optimize the simultaneous selection of the three parameters. Results of the comparison experiments using PSO-SVR and partial least squares show that the proposed signal reconstitution method is feasible and can eliminate noise in spectroscopy signals. The prediction accuracy of model using PSO-SVR method is also found to be better than that of other methods for near-infrared noninvasive glucose detection. PMID:27635151

  17. Improved CEEMDAN and PSO-SVR Modeling for Near-Infrared Noninvasive Glucose Detection.

    PubMed

    Li, Xiaoli; Li, Chengwei

    2016-01-01

    Diabetes is a serious threat to human health. Thus, research on noninvasive blood glucose detection has become crucial locally and abroad. Near-infrared transmission spectroscopy has important applications in noninvasive glucose detection. Extracting useful information and selecting appropriate modeling methods can improve the robustness and accuracy of models for predicting blood glucose concentrations. Therefore, an improved signal reconstruction and calibration modeling method is proposed in this study. On the basis of improved complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and correlative coefficient, the sensitive intrinsic mode functions are selected to reconstruct spectroscopy signals for developing the calibration model using the support vector regression (SVR) method. The radial basis function kernel is selected for SVR, and three parameters, namely, insensitive loss coefficient ε, penalty parameter C, and width coefficient γ, are identified beforehand for the corresponding model. Particle swarm optimization (PSO) is employed to optimize the simultaneous selection of the three parameters. Results of the comparison experiments using PSO-SVR and partial least squares show that the proposed signal reconstitution method is feasible and can eliminate noise in spectroscopy signals. The prediction accuracy of model using PSO-SVR method is also found to be better than that of other methods for near-infrared noninvasive glucose detection. PMID:27635151

  18. Improved CEEMDAN and PSO-SVR Modeling for Near-Infrared Noninvasive Glucose Detection

    PubMed Central

    Li, Xiaoli

    2016-01-01

    Diabetes is a serious threat to human health. Thus, research on noninvasive blood glucose detection has become crucial locally and abroad. Near-infrared transmission spectroscopy has important applications in noninvasive glucose detection. Extracting useful information and selecting appropriate modeling methods can improve the robustness and accuracy of models for predicting blood glucose concentrations. Therefore, an improved signal reconstruction and calibration modeling method is proposed in this study. On the basis of improved complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and correlative coefficient, the sensitive intrinsic mode functions are selected to reconstruct spectroscopy signals for developing the calibration model using the support vector regression (SVR) method. The radial basis function kernel is selected for SVR, and three parameters, namely, insensitive loss coefficient ε, penalty parameter C, and width coefficient γ, are identified beforehand for the corresponding model. Particle swarm optimization (PSO) is employed to optimize the simultaneous selection of the three parameters. Results of the comparison experiments using PSO-SVR and partial least squares show that the proposed signal reconstitution method is feasible and can eliminate noise in spectroscopy signals. The prediction accuracy of model using PSO-SVR method is also found to be better than that of other methods for near-infrared noninvasive glucose detection.

  19. Cost Implications to Health Care Payers of Improving Glucose Management among Adults with Type 2 Diabetes

    PubMed Central

    Nuckols, Teryl K; McGlynn, Elizabeth A; Adams, John; Lai, Julie; Go, Myong-Hyun; Keesey, Joan; Aledort, Julia E

    2011-01-01

    Objective To assess the cost implications to payers of improving glucose management among adults with type 2 diabetes. Data Source/Study Setting Medical-record data from the Community Quality Index (CQI) study (1996–2002), pharmaceutical claims from four Massachusetts health plans (2004–2006), Medicare Fee Schedule (2009), published literature. Study Design Probability tree depicting glucose management over 1 year. Data Collection/Extraction Methods We determined how frequently CQI study subjects received recommended care processes and attained Health Care Effectiveness Data and Information Set (HEDIS) treatment goals, estimated utilization of visits and medications associated with recommended care, assigned costs based on utilization, and then modeled how hospitalization rates, costs, and goal attainment would change if all recommended care was provided. Principal Findings Relative to current care, improved glucose management would cost U.S.$327 (U.S.$192–711 in sensitivity analyses) more per person with diabetes annually, largely due to antihyperglycemic medications. Cost-effectiveness to payers, defined as incremental annual cost per patient newly attaining any one of three HEDIS goals, would be U.S.$1,128; including glycemic crises reduces this to U.S.$555–1,021. Conclusions The cost of improving glucose management appears modest relative to diabetes-related health care expenditures. The incremental cost per patient newly attaining HEDIS goals enables payers to consider costs as well as outcomes that are linked to future profitability. PMID:21457256

  20. The World Oral Health Report 2003: continuous improvement of oral health in the 21st century--the approach of the WHO Global Oral Health Programme.

    PubMed

    Petersen, Poul Erik

    2003-12-01

    Chronic diseases and injuries are the leading health problems in all but a few parts of the world. The rapidly changing disease patterns throughout the world are closely linked to changing lifestyles, which include diets rich in sugars, widespread use of tobacco, and increased consumption of alcohol. In addition to socio-environmental determinants, oral disease is highly related to these lifestyle factors, which are risks to most chronic diseases as well as protective factors such as appropriate exposure to fluoride and good oral hygiene. Oral diseases qualify as major public health problems owing to their high prevalence and incidence in all regions of the world, and as for all diseases, the greatest burden of oral diseases is on disadvantaged and socially marginalized populations. The severe impact in terms of pain and suffering, impairment of function and effect on quality of life must also be considered. Traditional treatment of oral diseases is extremely costly in several industrialized countries, and not feasible in most low-income and middle-income countries. The WHO Global Strategy for Prevention and Control of Noncommunicable Diseases, added to the common risk factor approach is a new strategy for managing prevention and control of oral diseases. The WHO Oral Health Programme has also strengthened its work for improved oral health globally through links with other technical programmes within the Department for Noncommunicable Disease Prevention and Health Promotion. The current oral health situation and development trends at global level are described and WHO strategies and approaches for better oral health in the 21st century are outlined. PMID:15015736

  1. Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119.

    PubMed

    Park, Eun-Young; Kim, Eung-Hwi; Kim, Chul-Young; Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

    2016-01-01

    G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID:27391814

  2. Angiotensin 1-7 improves insulin sensitivity by increasing skeletal muscle glucose uptake in vivo.

    PubMed

    Echeverría-Rodríguez, Omar; Del Valle-Mondragón, Leonardo; Hong, Enrique

    2014-01-01

    The renin-angiotensin system (RAS) regulates skeletal muscle insulin sensitivity through different mechanisms. The overactivation of the ACE (angiotensin-converting enzyme)/Ang (angiotensin) II/AT1R (Ang II type 1 receptor) axis has been associated with the development of insulin resistance, whereas the stimulation of the ACE2/Ang 1-7/MasR (Mas receptor) axis improves insulin sensitivity. The in vivo mechanisms by which this axis enhances skeletal muscle insulin sensitivity are scarcely known. In this work, we investigated whether rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis and determined the effect of Ang 1-7 on rat skeletal muscle glucose uptake in vivo. Western blot analysis revealed the expression of ACE2 and MasR, while Ang 1-7 levels were detected in rat soleus muscle by capillary zone electrophoresis. The euglycemic clamp exhibited that Ang 1-7 by itself did not promote glucose transport, but it increased insulin-stimulated glucose disposal in the rat. In a similar manner, captopril (an ACE inhibitor) enhanced insulin-induced glucose uptake and this effect was blocked by the MasR antagonist A-779. Our results show for the first time that rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis of the RAS, and Ang 1-7 improves insulin sensitivity by enhancing insulin-stimulated glucose uptake in rat skeletal muscle in vivo. Thus, endogenous (systemic and/or local) Ang 1-7 could regulate insulin-mediated glucose transport in vivo.

  3. Improving Students with Rubric-Based Self-Assessment and Oral Feedback

    ERIC Educational Resources Information Center

    Barney, S.; Khurum, M.; Petersen, K.; Unterkalmsteiner, M.; Jabangwe, R.

    2012-01-01

    Rubrics and oral feedback are approaches to help students improve performance and meet learning outcomes. However, their effect on the actual improvement achieved is inconclusive. This paper evaluates the effect of rubrics and oral feedback on student learning outcomes. An experiment was conducted in a software engineering course on requirements…

  4. Evaluation of Student Reflection as a Route to Improve Oral Communication

    ERIC Educational Resources Information Center

    Mineart, Kenneth P.; Cooper, Matthew E.

    2016-01-01

    This study describes the use of guided self-reflection and peer feedback activities to improve student oral communication in a large ChE class (n ~ 100) setting. Student performance tracked throughout an experimental semester indicated both reflection activities accelerated improvement in oral communication over control; student perception of the…

  5. Structural Elucidation of a Novel Polysaccharide from Pseudostellaria heterophylla and Stimulating Glucose Uptake in Cells and Distributing in Rats by Oral.

    PubMed

    Chen, Jinlong; Pang, Wensheng; Shi, Wentao; Yang, Bin; Kan, Yongjun; He, Zhaodong; Hu, Juan

    2016-01-01

    The semi-refined polysaccharide of Pseudostellaria heterophylla is a complex polysaccharide that exhibits significantly hypoglycemic activities. A novel homogeneous polysaccharide, named as H-1-2, was isolated from the semi-refined polysaccharide. The mean molecular weight of H-1-2 was 1.4 × 10⁴ Da and it was only composed of d-glucose monosaccharide. Structure elucidation indicated that H-1-2 contains pyranride, and has the characteristics of the α-iso-head configuration, a non-reducing end (T-), 4-, 1,6-, and 1,4,6-connection, in all four ways to connect glucose. H-1-2 was a type of glucan, where chemical combination exists in the main chain between 1→4 linked glucose, and contains a small amount of 1,6-linked glucose, which was in the branched chain. In vitro HepG2, 3T3-L1, and L6 cells were used to assess cellular glucose consumption and cellular glucose uptake by glucose oxidase, and the transport of 2-NBDG fluorescence probe results showed that H-1-2 could clearly increase glucose uptake and utilization in muscle and adipose cells, which is beneficial to screen for in the discovery of anti-diabetes lead compounds. H-1-2 was labeled with radioisotopes ((99m)Tc-pertechnetate). (99m)Tc-labeled-H-1-2 was performed by SPECT/CT analysis images after oral administration in rats. At 4 h post ingestion, about 50% of the radioactivity was observed in the intestine. No significant radioactivity was found in the heart, liver, and kidney, conjecturing that absorption of (99m)Tc-labeled H-1-2 might, via intestinal mucosa, be absorbed into systemic circulation. This problem, as to whether the polysaccharide is absorbed orally, will need further examination. PMID:27649122

  6. Oral Glucose Tolerance Testing identifies HIV+ infected women with Diabetes Mellitus (DM) not captured by standard DM definition

    PubMed Central

    Tian, Fang; Anastos, Kathryn; Cohen, Mardge H; Tien, Phyllis C

    2016-01-01

    Objective HIV-infected (HIV+) individuals may have differential risk of diabetes mellitus (DM) compared to the general population, and the optimal diagnostic algorithm for DM in HIV+ persons remains unclear. We aimed to assess the utility of oral glucose tolerance testing (OGTT) for DM diagnosis in a cohort of women with or at risk for HIV infection. Methods Using American Diabetic Association DM definitions, DM prevalence and incidence were assessed among women enrolled in the Women’s Interagency HIV Study. DM was defined by 2-hour OGTT ≥ 200 mg/dL (DM_OGTT) or a clinical definition (DM_C) that included any of the following: (i) anti-diabetic medication use or self-reported DM confirmed by either fasting glucose (FG) ≥126 mg/dL or HbA1c ≥ 6.5%, (ii) FG ≥ 126 mg/dL confirmed by a second FG ≥ 126 mg/dL or HbA1c 6.5%, or (iii) HbA1c 6.5% confirmed by FG ≥ 126 mg/dL cohort. Results Overall, 390 women (285 HIV+, median age 43 years; 105 HIV−, median age 37 years) were enrolled between 2003-2006. Over half of all women were African American. Using DM_C, DM prevalence rates were 5.6% and 2.8% among HIV+ and HIV− women, respectively. Among HIV+ women, adding DM_OGTT to DM_C increased DM prevalence from 5.6% to 7.4%, a 31% increase in the number of diabetes cases diagnosed (p=0.02). In HIV− women, no additional cases were diagnosed by DM-OGTT. Conclusion In HIV+ women, OGTT identified DM cases that were not identified by a standardized clinical definition. Further investigation is needed to determine whether OGTT should be considered as an adjunctive tool for DM diagnosis in the setting of HIV infection. PMID:27066296

  7. Mechanisms of improved glucose handling after metabolic surgery: the big 6.

    PubMed

    Paszkiewicz, Rebecca L; Bergman, Richard N

    2016-07-01

    For some time, it has been clear that elevated glucose is detrimental to the organism. A plethora of medicines have been introduced to reduce the fasting and postprandial glucose levels (including insulin, glucagon-like peptide receptor 1 [GLP-1] agonists, and sodium-glucose co-transporter 2 [SGLT2] inhibitors, among others). Although these medications are useful to reduce tissue exposure to glucose, no single compound and no combination have been able to totally normalize the blood sugar. Thus, it was astonishing when it was reported that surgery of the gastrointestinal tract could not only reduce obesity but also normalize the blood sugar. These discoveries have transformed diabetes research. What is it about bariatric surgery that causes the remarkable amelioration of glucose homeostasis dysregulation? The answer to this million dollar question is a billion dollar answer. However, a new perspective could shed some light and help provide a clear path for investigation. Instead of asking what does bariatric surgery do to change the pathophysiology, we can ask what pathophysiology and risk factors confer a greater success with remission and improved disease state after surgery. Work from our laboratory and others can help to offer a physiologic basis for which mechanisms may be put into play when the anatomy is altered during surgery. Here, we do not offer an explanation of the mechanism of action of bariatric surgery, but rather provide a background on the regulation of blood glucose and how it is altered during both the diseased state and, as available, the remission state. PMID:27568470

  8. The evaluation of a multi-level oral health intervention to improve oral health practices among caregivers of preschool children.

    PubMed

    Vichayanrat, Tippanart; Steckler, Allan; Tanasugarn, Chanuantong; Lexomboon, Duangjai

    2012-03-01

    Abstract. This study reports the effects of a pilot multi-level oral health intervention on caregivers' oral health practices and their determinants. Quasi-experimental, pretest-posttest evaluations using a comparison group design were employed to evaluate the effectiveness of a proposed intervention for promoting caregiver oral health behavior. The intervention consisted of three components: home visits by lay health workers (LHWs), enhancing oral health education and services at health centers, and community mobilization. These components were designed to target factors at intrapersonal, interpersonal, organizational and community levels based on a Social Ecological Model (SEM). Four oral health behaviors associated with early childhood caries (infant bottle feeding, tooth brushing, snack consumption and fluoride use), and multi-level determinants were assessed during pre- and post-tests. The one-year intervention demonstrated a positive effect on tooth brushing, using toothpaste, and fluoride supplements, but did not have a significant effect on bottle feeding and snack consumption among children. The intervention also had no effect on dental caries; in fact caries increased in both control and experimental groups. The caregiver knowledge, attitudes, outcome expectations, and self-efficacy towards these behaviors were significantly increased in the experimental group after intervention. Caregivers in the experimental group received greater social support by LHWs and health center staff than those in the control group (p < 0.001). The program had an impact on integrating oral health services at health centers and community participation in children's oral health. These findings confirm multi-level factors influence reported oral health behavior, but not outcomes in terms of caries. Process evaluation is needed to determine actual implementation levels, barriers and suggests for modification of the program in the future to improve outcomes in terms of caries.

  9. Glucose-Reducing Effect of the ORMD-0801 Oral Insulin Preparation in Patients with Uncontrolled Type 1 Diabetes: A Pilot Study

    PubMed Central

    Eldor, Roy; Arbit, Ehud; Corcos, Asher; Kidron, Miriam

    2013-01-01

    The unpredictable behavior of uncontrolled type 1 diabetes often involves frequent swings in blood glucose levels that impact maintenance of a daily routine. An intensified insulin regimen is often unsuccessful, while other therapeutic options, such as amylin analog injections, use of continuous glucose sensors, and islet or pancreas transplantation are of limited clinical use. In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin) in addressing this resistant clinical state. Eight Type I diabetes patients with uncontrolled diabetes (HbA1c: 7.5–10%) were monitored throughout the 15-day study period by means of a blind continuous glucose monitoring device. Baseline patient blood glucose behavior was monitored and recorded over a five-day pretreatment screening period. During the ensuing ten-day treatment phase, patients were asked to conduct themselves as usual and to self-administer an oral insulin capsule three times daily, just prior to meal intake. CGM data sufficient for pharmacodynamics analyses were obtained from 6 of the 8 subjects. Treatment with ORMD-0801 was associated with a significant 24.4% reduction in the frequencies of glucose readings >200 mg/dL (60.1±7.9% pretreatment vs. 45.4±4.9% during ORMD-0801 treatment; p = 0.023) and a significant mean 16.6% decrease in glucose area under the curve (AUC) (66055±5547 mg/dL/24 hours vs. 55060±3068 mg/dL/24 hours, p = 0.023), with a greater decrease during the early evening hours. In conclusion, ORMD-0801 oral insulin capsules in conjunction with subcutaneous insulin injections, well tolerated and effectively reduced glycemia throughout the day. Trial Registration Clinicaltrials.gov NCT00867594. PMID:23593142

  10. Oral administration of SR-110, a peroxynitrite decomposing catalyst, enhances glucose homeostasis, insulin signaling, and islet architecture in B6D2F1 mice fed a high fat diet.

    PubMed

    Johns, Michael; Esmaeili Mohsen Abadi, Sakineh; Malik, Nehal; Lee, Joshua; Neumann, William L; Rausaria, Smita; Imani-Nejad, Maryam; McPherson, Timothy; Schober, Joseph; Kwon, Guim

    2016-04-15

    Peroxynitrite has been implicated in type 2 diabetes and diabetic complications. As a follow-up study to our previous work on SR-135 (Arch Biochem Biophys 577-578: 49-59, 2015), we provide evidence that this series of compounds are effective when administered orally, and their mechanisms of actions extend to the peripheral tissues. A more soluble analogue of SR-135, SR-110 (from a new class of Mn(III) bis(hydroxyphenyl)-dipyrromethene complexes) was orally administered for 2 weeks to B6D2F1 mice fed a high fat-diet (HFD). Mice fed a HFD for 4 months gained significantly higher body weights compared to lean diet-fed mice (52 ± 1.5 g vs 34 ± 1.3 g). SR-110 (10 mg/kg daily) treatment significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance as compared to HFD control or vehicle (peanut butter) group. SR-110 treatment enhanced insulin signaling in the peripheral organs, liver, heart, and skeletal muscle, and reduced lipid accumulation in the liver. Furthermore, SR-110 increased insulin content, restored islet architecture, decreased islet size, and reduced tyrosine nitration. These results suggest that a peroxynitrite decomposing catalyst is effective in improving glucose homeostasis and restoring islet morphology and β-cell insulin content under nutrient overload. PMID:26970045

  11. Exercise training is an effective alternative to estrogen supplementation for improving glucose homeostasis in ovariectomized rats

    PubMed Central

    MacDonald, Tara L; Ritchie, Kerry L; Davies, Sarah; Hamilton, Melissa J; Cervone, Daniel T; Dyck, David J

    2015-01-01

    The irreversible loss of estrogen (specifically 17-β-estradiol; E2) compromises whole-body glucose tolerance in women. Hormone replacement therapy (HRT) is frequently prescribed to treat estrogen deficiency, but has several deleterious side effects. Exercise has been proposed as an HRT substitute, however, their relative abilities to treat glucose intolerance are unknown. Thirty ovariectomized (OVX) and 20 SHAM (control) rats underwent glucose tolerance tests (GTT) 10 weeks post surgery. Area under the curve (AUC) for OVX rats was 60% greater than SHAM controls (P = 0.0005). Rats were then randomly assigned to the following treatment groups: SHAM sedentary (sed) or exercise (ex; 60 min, 5×/weeks), OVX sed, ex, or E2 (28 μg/kg bw/day) for 4 weeks. OVX ex rats experienced a ∼45% improvement in AUC relative to OVX sed rats, whereas OVX E2 underwent a partial reduction (17%; P = 0.08). Maximal insulin-stimulated glucose uptake in soleus and EDL was not impaired in OVX rats, or augmented with exercise or E2. Akt phosphorylation did not differ in soleus, EDL, or liver of any group. However, OVX ex and OVX E2 experienced greater increases in p-Akt Ser473 in VAT and SQ tissues compared with SHAM and OVX sed groups. Mitochondrial markers CS, COXIV, and core1 were increased in soleus posttraining in OVX ex rats. The content of COXIV was reduced by 52% and 61% in SQ of OVX sed and E2 rats, compared to SHAM controls, but fully restored in OVX ex rats. In summary, exercise restores glucose tolerance in OVX rats more effectively than E2. This is not reflected by alterations in muscle maximal insulin response, but increased insulin signaling in adipose depots may underlie whole-body improvements. PMID:26603453

  12. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats

    PubMed Central

    Niu, Ho-Shan; Liu, I-Min; Niu, Chiang-Shan; Ku, Po-Ming; Hsu, Chao-Tien; Cheng, Juei-Tang

    2016-01-01

    Background Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin), is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN), we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. Methods Streptozotocin (STZ) was used to induce type 1-like diabetes in rats (STZ-diabetic rats). In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. Results Oral administration of Du-Zhong (1 g/kg/day) to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-β) and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney. Conclusion Oral administration of Du-Zhong improves STZ-induced DN in rats by inhibiting TGF-β/Smad signaling and suppressing TGF-β/connective tissue growth factor expression. Therefore, active principle from Du-Zhong is suitable to develop as new agent for DN in the future. PMID:27041999

  13. What's ahead in glucose monitoring? New techniques hold promise for improved ease and accuracy.

    PubMed

    Bode, B W; Sabbah, H; Davidson, P C

    2001-04-01

    Advances in blood glucose monitoring have made it easier, more comfortable, and more practical for patients to monitor frequently. The new meters for intermittent monitoring are smaller and less dependent on technical aptitude than older models. They require less blood, and many provide downloadable information for glucose analysis. Data systems used with new meters provide valuable information that can dramatically improve glycemic control. Continuous glucose sensing (figure 4) is another major breakthrough in management of diabetes. Current systems allow only retrospective analyses, but real-time readings should be available in the near future. Such technological advances hold promise for preventing both hypoglycemia and hyperglycemia and for reducing the risk of long-term complications associated with diabetes. An artificial, mechanical islet cell may be the big next step toward bringing this disease under control. By combining continuous glucose monitoring data with continuous insulin delivery via an external or an implantable insulin pump, the outlook promises to be much brighter for patients with type 1 diabetes. PMID:11317468

  14. Improved Properties of Baker's Yeast Mutants Resistant to 2-Deoxy-d-Glucose

    PubMed Central

    Rincón, Ana M.; Codón, Antonio C.; Castrejón, Francisco; Benítez, Tahía

    2001-01-01

    We isolated spontaneous mutants from Saccharomyces cerevisiae (baker's yeast V1) that were resistant to 2-deoxy-d-glucose and had improved fermentative capacity on sweet doughs. Three mutants could grow at the same rate as the wild type in minimal SD medium (0.17% Difco yeast nitrogen base without amino acids and ammonium sulfate, 0.5% ammonium sulfate, 2% glucose) and had stable elevated levels of maltase and/or invertase under repression conditions but lower levels in maltose-supplemented media. Two of the mutants also had high levels of phosphatase active on 2-deoxy-d-glucose-6-phosphate. Dough fermentation (CO2 liberation) by two of the mutants was faster and/or produced higher final volumes than that by the wild type, both under laboratory and industrial conditions, when the doughs were supplemented with glucose or sucrose. However, the three mutants were slower when fermenting plain doughs. Fermented sweet bakery products obtained with these mutants were of better quality than those produced by the wild type, with regard to their texture and their organoleptic properties. PMID:11526034

  15. Serum Galanin Levels in Young Healthy Lean and Obese Non-Diabetic Men during an Oral Glucose Tolerance Test

    PubMed Central

    Sandoval-Alzate, Héctor Fabio; Agudelo-Zapata, Yessica; González-Clavijo, Angélica María; Poveda, Natalia E.; Espinel-Pachón, Cristian Felipe; Escamilla-Castro, Jorge Augusto; Márquez-Julio, Heidy Lorena; Alvarado-Quintero, Hernando; Rojas-Rodríguez, Fabián Guillermo; Arteaga-Díaz, Juan Manuel; Eslava-Schmalbach, Javier Hernando; Garcés-Gutiérrez, Maria Fernanda; Vrontakis, Maria; Castaño, Justo P.; Luque, Raul M.; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E.

    2016-01-01

    Galanin (GAL) is a neuropeptide involved in the homeostasis of energy metabolism. The objective of this study was to investigate the serum levels of GAL during an oral glucose tolerance test (OGTT) in lean and obese young men. This cross-sectional study included 30 obese non-diabetic young men (median 22 years; mean BMI 37 kg/m2) and 30 healthy lean men (median 23 years; mean BMI 22 kg/m2). Serum GAL was determined during OGTT. The results of this study include that serum GAL levels showed a reduction during OGTT compared with basal levels in the lean subjects group. Conversely, serum GAL levels increased significantly during OGTT in obese subjects. Serum GAL levels were also higher in obese non-diabetic men compared with lean subjects during fasting and in every period of the OGTT (p < 0.001). Serum GAL levels were positively correlated with BMI, total fat, visceral fat, HOMA–IR, total cholesterol, triglycerides and Leptin. A multiple regression analysis revealed that serum insulin levels at 30, 60 and 120 minutes during the OGTT is the most predictive variable for serum GAL levels (p < 0.001). In conclusion, serum GAL levels are significantly higher in the obese group compared with lean subjects during an OGTT. PMID:27550417

  16. Serum Galanin Levels in Young Healthy Lean and Obese Non-Diabetic Men during an Oral Glucose Tolerance Test.

    PubMed

    Sandoval-Alzate, Héctor Fabio; Agudelo-Zapata, Yessica; González-Clavijo, Angélica María; Poveda, Natalia E; Espinel-Pachón, Cristian Felipe; Escamilla-Castro, Jorge Augusto; Márquez-Julio, Heidy Lorena; Alvarado-Quintero, Hernando; Rojas-Rodríguez, Fabián Guillermo; Arteaga-Díaz, Juan Manuel; Eslava-Schmalbach, Javier Hernando; Garcés-Gutiérrez, Maria Fernanda; Vrontakis, Maria; Castaño, Justo P; Luque, Raul M; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E

    2016-01-01

    Galanin (GAL) is a neuropeptide involved in the homeostasis of energy metabolism. The objective of this study was to investigate the serum levels of GAL during an oral glucose tolerance test (OGTT) in lean and obese young men. This cross-sectional study included 30 obese non-diabetic young men (median 22 years; mean BMI 37 kg/m(2)) and 30 healthy lean men (median 23 years; mean BMI 22 kg/m(2)). Serum GAL was determined during OGTT. The results of this study include that serum GAL levels showed a reduction during OGTT compared with basal levels in the lean subjects group. Conversely, serum GAL levels increased significantly during OGTT in obese subjects. Serum GAL levels were also higher in obese non-diabetic men compared with lean subjects during fasting and in every period of the OGTT (p < 0.001). Serum GAL levels were positively correlated with BMI, total fat, visceral fat, HOMA-IR, total cholesterol, triglycerides and Leptin. A multiple regression analysis revealed that serum insulin levels at 30, 60 and 120 minutes during the OGTT is the most predictive variable for serum GAL levels (p < 0.001). In conclusion, serum GAL levels are significantly higher in the obese group compared with lean subjects during an OGTT. PMID:27550417

  17. Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization

    PubMed Central

    Wu, Xinle; Zhang, Jun; Ge, Hongfei; Gupte, Jamila; Baribault, Helene; Lee, Ki Jeong; Lemon, Bryan; Coberly, Suzanne; Gong, Yan; Pan, Zheng; Rulifson, Ingrid C.; Gardner, Jonitha; Richards, William G.; Li, Yang

    2015-01-01

    The polarization of tissue resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to positively impact obesity and insulin resistance. Here we show that the soluble form of the extracellular domain (ECD) of C-type lectin-like receptor 2, CLEC2, regulates Kupffer cell polarization in the liver and improves glucose and lipid parameters in diabetic animal models. Over-expression of Fc-CLEC2(ECD) in mice via in vivo gene delivery, or injection of recombinant Fc-CLEC2(ECD) protein, results in a reduction of blood glucose and liver triglyceride levels and improves glucose tolerance. Furthermore, Fc-CLEC2(ECD) treatment improves cytokine profiles and increases both the M2 macrophage population and the genes involved in the oxidation of lipid metabolism in the liver. These data reveal a previously unidentified role for CLEC2 as a regulator of macrophage polarity, and establish CLEC2 as a promising therapeutic target for treatment of diabetes and liver disease. PMID:26151067

  18. Global policy for improvement of oral health in the 21st century--implications to oral health research of World Health Assembly 2007, World Health Organization.

    PubMed

    Petersen, Poul Erik

    2009-02-01

    The World Health Organization (WHO) Global Oral Health Programme has worked hard over the past 5 years to increase the awareness of oral health worldwide as oral health is important component of general health and quality of life. Meanwhile, oral disease is still a major public health problem in high income countries and the burden of oral disease is growing in many low- and middle income countries. In the World Oral Health Report 2003, the WHO Global Oral Health Programme formulated the policies and necessary actions to the continuous improvement of oral health. The strategy is that oral disease prevention and the promotion of oral health needs to be integrated with chronic disease prevention and general health promotion as the risks to health are linked. The World Health Assembly (WHA) and the Executive Board (EB) are supreme governance bodies of WHO and for the first time in 25 years oral health was subject to discussion by those bodies in 2007. At the EB120 and WHA60, the Member States agreed on an action plan for oral health and integrated disease prevention, thereby confirming the approach of the Oral Health Programme. The policy forms the basis for future development or adjustment of oral health programmes at national level. Clinical and public health research has shown that a number of individual, professional and community preventive measures are effective in preventing most oral diseases. However, advances in oral health science have not yet benefited the poor and disadvantaged populations worldwide. The major challenges of the future will be to translate knowledge and experiences in oral disease prevention and health promotion into action programmes. The WHO Global Oral Health Programme invites the international oral health research community to engage further in research capacity building in developing countries, and in strengthening the work so that research is recognized as the foundation of oral heath policy at global level.

  19. Interprofessional Collaboration in Improving Oral Health for Special Populations.

    PubMed

    Glassman, Paul; Harrington, Maureen; Namakian, Maysa; Subar, Paul

    2016-10-01

    People with complex medical, physical, and psychological conditions are among the most underserved groups in receiving dental care and consequently have the most significant oral health disparities of any group. The traditional dental care delivery system is not able to deliver adequate services to these people with "special needs" for a variety of reasons. New systems of care are evolving that better serve the needs of these groups by using interprofessional teams to reach these individuals and integrate oral health services into social, educational, and general health systems. PMID:27671957

  20. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

    PubMed

    Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

    2010-01-01

    Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

  1. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

    PubMed

    Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

    2010-01-01

    Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline. PMID:20847403

  2. High glucose improves healing of periodontal wound by inhibiting proliferation and osteogenetic differentiation of human PDL cells.

    PubMed

    Li, Min; Li, Cheng-Zhang

    2016-02-01

    Periodontal ligament (PDL) cells play an important role in wound healing of periodontal tissues. Response of PDL cells' cellular activity to high-glucose concentration levels may be the key in understanding the relationship between periodontal disease and diabetes mellitus. We studied the effect of high-glucose medium on proliferation of PDL cells in vitro. PDL cells were cultured for 1, 4, 7, 10, 14 and 17 days in normal (1100 mg/l) glucose or in high (4500 mg/l) glucose medium. The 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for proliferation was performed. In order to evaluate the osteogenetic differentiation of human PDL cells, the cells were induced with normal- or high-glucose medium for 1, 7, 14, 21 and 28 days. The results indicated that high glucose significantly inhibited proliferation of PDL cells. Concerning the mineralised nodule formation, the percentage of calcified area to total culture dish of PDL cells in high glucose level was lower than that in normal glucose medium. The increase in alkaline phosphatase activity and collagen expression could be observed in high-glucose-containing osteogenetic factor. In conclusion, high glucose improves healing of periodontal wound by inhibiting proliferation and differentiation of PDL cells, which could explain for delayed periodontal regeneration and healing in diabetic patients.

  3. Teachers Engaging Parents as Tutors to Improve Oral Reading Fluency

    ERIC Educational Resources Information Center

    Kupzyk, Sara S.

    2012-01-01

    This dissertation examined the application of evidence-based tutoring for oral reading fluency (ORF) to a natural setting, using teachers as parent trainers. Measures used to determine the impact of parent tutoring included treatment integrity, student reading outcomes, attitudes towards involvement and reading, and social validity. Six teachers…

  4. Strategies Instruction to Improve the Preparation for English Oral Exams

    ERIC Educational Resources Information Center

    Abad, José Vicente; Alzate, Paula Andrea

    2016-01-01

    This article presents the results of an inter-institutional research study that assessed the impact of strategies instruction on students' preparation for and performance in oral exams. Two teacher-researchers at different universities trained 26 students in their respective B1-English-level courses in using language learning strategies. The study…

  5. Improving Oral Reading Fluency with a Peer-Mediated Intervention

    ERIC Educational Resources Information Center

    Hofstadter-Duke, Kristi L.; Daly, Edward J., III

    2011-01-01

    This study examined the effects of an experimentally derived, peer-delivered reading intervention on the oral reading fluency of a first-grade student who had been referred for poor reading fluency. Same-grade peers were trained to lead the target student through a structured intervention protocol based on the results of a brief experimental…

  6. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    PubMed

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  7. Patient Perspectives on Improving Oral Health-Care Practices Among People Living with HIV/AIDS

    PubMed Central

    Rajabiun, Serena; Fox, Jane E.; McCluskey, Amanda; Guevara, Ernesto; Verdecias, Niko; Jeanty, Yves; DeMayo, Michael; Mofidi, Mahyar

    2012-01-01

    This qualitative study explored the impact on oral health-care knowledge, attitudes, and practices among 39 people living with HIV/AIDS (PLWHA) participating in a national initiative aimed at increasing access to oral health care. Personal values and childhood dental experiences, beliefs about the importance of oral health in relation to HIV health, and concerns for appearance and self-esteem were found to be determinants of oral health knowledge and practice. Program participation resulted in better hygiene practices, improved self-esteem and appearance, relief of pain, and better physical and emotional health. In-depth exploration of the causes for these changes revealed a desire to continue with dental care due to the dental staff and environmental setting, and a desire to maintain overall HIV health, including oral health. Our findings emphasize the importance of addressing both personal values and contextual factors in providing oral health-care services to PLWHA. PMID:22547879

  8. The Resist Diabetes trial: Rationale, design, and methods of a hybrid efficacy/effectiveness intervention trial for resistance training maintenance to improve glucose homeostasis in older prediabetic adults

    PubMed Central

    Marinik, Elaina L.; Kelleher, Sarah; Savla, Jyoti; Winett, Richard A.; Davy, Brenda M.

    2014-01-01

    Advancing age is associated with reduced levels of physical activity, increased body weight and fat, decreased lean body mass, and a high prevalence of type 2 diabetes (T2D). Resistance training (RT) increases muscle strength and lean body mass, and reduces risk of T2D among older adults. The Resist Diabetes trial will determine if a social cognitive theory (SCT)-based intervention improves RT maintenance in older, prediabetic adults, using a hybrid efficacy/effectiveness approach. Sedentary, overweight/obese (BMI 25-39.9 kg/m2) adults aged 50-69 (N=170) with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) completed a supervised 3-month RT (2x/wk) Initiation Phase and were then randomly assigned (n=159; 94% retention) to one of two 6-month maintenance conditions: SCT or Standard care. The SCT intervention consisted of faded contacts compared to Standard care. Participants continue RT at an approved, self-selected community facility during maintenance. A subsequent 6-month period involves no contact for both conditions. Assessments occur at baseline and months 3 (post-initiation), 9 (post-intervention), and 15 (six months after no contact). Primary outcomes are prediabetes indices (i.e., impaired fasting and 2-hour glucose concentration) and strength. Secondary measures include insulin sensitivity, beta-cell responsiveness, and disposition index (oral glucose and C-peptide minimal model); adherence; body composition; and SCT measures. Resist Diabetes is the first trial to examine the effectiveness of a high fidelity SCT-based intervention for maintaining RT in older adults with prediabetes to improve glucose homeostasis. Successful application of SCT constructs for RT maintenance may support translation of our RT program for diabetes prevention into community settings. PMID:24252311

  9. Salacia Extract Improves Postprandial Glucose and Insulin Response: A Randomized Double-Blind, Placebo Controlled, Crossover Study in Healthy Volunteers

    PubMed Central

    Jeykodi, Shankaranarayanan; Deshpande, Jayant

    2016-01-01

    Thirty-five healthy subjects were randomly assigned to different doses of Salacia chinensis extract (200 mg, 300 mg, and 500 mg SCE) capsules and compared with placebo. It is a placebo controlled randomized crossover design study. Subjects were given oral sucrose solution along with capsules and plasma glucose and insulin responses were analyzed. Blood samples were collected at 0, 30, 60, 90, 120, and 180 minutes after administration. AUC insulin significantly lowered after ingestion of SCE. No significant adverse events were observed. Reducing glucose and insulin is very important in reducing postprandial hyperglycemia. PMID:27803937

  10. Glucose control and opportunities for health care improvement in a hospital setting.

    PubMed

    Salamah, Carole; Byxbe, Tara; Naffe, Aster; Vish, Nancy; Dejong, Sandra; Muldoon, Mary; Cheng, Dunlei; Adams, Jenny

    2011-01-01

    We initiated a study at Baylor Jack and Jane Hamilton Heart and Vascular Hospital to compare the sliding scale insulin (SSI) protocol used in 2006 with the SSI protocol currently used to treat diabetic patients admitted for procedures or surgery. An audit of patients' records revealed greater variation in staff compliance with the current protocol than with the previous one. In addition, it seemed that more patients were refusing insulin coverage under the current protocol than under the prior version. Although the study was aborted, the initial findings motivated us to identify obstacles to glucose control and to launch a health care improvement initiative to increase compliance with the SSI protocol. As a result of this process, the hospital has made several changes, including re-educating staff nurses, initiating competency checks of protocol interpretation, promoting patient education, and implementing early identification of inconsistent glucose control.

  11. Glucose- but not rice-based oral rehydration therapy enhances the production of virulence determinants in the human pathogen Vibrio cholerae.

    PubMed

    Kühn, Juliane; Finger, Flavio; Bertuzzo, Enrico; Borgeaud, Sandrine; Gatto, Marino; Rinaldo, Andrea; Blokesch, Melanie

    2014-12-01

    Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae, or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings. PMID:25474211

  12. Effectiveness of motivational interviewing at improving oral health: a systematic review

    PubMed Central

    Cascaes, Andreia Morales; Bielemann, Renata Moraes; Clark, Valerie Lyn; Barros, Aluísio J D

    2014-01-01

    OBJECTIVE To analyze the effectiveness of motivational interviewing (MI) at improving oral health behaviors (oral hygiene habits, sugar consumption, dental services utilization or use of fluoride) and dental clinical outcomes (dental plaque, dental caries and periodontal status). METHODS A systematic search of PubMed, LILACS, SciELO, PsyINFO, Cochrane and Google Scholar bibliographic databases was conducted looking for intervention studies that investigated MI as the main approach to improving the oral health outcomes investigated. RESULTS Of the 78 articles found, ten met the inclusion criteria, all based on randomized controlled trials. Most studies (n = 8) assessed multiple outcomes. Five interventions assessed the impact of MI on oral health behaviors and nine on clinical outcomes (three on dental caries, six on dental plaque, four on gingivitis and three on periodontal pockets). Better quality of evidence was provided by studies that investigated dental caries, which also had the largest population samples. The evidence of the effect of MI on improving oral health outcomes is conflicting. Four studies reported positive effects of MI on oral health outcomes whereas another four showed null effect. In two interventions, the actual difference between groups was not reported or able to be recalculated. CONCLUSIONS We found inconclusive effectiveness for most oral health outcomes. We need more and better designed and reported interventions to fully assess the impact of MI on oral health and understand the appropriate dosage for the counseling interventions. PMID:24789647

  13. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.

    PubMed

    Cefalu, William T; Wang, Zhong Q; Zhang, Xian H; Baldor, Linda C; Russell, James C

    2002-06-01

    Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.

  14. The Research of Improved Grey GM (1, 1) Model to Predict the Postprandial Glucose in Type 2 Diabetes

    PubMed Central

    Wang, Yannian; Wei, Fenfen; Sun, Changqing; Li, Quanzhong

    2016-01-01

    Diabetes may result in some complications and increase the risk of many serious health problems. The purpose of clinical treatment is to carefully manage the blood glucose concentration. If the blood glucose concentration is predicted, treatments can be taken in advance to reduce the harm to patients. For this purpose, an improved grey GM (1, 1) model is applied to predict blood glucose with a small amount of data, and especially in terms of improved smoothness it can get higher prediction accuracy. The original data of blood glucose of type 2 diabetes is acquired by CGMS. Then the prediction model is established. Finally, 50 cases of blood glucose from the Henan Province People's Hospital are predicted in 5, 10, 15, 20, 25, and 30 minutes, respectively, in advance to verify the prediction model. The prediction result of blood glucose is evaluated by the EGA, MSE, and MAE. Particularly, the prediction results of postprandial blood glucose are presented and analyzed. The result shows that the improved grey GM (1, 1) model has excellent performance in postprandial blood glucose prediction. PMID:27314034

  15. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model.

    PubMed

    Vial, Guillaume; Chauvin, Marie-Agnès; Bendridi, Nadia; Durand, Annie; Meugnier, Emmanuelle; Madec, Anne-Marie; Bernoud-Hubac, Nathalie; Pais de Barros, Jean-Paul; Fontaine, Éric; Acquaviva, Cécile; Hallakou-Bozec, Sophie; Bolze, Sébastien; Vidal, Hubert; Rieusset, Jennifer

    2015-06-01

    Imeglimin is the first in a new class of oral glucose-lowering agents currently in phase 2b development. Although imeglimin improves insulin sensitivity in humans, the molecular mechanisms are unknown. This study used a model of 16-week high-fat, high-sucrose diet (HFHSD) mice to characterize its antidiabetic effects. Six-week imeglimin treatment significantly decreased glycemia, restored normal glucose tolerance, and improved insulin sensitivity without modifying organs, body weights, and food intake. This was associated with an increase in insulin-stimulated protein kinase B phosphorylation in the liver and muscle. In liver mitochondria, imeglimin redirects substrate flows in favor of complex II, as illustrated by increased respiration with succinate and by the restoration of respiration with glutamate/malate back to control levels. In addition, imeglimin inhibits complex I and restores complex III activities, suggesting an increase in fatty acid oxidation, which is supported by an increase in hepatic 3-hydroxyacetyl-CoA dehydrogenase activity and acylcarnitine profile and the reduction of liver steatosis. Imeglimin also reduces reactive oxygen species production and increases mitochondrial DNA. Finally, imeglimin effects on mitochondrial phospholipid composition could participate in the benefit of imeglimin on mitochondrial function. In conclusion, imeglimin normalizes glucose tolerance and insulin sensitivity by preserving mitochondrial function from oxidative stress and favoring lipid oxidation in liver of HFHSD mice. PMID:25552598

  16. Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice

    PubMed Central

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-01-01

    Although recent studies have reported that Lactobacillus rhamnosus GG (LGG), the most extensively studied probiotic strain, exerts an anti-hyperglycemic effect on several rodent models, the underlying mechanism remains unclear. In this study, twenty male C57BL/KsJ-db/db (db/db) mice were divided into 2 groups, LGG-treated and control group, which received a daily dose of LGG (1 × 108 CFU per mouse) and PBS orally for 4 weeks, respectively. We observed that glucose tolerance was significantly improved in LGG-treated db/db mice. Insulin-stimulated Akt phosphorylation and GLUT4 translocation were higher in skeletal muscle of LGG-treated mice relative to their controls. It was also observed that LGG treatment caused significant reductions in endoplasmic reticulum (ER) stress in skeletal muscle and M1-like macrophage activation in white adipose tissues. Our results indicate that the anti-diabetic effect of LGG in db/db mice is associated with alleviated ER stress and suppressed macrophage activation, resulting in enhanced insulin sensitivity. These findings suggest a therapeutic potential of probiotics for prevention and treatment of type 2 diabetes. PMID:26060355

  17. Insulin-like growth factor-I improves glucose and lipid metabolism in type 2 diabetes mellitus.

    PubMed Central

    Zenobi, P D; Jaeggi-Groisman, S E; Riesen, W F; Røder, M E; Froesch, E R

    1992-01-01

    Hyperglycemia, hyperinsulinemia, and insulin resistance cause vascular disease in type 2 diabetes mellitus. Dietary treatment alone often fails and oral drugs or insulin enhance hyperinsulinemia. In previous studies, an intravenous bolus of recombinant human insulin-like growth factor-I (rhIGF-I) caused normoglycemia in insulin-resistant diabetics whereas rhIGF-I infusions lowered insulin and lipid levels in healthy humans, suggesting that rhIGF-I is effective in insulin-resistant states. Thus, eight type 2 diabetics on a diet received on five treatment days subcutaneous rhIGF-I (2 x 120 micrograms/kg) after five control days. Fasting and postprandial glucose, insulin, C-peptide, proinsulin, glucagon, triglyceride, insulin-like growth factor-I and -II, and growth hormone levels were determined. RhIGF-I administration increased total IGF-I serum levels 5.3-fold above control. During the control period mean (+/- SD) fasting glucose, insulin, C-peptide, and total triglyceride levels were 11.0 +/- 4.3 mmol/liter, 108 +/- 50 pmol/liter, 793 +/- 250 pmol/liter, and 3.1 +/- 2.7 mmol/liter, respectively, and decreased during treatment to a nadir of 6.6 +/- 2.5 mmol/liter, 47 +/- 18 pmol/liter, 311 +/- 165 pmol/liter, and 1.6 +/- 0.8 mmol/liter (P < 0.01), respectively. Postprandial areas under the glucose, insulin, and C-peptide curve decreased to 77 +/- 13 (P < 0.02), 52 +/- 11, and 60 +/- 9% (P < 0.01) of control, respectively. RhIGF-I decreased the proinsulin/insulin ratio whereas glucagon levels remained unchanged. The magnitude of the effects of rhIGF-I correlated with the respective control levels. Since rhIGF-I appears to improve insulin sensitivity directly and/or indirectly, it may become an interesting tool in type 2 diabetes and other states associated with insulin resistance. PMID:1469083

  18. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    PubMed Central

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  19. Improvements in Glucose Sensitivity and Stability of Trichoderma reesei β-Glucosidase Using Site-Directed Mutagenesis

    PubMed Central

    Amano, Yoshihiko

    2016-01-01

    Glucose sensitivity and pH and thermal stabilities of Trichoderma reesei Cel1A (Bgl II) were improved by site-directed mutagenesis of only two amino acid residues (L167W or P172L) at the entrance of the active site. The Cel1A mutant showed high glucose tolerance (50% of inhibitory concentration = 650 mM), glucose stimulation (2.0 fold at 50 mM glucose), and enhanced specific activity (2.4-fold) compared with those of the wild-type Cel1A. Furthermore, the mutant enzyme showed stability at a wide pH range of 4.5–9.0 and possessed high thermal stability up to 50°C with 80% of the residual activities compared with the stability seen at the pH range of 6.5–7.0 and temperatures of up to 40°C in the wild-type Cel1A. Kinetic studies for hydrolysis revealed that the Cel1A mutant was competitively inhibited by glucose at similar levels as the wild-type enzyme. Additionally, the mutant enzyme exhibited substrate inhibition, which gradually disappeared with an increasing glucose concentration. These data suggest that the glucose stimulation was caused by relieve the substrate inhibition in the presence of glucose. To conclude, all the properties improved by the mutagenesis would be great advantages in degradation of cellulosic biomass together with cellulases. PMID:26790148

  20. Improvements in Glucose Sensitivity and Stability of Trichoderma reesei β-Glucosidase Using Site-Directed Mutagenesis.

    PubMed

    Guo, Boyang; Amano, Yoshihiko; Nozaki, Kouichi

    2016-01-01

    Glucose sensitivity and pH and thermal stabilities of Trichoderma reesei Cel1A (Bgl II) were improved by site-directed mutagenesis of only two amino acid residues (L167W or P172L) at the entrance of the active site. The Cel1A mutant showed high glucose tolerance (50% of inhibitory concentration = 650 mM), glucose stimulation (2.0 fold at 50 mM glucose), and enhanced specific activity (2.4-fold) compared with those of the wild-type Cel1A. Furthermore, the mutant enzyme showed stability at a wide pH range of 4.5-9.0 and possessed high thermal stability up to 50 °C with 80% of the residual activities compared with the stability seen at the pH range of 6.5-7.0 and temperatures of up to 40 °C in the wild-type Cel1A. Kinetic studies for hydrolysis revealed that the Cel1A mutant was competitively inhibited by glucose at similar levels as the wild-type enzyme. Additionally, the mutant enzyme exhibited substrate inhibition, which gradually disappeared with an increasing glucose concentration. These data suggest that the glucose stimulation was caused by relieve the substrate inhibition in the presence of glucose. To conclude, all the properties improved by the mutagenesis would be great advantages in degradation of cellulosic biomass together with cellulases.

  1. Improving drug retention in liposomes by aging with the aid of glucose.

    PubMed

    Zhang, Wenli; Falconer, James R; Baguley, Bruce C; Shaw, John P; Kanamala, Manju; Xu, Hongtao; Wang, Guangji; Liu, Jianping; Wu, Zimei

    2016-05-30

    This paper describes a novel method to improve drug retention in liposomes for the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded in the aqueous phase of liposomes and the effects of aging conditions and drug loading levels on drug retention were investigated using an in vitro bio-relevant drug release test established in this study. The status of intra-liposomal drug was investigated using differential scanning calorimetry (DSC) and cryo-transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous tolerance of the formulations were simultaneously studied in rabbits following one-hour intravenous infusion via the ear vein. The presence of glucose during aging was found to be crucial to accelerate drug precipitation and to stabilize the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a prerequisite. Although no drug crystals were detected, DSC showed a lower phase-transition peak in the glucose-assisted aged ASL-liposomes, indicating interaction of phospholipids with the sugar. Cryo-TEM revealed more 'coffee bean' like drug precipitate in the ASL-liposomes aged in the glucose solution. In rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh liposomes, with no venous irritation observed. Inducing and stabilizing drug precipitation in the liposome cores by aging in the presence of sugar provided an easy approach to improve drug retention in liposomes. The study also highlighted the importance of bio-relevance of in vitro release methods to predict in vivo drug release. PMID:27021465

  2. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

    PubMed

    Scheen, André J

    2014-04-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

  3. A mixture of apple pomace and rosemary extract improves fructose consumption-induced insulin resistance in rats: modulation of sarcolemmal CD36 and glucose transporter-4

    PubMed Central

    Ma, Peng; Yao, Ling; Lin, Xuemei; Gu, Tieguang; Rong, Xianglu; Batey, Robert; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2016-01-01

    Apple pomace is a by-product of the processing of apple for juice, cider or wine preparation. Rosemary is a herb commonly used as spice and flavoring agent in food processing. Evidence suggests that both apple pomace and rosemary have rich bioactive molecules with numerous metabolic effects. To provide more information for using apple pomace and rosemary as functional foods for management of metabolism-associated disorders, the present study investigated the insulin-sensitizing effect of a mixture of apple pomace and rosemary extract (AR). The results showed that treatment with AR (500 mg/kg, daily, by gavage) for 5 weeks attenuated chronic liquid fructose consumption-induced increases in fasting plasma insulin concentration, the homeostasis model assessment of insulin resistance index and the adipose tissue insulin resistance index in rats. Mechanistically, AR suppressed fructose-induced acceleration of the clearance of plasma non-esterified fatty acids during oral glucose tolerance test, and decreased excessive triglyceride accumulation and the increased Oil Red O staining area in the gastrocnemius. Furthermore, AR restored fructose-induced overexpression of sarcolemmal CD36 that is known to contribute to etiology of insulin resistance by facilitating fatty acid uptake, and downregulation of sarcolemmal glucose transporter (GLUT)-4 that is the insulin-responsive glucose transporter. Thus, these results demonstrate that AR improves fructose-induced insulin resistance in rats via modulation of sarcolemmal CD36 and GLUT-4. PMID:27725859

  4. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

    PubMed

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach. PMID:26379428

  5. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update

    PubMed Central

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach. PMID:26379428

  6. [Improvements in oral anticoagulant therapy for atrial fibrillation].

    PubMed

    Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José

    2013-12-01

    For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.

  7. [Improvement of oral health at institutionalized patients. Choice and validation of an adapted oral hygiene kit in long-term care unit].

    PubMed

    Lacoste-Ferré, Marie-Hélène; Gendre, Charlotte; Rapp, Lucie; Gautrault, Sabrina; Hermabessière, Sophie; Rolland, Yves

    2014-09-01

    The initiatives to improve the quality are widely developed in the healthcare sector. So, an evaluation of the professional practices (EPP) concerning oral diseases in elderly was organized in the long term care unit of the teaching hospital of Toulouse. In the dynamic of this EPP, a pilot study consisted in estimating a new kit of oral hygiene. This hygiene kit was chosen according to defined criteria adapted to the elderly. The results show a clear improvement of the oral health measured with a specific index (Oral health assessment tool).

  8. Oral bovine serum concentrate improves cryptosporidial enteritis in calves.

    PubMed

    Hunt, Elaine; Fu, Qiang; Armstrong, Martha U; Rennix, Derralyn K; Webster, David W; Galanko, Joseph A; Chen, Wunian; Weaver, Eric M; Argenzio, Robert A; Rhoads, J Marc

    2002-03-01

    Cryptosporidium parvum produces a prolonged watery diarrhea unresponsive to conventional antimicrobials. Because of reported efficacy of antibody-based immunotherapy, we studied the effect of inexpensive, commercially available oral bovine serum concentrate (BSC) in experimental cryptosporidiosis. Twenty-four calves were treated with 57 g/d BSC (n = 12) or soy protein (n = 12) added to their standard whey protein-based milk replacer (227 g/2 L twice daily). Of the 24, 9 were also treated with L-glutamine (GLN), 8 g/L (50 mM) in the milk (5 calves in the BSC group and 4 in the soy group). Animals were inoculated with 10(8) cryptosporidium oocysts per os on d 8 of life and received oral rehydration on d 12-14. Eight uninfected controls were treated with BSC or soy protein. Fecal and urine volume and urinary Cr-EDTA excretion were measured. Animals were killed on d 18 of life. Cryptosporidiosis induced severe watery diarrhea lasting >9 d and produced a 25% increase in intestinal permeability, a 33% decrease in villous surface area, and a 40% reduction in mucosal lactase specific activity. Glutamine treatment had no effect on the diarrhea or any of the intestinal tests; and therefore pooled data were used to compare the 12 calves treated with BSC with the 12 treated with soy. In animals receiving BSC, peak diarrheal volume and intestinal permeability were reduced 33%, fewer oocysts were shed, intestinal crypts were significantly deeper, and villous surface area returned to normal by 9 d after infection (all p

  9. Study on an improved wavelet shift-invariant threshold denoising for pulsed laser induced glucose photoacoustic signals

    NASA Astrophysics Data System (ADS)

    Wang, Zhengzi; Ren, Zhong; Liu, Guodong

    2015-10-01

    Noninvasive measurement of blood glucose concentration has become a hotspot research in the world due to its characteristic of convenient, rapid and non-destructive etc. The blood glucose concentration monitoring based on photoacoustic technique has attracted many attentions because the detected signal is ultrasonic signals rather than the photo signals. But during the acquisition of the photoacoustic signals of glucose, the photoacoustic signals are not avoid to be polluted by some factors, such as the pulsed laser, electronic noises and circumstance noises etc. These disturbances will impact the measurement accuracy of the glucose concentration, So, the denoising of the glucose photoacoustic signals is a key work. In this paper, a wavelet shift-invariant threshold denoising method is improved, and a novel wavelet threshold function is proposed. For the novel wavelet threshold function, two threshold values and two different factors are set, and the novel function is high order derivative and continuous, which can be looked as the compromise between the wavelet soft threshold denoising and hard threshold denoising. Simulation experimental results illustrate that, compared with other wavelet threshold denoising, this improved wavelet shift-invariant threshold denoising has higher signal-to-noise ratio(SNR) and smaller root mean-square error (RMSE) value. And this improved denoising also has better denoising effect than others. Therefore, this improved denoising has a certain of potential value in the denoising of glucose photoacoustic signals.

  10. Boron nitride nanotubes included thermally cross-linked gelatin-glucose scaffolds show improved properties.

    PubMed

    Şen, Özlem; Culha, Mustafa

    2016-02-01

    Boron nitride nanotubes (BNNTs) are increasingly investigated for their medical and biomedical applications due to their unique properties such as resistance to oxidation, thermal and electrical insulation, and biocompatibility. BNNTs can be used to enhance mechanical strength of biomedical structures such as scaffolds in tissue engineering applications. In this study, we report the use of BNNTs and hydroxylated BNNTs (BNNT-OH) to improve the properties of gelatin-glucose scaffolds prepared with electrospinning technique. Human dermal fibroblast (HDF) cells are used for the toxicity assessment and cell seeding studies. It is found that the addition of BNNTs into the scaffold does not influence cell viability, decreases the scaffold degradation rate, and improves cell attachment and proliferation compared to only-gelatin scaffold.

  11. Continuous glucose monitors: use of waveform versus glycemic values in the improvements of glucose control, quality of life, and fear of hypoglycemia.

    PubMed

    Walker, Tomas C; Yucha, Carolyn B

    2014-05-01

    How patients are benefitting from continuous glucose monitoring (CGM) remains poorly understood. The focus on numerical glucose values persists, even though access to the glucose waveform and rate of change may contribute more to improved control. This pilot study compared outcomes of patients using CGMs with or without access to the numerical values on their CGM. Ten persons with type 1 diabetes, naïve to CGM use, enrolled in a 12-week study. Subjects were randomly assigned to either unmodified CGM receivers, or to CGM receivers that had their numerical values obscured but otherwise functioned normally. HbA1c, quality of life (QLI-D), and fear of hypoglycemia (HFS) were assessed, at baseline and at week 12. Baseline HbA1c for the entire group was 7.46 ± 1.27%. At week 12 the experimental group HbA1c reduction was 1.5 ± 0.9% (p < .05), the control group's reduction was 0.06 ± 0.61% (p > .05). Repeated measures testing revealed no significant difference in HbA1c reduction between groups. Both groups had reductions in HFS; these reductions were statistically significant within groups (p < .05), but not between groups. QLI-D indices demonstrated improvements (p < .05) in QLI-D total and the health and family subscales, but not between groups. The results of this pilot study suggest that benefits of CGM extend beyond reductions in HbA1c to reductions in fear of hypoglycemia and improvements in quality of life. The display of a numerical glucose value did not improve control when compared to numerically blinded units.

  12. Sodium‐glucose cotransporter 2 inhibitor luseogliflozin improves glycaemic control, assessed by continuous glucose monitoring, even on a low‐carbohydrate diet

    PubMed Central

    Nishimura, R.; Omiya, H.; Sugio, K.; Ubukata, M.; Sakai, S.

    2016-01-01

    This randomized, double‐blind, placebo‐controlled, crossover study was the first to determine the effects of luseogliflozin in combination with a low‐carbohydrate diet (LCD) on 24‐h glucose variability, assessed by continuous glucose monitoring (CGM). A total of 18 Japanese patients with type 2 diabetes were randomized into two groups, in which patients first received luseogliflozin 2.5 mg once daily then placebo for 8 days each, or vice versa. Patients took luseogliflozin or placebo with a normal‐carbohydrate diet (NCD) on day 7 and with the LCD on day 8. CGM was performed on both days. Luseogliflozin significantly reduced glucose exposure in terms of the area under the curve over the course of 24 h when administered with the NCD (difference vs placebo: −555.6 mg/dl·h [1 mg/dl = 0.0556 mmol/l]; p < 0.001) or with the LCD (−660.7 mg/dl·h; p < 0.001). No hypoglycaemia was observed over 24 h with either diet. Although glucose levels were lower with the LCD than with the NCD in the placebo treatment period, luseogliflozin with the LCD improved glycaemic control throughout the day to nearly the same extent as luseogliflozin with the NCD, without inducing hypoglycaemia. PMID:26639943

  13. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    PubMed

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results.

  14. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    PubMed

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results. PMID:26962830

  15. Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity.

    PubMed

    Ham, Mira; Choe, Sung Sik; Shin, Kyung Cheul; Choi, Goun; Kim, Ji-Won; Noh, Jung-Ran; Kim, Yong-Hoon; Ryu, Je-Won; Yoon, Kun-Ho; Lee, Chul-Ho; Kim, Jae Bum

    2016-09-01

    Glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway, plays important roles in redox regulation and de novo lipogenesis. It was recently demonstrated that aberrant upregulation of G6PD in obese adipose tissue mediates insulin resistance as a result of imbalanced energy metabolism and oxidative stress. It remains elusive, however, whether inhibition of G6PD in vivo may relieve obesity-induced insulin resistance. In this study we showed that a hematopoietic G6PD defect alleviates insulin resistance in obesity, accompanied by reduced adipose tissue inflammation. Compared with wild-type littermates, G6PD-deficient mutant (G6PD(mut)) mice were glucose tolerant upon high-fat-diet (HFD) feeding. Intriguingly, the expression of NADPH oxidase genes to produce reactive oxygen species was alleviated, whereas that of antioxidant genes was enhanced in the adipose tissue of HFD-fed G6PD(mut) mice. In diet-induced obesity (DIO), the adipose tissue of G6PD(mut) mice decreased the expression of inflammatory cytokines, accompanied by downregulated proinflammatory macrophages. Accordingly, macrophages from G6PD(mut) mice greatly suppressed lipopolysaccharide-induced proinflammatory signaling cascades, leading to enhanced insulin sensitivity in adipocytes and hepatocytes. Furthermore, adoptive transfer of G6PD(mut) bone marrow to wild-type mice attenuated adipose tissue inflammation and improved glucose tolerance in DIO. Collectively, these data suggest that inhibition of macrophage G6PD would ameliorate insulin resistance in obesity through suppression of proinflammatory responses. PMID:27284106

  16. Corticosteroid-binding globulin, cortisol, free cortisol, and sex hormone-binding globulin responses following oral glucose challenge in spinal cord-injured and able-bodied men.

    PubMed

    Lewis, J G; Jones, L M; Legge, M; Elder, P A

    2010-11-01

    Circulating cortisol, corticosteroid-binding globulin, and sex hormone-binding globulin were measured retrospectively in plasma samples following the oral glucose tolerance test in 20 spinal cord-injured men and 20 able-bodied controls. Plasma-free cortisol responses attenuated more rapidly in the able-bodied men, compared to spinal cord-injured subjects, due to significant rise in circulating corticosteroid-binding globulin whereas changes in total plasma cortisol were similar in both groups. The changes in plasma-free cortisol in both groups paralleled changes in insulin and glucose and show that spinal cord-injured men had heightened exposure to free cortisol during this dynamic test. This raises the possibility that the mechanism of abdominal obesity and the propensity towards insulin resistance in spinal cord-injured men could be subtly mediated by perturbations in free cortisol. There were no significant changes in plasma sex hormone-binding globulin in either group.

  17. Metabolic Engineering of Gluconobacter oxydans for Improved Growth Rate and Growth Yield on Glucose by Elimination of Gluconate Formation▿

    PubMed Central

    Krajewski, Vera; Simić, Petra; Mouncey, Nigel J.; Bringer, Stephanie; Sahm, Hermann; Bott, Michael

    2010-01-01

    Gluconobacter oxydans N44-1, an obligatory aerobic acetic acid bacterium, oxidizes glucose primarily in the periplasm to the end products 2-ketogluconate and 2,5-diketogluconate, with intermediate formation of gluconate. Only a minor part of the glucose (less than 10%) is metabolized in the cytoplasm after conversion to gluconate or after phosphorylation to glucose-6-phosphate via the only functional catabolic routes, the pentose phosphate pathway and the Entner-Doudoroff pathway. This unusual method of glucose metabolism results in a low growth yield. In order to improve it, we constructed mutants of strain N44-1 in which the gene encoding the membrane-bound glucose dehydrogenase was inactivated either alone or together with the gene encoding the cytoplasmic glucose dehydrogenase. The growth and product formation from glucose of the resulting strains, N44-1 mgdH::kan and N44-1 ΔmgdH sgdH::kan, were analyzed. Both mutant strains completely consumed the glucose but produced neither gluconate nor the secondary products 2-ketogluconate and 2,5-diketogluconate. Instead, carbon dioxide formation of the mutants increased by a factor of 4 (N44-1 mgdH::kan) or 5.5 (N44-1 ΔmgdH sgdH::kan), and significant amounts of acetate were produced, presumably by the activities of pyruvate decarboxylase and acetaldehyde dehydrogenase. Most importantly, the growth yields of the two mutants increased by 110% (N44-1 mgdH::kan) and 271% (N44-1 ΔmgdH sgdH::kan). In addition, the growth rates improved by 39% (N44-1 mgdH::kan) and 78% (N44-1 ΔmgdH sgdH::kan), respectively, compared to the parental strain. These results show that the conversion of glucose to gluconate and ketogluconates has a strong negative impact on the growth of G. oxydans. PMID:20453146

  18. Dyrk1A induces pancreatic β cell mass expansion and improves glucose tolerance.

    PubMed

    Rachdi, Latif; Kariyawasam, Dulanjalee; Aïello, Virginie; Herault, Yann; Janel, Nathalie; Delabar, Jean-Maurice; Polak, Michel; Scharfmann, Raphaël

    2014-01-01

    Type 2 diabetes is caused by a limited capacity of insulin-producing pancreatic β cells to increase their mass and function in response to insulin resistance. The signaling pathways that positively regulate functional β cell mass have not been fully elucidated. DYRK1A (also called minibrain/MNB) is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. A significant amount of data implicates DYRK1A in brain growth and Down syndrome, and recent data indicate that Dyrk1A haploinsufficient mice have a low functional β cell mass. Here we ask whether Dyrk1A upregulation could be a way to increase functional β cell mass. We used mice overexpressing Dyrk1A under the control of its own regulatory sequences (mBACTgDyrk1A). These mice exhibit decreased glucose levels and hyperinsulinemia in the fasting state. Improved glucose tolerance is observed in these mice as early as 4 weeks of age. Upregulation of Dyrk1A in β cells induces expansion of β cell mass through increased proliferation and cell size. Importantly, mBACTgDyrk1A mice are protected against high-fat-diet-induced β cell failure through increase in β cell mass and insulin sensitivity. These studies show the crucial role of the DYRK1A pathway in the regulation of β cell mass and carbohydrate metabolism in vivo. Activating the DYRK1A pathway could thus represent an innovative way to increase functional β cell mass. PMID:24870561

  19. Improvement of the stability and activity of immobilized glucose oxidase on modified iron oxide magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Abbasi, Mahboube; Amiri, Razieh; Bordbar, Abdol-Kalegh; Ranjbakhsh, Elnaz; Khosropour, Ahmad-Reza

    2016-02-01

    Immobilized proteins and enzymes are widely investigated in the medical field as well as the food and environmental fields. In this study, glucose oxidase (GOX) was covalently immobilized on the surface of modified iron oxide magnetic nanoparticles (MIMNs) to produce a bioconjugate complex. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to the size, shape and structure characterization of the MIMNs. Binding of GOX to these MIMNs was confirmed by using FT-IR spectroscopy. The stability of the immobilized and free enzyme at different temperature and pH values was investigated by measuring the enzymatic activity. These studies reveal that the enzyme's stability is enhanced by immobilization. Further experiments showed that the storage stability of the enzyme is improved upon binding to the MIMNs. The results of kinetic measurements suggest that the effect of the immobilization process on substrate and product diffusion is small. Such bioconjugates can be considered as a catalytic nanodevice for accelerating the glucose oxidation reaction for biotechnological purposes.

  20. Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.

    PubMed

    Walton, R Grace; Zhu, Beibei; Unal, Resat; Spencer, Michael; Sunkara, Manjula; Morris, Andrew J; Charnigo, Richard; Katz, Wendy S; Daugherty, Alan; Howatt, Deborah A; Kern, Philip A; Finlin, Brian S

    2015-05-01

    Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure.

  1. Site-specific mouth rinsing can improve oral odor by altering bacterial counts

    PubMed Central

    Alqumber, Mohammed A.; Arafa, Khaled A.

    2014-01-01

    Objectives: To determine whether site-specific mouth rinsing with oral disinfectants can improve oral odor beyond the traditional panoral mouth disinfection with mouth rinses by targeting specifically oral malodor implicated anaerobic bacteria Methods: Twenty healthy fasting subjects volunteered for a blinded prospective, descriptive correlational crossover cross-section clinical trial conducted during the month of Ramadan between July and August 2013 in Albaha province in Saudi Arabia involving the application of Listerine® Cool Mint® mouth rinse by either the traditional panoral rinsing method, or a site-specific disinfection method targeting the subgingival and supragingival plaque and the posterior third of the tongue dorsum, while avoiding the remaining locations within the oral cavity. The viable anaerobic and aerobic bacterial counts, volatile sulfur compounds (VSCs) levels, organoleptic assessment of oral odor, and the tongue-coating index were compared at baseline, one, 5, and 9 hours after the treatment. Results: The site-specific disinfection method reduced the VSCs and anaerobic bacterial loads while keeping the aerobic bacterial numbers higher than the traditional panoral rinsing method. Conclusion: Site-specific disinfection can more effectively maintain a healthy oral cavity by predominantly disinfecting the niches of anaerobic bacteria within the oral cavity. PMID:25399224

  2. Erythropoietin inhibits gluconeogenesis and inflammation in the liver and improves glucose intolerance in high-fat diet-fed mice.

    PubMed

    Meng, Ran; Zhu, Dalong; Bi, Yan; Yang, Donghui; Wang, Yaping

    2013-01-01

    Erythropoietin (EPO) has multiple biological functions, including the modulation of glucose metabolism. However, the mechanisms underlying the action of EPO are still obscure. This study is aimed at investigating the potential mechanisms by which EPO improves glucose tolerance in an animal model of type 2 diabetes. Male C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks and then treated with EPO (HFD-EPO) or vehicle saline (HFD-Con) for two week. The levels of fasting blood glucose, serum insulin and glucose tolerance were measured and the relative levels of insulin-related phosphatidylinositol 3-kinase (PI3K)/Akt, insulin receptor (IR) and IR substrate 1 (IRS1) phosphorylation were determined. The levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6- phosphatase (G6Pase), toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α and IL-6 expression and nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK) and p38 MAPK activation in the liver were examined. EPO treatment significantly reduced the body weights and the levels of fasting blood glucose and serum insulin and improved the HFD-induced glucose intolerance in mice. EPO treatment significantly enhanced the levels of Akt, but not IR and IRS1, phosphorylation, accompanied by inhibiting the PEPCK and G6Pase expression in the liver. Furthermore, EPO treatment mitigated the HFD-induced inflammatory TNF-α and IL-6 production, TLR4 expression, NF-κB and JNK, but not ERK and p38 MAPK, phosphorylation in the liver. Therefore, our data indicated that EPO treatment improved glucose intolerance by inhibiting gluconeogenesis and inflammation in the livers of HFD-fed mice. PMID:23326455

  3. Brief Report: Remotely Delivered Video Modeling for Improving Oral Hygiene in Children with ASD: A Pilot Study

    ERIC Educational Resources Information Center

    Popple, Ben; Wall, Carla; Flink, Lilli; Powell, Kelly; Discepolo, Keri; Keck, Douglas; Mademtzi, Marilena; Volkmar, Fred; Shic, Frederick

    2016-01-01

    Children with autism have heightened risk of developing oral health problems. Interventions targeting at-home oral hygiene habits may be the most effective means of improving oral hygiene outcomes in this population. This randomized control trial examined the effectiveness of a 3-week video-modeling brushing intervention delivered to patients over…

  4. Effect of Oral Sebacic Acid on Postprandial Glycemia, Insulinemia, and Glucose Rate of Appearance in Type 2 Diabetes

    PubMed Central

    Iaconelli, Amerigo; Gastaldelli, Amalia; Chiellini, Chiara; Gniuli, Donatella; Favuzzi, Angela; Binnert, Christophe; Macé, Katherine; Mingrone, Geltrude

    2010-01-01

    OBJECTIVE Dicarboxylic acids are natural products with the potential of being an alternate dietary source of energy. We aimed to evaluate the effect of sebacic acid (a 10-carbon dicarboxylic acid; C10) ingestion on postprandial glycemia and glucose rate of appearance (Ra) in healthy and type 2 diabetic subjects. Furthermore, the effect of C10 on insulin-mediated glucose uptake and on GLUT4 expression was assessed in L6 muscle cells in vitro. RESEARCH DESIGN AND METHODS Subjects ingested a mixed meal (50% carbohydrates, 15% proteins, and 35% lipids) containing 0 g (control) or 10 g C10 in addition to the meal or 23 g C10 as a substitute of fats. RESULTS In type 2 diabetic subjects, the incremental glucose area under the curve (AUC) decreased by 42% (P < 0.05) and 70% (P < 0.05) in the 10 g C10 and 23 g C10 groups, respectively. At the largest amounts used, C10 reduced the glucose AUC in healthy volunteers also. When fats were substituted with 23 g C10, AUC of Ra was significantly reduced on the order of 18% (P < 0.05) in both healthy and diabetic subjects. The insulin-dependent glucose uptake by L6 cells was increased in the presence of C10 (38.7 ± 10.3 vs. 11.4 ± 5.4%; P = 0.026). This increase was associated with a 1.7-fold raise of GLUT4. CONCLUSIONS Sebacic acid significantly reduced hyperglycemia after a meal in type 2 diabetic subjects. This beneficial effect was associated with a reduction in glucose Ra, probably due to lowered hepatic glucose output and increased peripheral glucose disposal. PMID:20724647

  5. Use of hydrogel coating to improve the performance of implanted glucose sensors.

    PubMed

    Yu, Bazhang; Wang, Chunyan; Ju, Young Min; West, Leigh; Harmon, Julie; Moussy, Yvonne; Moussy, Francis

    2008-03-14

    In order to protect implanted glucose sensors from biofouling, novel hydrogels (146-217% water by mass) were developed based on a copolymer of hydroxyethyl methacrylate (HEMA) and 2,3-dihydroxypropyl methacrylate (DHPMA). The porosity and mechanical properties of the hydrogels were improved using N-vinyl-2-pyrrolidinone (VP) and ethyleneglycol dimethacrylate (EGDMA). The results of SEM and DSC FT-IT analyses showed that the hydrogel (VP30) produced from a monomeric mixture of 34.5% HEMA, 34.5% DHPMA, 30% VP and 1% EDGMA (mol%) had an excellent pore structure, high water content at swelling equilibrium (W eq=166% by mass) and acceptable mechanical properties. Two kinds of VP30-coated sensors, Pt/GOx/VP30 and Pt/GOx/epoxy-polyurethane (EPU)/VP30 sensors were examined in glucose solutions during a period of 4 weeks. The Pt/GOx/VP30 sensors produced large response currents but the response linearity was poor. Therefore, further studies were focused on the Pt/GOx/EPU/VP30 sensors. With a diffusion-limiting epoxy-polyurethane membrane, the linearity was improved (2-30 mM) and the response time was within 5 min. Eight Pt/GOx/EPU/VP30 sensors were subcutaneously implanted in rats and tested once per week over 4 weeks. All of the implanted sensors kept functioning for at least 21 days and 3 out of 8 sensors still functioned at day 28. Histology revealed that the fibrous capsules surrounding hydrogel-coated sensors were thinner than those surrounding Pt/GOx/EPU sensors after 28 days of implantation. PMID:18182283

  6. Combining large area fluorescence with multiphoton microscopy for improved detection of oral epithelial neoplasia (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-03-01

    Volumetric Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia representing the complex microstructural organization of mucosa, potentially providing high specificity for detection of neoplasia, but is limited by small imaging area. Large area fluorescence methods on the other hand show high sensitivity appropriate for screening but are hampered by low specificity. In this study, we apply MPAM-SHGM following guidance from large area fluorescence, by either autofluorescence or a targeted metabolic fluorophore, as a potentially clinically viable approach for detection of oral neoplasia. Sites of high neoplastic potentially were identified by large area red/green autofluorescence or by a fluorescently labelled deoxy-glucose analog, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) to highlight areas of high glucose uptake across the buccal pouch of a hamster model for OSCC. Follow-up MPAM-SHGM was conducted on regions of interests (ROIs) to assess whether microscopy would reveal microscopic features associated with neoplasia to confirm or exclude large area fluorescence findings. Parameters for analysis included cytologic metrics, 3D epithelial connective tissue interface metrics (MPAM-SHGM) and intensity of fluorescence (widefield). Imaged sites were biopsied and processed for histology and graded by a pathologist. A small sample of human ex vivo tissues were also imaged. A generalized linear model combining image metrics from large area fluorescence and volumetric MPAM-SHGM indicated the ability to delineate normal and inflammation from neoplasia.

  7. Improving oral healthcare: improving the quality of life for patients after a stroke.

    PubMed

    Tran, Phuong; Mannen, Jana

    2009-01-01

    With the increase in the elderly population, the prevalence of systemic diseases such as strokes and heart attacks will also increase. Persons who have had a stroke will be more susceptible to mistreatment, neglect, abuse, and aspiration pneumonia. The expansion of the elderly population will make the training of professional healthcare workers and other auxiliaries extremely important. Quality of life can be maintained if poor oral health is reduced through better daily oral hygiene practices. Informing others about the known association between oral health and systemic diseases will increase the awareness of the need for good oral hygiene in order to reduce the risk of systemic diseases. Healthcare professionals must also be able to recognize, document, and report to Adult Protective Services suspected abuse such as physical and dental neglect. The networking of healthcare providers with Adult Protective Services and other professional disciplines will provide a collaborative approach to assure successful integration of healthcare protocols for the elderly population.

  8. Baselines representing blood glucose clearance improve in vitro prediction of the glycaemic impact of customarily consumed food quantities.

    PubMed

    Monro, John A; Mishra, Suman; Venn, Bernard

    2010-01-01

    Glycaemic responses to foods reflect the balance between glucose loading into, and its clearance from, the blood. Current in vitro methods for glycaemic analysis do not take into account the key role of glucose disposal. The present study aimed to develop a food intake-sensitive method for measuring the glycaemic impact of food quantities usually consumed, as the difference between release of glucose equivalents (GGE) from food during in vitro digestion and a corresponding estimate of clearance of them from the blood. Five foods - white bread, fruit bread, muesli bar, mashed potato and chickpeas - were consumed on three occasions by twenty volunteers to provide blood glucose response (BGR) curves. GGE release during in vitro digestion of the foods was also plotted. Glucose disposal rates estimated from downward slopes of the BGR curves allowed GGE dose-dependent cumulative glucose disposal to be calculated. By subtracting cumulative glucose disposal from cumulative in vitro GGE release, accuracy in predicting the in vivo glycaemic effect from in vitro GGE values was greatly improved. GGE(in vivo) = 0.99GGE(in vitro)+0.75 (R(2) 0.88). Furthermore, the difference between the curves of cumulative GGE release and disposal closely mimicked in vivo incremental BGR curves. We conclude that valid measurement of the glycaemic impact of foods may be obtained in vitro, and expressed as grams of glucose equivalents per food quantity, by taking account not only of GGE release from food during in vitro digestion, but also of blood glucose clearance in response to the food quantity.

  9. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans.

    PubMed

    Pisprasert, Veeradej; Ingram, Katherine H; Lopez-Davila, Maria F; Munoz, A Julian; Garvey, W Timothy

    2013-04-01

    OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SI(is)OGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males.

  10. Study on an improved wavelet threshold denoising for the time-resolved photoacoustic signals of the glucose solution

    NASA Astrophysics Data System (ADS)

    Ren, Zhong; Liu, Guodong; Huang, Zhen

    2015-08-01

    Although the time-domain method, frequency-domain method and wavelet-domain method can used into signal denoising or filtering, the denoising of blood glucose photoacoustic signals are limited due to some advantages. In this paper, an improved wavelet threshold denoising method is used to remove the noise of the blood glucose photoacoustic signals. In order to overcome some drawbacks of classical wavelet threshold denoising, an improved wavelet threshold function was proposed. In the simulation experiments, the different denoising results are compared between this improved wavelet threshold function and other functions. And the experiments of this improved wavelet threshold function into the denoising of the time-resolved photoacoustic signals of glucose solution are performed. The experimental result verifies that the improved wavelet threshold function denoising is available. The improved wavelet threshold function has better flexibility than others due to the usage of two threshold values and two factors. So, the improved wavelet threshold function has the potential value in the denoising field of blood glucose photoacoustic signals.

  11. Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men.

    PubMed

    Dengel, D R; Hagberg, J M; Pratley, R E; Rogus, E M; Goldberg, A P

    1998-09-01

    The clustering of metabolic abnormalities often associated with hypertension, including insulin resistance, glucose intolerance, and dyslipidemia, in middle-aged men may be the result of a decrease in cardiovascular fitness (VO2max) and the accumulation of body fat with aging. This study examines the effects of a 6-month program of aerobic exercise training plus weight loss (AEX+WL) on VO2max, body composition, blood pressure (BP), glucose and insulin responses during an oral glucose tolerance test (OGTT), glucose infusion rates (GIR) during 3-dose hyperinsulinemic-euglycemic clamps at insulin infusion rates of 120, 600, and 3,000 pmol x m(-2) x min(-1), and plasma lipoprotein levels. Compared with eight non-obese, normotensive, sedentary men (age, 62+/-2 years; 19%+/-2% fat; BP, 117+/-4/72+/-2 mm Hg), the nine obese, hypersensitive, sedentary men studied (age, 56+/-1 year; 32%+/-1% body fat; BP, 147+/-3/93+/-2 mm Hg) initially had a larger waist girth and waist-to-hip ratio (WHR) and were more hyperinsulinemic and insulin resistant with lower GIR at the two lower insulin infusion rates of the clamp and had a 2.9-fold higher EC50, the insulin concentration producing a half-maximal increase in GIR. They had higher triglyceride (TG) and lower high-density lipoprotein cholesterol (HDL-C) levels. The AEX+WL intervention reduced body weight by 9%, percent body fat by 21%, waist girth by 9%, and WHR by 3%, and increased VO2max by 16% (P < .01 for all). This was associated with decreases of 14+/-3 mm Hg in systolic and 10+/-2 mm Hg in diastolic BP, significant changes in GIR at the low (+42%) and intermediate (+39%) insulin infusion rates and EC50 (-39%) and in glucose (-21%) and insulin (-51%) responses during OGTT (P < .02 for all). AEX+WL also lowered total cholesterol by 14% and TG by 34%, and raised HDL2-C levels twofold (P < .01 for all). Thus, a 6-month AEX+WL intervention substantially lowers BP and improves glucose and lipid metabolism in obese, sedentary

  12. Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals.

    PubMed

    McClements, David Julian; Xiao, Hang

    2014-07-25

    The oral bioavailability of many lipophilic bioactive agents (pharmaceuticals and nutraceuticals) is limited due to various physicochemical and physiological processes: poor release from food or drug matrices; low solubility in gastrointestinal fluids; metabolism or chemical transformation within the gastrointestinal tract; low epithelium cell permeability. The bioavailability of these agents can be improved by specifically designing food matrices that control their release, solubilization, transport, metabolism, and absorption within the gastrointestinal tract. This article discusses the impact of food composition and structure on oral bioavailability, and how this knowledge can be used to design excipient foods for improving the oral bioavailability of lipophilic bioactives. Excipient foods contain ingredients or structures that may have no bioactivity themselves, but that are able to promote the bioactivity of co-ingested bioactives. These bioactives may be lipophilic drugs in pharmaceutical preparations (such as capsules, pills, or syrups) or nutraceuticals present within food matrices (such as natural or processed foods and beverages). PMID:24760211

  13. Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions

    PubMed Central

    Little, Peter J; Osman, Narin; de Dios, Stephanie T; Cemerlang, Nelly; Ballinger, Mandy; Nigro, Julie

    2007-01-01

    Background Inhibition of vascular smooth muscle cell (vSMC) proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs) inhibit vSMC proliferation but it has been reported that they anomalously stimulate [3H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [3H]-thymidine incorporation. Methods VSMC proliferation was investigated by [3H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [3H]-thymidine uptake. Cell cycle events were analyzed by FACS. Results VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose) and high (25 mM glucose) increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P < 0.05 and P < 0.001, respectively). We confirmed an earlier report that troglitazone (at low concentrations) causes enhanced incorporation of [3H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [3H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations

  14. Application of time-resolved glucose concentration photoacoustic signals based on an improved wavelet denoising

    NASA Astrophysics Data System (ADS)

    Ren, Zhong; Liu, Guodong; Huang, Zhen

    2014-10-01

    Real-time monitoring of blood glucose concentration (BGC) is a great important procedure in controlling diabetes mellitus and preventing the complication for diabetic patients. Noninvasive measurement of BGC has already become a research hotspot because it can overcome the physical and psychological harm. Photoacoustic spectroscopy is a well-established, hybrid and alternative technique used to determine the BGC. According to the theory of photoacoustic technique, the blood is irradiated by plused laser with nano-second repeation time and micro-joule power, the photoacoustic singals contained the information of BGC are generated due to the thermal-elastic mechanism, then the BGC level can be interpreted from photoacoustic signal via the data analysis. But in practice, the time-resolved photoacoustic signals of BGC are polluted by the varities of noises, e.g., the interference of background sounds and multi-component of blood. The quality of photoacoustic signal of BGC directly impacts the precision of BGC measurement. So, an improved wavelet denoising method was proposed to eliminate the noises contained in BGC photoacoustic signals. To overcome the shortcoming of traditional wavelet threshold denoising, an improved dual-threshold wavelet function was proposed in this paper. Simulation experimental results illustrated that the denoising result of this improved wavelet method was better than that of traditional soft and hard threshold function. To varify the feasibility of this improved function, the actual photoacoustic BGC signals were test, the test reslut demonstrated that the signal-to-noises ratio(SNR) of the improved function increases about 40-80%, and its root-mean-square error (RMSE) decreases about 38.7-52.8%.

  15. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans.

    PubMed

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E; Saraf, Manish K; Labbe, Sebastien M; Hurren, Nicholas M; Yfanti, Christina; Chao, Tony; Andersen, Clark R; Cesani, Fernando; Hawkins, Hal; Sidossis, Labros S

    2014-12-01

    Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT(+) group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.

  16. Salidroside improves glucose homeostasis in obese mice by repressing inflammation in white adipose tissues and improving leptin sensitivity in hypothalamus

    PubMed Central

    Wang, Meihong; Luo, Lan; Yao, Lili; Wang, Caiping; Jiang, Ketao; Liu, Xiaoyu; Xu, Muchen; Shen, Ningmei; Guo, Shaodong; Sun, Cheng; Yang, Yumin

    2016-01-01

    Salidroside is a functionally versatile natural compound from the perennial flowering plant Rhodiola rosea L. Here, we examined obese mice treated with salidroside at the dosage of 50 mg/kg/day for 48 days. Mice treated with salidroside showed slightly decreased food intake, body weight and hepatic triglyceride content. Importantly, salidroside treatment significantly improved glucose and insulin tolerance. It also increased insulin singling in both liver and epididymal white adipose tissue (eWAT). In addition, salidroside markedly ameliorated hyperglycemia in treated mice, which is likely due to the suppression of gluconeogenesis by salidroside as the protein levels of a gluconeogenic enzyme G6Pase and a co-activator PGC-1α were all markedly decreased. Further analysis revealed that adipogenesis in eWAT was significantly decreased in salidroside treated mice. The infiltration of macrophages in eWAT and the productions of pro-inflammatory cytokines were also markedly suppressed by salidroside. Furthermore, the leptin signal transduction in hypothalamus was improved by salidroside. Taken together, these euglycemic effects of salidroside may due to repression of adipogenesis and inflammation in eWAT and stimulation of leptin signal transduction in hypothalamus. Thus, salidroside might be used as an effective anti-diabetic agent. PMID:27145908

  17. Reducing blood glucose levels in TIDM mice with an orally administered extract of sericin from hIGF-I-transgenic silkworm cocoons.

    PubMed

    Song, Zuowei; Zhang, Mengyao; Xue, Renyu; Cao, Guangli; Gong, Chengliang

    2014-05-01

    In previous studies, we reported that the blood glucose levels of mice with type I diabetes mellitus (TIDM) was reduced with orally administered silk gland powder from silkworms transgenic for human insulin-like growth factor-I (hIGF-I). However, potential safety hazards could not be eliminated because the transgenic silk gland powder contained heterologous DNA, including the green fluorescent protein (gfp) and neomycin resistance (neo) genes. These shortcomings might be overcome if the recombinant hIGF-I were secreted into the sericin layer of the cocoon. In this study, silkworm eggs were transfected with a novel piggyBac transposon vector, pigA3GFP-serHS-hIGF-I-neo, containing the neo, gfp, and hIGF-I genes controlled by the sericin-1 (ser-1) promoter with the signal peptide DNA sequence of the fibrin heavy chain (Fib-H) and a helper plasmid containing the piggyBac transposase sequence under the control of the Bombyx mori actin 3 (A3) promoter, using sperm-mediated gene transfer to generate the transformed silkworms. The hIGF-I content estimated by enzyme-linked immunosorbent assay was approximately 162.7 ng/g. To estimate the biological activity of the expressed hIGF-I, streptozotocin-induced TIDM mice were orally administered sericin from the transgenic silkworm. The blood glucose levels of the mice were significantly reduced, suggesting that the extract from the transgenic hIGF-I silkworm cocoons can be used as an orally administered drug.

  18. Improving Oral Reading in Mentally Handicapped Adults through Increased Opportunity and Practice.

    ERIC Educational Resources Information Center

    Gillette, Tracy L.

    A project developed a plan to improve oral reading in 12 mentally handicapped adults by stressing observation of punctuation marks, reading in phrases, using proper volume, and increasing confidence levels. Identifying the parts of a book and identifying new words were also included. The 12 students were reading below their potential, as shown by…

  19. Improving the Awareness of Personal and Oral Hygiene in Second Graders.

    ERIC Educational Resources Information Center

    Meleskie-Lippert, Kathleen

    The practicum reported here involved the design of a hygiene awareness unit to help 30 second-grade students in an inner-city school become aware of and improve their personal and oral hygiene, and to provide necessary knowledge concerning pediculosis. Surveys of students and faculty prior to the program demonstrated the need for such a program as…

  20. Display of Glucose Distributions by Date, Time of Day, and Day of Week: New and Improved Methods

    PubMed Central

    Rodbard, David

    2009-01-01

    Objective There is a need for improved methods for display of glucose distributions to facilitate comparisons by date, time of day, day of the week, and other variables for data obtained using self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM). Method Stacked bar charts are utilized for multiple ranges of glucose values, e.g., very low, low, borderline low, target range, borderline high, high, and very high. Glucose ranges for these categories can be defined by the user, e.g., <40, 40–70, 71–80, 81–140, 141–180, 181–250, and 251–400 mg/dl. Glucose distributions can be displayed by time of day, in relation to meals, by date, or by day of week. The graphic display can be generated using general purpose spreadsheet software such as Microsoft Excel or with special purpose software. Result Stacked bar charts are extremely compact and effective. They facilitate comparison of multiple days, multiple time segments within a day, preprandial and postprandial glucose levels, days of the week, treatment periods, patients, and groups of patients. They are superior to use of pie charts in terms of compactness and in their ability to facilitate comparisons using multiple criteria and multiple subsets of the data. One can identify episodes of hypoglycemia and hyperglycemia and can display standard errors of estimates of percentages. Interpretation of these graphs is readily learned and requires minimal training. Conclusion Use of stacked bar charts is generally superior to use of pie charts for display of glucose distributions and can potentially facilitate the analysis and interpretation of SMBG and CGM data. PMID:20144393

  1. Comparison of the enhancement of plasma glucose levels in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats by oral administration of sucrose or maple syrup.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa; Taga, Atsushi

    2013-01-01

    Maple syrup is used as a premium natural sweeter, and is known for being good for human health. In the present study, we investigate whether maple syrup is suitable as a sweetener in the management of type 2 diabetes using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. OLETF rats develop type 2 diabetes mellitus by 30 weeks of age, and 60-week-old OLETF rats show hyperglycemia and hypoinsulinemia via pancreatic β-cell dysfunction. The administration of sucrose or maple syrup following an OGT test increased plasma glucose (PG) levels in OLETF rats, but the enhancement in PG following the oral administration of maple syrup was lower than in the case of sucrose administration in both 30- and 60-week-old OLETF rats. Although, the insulin levels in 30-week-old OLETF rats also increased following the oral administration of sucrose or maple syrup, no increase in insulin levels was seen in 60-week-old OLETF rats following the oral administration of either sucrose or maple syrup. No significant differences were observed in insulin levels between sucrose- and maple syrup-administered OLETF rats at either 30 or 60 weeks of age. The present study strongly suggests that the maple syrup may have a lower glycemic index than sucrose, which may help in the prevention of type 2 diabetes.

  2. Effectiveness of an educational video in improving oral health knowledge in a hospital setting

    PubMed Central

    Shah, Naseem; Mathur, Vijay Prakash; Kathuria, Vartika; Gupta, Tanupriya

    2016-01-01

    Introduction: Prevention of oral diseases can be achieved by preventive measures. There is an educational component associated to the preventive aspect. Health education is a cornerstone to the success of a preventive programme. Health education has always been regarded as a primary tool in imparting awareness, bringing changes in healthy behaviors and improved life. Aim: To assess the effectiveness of an Educational Video in improving oral health knowledge of subjects in a hospital setting. Methodology: The study was conducted in Outpatient Department, CDER, AIIMS. This was a cross sectional interventional study. In the present study a total of 109 subjects were considered those who completed pre and post intervention questionnaire. In order to assess baseline oral health knowledge, a-14 itemed questionnaire was specially designed, based on the contents of video and was pre-tested on 10 patients. Pre-intervention knowledge was assessed and then the 30-minute video was shown. Following this, post-exposure knowledge was assessed using the same questionnaire. Change in the knowledge score amongst the subjects was assessed pre and post-intervention (showing the video film). Results: Paired t- test was used to analyze the data. Pre-intervention mean knowledge score was 9.49±2.09 which increased to 11.55±1.60 post-intervention; the difference was statistically significant (P < 0.001). Conclusions: It was found that increase in knowledge score was statistically significant after exposure to an educational video film in a hospital setting. Incorporation of video in imparting oral health education can be an effective tool in improving oral health knowledge, which can impact the oral health behavior of people and community. PMID:27433049

  3. Oral anticancer drugs: mechanisms of low bioavailability and strategies for improvement.

    PubMed

    Stuurman, Frederik E; Nuijen, Bastiaan; Beijnen, Jos H; Schellens, Jan H M

    2013-06-01

    The use of oral anticancer drugs has increased during the last decade, because of patient preference, lower costs, proven efficacy, lack of infusion-related inconveniences, and the opportunity to develop chronic treatment regimens. Oral administration of anticancer drugs is, however, often hampered by limited bioavailability of the drug, which is associated with a wide variability. Since most anticancer drugs have a narrow therapeutic window and are dosed at or close to the maximum tolerated dose, a wide variability in the bioavailability can have a negative impact on treatment outcome. This review discusses mechanisms of low bioavailability of oral anticancer drugs and strategies for improvement. The extent of oral bioavailability depends on many factors, including release of the drug from the pharmaceutical dosage form, a drug's stability in the gastrointestinal tract, factors affecting dissolution, the rate of passage through the gut wall, and the pre-systemic metabolism in the gut wall and liver. These factors are divided into pharmaceutical limitations, physiological endogenous limitations, and patient-specific limitations. There are several strategies to reduce or overcome these limitations. First, pharmaceutical adjustment of the formulation or the physicochemical characteristics of the drug can improve the dissolution rate and absorption. Second, pharmacological interventions by combining the drug with inhibitors of transporter proteins and/or pre-systemic metabolizing enzymes can overcome the physiological endogenous limitations. Third, chemical modification of a drug by synthesis of a derivative, salt form, or prodrug could enhance the bioavailability by improving the absorption and bypassing physiological endogenous limitations. Although the bioavailability can be enhanced by various strategies, the development of novel oral products with low solubility or cell membrane permeability remains cumbersome and is often unsuccessful. The main reasons are

  4. Oral anticancer drugs: mechanisms of low bioavailability and strategies for improvement.

    PubMed

    Stuurman, Frederik E; Nuijen, Bastiaan; Beijnen, Jos H; Schellens, Jan H M

    2013-06-01

    The use of oral anticancer drugs has increased during the last decade, because of patient preference, lower costs, proven efficacy, lack of infusion-related inconveniences, and the opportunity to develop chronic treatment regimens. Oral administration of anticancer drugs is, however, often hampered by limited bioavailability of the drug, which is associated with a wide variability. Since most anticancer drugs have a narrow therapeutic window and are dosed at or close to the maximum tolerated dose, a wide variability in the bioavailability can have a negative impact on treatment outcome. This review discusses mechanisms of low bioavailability of oral anticancer drugs and strategies for improvement. The extent of oral bioavailability depends on many factors, including release of the drug from the pharmaceutical dosage form, a drug's stability in the gastrointestinal tract, factors affecting dissolution, the rate of passage through the gut wall, and the pre-systemic metabolism in the gut wall and liver. These factors are divided into pharmaceutical limitations, physiological endogenous limitations, and patient-specific limitations. There are several strategies to reduce or overcome these limitations. First, pharmaceutical adjustment of the formulation or the physicochemical characteristics of the drug can improve the dissolution rate and absorption. Second, pharmacological interventions by combining the drug with inhibitors of transporter proteins and/or pre-systemic metabolizing enzymes can overcome the physiological endogenous limitations. Third, chemical modification of a drug by synthesis of a derivative, salt form, or prodrug could enhance the bioavailability by improving the absorption and bypassing physiological endogenous limitations. Although the bioavailability can be enhanced by various strategies, the development of novel oral products with low solubility or cell membrane permeability remains cumbersome and is often unsuccessful. The main reasons are

  5. Oratoria Online: The Use of Technology Enhaced Learning to Improve Students' Oral Skills

    NASA Astrophysics Data System (ADS)

    Dornaleteche, Jon

    New ITCs have proven to be useful tools for implementing innovating didactic and pedagogical formula oriented to enhance students' en teachers' creativity. The up-and-coming massive e-learning and blended learning projects are clear examples of such a phenomenon. The teaching of oral communication offers a perfect scenario to experiment with these formulas. Since the traditional face to face approach for teaching 'Speech techniques' does not keep up with the new digital environment that surround students, it is necessary to move towards an 'Online oratory' model focused on using TEL to improve oral skills.

  6. Improvement of Glucose Metabolism in the Visual Cortex Accompanies Visual Field Recovery in a Patient with Hemianopia.

    PubMed

    Suzuki, Yukihisa; Kiyosawa, Motohiro; Oda, Keiichi; Ishiwata, Kiich; Ishii, Kenji

    2016-01-01

    Damage to the visual cortex or the geniculostriatal pathways could cause homonymous visual field (VF) defects at the contralateral side of the lesion. In clinical practice, it is known that the VF defects are gradually recovered over months on the cases. We report a case with recovered homonymous hemianopia following an infarction in the visual cortex by positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-flumazenil (FMZ). A 58-year-old man experienced defect of left VF, and magnetic resonance imaging (MRI) revealed a localized infarction in the right occipital lobe. Goldmann VF perimetry revealed left homonymous hemianopia, but central VF was intact. Three months after the onset of infarction, we measured cerebral glucose metabolism with FDG and FMZ binding using PET. FMZ binding reflects the density of surviving neurons. Moreover, eight months after the onset, FDG-PET scan was performed. Goldmann VF perimetry was also performed at the same times of PET examinations. Decrease of cerebral glucose metabolism in the right anterior striate cortex was observed at three months after onset, while FMZ binding in the same area did not decrease in the patient. At eight months after onset, we observed recovery of VF and improvement of cerebral glucose metabolism in the anterior striate cortex. We presented change of cerebral glucose metabolism using PET accompanying improvement of VF. Evaluation of cerebral glucose metabolism and FMZ binding in the striate cortex is useful for estimating the prognosis of hemianopia caused by organic brain damage. PMID:27039943

  7. Improvement of Glucose Metabolism in the Visual Cortex Accompanies Visual Field Recovery in a Patient with Hemianopia.

    PubMed

    Suzuki, Yukihisa; Kiyosawa, Motohiro; Oda, Keiichi; Ishiwata, Kiich; Ishii, Kenji

    2016-01-01

    Damage to the visual cortex or the geniculostriatal pathways could cause homonymous visual field (VF) defects at the contralateral side of the lesion. In clinical practice, it is known that the VF defects are gradually recovered over months on the cases. We report a case with recovered homonymous hemianopia following an infarction in the visual cortex by positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-flumazenil (FMZ). A 58-year-old man experienced defect of left VF, and magnetic resonance imaging (MRI) revealed a localized infarction in the right occipital lobe. Goldmann VF perimetry revealed left homonymous hemianopia, but central VF was intact. Three months after the onset of infarction, we measured cerebral glucose metabolism with FDG and FMZ binding using PET. FMZ binding reflects the density of surviving neurons. Moreover, eight months after the onset, FDG-PET scan was performed. Goldmann VF perimetry was also performed at the same times of PET examinations. Decrease of cerebral glucose metabolism in the right anterior striate cortex was observed at three months after onset, while FMZ binding in the same area did not decrease in the patient. At eight months after onset, we observed recovery of VF and improvement of cerebral glucose metabolism in the anterior striate cortex. We presented change of cerebral glucose metabolism using PET accompanying improvement of VF. Evaluation of cerebral glucose metabolism and FMZ binding in the striate cortex is useful for estimating the prognosis of hemianopia caused by organic brain damage.

  8. A 12 week aerobic exercise program improves fitness, hepatic insulin sensitivity and glucose metabolism in obese Hispanic adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rise in obesity related morbidity in children and adolescents requires urgent prevention and treatment strategies. Strictly controlled exercise programs might be useful tools to improve insulin sensitivity and glucose kinetics. Our objective was to test the hypothesis that a 12-wk aerobic exerci...

  9. Improved oral absorption of exenatide using an original nanoencapsulation and microencapsulation approach.

    PubMed

    Soudry-Kochavi, Liat; Naraykin, Natalya; Nassar, Taher; Benita, Simon

    2015-11-10

    Oral delivery is the most convenient and favorable route for chronic administration of peptides and proteins to patients. However, many obstacles are faced when developing such a delivery route. Nanoparticles (NPs) are among the leading innovative solutions for delivery of these drugs. Exenatide is a peptidic drug administered subcutaneously (SC) twice a day chronically as an add-on therapy for the worldwide pandemic disease, diabetes. Many attempts to develop oral nanocarriers for this drug have been unsuccessful due to the inability to retain this hydrophilic macromolecule under sink conditions or to find a suitable cross-linker which does not harm the chemical integrity of the peptide. In this study, we report about an original oral delivery solution based on a mixture of albumin and dextran NPs cross-linked using sodium trimetaphosphate (STMP). Moreover, we suggest a second defense line of gastro-resistant microparticles (MPs) composed of an appropriate ratio of Eudragit® L100-55 (Eudragit L) and hydroxypropylmethylcellulose (HPMC), for additional protection to these NPs presumably allowing them to be absorbed in the intestine intact. Our results demonstrate that such a system indeed improves the relative oral bioavailability of exenatide to a level of about 77% compared to subcutaneous injection due to the presence of dextran in the coating wall of the NPs which apparently promotes the lymphatic uptake in the enterocytes. This technology may be a milestone on the way to deliver other peptides and proteins orally. PMID:26381898

  10. Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption.

    PubMed

    Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin

    2016-09-10

    Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40μM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine. PMID:27377011

  11. Improving dissolution and oral bioavailability of pranlukast hemihydrate by particle surface modification with surfactants and homogenization

    PubMed Central

    Ha, Eun-Sol; Baek, In-hwan; Yoo, Jin-Wook; Jung, Yunjin; Kim, Min-Soo

    2015-01-01

    The present study was carried out to develop an oral formulation of pranlukast hemihydrate with improved dissolution and oral bioavailability using a surface-modified microparticle. Based on solubility measurements, surface-modified pranlukast hemihydrate microparticles were manufactured using the spray-drying method with hydroxypropylmethyl cellulose, sucrose laurate, and water and without the use of an organic solvent. The hydrophilicity of the surface-modified pranlukast hemihydrate microparticle increased, leading to enhanced dissolution and oral bioavailability of pranlukast hemihydrate without a change in crystallinity. The surface-modified microparticles with an hydroxypropylmethyl cellulose/sucrose laurate ratio of 1:2 showed rapid dissolution of up to 85% within 30 minutes in dissolution medium (pH 6.8) and oral bioavailability higher than that of the commercial product, with approximately 2.5-fold and 3.9-fold increases in area under the curve (AUC0→12 h) and peak plasma concentration, respectively. Therefore, the surface-modified microparticle is an effective oral drug delivery system for the poorly water-soluble therapeutic pranlukast hemihydrate. PMID:26150699

  12. A Soluble Activin Receptor Type IIB Does Not Improve Blood Glucose in Streptozotocin-Treated Mice

    PubMed Central

    Wang, Qian; Guo, Tingqing; Portas, Jennifer; McPherron, Alexandra C.

    2015-01-01

    Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of MSTN signaling has been shown to increase muscle mass and prevent the development of obesity, insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin (STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also elevated serum levels of the glucocorticoid corticosterone. These results suggest that although MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving health in patients with T1DM. PMID:25561902

  13. Central action of FGF19 reduces hypothalamic AGRP/NPY neuron activity and improves glucose metabolism.

    PubMed

    Marcelin, Geneviève; Jo, Young-Hwan; Li, Xiaosong; Schwartz, Gary J; Zhang, Ying; Dun, Nae J; Lyu, Rong-Ming; Blouet, Clémence; Chang, Jaw K; Chua, Streamson

    2014-02-01

    Tight control of glucose excursions has been a long-standing goal of treatment for patients with type 2 diabetes mellitus in order to ameliorate the morbidity and mortality associated with hyperglycemia. Fibroblast growth factor (FGF) 19 is a hormone-like enterokine released postprandially that emerged as a potential therapeutic agent for metabolic disorders, including diabetes and obesity. Remarkably, FGF19 treatment has hypoglycemic actions that remain potent in models of genetic and acquired insulin resistance. Here, we provided evidence that the central nervous system responds to FGF19 administered in the periphery. Then, in two mouse models of insulin resistance, leptin-deficiency and high-fat diet feeding, third intra-cerebro-ventricular infusions of FGF19 improved glycemic status, reduced insulin resistance and potentiated insulin signaling in the periphery. In addition, our study highlights a new mechanism of central FGF19 action, involving the suppression of AGRP/NPY neuronal activity. Overall, our work unveils novel regulatory pathways induced by FGF19 that will be useful in the design of novel strategies to control diabetes in obesity. PMID:24567901

  14. Metabolic engineering for improving anthranilate synthesis from glucose in Escherichia coli

    PubMed Central

    Balderas-Hernández, Víctor E; Sabido-Ramos, Andrea; Silva, Patricia; Cabrera-Valladares, Natividad; Hernández-Chávez, Georgina; Báez-Viveros, José L; Martínez, Alfredo; Bolívar, Francisco; Gosset, Guillermo

    2009-01-01

    Background Anthranilate is an aromatic amine used industrially as an intermediate for the synthesis of dyes, perfumes, pharmaceuticals and other classes of products. Chemical synthesis of anthranilate is an unsustainable process since it implies the use of nonrenewable benzene and the generation of toxic by-products. In Escherichia coli anthranilate is synthesized from chorismate by anthranilate synthase (TrpED) and then converted to phosphoribosyl anthranilate by anthranilate phosphoribosyl transferase to continue the tryptophan biosynthetic pathway. With the purpose of generating a microbial strain for anthranilate production from glucose, E. coli W3110 trpD9923, a mutant in the trpD gene that displays low anthranilate producing capacity, was characterized and modified using metabolic engineering strategies. Results Sequencing of the trpED genes from E. coli W3110 trpD9923 revealed a nonsense mutation in the trpD gene, causing the loss of anthranilate phosphoribosyl transferase activity, but maintaining anthranilate synthase activity, thus causing anthranilate accumulation. The effects of expressing genes encoding a feedback inhibition resistant version of the enzyme 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (aroGfbr), transketolase (tktA), glucokinase (glk) and galactose permease (galP), as well as phosphoenolpyruvate:sugar phosphotransferase system (PTS) inactivation on anthranilate production capacity, were evaluated. In shake flask experiments with minimal medium, strains W3110 trpD9923 PTS- and W3110 trpD9923/pJLBaroGfbrtktA displayed the best production parameters, accumulating 0.70–0.75 g/L of anthranilate, with glucose-yields corresponding to 28–46% of the theoretical maximum. To study the effects of extending the growth phase on anthranilate production a fed-batch fermentation process was developed using complex medium, where strain W3110 trpD9923/pJLBaroGfbrtktA produced 14 g/L of anthranilate in 34 hours. Conclusion This work constitutes

  15. One-step self-assembled nanomicelles for improving the oral bioavailability of nimodipine

    PubMed Central

    Luo, Jing-Wen; Zhang, Zhi-Rong; Gong, Tao; Fu, Yao

    2016-01-01

    Our study aimed to develop a self-assembled nanomicelle for oral administration of nimodipine (NIM) with poor water solubility. Using Solutol® HS15, the NIM-loaded self-assembled nanomicelles displayed a near-spherical morphology with a narrow size distribution of 12.57±0.21 nm (polydispersity index =0.071±0.011). Compared with Nimotop® (NIM tablets), the intestinal absorption of NIM from NIM nanomicelle in rats was improved by 3.13- and 2.25-fold in duodenum and jejunum at 1 hour after oral administration. The cellular transport of NIM nanomicelle in Caco-2 cell monolayers was significantly enhanced compared to that of Nimotop®. Regarding the transport pathways, clathrin, lipid raft/caveolae, and macropinocytosis mediated the cell uptake of NIM nanomicelles, while P-glycoprotein and endoplasmic reticulum/Golgi complex (ER/Golgi) pathways were involved in exocytosis. Pharmacokinetic studies in our research laboratory have showed that the area under the plasma concentration–time curve (AUC0–∞) of NIM nanomicelles was 3.72-fold that of Nimotop® via oral administration in rats. Moreover, the NIM concentration in the brain from NIM nanomicelles was dramatically improved. Therefore, Solutol® HS15-based self-assembled nanomicelles represent a promising delivery system to enhance the oral bioavailability of NIM. PMID:27042060

  16. Self-microemulsifying drug delivery system for improved oral bioavailability of dipyridamole: preparation and evaluation.

    PubMed

    Guo, Feng; Zhong, Haijun; He, Jing; Xie, Baogang; Liu, Fen; Xu, Helin; Liu, Minmin; Xu, Chunlian

    2011-07-01

    Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility.

  17. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability.

    PubMed

    Tran, Thanh Huyen; Guo, Yi; Song, Donghui; Bruno, Richard S; Lu, Xiuling

    2014-03-01

    Quercetin is a dietary flavonoid with potential chemoprotective effects, but has low bioavailability because of poor aqueous solubility and low intestinal absorption. A quercetin-containing self-nanoemulsifying drug delivery system (Q-SNEDDS) was developed to form oil-in-water nanoemulsions in situ for improving quercetin oral bioavailability. On the basis of the quercetin solubility, emulsifying ability, and stability after dispersion in an aqueous phase, an optimal SNEDDS consisting of castor oil, Tween® 80, Cremophor® RH 40, and PEG 400 (20:16:34:30, w/w) was identified. Upon mixing with water, Q-SNEDDS formed a nanoemulsion having a droplet size of 208.8 ± 4.5 nm and zeta potential of -26.3 ± 1.2 mV. The presence of Tween® 80 and PEG 400 increased quercetin solubility and maintained supersaturated quercetin concentrations (5 mg/mL) for >1 month. The optimized Q-SNEDDS significantly improved quercetin transport across a human colon carcinoma (Caco-2) cell monolayer. Fluorescence imaging demonstrated rapid absorption of the Q-SNEDDS within 40 min of oral ingestion. Following oral administration of Q-SNEDDS in rats (15 mg/kg), the area under the concentration curve and maximum concentration of plasma quercetin after 24 h increased by approximately twofold and threefold compared with the quercetin control suspension. These data suggest that this Q-SNEDDS formulation can enhance the solubility and oral bioavailability of quercetin for appropriate clinical application.

  18. Nimodipine nanocrystals for oral bioavailability improvement: preparation, characterization and pharmacokinetic studies.

    PubMed

    Fu, Qiang; Sun, Jin; Zhang, Dong; Li, Mo; Wang, Yongjun; Ling, Guixia; Liu, Xiaohong; Sun, Yinghua; Sui, Xiaofan; Luo, Cong; Sun, Le; Han, Xiaopeng; Lian, He; Zhu, Meng; Wang, Siling; He, Zhonggui

    2013-09-01

    This study intended to develop nimodipine (NMD) nanocrystals with different sizes for oral administration and to investigate the relationship between dissolution and pharmacokinetics for NMD nanocrystals and Nimotop(®). NMD nanocrystals were prepared by combination of microprecipitation and high pressure homogenization and were further lyophilized. The particle size, morphology and aqueous solubility of the NMD nanocrystals were determined. With Nimotop(®) as the control, the dissolution rate was evaluated and the pharmacokinetic study was undertaken in beagle dogs. NMD nanocrystals with mean diameters of about 159.0, 503.0 and 833.3 nm were prepared, respectively. The lyophilization didn't affect the particle sizes of the redispersed nanocrystals. The aqueous solubility was significantly improved and displayed a size-dependent manner. The nanocrystals exhibited lower dissolution patterns than Nimotop(®) under non-sink condition, but bioavailability of the two nanocrystals (159.0 and 833.3 nm) was equivalent, about 2.6-fold higher than Nimotop(®). In conclusion, oral nanocrystal drug delivery system was a promising strategy in improving the oral bioavailability of poorly soluble or insoluble drugs. But we could not establish a favorable in vitro in vivo correlation for NMD nanocrystals and Nimotop(®) and thus the oral absorption mechanism of the NMD nanocrystals required further study.

  19. One-step self-assembled nanomicelles for improving the oral bioavailability of nimodipine.

    PubMed

    Luo, Jing-Wen; Zhang, Zhi-Rong; Gong, Tao; Fu, Yao

    2016-01-01

    Our study aimed to develop a self-assembled nanomicelle for oral administration of nimodipine (NIM) with poor water solubility. Using Solutol(®) HS15, the NIM-loaded self-assembled nanomicelles displayed a near-spherical morphology with a narrow size distribution of 12.57 ± 0.21 nm (polydispersity index =0.071 ± 0.011). Compared with Nimotop(®) (NIM tablets), the intestinal absorption of NIM from NIM nanomicelle in rats was improved by 3.13- and 2.25-fold in duodenum and jejunum at 1 hour after oral administration. The cellular transport of NIM nanomicelle in Caco-2 cell monolayers was significantly enhanced compared to that of Nimotop(®). Regarding the transport pathways, clathrin, lipid raft/caveolae, and macropinocytosis mediated the cell uptake of NIM nanomicelles, while P-glycoprotein and endoplasmic reticulum/Golgi complex (ER/Golgi) pathways were involved in exocytosis. Pharmacokinetic studies in our research laboratory have showed that the area under the plasma concentration-time curve (AUC0-∞) of NIM nanomicelles was 3.72-fold that of Nimotop(®) via oral administration in rats. Moreover, the NIM concentration in the brain from NIM nanomicelles was dramatically improved. Therefore, Solutol(®) HS15-based self-assembled nanomicelles represent a promising delivery system to enhance the oral bioavailability of NIM. PMID:27042060

  20. Simultaneously improving stability and specificity of cell surface displayed glucose dehydrogenase mutants to construct whole-cell biocatalyst for glucose biosensor application.

    PubMed

    Liang, Bo; Lang, Qiaolin; Tang, Xiangjiang; Liu, Aihua

    2013-11-01

    The improved stability and substrate specificity of cell surface displayed glucose dehydrogenase (GDH) mutants by replacing four amino acids from Bacillus subtilis by using site-directed mutagenesis was systematically investigated. A series of mutated GDHs including E170R/Q252L, V149K/E170R/Q252L, E170R/Q252L/G259A and V149K/E170R/Q252L/G259A, were fused to the ice nucleation protein for displaying on cell surface of Eschericia coli. Q252L/E170R/V149K, Q252L/E170R/G259A and Q252L/E170R/V149K/G259A variants were found stable at a wide pH range and shown excellent thermostability. Especially, the Q252L/E170R/V149K/G259A mutant showed half-life of ~3.8days at 70 °C. Q252L/E170R/V149K/G259A variant exhibited the narrowest substrate specificity for d-glucose. The whole cell displayed GDH mutant could be cultured in a large scale with excellent enzyme activity and productivity. In addition, a sensitive and stable electrochemical glucose biosensor can be prepared using the GDH-mutant bacteria modified electrode. Thus, the whole cell biocatalysts are promising candidates for exploitation in a wide range of industrial applications. PMID:24012845

  1. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

    PubMed

    Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

    2015-01-01

    Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

  2. Glucose tolerance test - non-pregnant

    MedlinePlus

    Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test ... The most common glucose tolerance test is the oral glucose tolerance test (OGTT). Before the test begins, a sample of blood will be taken. You will then ...

  3. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability.

    PubMed

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and β-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95 ± 2.80% drug release in 60 min was observed in comparison to 24.85 ± 2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66 ± 1.52 s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed β-CD-ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. PMID:26478377

  4. Amorphous solid dispersion successfully improved oral exposure of ADX71943 in support of toxicology studies.

    PubMed

    Ayad, Mohamad H; Bonnet, Beatrice; Quinton, Jacques; Leigh, Matthew; Poli, Sonia M

    2013-09-01

    ADX71943 is a potent and selective GABA(b) receptor positive allosteric modulator (PAM) which exhibits poor aqueous solubility at all physiologically relevant pHs. The aim of this study was to identify an adequate formulation to improve the solubility of ADX71943 to achieve a sufficiently high plasma exposure after oral administration to support the toxicology program. Considering the overall physicochemical properties and the low solubility of ADX71943 in a variety of solvents, solid dispersion, and particle size reduction have been successfully chosen as potential strategies to improve its oral bioavailability. Both technologies have proven useful in improving the in vitro dissolution profile and as a result of the solubility enhancement, higher bioavailability was obtained in vivo. As the solid dispersion gave better bioavailability (30-fold compared with the neat active pharmaceutical ingredient (API)), this formulation was selected for the toxicology study. Changing the crystalline form of ADX71943 into amorphous state by preparing a solid dispersion has greatly improved its oral bioavailability and has allowed achieving the required plasma concentration needed in toxicology studies.

  5. A carrier-mediated prodrug approach to improve the oral absorption of antileukemic drug decitabine.

    PubMed

    Zhang, Youxi; Sun, Jin; Gao, Yikun; Jin, Ling; Xu, Youjun; Lian, He; Sun, Yongbing; Sun, Yinghua; Liu, Jianyu; Fan, Rui; Zhang, Tianhong; He, Zhonggui

    2013-08-01

    Decitabine (5-aza-2'-deoxycytidine, DAC) is a novel DNA methyltransferase (DNMT) inhibitor for the treatment of myelodysplastic syndrome, acute and chronic myeloid leukemia. However, it exhibits a low oral bioavailability (only 9% in mice), because of low permeability across the intestine membrane and rapid metabolism to inactive metabolite. To utilize the carrier-mediated prodrug approach for improved absorption of decitabine, a series of amino acid-decitabine conjugates were synthesized to target the intestinal membrane transporter, hPepT1. The Caco-2 permeability of the prodrugs was screened, and two l-val (aliphatic, compound 4a) and l-phe (aromatic, compound 4c) prodrugs with higher permeability were selected for further studies. The uptake of Gly-Sar by Caco-2 cells could be competitively inhibited by compounds 4a and 4c, with IC50 being 2.20 ± 0.28 mM and 3.46 ± 0.16 mM, respectively. The uptake of compounds 4a and 4c was markedly increased in the leptin-treated Caco-2 cells compared with the control Caco-2 cells, suggesting that hPepT1-mediated transport contributes to oral absorption of compounds 4a and 4c. The prodrugs were evaluated for their stability in various phosphate buffers, rat plasma, tissue homogenates, and gastrointestinal fluids. Compounds 4a and 4c were stable in gastrointestinal tract at pH 6.0 but could be quickly converted into DAC in plasma and tissue homogenates after absorption. The oral absolute bioavailability of DAC was 46.7%, 50.9%, and 26.9% after compounds 4a, 4c, and DAC were orally administered to rats at a dose of 15 mg/kg, respectively. The bioavailability of compounds 4a and 4c in rats was both reduced to about 32% when orally coadministrated with typical hPepT1 substrate Gly-Sar (150 mg/kg). Overall, compounds 4a and 4c can significantly enhance the intestinal membrane permeability of DAC, followed by rapid and mostly bioactivation to parent drug in intestinal and hepatic tissues before entry into systemic circulation

  6. Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity

    PubMed Central

    Martinez-Hervas, Sergio; Navarro, Inmaculada; Real, Jose T.; Artero, Ana; Peiro, Marta; Gonzalez-Navarro, Herminia; Carmena, Rafael; Ascaso, Juan F.

    2016-01-01

    Aims To evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses. Methods We included 20 subjects with abdominal obesity (waist circumference > 102 cm for men and > 88 cm for women) and 20 healthy lean controls (waist circumference < 102 cm for men and < 88 cm for women). After 12 hours of fasting we performed a standardized fat load test (0–8 hours) with supracal® (50 g/m2). We determined metabolic parameters, oxidized and reduced glutathione, and malondialdehyde. Results In both groups, insulin, HOMA, oxidized/reduced glutathione ratio, and malondialdehyde significantly decreased in the postprandial state after the OFLT. All these parameters were significantly higher in the abdominal obesity group at baseline and during all the postprandial points, but the reduction from the baseline levels was significantly higher in the abdominal obesity group. Conclusion Unsaturated fat improves insulin resistance and oxidative stress status. It is possible that a consumption of unsaturated fat could be beneficial even in subjects with abdominal obesity in postprandial state. PMID:27537847

  7. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production

    PubMed Central

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng

    2016-01-01

    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  8. Influence of Oral Antidiabetic Drugs on Hyperglycemic Response to Foods in Persons with Type 2 Diabetes Mellitus as Assessed by Continuous Glucose Monitoring System: A Pilot Study

    PubMed Central

    Karolina, Peterson; Chlup, Rudolf; Jana, Zapletalova; Kohnert, Klaus Dieter; Kudlova, Pavla; Bartek, Josef; Nakladalova, Marie; Doubravova, Blanka; Seckar, Pavel

    2010-01-01

    Background The purpose of this prospective open-label trial was (1) to assess the influence of oral antidiabetic drugs (OAD) on the glycemic index (GI), glucose response curves (GRCs), daily mean plasma glucose (MPG) and (2) to compare the GI of foods in persons with OAD-treated type 2 diabetes mellitus (T2DM) with the respective GI in healthy persons (HP). Methods Tested foods containing 50 g of carbohydrates were eaten for breakfast and dinner after 10 and 4 h of fasting, respectively. Glycemic index, GRC, and MPG were obtained using the CGMS®System Gold™ (CGMS). In T2DM patients [n = 16; age (mean ± standard error) 56.0 ± 2.25 years], foods were tested four times: tests 1, 2, and 3 were performed within one week in which placebo was introduced on day 2, and test 4 was carried out five weeks after reintroduction of OAD. Glycemic indexes, GRC, and MPG from tests 1, 2, 3, and 4 were compared. In a control group of 20 HP (age 24.4 ± 0.71 years), the mean GIs were calculated as the mean from 20 subject-related GIs. Results In T2DM patients, subject-related assessment of GIs, GRC, and MPG distinguished persons with and without OAD effect. Nevertheless, the group-related GIs and the MPG on days 2, 8, and 39 showed no significant difference. There was no significant difference between the GIs in OAD-treated T2DM patients (test 4) versus HP (except in apple baby food). Glucose response curves were significantly larger in T2DM patients (test 4) versus HP. Conclusions Determination of GRC and subject-related GI using the CGMS appears to be a potential means for the evaluation of efficacy of OAD treatment. Further studies are underway. PMID:20663465

  9. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes.

    PubMed

    Lu, Ting; Sheng, Hongguang; Wu, Johnna; Cheng, Yuan; Zhu, Jianming; Chen, Yan

    2012-06-01

    For thousands of years, cinnamon has been used as a traditional treatment in China. However, there are no studies to date that investigate whether cinnamon supplements are able to aid in the treatment of type 2 diabetes in Chinese subjects. We hypothesized cinnamon should be effective in improving blood glucose control in Chinese patients with type 2 diabetes. To address this hypothesis, we performed a randomized, double-blinded clinical study to analyze the effect of cinnamon extract on glycosylated hemoglobin A(1c) and fasting blood glucose levels in Chinese patients with type 2 diabetes. A total of 66 patients with type 2 diabetes were recruited and randomly divided into 3 groups: placebo and low-dose and high-dose supplementation with cinnamon extract at 120 and 360 mg/d, respectively. Patients in all 3 groups took gliclazide during the entire 3 months of the study. Both hemoglobin A(1c) and fasting blood glucose levels were significantly reduced in patients in the low- and high-dose groups, whereas they were not changed in the placebo group. The blood triglyceride levels were also significantly reduced in the low-dose group. The blood levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and liver transaminase remained unchanged in the 3 groups. In conclusion, our study indicates that cinnamon supplementation is able to significantly improve blood glucose control in Chinese patients with type 2 diabetes.

  10. Improved xylanase production by Trichoderma reesei grown on L-arabinose and lactose or D-glucose mixtures.

    PubMed

    Xiong, H; Turunen, O; Pastinen, O; Leisola, M; von Weymarn, N

    2004-04-01

    Trichoderma reesei Rut C-30 was grown on eight different natural or rare aldopentoses as the main carbon source and on mixtures of an aldopentose with D-glucose or lactose. The fungal cells consumed all aldopentoses tested, except L-xylose and L-ribose. The highest total xylanase and cellulase activities were achieved when cells were grown on L-arabinose as the main carbon source. The total xylanase activity produced by cells grown on L-arabinose was even higher than that produced by cells grown on an equal amount of lactose. In co-metabolism of D-glucose (15 g l(-1)) and L-arabinose (5 g l(-1)), the total volumetric and specific xylanase productivities were improved (derepressed) approximately 23- and 18-fold, respectively, compared to a cultivation on only D-glucose (20 g l(-1)). In a similar experiment, in which cells were grown on a mixture of lactose and L-arabinose, the xylanase productivity was approximately doubled, compared to a cultivation on only lactose. The cellulase productivities, however, were not improved by the addition of L-arabinose. Compared with a typical industrial fungal enzyme production process with lactose as the main carbon source, better volumetric and specific xylanase productivities were achieved both on a lactose/arabinose mixture and on a glucose/arabinose mixture.

  11. Green tea leaf extract improves lipid and glucose homeostasis in a fructose-fed insulin-resistant hamster model.

    PubMed

    Li, Rachel W; Douglas, Teresa D; Maiyoh, Geoffrey K; Adeli, Khosrow; Theriault, Andre G

    2006-03-01

    The present study evaluated the effect of green tea (Camellia sinensis L.) leaf extract on triglyceride and glucose homeostasis in a fructose-fed hypertriglyceridemic, insulin-resistant hamster model. There was a significant decrease in plasma triglyceride levels following supplementation of the green tea epigallocatechin gallate-enriched extract (42% at 150 mg/(kg day) to 62% at 300 mg/(kg day) for 4 weeks). Compared to baseline, the fructose control group at the end of the study showed elevated serum insulin and apolipoprotein B levels, and decreased serum adiponectin levels. The fructose/green tea extract group showed a reversal in all of these metabolic defects, including an improvement in glucose levels during a glucose tolerance test. Triglyceride content was also examined in various tissues and compared to the control fructose group; supplementation of the green tea extract (300 mg/kg) reduced triglyceride content in liver and heart tissues. There was molecular evidence of improved lipid and glucose homeostasis based on peroxisome proliferator-activated receptor (PPAR) protein expression. Compared to the control fructose group, supplementation of the green tea extract (300 mg/kg) significantly increased PPARalpha and PPARgamma protein expression. In summary, the data suggest that intake of the green tea extract ameliorated the fructose-induced hypertriglyceridemia and the insulin-resistant state in part through PPAR.

  12. Chewing xylitol gum improves self-rated and objective indicators of oral health status under conditions interrupting regular oral hygiene.

    PubMed

    Hashiba, Takafumi; Takeuchi, Kenji; Shimazaki, Yoshihiro; Takeshita, Toru; Yamashita, Yoshihisa

    2015-01-01

    Chewing xylitol gum provides oral health benefits including inhibiting Streptococcus mutans plaque. It is thought to be especially effective in conditions where it is difficult to perform daily oral cleaning. Our study aim was to determine the effects of chewing xylitol gum on self-rated and objective oral health status under a condition interfering with oral hygiene maintenance. A randomized controlled intervention trial was conducted on 55 healthy ≥ 20-year-old men recruited from the Japan Ground Self Defense Force who were undergoing field training. Participants were randomly assigned to a test group (chewing gum; n = 27) or a control group (no gum; n = 28) and the researchers were blinded to the group assignments. The Visual Analog Scale (VAS) scores of oral conditions subjectively evaluated oral health, and the stimulated salivary bacteria quantity objectively evaluated oral health 1 day before field training (baseline) and 4 days after the beginning of field training (follow-up). VAS scores of all three oral conditions significantly increased in the control group (malodor: p < 0.001; discomfort: p < 0.001; dryness: p < 0.001), but only two VAS scores increased in the test group (malodor: p = 0.021; discomfort: p = 0.002). The number of salivary total bacteria significantly increased in the control group (p < 0.01), while no significant change was observed in the test group (p = 0.668). Chewing xylitol gum positively affects self-rated and objective oral health status by controlling oral hygiene under conditions that interfere with oral hygiene maintenance. PMID:25744362

  13. Detection of orally administered inositol stereoisomers in mouse blood plasma and their effects on translocation of glucose transporter 4 in skeletal muscle cells.

    PubMed

    Yamashita, Yoko; Yamaoka, Masaru; Hasunuma, Tomohisa; Ashida, Hitoshi; Yoshida, Ken-ichi

    2013-05-22

    Simple pharmacological studies on inositol stereoisomers are presented in this study. Male ICR mice were orally administered 1 g/kg BW of three inositol stereoisomers, myo-inositol (MI), d-chiro-inositol (DCI), and scyllo-inositol (SI), and blood plasma samples and skeletal muscle fractions were prepared after an hour. The plasma samples were subjected to gas chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS) analysis. None of the three stereoisomers was seen in untreated samples, but substantial amounts ranging from 2.5 to 6.5 mM were detected only after administration, indicating that orally administered inositol stereoisomers were readily absorbed and their levels elevated in the bloodstream. In addition, plasma of SI-administered animals contained substantial MI, suggesting a possible metabolic conversion of SI to MI. In the skeletal muscle fractions, glucose transporter type 4 (GLUT4) content in the plasma membrane increased, indicating that inositol stereoisomers stimulated GLUT4 translocation.

  14. Increasing intravenous infusions of glucose improve body condition but not lactation performance in midlactation dairy cows.

    PubMed

    Al-Trad, B; Reisberg, K; Wittek, T; Penner, G B; Alkaassem, A; Gäbel, G; Fürll, M; Aschenbach, J R

    2009-11-01

    The present study was intended to test whether intravenously applied glucose would elicit dose effects on lactation performance similar to those observed after gastrointestinal glucose application. Six midlactation cows received intravenous glucose infusions (GI), increasing by 1.25% of the calculated net energy for lactation (NE(L)) requirement per day, whereas control cows received volume-equivalent saline infusions (SI). Measurements and samples were taken at surplus glucose dose levels of 0, 10, 20, and 30% of the NE(L) requirement, respectively. Body weight and backfat thickness increased linearly with increasing glucose dose for cows on GI compared with SI. No differences were observed in daily feed intake, milk energy output, and energy-corrected milk yield between treatments. However, milk protein percentage and yield increased linearly with the dose of glucose infused in the GI group. Although milk lactose was not affected by treatment during the infusion period, milk lactose percentage and yield decreased for GI, but not SI, once infusions ceased. Based on 5 diurnal blood samples, daily mean and maximum concentrations of plasma glucose and serum insulin showed linear increases with increasing GI, whereas their daily minimum concentrations were unaffected. At GI of 30% of the NE(L) requirement, marked hyperglycemia and hyperinsulinemia were observed at 1600 h (i.e., 1 h postprandially), coinciding with glucosuria. The revised quantitative insulin-sensitivity check index indicated linear development of insulin resistance for the GI treatment but no such change in SI cows. Glucose infusion decreased daily mean and maximum serum beta-hydroxybutyrate and daily minimum nonesterified fatty acid concentrations relative to SI, whereas serum urea nitrogen was only numerically decreased by GI. No changes were observed in the serum activities of gamma-glutamyl transferase and aspartate transaminase and in the serum concentrations of bilirubin and macrominerals

  15. Periodic 48 h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis

    PubMed Central

    2012-01-01

    Background Adipocyte numbers and peroxisome proliferators activated receptorγ (PPARγ) expression of retroperitoneal tissue increased while area under the curve (AUC) during the glucose tolerance test (GTT) was reduced in rats subjected to certain feed withdrawal (FW) regimens. Thus, using pigs as the experimental model, the hypothesis that FW regimens influence glucose tolerance by influencing fat cell function was evaluated with the objective of determining the effect of a single (FWx1; at age of 19 wk for 48 h) or periodic, multiple (FWx4; 24 h FW at 7 and 11 wk of age and 48 h FW at 15 and 19 wk of age) FW on AUC of glucose and insulin during the GTT relative to pigs that did not experience FW (Control). Methods Growth, body composition, adipocyte numbers, PPARγ expression, lipogenic potential as glucose uptake into fat of adipocytes of varying diameter in omental (OM) and subcutaneous (SQ) fat as affected by FW regimens were determined in pigs initiated into the study at 5 wk of age and fed the same diet, ad libitum. Results Blood glucose concentrations for prior to and 120 min post glucose meal tended to be lower (p = 0.105 and 0.097, respectively) in pigs in FW treatments. In OM fat; cell numbers, glucose Universal14C [U14C] incorporation into fat and rate of incorporation per 104 cells was greatest for cells with diameters of 90-119 μm. Pigs undergoing FWx4 tended to have greater (p = 0.0685; by 191%) number of adipocytes, increased (p = 0.0234) glucose U14C incorporation into adipocytes and greater (p = 0.0872) rate of glucose uptake into cells of 119-150 μm diameter than of cells from control or FWx1 pigs. Subcutaneous adipocyte numbers in 22-60 and 61-90 μm diameter ranges from pigs in FWx1 tended to be greater (p = 0.08 and 0.06, respectively) than for those in FWx4 treatment, yet PPARγ expression and total cell number were not affected by treatment. Conclusions Results suggest that FW regimens influence fat cell function or lipogenesis rather

  16. Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals.

    PubMed

    Kameswara Rao, B; Giri, R; Kesavulu, M M; Apparao, C

    2001-01-01

    The effect of administration of different doses of Pterocarpus santalinus L. bark extracts in normal and diabetic rats, on blood glucose levels was evaluated in this study. Among the three fractions (aqueous, ethanol and hexane), ethanolic fraction at the dose of 0.25 g/kg body weight showed maximum antihyperglycemic activity. The same dose did not cause any hypoglycemic activity in normal rats. The results were compared with the diabetic rats treated with glibenclamide and the antihyperglycemic activity of ethanolic extract of PS bark at the dose of 0.25 g/kg b.w. was found to be more effective than that of glibenclamide. PMID:11137350

  17. Acetaminophen-containing chewable tablets with suppressed bitterness and improved oral feeling.

    PubMed

    Suzuki, Hiroyuki; Onishi, Hiraku; Hisamatsu, Seiji; Masuda, Kosuke; Takahashi, Yuri; Iwata, Masanori; Machida, Yoshiharu

    2004-06-18

    The aim of this study was to develop acetaminophen chewable tablets with suppressed bitterness and improved oral feeling by examination of hard fats as the matrix base and of sweetening agents as corrigents. Witepsol H-15, W-35, S-55, E-75 and E-85, and Witocan H and 42/44 were used as hard fats. Witocan H and 42/44 were selected in view of improved oral feeling. Witocan H/Witocan 42/44 mixture tablets showed different melting characteristics and drug release rates dependent on their ratios, and those with the Witocan H/Witocan 42/44 ratio of 92.5% (w/w) and more showed good drug release. Sucrose, xylitol, saccharin, saccharin sodium, aspartame and sucralose were used as sweetening agents, and applied alone or with Benecoat BMI-40 or cocoa powder. The Witocan H tablet with 1% (w/w) saccharin plus 5% (w/w) Benecoat BMI-40 (Sc1-B5), and the Witocan H/Witocan 42/44 (92.5:7.5, w/w) mixture tablet with 1% (w/w) aspartame plus 5% (w/w) Benecoat BMI-40 suppressed bitterness and sweetness excellently, but the former tablet showed better drug release. Thus, the Witocan H tablet with Sc1-B5 is suggested as the best acetaminophen chewable tablet, exhibiting suppressed bitterness, low sweetness, improved oral feeling and good drug release.

  18. Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion

    PubMed Central

    2016-01-01

    Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281). PMID:26839476

  19. Oral delivery of shRNA based on amino acid modified chitosan for improved antitumor efficacy.

    PubMed

    Zheng, Hao; Tang, Cui; Yin, Chunhua

    2015-11-01

    In this investigation, chitosan-histidine-cysteine (CHC) was engineered for oral delivery of Survivin short hairpin RNA (shRNA)-expressing plasmid DNA (shSur-pDNA) to promote hepatoma regression through integrating the advantages of histidine and cysteine to conquer serial cellular and systemic barriers. CHC could effectively encapsulate shSur-pDNA to form compact nanocomplexes (NC) at adequate weight ratios. Sequential modification with histidine and cysteine conferred CHC NC with the beneficial attributes for shRNA delivery including improved stability, facilitated internalization, promoted endosomal escape, increased nuclear localization, and GSH-responsive release, which contributed to their superior performance in terms of apoptosis promotion, proliferation inhibition, and Survivin down-regulation of tumor cells. More importantly, in hepatoma-bearing mice, orally delivered CHC NC overweighed chitosan counterparts with respect to suppressed Survivin expression, retarded tumor growth, and prolonged surviving time, owing to their above-mentioned merits in combination with enhanced intestinal permeation. Especially, rapid intracellular release of CHC NC with lower molecular weight of 30 kDa (CHC30 NC) might be responsible for the most satisfactory antitumor efficacy with tumor inhibition ratio (TIR) of 92.5%, which rendered CHC30 NC a promising vehicle for oral delivery of shRNA. This investigation would shed light on the deliberate design of oral shRNA delivery vehicles to mediate effective antitumor efficacy. PMID:26310108

  20. Improvement in cardiac performance by oral long-acting theophylline in chronic obstructive pulmonary disease.

    PubMed

    Matthay, R A; Berger, H J; Davies, R; Loke, J; Gottschalk, A; Zaret, B L

    1982-11-01

    Although oral theophylline is a widely used bronchodilator in chronic obstructive pulmonary disease (COPD), its effects upon cardiac performance have not been fully established. The effect of slow release oral theophylline upon right ventricular and left ventricular ejection fraction was evaluated using first-pass quantitative radionuclide angiocardiography in 15 patients with COPD. After 72 hours of therapy, oral theophylline significantly increased right ventricular ejection fraction (42% to 48%, p less than 0.005). In 7 of 10 patients with depressed baseline right ventricular performance, including two with cor pulmonale, right ventricular ejection fraction normalized (greater than or equal to 45%). After long-term therapy, an average of 16 weeks, right ventricular fraction also increased (43% to 48%, p less than 0.005). Left ventricular ejection fraction improved significantly from 64% to 68% (p less than 0.05) at 72 hours and from 61% to 65% (p less than 0.025) after long-term therapy. These data indicate that oral theophylline produces a sustained modest enhancement of resting biventricular performance in COPD.

  1. Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia

    PubMed Central

    Eik, W.; Marcon, S.S.; Krupek, T.; Previdelli, I.T.S.; Pereira, O.C.N.; Silva, M.A.R.C.P.; Bazotte, R.B.

    2016-01-01

    We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia

  2. Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia.

    PubMed

    Eik, W; Marcon, S S; Krupek, T; Previdelli, I T S; Pereira, O C N; Silva, M A R C P; Bazotte, R B

    2016-07-11

    We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia

  3. Partial Inhibition of Adipose Tissue Lipolysis Improves Glucose Metabolism and Insulin Sensitivity Without Alteration of Fat Mass

    PubMed Central

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet–fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  4. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    PubMed

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  5. Brief Report: Remotely Delivered Video Modeling for Improving Oral Hygiene in Children with ASD: A Pilot Study.

    PubMed

    Popple, Ben; Wall, Carla; Flink, Lilli; Powell, Kelly; Discepolo, Keri; Keck, Douglas; Mademtzi, Marilena; Volkmar, Fred; Shic, Frederick

    2016-08-01

    Children with autism have heightened risk of developing oral health problems. Interventions targeting at-home oral hygiene habits may be the most effective means of improving oral hygiene outcomes in this population. This randomized control trial examined the effectiveness of a 3-week video-modeling brushing intervention delivered to patients over the internet. Eighteen children with autism were assigned to an Intervention or Control video condition. Links to videos were delivered via email twice daily. Blind clinical examiners provided plaque index ratings at baseline, midpoint, and endpoint. Results show oral hygiene improvements in both groups, with larger effect sizes in the Intervention condition. The findings provide preliminary support for the use of internet-based interventions to improve oral hygiene for children with autism.

  6. A Comparison of Case Study and Traditional Teaching Methods for Improvement of Oral Communication and Critical-Thinking Skills

    ERIC Educational Resources Information Center

    Noblitt, Lynnette; Vance, Diane E.; Smith, Michelle L. DePoy

    2010-01-01

    This study compares a traditional paper presentation approach and a case study method for the development and improvement of oral communication skills and critical-thinking skills in a class of junior forensic science majors. A rubric for rating performance in these skills was designed on the basis of the oral communication competencies developed…

  7. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    SciTech Connect

    Das, Joydeep; Vasan, Vandana; Sil, Parames C.

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  8. Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

    PubMed Central

    Ojo, Opeolu O.; Srinivasan, Dinesh K.; Owolabi, Bosede O.; Vasu, Srividya; Conlon, J. Michael; Flatt, Peter R.; Abdel-Wahab, Yasser H. A.

    2015-01-01

    The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca2+. Insulinotropic activity was attenuated by activation of KATP channels, inhibition of voltage-dependent Ca2+ channels and chelation of extracellular Ca2+. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin-2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for

  9. Low glycaemic index diets improve glucose tolerance and body weight in women with previous history of gestational diabetes: a six months randomized trial

    PubMed Central

    2013-01-01

    Background Gestational Diabetes Mellitus (GDM) increases risks for type 2 diabetes and weight management is recommended to reduce the risk. Conventional dietary recommendations (energy-restricted, low fat) have limited success in women with previous GDM. The effect of lowering Glycaemic Index (GI) in managing glycaemic variables and body weight in women post-GDM is unknown. Objective To evaluate the effects of conventional dietary recommendations administered with and without additional low-GI education, in the management of glucose tolerance and body weight in Asian women with previous GDM. Method Seventy seven Asian, non-diabetic women with previous GDM, between 20- 40y were randomised into Conventional healthy dietary recommendation (CHDR) and low GI (LGI) groups. CHDR received conventional dietary recommendations only (energy restricted, low in fat and refined sugars, high-fibre). LGI group received advice on lowering GI in addition. Fasting and 2-h post-load blood glucose after 75 g oral glucose tolerance test (2HPP) were measured at baseline and 6 months after intervention. Anthropometry and dietary intake were assessed at baseline, three and six months after intervention. The study is registered at the Malaysian National Medical Research Register (NMRR) with Research ID: 5183. Results After 6 months, significant reductions in body weight, BMI and waist-to-hip ratio were observed only in LGI group (P<0.05). Mean BMI changes were significantly different between groups (LGI vs. CHDR: -0.6 vs. 0 kg/m2, P= 0.03). More subjects achieved weight loss ≥5% in LGI compared to CHDR group (33% vs. 8%, P=0.01). Changes in 2HPP were significantly different between groups (LGI vs. CHDR: median (IQR): -0.2(2.8) vs. +0.8 (2.0) mmol/L, P=0.025). Subjects with baseline fasting insulin≥2 μIU/ml had greater 2HPP reductions in LGI group compared to those in the CHDR group (−1.9±0.42 vs. +1.31±1.4 mmol/L, P<0.001). After 6 months, LGI group diets showed significantly lower

  10. Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats

    PubMed Central

    2013-01-01

    Background Glucose intolerance and cardiovascular complications are major symptoms in patients with diabetes. Many therapies have proven beneficial in treating diabetes in animals by protecting the cardiovascular system and increasing glucose utilization. In this study, we evaluated the effects of caffeic acid phenethyl amide (CAPA) on glucose homeostasis and vascular function in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Diabetes (blood glucose levels > 350 mg/dL), was induced in Wistar rats by a single intravenous injection of 60 mg/kg STZ. Hypoglycemic effects were then assessed in normal and type 1 diabetic rats. In addition, coronary blood flow in Langendorff-perfused hearts was evaluated in the presence or absence of nitric oxide synthase (NOS) inhibitor. The thoracic aorta was used to measure vascular response to phenylephrine. Finally, the effect of chronic treatment of CAPA and insulin on coronary artery flow and vascular response to phenylephrine were analyzed in diabetic rats. Results Oral administration of 0.1 mg/kg CAPA decreased plasma glucose in normal (32.9 ± 2.3% decrease, P < 0.05) and diabetic rats (11.8 ± 5.5% decrease, P < 0.05). In normal and diabetic rat hearts, 1–10 μM CAPA increased coronary flow rate, and this increase was abolished by 10 μM NOS inhibitor. In the thoracic aorta, the concentration/response curve of phenylephrine was right-shifted by administration of 100 μM CAPA. Coronary flow rate was reduced to 7.2 ± 0.2 mL/min at 8 weeks after STZ-induction. However, 4 weeks of treatment with CAPA (3 mg/kg, intraperitoneal, twice daily) started at 4 weeks after STZ induction increased flow rate to 11.2 ± 0.5 mL/min (P < 0.05). In addition, the contractile response induced by 1 μM phenylephrine increased from 6.8 ± 0.6 mN to 11.4 ± 0.4 mN (P < 0.05) and 14.9 ± 1.4 mN (P < 0.05) by insulin (1 IU/kg, intraperitoneal) or CAPA treatment, respectively. Conclusions CAPA induced hypoglycemic activity, increased

  11. Hepatocyte retinoid X receptor-alpha-deficient mice have reduced food intake, increased body weight, and improved glucose tolerance.

    PubMed

    Wan, Yu-Jui Yvonne; Han, Guang; Cai, Yan; Dai, Tiane; Konishi, Tamiko; Leng, Ai-She

    2003-02-01

    Hepatocyte retinoid X receptor (RXR)alpha-deficient mice and wild-type mice were fed either a regular or a high-saturated-fat diet for 12 wk to study the functional role of hepatocyte RXRalpha in fatty acid and carbohydrate metabolism. Food intake was significantly reduced in hepatocyte RXRalpha-deficient mice when either diet was used. The amount of food intake was negatively associated with serum leptin level. Although mutant mice ate less, body weight and fat content were significantly higher in mutant than wild-type mice. Examination of the expression of peroxisome proliferator-activated receptor-alpha target genes indicated that the peroxisome proliferator-activated receptor-alpha-mediated pathway was compromised in the mutant mice, which, in turn, might affect fatty-acid metabolism and result in increased body weight and fat content. Although mutant mice were obese, they demonstrated the same degree of insulin sensitivity and the same level of serum insulin as the wild-type mice. However, these mutant mice have improved glucose tolerance. To explore a mechanism that may be responsible for the improved glucose tolerance, serum IGF-I level was examined. Serum IGF-1 level was significantly increased in mutant mice compared with wild-type mice. Taken together, hepatocyte RXRalpha deficiency increases leptin level and reduces food intake. Those mice also develop obesity, with an unexpected improvement of glucose tolerance. The result also suggests that an increase in serum IGF-I level might be one of the mechanisms leading to improved glucose tolerance in hepatocyte RXRalpha-deficient mice.

  12. Transient Receptor Potential Vanilloid 1 Activation Enhances Gut Glucagon-Like Peptide-1 Secretion and Improves Glucose Homeostasis

    PubMed Central

    Wang, Peijian; Yan, Zhencheng; Zhong, Jian; Chen, Jing; Ni, Yinxing; Li, Li; Ma, Liqun; Zhao, Zhigang; Liu, Daoyan; Zhu, Zhiming

    2012-01-01

    Type 2 diabetes mellitus (T2DM) is rapidly prevailing as a serious global health problem. Current treatments for T2DM may cause side effects, thus highlighting the need for newer and safer therapies. We tested the hypothesis that dietary capsaicin regulates glucose homeostasis through the activation of transient receptor potential vanilloid 1 (TRPV1)-mediated glucagon-like peptide-1 (GLP-1) secretion in the intestinal cells and tissues. Wild-type (WT) and TRPV1 knockout (TRPV1−/−) mice were fed dietary capsaicin for 24 weeks. TRPV1 was localized in secretin tumor cell-1 (STC-1) cells and ileum. Capsaicin stimulated GLP-1 secretion from STC-1 cells in a calcium-dependent manner through TRPV1 activation. Acute capsaicin administration by gastric gavage increased GLP-1 and insulin secretion in vivo in WT but not in TRPV1−/− mice. Furthermore, chronic dietary capsaicin not only improved glucose tolerance and increased insulin levels but also lowered daily blood glucose profiles and increased plasma GLP-1 levels in WT mice. However, this effect was absent in TRPV1−/− mice. In db/db mice, TRPV1 activation by dietary capsaicin ameliorated abnormal glucose homeostasis and increased GLP-1 levels in the plasma and ileum. The present findings suggest that TRPV1 activation–stimulated GLP-1 secretion could be a promising approach for the intervention of diabetes. PMID:22664955

  13. Lipids-based nanostructured lipid carriers (NLCs) for improved oral bioavailability of sirolimus.

    PubMed

    Yu, Qin; Hu, Xiongwei; Ma, Yuhua; Xie, Yunchang; Lu, Yi; Qi, Jianping; Xiang, Li; Li, Fengqian; Wu, Wei

    2016-05-01

    The main purpose of this study was to improve the oral bioavailability of sirolimus (SRL), a poorly water-soluble immunosuppressant, by encapsulating into lipids-based nanostructured lipid carriers (NLCs). SRL-loaded NLCs (SRL-NLCs) were prepared by a high-pressure homogenization method with glycerol distearates (PRECIROL ATO-5) as the solid lipid, oleic acid as the liquid lipids, and Tween 80 as the emulsifier. The SRL-NLCs prepared under optimum conditions was spherical in shape with a mean particle size of about 108.3 nm and an entrapment efficiency of 99.81%. In vitro release of SRL-NLCs was very slow, about 2.15% at 12 h, while in vitro lipolysis test showed fast digestion of the NLCs within 1 h. Relative oral bioavailability of SRL-NLCs in Beagle dogs was 1.81-folds that of the commercial nanocrystalline sirolimus tablets Rapamune®. In conclusion, the NLCs show potential to improve the oral bioavailability of SRL. PMID:27187522

  14. Formulation of 20(S)-protopanaxadiol nanocrystals to improve oral bioavailability and brain delivery.

    PubMed

    Chen, Chen; Wang, Lisha; Cao, Fangrui; Miao, Xiaoqing; Chen, Tongkai; Chang, Qi; Zheng, Ying

    2016-01-30

    The aim of this study was to fabricate 20(S)-protopanaxadiol (PPD) nanocrystals to improve PPD's oral bioavailability and brain delivery. PPD nanocrystals were fabricated using an anti-solvent precipitation approach where d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was optimized as the stabilizer. The fabricated nanocrystals were nearly spherical with a particle size and drug loading of 90.44 ± 1.45 nm and 76.92%, respectively. They are in the crystalline state and stable at 4°C for at least 1 month. More than 90% of the PPD could be rapidly released from the nanocrystals, which was much faster than the physical mixture and PPD powder. PPD nanocrystals demonstrated comparable permeability to solution at 2.52 ± 0.44×10(-5)cm/s on MDCK monolayers. After oral administration of PPD nanocrystals to rats, PPD was absorbed quickly into the plasma and brain with significantly higher Cmax and AUC0-t compared to those of the physical mixture. However, no brain targeting was observed, as the ratios of the plasma AUC0-t to brain AUC0-t for the two groups were similar. In summary, PPD nanocrystals are a potential oral delivery system to improve PPD's poor bioavailability and its delivery into the brain for neurodegenerative disease and intracranial tumor therapies in the future.

  15. Substrate-specific modifications on magnetic iron oxide nanoparticles as an artificial peroxidase for improving sensitivity in glucose detection.

    PubMed

    Liu, Yanping; Yu, Faquan

    2011-04-01

    Magnetic iron oxide nanoparticles (MION) were recently found to act as a peroxidase with intrinsic advantages over natural counterparts. Their limited affinity toward catalysis substrates, however, dramatically reduces their utility. In this paper, some effective groups were screened out and conjugated on MION as substrate-specific modifications for improving MION's affinity to substrates and hence utility. Nanoparticles of four different superficial structures were synthesized and characterized by TEM, size, zeta potential and SQUID, and assayed for peroxidase activity. Glucose detection was selected as an application model system to evaluate the bonus thereof. Catalysis was found to follow Michaelis-Menten kinetics. Sulfhydryl groups incorporated on MION (SH-MION) notably improve the affinity toward a substrate (hydrogen peroxide) and so do amino groups (NH₂-MION) toward another substrate, proved by variation in the determined kinetic parameters. A synergistically positive effect was observed and an apparently elevated detection sensitivity and a significantly lowered detection limit of glucose were achieved when integrated with both sulfhydryl and amino groups (SH-NH₂-MION). Our findings suggest that substrate-specific surface modifications are a straightforward and robust strategy to improve MION peroxidase-like activity. The high activity extends magnetic nanoparticles to wide applications other than glucose detection. PMID:21368352

  16. DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression

    PubMed Central

    Abu-Farha, Mohamed; Cherian, Preethi; Al-Khairi, Irina; Tiss, Ali; Khadir, Abdelkrim; Kavalakatt, Sina; Warsame, Samia; Dehbi, Mohammed; Behbehani, Kazem; Abubaker, Jehad

    2015-01-01

    Heat shock response (HSR) is an essential host-defense mechanism that is dysregulated in obesity-induced insulin resistance and type 2 diabetes (T2D). Our recent data demonstrated that DNAJB3 was downregulated in obese human subjects and showed negative correlation with inflammatory markers. Nevertheless, DNAJB3 expression pattern in diabetic subjects and its mode of action are not yet known. In this study, we showed reduction in DNAJB3 transcript and protein levels in PBMC and subcutaneous adipose tissue of obese T2D compared to obese non-diabetic subjects. Overexpression of DNAJB3 in HEK293 and 3T3-L1 cells reduced JNK, IRS-1 Ser-307 phosphorylation and enhanced Tyr-612 phosphorylation suggesting an improvement in IRS-1 signaling. Furthermore, DNAJB3 mediated the PI3K/AKT pathway activation through increasing AKT and AS160 phosphorylation. AS160 mediates the mobilization of GLUT4 transporter to the cell membrane and thereby improves glucose uptake. Using pre-adipocytes cells we showed that DNAJB3 overexpression caused a significant increase in the glucose uptake, possibly through its phosphorylation of AS160. In summary, our results shed the light on the possible role of DNAJB3 in improving insulin sensitivity and glucose uptake through JNK repression and suggest that DNAJB3 could be a potential target for therapeutic treatment of obesity-induced insulin resistance. PMID:26400768

  17. Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats.

    PubMed

    Gorain, Bapi; Choudhury, Hira; Kundu, Amit; Sarkar, Lipi; Karmakar, Sanmoy; Jaisankar, P; Pal, Tapan Kumar

    2014-03-01

    Olmesartan medoxomil (OM) is hydrolyzed to its active metabolite olmesartan by the action of aryl esterase to exert its antihypertensive actions by selectively blocking angiotensin II-AT1 receptor. Poor aqueous solubility and uncontrolled enzymatic conversion of OM to its poorly permeable olmesartan limits its oral bioavailability. The aim of the current study was to formulate a novel nanoemulsion of OM to improve its pharmacokinetics and therapeutic efficacy. The oil-in-water (o/w) nanoemulsion of OM was developed using lipoid purified soybean oil 700, sefsol 218 and solutol HS 15. We have characterized the nanoemulsions by considering their thermodynamic stability, morphology, droplet size, zeta potential and viscosity and in vitro drug release characteristics in fasting state simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.5). The thermodynamically stable nanoemulsions comprises of spherical nanometer sized droplets (<50 nm) with low polydispersity index showed enhanced permeability through the Caco-2 cell monolayer. The concentration of active olmesartan in rat plasma following oral absorption study was determined by our validated LC-MS/MS method. The result of the pharmacokinetic study showed 2.8-fold increased in area under the curve (AUC0-27) of olmesartan upon oral administration of OM nanoemulsion and sustained release profile. Subsequent, in vivo studies with nanoemulsion demonstrated better and prolonged control of experimentally induced hypertension with 3-fold reduction in conventional dose. By analysing the findings of the present investigations based on stability study, Caco-2 permeability, pharmacokinetic profile and pharmacodynamic evaluation indicated that the nanoemulsion of OM (OMF6) could significantly enhance the oral bioavailability of relatively insoluble OM contributing to improved clinical application.

  18. Nanoemulsion strategy for olmesartan medoxomil improves oral absorption and extended antihypertensive activity in hypertensive rats.

    PubMed

    Gorain, Bapi; Choudhury, Hira; Kundu, Amit; Sarkar, Lipi; Karmakar, Sanmoy; Jaisankar, P; Pal, Tapan Kumar

    2014-03-01

    Olmesartan medoxomil (OM) is hydrolyzed to its active metabolite olmesartan by the action of aryl esterase to exert its antihypertensive actions by selectively blocking angiotensin II-AT1 receptor. Poor aqueous solubility and uncontrolled enzymatic conversion of OM to its poorly permeable olmesartan limits its oral bioavailability. The aim of the current study was to formulate a novel nanoemulsion of OM to improve its pharmacokinetics and therapeutic efficacy. The oil-in-water (o/w) nanoemulsion of OM was developed using lipoid purified soybean oil 700, sefsol 218 and solutol HS 15. We have characterized the nanoemulsions by considering their thermodynamic stability, morphology, droplet size, zeta potential and viscosity and in vitro drug release characteristics in fasting state simulated gastric fluid (pH 1.2) and intestinal fluid (pH 6.5). The thermodynamically stable nanoemulsions comprises of spherical nanometer sized droplets (<50 nm) with low polydispersity index showed enhanced permeability through the Caco-2 cell monolayer. The concentration of active olmesartan in rat plasma following oral absorption study was determined by our validated LC-MS/MS method. The result of the pharmacokinetic study showed 2.8-fold increased in area under the curve (AUC0-27) of olmesartan upon oral administration of OM nanoemulsion and sustained release profile. Subsequent, in vivo studies with nanoemulsion demonstrated better and prolonged control of experimentally induced hypertension with 3-fold reduction in conventional dose. By analysing the findings of the present investigations based on stability study, Caco-2 permeability, pharmacokinetic profile and pharmacodynamic evaluation indicated that the nanoemulsion of OM (OMF6) could significantly enhance the oral bioavailability of relatively insoluble OM contributing to improved clinical application. PMID:24388859

  19. A nanostructured liquid crystalline formulation of 20(S)-protopanaxadiol with improved oral absorption.

    PubMed

    Jin, Xin; Zhang, Zhen-Hai; Li, Song-Lin; Sun, E; Tan, Xiao-Bin; Song, Jie; Jia, Xiao-Bin

    2013-01-01

    As with many other anti-cancer agents, 20(S)-protopanaxadiol (PPD) has a low oral absorption. In this study, in order to improve the oral bioavailability of PPD, the cubic nanoparticles that it contains were used to enhance absorption. Therefore, the cubic nanoparticle loaded PPD were prepared through the fragmentation of the glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and were verified by transmission electron microscope, small angle X-ray scattering and differential scanning calorimetry. The in vitro release of 20(S)-protopanaxadiol from these nanoparticles was less than 5% at 12h. And then Caco-2 cell monolayer model was used to evaluate the absorption of PPD in vitro. Meanwhile the rat intestinal perfusion model and bioavailability were also estimated in vivo. The results showed that, in the Caco-2 cell model, the PPD-cubosome could increase the permeability values from the apical (AP) to the basolateral (BL) of PPD at 53%. The result showed that the four-site rat intestinal perfusion model was consistent with the Caco-2 cell model. And the result of a pharmacokinetic study in rats showed that the relative bioavailability of the PPD-cubosome (AUC(0-∞)) compared with the raw PPD (AUC(0-∞)) was 169%. All the results showed that the PPD-cubosome enhanced bioavailability was likely due to the increased absorption by the cubic nanoparticles rather than by the improved release. Hence, the cubic nanoparticles may be a promising oral carrier for the drugs that have a poor oral absorption.

  20. CNS Vitamin D improves glucose tolerance, hepatic insulin sensitivity, and reverses diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low vitamin D levels have been correlated to both obesity and the development of type 2 diabetes (T2DM) although no causative mechanisms have been established. Vitamin D receptors are present in the hypothalamus, a region important in both weight and glucose regulation. The role of these receptors, ...

  1. A chimeric NST repressor has the potential to improve glucose productivity from plant cell walls.

    PubMed

    Iwase, Akira; Hideno, Akihiro; Watanabe, Keiji; Mitsuda, Nobutaka; Ohme-Takagi, Masaru

    2009-07-15

    Bioethanol might be produced more economically and with less ecological impact (with reduced exploitation of food crops) if we could increase the production of glucose from the cellulosic materials in plant cell walls. However, plant cell walls are relatively resistant to enzymatic and physicochemical hydrolysis and, therefore, it is necessary to develop methods for reducing such resistance. Changes in plant cell wall materials, by genetic engineering, that render them more easily hydrolyzable to glucose might be a valuable approach to this problem. We showed previously that, in Arabidopsis, NAC secondary wall thickening-promoting factor1 (NST1) and NST3 are key regulators of secondary wall formation. We report here that transgenic Arabidopsis plants that expressed a chimeric repressor derived from NST1 produced cell wall materials that were twice as susceptible to both enzymatic and physicochemical hydrolysis as those from wild-type plants. The yields of glucose from both fresh and dry biomass were increased in the chimeric repressor lines. Use of the NST1 chimeric repressor might enhance production of glucose from plant cell walls, by changing the nature of the cell walls themselves.

  2. Addition of glucose oxidase for the improvement of refrigerated dough quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Refrigerated dough encompasses a wide range of products and is a very popular choice for consumers. Two of the largest problems that occur during refrigerated dough storage are dough syruping and loss of dough strength. The goal of this study was to evaluate glucose oxidase as an additive to refri...

  3. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms.

    PubMed

    Xie, Xiaoxia; Tao, Qing; Zou, Yina; Zhang, Fengyi; Guo, Miao; Wang, Ying; Wang, Hui; Zhou, Qian; Yu, Shuqin

    2011-09-14

    The overall goal of this paper was to develop poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) of curcumin (CUR), named CUR-PLGA-NPs, and to study the effect and mechanisms enhancing the oral bioavailability of CUR. CUR-PLGA-NPs were prepared according to a solid-in-oil-in-water (s/o/w) solvent evaporation method and exhibited a smooth and spherical shape with diameters of about 200 nm. Characterization of CUR-PLGA-NPs showed CUR was successfully encapsulated on the PLGA polymer. The entrapment efficiency and loading rate of CUR were 91.96 and 5.75%, respectively. CUR-PLGA-NPs showed about 640-fold in water solubility relative to that of n-CUR. A sustained CUR release to a total of approximately 77% was discovered from CUR-PLGA-NPs in artificial intestinal juice, but only about 48% in artificial gastric juice. After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native curcumin. The results showed that the effect in improving oral bioavailability of CUR may be associated with improved water solubility, higher release rate in the intestinal juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein (P-gp)-mediated efflux, and increased residence time in the intestinal cavity. Thus, encapsulating hydrophobic drugs on PLGA polymer is a promising method for sustained and controlled drug delivery with improved bioavailability of Biopharmaceutics Classification System (BCS) class IV, such as CUR. PMID:21797282

  4. An oral nutraceutical containing antioxidants, minerals and glycosaminoglycans improves skin roughness and fine wrinkles.

    PubMed

    Udompataikul, M; Sripiroj, P; Palungwachira, P

    2009-12-01

    Various nutraceuticals (dietary supplements) are claimed to have cutaneous antiageing properties, however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of an oral nutraceutical containing antioxidants, minerals and glycosaminoglycans on cutaneous ageing. In this double-blind, placebo-controlled trial, 60 women aged 35-60 years were randomized to receive oral dietary supplement (n = 30) or placebo (n = 30), once daily for 12 weeks. The depth of skin roughness and fine wrinkles were measured using surface evaluation of skin parameters for living skin (Visioscan) at baseline, and at the 4, 8 and 12 weeks of treatment. Surface evaluation using a replica film (Visiometer) at baseline and at the 12th week of treatment was also carried out. Statistical differences in objective skin improvement were assessed by the independent t-test. The volunteers' satisfaction was tested using the chi-squared test. The baseline depth of skin roughness and fine wrinkles in the treatment group and the placebo group were 100.5 and 100 mum, respectively. At the end of the study, the depth of skin roughness and fine wrinkles in the treatment group showed a 21.2% improvement, whereas improvement in the control group was 1.7%. This difference was statistically significant (P < 0.001). With regard to the volunteers' satisfaction, there was no statistically significant decrease in the homogenization of skin colour, however, a statistically significant reduction in pore size and depth of skin roughness and fine wrinkles were observed (P < 0.05). No side effects were noted throughout the study. The oral dietary supplement containing antioxidants, minerals and glycosaminoglycans improved skin roughness and fine wrinkles but did not affect skin colour change in female volunteers.

  5. Ampicillin-Improved Glucose Tolerance in Diet-Induced Obese C57BL/6NTac Mice Is Age Dependent

    PubMed Central

    Rune, I.; Hansen, C. H. F.; Ellekilde, M.; Nielsen, D. S.; Skovgaard, K.; Rolin, B. C.; Lykkesfeldt, J.; Josefsen, K.; Tranberg, B.; Kihl, P.; Hansen, A. K.

    2013-01-01

    Ampicillin has been shown to improve glucose tolerance in mice. We hypothesized that this effect is present only if treatment is initiated prior to weaning and that it disappears when treatment is terminated. High-fat fed C57BL/6NTac mice were divided into groups that received Ampicillin at different ages or not at all. We found that both diet and Ampicillin significantly changed the gut microbiota composition in the animals. Furthermore, there was a significant improvement in glucose tolerance in Ampicillin-treated, five-week-old mice compared to nontreated mice in the control group. At study termination, expressions of mRNA coding for tumor necrosis factor, serum amyloid A, and lactase were upregulated, while the expression of tumor necrosis factor (ligand) superfamily member 15 was downregulated in the ileum of Ampicillin-treated mice. Higher dendritic cell percentages were found systemically in high-fat diet mice, and a lower tolerogenic dendritic cell percentage was found both in relation to high-fat diet and late Ampicillin treatment. The results support our hypothesis that a “window” exists early in life in which an alteration of the gut microbiota affects glucose tolerance as well as development of gut immunity and that this window may disappear after weaning. PMID:24369539

  6. Novel strategies to improve co-fermentation of pentoses with D-glucose by recombinant yeast strains in lignocellulosic hydrolysates.

    PubMed

    Oreb, Mislav; Dietz, Heiko; Farwick, Alexander; Boles, Eckhard

    2012-01-01

    Economically feasible production of second-generation biofuels requires efficient co-fermentation of pentose and hexose sugars in lignocellulosic hydrolysates under very harsh conditions. Baker's yeast is an excellent, traditionally used ethanol producer but is naturally not able to utilize pentoses. This is due to the lack of pentose-specific transporter proteins and enzymatic reactions. Thus, natural yeast strains must be modified by genetic engineering. Although the construction of various recombinant yeast strains able to ferment pentose sugars has been described during the last two decades, their rates of pentose utilization is still significantly lower than D-glucose fermentation. Moreover, pentoses are only fermented after D-glucose is exhausted, resulting in an uneconomical increase in the fermentation time. In this addendum, we discuss novel approaches to improve utilization of pentoses by development of specific transporters and substrate channeling in enzyme cascades. PMID:22892590

  7. Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate

    PubMed Central

    Seo, Jae Hong; Park, Jung Bae; Choi, Woong-Kee; Park, Sunhwa; Sung, Yun Jin; Oh, Euichaul; Bae, Soo Kyung

    2015-01-01

    Objective Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol. Methods Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base. Results The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base. Conclusion This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and cilostazol besylate at doses lower than the usually recommended dosage, so that it can be established as an alternative to the marketed cilostazol tablet. PMID:26251575

  8. Glucose sensing using near-infrared surface-enhanced Raman spectroscopy: gold surfaces, 10-day stability, and improved accuracy.

    PubMed

    Stuart, Douglas A; Yonzon, Chanda Ranjit; Zhang, Xiaoyu; Lyandres, Olga; Shah, Nilam C; Glucksberg, Matthew R; Walsh, Joseph T; Van Duyne, Richard P

    2005-07-01

    This research presents the achievement of significant milestones toward the development of a minimally invasive, continuously monitoring, glucose-sensing platform based on the optical quantitation of glucose in interstitial fluid. We expand our initial successes in the measurement of glucose by surface-enhanced Raman scattering (SERS), demonstrating substantial improvements not only in the quality and optical properties of the substrate system itself but also in the robustness of the measurement methodology and the amenability of the technique to compact, diode laser-based instrumentation. Herein, we compare the long-term stability of gold to silver film over nanosphere (AuFON, AgFON) substrates functionalized with a partitioning self-assembled monolayer (SAM) using both electrochemical and SERS measurements. AuFONs were found to be stable for a period of at least 11 days. The switch to AuFONs not only provides a more stable surface for SAM formation but also yields better chemometric results, with improved calibration and validation over a range of 0.5-44 mM (10-800 mg/dL). Measured values for glucose concentrations in phosphate-buffered saline (pH approximately 7.4) based on 160 independent SERS measurements on AuFONs have a root-mean-square error of prediction of 2.7 mM (49.5 mg/dL), with 91% of the values falling within an extended A-B range on an expanded Clarke error grid. Furthermore, AuFONs exhibit surface plasmon resonances at longer wavelengths than similar AgFONs, which make them more efficient for SERS at near-infrared wavelengths, enabling the use of low-power diode lasers in future devices.

  9. Oral administration of squid lecithin-transphosphatidylated phosphatidylserine improves memory impairment in aged rats.

    PubMed

    Lee, Bombi; Sur, Bong-Jun; Han, Jeong-Jun; Shim, Insop; Her, Song; Lee, Yang-Seok; Lee, Hye-Jung; Hahm, Dae-Hyun

    2015-01-01

    Recently, lecithin-derived phosphatidylserine (PS), which originates from marine life, has received much attention as a viable alternative to bovine cerebral cortex PS. In this study, the use of squid phosphatidylcholine-transphosphatidylated PS (SQ-PS) was evaluated through examination of its ameliorating effects on age-associated learning and memory deficits in rats. Aged rats were orally administered SQ-PS (10, 20, or 50 mg/kg per day) once a day for seven days 30 min prior to behavioral assessment in a Morris water maze. SQ-PS administration produced significant dose-dependent improvements in escape latency for finding the platform in the Morris water maze in the aged rats even though Soy-PS administration also exhibited comparable improvements with SQ-PS. Biochemical alterations in the hippocampal cholinergic system, including changes in choline acetyltransferase and acetylcholinesterase immunoreactivity, were consistent with the behavioral results. In addition, SQ-PS treatment significantly restored age-associated decreases of choline transporter and muscarinic acetylcholine receptor type 1 mRNA expression in the hippocampus. These results demonstrate that orally administered SQ-PS dose-dependently aids in the improvement of memory deficits that occur during normal aging in rats. This suggests that SQ-PS may be a useful therapeutic agent in the treatment of diminished memory function in elderly people.

  10. Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency.

    PubMed

    Park, N C; Yan, B Q; Chung, J M; Lee, K M

    2003-06-01

    In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculoskeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency. PMID:12898792

  11. Progesterone receptor knockout mice have an improved glucose homeostasis secondary to -cell proliferation

    NASA Astrophysics Data System (ADS)

    Picard, Frédéric; Wanatabe, Mitsuhiro; Schoonjans, Kristina; Lydon, John; O'Malley, Bert W.; Auwerx, Johan

    2002-11-01

    Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female db/db mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and db/db mice. Furthermore, female, but not male, PR-/- mice had lower fasting glycemia than PR+/+ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-/- mice were larger and secreted more insulin consequent to an increase in -cell mass due to an increase in -cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.

  12. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations.

    PubMed

    Guzmán, Héctor R; Tawa, Mark; Zhang, Zhong; Ratanabanangkoon, Pasut; Shaw, Paul; Gardner, Colin R; Chen, Hongming; Moreau, Jean-Pierre; Almarsson, Orn; Remenar, Julius F

    2007-10-01

    Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form of Celebrex(R) showed approximately 40% absolute bioavailability in a cross-over experiment. An in vitro-in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a 'spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors ('parachutes') were shown to provide both enhanced dissolution and high oral bioavailability.

  13. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations.

    PubMed

    Guzmán, Héctor R; Tawa, Mark; Zhang, Zhong; Ratanabanangkoon, Pasut; Shaw, Paul; Gardner, Colin R; Chen, Hongming; Moreau, Jean-Pierre; Almarsson, Orn; Remenar, Julius F

    2007-10-01

    Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form of Celebrex(R) showed approximately 40% absolute bioavailability in a cross-over experiment. An in vitro-in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a 'spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors ('parachutes') were shown to provide both enhanced dissolution and high oral bioavailability. PMID:17518357

  14. Value of Self-Monitoring Blood Glucose Pattern Analysis in Improving Diabetes Outcomes

    PubMed Central

    Parkin, Christopher G.; Davidson, Jaime A.

    2009-01-01

    Self-monitoring of blood glucose (SMBG) is an important adjunct to hemoglobin A1c (HbA1c) testing. This action can distinguish between fasting, preprandial, and postprandial hyperglycemia; detect glycemic excursions; identify and monitor resolution of hypoglycemia; and provide immediate feedback to patients about the effect of food choices, activity, and medication on glycemic control. Pattern analysis is a systematic approach to identifying glycemic patterns within SMBG data and then taking appropriate action based upon those results. The use of pattern analysis involves: (1) establishing pre- and postprandial glucose targets; (2) obtaining data on glucose levels, carbohydrate intake, medication administration (type, dosages, timing), activity levels and physical/emotional stress; (3) analyzing data to identify patterns of glycemic excursions, assessing any influential factors, and implementing appropriate action(s); and (4) performing ongoing SMBG to assess the impact of any therapeutic changes made. Computer-based and paper-based data collection and management tools can be developed to perform pattern analysis for identifying patterns in SMBG data. This approach to interpreting SMBG data facilitates rational therapeutic adjustments in response to this information. Pattern analysis of SMBG data can be of equal or greater value than measurement of HbA1c levels. PMID:20144288

  15. SRA Gene Knockout Protects against Diet-induced Obesity and Improves Glucose Tolerance*

    PubMed Central

    Liu, Shannon; Sheng, Liang; Miao, Hongzhi; Saunders, Thomas L.; MacDougald, Ormond A.; Koenig, Ronald J.; Xu, Bin

    2014-01-01

    We have recently shown that the non-coding RNA, steroid receptor RNA activator (SRA), functions as a transcriptional coactivator of PPARγ and promotes adipocyte differentiation in vitro. To assess SRA function in vivo, we have generated a whole mouse Sra1 gene knock-out (SRA−/−). Here, we show that the Sra1 gene is an important regulator of adipose tissue mass and function. SRA is expressed at a higher level in adipose tissue than other organs in wild type mice. SRA−/− mice are resistant to high fat diet-induced obesity, with decreased fat mass and increased lean content. This lean phenotype of SRA−/− mice is associated with decreased expression of a subset of adipocyte marker genes and reduced plasma TNFα levels. The SRA−/− mice are more insulin sensitive, as evidenced by reduced fasting insulin, and lower blood glucoses in response to IP glucose and insulin. In addition, the livers of SRA−/− mice have fewer lipid droplets after high fat diet feeding, and the expression of lipogenesis-associated genes is decreased. To our knowledge, these data are the first to indicate a functional role for SRA in adipose tissue biology and glucose homeostasis in vivo. PMID:24675075

  16. Boehmeria nivea Stimulates Glucose Uptake by Activating Peroxisome Proliferator-Activated Receptor Gamma in C2C12 Cells and Improves Glucose Intolerance in Mice Fed a High-Fat Diet

    PubMed Central

    Kim, Sung Hee; Sung, Mi Jeong; Park, Jae Ho; Yang, Hye Jeong; Hwang, Jin-Taek

    2013-01-01

    We examined the antidiabetic property of Boehmeria nivea (L.) Gaud. Ethanolic extract of Boehmeria nivea (L.) Gaud. (EBN) increased the uptake of 2-[N-(nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose in C2C12 myotubes. To examine the mechanisms underlying EBN-mediated increase in glucose uptake, we examined the transcriptional activity and expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), a pivotal target for glucose metabolism in C2C12 myotubes. We found that the EBN increased both the transcriptional activity and mRNA expression levels of PPAR-γ. In addition, we measured phosphorylation and expression levels of other targets of glucose metabolism, such as AMP-activated protein kinase (AMPK) and protein kinase B (Akt/PKB). We found that EBN did not alter the phosphorylation or expression levels of these proteins in a time- or dose-dependent manner, which suggested that EBN stimulates glucose uptake through a PPAR-γ-dependent mechanism. Further, we investigated the antidiabetic property of EBN using mice fed a high-fat diet (HFD). Administration of 0.5% EBN reduced the HFD-induced increase in body weight, total cholesterol level, and fatty liver and improved the impaired fasting glucose level, blood insulin content, and glucose intolerance. These results suggest that EBN had an antidiabetic effect in cell culture and animal systems and may be useful for preventing diabetes. PMID:23690860

  17. Improved Accuracy of Continuous Glucose Monitoring Systems in Pediatric Patients with Diabetes Mellitus: Results from Two Studies

    PubMed Central

    2016-01-01

    Abstract Objective: This study was designed to evaluate accuracy, performance, and safety of the Dexcom (San Diego, CA) G4® Platinum continuous glucose monitoring (CGM) system (G4P) compared with the Dexcom G4 Platinum with Software 505 algorithm (SW505) when used as adjunctive management to blood glucose (BG) monitoring over a 7-day period in youth, 2–17 years of age, with diabetes. Research Design and Methods: Youth wore either one or two sensors placed on the abdomen or upper buttocks for 7 days, calibrating the device twice daily with a uniform BG meter. Participants had one in-clinic session on Day 1, 4, or 7, during which fingerstick BG measurements (self-monitoring of blood glucose [SMBG]) were obtained every 30 ± 5 min for comparison with CGM, and in youth 6–17 years of age, reference YSI glucose measurements were obtained from arterialized venous blood collected every 15 ± 5 min for comparison with CGM. The sensor was removed by the participant/family after 7 days. Results: In comparison of 2,922 temporally paired points of CGM with the reference YSI measurement for G4P and 2,262 paired points for SW505, the mean absolute relative difference (MARD) was 17% for G4P versus 10% for SW505 (P < 0.0001). In comparison of 16,318 temporally paired points of CGM with SMBG for G4P and 4,264 paired points for SW505, MARD was 15% for G4P versus 13% for SW505 (P < 0.0001). Similarly, error grid analyses indicated superior performance with SW505 compared with G4P in comparison of CGM with YSI and CGM with SMBG results, with greater percentages of SW505 results falling within error grid Zone A or the combined Zones A plus B. There were no serious adverse events or device-related serious adverse events for either the G4P or the SW505, and there was no sensor breakoff. Conclusions: The updated algorithm offers substantial improvements in accuracy and performance in pediatric patients with diabetes. Use of CGM with improved performance has

  18. Improving Oral Hygiene in Institutionalised Elderly by Educating Their Caretakers in Bangalore City, India: a Randomised Control Trial

    PubMed Central

    Khanagar, Sanjeev; Naganandini, S.; Tuteja, Jaspreet Singh; Naik, Sachin; Satish, G.; Divya, K.T.

    2015-01-01

    Background The population of older people, as well as the number of dependent older people, is steadily increasing; those unable to live independently at home are being cared for in a range of settings. Practical training for nurses and auxiliary care staff has frequently been recommended as a way of improving oral health care for functionally dependent elderly. The aim was improve oral hygiene in institutionalized elderly in Bangalore city by educating their caregivers. Methods The study is a cluster randomized intervention trial with an elderly home as unit of randomization in which 7 out of 65 elderly homes were selected. Oral health knowledge of caregivers was assessed using a pre-tested pro forma and later oral-health education was provided to the caregivers of the study group. Oral hygiene status of elderly residents was assessed by levels of debris, plaque of dentate and denture plaque, and denture stomatitis of denture wearing residents, respectively. Oral-health education to the caregivers of control group was given at the end of six months Results There was significant improvement in oral-health knowledge of caregivers from the baseline and also a significant reduction of plaque score from baseline score of 3.17 ± 0.40 to 1.57 ± 0.35 post-intervention (p < .001), debris score 2.87 ± 0.22 to 1.49 ± 0.34 (p < .001), denture plaque score 3.15 ± 0.47 to 1.21 ± 0.27 (p < .001), and denture stomatitis score 1.43 ± 0.68 to 0.29 ± 0.53 (p < .001). Conclusions The result of the present study showed that there was a significant improvement in the oral-health knowledge among the caregivers and oral-hygiene status of the elderly residents. PMID:26495047

  19. Okara ameliorates glucose tolerance in GK rats.

    PubMed

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-05-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  20. Glucose control.

    PubMed

    Preiser, Jean-Charles

    2013-01-01

    Stress-related hyperglycemia is a common finding in acutely ill patients, and is related to the severity and outcome of the critical illness. The pathophysiology of stress hyperglycemia includes hormonal and neural signals, leading to increased production of glucose by the liver and peripheral insulin resistance mediated by the translocation of transmembrane glucose transporters. In one pioneering study, tight glycemic control by intensive insulin therapy in critically ill patients was associated with improved survival. However, this major finding was not confirmed in several other prospective randomized controlled trials. The reasons underlying the discrepancy between the first and the subsequent studies could include nutritional strategy (amount of calories provided, use of parenteral nutrition), case-mix, potential differences in the optimal blood glucose level (BG) in different types of patients, hypoglycemia and its correction, and the magnitude of glucose variability. Therefore, an improved understanding of the physiology and pathophysiology of glycemic regulation during acute illness is needed. Safe and effective glucose control will need improvement in the definition of optimal BG and in the measurement techniques, perhaps including continuous monitoring of insulin algorithms and closed-loop systems. PMID:23075589

  1. Oral iodinated activated charcoal improves lung function in patients with COPD.

    PubMed

    Skogvall, Staffan; Erjefält, Jonas S; Olin, Anders I; Ankerst, Jaro; Bjermer, Leif

    2014-06-01

    The effect of 8 weeks treatment with oral iodinated activated charcoal (IAC) on lung function of patients with moderate chronic obstructive pulmonary disease (COPD) was examined in a double blind randomized placebo controlled parallel group study with 40 patients. In the IAC group, patients showed a statistically significant improvement of FEV1 baseline by 130 ml compared to placebo, corresponding to 8.2% improvement (p = 0.031*). Correlation statistics revealed that the improvement of FEV1 baseline was significantly correlated both to FEV1 post-bronchodilator (p = 0.0020**) and FEV1 post-exercise (0.033*) values. This demonstrates that the improved baseline lung function by IAC did not inhibit a further beta2-adrenoceptor relaxation, and thus that patients did not reach a limit for maximal improvement of the lung function after IAC treatment. Eight patients in the IAC group developed abnormal thyroid hormone levels transiently during the treatment. This side effect was not correlated to improvement of lung function (p = 0.82). No serious adverse effects directly related to the treatment were recorded. In summary, this study demonstrates that iodinated activated charcoal surprisingly and significantly improved lung function of patients with moderate COPD. The underlying mechanism of action is unclear, but is likely to be different from the drugs used today. The immediate conclusion is that further studies are now justified in order to determine clinical efficacy of IAC in COPD and explore possible mechanisms of action.

  2. Jiang Tang Xiao Ke Granule, a Classic Chinese Herbal Formula, Improves the Effect of Metformin on Lipid and Glucose Metabolism in Diabetic Mice

    PubMed Central

    Zhang, Yi; An, Hong; Pan, Si-Yuan; Zhao, Dan-Dan; Zuo, Jia-Cheng; Li, Xiao-Ke; Gao, Ya; Mu, Qian-Qian; Yu, Na; Ma, Yue; Mo, Fang-Fang; Gao, Si-Hua

    2016-01-01

    In the present study, the hypoglycemic, hypolipidemic, and antioxidative effects of metformin (MET) combined with Jiang Tang Xiao Ke (JTXK) granule derived from the “Di Huang Tang” were evaluated in mice with type 2 diabetes mellitus (DM) induced by high-fat diet/streptozotocin. DM mice were orally treated with MET (0.19 g/kg) either alone or combined with different doses (1.75, 3.5, or 7 g/kg) of JTXK for 4 weeks. Results showed that the serum and hepatic glucose, lipids, and oxidative stress levels were elevated in DM mice, when compared with the normal mice. MET treatment decreased FBG and serum glucagon levels of DM mice. Combination treatment with MET and JTXK 3.5 g/kg increased the hypoglycemia and insulin sensitivity at 4 weeks when compared with the DM mice treated with MET alone. However, neither MET nor MET/JTXK treatment could completely reverse the hyperglycemia in DM mice. JTXK enhanced the serum triglyceride (TG) and hepatic lipid-lowering effect of MET in a dose-dependent manner in DM mice. JTXK 1.75 and 3.5 g/kg improved the hepatoprotective effect of MET in DM mice. Synergistic effect of combination treatment with MET and JTXK on antioxidant stress was also found in DM mice compared with MET alone. PMID:27418937

  3. Jiang Tang Xiao Ke Granule, a Classic Chinese Herbal Formula, Improves the Effect of Metformin on Lipid and Glucose Metabolism in Diabetic Mice.

    PubMed

    Zhang, Yi; An, Hong; Pan, Si-Yuan; Zhao, Dan-Dan; Zuo, Jia-Cheng; Li, Xiao-Ke; Gao, Ya; Mu, Qian-Qian; Yu, Na; Ma, Yue; Mo, Fang-Fang; Gao, Si-Hua

    2016-01-01

    In the present study, the hypoglycemic, hypolipidemic, and antioxidative effects of metformin (MET) combined with Jiang Tang Xiao Ke (JTXK) granule derived from the "Di Huang Tang" were evaluated in mice with type 2 diabetes mellitus (DM) induced by high-fat diet/streptozotocin. DM mice were orally treated with MET (0.19 g/kg) either alone or combined with different doses (1.75, 3.5, or 7 g/kg) of JTXK for 4 weeks. Results showed that the serum and hepatic glucose, lipids, and oxidative stress levels were elevated in DM mice, when compared with the normal mice. MET treatment decreased FBG and serum glucagon levels of DM mice. Combination treatment with MET and JTXK 3.5 g/kg increased the hypoglycemia and insulin sensitivity at 4 weeks when compared with the DM mice treated with MET alone. However, neither MET nor MET/JTXK treatment could completely reverse the hyperglycemia in DM mice. JTXK enhanced the serum triglyceride (TG) and hepatic lipid-lowering effect of MET in a dose-dependent manner in DM mice. JTXK 1.75 and 3.5 g/kg improved the hepatoprotective effect of MET in DM mice. Synergistic effect of combination treatment with MET and JTXK on antioxidant stress was also found in DM mice compared with MET alone. PMID:27418937

  4. Novel Lipid-Free Nanoformulation for Improving Oral Bioavailability of Coenzyme Q10

    PubMed Central

    Zhou, Huafeng; Liu, Guoqing; Zhang, Jing; Sun, Ning; Duan, Mingxing; Yan, Zemin; Xia, Qiang

    2014-01-01

    To improve the bioavailability of orally administered lipophilic coenzyme Q10 (CoQ10), we formulated a novel lipid-free nano-CoQ10 system stabilized by various surfactants. Nano-CoQ10s, composed of 2.5% (w/w) CoQ10, 1.67% (w/w) surfactant, and 41.67% (w/w) glycerol, were prepared by hot high-pressure homogenization. The resulting formulations were characterized by particle size, zeta potential, differential scanning calorimetry, and cryogenic transmission electron microscopy. We found that the mean particle size of all nano-CoQ10s ranged from 66.3 ± 1.5 nm to 92.7 ± 1.5 nm and the zeta potential ranged from −12.8 ± 1.4 mV to −41.6 ± 1.4 mV. The CoQ10 in nano-CoQ10s likely existed in a supercooled state, and nano-CoQ10s stored in a brown sealed bottle were stable for 180 days at 25°C. The bioavailability of CoQ10 was evaluated following oral administration of CoQ10 formulations in Sprague-Dawley rats. Compared to the values observed following administration of CoQ10-Suspension, nano-CoQ10 modified with various surfactants significantly increased the maximum plasma concentration and the area under the plasma concentration-time curve. Thus, the lipid-free system of a nano-CoQ10 stabilized with a surfactant may be an effective vehicle for improving oral bioavailability of CoQ10. PMID:24995328

  5. Lecithin-based novel cationic nanocarriers (Leciplex) II: improving therapeutic efficacy of quercetin on oral administration.

    PubMed

    Date, Abhijit A; Nagarsenker, Mangal S; Patere, Shilpa; Dhawan, Vivek; Gude, R P; Hassan, P A; Aswal, V; Steiniger, Frank; Thamm, Jana; Fahr, Alfred

    2011-06-01

    The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

  6. Probiotic Lactobacillus gasseri SBT2055 improves glucose tolerance and reduces body weight gain in rats by stimulating energy expenditure.

    PubMed

    Shirouchi, Bungo; Nagao, Koji; Umegatani, Minami; Shiraishi, Aya; Morita, Yukiko; Kai, Shunichi; Yanagita, Teruyoshi; Ogawa, Akihiro; Kadooka, Yukio; Sato, Masao

    2016-08-01

    Probiotic Lactobacillus gasseri SBT2055 (LG2055) reduces postprandial TAG absorption and exerts anti-obesity effects in rats and humans; however, the underlying mechanisms are not fully understood. In the present study, we addressed the mechanistic insights of the anti-obesity activity of LG2055 by feeding Sprague-Dawley rats diets containing skimmed milk fermented or not by LG2055 for 4 weeks and by analysing energy expenditure, glucose tolerance, the levels of SCFA in the caecum and serum inflammatory markers. Rats fed the LG2055-containing diet demonstrated significantly higher carbohydrate oxidation in the dark cycle (active phase for rats) compared with the control group, which resulted in a significant increase in energy expenditure. LG2055 significantly reduced cumulative blood glucose levels (AUC) compared with the control diet after 3 weeks and increased the molar ratio of butyrate:total SCFA in the caecum after 4 weeks. Furthermore, the LG2055-supplemented diet significantly reduced the levels of serum amyloid P component - an indicator of the inflammatory process. In conclusion, our results demonstrate that, in addition to the inhibition of dietary TAG absorption reported previously, the intake of probiotic LG2055 enhanced energy expenditure via carbohydrate oxidation, improved glucose tolerance and attenuated inflammation, suggesting multiple additive and/or synergistic actions underlying the anti-obesity effects exerted by LG2055. PMID:27267802

  7. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

    PubMed Central

    Clarkson, P; Adams, M R; Powe, A J; Donald, A E; McCredie, R; Robinson, J; McCarthy, S N; Keech, A; Celermajer, D S; Deanfield, J E

    1996-01-01

    In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process. PMID:8621785

  8. Development of solid lipid nanoparticles as carriers for improving oral bioavailability of glibenclamide.

    PubMed

    Gonçalves, L M D; Maestrelli, F; Di Cesare Mannelli, L; Ghelardini, C; Almeida, A J; Mura, P

    2016-05-01

    A solid lipid nanoparticle (SLN) formulation was developed with the aim of improving the oral bioavailability and the therapeutic effectiveness of glibenclamide (GLI), a poorly water-soluble drug used in the treatment of type 2 diabetes. The SLN was prepared using different lipid components (Precirol® and Compritol®) and preparation procedures. Precirol-based SLN, obtained with the emulsion of solvent evaporation technique gave the best results and was selected for drug loading. Addition of lecithin to the SLN core or PEG coating was effective in increasing the nanoparticles stability in simulated gastric solution. Both such formulations were stable after one month storage at 5±3°C, exhibited the absence of in vitro cytotoxicity, and presented a similar in vitro prolonged-release, reaching 100% release after 24h. The lecithin-containing GLI-loaded SLN formulation, selected for in vivo studies in virtue of its higher EE% than the PEG-coated formulation (70.3% vs 19.6%), showed a significantly stronger hypoglycemic effect with respect to the drug alone, in terms of both shorter onset time and longer duration of the effect. These positive results indicated that the proposed SLN approach was successful in improving GLI oral bioavailability, confirming its potential as an effective delivery system for a suitable therapy of diabetes. PMID:26925503

  9. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome

    PubMed Central

    Kaska, Lukasz; Sledzinski, Tomasz; Chomiczewska, Agnieszka; Dettlaff-Pokora, Agnieszka; Swierczynski, Julian

    2016-01-01

    Clinical studies have indicated that circulating bile acid (BA) concentrations increase following bariatric surgery, especially following malabsorptive procedures such as Roux-en-Y gastric bypasses (RYGB). Moreover, total circulating BA concentrations in patients following RYGB are positively correlated with serum glucagon-like peptide-1 concentrations and inversely correlated with postprandial glucose concentrations. Overall, these data suggest that the increased circulating BA concentrations following bariatric surgery - independently of calorie restriction and body-weight loss - could contribute, at least in part, to improvements in insulin sensitivity, incretin hormone secretion, and postprandial glycemia, leading to the remission of type-2 diabetes (T2DM). In humans, the primary and secondary BA pool size is dependent on the rate of biosynthesis and the enterohepatic circulation of BAs, as well as on the gut microbiota, which play a crucial role in BA biotransformation. Moreover, BAs and gut microbiota are closely integrated and affect each other. Thus, the alterations in bile flow that result from anatomical changes caused by bariatric surgery and changes in gut microbiome may influence circulating BA concentrations and could subsequently contribute to T2DM remission following RYGB. Research data coming largely from animal and cell culture models suggest that BAs can contribute, via nuclear farnezoid X receptor (FXR) and membrane G-protein-receptor (TGR-5), to beneficial effects on glucose metabolism. It is therefore likely that FXR, TGR-5, and BAs play a similar role in glucose metabolism following bariatric surgery in humans. The objective of this review is to discuss in detail the results of published studies that show how bariatric surgery affects glucose metabolism and subsequently T2DM remission.

  10. Plants and other natural products used in the management of oral infections and improvement of oral health.

    PubMed

    Chinsembu, Kazhila C

    2016-02-01

    Challenges of resistance to synthetic antimicrobials have opened new vistas in the search for natural products. This article rigorously reviews plants and other natural products used in oral health: Punica granatum L. (pomegranate), Matricaria recutita L. (chamomile), Camellia sinensis (L.) Kuntze (green tea), chewing sticks made from Diospyros mespiliformis Hochst. ex A.D.C., Diospyros lycioides Desf., and Salvadora persica L. (miswak), honey and propolis from the manuka tree (Leptospermum scoparium J.R. Forst. & G. Forst.), rhein from Rheum rhabarbarum L. (rhubarb), dried fruits of Vitis vinifera L. (raisins), essential oils, probiotics and mushrooms. Further, the review highlights plants from Africa, Asia, Brazil, Mexico, Europe, and the Middle East. Some of the plants' antimicrobial properties and chemical principles have been elucidated. While the use of natural products for oral health is prominent in resource-poor settings, antimicrobial testing is mainly conducted in the following countries (in decreasing order of magnitude): India, South Africa, Brazil, Japan, France, Egypt, Iran, Mexico, Kenya, Switzerland, Nigeria, Australia, Uganda, and the United Kingdom. While the review exposes a dire gap for more studies on clinical efficacy and toxicity, the following emerging trend was noted: basic research on plants for oral health is mainly done in Brazil, Europe and Australia. Brazil, China, India and New Zealand generally conduct value addition of natural products for fortification of toothpastes. African countries focus on bioprospecting and primary production of raw plants and other natural products with antimicrobial efficacies. The Middle East and Egypt predominantly research on plants used as chewing sticks. More research and funding are needed in the field of natural products for oral health, especially in Africa where oral diseases are fuelled by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). PMID:26522671

  11. Plants and other natural products used in the management of oral infections and improvement of oral health.

    PubMed

    Chinsembu, Kazhila C

    2016-02-01

    Challenges of resistance to synthetic antimicrobials have opened new vistas in the search for natural products. This article rigorously reviews plants and other natural products used in oral health: Punica granatum L. (pomegranate), Matricaria recutita L. (chamomile), Camellia sinensis (L.) Kuntze (green tea), chewing sticks made from Diospyros mespiliformis Hochst. ex A.D.C., Diospyros lycioides Desf., and Salvadora persica L. (miswak), honey and propolis from the manuka tree (Leptospermum scoparium J.R. Forst. & G. Forst.), rhein from Rheum rhabarbarum L. (rhubarb), dried fruits of Vitis vinifera L. (raisins), essential oils, probiotics and mushrooms. Further, the review highlights plants from Africa, Asia, Brazil, Mexico, Europe, and the Middle East. Some of the plants' antimicrobial properties and chemical principles have been elucidated. While the use of natural products for oral health is prominent in resource-poor settings, antimicrobial testing is mainly conducted in the following countries (in decreasing order of magnitude): India, South Africa, Brazil, Japan, France, Egypt, Iran, Mexico, Kenya, Switzerland, Nigeria, Australia, Uganda, and the United Kingdom. While the review exposes a dire gap for more studies on clinical efficacy and toxicity, the following emerging trend was noted: basic research on plants for oral health is mainly done in Brazil, Europe and Australia. Brazil, China, India and New Zealand generally conduct value addition of natural products for fortification of toothpastes. African countries focus on bioprospecting and primary production of raw plants and other natural products with antimicrobial efficacies. The Middle East and Egypt predominantly research on plants used as chewing sticks. More research and funding are needed in the field of natural products for oral health, especially in Africa where oral diseases are fuelled by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).

  12. Toward improving the oral health of Americans: an overview of oral health status, resources, and care delivery. Oral Health Coordinating Committee, Public Health Service.

    PubMed Central

    1993-01-01

    Dental and oral diseases may well be the most prevalent and preventable conditions affecting Americans. More than 50 percent of U.S. children, 96 percent of employed U.S. adults, and 99.5 percent of Americans 65 years and older have experienced dental caries (also called cavities). Millions of Americans suffer from periodontal diseases and other oral conditions, and more than 17 million Americans, including 10 million Americans 65 years or older, have lost all of their teeth. Preventive dental services are known to be effective in preventing and controlling dental diseases. Unfortunately, groups at highest risk for disease--the poor and minorities--have lower rates of using dental care than the U.S. average. Cost is the principal barrier to dental care for many Americans. Of the $38.7 billion spent for dental services in 1992, public programs, including Medicaid, paid for less than 4 percent of dental expenditures. More than 90 percent of care was paid for either out-of-pocket by dental consumers or through private dental insurance. Americans are at risk for other oral health problems as well. Oropharyngeal cancer strikes approximately 30,000 Americans each year and results in an estimated 8,000 deaths annually. Underlying medical or handicapping conditions, ranging from rare genetic diseases to more common chronic diseases, affect millions of Americans and can lead to oral health problems. Among persons with compromised immune systems, oral diseases and conditions can have a significant impact on health. Oral diseases and conditions, though nearly universal, can be prevented easily and controlled at reasonable cost.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8265750

  13. Targeting blood glucose management in school improves glycemic control in children with poorly controlled type 1 diabetes mellitus.

    PubMed

    Nguyen, Thanh M; Mason, Kimberly J; Sanders, Cynthia G; Yazdani, Parvin; Heptulla, Rubina A

    2008-10-01

    We hypothesized that school nurse supervision of glucose and insulin-dose adjustment significantly improves the hemoglobinA(1c) (HbA(1c)) level in pediatric patients with poorly controlled type 1 diabetes mellitus (HbA(1c) > or = 9%). A total of 36 subjects were enrolled and 18 subjects were randomized to receive the 3-month intervention. Their average HbA(1c) was lowered by 1.6%, suggesting that this intervention helps this difficult group of patients.

  14. Improved docosahexaenoic acid production in Aurantiochytrium by glucose limited pH-auxostat fed-batch cultivation.

    PubMed

    Janthanomsuk, Panyawut; Verduyn, Cornelis; Chauvatcharin, Somchai

    2015-11-01

    Fed-batch, pH auxostat cultivation of the docosahexaenoic acid (DHA)-producing microorganism Aurantiochytrium B072 was performed to obtain high cell density and record high productivity of both total fatty acid (TFA) and DHA. Using glucose feeding by carbon excess (C-excess) and by C-limitation at various feeding rates (70%, 50% or 20% of C-excess), high biomass density was obtained and DHA/TFA content (w/w) was improved from 30% to 37% with a 50% glucose feed rate when compared with C-excess. To understand the biochemistry behind these improvements, lipogenic enzyme assays and in silico metabolic flux calculations were used and revealed that enzyme activity and C-fluxes to TFA were reduced with C-limited feeding but that the carbon flux to the polyketide synthase pathway increased relative to the fatty acid synthase pathway. As a result, a new strategy to improve the DHA to TFA content while maintaining relatively high DHA productivity is proposed. PMID:26298403

  15. Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

    PubMed

    Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

    2015-09-01

    Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups

  16. Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

    PubMed

    Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

    2015-09-01

    Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups

  17. Improving the Oral Health of Residents with Intellectual and Developmental Disabilities: An Oral Health Strategy and Pilot Study

    PubMed Central

    Binkley, Catherine J.; Johnson, Knowlton W.; Abadi, Melissa; Thompson, Kirsten; Shamblen, Stephen R.; Young, Linda; Zaksek, Brigit

    2014-01-01

    This article presents an oral health (OH) strategy and pilot study focusing on individuals with intellectual and/or developmental disabilities (IDD) living in group homes. The strategy consists of four components: (1) planned action in the form of the behavioral contract and caregiver OH action planning; (2) capacity building through didactic and observation learning training; (3) environmental adaptations consisting of additional oral heath devices and strategies to create a calm atmosphere; and (4) reinforcement by post-training coaching. A pilot study was conducted consisting of pre- and post-assessment data collected one week before and one week after implementing a one-month OH strategy. The study sample comprised 11 group homes with 21 caregivers and 25 residents with IDD from one service organization in a Midwestern city. A process evaluation found high-quality implementation of the OH strategy as measured by dosage, fidelity, and caregiver reactions to implementing the strategy. Using repeated cross-sectional and repeated measures analyses, we found statistically significant positive changes in OH status and oral hygiene practices of residents. Caregiver self-efficacy as a mechanism of change was not adequately evaluated; however, positive change was found in some but not all types of caregiver OH support that were assessed. Lessons learned from implementing the pilot study intervention and evaluation are discussed, as are the next steps in conducting an efficacy study of the OH strategy. PMID:25137553

  18. Improving the oral health of residents with intellectual and developmental disabilities: an oral health strategy and pilot study.

    PubMed

    Binkley, Catherine J; Johnson, Knowlton W; Abadi, Melissa; Thompson, Kirsten; Shamblen, Stephen R; Young, Linda; Zaksek, Brigit

    2014-12-01

    This article presents an oral health (OH) strategy and pilot study focusing on individuals with intellectual and/or developmental disabilities (IDD) living in group homes. The strategy consists of four components: (1) planned action in the form of the behavioral contract and caregiver OH action planning; (2) capacity building through didactic and observation learning training; (3) environmental adaptations consisting of additional oral heath devices and strategies to create a calm atmosphere; and (4) reinforcement by post-training coaching. A pilot study was conducted consisting of pre- and post-assessment data collected 1 week before and 1 week after implementing a 1-month OH strategy. The study sample comprised 11 group homes with 21 caregivers and 25 residents with IDD from one service organization in a Midwestern city. A process evaluation found high-quality implementation of the OH strategy as measured by dosage, fidelity, and caregiver reactions to implementing the strategy. Using repeated cross-sectional and repeated measures analyses, we found statistically significant positive changes in OH status and oral hygiene practices of residents. Caregiver self-efficacy as a mechanism of change was not adequately evaluated; however, positive change was found in some but not all types of caregiver OH support that were assessed. Lessons learned from implementing the pilot study intervention and evaluation are discussed, as are the next steps in conducting an efficacy study of the OH strategy. PMID:25137553

  19. MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients.

    PubMed

    Nichols-Vinueza, Diana X; White, Matthew T; Powell, Andrew J; Banka, Puja; Neufeld, Ellis J

    2014-07-01

    Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan® ) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care.

  20. MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients.

    PubMed

    Nichols-Vinueza, Diana X; White, Matthew T; Powell, Andrew J; Banka, Puja; Neufeld, Ellis J

    2014-07-01

    Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan® ) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care. PMID:24652616

  1. Distribution of proteins similar to IIIManH and IIIManL of the Streptococcus salivarius phosphoenolpyruvate:mannose-glucose phosphotransferase system among oral and nonoral bacteria.

    PubMed Central

    Pelletier, M; Frenette, M; Vadeboncoeur, C

    1995-01-01

    In Streptococcus salivarius, the phosphoenolpyruvate (PEP):mannose-glucose phosphotransferase system, which concomitantly transports and phosphorylates mannose, glucose, fructose, and 2-deoxyglucose, is composed of the general energy-coupling proteins EI and HPr, the specific membrane-bound IIIMan, and two forms of a protein called IIIMan, with molecular weights of 38,900 (IIIManH) and 35,200 (IIIManL), that are found in the cytoplasm as well as associated with the membrane. Several lines of evidence suggest that IIIManH and/or IIIManL are involved in the control of sugar metabolism. To determine whether other bacteria possess these proteins, we tested for their presence in 28 oral streptococcus strains, 3 nonoral streptococcus strains, 2 lactococcus strains, 2 enterococcus strains, 2 bacillus strains, 1 lactobacillus strain, Staphylococcus aureus, and Escherichia coli. Three approaches were used to determine whether the IIIMan proteins were present in these bacteria: (i) Western blot (immunoblot) analysis of cytoplasmic and membrane proteins, using anti-IIIManH and anti-IIIManH rabbit polyclonal antibodies; (ii) analysis of PEP-dependent phosphoproteins by polyacrylamide gel electrophoresis; and (iii) inhibition by anti-IIIMan antibodies of the PEP-dependent phosphorylation of 2-deoxyglucose (a mannose analog) by crude cellular extracts. Only the species S. salivarius and Streptococcus vestibularis possessed the two forms of IIIMan. Fifteen other streptococcal species possessed one protein with a molecular weight between 35,200 and 38,900 that cross-reacted with both antibodies. In the case of 9 species, a protein possessing the same electrophoretic mobility was phosphorylated at the expense of PEP. No such phosphoprotein, however, could be detected in the other six species. A III(Man)-like protein with a molecular weight of 35,500 was also detected in Lactobacillus casei by Western blot experiments as well as by PEP-dependent phosphoprotein analysis, and a

  2. Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies.

    PubMed

    Parveen, Rabea; Baboota, Sanjula; Ali, Javed; Ahuja, Alka; Vasudev, Suruchi S; Ahmad, Sayeed

    2011-07-15

    Silymarin, obtained from Silybum marianum is used for hepatoprotection and having poor aqueous solubility and low bioavailability. Therefore, it was thought to incorporate the drug into oil-in-water (o/w) based nanocarrier to increase its oral bioavailability. In the present study, o/w nanocarrier was prepared by titration method and was characterized for droplet size, viscosity, etc. In vitro drug release was carried out by dialysis membrane method. A pharmacokinetic study was performed to determine maximum plasma concentration (C(max)), area under the curve (AUC), etc. and hepatoprotective activity was evaluated in terms of serum enzyme estimation. The optimized nanoemulsion formulation consisted of sefsol-218 as oil, tween 80 as a surfactant and ethanol as a co-surfactant having nano-droplet size and low viscosity. In vitro dissolution studies showed higher drug release from nanoemulsion as compared to bulk drug suspension. The AUC and C(max) of nanoemulsion after oral administration were 4-fold and 6-fold higher than those of drug suspension of silymarin. The results of pharmacokinetic studies showed better effects of developed nanoemulsion than drug suspension and marketed formulation. The present study showed that the nanoemulsion being a versatile technology has the potential to improve the biopharmaceutics properties of silymarin.

  3. Aminoalkylmethacrylate copolymer E improves oral bioavailability of YM466 by suppressing drug-bile interaction.

    PubMed

    Takemura, Shigeo; Kondo, Hiromu; Watanabe, Shunsuke; Sako, Kazuhiro; Ogawara, Ken-Ichi; Higaki, Kazutaka

    2013-09-01

    The aim of this study was to find out polymeric compounds that can inhibit the interaction between YM466, a novel anticoagulant, and bile to improve its oral bioavailability. In vitro ultrafiltration method using extract gall powder was useful to detect the formation of insoluble complex of YM466 with bile and also used to select a polymer that can inhibit the interaction between YM466 and bile. The in vitro studies revealed that aminoalkylmethacrylate (AAM) copolymer E, a polymethacrylate, dose-dependently inhibited the interaction between YM466 and bile and that this polymer could interact with bile salt, but not with YM466, possibly by electrostatic and/or hydrophobic interactions. The coadministration of AAM copolymer E with YM466 to rats dose-dependently increased the plasma concentration of YM466 and it was found that the oral dose of the polymer three times of YM466 (polymer to drug ratio in weight, P-D ratio, 3) significantly increased AUC0-1 h of YM466 to 2.6-fold of that of YM466 alone. Considering the condition of therapeutic use of YM466 and the maximum tolerated dose of the polymer, the formulation of P-D ratio 3 would be clinically practical and promising from the viewpoint of safety.

  4. Preparation and evaluation of ibuprofen-loaded microemulsion for improvement of oral bioavailability.

    PubMed

    Hu, Liandong; Yang, Jianxue; Liu, Wei; Li, Li

    2011-01-01

    The purpose of the current study was to improve the solubility of ibuprofen, a poorly water-soluble drug, in a microemulsion system that is suitable for oral administration. Microemulsion was prepared using different sorts of oils, surfactants, and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The formulations were characterized by solubility of the drug in the vehicle, droplet size, and drug release. The optimal formulation consists of 17% Labrafil M 1944CS, 28% Cremophor RH40/Transcutol P (3:1, w/w), and 55% water, with a maximum solubility of ibuprofen up to 60.3 mg/ml. The mean droplet size of microemulsion was 57 nm. The pharmacokinetic study of microemulsion was performed in rats and compared with granule formulation. The microemulsion has significantly increased the C(max) and area under the curve (AUC) compared to that of the granule (p < 0.05). The relative bioavailability of ibuprofen in microemulsions was 1.9-fold higher than that of the granule. These results indicated that this novel microemulsion is a useful formulation for enhancing the oral bioavailability of ibuprofen. PMID:20942639

  5. Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug.

    PubMed

    Funakoshi, Yuka; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2013-07-15

    A pharmacokinetic study was performed in rats to evaluate the oral absorption ratios of nanoparticle suspensions containing the poorly water-soluble compound nifedipine (NI) and two different types of lipids, including hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol. NI-lipid nanoparticle (LN) suspensions with a mean particle size of 48.0 nm and a zeta potential of -57.2 mV were prepared by co-grinding combined with a high-pressure homogenization process. The oral administration of NI-LN suspensions to rats led to a significant increase in the NI plasma concentration, and the area under the curve (AUC) value was found to be 108 min μg mL⁻¹, indicating a 4-fold increase relative to the NI suspensions. A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions. These results therefore indicated that lipid nanoparticles prepared using only two types of phospholipid with a mean particle size of less than 50 nm could improve the absorption of the poorly water-soluble drug.

  6. Modified-chitosan nanoparticles: Novel drug delivery systems improve oral bioavailability of doxorubicin.

    PubMed

    Khdair, Ayman; Hamad, Islam; Alkhatib, Hatim; Bustanji, Yasser; Mohammad, Mohammad; Tayem, Rabab; Aiedeh, Khaled

    2016-10-10

    The efficacy of most anticancer drugs is highly limited in vivo due mainly to poor pharmacokinetics behavior including poor bioavailability after extravascular administration. We have developed novel chitosan-modified polymeric nanoparticles for oral as well as i.v. administration. Nanoparticles were developed utilizing the double emulsion solvent evaporation technique for sustained delivery of various anticancer drugs. Chitosan diacetate (CDA) and chitosan triacetate (CTA) polymers were previously modified in our laboratory and used as novel matrix. Nanoparticles, loaded with various anticancer drugs, were characterized for particle size using dynamic light scattering as well as transmission electron microscopy and net surface charge using dynamic light scattering. Particles size was below 100nm in diameter and zeta potential ranged - (25-30). Encapsulation efficiency of anticancer drugs varied considerably and was dependent on the physicochemical characteristics of the encapsulated drug. However, chitosan triacetate nanoparticles showed relatively higher encapsulation efficiency than chitosan diacetate nanoparticles. In vitro release of encapsulated drugs was sustained over a period of 14days. Nanoparticles enhanced cellular accumulation of encapsulated drugs, compared to the free drugs, in vitro in MCF-7 and Caco-II tumor cell lines. In conclusion, diacetate and triacetate chitosan are novel polymers that can be used to formulate nanoparticles which efficiently encapsulated anticancer drugs, and sustained the release and enhanced tumor cellular uptake of these drugs. Further, chitosan triacetate nanoparticles enhanced oral bioavailability of doxorubicin. CDA and CTA nanoparticles can be used to efficiently deliver anticancer drugs and improve their in vivo profile. PMID:27473308

  7. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    PubMed Central

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele; Oprea, Tudor I.; Benet, Leslie Z.

    2012-01-01

    In modeling blood–brain barrier (BBB) passage, in silico models have yielded ~80% prediction accuracy, and are currently used in early drug discovery. Being derived from molecular structural information only, these models do not take into account the biological factors responsible for the in vivo outcome. Passive permeability and P-glycoprotein (Pgp, ABCB1) efflux have been successfully recognized to impact xenobiotic extrusion from the brain, as Pgp is known to play a role in limiting the BBB penetration of oral drugs in humans. However, these two properties alone fail to explain the BBB penetration for a significant number of marketed central nervous system (CNS) agents. The Biopharmaceutics Drug Disposition Classification System (BDDCS) has proved useful in predicting drug disposition in the human body, particularly in the liver and intestine. Here we discuss the value of using BDDCS to improve BBB predictions of oral drugs. BDDCS class membership was integrated with in vitro Pgp efflux and in silico permeability data to create a simple 3-step classification tree that accurately predicted CNS disposition for more than 90% of 153 drugs in our data set. About 98% of BDDCS class 1 drugs were found to markedly distribute throughout the brain; this includes a number of BDDCS class 1 drugs shown to be Pgp substrates. This new perspective provides a further interpretation of how Pgp influences the sedative effects of H1-histamine receptor antagonists. PMID:22261306

  8. Improving Oral Bioavailability of Sorafenib by Optimizing the "Spring" and "Parachute" Based on Molecular Interaction Mechanisms.

    PubMed

    Liu, Chengyu; Chen, Zhen; Chen, Yuejie; Lu, Jia; Li, Yuan; Wang, Shujing; Wu, Guoliang; Qian, Feng

    2016-02-01

    Sorafenib is a clinically important oral tyrosine kinase inhibitor for the treatment of various cancers. However, the oral bioavailability of sorafenib tablet (Nexavar) is merely 38-49% relative to the oral solution, due to the low aqueous solubility of sorafenib and its relatively high daily dose. It is desirable to improve the oral bioavailability of sorafenib to expand the therapeutic window, reduce the drug resistance, and enhance patient compliance. In this study, we observed that the solubility of sorafenib could be increased ∼50-fold in the coexistence of poly(vinylpyrrolidone-vinyl acetate) (PVP-VA) and sodium lauryl sulfate (SLS), due to the formation of PVP-VA/SLS complexes at a lower critical aggregation concentration. The enhanced solubility provided a faster initial sorafenib dissolution rate, analogous to a forceful "spring" to release drug into solution, from tablets containing both PVP-VA and SLS. However, SLS appears to impair the ability of PVP-VA to act as an efficient "parachute" to keep the drug in solution and maintain drug supersaturation. Using 2D (1)H NMR, (13)C NMR, and FT-IR analysis, we concluded that the solubility enhancement and supersaturation of sorafenib were achieved by PVP-VA/SLS complexes and PVP-VA/sorafenib interaction, respectively, both through molecular interactions hinged on the PVP-VA VA groups. Therefore, a balance between "spring" and "parachute" must be carefully considered in formulation design. To confirm the in vivo relevance of these molecular interaction mechanisms, we prepared three tablet formulations containing PVP-VA alone, SLS alone, and PVP-VA/SLS in combination. The USP II in vitro dissolution and dog pharmacokinetic in vivo evaluation showed clear differentiation between these three formulations, and also good in vitro-in vivo correlation. The formulation containing PVP-VA alone demonstrated the best bioavailability with 1.85-fold and 1.79-fold increases in Cmax and AUC, respectively, compared with the

  9. Improving Oral Bioavailability of Sorafenib by Optimizing the "Spring" and "Parachute" Based on Molecular Interaction Mechanisms.

    PubMed

    Liu, Chengyu; Chen, Zhen; Chen, Yuejie; Lu, Jia; Li, Yuan; Wang, Shujing; Wu, Guoliang; Qian, Feng

    2016-02-01

    Sorafenib is a clinically important oral tyrosine kinase inhibitor for the treatment of various cancers. However, the oral bioavailability of sorafenib tablet (Nexavar) is merely 38-49% relative to the oral solution, due to the low aqueous solubility of sorafenib and its relatively high daily dose. It is desirable to improve the oral bioavailability of sorafenib to expand the therapeutic window, reduce the drug resistance, and enhance patient compliance. In this study, we observed that the solubility of sorafenib could be increased ∼50-fold in the coexistence of poly(vinylpyrrolidone-vinyl acetate) (PVP-VA) and sodium lauryl sulfate (SLS), due to the formation of PVP-VA/SLS complexes at a lower critical aggregation concentration. The enhanced solubility provided a faster initial sorafenib dissolution rate, analogous to a forceful "spring" to release drug into solution, from tablets containing both PVP-VA and SLS. However, SLS appears to impair the ability of PVP-VA to act as an efficient "parachute" to keep the drug in solution and maintain drug supersaturation. Using 2D (1)H NMR, (13)C NMR, and FT-IR analysis, we concluded that the solubility enhancement and supersaturation of sorafenib were achieved by PVP-VA/SLS complexes and PVP-VA/sorafenib interaction, respectively, both through molecular interactions hinged on the PVP-VA VA groups. Therefore, a balance between "spring" and "parachute" must be carefully considered in formulation design. To confirm the in vivo relevance of these molecular interaction mechanisms, we prepared three tablet formulations containing PVP-VA alone, SLS alone, and PVP-VA/SLS in combination. The USP II in vitro dissolution and dog pharmacokinetic in vivo evaluation showed clear differentiation between these three formulations, and also good in vitro-in vivo correlation. The formulation containing PVP-VA alone demonstrated the best bioavailability with 1.85-fold and 1.79-fold increases in Cmax and AUC, respectively, compared with the

  10. Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice.

    PubMed

    Ejaz, Asma; Martinez-Guino, Laura; Goldfine, Allison B; Ribas-Aulinas, Francesc; De Nigris, Valeria; Ribó, Sílvia; Gonzalez-Franquesa, Alba; Garcia-Roves, Pablo M; Li, Elizabeth; Dreyfuss, Jonathan M; Gall, Walt; Kim, Jason K; Bottiglieri, Teodoro; Villarroya, Francesc; Gerszten, Robert E; Patti, Mary-Elizabeth; Lerin, Carles

    2016-04-01

    Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans. PMID:26858359

  11. G protein-coupled receptors: signalling and regulation by lipid agonists for improved glucose homoeostasis.

    PubMed

    Moran, Brian M; Flatt, Peter R; McKillop, Aine M

    2016-04-01

    G protein-coupled receptors (GPCRs) play a pivotal role in cell signalling, controlling many processes such as immunity, growth, cellular differentiation, neurological pathways and hormone secretions. Fatty acid agonists are increasingly recognised as having a key role in the regulation of glucose homoeostasis via stimulation of islet and gastrointestinal GPCRs. Downstream cell signalling results in modulation of the biosynthesis, secretion, proliferation and anti-apoptotic pathways of islet and enteroendocrine cells. GPR40 and GPR120 are activated by long-chain fatty acids (>C12) with both receptors coupling to the Gαq subunit that activates the Ca(2+)-dependent pathway. GPR41 and GPR43 are stimulated by short-chain fatty acids (C2-C5), and activation results in binding to Gαi that inhibits the adenylyl cyclase pathway attenuating cAMP production. In addition, GPR43 also couples to the Gαq subunit augmenting intracellular Ca(2+) and activating phospholipase C. GPR55 is specific for cannabinoid endogenous agonists (endocannabinoids) and non-cannabinoid fatty acids, which couples to Gα12/13 and Gαq proteins, leading to enhancing intracellular Ca(2+), extracellular signal-regulated kinase 1/2 (ERK) phosphorylation and Rho kinase. GPR119 is activated by fatty acid ethanolamides and binds to Gαs utilising the adenylate cyclase pathway, which is dependent upon protein kinase A. Current research indicates that GPCR therapies may be approved for clinical use in the near future. This review focuses on the recent advances in preclinical diabetes research in the signalling and regulation of GPCRs on islet and enteroendocrine cells involved in glucose homoeostasis.

  12. Improving the Safety of Oral Chemotherapy at an Academic Medical Center

    PubMed Central

    Casella, Erica; Capozzi, Donna; McGettigan, Suzanne; Gangadhar, Tara C.; Schuchter, Lynn; Myers, Jennifer S.

    2016-01-01

    Purpose: Over the last decade, the use of oral chemotherapy (OC) for the treatment of cancer has dramatically increased. Despite their route of administration, OCs pose many of the same risks as intravenous agents. In this quality improvement project, we sought to examine our current process for the prescription of OC at the Abramson Cancer Center of the University of Pennsylvania and to improve on its safety. Methods: A multidisciplinary team that included oncologists, advanced-practice providers, and pharmacists was formed to analyze the current state of our OC practice. Using Lean Six Sigma quality improvement tools, we identified a lack of pharmacist review of the OC prescription as an area for improvement. To address these deficiencies, we used our electronic medical system to route OC orders placed by treating providers to an oncology-specific outpatient pharmacist at the Abramson Cancer Center for review. Results: Over 7 months, 63 orders for OC were placed for 45 individual patients. Of the 63 orders, all were reviewed by pharmacists, and, as a result, 22 interventions were made (35%). Types of interventions included dosage adjustment (one of 22), identification of an interacting drug (nine of 22), and recommendations for additional drug monitoring (12 of 22). Conclusion: OC poses many of the same risks as intravenous chemotherapy and should be prescribed and reviewed with the same oversight. At our institution, involvement of an oncology-trained pharmacist in the review of OC led to meaningful interventions in one third of the orders. PMID:26733627

  13. The Importance of Oral Communication Skills and a Graduate Course to Help Improve These Skills

    ERIC Educational Resources Information Center

    Wilkes, Garth L.

    2012-01-01

    This article addresses the importance of oral communication and many of its fundamental underlying principles. Emphasis is placed on oral presentations, particularly those used in science and engineering. Following this, the author provides a brief outline of an elective graduate level oral communications course that was developed and utilized to…

  14. The effects of targeting improvements in urine glucose on metabolic control in children with insulin dependent diabetes.

    PubMed

    Epstein, L H; Beck, S; Figueroa, J; Farkas, G; Kazdin, A E; Daneman, D; Becker, D

    1981-01-01

    A treatment program designed to increase the percentage of negative urine tests was implemented using a multiple-baseline across groups design in a sample of 19 families of children with insulin dependent diabetes. The treatment involved instruction in insulin adjustment, decrease in intake of simple sugars and saturated fats, and increase in exercise, along with teaching the parents to support improvements in children's self-regulatory behaviors using a point economy and praise. New procedures designed to measure and reinforce adherence to the urine testing regimen were developed. Results showed significant increases in percentage of negative urines consistent with implementation of treatment across the three treatment groups, which were maintained over the follow-up period. Metabolic measures of control, including glycosylated hemoglobin and serum glucose did not show improvements even though the relationship between the percentage of negative urine tests and glycosylated hemoglobin was very high during treatment.

  15. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics

    PubMed Central

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  16. The oral glucose tolerance test for the diagnosis of diabetes mellitus in patients during acute coronary syndrome hospitalization: a meta-analysis of diagnostic test accuracy

    PubMed Central

    2012-01-01

    Background The appropriateness of the routine performance of an oral glucose tolerance test (OGTT) to screen for diabetes mellitus (DM) during acute coronary syndrome hospitalization is still under debate. Methods A systematic search of databases (MEDLINE [1985 to March 2012], EMBASE [1985 to March 2012]) was conducted. All prospective cohort studies assessing the accuracy or reproducibility of an OGTT in ACS or non-ACS individuals were included. A bivariate model was used to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was explored using subgroup analysis and meta-regression. Results Fifteen studies with 8,027 participants were included (10 ACS and 5 non-ACS studies). The pooled results on SEN, SPE, PLR, NLR, and DOR were 0.70 (95% CI, 0.60-0.78), 0.91 (95% CI, 0.86-0.94), 7.6 (95% CI, 4.9-11.7), 0.33 (95% CI, 0.25-0.45), and 23 (95% CI, 12–41), respectively. The OGTT has a slightly lower SPE in diagnosing DM in ACS than in non-ACS patients (0.86 [95% CI 0.81-0.92] versus 0.95 [95% CI 0.93-0.98], p<0.01), while the SEN values are comparable (0.71 [95% CI 0.60-0.82] versus 0.67 [95% CI 0.54-0.81], p=0.43). After adjusting the interval between repeated tests and age, the meta-regression did not show a difference in DOR between ACS and non-ACS studies. Conclusions Despite the discrepancy in the interval between the two OGTTs, performing an OGTT in patients with ACS provides accuracy that is similar to that in in non-ACS patients. It is reasonable to screen patients hospitalized for ACS for previously undiagnosed DM using an OGTT. PMID:23270530

  17. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.

    PubMed

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  18. North Carolina physician-based preventive oral health services improve access and use among young Medicaid enrollees.

    PubMed

    Kranz, Ashley M; Lee, Jessica; Divaris, Kimon; Baker, A Diane; Vann, William

    2014-12-01

    To combat disparities in oral health and access to dental care among infants and toddlers, most state Medicaid programs now reimburse physician-based preventive oral health services such as fluoride varnish applications. We used geospatial data to examine the distribution of dental and medical Medicaid providers of pediatric oral health services throughout North Carolina to determine if these services have improved access to care for Medicaid enrollees younger than age three. We then used claims data to examine the association between distance from these practices and use of dental services for a cohort of approximately 1,000 young children. Among one hundred counties, four counties had no physician-based preventive oral health services, and nine counties had no dental practice. While children who lived farther from the nearest dental practice were less likely to make dental visits, distance from physician-based preventive oral health services did not predict utilization. For young Medicaid enrollees, oral health services provided in medical offices can improve access and increase utilization.

  19. [Application of diversified teaching methods to improve the teaching effects in the course of oral histology and pathology].

    PubMed

    Tian, Zhen; Li, Lei; Wang, Li-zhen; Hu, Yu-hua; Zhang, Chun-ye; Li, Jiang

    2016-02-01

    Oral histology and pathology is one of the most important courses in stomatological education which works as a bridge between basic medical courses and clinical courses of oral science. The knowledge of oral histopathology may help the students to correctly understand the histogenesis and development of oral diseases and provide the information for correct treatment and prevention. In order to make the students grasp the necessary basic theories, increase the interest in learning, and improve the teaching effect, we explored a diversified teaching system which included diverse teaching modes, online courses and courseware construction. The application of this system offered the interaction between students and teachers and combination of classes with the internet, and made the boring pathological knowledge be associated with clinical practice. These diversified teaching methods had been used in practice and obtained good teaching results.

  20. [Application of diversified teaching methods to improve the teaching effects in the course of oral histology and pathology].

    PubMed

    Tian, Zhen; Li, Lei; Wang, Li-zhen; Hu, Yu-hua; Zhang, Chun-ye; Li, Jiang

    2016-02-01

    Oral histology and pathology is one of the most important courses in stomatological education which works as a bridge between basic medical courses and clinical courses of oral science. The knowledge of oral histopathology may help the students to correctly understand the histogenesis and development of oral diseases and provide the information for correct treatment and prevention. In order to make the students grasp the necessary basic theories, increase the interest in learning, and improve the teaching effect, we explored a diversified teaching system which included diverse teaching modes, online courses and courseware construction. The application of this system offered the interaction between students and teachers and combination of classes with the internet, and made the boring pathological knowledge be associated with clinical practice. These diversified teaching methods had been used in practice and obtained good teaching results. PMID:27063324

  1. Zinc-fortified oral rehydration solution improved intestinal permeability and small intestinal mucosal recovery.

    PubMed

    Tran, Cuong D; Hawkes, Joanna; Graham, Robin D; Kitchen, Julie L; Symonds, Erin L; Davidson, Geoffrey P; Butler, Ross N

    2015-06-01

    A randomized double-blind placebo-controlled study was conducted in children admitted to hospital with gastroenteritis (≥3 loose stools per day). All were treated for 5 days following admission with either zinc (Zn, 3 mg) or without Zn-fortified rice-based oral rehydration solution (ORS). (13)C-sucrose breath test (SBT) and intestinal permeability (lactulose/rhamnose or L/R ratio) were performed concurrently prior to commencement of ORS with or without Zn and at day 5 post-admission. There was a significant improvement in the SBT results in both the Zn-fortified group, median (5th-95th percentile) 2.1% (0.4% to 8.3%) versus 4.4% (0.4% to 10.4%), P < .05, and control group, 1.4% (0.1% to 5.4%) versus 4.3% (0.4% to 11.4%), P < .05, between the day of admission and day 5 post-admission. In the Zn-fortified group, there was also a significant improvement in L/R ratio between the day of admission and day 5 post-admission, 53.0 (19.5-90.6) versus 17.7 (13.4-83.2), P < .05. Low levels of Zn improved intestinal permeability but did not enhance short-term recovery following diarrheal illness.

  2. Polyacetylenes from carrots (Daucus carota) improve glucose uptake in vitro in adipocytes and myotubes.

    PubMed

    El-Houri, Rime B; Kotowska, Dorota; Christensen, Kathrine B; Bhattacharya, Sumangala; Oksbjerg, Niels; Wolber, Gerhard; Kristiansen, Karsten; Christensen, Lars P

    2015-07-01

    A dichloromethane (DCM) extract of carrot roots was found to stimulate insulin-dependent glucose uptake (GU) in adipocytes in a dose dependent manner. Bioassay-guided fractionation of the DCM extract resulted in the isolation of the polyacetylenes falcarinol and falcarindiol. Both polyacetylenes were able to significantly stimulate basal and/or insulin-dependent GU in 3T3-L1 adipocytes and porcine myotube cell cultures in a dose-dependent manner. Falcarindiol increased peroxisome proliferator-activated receptor (PPAR)γ-mediated transactivation significantly at concentrations of 3, 10 and 30 μM, while PPARγ-mediated transactivation by falcarinol was only observed at 10 μM. Docking studies accordingly indicated that falcarindiol binds to the ligand binding domain of PPARγ with higher affinity than falcarinol and that both polyacetylenes exhibit characteristics of PPARγ partial agonists. Falcarinol was shown to inhibit adipocyte differentiation as evident by gene expression studies and Oil Red O staining, whereas falcarindiol did not inhibit adipocyte differentiation, which indicates that these polyacetylenes have distinct modes of action. The results of the present study suggest that falcarinol and falcarindiol may represent scaffolds for novel partial PPARγ agonists with possible antidiabetic properties.

  3. Polyacetylenes from carrots (Daucus carota) improve glucose uptake in vitro in adipocytes and myotubes.

    PubMed

    El-Houri, Rime B; Kotowska, Dorota; Christensen, Kathrine B; Bhattacharya, Sumangala; Oksbjerg, Niels; Wolber, Gerhard; Kristiansen, Karsten; Christensen, Lars P

    2015-07-01

    A dichloromethane (DCM) extract of carrot roots was found to stimulate insulin-dependent glucose uptake (GU) in adipocytes in a dose dependent manner. Bioassay-guided fractionation of the DCM extract resulted in the isolation of the polyacetylenes falcarinol and falcarindiol. Both polyacetylenes were able to significantly stimulate basal and/or insulin-dependent GU in 3T3-L1 adipocytes and porcine myotube cell cultures in a dose-dependent manner. Falcarindiol increased peroxisome proliferator-activated receptor (PPAR)γ-mediated transactivation significantly at concentrations of 3, 10 and 30 μM, while PPARγ-mediated transactivation by falcarinol was only observed at 10 μM. Docking studies accordingly indicated that falcarindiol binds to the ligand binding domain of PPARγ with higher affinity than falcarinol and that both polyacetylenes exhibit characteristics of PPARγ partial agonists. Falcarinol was shown to inhibit adipocyte differentiation as evident by gene expression studies and Oil Red O staining, whereas falcarindiol did not inhibit adipocyte differentiation, which indicates that these polyacetylenes have distinct modes of action. The results of the present study suggest that falcarinol and falcarindiol may represent scaffolds for novel partial PPARγ agonists with possible antidiabetic properties. PMID:25970571

  4. Intestinal-borne dermatoses significantly improved by oral application of Escherichia coli Nissle 1917

    PubMed Central

    Manzhalii, Elina; Hornuss, Daniel; Stremmel, Wolfgang

    2016-01-01

    AIM: To evaluate the effect of oral Escherichia coli (E. coli) Nissle application on the outcome of intestinal-borne dermatoses. METHODS: In a randomized, controlled, non-blinded prospective clinical trial 82 patients with intestinal-borne facial dermatoses characterized by an erythematous papular-pustular rash were screened. At the initiation visit 37 patients entered the experimental arm and 20 patients constituted the control arm. All 57 patients were treated with a vegetarian diet and conventional topical therapy of the dermatoses with ointments containing tetracycline, steroids and retinoids. In the experimental arm patients received a one month therapy with oral E. coli Nissle at a maintenance dose of 2 capsules daily. The experimental group was compared to a non-treatment group only receiving the diet and topical therapy. The primary outcome parameter was improvement of the dermatoses, secondary parameters included life quality and adverse events. In addition the immunological reaction profile (IgA, interleucin-8 and interferon-α) was determined. Furthermore the changes of stool consistency and the microbiota composition over the time of intervention were recorded. RESULTS: Eighty-nine percent of the patients with acne, papular-pustular rosacea and seborrhoic dermatitis responded to E. coli Nissle therapy with significant amelioration or complete recovery in contrast to 56% in the control arm (P < 0.01). Accordingly, in the E. coli Nissle treated patients life quality improved significantly (P < 0.01), and adverse events were not recorded. The clinical improvement was associated with a significant increase of IgA levels to normal values in serum as well as suppression of the proinflammatory cytokine IL-8 (P < 0.01 for both parameters). In the E. coli Nissle treated group a shift towards a protective microbiota with predominance of bifidobacteria and lactobacteria (> 107 CFU/g stool) was observed in 79% and 63% of the patients, respectively (P < 0

  5. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

    SciTech Connect

    Wright, Catherine S.; Berends, Rebecca F.; Flint, David J.; Martin, Patricia E.M.

    2013-02-15

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ► Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ► Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ► IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ► Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.

  6. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice

    PubMed Central

    DiSilvestro, David J.; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L. James; Kalyanasundaram, Anuradha; Gilor, Chen L.; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  7. Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight.

    PubMed

    Li, Yong-Qi; Shrestha, Yogendra B; Chen, Min; Chanturiya, Tatyana; Gavrilova, Oksana; Weinstein, Lee S

    2016-01-12

    Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight. PMID:26712027

  8. Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight

    PubMed Central

    Li, Yong-Qi; Shrestha, Yogendra B.; Chen, Min; Chanturiya, Tatyana; Gavrilova, Oksana; Weinstein, Lee S.

    2016-01-01

    Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight. PMID:26712027

  9. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    PubMed

    DiSilvestro, David J; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L James; Kalyanasundaram, Anuradha; Gilor, Chen L; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  10. Serum Bile Acids Are Higher in Humans With Prior Gastric Bypass: Potential Contribution to Improved Glucose and Lipid Metabolism

    PubMed Central

    Patti, Mary-Elizabeth; Houten, Sander M.; Bianco, Antonio C.; Bernier, Raquel; Larsen, P. Reed; Holst, Jens J.; Badman, Michael K.; Maratos-Flier, Eleftheria; Mun, Edward C.; Pihlajamaki, Jussi; Auwerx, Johan; Goldfine, Allison B.

    2015-01-01

    The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 ± 4.84 µmol/l) than in both overweight (3.59 ± 1.95, P = 0.005, Ov) and severely obese (3.86 ± 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P < 0.05). Total bile acids were inversely correlated with 2-h post-meal glucose (r = −0.59, P < 0.003) and fasting triglycerides (r = −0.40, P = 0.05), and positively correlated with adiponectin (r = −0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = −0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB. PMID:19360006

  11. Internet-Based Contingency Management to Improve Adherence with Blood Glucose Testing Recommendations for Teens with Type 1 Diabetes

    ERIC Educational Resources Information Center

    Raiff, Bethany R.; Dallery, Jesse

    2010-01-01

    The current study used Internet-based contingency management (CM) to increase adherence with blood glucose testing to at least 4 times daily. Four teens diagnosed with Type 1 diabetes earned vouchers for submitting blood glucose testing videos over a Web site. Participants submitted a mean of 1.7 and 3.1 blood glucose tests per day during the 2…

  12. Non-dental primary care providers’ views on challenges in providing oral health services and strategies to improve oral health in Australian rural and remote communities: a qualitative study

    PubMed Central

    Barnett, Tony; Hoang, Ha; Stuart, Jackie; Crocombe, Len

    2015-01-01

    Objectives To investigate the challenges of providing oral health advice/treatment as experienced by non-dental primary care providers in rural and remote areas with no resident dentist, and their views on ways in which oral health and oral health services could be improved for their communities. Design Qualitative study with semistructured interviews and thematic analysis. Setting Four remote communities in outback Queensland, Australia. Participants 35 primary care providers who had experience in providing oral health advice to patients and four dental care providers who had provided oral health services to patients from the four communities. Results In the absence of a resident dentist, rural and remote residents did present to non-dental primary care providers with oral health problems such as toothache, abscess, oral/gum infection and sore mouth for treatment and advice. Themes emerged from the interview data around communication challenges and strategies to improve oral health. Although, non-dental care providers commonly advised patients to see a dentist, they rarely communicated with the dentist in the nearest regional town. Participants proposed that oral health could be improved by: enabling access to dental practitioners, educating communities on preventive oral healthcare, and building the skills and knowledge base of non-dental primary care providers in the field of oral health. Conclusions Prevention is a cornerstone to better oral health in rural and remote communities as well as in more urbanised communities. Strategies to improve the provision of dental services by either visiting or resident dental practitioners should include scope to provide community-based oral health promotion activities, and to engage more closely with other primary care service providers in these small communities. PMID:26515687

  13. Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients.

    PubMed

    Bossola, Maurizio; Giungi, Stefania; Tazza, Luigi; Luciani, Giovanna

    2007-01-01

    Metabolic acidosis, a frequent event in hemodialysis patients, has been implicated as a potential cause of protein-energy malnutrition. Unfortunately, correction of metabolic acidosis by means of high bicarbonate concentration in the dialysate does not seem to lead to significant changes in nutritional parameters. The project was a single-arm, open-label, 12-month pilot study at a university-based tertiary care center aimed at evaluating whether correction of metabolic acidosis through long-term oral sodium bicarbonate supplementation improves serum albumin levels and other nutritional parameters in patients undergoing maintenance hemodialysis. Twenty highly acidotic hemodialysis patients patients were invited to consume an oral supplementation of sodium bicarbonate (1 g, thrice daily), for 12 months. Patients were followed at baseline and every month, until month 12. At each follow-up visit, dry body weight, BMI, blood pressure, presence of edema, venous bicarbonate, and serum albumin were measured. Total lymphocyte count, fasting total cholesterol and C-reactive protein were assessed every 2 months. At baseline and at 12 months, the subjective global assessment of nutritional status and the protein equivalent of nitrogen appearance normalized to actual body weight were determined. Plasma bicarbonate level rose from 18.1 +/- 2.7 to 22.1 +/- 4.5 mmol/l after 10 months (p = 0.001). Mean serum albumin levels were 3.8 +/- 0.2 mg/dl at baseline and 3.9 +/- 0.2 at the end of the study. Repeated measure ANOVA showed that there was no significant effect of bicarbonate treatment on serum albumin levels (p = 0.29), dry weight (p = 0.1), serum total cholesterol (p = 0.97), total lymphocyte count (p = 0.69), or C-reactive protein (p = 0.85). Mean subjective global assessment score was 4.53 +/- 0.37 at baseline and 4.58 +/- 0.54 at 12 months (p = 0.1). Mean nPNA (g/kg/day) was 0.86 +/- 0.05 at baseline and 0.85 +/- 0.08 at month 12. The present study demonstrates that long

  14. [A case of infective endocarditis (IE) improving with orally administered amoxicillin (AMPC)].

    PubMed

    Sakaki, T; Dotsu, Y; Masuyama, Y; Inoue, Y; Ishiguro, M; Koga, H; Hayashi, T; Kohno, S; Yamaguchi, K; Imamura, T

    1989-04-01

    Progress in chemotherapy and cardiosurgery has remarkably decreased the mortality due to infective endocarditis (IE) in recent years. In chemotherapy for IE, parental administration of antibiotics has been used routinely, the patients suffer from the psychological and physiological burden due to frequent injections and long period of therapy, even though the therapy for IE is successful. In this report, we present a case of IE caused by S. mitis, which was remarkably improved by oral administration of AMPC. A case, 69. y.o. female. She felt like a common cold and visited a G.P. Cardiomegaly was pointed out and positive inflammatory findings in serological examination were found. A low grade fever continued, and she was admitted to the hospital. Blood cultures were positive for S. mitis. For further examination, she was transferred to the university hospital. Based on the extensive blood cultures and cardioechogram, she was diagnosed IE caused by S. mitis. Because there were no symptoms of heart failure, we decided to try oral administration of AMPC, 4 g/day or 6 g/day at an interval of 6 hours. On the second day of therapy, the blood culture turned to be negative for pathogens, and on the fourth day body temperature became normal. On about the 60th day, the CRP finding became negative. Concentrations in the serum of AMPC were more than 10 folds of AMPC-MIC (0.5 microgram/ml) for S. mitis. The patient, however, suffer from complications of lung embolism and was operated for exchange of heart valves. After surgery, she has been well without any symptoms from IE. PMID:2506299

  15. Oral Administration of Fermented Probiotics Improves the Condition of Feces in Adult Horses

    PubMed Central

    ISHIZAKA, Saori; MATSUDA, Akira; AMAGAI, Yosuke; OIDA, Kumiko; JANG, Hyosun; UEDA, Yuko; TAKAI, Masaki; TANAKA, Akane; MATSUDA, Hiroshi

    2014-01-01

    ABSTRACT The effects of probiotics on horses are still controversial. The present study was a randomized, double-blinded, placebo-controlled crossover study designed to evaluate the ability of probiotics to improve intestinal conditions in adult horses. Fermented probiotics were administered to 10 healthy adult geldings for 28 days. The clinical condition of the horses was monitored daily, and the blood and feces were biochemically analyzed every 14 days. In the probiotic-treated group, the concentration of carboxylic acids in the feces was increased at days 14 and 28. In contrast to the fecal pH in the control group, which increased at days 14 and 28, the fecal pH in the probiotic-treated group did not increase. Additionally, the relative amounts of enteropathogenic bacterial DNA were diminished in the probiotic-treated group. These results suggest that probiotic bacteria proliferated in the equine intestine. No instances of abnormal clinical conditions or abnormal values in blood tests were observed throughout the study. Oral administration of fermented probiotics may have the ability to improve the intestinal environment biochemically and microbiologically without the risk of adverse effects. PMID:25558179

  16. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice.

    PubMed

    Tomimoto, Daisuke; Okuma, Chihiro; Ishii, Yukihito; Kobayashi, Akio; Ohta, Takeshi; Kakutani, Makoto; Imanaka, Tsuneo; Ogawa, Nobuya

    2015-09-01

    Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet-induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT-553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-α mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight.

  17. A Pacifier-Activated Music Player With Mother’s Voice Improves Oral Feeding in Preterm Infants

    PubMed Central

    Chorna, Olena D.; Slaughter, James C.; Wang, Lulu; Stark, Ann R.

    2014-01-01

    OBJECTIVES: We conducted a randomized trial to test the hypothesis that mother’s voice played through a pacifier-activated music player (PAM) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants. METHODS: Preterm infants between 34 0/7 and 35 6/7 weeks’ postmenstrual age, including those with brain injury, who were taking at least half their feedings enterally and less than half orally, were randomly assigned to receive 5 daily 15-minute sessions of either PAM with mother’s recorded voice or no PAM, along with routine nonnutritive sucking and maternal care in both groups. Assignment was masked to the clinical team. RESULTS: Ninety-four infants (46 and 48 in the PAM intervention and control groups, respectively) completed the study. The intervention group had significantly increased oral feeding rate (2.0 vs 0.9 mL/min, P < .001), oral volume intake (91.1 vs 48.1 mL/kg/d, P = .001), oral feeds/day (6.5 vs 4.0, P < .001), and faster time-to-full oral feedings (31 vs 38 d, P = .04) compared with controls. Weight gain and cortisol levels during the 5-day protocol were not different between groups. Average hospital stays were 20% shorter in the PAM group, but the difference was not significant (P = .07). CONCLUSIONS: A PAM using mother’s voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth. PMID:24534413

  18. VISP 2.0: Methodological Considerations for the Design and Implementation of an Audiodescription Based App to Improve Oral Skills

    ERIC Educational Resources Information Center

    Ibáñez Moreno, Ana; Vermeulen, Anna

    2015-01-01

    In this paper the methodological steps taken in the conception of a new mobile application (app) are introduced. This app, called VISP (Videos for Speaking), is easily accessible and manageable, and is aimed at helping students of English as a Foreign Language (EFL) to improve their idiomaticity in their oral production. In order to do so, the app…

  19. Comparison of Two Oral Reading Feedback Strategies in Improving Reading Comprehension of School-Age Children with Low Reading Ability

    ERIC Educational Resources Information Center

    Crowe, Linda K.

    2005-01-01

    This study compared the effects of two oral reading feedback strategies in improving the reading comprehension of eight school-age children with low reading ability. Participants were assigned to one of two intervention groups matched on age, grade, gender, and general reading performance. Intervention 1 (I1) used traditional decoding-based…

  20. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    PubMed

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance. PMID:20660065

  1. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    PubMed

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance.

  2. Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

    PubMed Central

    Kaplon, Rachelle E.; Hill, Sierra D.; Bispham, Nina Z.; Santos-Parker, Jessica R.; Nowlan, Molly J.; Snyder, Laura L.; Chonchol, Michel; LaRocca, Thomas J.; McQueen, Matthew B.; Seals, Douglas R.

    2016-01-01

    We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass<2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ∼30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ∼30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass≥2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO. PMID:27208415

  3. Improved Safety, Bioavailability and Pharmacokinetics of Zidovudine through Lactoferrin Nanoparticles during Oral Administration in Rats

    PubMed Central

    C., Bhaskar; Golla, Kishore; Kondapi, Anand K.

    2015-01-01

    Zidovudine (AZT) is one of the most referred antiretroviral drug. In spite of its higher bioavailability (50–75%) the most important reason of its cessation are bone marrow suppression, anemia, neutropenia and various organs related toxicities. This study aims at the improvement of oral delivery of AZT through its encapsulation in lactoferrin nanoparticles (AZT-lactonano). The nanoparticles (NPs) are of 50–60 nm in size and exhibit 67% encapsulation of the AZT. They are stable in simulated gastric and intestinal fluids. Anti-HIV-1 activity of AZT remains unaltered in nanoformulation in acute infection. The bioavailability and tissue distribution of AZT is higher in blood followed by liver and kidney. AZT-lactonano causes the improvement of pharmacokinetic profile as compared to soluble AZT; a more than 4 fold increase in AUC and AUMC in male and female rats. The serum Cmax for AZT-lactonano was increased by 30%. Similarly there was nearly 2-fold increase in Tmax and t1/2. Our in vitro study confirms that, the endosomal pH is ideal for drug release from NPs and shows constant release from up to 96h. Bone marrow micronucleus assay show that nanoformulation exhibits approximately 2fold lower toxicity than soluble form. Histopathological and biochemical analysis further confirms that less or no significant organ toxicities when nanoparticles were used. AZT-lactonano has shown its higher efficacy, low organs related toxicities, improved pharmacokinetics parameter while keeping the antiviral activity intact. Thus, the nanoformulation are safe for the target specific drug delivery. PMID:26461917

  4. Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults.

    PubMed

    Kaplon, Rachelle E; Hill, Sierra D; Bispham, Nina Z; Santos-Parker, Jessica R; Nowlan, Molly J; Snyder, Laura L; Chonchol, Michel; LaRocca, Thomas J; McQueen, Matthew B; Seals, Douglas R

    2016-06-01

    We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass less than 2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ~30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ~30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass ≥ 2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO. PMID:27208415

  5. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy.

    PubMed

    Connolly, Anne M; Schierbecker, Jeanine; Renna, Renee; Florence, Julaine

    2002-12-01

    Daily prednisone improves strength in boys with Duchenne muscular dystrophy, but side effects are almost universal. We used a different dosing regimen of prednisone to determine if benefit to boys with Duchenne muscular dystrophy might be maintained with fewer side effects. Twice weekly oral prednisone was given each Friday and Saturday (5mg/kg/dose). This total dose is twice as high as the daily low dosage prednisone regimen (0.75 mg/kg/day). Twenty boys (8.0+/-1.2 years) were treated. Historical control groups included 18 untreated boys (6.1+/-1.6 years) and four boys (7.3+/-0.6 years) treated with daily prednisone. Strength (using a hand-held manometer and grip meter) and timed functional testing were measured. There was an improvement in upper extremity strength for 95% of boys (n=20) at 6 months using quantitative strength testing. Improvement in lower extremity strength occurred in all boys with antigravity quadriceps strength (17/17). The improvement (P=0.001 for proximal upper extremities; P=0.002 for grip; and P<0.0001 for proximal lower extremities) was significant compared to untreated boys. Sixteen boys were treated continuously for more than 12 months (22+/-1.5 months). Of these, 15 remained significantly stronger than prior to treatment and 8/16 showed additional gains in strength after six months of treatment. Six boys were on the weekly prednisolone 2 years or longer without interruption. All six had upper and lower extremity strength at follow-up that was as good or better than at baseline. Functional testing improved in boys less than 8 years without contractures. Three boys without antigravity quadriceps strength at the start of treatment lost the ability to walk unassisted within 6 months. Eight other boys lost the ability to ambulate unassisted between 12 and 24 months of treatment. In each, progressive contractures developed. Linear growth was maintained in all boys on weekly treatment. Obesity rates did not differ from untreated boys. Twice

  6. Evidence-Based Health Promotion in Nursing Homes: A Pilot Intervention to Improve Oral Health

    ERIC Educational Resources Information Center

    Cadet, Tamara J.; Berrett-Abebe, Julie; Burke, Shanna L.; Bakk, Louanne; Kalenderian, Elsbeth; Maramaldi, Peter

    2016-01-01

    Nursing home residents over the age of 65 years are at high risk for poor oral health and related complications such as pneumonia and adverse diabetes outcomes. A preliminary study found that Massachusetts' nursing homes generally lack the training and resources needed to provide adequate oral health care to residents. In this study, an…

  7. Potential of Text-Based Internet Chats for Improving Oral Fluency in a Second Language

    ERIC Educational Resources Information Center

    Blake, Christopher

    2009-01-01

    Although a number of studies have reported on the positive effects of Internet chats in the second language classroom, to the best of my knowledge no studies to date have examined the effect of text-based chats on oral fluency development. This exploratory study addressed the above question by examining the oral fluency development of 34 English…

  8. Improving Professionalism in the Engineering Curriculum through a Novel Use of Oral Presentations

    ERIC Educational Resources Information Center

    Berjano, Enrique; Sales-Nebot, Laura; Lozano-Nieto, Albert

    2013-01-01

    This hypothesis is based on the fact that oral presentations in the context of engineering education could be used not only to develop oral communication skills but also to augment the professionalism in the curriculum. The methodological innovation is first described, which allows encouraging the capacity of summarising ideas, teamwork,…

  9. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    SciTech Connect

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  10. Oral administration of an immunostimulatory DNA sequence from Bifidobacterium longum improves Th1/Th2 balance in a murine model.

    PubMed

    Takahashi, Noritoshi; Kitazawa, Haruki; Iwabuchi, Noriyuki; Xiao, Jin-Zhong; Miyaji, Kazuhiro; Iwatsuki, Keiji; Saito, Tadao

    2006-08-01

    We have reported the antiallergic activities of the immunostimulatory oligodeoxynucleotide (ODN) BL07S, identified from genomic DNA of Bifidobacterium longum BB536 from in vitro and in vivo studies. The present study evaluated the efficiency of ODN BL07S in preventing allergic responses by oral administration. Oral administration of BL07S suppressed serum ovalbumin (OVA)-specific immunoglobulin (Ig) E levels and improved the OVA-specific IgG2a/IgG1 ratio. ODN BL07S increased Th1 cytokine and decreased Th2 cytokine production in splenocytes. These results suggest that immunostimulatory ODNs are potentially associated with the antiallergic effects of probiotics.

  11. Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo.

    PubMed

    Mou, K H; Han, D; Liu, W L; Li, P

    2016-07-25

    Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable. PMID:27464024

  12. Improvement of oral bioavailability of lovastatin by using nanostructured lipid carriers

    PubMed Central

    Zhou, Jun; Zhou, Daxin

    2015-01-01

    Nanostructured lipid carriers (NLCs) have been one of the systems of choice for improving the oral bioavailability of drugs with poor water solubility. In the present study, lovastatin (LVT)-loaded NLCs (LVT-NLCs) were successfully prepared by hot high-pressure homogenization method with high entrapment efficiency, drug loading, and satisfactory particle size distribution. The particles had almost spherical and uniform shapes and were well dispersed with a particle size of <50 nm (23.5±1.6 nm) and a low polydispersity index (0.17±0.05 mV). The result of stability showed that the LVT-NLCs dispersion maintained excellent stability without exhibiting any aggregation, precipitation, or phase separation at 4°C for 6 months of storage. The LVT release data from all developed solid lipid nanoparticles (SLNs) and NLCs were best fitted to a Ritger–Peppas kinetic model (0.9832 and 0.9783 for NLCs and SLNs, respectively). This indicated that the release of LVT from the SLNs and NLCs was due to a combination of drug diffusion and erosion from the lipid matrix. The pharmacokinetic and pharmacodynamic results show that LVT-NLCs were better compared to free drug, which could be attributed to an increase in bioavailability. PMID:26425076

  13. Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs

    PubMed Central

    Khan, Saba; Baboota, Sanjula; Ali, Javed; Khan, Sana; Narang, Ramandeep Singh; Narang, Jasjeet Kaur

    2015-01-01

    Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs. PMID:26682188

  14. Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs.

    PubMed

    Khan, Saba; Baboota, Sanjula; Ali, Javed; Khan, Sana; Narang, Ramandeep Singh; Narang, Jasjeet Kaur

    2015-01-01

    Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs. PMID:26682188

  15. Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients.

    PubMed

    Gual-Frau, Josep; Abad, Carlos; Amengual, María J; Hannaoui, Naim; Checa, Miguel A; Ribas-Maynou, Jordi; Lozano, Iris; Nikolaou, Alexandros; Benet, Jordi; García-Peiró, Agustín; Prats, Juan

    2015-09-01

    Infertile males with varicocele have the highest percentage of sperm cells with damaged DNA, compared to other infertile groups. Antioxidant treatment is known to enhance the integrity of sperm DNA; however, there are no data on the effects in varicocele patients. We thus investigated the potential benefits of antioxidant treatment specifically in grade I varicocele males. Twenty infertile patients with grade I varicocele were given multivitamins (1500 mg L-Carnitine, 60 mg vitamin C, 20 mg coenzyme Q10, 10 mg vitamin E, 200 μg vitamin B9, 1 μg vitamin B12, 10 mg zinc, 50 μg selenium) daily for three months. Semen parameters including total sperm count, concentration, progressive motility, vitality, and morphology were determined before and after treatment. In addition, sperm DNA fragmentation and the amount of highly degraded sperm cells were analyzed by Sperm Chromatin Dispersion. After treatment, patients showed an average relative reduction of 22.1% in sperm DNA fragmentation (p = 0.02) and had 31.3% fewer highly degraded sperm cells (p = 0.07). Total numbers of sperm cells were increased (p = 0.04), but other semen parameters were unaffected. These data suggest that sperm DNA integrity in grade I varicocele patients may be improved by oral antioxidant treatment.

  16. Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo

    PubMed Central

    Mou, K.H.; Han, D.; Liu, W.L.; Li, P.

    2016-01-01

    Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable. PMID:27464024

  17. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms.

    PubMed

    Zhang, Yiying; Guo, Kaiying; LeBlanc, Robert E; Loh, Daniella; Schwartz, Gary J; Yu, Yi-Hao

    2007-06-01

    Leucine, as an essential amino acid and activator of mTOR (mammalian target of rapamycin), promotes protein synthesis and suppresses protein catabolism. However, the effect of leucine on overall glucose and energy metabolism remains unclear, and whether leucine has beneficial effects as a long-term dietary supplement has not been examined. In the present study, we doubled dietary leucine intake via leucine-containing drinking water in mice with free excess to either a rodent chow or a high-fat diet (HFD). While it produced no major metabolic effects in chow-fed mice, increasing leucine intake resulted in up to 32% reduction of weight gain (P < 0.05) and a 25% decrease in adiposity (P < 0.01) in HFD-fed mice. The reduction of adiposity resulted from increased resting energy expenditure associated with increased expression of uncoupling protein 3 in brown and white adipose tissues and in skeletal muscle, while food intake was not decreased. Increasing leucine intake also prevented HFD-induced hyperglycemia, which was associated with improved insulin sensitivity, decreased plasma concentrations of glucagon and glucogenic amino acids, and downregulation of hepatic glucose-6-phosphatase. Additionally, plasma levels of total and LDL cholesterol were decreased by 27% (P < 0.001) and 53% (P < 0.001), respectively, in leucine supplemented HFD-fed mice compared with the control mice fed the same diet. The reduction in cholesterol levels was largely independent of leucine-induced changes in adiposity. In conclusion, increases in dietary leucine intake substantially decrease diet-induced obesity, hyperglycemia, and hypercholesterolemia in mice with ad libitum consumption of HFD likely via multiple mechanisms.

  18. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice

    PubMed Central

    Rune, Ida; Rolin, Bidda; Larsen, Christian; Nielsen, Dennis Sandris; Kanter, Jenny E.; Bornfeldt, Karin E.; Lykkesfeldt, Jens; Buschard, Karsten; Kirk, Rikke Kaae; Christoffersen, Berit; Fels, Johannes Josef; Josefsen, Knud; Kihl, Pernille; Hansen, Axel Kornerup

    2016-01-01

    The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings

  19. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.

    PubMed

    Rune, Ida; Rolin, Bidda; Larsen, Christian; Nielsen, Dennis Sandris; Kanter, Jenny E; Bornfeldt, Karin E; Lykkesfeldt, Jens; Buschard, Karsten; Kirk, Rikke Kaae; Christoffersen, Berit; Fels, Johannes Josef; Josefsen, Knud; Kihl, Pernille; Hansen, Axel Kornerup

    2016-01-01

    The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings

  20. Combined physical and chemical immobilization of glucose oxidase in alginate microspheres improves stability of encapsulation and activity.

    PubMed

    Zhu, Huiguang; Srivastava, Rohit; Brown, J Quincy; McShane, Michael J

    2005-01-01

    Chemical sensors utilizing immobilized enzymes and proteins are important for monitoring chemical processes and biological systems. In this study, calcium-cross-linked alginate hydrogel microspheres were fabricated as enzyme carriers by an emulsification technique. Glucose oxidase (GOx) was encapsulated in alginate microspheres using three different methods: physical entrapment (emulsion), chemical conjugation (conjugation), and a combination of physical entrapment and chemical conjugation (emulsion-conjugation). Nano-organized coatings were applied on alginate/GOx microspheres using the layer-by-layer self-assembly technique in order to stabilize the hydrogel/enzyme system under biological environment. The encapsulation of GOx and formation of nanofilm coating on alginate microspheres were verified with FTIR spectral analysis, zeta-potential analysis, and confocal laser scanning microscopy. To compare both the immobilization properties of enzyme encapsulation techniques and the influence of nanofilms with uncoated microspheres, the relationship between enzyme loading, release, and effective GOx activity (enzyme activity per unit protein loading) were studied over a period of four weeks. The results produced four key findings: (1) the emulsion-conjugation technique improved the stability of GOx in alginate microspheres compared to the emulsion technique, reducing the GOx leaching from microsphere from 50% to 17%; (2) the polyelectrolyte nanofilm coatings increased the GOx stability over time, but also reduced the effective GOx activity; (3) the effective GOx activity for the emulsion-conjugation technique (about 3.5 x 10(-)(5) AU microg(-)(1) s(-)(1)) was higher than that for other methods, and did not change significantly over four weeks; and (4) the GOx concentration, when compared after one week for microspheres with three bilayers of poly(allylamine hydrochloride)/sodium poly(styrene sulfonate) ({PAH/PSS}) coating, was highest for the emulsion

  1. Black Adzuki Bean (Vigna angularis) Extract Protects Pancreatic β Cells and Improves Glucose Tolerance in C57BL/6J Mice Fed a High-Fat Diet.

    PubMed

    Kim, Mina; Kim, Dae Keun; Cha, Youn-Soo

    2016-05-01

    Adzuki beans have long been cultivated as a food and folk medicine in East Asia. In this study, we investigated the effect of black adzuki bean (BAB) extract on pancreatic cells and determined their mechanism of action in impaired glucose tolerance in an animal model of type 2 diabetes. In addition, we performed functional gene annotation analysis to identify genes related to the regulation of glucose metabolism and insulin response. Treatment of pancreatic β cells with BAB extract (0.2 mg/mL) led to tolerance of the high glucose-induced glucotoxicity, resulting in a similar viability as cells maintained in normal glucose media. In addition, dietary supplementation with BAB extract significantly (P < .05) improved hyperglycemia and homeostasis model assessment of insulin resistance index (HOMA-IR) in high-fat diet-induced glucose-intolerant obese C57BL/6J mice. Our results suggest that BAB extract ameliorates hyperglycemia and glucose intolerance, and lowers HOMA-IR by regulating insulin secretion and response, and by maintaining the integrity of pancreatic β cells exposed to hyperglycemic conditions. PMID:27070495

  2. Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans.

    PubMed

    Dahmus, Jessica D; Bruning, Rebecca S; Kenney, W Larry; Alexander, Lacy M

    2013-08-15

    Platelet P₂Y₁₂-ADP and COX-1 receptor inhibition with oral clopidogrel (CLO) and low-dose aspirin (ASA), respectively, attenuates reflex-mediated cutaneous vasodilation, but little is known about how these medications affect local vasodilatory signaling. Reactive hyperemia (RH) results in vasodilation that is mediated by sensory nerves and endothelium-derived hyperpolarization factors (EDHF) through large-conductance calcium-activated potassium channels, whereas slow local heating (LH) elicits vasodilation largely through the production of nitric oxide (NO). We hypothesized that CLO and ASA would attenuate locally mediated cutaneous vasodilation assessed by RH and LH (0.5°C/min). In a randomized, cross-over, double-blind placebo-controlled study, nine healthy men and women (56 ± 1 yr) took CLO (75 mg), ASA (81 mg), and placebo for 7 days. Skin blood flow was measured (laser-Doppler flowmetry, LDF) and cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal CVC (%CVCmax: 43°C and 28 mM sodium nitroprusside). RH response parameters, including area under the curve (AUC), total hyperemic response (THR), and the decay constant tau (λ) were calculated. NO-dependent vasodilation during LH was assessed by calculating the difference in %CVCmax between a control site and an NO synthase-inhibited site (10 mM l-NAME: intradermal microdialysis). CLO augmented the AUC and THR (AUCclo = 3,783 ± 342; THRclo = 2,306 ± 266% CVCmax/s) of the RH response compared with ASA (AUCASA = 3,101 ± 325; THRASA = 1,695 ± 197% CVCmax/s) and placebo (AUCPlacebo = 3,000 ± 283; THRPlacebo = 1,675 ± 170% CVCmax/s; all P < 0.0001 vs. CLO). There was no difference in the LH response or calculated NO-dependent vasodilation among treatments (all P > 0.05). Oral CLO treatment augments vasodilation during RH but not LH, suggesting that CLO may improve cutaneous microvascular function.

  3. Nanosuspensions Containing Oridonin/HP-β-Cyclodextrin Inclusion Complexes for Oral Bioavailability Enhancement via Improved Dissolution and Permeability.

    PubMed

    Zhang, Xingwang; Zhang, Tianpeng; Lan, Yali; Wu, Baojian; Shi, Zhihai

    2016-04-01

    Chemotherapy via oral route of anticancer drugs offers much convenience and compliance to patients. However, oral chemotherapy has been challenged by limited absorption due to poor drug solubility and intestinal efflux. In this study, we aimed to develop a nanosuspension formulation of oridonin (Odn) using its cyclodextrin inclusion complexes to enhance oral bioavailability. Nanosuspensions containing Odn/2 hydroxypropyl-β-cyclodextrin inclusion complexes (Odn-CICs) were prepared by a solvent evaporation followed by wet media milling technique. The nanosuspensions were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and dissolution. The resulting nanosuspensions were approximately 313.8 nm in particle size and presented a microcrystal morphology. Nanosuspensions loading Odn-CICs dramatically enhanced the dissolution of Odn. Further, the intestinal effective permeability of Odn was markedly enhanced in the presence of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and poloxamer. Bioavailability studies showed that nanosuspensions with Odn-CICs can significantly promote the oral absorption of Odn with a relative bioavailability of 213.99% (Odn suspensions as reference). Odn itself possesses a moderate permeability and marginal intestinal metabolism. Thus, the enhanced bioavailability for Odn-CIC nanosuspensions can be attributed to improved dissolution and permeability by interaction with absorptive epithelia and anti-drug efflux. Nanosuspensions prepared from inclusion complexes may be a promising approach for the oral delivery of anticancer agents.

  4. Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection

    NASA Astrophysics Data System (ADS)

    Jiang, Ching-Fen; Wang, Chih-Yu; Chiang, Chun-Ping

    2011-07-01

    Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R/B ratio, and R/G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R/G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer.

  5. Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats.

    PubMed

    Zhu, Yuan; Wang, Miaomiao; Zhang, Jiajia; Peng, Wei; Firempong, Caleb Kesse; Deng, Wenwen; Wang, Qilong; Wang, Shicheng; Shi, Feng; Yu, Jiangnan; Xu, Ximing; Zhang, Weiming

    2015-04-01

    This study innovatively prepared an effective capsaicin-loaded liposome, a nanoformulation with fewer irritants, for oral administration. The in vitro and in vivo properties of the liposomal encapsulation were investigated and the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol, sodium cholate and isopropyl myristate was prepared using film-dispersion method. A level A in vitro-in vivo correlation (IVIVC) was established for the first time, which demonstrated an excellent IVIVC of both formulated and free capsaicin in oral administration. Physicochemical characterizations including mean particle size, zeta (ζ) potential and average encapsulation efficiency of capsaicin-loaded liposome were found to be 52.2 ± 1.3 nm, -41.5 ± 2.71 mv and 81.9 ± 2.43 %, respectively. In vivo, liposomal encapsulation allowed a 3.34-fold increase in relative bioavailability compared to free capsaicin. The gastric mucosa irritation studies indicated that the liposomal system was a safe carrier for oral administration. These results support the fact that capsaicin, an effective drug for the treatment of neuropathic pain, could be encapsulated in liposome for improved oral bioavailability. The excellent IVIVC of capsaicin-loaded liposome could also be a promising tool in liposomal formulation development with an added advantage of reduced animal testing.

  6. Improving oral bioavailability of metformin hydrochloride using water-in-oil microemulsions and analysis of phase behavior after dilution.

    PubMed

    Li, Yuan; Song, Jiaqi; Tian, Ning; Cai, Jie; Huang, Meihong; Xing, Qiao; Wang, Yalong; Wu, Chuanbin; Hu, Haiyan

    2014-10-01

    Microemulsions show significant promise for enhancing the oral bioavailability of biopharmaceutics classification system (BCS) class II drugs, but how about class III drugs remains unclear. Here we employed metformin hydrochloride (MET) as the model drug and prepared drug-loaded water-in-oil (W/O) microemulsions selecting different hydrophile-lipophile balance (HLB) surfactant systems, using HLB 8 as a cut-off. We examined the phase behaviors of microemulsions after dilution and attempted to correlate these behaviors to drug oral bioavailability. ME-A, including a lower content of surfactants (35%), underwent a transition of W/O emulsion and then became a stable O/W emulsion in a light milky appearance; ME-B, in contrast, introducing a higher content of surfactants (45%), still remained transparent or semitransparent upon dilution. Unexpectedly, ME-A showed significantly higher oral bioavailability, which can be reduced by blocking the lymphatic absorption pathway. Comparatively, the AUC of ME-B is lower, close to MET solution. Both microemulsions behaved similarly in intestinal perfusion test because of the dilution before perfusion, lacking of the important phase transition of W/O emulsion. These findings suggest that W/O microemulsions improve oral bioavailability of BCS class III drug by promoting lymphatic absorption. Analyzing the phase behavior of microemulsions after dilution may help predict the drug oral bioavailability and optimize formulations.

  7. A New-Generation Continuous Glucose Monitoring System: Improved Accuracy and Reliability Compared with a Previous-Generation System

    PubMed Central

    Bailey, Timothy; Watkins, Elaine; Liljenquist, David; Price, David; Nakamura, Katherine; Boock, Robert; Peyser, Thomas

    2013-01-01

    Abstract Background Use of continuous glucose monitoring (CGM) systems can improve glycemic control, but widespread adoption of CGM utilization has been limited, in part because of real and perceived problems with accuracy and reliability. This study compared accuracy and performance metrics for a new-generation CGM system with those of a previous-generation device. Subjects and Methods Subjects were enrolled in a 7-day, open-label, multicenter pivotal study. Sensor readings were compared with venous YSI measurements (blood glucose analyzer from YSI Inc., Yellow Springs, OH) every 15 min (±5 min) during in-clinic visits. The aggregate and individual sensor accuracy and reliability of a new CGM system, the Dexcom® (San Diego, CA) G4™ PLATINUM (DG4P), were compared with those of the previous CGM system, the Dexcom SEVEN® PLUS (DSP). Results Both study design and subject characteristics were similar. The aggregate mean absolute relative difference (MARD) for DG4P was 13% compared with 16% for DSP (P<0.0001), and 82% of DG4P readings were within ±20 mg/dL (for YSI ≤80 mg/dL) or 20% of YSI values (for YSI >80 mg/dL) compared with 76% for DSP (P<0.001). Ninety percent of the DG4P sensors had an individual MARD ≤20% compared with only 76% of DSP sensors (P=0.015). Half of DG4P sensors had a MARD less than 12.5% compared with 14% for the DSP sensors (P=0.028). The mean absolute difference for biochemical hypoglycemia (YSI <70 mg/dL) for DG4P was 11 mg/dL compared with 16 mg/dL for DSP (P<0.001). Conclusions The performance of DG4P was significantly improved compared with that of DSP, which may increase routine clinical use of CGM and improve patient outcomes. PMID:23777402

  8. Improvement of oral availability of ginseng fruit saponins by a proliposome delivery system containing sodium deoxycholate

    PubMed Central

    Hao, Fei; He, Yanxi; Sun, Yating; Zheng, Bin; Liu, Yan; Wang, Xinmei; Zhang, Yongkai; Lee, Robert J.; Teng, Lirong; Xie, Jing

    2015-01-01

    Ginseng fruit saponins (GFS) extracted from the ginseng fruit are the bioactive triterpenoid saponin components. The aim of the present study was to develop a drug delivery system called proliposome using sodium deoxycholate (NaDC) as a bile salt to improve the oral bioavailability of GFS in rats. The liposomes of GFS were prepared by a conventional ethanol injection and formed the solid proliposomes (P-GFS) using spray drying method on mannitol carriers. The formulation of P-GFS was optimized using the response surface methodology. The physicochemical properties of liposome suspensions including encapsulation efficiency, in vitro drug release studies, particle size of the reconstituted liposome were tested. The solid state characterization studies using the method of Field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) and Differential scanning colorimetric (DSC) were tested to study the molecular state of P-GFS and to indicate the interactions among the formulation ingredients. In vitro studies showed a delayed release of ginsenoside Re (GRe). In vivo studies were carried out in rats. The concentrations of GRe in plasma of rats and its pharmacokinetic behaviors after oral administration of GFS, Zhenyuan tablets (commercial dosage form of GFS) and P-GFS were studied using ultra performance liquid chromatography tandem mass spectrometry. It was founded that the GRe concentration time curves of GFS, Zhenyuan tablets and P-GFS were much more different in rats. Pharmacokinetic behaviors of P-GFS showed a second absorption peak on the concentration time curve. The pharmacokinetic parameters of GFS, Zhenyuan tablets, P-GFS in rats were separately listed as follows: T max 0.25 h, C max 474.96 ± 66.06 ng/ml and AUC0−∞ 733.32 ± 113.82 ng/ml h for GFS; T max 0.31 ± 0.043 h, C max 533.94 ± 106.54 ng/ml and AUC0−∞ 1151.38 ± 198.29 ng/ml h for Zhenyuan tablets; T max 0.5 h, C max 680.62 ± 138.051 ng/ml and

  9. Improving oral health status of preschool children using motivational interviewing method

    PubMed Central

    Mohammadi, Tayebeh Malek; Hajizamani, Abolghasem; Bozorgmehr, Elham

    2015-01-01

    Background: Oral diseases are common chronic diseases that are affected by human health behavior. One-way to promote health behaviors can be achieved through education. The present study aims to assess the effect of an oral health education program using motivational interviewing (MI) method on oral health status of preschool children. Materials and Methods: This study recruited 222 volunteer children and their parents from 10 elementary schools into a community trial. At baseline, plaque, gingival and decayed, missing, and filled teeth indexes were measured in the children. They were randomly allocated into test groups where they and their parents received oral health education using MI and the control group received traditional oral health education. The test group had recall and postal reminder during 6 months of the study, but there was no reminder for the control group. After 6 months, the same oral health indexes were measured. Data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA) by t-test, Mann-Whitney and Wilcoxon signed ranks test. P < 0.05 was considered as significant. Results: The results showed that after both oral health education programs, differences of plaque index (PI) (P = 0.000) and gingival index (P = 0.000) were significant between the two groups. The number of children with healthy gingiva and low PI were more frequent in the test group after intervention. Conclusion: Considering the limitations of this study, oral health status of children after education of parents using MI was observed, and it should be considered in oral health education programs. PMID:26604963

  10. Improving communication through publications: contributions of American oral and maxillofacial surgery.

    PubMed

    Laskin, Daniel M

    2004-01-01

    The Journal of Oral Surgery was the first specialty publication in the United States and since 1943 it, its successor, the Journal of Oral and Maxillofacial Surgery, and other publications of the American Association of Oral and Maxillofacial Surgeons have been committed to communication within the specialty, among dental specialties, and with dentists in general practice. A review of back issues of the journal is a history of the development of the specialty. AAOMS publications are intended to share emerging scientific and clinical knowledge, inform and educate all dentists, and establish standards for quality patient care.

  11. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    PubMed

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice. PMID:27430421

  12. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    PubMed

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice.

  13. The mechanism of self-assembled mixed micelles in improving curcumin oral absorption: In vitro and in vivo.

    PubMed

    Wang, Jinling; Ma, Wenzhuan; Tu, Pengfei

    2015-09-01

    Curcumin-loaded self-assembled polymeric micelles (Cur-PMs) were designed to increase oral bioavailability of curcumin and investigate the oral absorption mechanism in vitro and in vivo. The Cur-PMs were spherical nano-size particles 17.82±0.33nm in size, with a drug loading of 3.52±0.18%, and encapsulation efficiency as high as 93.08±2.23%. The intestinal absorption of Cur-PMs in the duodenum, jejunum, and ileum was 3.09-, 6.48-, and 1.78-fold greater than that of curcumin solution (Cur-Sol) at 0.5h. The cellular uptake of Cur-PMs in Caco-2 cells was significantly enhanced in comparison with Cur-Sol by caveolae-mediated and clathrin-mediated endocytosis. Moreover, the apparent permeability coefficient (Papp) of Cur-PMs was 3.50-fold higher than that of Cur-Sol in Caco-2 transport studies. The transport mechanism of Cur-PMs into the system circulation was not paracellular transport through opening the tight junctions, but was by energy-dependent, macropinocytic transcytosis and lymphatic transport pathways. Furthermore, the AUC(0-t) value of Cur-PMs was improved 2.87-fold compared with that of Cur-Sol after oral administration in rats. Therefore, self-assembled polymeric micelles could be a promising vehicle to efficiently improve the oral absorption of curcumin.

  14. Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients☆

    PubMed Central

    Marquis-Gravel, Guillaume; Hayami, Douglas; Juneau, Martin; Nigam, Anil; Guilbeault, Valérie; Latour, Élise; Gayda, Mathieu

    2015-01-01

    Objectives To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. Methods The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2–3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Results Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Conclusion Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID:26844086

  15. Diagnostic effectiveness of 75 g oral glucose tolerance test for gestational diabetes in India based on the International Association of the Diabetes and Pregnancy Study Groups guidelines

    PubMed Central

    Nikhat, Irfana; Nirmalan, Praveen K

    2013-01-01

    Background To determine the diagnostic effectiveness of the fasting and one-hour plasma glucose levels for gestational diabetes (GDM) based on International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Methods A Cross-sectional study that included 2348 pregnant women booked for antenatal care in 2011 at a tertiary care perinatal institute. Pregnant women underwent a 75 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. Outcome measures include the incidence of GDM based on the IADPSG criteria and the diagnostic effectiveness of the recommended fasting and one-hour plasma glucose cut-off if used in isolation. Results The incidence of GDM was 21.81% (n = 520, 95% CI: 20.15, 23.57) with the IADPSG criteria. A fasting plasma glucose cut-off 92 mg/dL, in isolation, correctly classified 87.16% of GDM, with a specificity of 96.08%, clinically significant positive likelihood ratio (14.08) and a post-test probability of 79.71%. The one-hour 75 g test, in isolation, correctly classified 85.74% of GDM, had specificity of 99.68% and clinically significant positive likelihood ratio (111.12) and post-test probability of 96.87%. The application of the World Health Organization criteria would misclassify 11.91% (95% CI: 10.66, 13.26) of GDM as normal. Conclusions Additional testing of plasma glucose levels can be avoided for 18.25% (n = 435, 95% CI: 16.73, 19.84) if the IADPSG diagnostic criteria for GDM are applied with exit on a positive fasting or one-hour test result.

  16. Patterned orocutaneous therapy improves sucking and oral feeding in preterm infants

    PubMed Central

    Poore, M; Zimmerman, E; Barlow, SM; Wang, J; Gu, F

    2008-01-01

    Aim To determine whether NTrainer patterned orocutaneous therapy affects preterm infants' non-nutritive suck and/or oral feeding success. Subjects Thirty-one preterm infants (mean gestational age 29.3 weeks) who demonstrated minimal non-nutritive suck output and delayed transition to oral feeds at 34 weeks post-menstrual age. Intervention NTrainer treatment was provided to 21 infants. The NTrainer promotes non-nutritive suck output by providing patterned orocutaneous stimulation through a silicone pacifier that mimics the temporal organization of suck. Method Infants' non-nutritive suck pressure signals were digitized in the NICU before and after NTrainer therapy and compared to matched controls. Non-nutritive suck motor pattern stability was calculated based on infants' time- and amplitude-normalized digital suck pressure signals, producing a single value termed the Non-Nutritive Suck Spatiotemporal Index. Percent oral feeding was the other outcome of interest, and revealed the NTrainer's ability to advance the infant from gavage to oral feeding. Results Multilevel regression analyses revealed that treated infants manifest a disproportionate increase in suck pattern stability and percent oral feeding, beyond that attributed to maturational effects alone. Conclusion The NTrainer patterned orocutaneous therapy effectively accelerates non-nutritive suck development and oral feeding success in preterm infants who are at risk for oromotor dysfunction. PMID:18462468

  17. A Review of Clinical Trials Conducted With Oral, Multicomponent Dietary Supplements for Improving Photoaged Skin.

    PubMed

    Birnbaum, Jay; Le Moigne, Anne; Dispensa, Lisa; Buchner, Larry

    2015-12-01

    Although the FDA does not require documentation of efficacy of dietary supplements, prospective clinical studies, including randomized controlled trials, have been conducted with individual micronutrients alone and in combination with other ingredients for promoting skin health. Proposed mechanisms include antioxidation, anti-inflammation, photoprotection, collagen formation, reductions in matrix metalloproteinases, and other effects on photoaging. Literature searches were conducted to identify clinical trials assessing multicomponent dietary supplement formulations on photoaging outcomes. Sixteen studies of various nutrient and non-nutrient ingredients, including essential micronutrients (vitamins, minerals), plant extracts (polyphenols, carotenoids), and marine- or animal-derived ingredients, were identified. Studies were single center, 2-12 months in duration, primarily enrolled women, and evaluated numerous outcomes, including investigator/subject assessments and instrumental/objective measures. Methods to control for potential confounders were implemented in some studies, including limiting sun exposure, cosmetic procedures, and changes in dietary habits/body weight. Given the range of different products, clinical/methodologic heterogeneity, insufficient detail in reporting, and lack of comparable outcome measures, quantitative analysis of results was not possible. Results of individual studies revealed significant improvements from baseline for the dietary supplement group(s) on ≥ 1 endpoint across all studies; significant differences from placebo were observed in 7 of 12 controlled studies (although only 1 study designated a prospectively defined primary endpoint). Most products had only been tested in 1 study; confirmatory studies were rarely conducted per the publicly available literature. Meaningful assessment of dietary supplements, which typically contain nutrients found in the diet, requires unique methodologic considerations and endpoints

  18. Pharmacokinetics study of arteether loaded solid lipid nanoparticles: an improved oral bioavailability in rats.

    PubMed

    Dwivedi, Pankaj; Khatik, Renuka; Khandelwal, Kiran; Taneja, Isha; Raju, Kanumuri Siva Rama; Wahajuddin; Paliwal, Sarvesh Kumar; Dwivedi, Anil Kumar; Mishra, Prabhat Ranjan

    2014-05-15

    Arteether (ART), an artemisinin derivative, is a life saving drug for multiple drug resistant malaria. It has a deliverance effect in Falciparum malaria and cerebral malaria. We have prepared solid lipid nanoparticles (SLN) by high pressure homogenization (HPH) technique. ART-loaded SLN (ART-SLN) has been produced reproducibly with homogeneous particle size. ART-SLN was characterized for their size measured by Zetasizer Nano-ZS, Malvern, UK and by high resolution transmission electron microscopy (HR-TEM) and which was found to be 100 ± 11.2 nm. The maximum percentage entrapment efficiency (%EE) determined with the high-performance liquid chromatography (HPLC) has been found to be 69 ± 4.2% in ART-SLN-3. The release pattern from ART-SLN revealed that the release of ART is slow but time-dependent manner, which is desirable as it will help to protect the acid degradation of ART in stomach. The percentage cytotoxicity of blank SLN has been found within the acceptable range. The pharmacokinetics results indicated that ART-SLN-3 absorption has been significantly enhanced in comparison to ART in aqueous suspension and ART in ground nut oil (GNO) in rats. The % relative bioavailability (RB%) of ART-SLN to the ART in GNO and ART in aqueous suspension in rats was 169.99% and 7461%, respectively which was found to be significantly high in both the cases. From the results, it can be concluded that ART-SLN offers a new approach to improve the oral bioavailability of ART.

  19. Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease.

    PubMed

    Rossman, Matthew J; Trinity, Joel D; Garten, Ryan S; Ives, Stephen J; Conklin, Jamie D; Barrett-O'Keefe, Zachary; Witman, Melissa A H; Bledsoe, Amber D; Morgan, David E; Runnels, Sean; Reese, Van R; Zhao, Jia; Amann, Markus; Wray, D Walter; Richardson, Russell S

    2015-09-01

    The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.

  20. Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease

    PubMed Central

    Rossman, Matthew J.; Trinity, Joel D.; Garten, Ryan S.; Ives, Stephen J.; Conklin, Jamie D.; Barrett-O'Keefe, Zachary; Witman, Melissa A. H.; Bledsoe, Amber D.; Morgan, David E.; Runnels, Sean; Reese, Van R.; Zhao, Jia; Amann, Markus; Wray, D. Walter

    2015-01-01

    The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population. PMID:26188020

  1. A Review of Clinical Trials Conducted With Oral, Multicomponent Dietary Supplements for Improving Photoaged Skin.

    PubMed

    Birnbaum, Jay; Le Moigne, Anne; Dispensa, Lisa; Buchner, Larry

    2015-12-01

    Although the FDA does not require documentation of efficacy of dietary supplements, prospective clinical studies, including randomized controlled trials, have been conducted with individual micronutrients alone and in combination with other ingredients for promoting skin health. Proposed mechanisms include antioxidation, anti-inflammation, photoprotection, collagen formation, reductions in matrix metalloproteinases, and other effects on photoaging. Literature searches were conducted to identify clinical trials assessing multicomponent dietary supplement formulations on photoaging outcomes. Sixteen studies of various nutrient and non-nutrient ingredients, including essential micronutrients (vitamins, minerals), plant extracts (polyphenols, carotenoids), and marine- or animal-derived ingredients, were identified. Studies were single center, 2-12 months in duration, primarily enrolled women, and evaluated numerous outcomes, including investigator/subject assessments and instrumental/objective measures. Methods to control for potential confounders were implemented in some studies, including limiting sun exposure, cosmetic procedures, and changes in dietary habits/body weight. Given the range of different products, clinical/methodologic heterogeneity, insufficient detail in reporting, and lack of comparable outcome measures, quantitative analysis of results was not possible. Results of individual studies revealed significant improvements from baseline for the dietary supplement group(s) on ≥ 1 endpoint across all studies; significant differences from placebo were observed in 7 of 12 controlled studies (although only 1 study designated a prospectively defined primary endpoint). Most products had only been tested in 1 study; confirmatory studies were rarely conducted per the publicly available literature. Meaningful assessment of dietary supplements, which typically contain nutrients found in the diet, requires unique methodologic considerations and endpoints

  2. Trefoil Factor 3 (TFF3) Is Regulated by Food Intake, Improves Glucose Tolerance and Induces Mucinous Metaplasia

    PubMed Central

    Ge, Hongfei; Gardner, Jonitha; Wu, Xiaosu; Rulifson, Ingrid; Wang, Jinghong; Xiong, Yumei; Ye, Jingjing; Belouski, Edward; Cao, Ping; Tang, Jie; Lee, Ki Jeong; Coberly, Suzanne; Wu, Xinle; Gupte, Jamila; Miao, Lynn; Yang, Li; Nguyen, Natalie; Shan, Bei; Yeh, Wen-Chen; Véniant, Murielle M.; Li, Yang; Baribault, Helene

    2015-01-01

    Trefoil factor 3 (TFF3), also called intestinal trefoil factor or Itf, is a 59 amino acid peptide found as a homodimer predominantly along the gastrointestinal tract and in serum. TFF3 expression is elevated during gastrointestinal adenoma progression and has been shown to promote mucosal wound healing. Here we show that in contrast to other trefoil factor family members, TFF1 and TFF2, TFF3 is highly expressed in mouse duodenum, jejunum and ileum and that its expression is regulated by food intake. Overexpression of TFF3 using a recombinant adeno-associated virus (AAV) vector, or daily administration of recombinant TFF3 protein in vivo improved glucose tolerance in a diet-induced obesity mouse model. Body weight, fasting insulin, triglyceride, cholesterol and leptin levels were not affected by TFF3 treatment. Induction of mucinous metaplasia was observed in mice with AAV-mediated TFF3 overexpression, however, no such adverse histological effect was seen after the administration of recombinant TFF3 protein. Altogether these results suggest that the therapeutic potential of targeting TFF3 to treat T2D may be limited. PMID:26083576

  3. Targeting of the circadian clock via CK1δ/ε to improve glucose homeostasis in obesity

    PubMed Central

    Cunningham, Peter S.; Ahern, Siobhán A.; Smith, Laura C.; da Silva Santos, Carla S.; Wager, Travis T.; Bechtold, David A.

    2016-01-01

    Growing evidence indicates that disruption of our internal timing system contributes to the incidence and severity of metabolic diseases, including obesity and type 2 diabetes. This is perhaps not surprising since components of the circadian clockwork are tightly coupled to metabolic processes across the body. In the current study, we assessed the impact of obesity on the circadian system in mice at a behavioural and molecular level, and determined whether pharmacological targeting of casein kinase 1δ and ε (CK1δ/ε), key regulators of the circadian clock, can confer metabolic benefit. We demonstrate that although behavioural rhythmicity was maintained in diet-induced obesity (DIO), gene expression profiling revealed tissue-specific alteration to the phase and amplitude of the molecular clockwork. Clock function was most significantly attenuated in visceral white adipose tissue (WAT) of DIO mice, and was coincident with elevated tissue inflammation, and dysregulation of clock-coupled metabolic regulators PPARα/γ. Further, we show that daily administration of a CK1δ/ε inhibitor (PF-5006739) improved glucose tolerance in both DIO and genetic (ob/ob) models of obesity. These data further implicate circadian clock disruption in obesity and associated metabolic disturbance, and suggest that targeting of the clock represents a therapeutic avenue for the treatment of metabolic disorders. PMID:27439882

  4. Selection of improved Beauveria bassiana (Bals.) Vuill. strains based on 2-deoxy-D-glucose resistance and physiological analysis.

    PubMed

    Robledo-Monterrubio, M; Alatorre-Rosas, R; Viniegra-González, G; Loera, O

    2009-07-01

    A series of 2-deoxy-D-glucose resistant mutants was obtained from wild type Beauveria bassiana 88 (Bb 88) by UV irradiation. Five mutants were characterized on Sabouraud Dextrose Agar and Chitin Agar for both radial extension rate (V(r)) and specific growth rate (micro). These values were obtained after adjusting morphometric data to a mathematical model used for filamentous fungi. Additionally, the protease and lipase potency index, conidial size, viability, and production levels were analyzed. The highest values for those physiological measurements were obtained by mutant 882.5 which, relative to Bb 88, showed a 30% reduction in half-life (LT(50)) on Sphenarium purpurascens, 70% on Acheta domesticus, and 71% on Tenebrio molitor larvae and adults. The half lethal concentration (LC(50)) on T. molitor larvae was 2.8 x 10(5)conidia/mL (con/mL) and 1.5 x 10(6)con/mL, respectively, for mutant 882.5 and Bb 88. This demonstrates that mutant 882.5 is more virulent, with up to an 80% reduction in LC(50). This work provides a convenient method for improving strains to be used in biocontrol as a suitable alternative to transgenic constructs. PMID:19463827

  5. Does an L-glutamine-containing, Glucose-free, Oral Rehydration Solution Reduce Stool Output and Time to Rehydrate in Children with Acute Diarrhoea? A Double-blind Randomized Clinical Trial

    PubMed Central

    Gutiérrez, Claudia; Villa, Sofía; Mota, Felipe R.; Calva, Juan J.

    2007-01-01

    This study assessed whether an oral rehydration solution (ORS) in which glucose is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard glucose-based rehydration solution recommended by the World Health Organization (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea. In a double-blind, randomized controlled trial in a Mexican hospital, 147 dehydrated children, aged 1–60 month(s), were assigned either to the WHO-ORS (74 children), or to the L-glutamine ORS (73 children) and followed until successful rehydration. There were no significant differences between the groups in stool output during the first four hours, time to successful rehydration, volume of ORS required for rehydration, urinary output, and vomiting. This was independent of rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems not to offer greater clinical benefit than the standard WHO-ORS in mildly-to-moderately-dehydrated children with acute non-cholera diarrhoea. PMID:18330060

  6. Modification of glucose import capacity in Escherichia coli: physiologic consequences and utility for improving DNA vaccine production

    PubMed Central

    2013-01-01

    Background The bacterium Escherichia coli can be grown employing various carbohydrates as sole carbon and energy source. Among them, glucose affords the highest growth rate. This sugar is nowadays widely employed as raw material in industrial fermentations. When E. coli grows in a medium containing non-limiting concentrations of glucose, a metabolic imbalance occurs whose main consequence is acetate secretion. The production of this toxic organic acid reduces strain productivity and viability. Solutions to this problem include reducing glucose concentration by substrate feeding strategies or the generation of mutant strains with impaired glucose import capacity. In this work, a collection of E. coli strains with inactive genes encoding proteins involved in glucose transport where generated to determine the effects of reduced glucose import capacity on growth rate, biomass yield, acetate and production of an experimental plasmid DNA vaccine (pHN). Results A group of 15 isogenic derivatives of E. coli W3110 were generated with single and multiple deletions of genes encoding glucose, mannose, beta-glucoside, maltose and N-acetylglucosamine components of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), as well as the galactose symporter and the Mgl galactose/glucose ABC transporter. These strains were characterized by growing them in mineral salts medium supplemented with 2.5 g/L glucose. Maximum specific rates of glucose consumption (qs) spanning from 1.33 to 0.32 g/g h were displayed by the group of mutants and W3110, which resulted in specific growth rates ranging from 0.65-0.18 h-1. Acetate accumulation was reduced or abolished in cultures with all mutant strains. W3110 and five selected mutant derivatives were transformed with pHN. A 3.2-fold increase in pHN yield on biomass was observed in cultures of a mutant strain with deletion of genes encoding the glucose and mannose PTS components, as well as Mgl. Conclusions The group of E. coli mutants

  7. Improving 18F-Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography Imaging in Alzheimer's Disease Studies

    PubMed Central

    Knešaurek, Karin

    2015-01-01

    The goal was to improve Alzheimer's 2-deoxy-2-18F-fluoro-D-glucose (18F FDG)-positron emission tomography (PET)/computed tomography (CT) imaging through application of a novel, hybrid Fourier-wavelet windowed Fourier transform (WFT) restoration technique, in order to provide earlier and more accurate clinical results. General Electric Medical Systems downward-looking sonar PET/CT 16 slice system was used to acquire studies. Patient data were acquired according the Alzheimer's disease Neuroimaging Initiative (ADNI) protocol. Here, we implemented Fourier-wavelet regularized restoration, with a Butterworth low-pass filter, order n = 6 and a cut-off frequency f = 0.35 cycles/pixel and wavelet (Daubechies, order 2) noise suppression. The original (PET-O) and restored (PET-R) ADNI subject PET images were compared using the Alzheimer's discrimination analysis by dedicated software. Forty-two PET/CT scans were used in the study. They were performed on eleven ADNI subjects at intervals of approximately 6 months. The final clinical diagnosis was used as a gold standard. For three subjects, the final clinical diagnosis was mild cognitive impairment and those 13 PET/CT studies were not included in the final comparison, as the result was considered as inconclusive. Using the reminding 29 PET/CT studies (23 AD and 6 normal), the sensitivity and specificity of the PET-O and PET-R were calculated. The sensitivity was 0.65 and 0.96 for PET-O and PET-R, respectively, and the specificity was 0.67 and 0.50 for PET-O and PET-R. The accuracy was 0.66 and 0.86 for PET-O and PET-R, respectively. The results of the study demonstrated that the accuracy of three-dimensional brain F-18 FDG PET images was significantly improved by Fourier-wavelet restoration filtering. PMID:26420987

  8. Improving (18)F-Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography Imaging in Alzheimer's Disease Studies.

    PubMed

    Knešaurek, Karin

    2015-01-01

    The goal was to improve Alzheimer's 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F FDG)-positron emission tomography (PET)/computed tomography (CT) imaging through application of a novel, hybrid Fourier-wavelet windowed Fourier transform (WFT) restoration technique, in order to provide earlier and more accurate clinical results. General Electric Medical Systems downward-looking sonar PET/CT 16 slice system was used to acquire studies. Patient data were acquired according the Alzheimer's disease Neuroimaging Initiative (ADNI) protocol. Here, we implemented Fourier-wavelet regularized restoration, with a Butterworth low-pass filter, order n = 6 and a cut-off frequency f = 0.35 cycles/pixel and wavelet (Daubechies, order 2) noise suppression. The original (PET-O) and restored (PET-R) ADNI subject PET images were compared using the Alzheimer's discrimination analysis by dedicated software. Forty-two PET/CT scans were used in the study. They were performed on eleven ADNI subjects at intervals of approximately 6 months. The final clinical diagnosis was used as a gold standard. For three subjects, the final clinical diagnosis was mild cognitive impairment and those 13 PET/CT studies were not included in the final comparison, as the result was considered as inconclusive. Using the reminding 29 PET/CT studies (23 AD and 6 normal), the sensitivity and specificity of the PET-O and PET-R were calculated. The sensitivity was 0.65 and 0.96 for PET-O and PET-R, respectively, and the specificity was 0.67 and 0.50 for PET-O and PET-R. The accuracy was 0.66 and 0.86 for PET-O and PET-R, respectively. The results of the study demonstrated that the accuracy of three-dimensional brain F-18 FDG PET images was significantly improved by Fourier-wavelet restoration filtering.

  9. FV-162 is a novel, orally bioavailable, irreversible proteasome inhibitor with improved pharmacokinetics displaying preclinical efficacy with continuous daily dosing.

    PubMed

    Wang, Z; Dove, P; Wang, X; Shamas-Din, A; Li, Z; Nachman, A; Oh, Y J; Hurren, R; Ruschak, A; Climie, S; Press, B; Griffin, C; Undzys, E; Aman, A; Al-awar, R; Kay, L E; O'Neill, D; Trudel, S; Slassi, M; Schimmer, A D

    2015-01-01

    Approved proteasome inhibitors have advanced the treatment of multiple myeloma but are associated with serious toxicities, poor pharmacokinetics, and most with the inconvenience of intravenous administration. We therefore sought to identify novel orally bioavailable proteasome inhibitors with a continuous daily dosing schedule and improved therapeutic window using a unique drug discovery platform. We employed a fluorine-based medicinal chemistry technology to synthesize 14 novel analogs of epoxyketone-based proteasome inhibitors and screened them for their stability, ability to inhibit the chymotrypsin-like proteasome, and antimyeloma activity in vitro. The tolerability, pharmacokinetics, pharmacodynamic activity, and antimyeloma efficacy of our lead candidate were examined in NOD/SCID mice. We identified a tripeptide epoxyketone, FV-162, as a metabolically stable, potent proteasome inhibitor cytotoxic to human myeloma cell lines and primary myeloma cells. FV-162 had limited toxicity and was well tolerated on a continuous daily dosing schedule. Compared with the benchmark oral irreversible proteasome inhibitor, ONX-0192, FV-162 had a lower peak plasma concentration and longer half-life, resulting in a larger area under the curve (AUC). Oral FV-162 treatment induced rapid, irreversible inhibition of chymotrypsin-like proteasome activity in murine red blood cells and inhibited tumor growth in a myeloma xenograft model. Our data suggest that oral FV-162 with continuous daily dosing schedule displays a favorable safety, efficacy, and pharmacokinetic profile in vivo, identifying it as a promising lead for clinical evaluation in myeloma therapy.

  10. Nanomemulsion of megestrol acetate for improved oral bioavailability and reduced food effect.

    PubMed

    Li, Yixian; Song, Chung Kil; Kim, Min-Kyoung; Lim, Hyosang; Shen, Qingbo; Lee, Don Haeng; Yang, Su-Geun

    2015-10-01

    Megestrol acetate (MGA) belongs to the BCS class II drugs with low solubility and high permeability, and its oral absorption in conventional dosage form MGA microcrystal suspension (MGA MS) is very limited and greatly affected by food. In this study, MGA nanoemulsion (MGA NE) was formulated based on solubility, phase-diagram and release studies. Then oral bioavailability of MGA NE and MGA MS was evaluated. A randomized two-way crossover trial was conducted on six male dogs under fed and fasting conditions. Blood concentrations of MGA were analyzed using LC-MS/MS. MGA NE yielded 5.00-fold higher oral bioavailability in fasting conditions and displayed more stable absorption profiles after food intake compared with MGA MS.

  11. Improving professionalism in the engineering curriculum through a novel use of oral presentations

    NASA Astrophysics Data System (ADS)

    Berjano, Enrique; Sales-Nebot, Laura; Lozano-Nieto, Albert

    2013-05-01

    This hypothesis is based on the fact that oral presentations in the context of engineering education could be used not only to develop oral communication skills but also to augment the professionalism in the curriculum. The methodological innovation is first described, which allows encouraging the capacity of summarising ideas, teamwork, assertiveness, listening skills and constructive criticism. Second, the preliminary results from two pilot groups of students during two academic years are analysed. Finally, the paper reflects on the possibilities of expanding this method to pre-university studies.

  12. Comparison of Vaginal versus Oral Estradiol Administration in Improving the Visualization of Transformation Zone (TZ) during Colposcopy

    PubMed Central

    Makkar, Binni; Batra, Swaraj; Gandhi, Gauri; Goswami, Deepti; Zutshi, Vijay

    2016-01-01

    Introduction Colposcopy is an important diagnostic tool in the evaluation of patients with abnormal pap smears. However, in 10-20% transformation zone (TZ)/squamo-columnar junction is not completely visualized and these patients are deemed to have an incomplete colposcopy examination. Such patients usually require conization, a procedure associated with significant morbidity. Various agents like misoprostol, estrogens and laminaria tents have been used in the past to overcome the non-visualization of TZ. Aim The present study was conducted with the aim to compare the efficacy of vaginal versus oral estradiol administration in overcoming incomplete colposcopy. Materials and Methods Forty patients with non/partially visualized TZ during colposcopy were recruited for the study. These patients were randomly distributed into two groups: In Group I, 25μg estradiol was administered intravaginally daily for seven consecutive days followed by a repeat colposcopy on day 8. In Group II, a seven day course of 25μg oral estradiol was followed by a repeat colposcopy on day 8. The efficacy of the two regimens in improving visualization of the TZ on colposcopy and their adverse effect profile was compared. Results Vaginal estradiol had an overall efficacy of 70% in improving visualization of the TZ as compared to oral estradiol which was effective in 50% of patients (p-value-0.19). Major adverse effects in both the group of patients were nausea and vaginal discharge with no significant differences among the two groups. Conclusion Both vaginal and oral estrogens had comparable efficacy and similar adverse effect profile in improving visualization of the TZ. PMID:27630912

  13. Development of isradipine loaded self-nano emulsifying powders for improved oral delivery: in vitro and in vivo evaluation.

    PubMed

    Ramasahayam, Bindu; Eedara, Basanth Babu; Kandadi, Prabhakar; Jukanti, Raju; Bandari, Suresh

    2015-05-01

    Isradipine (ISR) is a potent calcium channel blocker with low oral bioavailability due to low aqueous solubility, extensive first-pass metabolism and P-glycoprotein (P-gp)-mediated efflux transport. In the present investigation, an attempt was made to develop isradipine-loaded self-nano emulsifying powders (SNEP) for improved oral delivery. The liquid self-nano emulsifying formulations (L-SNEF/SNEF) of isradipine were developed using vehicles with highest drug solubility, i.e. Labrafil® M 2125 CS as oil phase, Capmul® MCM L8 and Cremophor® EL as surfactant/co-surfactant mixture. The developed formulations revealed desirable characteristics of self-emulsifying system such as nano-size globules ranging from 32.7 to 40.2 nm, rapid emulsification (around 60 s), thermodynamic stability and robustness to dilution. The optimized stable self-nano emulsifying formulation (SNEF2) was transformed into SNEP using Neusilin US2 (SNEP(N)) as adsorbent inert carrier, which exhibited similar characteristics of liquid SNEF. The solid state characterization of SNEP(N) by Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopic studies shown transformation of crystalline drug into amorphous form or molecular state without any chemical interaction. The in vitro dissolution of SNEP(N) compared to pure drug was indicated by 18-fold increased drug release within 5 min. In vivo pharmacokinetic studies in Wistar rats showed significant improvement of oral bioavailability of isradipine from SNEP(N) with 3- and 2.5-fold increments in peak drug concentration (C(max)), area under curve (AUC(0-∞)) compared to pure isradipine. In conclusion, these results signify the improved oral delivery of isradipine from developed SNEP.

  14. Comparison of Vaginal versus Oral Estradiol Administration in Improving the Visualization of Transformation Zone (TZ) during Colposcopy

    PubMed Central

    Makkar, Binni; Batra, Swaraj; Gandhi, Gauri; Goswami, Deepti; Zutshi, Vijay

    2016-01-01

    Introduction Colposcopy is an important diagnostic tool in the evaluation of patients with abnormal pap smears. However, in 10-20% transformation zone (TZ)/squamo-columnar junction is not completely visualized and these patients are deemed to have an incomplete colposcopy examination. Such patients usually require conization, a procedure associated with significant morbidity. Various agents like misoprostol, estrogens and laminaria tents have been used in the past to overcome the non-visualization of TZ. Aim The present study was conducted with the aim to compare the efficacy of vaginal versus oral estradiol administration in overcoming incomplete colposcopy. Materials and Methods Forty patients with non/partially visualized TZ during colposcopy were recruited for the study. These patients were randomly distributed into two groups: In Group I, 25μg estradiol was administered intravaginally daily for seven consecutive days followed by a repeat colposcopy on day 8. In Group II, a seven day course of 25μg oral estradiol was followed by a repeat colposcopy on day 8. The efficacy of the two regimens in improving visualization of the TZ on colposcopy and their adverse effect profile was compared. Results Vaginal estradiol had an overall efficacy of 70% in improving visualization of the TZ as compared to oral estradiol which was effective in 50% of patients (p-value-0.19). Major adverse effects in both the group of patients were nausea and vaginal discharge with no significant differences among the two groups. Conclusion Both vaginal and oral estrogens had comparable efficacy and similar adverse effect profile in improving visualization of the TZ.

  15. Improvement of oral bioavailability of flurbiprofen from flurbiprofen/beta-cyclodextrin inclusion complex by action of cinnarizine.

    PubMed

    Tokumura, Tadakazu; Muraoka, Atsushi; Machida, Yoshiharu

    2009-09-01

    Improvement of the oral bioavailability of flurbiprofen (Flu) after oral administration of flurbiprofen/beta-cyclodextrin inclusion complex (Flu/beta-CD) by the action of cinnarizine (CN) was investigated. Flu and Flu/beta-CD were administered orally to fasted rats at a dose of 20mg/kg as Flu. Thirty minutes after drug administration, CN dissolved in pH 4.0 buffer solution or pH 4.0 buffer solution alone was administered to the rats. The dose of CN was 0.17 mg/kg. Blood samples were taken from rats and Flu concentrations in plasma samples were determined by HPLC. It was found from the comparison of Flu and Flu with CN (Flu+CN) that CN had no effect on plasma concentrations of Flu after oral administration of Flu. The mean plasma levels after oral administration of Flu/beta-CD with CN (Flu/beta-CD+CN) were larger not only than those of Flu and Flu+CN but also than those of Flu/beta-CD. The value of C(max) in Flu/beta-CD+CN was significantly larger than that of Flu/beta-CD. This is considered to be caused by the action of CN as a competing agent. This mechanism was supported by the result of solubility study in which Flu solubility in beta-CD solution decreased with the addition of CN. It was found from these results that CN had strong ability as a competing agent in vivo. PMID:19442722

  16. A Continuous Glucose Monitoring System (CGMS) - a promising approach for improving metabolic control in persons with type 1 Diabetes mellitus treated by insulin pumps.

    PubMed

    Mlcák, Petr; Fialová, Jana; Trnková, Katerina; Chlup, Rudolf

    2004-07-01

    This pilot study deals with the possibilities of a Continuous Glucose Monitoring System (CGMS, Minimed- Medtronic) to optimize insulin substitution. Ten persons with type 1 diabetes mellitus treated by means of an insulin pump entered the study and eight of them completed the protocol. CGMS was introduced for a period of 5 days. The standard dinner (60 g of carbohydrates) and overnight fasting were designed to ensure standard night conditions in all persons in the study while maintaining their usual daily eating routine, physical exercise and assessment of prandial insulin boluses. The only adaptation of basal rates of insulin pump was performed on day 3. Comparison of the mean plasma glucose concentration (0:00-24:00 hrs) between day 2 (before adaptation) and day 4 (following adaptation) was made. An independent comparison of the mean plasma glucose concentration between the night from day 2 till day 3 (22:00-6:00 hrs) and the night from day 4 till day 5 (22:00-6:00 hrs) was performed. The mean plasma glucose investigated by means of CGMS improved in the 24-hour period in 5 out of 8 persons and in the night fasting period (22:00 to 6 hrs) in 6 out of 8 persons. The CGMS is a useful means for assessment of the effectiveness of basal rate and prandial insulin doses in persons with type 1 diabetes treated by means of an insulin pump. However, further studies are necessary to improve the algorithm for insulin substitution.

  17. Sustained improvement in glucose homeostasis in lean and obese mice following chronic administration of the β3 agonist SR 58611A

    PubMed Central

    Williams, Celia A; Shih, Mei-Fen; Taberner, Peter V

    1999-01-01

    Acute SR 58611A (0.25 mg kg−1), was effective in reducing the blood glucose response to a glucose tolerance test (GTT) in normal lean (control) and spontaneously obese/diabetic CBA/Ca mice and to be equipotent to 1.25 mg kg−1 glibenclamide in lean mice.Neither brown (BAT) nor white (WAT) adipose tissue lipogenesis was altered by acute SR 58611A (2–8 mg kg−1) in lean mice, but both increased significantly at the higher doses in the obese mice.Acute SR 58611A produced a hypoglycaemia 40 min after dosing in lean and obese animals, the duration and potency of which was less than that of glibenclamide. Plasma insulin levels increased 20 min after acute SR 58611A and glibenclamide in lean and obese mice.Chronic treatment (0.25 mg kg−1, 15 days) with SR 58611A increased its effectiveness in improving glucose tolerance, but did not affect the body weight (BW) or food intake of either lean or obese mice.Acute and chronic SR 58611A prolonged the hypoglycaemic effect of exogenous insulin in lean but not obese mice.In fed and fasted lean mice and in fasted obese mice chronic SR 58611A produced an acute hypoglycaemia 30 min post administration which was greater than after a single dose.SR 58611A maintained its effectiveness in improving glucose tolerance in lean and obese mice over a dosing period of 15 days. The improvement in glucose tolerance was achieved at a dose less than that required to stimulate adipose tissue lipogenesis and which did not affect food intake or body weight. PMID:10602340

  18. Improving Undergraduate Nursing Research Education: The Effectiveness of Collecting and Analyzing Oral Histories.

    ERIC Educational Resources Information Center

    Duggleby, Wendy

    1998-01-01

    Nine oral histories of retired nurses were collected by 18 nursing students, whose attitudes toward nursing research were significantly more positive compared to 20 nonparticipants. Themes elicited from the histories showed the influence of World War II, technology, and intensive care on nursing practice in this century. (SK)

  19. Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation

    PubMed Central

    Yang, Rui; Huang, Xin; Dou, Jinfeng; Zhai, Guangxi; Su, Lequn

    2013-01-01

    Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance the solubility and oral bioavailability of oleanolic acid. The formulation design was optimized by solubility assay, compatibility tests, and pseudoternary phase diagrams. The morphology, droplet size distribution, zeta potential, viscosity, electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic acid were studied in detail. Compared with oleanolic acid solution, the in vitro release of oleanolic acid from SMEDDS showed that the drug could be released in a sustained manner. A highly selective and sensitive high-performance liquid chromatographymass spectrometry method was developed for determination of oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats. Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was achieved for the SMEDDS compared with the marketed product in tablet form. Our studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid via the oral route. PMID:23966781

  20. Improving Reading Rate Activities for EFL Students: Timed Reading and Repeated Oral Reading

    ERIC Educational Resources Information Center

    Chang, Anna C. -S.

    2012-01-01

    This study investigates the effect of timed reading (TR) and repeated oral reading (RR) on 35 adult students of English as a foreign language. Students in the TR (n =18) and RR (n =17) groups read 52 and 26 passages respectively over a 13-week period. Reading rates and comprehension levels were measured at three occasions: pre-intervention,…

  1. Using Audio Description to Improve FLL Students' Oral Competence in MALL: Methodological Preliminaries

    ERIC Educational Resources Information Center

    Ibáñez Moreno, Ana; Vermeulen, Anna; Jordano, Maria

    2016-01-01

    During the last decades of the 20th century, audiovisual products began to be audio described in order to make them accessible to blind and visually impaired people (Benecke, 2004). This means that visual information is orally described in the gaps between dialogues. In order to meet the wishes of the so-called On Demand (OD) generation that wants…

  2. Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation.

    PubMed

    Yang, Rui; Huang, Xin; Dou, Jinfeng; Zhai, Guangxi; Su, Lequn

    2013-01-01

    Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance the solubility and oral bioavailability of oleanolic acid. The formulation design was optimized by solubility assay, compatibility tests, and pseudoternary phase diagrams. The morphology, droplet size distribution, zeta potential, viscosity, electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic acid were studied in detail. Compared with oleanolic acid solution, the in vitro release of oleanolic acid from SMEDDS showed that the drug could be released in a sustained manner. A highly selective and sensitive high-performance liquid chromatographymass spectrometry method was developed for determination of oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats. Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was achieved for the SMEDDS compared with the marketed product in tablet form. Our studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid via the oral route.

  3. The Impact of Text-Based CMC on Improving L2 Oral Fluency

    ERIC Educational Resources Information Center

    Razagifard, P.

    2013-01-01

    This paper reports on a study investigating the potential effect of synchronous and asynchronous text-based computer-mediated communication (CMC) on oral fluency development of second-language (L2) learners. Sixty-three intermediate learners of English were randomly assigned to one of three groups (two experimental groups and one control group),…

  4. Discussing Stories: On How a Dialogic Reading Intervention Improves Kindergartners' Oral Narrative Construction

    ERIC Educational Resources Information Center

    Lever, Rosemary; Senechal, Monique

    2011-01-01

    Oral narrative skills are assumed to develop through parent-child interactive routines. One such routine is shared reading. A causal link between shared reading and narrative knowledge, however, has not been clearly established. The current research tested whether an 8-week shared reading intervention enhanced the fictional narrative skills of…

  5. A Virtual Environment to Improve the Detection of Oral-Facial Malfunction in Children with Cerebral Palsy.

    PubMed

    Martín-Ruiz, María-Luisa; Máximo-Bocanegra, Nuria; Luna-Oliva, Laura

    2016-03-26

    The importance of an early rehabilitation process in children with cerebral palsy (CP) is widely recognized. On the one hand, new and useful treatment tools such as rehabilitation systems based on interactive technologies have appeared for rehabilitation of gross motor movements. On the other hand, from the therapeutic point of view, performing rehabilitation exercises with the facial muscles can improve the swallowing process, the facial expression through the management of muscles in the face, and even the speech of children with cerebral palsy. However, it is difficult to find interactive games to improve the detection and evaluation of oral-facial musculature dysfunctions in children with CP. This paper describes a framework based on strategies developed for interactive serious games that is created both for typically developed children and children with disabilities. Four interactive games are the core of a Virtual Environment called SONRIE. This paper demonstrates the benefits of SONRIE to monitor children's oral-facial difficulties. The next steps will focus on the validation of SONRIE to carry out the rehabilitation process of oral-facial musculature in children with cerebral palsy.

  6. Preparation and Characterization of Microemulsions of Myricetin for Improving Its Antiproliferative and Antioxidative Activities and Oral Bioavailability.

    PubMed

    Guo, Rui Xue; Fu, Xiong; Chen, Jian; Zhou, Lin; Chen, Gu

    2016-08-17

    To improve the bioactivity and oral bioavailability of myricetin, a microemulsion formulation was successfully developed, which consisted of Cremophor RH40 (12%), Tween 80 (6%), Transcutol HP (9%), WL 1349 (18%), and distilled water (55%). With lower content of surfactants and higher stability after dilution and storage for 6 months, the optimized myricetin microemulsion (MYR-ME) could dramatically enhance the solubility of myricetin 1225 times that in water. MYR-ME significantly increased antiproliferative activity against human cancer cell HepG2 without influence on normal cell LO2. It also notably improved the cellular antioxidative activity of myricetin. Furthermore, the oral bioavailability of myricetin was remarkably enhanced by MYR-ME in Sprague-Dawley rats after oral administration, which was 14.43-fold that with myricetin suspension. Therefore, the MYR-ME developed here could be used as a potential carrier for myricetin with substantially enhanced bioactivities and bioavailability and might promote myricetin's future utilization in functional foods and cosmetics. PMID:27455843

  7. A Virtual Environment to Improve the Detection of Oral-Facial Malfunction in Children with Cerebral Palsy

    PubMed Central

    Martín-Ruiz, María-Luisa; Máximo-Bocanegra, Nuria; Luna-Oliva, Laura

    2016-01-01

    The importance of an early rehabilitation process in children with cerebral palsy (CP) is widely recognized. On the one hand, new and useful treatment tools such as rehabilitation systems based on interactive technologies have appeared for rehabilitation of gross motor movements. On the other hand, from the therapeutic point of view, performing rehabilitation exercises with the facial muscles can improve the swallowing process, the facial expression through the management of muscles in the face, and even the speech of children with cerebral palsy. However, it is difficult to find interactive games to improve the detection and evaluation of oral-facial musculature dysfunctions in children with CP. This paper describes a framework based on strategies developed for interactive serious games that is created both for typically developed children and children with disabilities. Four interactive games are the core of a Virtual Environment called SONRIE. This paper demonstrates the benefits of SONRIE to monitor children’s oral-facial difficulties. The next steps will focus on the validation of SONRIE to carry out the rehabilitation process of oral-facial musculature in children with cerebral palsy. PMID:27023561

  8. Optical coherence tomography technique for noninvasive blood glucose monitoring: phantom, animal, and human studies

    NASA Astrophysics Data System (ADS)

    Larin, Kirill V.; Ashitkov, Taras V.; Larina, Irina V.; Petrova, Irina Y.; Eledrisi, Mohsen S.; Motamedi, Massoud; Esenaliev, Rinat O.

    2002-06-01

    Continuous noninvasive monitoring of blood glucose concentration can improve management of Diabetes Mellitus, reduce mortality, and considerably improve quality of life of diabetic patients. Recently, we proposed to use the OCT technique for noninvasive glucose monitoring. In this paper, we tested noninvasive blood glucose monitoring with the OCT technique in phantoms, animals, and human subjects. An OCT system with the wavelength of 1300 nm was used in our experiments. Phantom studies performed on aqueous suspensions of polystyrene microspheres and milk showed 3.2% decrease of exponential slope of OCT signals when glucose concentration increased from 0 to 100 mM. Theoretical calculations based on the Mie theory of scattering support the results obtained in phantoms. Bolus glucose injections and glucose clamping experiments were performed in animals (New Zealand rabbits and Yucatan micropigs). Good correlation between changes in the OCT signal slope and actual blood glucose concentration were observed in these experiments. First studies were performed in healthy human subjects (using oral glucose tolerance tests). Dependence of the slope of the OCT signals on the actual blood glucose concentration was similar to that obtained in animal studies. Our studies suggest that the OCT technique can potentially be used for noninvasive blood glucose monitoring.

  9. Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

    PubMed

    Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

    2016-01-01

    Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.

  10. CD36-deficient congenic strains show improved glucose tolerance and distinct shifts in metabolic and transcriptomic profiles.

    PubMed

    Šedová, L; Liška, F; Křenová, D; Kazdová, L; Tremblay, J; Krupková, M; Corbeil, G; Hamet, P; Křen, V; Šeda, O

    2012-07-01

    Deficiency of fatty acid translocase Cd36 has been shown to have a major role in the pathogenesis of metabolic syndrome in the spontaneously hypertensive rat (SHR). We have tested the hypothesis that the effects of Cd36 mutation on the features of metabolic syndrome are contextually dependent on genomic background. We have derived two new congenic strains by introgression of limited chromosome 4 regions of SHR origin, both including the defective Cd36 gene, into the genetic background of a highly inbred model of insulin resistance and dyslipidemia, polydactylous (PD) rat strain. We subjected standard diet-fed adult males of PD and the congenic PD.SHR4 strains to metabolic, morphometric and transcriptomic profiling. We observed significantly improved glucose tolerance and lower fasting insulin levels in PD.SHR4 congenics than in PD. One of the PD.SHR4 strains showed lower triglyceride concentrations across major lipoprotein fractions combined with higher levels of low-density lipoprotein cholesterol compared with the PD progenitor. The hepatic transcriptome assessment revealed a network of genes differentially expressed between PD and PD.SHR4 with significant enrichment by members of the circadian rhythmicity pathway (Arntl (Bmal1), Clock, Nfil3, Per2 and Per3). In summary, the introduction of the chromosome 4 region of SHR origin including defective Cd36 into the PD genetic background resulted in disconnected shifts of metabolic profile along with distinct changes in hepatic transcriptome. The synthesis of the current results with those obtained in other Cd36-deficient strains indicates that the eventual metabolic effect of a deleterious mutation s