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Sample records for acute intensive insulin

  1. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  2. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    PubMed Central

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.

  3. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    PubMed Central

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE. PMID:27695421

  4. Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

    PubMed Central

    Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

    2015-01-01

    Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

  5. Acute Glucagon Induces Postprandial Peripheral Insulin Resistance

    PubMed Central

    Patarrão, Rita S.; Lautt, W. Wayne; Macedo, M. Paula

    2015-01-01

    Glucagon levels are often moderately elevated in diabetes. It is known that glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn is associated with decreased postprandial insulin sensitivity. Given that cAMP pathway controls GSH levels we tested whether insulin sensitivity decreases after intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated whether glucagon promotes insulin resistance through decreasing hepatic GSH levels.Insulin sensitivity was determined in fed male Sprague-Dawley rats using a modified euglycemic hyperinsulinemic clamp in the postprandial state upon ipv administration of DBcAMP as well as glucagon infusion. Glucagon effects on insulin sensitivity was assessed in the presence or absence of postprandial insulin sensitivity inhibition by administration of L-NMMA. Hepatic GSH and NO content and plasma levels of NO were measured after acute ipv glucagon infusion. Insulin sensitivity was assessed in the fed state and after ipv glucagon infusion in the presence of GSH-E. We founf that DBcAMP and glucagon produce a decrease of insulin sensitivity, in a dose-dependent manner. Glucagon-induced decrease of postprandial insulin sensitivity correlated with decreased hepatic GSH content and was restored by administration of GSH-E. Furthermore, inhibition of postprandial decrease of insulin sensitivity L-NMMA was not overcome by glucagon, but glucagon did not affect hepatic and plasma levels of NO. These results show that glucagon decreases postprandial insulin sensitivity through reducing hepatic GSH levels, an effect that is mimicked by increasing cAMP hepatic levels and requires physiological NO levels. These observations support the hypothesis that glucagon acts via adenylate cyclase to decrease hepatic GSH levels and induce insulin resistance. We suggest that the glucagon-cAMP-GSH axis is a potential therapeutic target to address insulin resistance in pathological conditions. PMID:25961284

  6. Insulin therapy in the pediatric intensive care unit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units, and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic a...

  7. 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

  8. Intensive insulin therapy to maintain normoglycemia after cardiac surgery.

    PubMed

    Van den Berghe, G

    2011-01-01

    Drugs used in the perioperative period could have an effect on survival as recently pointed out by an international consensus conference on the reduction in mortality in cardiac anesthesia and intensive care. Insulin infusion to achieve a strict glycemic control is the best example of how an ancillary (i.e. non-surgical) drug/technique/strategy might influence survival rates in patients undergoing cardiac surgery. The author of this "expert opinion" presents her insights into the use of insulin in this setting and suggest that based on available evidence based medicine, insulin infusion, titrated to "normoglycemia" is a complex intervention, that not only requires the simple administration of a "drug", the hormone insulin, but also needs tools and skills to accurately measure and control blood glucose to achieve normoglycemia while avoiding hypoglycemia and large glucose fluctuations. PMID:23439402

  9. Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats

    PubMed Central

    de Oliveira, Camila Aparecida Machado; Paiva, Mauricio Ferreira; Mota, Clécia Alencar Soares; Ribeiro, Carla; de Almeida Leme, José Alexandre Curiacos; Luciano, Eliete

    2010-01-01

    To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary. At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets. PMID:21099318

  10. Effects of changes in basal/total daily insulin ratio in type 2 diabetes patients on intensive insulin therapy including insulin glargine (JUN-LAN Study 6).

    PubMed

    Tamaki, Motoyuki; Shimizu, Tomoaki; Kanazawa, Akio; Fujitani, Yoshio; Watada, Hirotaka; Kawamori, Ryuzo; Hirose, Takahisa

    2008-08-01

    Intensive insulin therapy composed of bolus and basal insulin has been believed as the most powerful recipe for glycemic control of both type 1 and type 2 diabetes. In this study, we investigated the effects of changes in basal/total daily insulin ratio (B/TD ratio) in type 2 diabetes patients on intensive insulin therapy including insulin glargine. The B/TD ratio used in our Japanese patients was about 0.35, and the ratio was increased up to about 0.46+/-0.12 without change of total insulin daily dose. After 24-week-treatment, mean glycated albumin of the patients whose B/TD ratio was increased was significantly lower than those of the patients whose B/TD ratio was not changed. Our results suggest that adequate supplementation of basal insulin may be important for maximum effect of bolus insulin even in Japanese who have serious defect in postprandial rapid insulin secretion.

  11. Short acting insulin analogues in intensive care unit patients

    PubMed Central

    Bilotta, Federico; Guerra, Carolina; Badenes, Rafael; Lolli, Simona; Rosa, Giovanni

    2014-01-01

    Blood glucose control in intensive care unit (ICU) patients, addressed to actively maintain blood glucose concentration within defined thresholds, is based on two major therapeutic interventions: to supply an adequate calories load and, when necessary, to continuously infuse insulin titrated to patients needs: intensive insulin therapy (IIT). Short acting insulin analogues (SAIA) have been synthesized to improve the chronic treatment of patients with diabetes but, because of the pharmacokinetic characteristics that include shorter on-set and off-set, they can be effectively used also in ICU patients and have the potential to be associated with a more limited risk of inducing episodes of iatrogenic hypoglycemia. Medical therapies carry an intrinsic risk for collateral effects; this can be more harmful in patients with unstable clinical conditions like ICU patients. To minimize these risks, the use of short acting drugs in ICU patients have gained a progressively larger room in ICU and now pharmaceutical companies and researchers design drugs dedicated to this subset of medical practice. In this article we report the rationale of using short acting drugs in ICU patients (i.e., sedation and treatment of arterial hypertension) and we also describe SAIA and their therapeutic use in ICU with the potential to minimize iatrogenic hypoglycemia related to IIT. The pharmacodynamic and pharmachokinetic characteristics of SAIA will be also discussed. PMID:24936244

  12. Acute Psychological Stress Results in the Rapid Development of Insulin Resistance

    PubMed Central

    Li, Li; Li, Xiaohua; Zhou, Wenjun; Messina, Joseph L.

    2013-01-01

    In recent years, the roles of chronic stress and depression as an independent risk factor for decreased insulin sensitivity and the development of diabetes have been increasingly recognized. However, an understanding and the mechanisms linking insulin resistance and acute psychological stress are very limited. We hypothesized that acute psychological stress may cause the development of insulin resistance, which may be a risk factor in developing type 2 diabetes. We tested the hypothesis in a well-established mouse model using 180 episodes of inescapable foot shock (IES), followed by a behavioral escape test. In this study, mice that received IES treatment were tested for acute insulin resistance by measuring glucose metabolism and insulin signaling. When compared to normal and sham mice, mice that were exposed to IES resulting in escape failure (defined as IES with behavioral escape failure) displayed elevated blood glucose levels in both glucose tolerance and insulin tolerance tests. Furthermore, mice with IES exposure and behavioral escape failure exhibited impaired hepatic insulin signaling via the insulin-induced insulin receptor/insulin receptor substrate 1/Akt pathway, without affecting similar pathways in skeletal muscle, adipose tissue and brain. Additionally, a rise in murine growth-related oncogene KC/GRO was associated with impaired glucose metabolism in IES mice, suggesting a mechanism by which psychological stress by IES may influence glucose metabolism. The present results indicate that psychological stress induced by IES can acutely alter hepatic responsiveness to insulin and affect whole-body glucose metabolism. PMID:23444388

  13. Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance

    PubMed Central

    Malin, Steven K.; Rynders, Corey A.; Weltman, Judy Y.; Barrett, Eugene J.; Weltman, Arthur

    2016-01-01

    Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes. PMID:27111219

  14. Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats

    PubMed Central

    Zhang, Ning; Liang, Hanyu; Farese, Robert V.; Li, Ji

    2015-01-01

    Aims To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. Materials and Methods For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Results Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Conclusions Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo. PMID:26196892

  15. Effect of insulin on the inflammatory and acute phase response after burn injury.

    PubMed

    Jeschke, Marc G; Boehning, Darren F; Finnerty, Celeste C; Herndon, David N

    2007-09-01

    After a severe burn, the liver plays a pivotal role by modulating inflammatory processes, metabolic pathways, immune functions, and the acute phase response. Therefore, liver integrity and function are important for recovery. A thermal injury, however, causes hepatic damage by inducing hepatic edema, fatty infiltration, hepatocyte apoptosis, and metabolic derangements associated with insulin resistance and impaired insulin signaling. In preliminary studies, we found that these pathophysiological processes are related to hepatic inflammation, altered intracellular signaling, and mitochondrial dysfunction. We hypothesize that modulation of these processes with insulin could improve hepatic structure and function and, therefore, outcome of burned and critically ill patients. Insulin administration improves survival and decreases the rate of infections in severely burned and critically ill patients. Here, we show that insulin administration decreases the synthesis of proinflammatory cytokines and signal transcription factors and improves hepatic structure and function after a severe burn injury; insulin also restores hepatic homeostasis and improves hepatic dysfunction postburn via alterations in the signaling cascade.

  16. Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy

    PubMed Central

    Dal, Stéphanie; Jeandidier, Nathalie; Seyfritz, Elodie; Bietiger, William; Péronet, Claude; Moreau, François; Pinget, Michel; Maillard, Elisa

    2015-01-01

    Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg). Untreated rats and rats administered Insuplant® (2 UI/200 g/day) through a subcutaneous osmotic pump for one or four weeks were compared with non-diabetic controls. Body weight, fructosamine level, total cholesterol, Insulin Growth Factor-1 (IGF-1) level, lipid peroxidation, and total antioxidant capacity were measured. Hepatic injury was determined through the measurement of glycogen content, reactive oxygen species (ROS) production, and macrophage infiltration. Liver oxidative stress status was evaluated through the measurement of superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) expression, and p38 mitogen-activated protein kinase (p38MAPK) activation. Induction of diabetes led to increased plasma oxidative stress and inflammation. Moreover, ROS production and macrophage infiltration increased in addition to SOD, CAT, and NADPH oxidase expression. Intensive insulin therapy improved metabolic control in diabetic animals as seen by a restoration of hepatic glycogen, plasma IGF-1 levels, and a decrease in plasma oxidative stress. However, insulin treatment did not result in a decrease in acute inflammation in diabetic rats as seen by continued ROS production and macrophage infiltration in the liver, and a decrease of p38MAPK activation. These results suggest that the onset of diabetes induces liver oxidative stress and inflammation, and that subcutaneous insulin administration cannot completely reverse these changes. Targeting oxidative stress and/or inflammation in diabetic patients could be an interesting strategy to improve therapeutic options. PMID:26385497

  17. Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy.

    PubMed

    Dal, Stéphanie; Jeandidier, Nathalie; Seyfritz, Elodie; Bietiger, William; Péronet, Claude; Moreau, François; Pinget, Michel; Maillard, Elisa; Sigrist, Séverine

    2016-01-01

    Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg). Untreated rats and rats administered Insuplant® (2 UI/200 g/day) through a subcutaneous osmotic pump for one or four weeks were compared with non-diabetic controls. Body weight, fructosamine level, total cholesterol, Insulin Growth Factor-1 (IGF-1) level, lipid peroxidation, and total antioxidant capacity were measured. Hepatic injury was determined through the measurement of glycogen content, reactive oxygen species (ROS) production, and macrophage infiltration. Liver oxidative stress status was evaluated through the measurement of superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) expression, and p38 mitogen-activated protein kinase (p38MAPK) activation. Induction of diabetes led to increased plasma oxidative stress and inflammation. Moreover, ROS production and macrophage infiltration increased in addition to SOD, CAT, and NADPH oxidase expression. Intensive insulin therapy improved metabolic control in diabetic animals as seen by a restoration of hepatic glycogen, plasma IGF-1 levels, and a decrease in plasma oxidative stress. However, insulin treatment did not result in a decrease in acute inflammation in diabetic rats as seen by continued ROS production and macrophage infiltration in the liver, and a decrease of p38MAPK activation. These results suggest that the onset of diabetes induces liver oxidative stress and inflammation, and that subcutaneous insulin administration cannot completely reverse these changes. Targeting oxidative stress and/or inflammation in diabetic patients could be an interesting strategy to improve therapeutic options.

  18. Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation.

    PubMed

    Bajpeyi, Sudip; Tanner, Charles J; Slentz, Cris A; Duscha, Brian D; McCartney, Jennifer S; Hickner, Robert C; Kraus, William E; Houmard, Joseph A

    2009-04-01

    The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of approximately 12 miles/wk, 1,200 kcal/wk at 40-55% peak O(2) consumption (Vo(2peak)), 200 min exercise/wk], 2) low volume/vigorous intensity ( approximately 12 miles/wk, 1,200 kcal/wk at 65-80% Vo(2peak), 125 min/wk), and 3) high volume/vigorous intensity ( approximately 20 miles/wk, 2,000 kcal/wk at 65-80% Vo(2peak), 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, S(I)) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. S(I) increased with training compared with the sedentary condition (P < or = 0.05) at 16-24 h with all of the exercise prescriptions. S(I) decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days S(I) was significantly elevated compared with sedentary (P < or = 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.

  19. [Principles of intensive care in severe acute pancreatitis in 2008].

    PubMed

    Darvas, Katalin; Futó, Judit; Okrös, Ilona; Gondos, Tibor; Csomós, Akos; Kupcsulik, Péter

    2008-11-23

    Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate

  20. [Principles of intensive care in severe acute pancreatitis in 2008].

    PubMed

    Darvas, Katalin; Futó, Judit; Okrös, Ilona; Gondos, Tibor; Csomós, Akos; Kupcsulik, Péter

    2008-11-23

    Acute pancreatitis is a dynamic, often progressive disease; 14-20% require intensive care in its severe form due to multiorgan dysfunction and/or failure. This review was created using systematic literature review of articles published on this subject in the last 5 years. The outcome of severe acute pancreatitis is determined by the inflammatory response and multiorgan dysfunction - the prognostic scores (Acute Physiology and Chronic Health Evaluation, Glasgow Prognostic Index, Sepsis-related Organ Failure Assessment, Multi Organ Dysfunction Syndrome Scale, Ranson Scale) can be used to determine outcome. Clinical signs (age, coexisting diseases, confusion, obesity) and biochemistry values (serum amylase, lipase, C-reactive protein, procalcitonin, creatinine, urea, calcium) have important prognostic roles as well. Early organ failure increases the risk of late abdominal complications and mortality. Intensive care can provide appropriate multi-function patient monitoring which helps in early recognition of complications and appropriate target-controlled treatment. Treatment of severe acute pancreatitis aims at reducing systemic inflammatory response and multiorgan dysfunction and, on the other side, at increasing the anti-inflammatory response. Oral starvation for 24-48 hours is effective in reducing the exocrine activity of the pancreas; the efficacy of protease inhibitors is questionable. Early intravascular volume resuscitation and stable haemodynamics improve microcirculation. Early oxygen therapy and mechanical ventilation provide adequate oxygenation. Electrolyte and acid-base control can be as important as tight glucose control. Adequate pain relief can be achieved by thoracic epidural catheterization. Early enteral nutrition with immunonutrition should be used. There is evidence that affecting the coagulation cascade by activated protein C can play a role in reducing the inflammatory response. The complex therapy of acute pancreatitis includes appropriate

  1. Effect of patient-selected intensive insulin therapy on quality of life.

    PubMed

    Chantelau, E; Schiffers, T; Schütze, J; Hansen, B

    1997-02-01

    The purpose of the study was to assess quality of life in patients with IDDM in relation to the type of insulin therapy. Two patient cohorts were studied. In cohort A, 77 patients deliberately intensified their traditional insulin injection therapy from up to two daily injections with syringe to multiple daily injections with insulin-pen; in cohort B, 55 patients changed from intensive therapy with pen to insulin pump-treatment (CSII). The therapeutic regimens were changed during a 5-day in-patient treatment and teaching course. The DCCT questionnaire was applied before and up to 6 months after changing of therapy. Treatment satisfaction increased after intensification of insulin therapy in both groups, mainly due to greater flexibility with leisure-time activities, and with the diet. Pump-users reported reduced problems with hypoglycemia (P < 0.02). HbA1c indicating acceptable metabolic control already before the study, remained unchanged. Therapy-associated inconvenience, mainly in association with lifestyle, improved in IDDM patients deliberately intensifying their insulin therapy by pens or pumps (CSII). Pump-treatment, rather than pen-therapy, conferred particular protection from hypoglycaemia.

  2. High intensity interval training improves liver and adipose tissue insulin sensitivity

    PubMed Central

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

  3. Effects of different intensities of physical exercise on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of obese mice

    PubMed Central

    Marinho, Rodolfo; de Moura, Leandro Pereira; Rodrigues, Bárbara de Almeida; Pauli, Luciana Santos Souza; da Silva, Adelino Sanchez Ramos; Ropelle, Eloize Cristina Chiarreotto; de Souza, Claudio Teodoro; Cintra, Dennys Esper Corrêa; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2014-01-01

    ABSTRACT Objective: To investigate the effects of different intensities of acute exercise on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of obese mice. Methods: Swiss mice were randomly divided into four groups, and fed either a standard diet (control group) or high fat diet (obese sedentary group and obese exercise group 1 and 2) for 12 weeks. Two different exercise protocols were used: swimming for 1 hour with or without an overload of 5% body weight. The insulin tolerance test was performed to estimate whole-body sensitivity. Western blot technique was used to determine protein levels of protein kinase B/Akt and phosphorylation by protein Kinase B/Akt in mice skeletal muscle. Results: A single bout of exercise inhibited the high fat diet-induced insulin resistance. There was increase in phosphorylation by protein kinase B/Akt serine, improve in insulin signaling and reduce of fasting glucose in mice that swam for 1 hour without overload and mice that swan for 1 hour with overload of 5%. However, no significant differences were seen between exercised groups. Conclusion: Regardless of intensity, aerobic exercise was able to improve insulin sensitivity and phosphorylation by protein kinase B/Ak, and proved to be a good form of treatment and prevention of type 2 diabetes. PMID:24728251

  4. The future is now: software-guided intensive insulin therapy in the critically ill.

    PubMed

    Rattan, Rishi; Nasraway, Stanley A

    2013-03-01

    Since the development of intensive insulin therapy for the critically ill adult, tight glycemic control (TGC) has become increasingly complicated to apply and achieve. Software-guided (SG) algorithms for insulin dosing represent a new method to achieve euglycemia in critical illness. We provide an overview of the state of SG TGC with an eye to the future. The current milieu is disorganized, with little research that incorporates newer variables of dysglycemia, such as glycemic variability. To develop and implement better algorithms, scientists, programmers, and clinicians need to standardize measurements and variables.

  5. The Future Is Now: Software-Guided Intensive Insulin Therapy in the Critically Ill

    PubMed Central

    Rattan, Rishi; Nasraway, Stanley A.

    2013-01-01

    Since the development of intensive insulin therapy for the critically ill adult, tight glycemic control (TGC) has become increasingly complicated to apply and achieve. Software-guided (SG) algorithms for insulin dosing represent a new method to achieve euglycemia in critical illness. We provide an overview of the state of SG TGC with an eye to the future. The current milieu is disorganized, with little research that incorporates newer variables of dysglycemia, such as glycemic variability. To develop and implement better algorithms, scientists, programmers, and clinicians need to standardize measurements and variables. PMID:23567013

  6. 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

  7. An acute bout of endurance exercise but not sprint interval exercise enhances insulin sensitivity.

    PubMed

    Brestoff, Jonathan R; Clippinger, Benjamin; Spinella, Thomas; von Duvillard, Serge P; Nindl, Bradley C; Nindl, Bradley; Arciero, Paul J

    2009-02-01

    An acute bout of endurance exercise (EE) enhances insulin sensitivity, but the effects of sprint interval exercise (SIE) have not yet been described. We sought to compare insulin sensitivity at baseline and after an acute bout of EE and SIE in healthy men (n = 8) and women (n = 5) (age, 20.7 +/- 0.3 years; peak oxygen consumption (VO2 peak), 42.6 +/- 1.7 mL.kg(-1).min(-1); <1.5 days.week(-1) structured exercise; body fat, 21.1 +/- 1.9%). Subjects underwent 3 oral glucose tolerance tests (OGTT(s)) the day after each of the following 3 conditions: no exercise, baseline (OGTT(B)); SIE at approximately 125% VO(2 peak) (OGTT(SIE)); and EE at approximately 75% VO(2 peak )(OGTT(EE)). SIE and EE sessions were randomized for each subject. Subjects consumed identical meals the day preceding each OGTT. Two insulin sensitivity indices - composite whole-body insulin sensitivity index (ISI-COMP) and ISI-hepatic insulin sensitivity (HOMA) - were calculated, using previously validated formulas (ISI-COMP = 10 000/ radical(glucose(fasting)) x insulin(fasting) x glucose(mean OGTT) x insulin(mean OGTT)); ISI-HOMA = 22.5/(insulin(fasting) x glucose(fasting)), and the plasma concentrations of cytokines interleukin-6 and tumor necrosis factor-alpha were measured. There were no differences by sex for any condition (men vs. women, p > 0.05). Pearson's correlation coefficients between ISI-COMP and ISI-HOMA for each condition were highly correlated (p < 0.01), and followed similar patterns of response. ISI-COMP(EE) was 71.4% higher than ISI-COMP(B) (8.4 +/- 1.4 vs. 4.9 +/- 1.0; p < 0.01) and 40.0% higher than ISI-COMPSIE (8.4 +/- 1.4 vs. 6.0 +/- 1.5; p < 0.05), but there was no difference between ISI-COMP(B) and ISI-COMP(SIE) (p = 0.182). VO(2 peak) was highly correlated with both ISI-COMP and ISI-HOMA during baseline and SIE test conditions (p < 0.02). These findings demonstrate that an acute bout of EE, but not SIE, increases insulin sensitivity relative to a no-exercise control condition

  8. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice.

    PubMed

    Kurauti, Mirian A; Freitas-Dias, Ricardo; Ferreira, Sandra M; Vettorazzi, Jean F; Nardelli, Tarlliza R; Araujo, Hygor N; Santos, Gustavo J; Carneiro, Everardo M; Boschero, Antonio C; Rezende, Luiz F; Costa-Júnior, José M

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60-70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  9. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice.

    PubMed

    Kurauti, Mirian A; Freitas-Dias, Ricardo; Ferreira, Sandra M; Vettorazzi, Jean F; Nardelli, Tarlliza R; Araujo, Hygor N; Santos, Gustavo J; Carneiro, Everardo M; Boschero, Antonio C; Rezende, Luiz F; Costa-Júnior, José M

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60-70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe.

  10. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice

    PubMed Central

    Ferreira, Sandra M.; Vettorazzi, Jean F.; Nardelli, Tarlliza R.; Araujo, Hygor N.; Santos, Gustavo J.; Carneiro, Everardo M.; Boschero, Antonio C.; Rezende, Luiz F.; Costa-Júnior, José M.

    2016-01-01

    The effects of exercise on insulin clearance and IDE expression are not yet fully elucidated. Here, we have explored the effect of acute exercise on insulin clearance and IDE expression in lean mice. Male Swiss mice were subjected to a single bout of exercise on a speed/angle controlled treadmill for 3-h at approximately 60–70% of maximum oxygen consumption. As expected, acute exercise reduced glycemia and insulinemia, and increased insulin tolerance. The activity of AMPK-ACC, but not of IR-Akt, pathway was increased in the liver and skeletal muscle of trained mice. In an apparent contrast to the reduced insulinemia, glucose-stimulated insulin secretion was increased in isolated islets of these mice. However, insulin clearance was increased after acute exercise and was accompanied by increased expression of the insulin-degrading enzyme (IDE), in the liver and skeletal muscle. Finally, C2C12, but not HEPG2 cells, incubated at different concentrations of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 3-h, showed increased expression of IDE. In conclusion, acute exercise increases insulin clearance, probably due to an augmentation of IDE expression in the liver and skeletal muscle. The elevated IDE expression, in the skeletal muscle, seems to be mediated by activation of AMPK-ACC pathway, in response to exercise. We believe that the increase in the IDE expression, comprise a safety measure to maintain glycemia at or close to physiological levels, turning physical exercise more effective and safe. PMID:27467214

  11. Skin temperature reveals the intensity of acute stress

    PubMed Central

    Herborn, Katherine A.; Graves, James L.; Jerem, Paul; Evans, Neil P.; Nager, Ruedi; McCafferty, Dominic J.; McKeegan, Dorothy E.F.

    2015-01-01

    Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research. PMID:26434785

  12. Effects of intensive insulin therapy upon pancreatic β cell function in patients newly diagnosed with type II diabetes

    PubMed Central

    Wang, Defeng; Sun, Li; Song, Guangyao; Chen, Shuchun

    2015-01-01

    Objective: This study was designed to evaluate the clinical efficacy of intensive insulin therapy for patients newly diagnosed with type 2 diabetes. Methods: A total of 219 patients newly diagnosed with type 2 diabetes were randomly assigned into insulin group (n = 55), gliclazide group (n = 52), metformin group (n = 55) and pioglitazone group (n = 57). On the basis of diet and physical interventions, patients in the insulin group received intensive insulin therapy. Those in other three groups were given oral intake of medication. All treatment schemes endured for 12 weeks. A variety of indexes including fasting blood-glucose (FPG), FPG at 2 h after diet (FPG 2 h), hemoglobin A1 c (HbAlc), area under the curve (AUC) for insulin (insulin AUC) after glucose load, C-peptide AUC after glucose load (C-peptide AUC), changes in insulin secretion index (Homa-β) and insulin resistance index( Homa-IR) were accurately measured and statistically among different groups. Results: The insulin AUC at 0-30 min, C-peptide AUC at 0-30 min and Homa-β in the insulin group were equally significantly higher compared with those levels in the other three groups. In addition, the level of Homa-IR in the insulin, metformin and pioglitazone groups were all significantly reduced compared with the values prior to respective treatment (all P < 0.05). Conclusion: Compared with oral administration of hypoglycemic drugs, intensive insulin therapy is able to better improve pancreatic β cell function and insulin resistance for newly-diagnosed type 2 diabetes patients. PMID:25785143

  13. Insulin

    MedlinePlus

    ... pump is connected to your body by a flexible tube that has a tip that sticks under your skin. A cartridge of insulin is put in the pump. The insulin flows through the tube into your body. The pump controls how much insulin goes into your body. The ...

  14. Acute high-intensity endurance exercise is more effective than moderate-intensity exercise for attenuation of postprandial triglyceride elevation.

    PubMed

    Trombold, Justin R; Christmas, Kevin M; Machin, Daniel R; Kim, Il-Young; Coyle, Edward F

    2013-03-15

    Acute exercise has been shown to attenuate postprandial plasma triglyceride elevation (PPTG). However, the direct contribution of exercise intensity is less well understood. The purpose of this study was to examine the effects of exercise intensity on PPTG and postprandial fat oxidation. One of three experimental treatments was performed in healthy young men (n = 6): nonexercise control (CON), moderate-intensity exercise (MIE; 50% Vo2peak for 60 min), or isoenergetic high-intensity exercise (HIE; alternating 2 min at 25% and 2 min at 90% Vo2peak). The morning after the exercise, a standardized meal was provided (16 kcal/kg BM, 1.02 g fat/kg, 1.36 g CHO/kg, 0.31 g PRO/kg), and measurements of plasma concentrations of triglyceride (TG), glucose, insulin, and β-hydroxybutyrate were made in the fasted condition and hourly for 6 h postprandial. Indirect calorimetry was used to determine fat oxidation in the fasted condition and 2, 4, and 6 h postprandial. Compared with CON, both MIE and HIE significantly attenuated PPTG [incremental AUC; 75.2 (15.5%), P = 0.033, and 54.9 (13.5%), P = 0.001], with HIE also significantly lower than MIE (P = 0.03). Postprandial fat oxidation was significantly higher in MIE [83.3 (10.6%) of total energy expenditure] and HIE [89.1 (9.8) %total] compared with CON [69.0 (16.1) %total, P = 0.039, and P = 0.018, respectively], with HIE significantly greater than MIE (P = 0.012). We conclude that, despite similar energy expenditure, HIE was more effective than MIE for lowering PPTG and increasing postprandial fat oxidation.

  15. Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

    PubMed Central

    2014-01-01

    Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

  16. Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial metabolism and insulin secretion.

    PubMed

    Ainscow, E K; Zhao, C; Rutter, G A

    2000-07-01

    Islet beta-cells express low levels of lactate dehydrogenase and have high glycerol phosphate dehydrogenase activity. To determine whether this configuration favors oxidative glucose metabolism via mitochondria in the beta-cell and is important for beta-cell metabolic signal transduction, we have determined the effects on glucose metabolism and insulin secretion of acute overexpression of the skeletal muscle isoform of lactate dehydrogenase (LDH)-A. Monitored in single MIN6 beta-cells, LDH hyperexpression (achieved by intranuclear cDNA microinjection or adenoviral infection) diminished the response to glucose of both phases of increases in mitochondrial NAD(P)H, as well as increases in mitochondrial membrane potential, cytosolic free ATP, and cystolic free Ca2+. These effects were observed at all glucose concentrations, but were most pronounced at submaximal glucose levels. Correspondingly, adenoviral vector-mediated LDH-A overexpression reduced insulin secretion stimulated by 11 mmol/l glucose and the subsequent response to stimulation with 30 mmol/l glucose, but it was without significant effect when the concentration of glucose was raised acutely from 3 to 30 mmol/l. Thus, overexpression of LDH activity interferes with normal glucose metabolism and insulin secretion in the islet beta-cell type, and it may therefore be directly responsible for insulin secretory defects in some forms of type 2 diabetes. The results also reinforce the view that glucose-derived pyruvate metabolism in the mitochondrion is critical for glucose-stimulated insulin secretion in the beta-cell.

  17. Novel Zn2+ Modulated GPR39 Receptor Agonists Do Not Drive Acute Insulin Secretion in Rodents

    PubMed Central

    Yasuda, Shin-ichiro; Tsuchida, Takuma; Oguma, Takahiro; Marley, Anna; Wennberg-Huldt, Charlotte; Hovdal, Daniel; Fukuda, Hajime; Yoneyama, Yukimi; Sasaki, Kazuyo; Johansson, Anders; Lundqvist, Sara; Brengdahl, Johan; Isaacs, Richard J.; Brown, Daniel; Geschwindner, Stefan; Benthem, Lambertus; Priest, Claire; Turnbull, Andrew

    2015-01-01

    Type 2 diabetes (T2D) occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion in vivo. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn2+ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO) mice and Zucker fatty rats. It is concluded that Zn2+ modulated GPR39 agonists do not acutely stimulate insulin release in rodents. PMID:26720709

  18. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.

    PubMed

    Jedrzkiewicz, Sean; Parker, John D

    2013-05-01

    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P < .015; 95% confidence intervals 0.25-0.77). There was also an increase in the HOMA-IR index; on visit 1, the median HOMA-IR (interquartile range) was 5.2 (3.9) versus 6.9 (6.8) on visit 3 (P < .015). Other indices of glucose metabolism did not change. These observations document that GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans.

  19. Serum estradiol but not gonadotropin levels decrease acutely after insulin-induced hypoglycemia in cycling women.

    PubMed

    Bing-You, R G; Spratt, D I

    1992-10-01

    Although corticotropin-releasing hormone (CRH) acutely suppresses gonadotropin-releasing hormone (GnRH) secretion in animal models, its effect on the hypothalamic-pituitary-gonadal axis in humans is not well defined. To further evaluate the acute effects of adrenal axis activation on the hypothalamic-pituitary-gonadal axis in humans, we employed a model of insulin-induced hypoglycemia to stimulate endogenous CRH secretion in eight cycling women. Serum samples were obtained immediately before and 15, 30, 45, 60, 75, 90, and 120 min following iv insulin (0.15 U/kg) or saline injection. To ensure that the degree of hypothalamic-pituitary-adrenal activation in our subjects was similar to that observed in severely ill patients with hypogonadotropism, serum cortisol (F) levels were also measured in a group of acutely ill patients selected to have hypogonadotropism. All women experienced symptomatic hypoglycemia after insulin injection. Differences between serum F levels in hypoglycemic vs. control sessions were evident at 30 min (P < 0.01) and maximum at 120 min (P < 0.0001) after insulin injection. Serum estradiol levels were significantly lower following hypoglycemia than during control sessions (P < 0.001). In contrast, serum LH and FSH levels were not significantly different between control and hypoglycemic sessions. Peak serum F levels in these hypoglycemic women were similar to F levels in critically ill patients with hypogonadotropism. These results demonstrate that stress and/or hypoglycemia can acutely decrease circulating estradiol levels. In addition, these data suggest that endogenous CRH does not play a major role in acute suppression of GnRH (over 2 h) in humans. Further studies are required to identify longer term effects of CRH on GnRH secretion which may be present in hypothalamic amenorrhea or hypogonadotropic hypogonadism of critical illness.

  20. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    PubMed

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. PMID:27511839

  1. Effects of smoking cessation, acute re-exposure and nicotine replacement in smokers on AIR® inhaled insulin pharmacokinetics and glucodynamics

    PubMed Central

    Pan, Alan X; de la Peña, Amparo; Yeo, Kwee P; Chan, Clark; Loh, Mei T; Wise, Stephen D; Silverman, Bernard L; Muchmore, Douglas B

    2008-01-01

    Aims To explore the effects of smoking cessation and acute smoking re-exposure on the pharmacokinetic (PK) and glucodynamic (GD) profiles of AIR® inhaled insulin (AIR Insulin) with or without nicotine replacement therapy (NRT). Methods Nondiabetic smokers (n = 24) with normal pulmonary function completed a two-phase (four-period), open-label, randomized euglycaemic clamp study. During the initial study phase, subjects underwent glucose clamps following AIR Insulin dosing, shortly after smoking, 8–12 h after smoking, or following subcutaneous insulin lispro shortly after smoking. AIR Insulin PK and GD were again assessed during and after a 4-week smoking-cessation period with or without NRT. In the last study period, subjects smoked one cigarette shortly before final AIR Insulin dosing and glucose clamp, to study the effect of acute smoking re-exposure on inhaled insulin PK and GD. Results Compared with the preceding active smoking phase, the administration of AIR Insulin in nondiabetic subjects undergoing a 4-week period of smoking abstinence resulted in a decrease in PK and GD of approximately 25% (P = 0.008 for both), an effect which was greater in subjects using NRT. Following rechallenge with a single cigarette (without NRT), GD response to AIR Insulin increased significantly (P = 0.006) towards precessation levels, relative to smoking abstinence. In subjects using NRT, however, the increase in GD was less pronounced. Conclusion Smoking, smoking cessation and acute re-exposure with a single cigarette are associated with clinically significant alterations in AIR Insulin pharmacokinetics and glucodynamics. AIR Insulin should not be used by smokers or those at risk for recidivism. What is already known about this subject Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the

  2. Acute renal failure in the intensive care unit.

    PubMed

    Weisbord, Steven D; Palevsky, Paul M

    2006-06-01

    Acute renal failure (ARF) is a common complication in critically ill patients, with ARF requiring renal replacement therapy (RRT) developing in approximately 5 to 10% of intensive care unit (ICU) patients. Epidemiological studies have demonstrated that ARF is an independent risk factor for mortality. Interventions to prevent the development of ARF are currently limited to a small number of settings, primarily radiocontrast nephropathy and rhabdomyolysis. There are no effective pharmacological agents for the treatment of established ARF. Renal replacement therapy remains the primary treatment for patients with severe ARF; however, the data guiding selection of modality of RRT and the optimal timing of initiation and dose of therapy are inconclusive. This review focuses on the epidemiology and diagnostic approach to ARF in the ICU and summarizes our current understanding of therapeutic approaches including RRT.

  3. Intensive Insulin Therapy in Critically Ill Hospitalized Patients: Making It Safe and Effective

    PubMed Central

    Klonoff, David C

    2011-01-01

    Intensive insulin therapy (IIT) for hyperglycemia in critically ill patients has become a standard practice. Target levels for glycemia have fluctuated since 2000, as evidence initially indicated that tight glycemic control to so-called normoglycemia (80–110 mg/dl) leads to the lowest morbidity and mortality without hypoglycemic complications. Subsequent studies have demonstrated minimal clinical benefit combined with greater hypoglycemic morbidity and mortality with tight glycemic control in this population. The consensus glycemic targets were then liberalized to the mid 100s (mg/dl). Handheld POC blood glucose (BG) monitors have migrated from the outpatient setting to the hospital environment because they save time and money for managing critically ill patients who require IIT. These devices are less accurate than hospital-grade POC blood analyzers or central laboratory analyzers. Three questions must be answered to understand the role of IIT for defined populations of critically ill patients: (1) How safe is IIT, with various glycemic targets, from the risk of hypoglycemia? (2) How tightly must BG be controlled for this approach to be effective? (3) What role does the accuracy of BG measurements play in affecting the safety of this method? For each state of impaired glucose regulation seen in the hospital, such as hyperglycemia, hypoglycemia, or glucose variability, the benefits, risks, and goals of treatment, including IIT, might differ. With improved accuracy of BG monitors, IIT might be rendered even more intensive than at present, because patients will be less likely to receive inadvertent overdosages of insulin. Greater doses of insulin, but with dosing based on more accurate glucose levels, might result in less hypoglycemia, less hyperglycemia, and less glycemic variability. PMID:21722591

  4. PKA Enhances the Acute Insulin Response Leading to the Restoration of Glucose Control

    PubMed Central

    Kaihara, Kelly A.; Dickson, Lorna M.; Ellenbroek, Johanne H.; Orr, Caitlin M.D.; Layden, Brian T.

    2015-01-01

    Diabetes arises from insufficient insulin secretion and failure of the β-cell mass to persist and expand. These deficits can be treated with ligands to Gs-coupled G-protein-coupled receptors that raise β-cell cAMP. Here we studied the therapeutic potential of β-cell cAMP-dependent protein kinase (PKA) activity in restoring glucose control using β-caPKA mice. PKA activity enhanced the acute insulin response (AIR) to glucose, which is a primary determinant of the efficacy of glucose clearance. Enhanced AIR improved peripheral insulin action, leading to more rapid muscle glucose uptake. In the setting of pre-established glucose intolerance caused by diet-induced insulin resistance or streptozotocin-mediated β-cell mass depletion, PKA activation enhanced β-cell secretory function to restore glucose control, primarily through augmentation of the AIR. Enhanced AIR and improved glucose control were maintained through 16 weeks of a high-fat diet and aging to 1 year. Importantly, improved glucose tolerance did not increase the risk for hypoglycemia, nor did it rely upon hyperinsulinemia or β-cell hyperplasia, although PKA activity was protective for β-cell mass. These data highlight that improving β-cell function through the activation of PKA has a large and underappreciated capacity to restore glucose control with minimal risk for adverse side effects. PMID:25475437

  5. Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

    PubMed

    Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

    2016-01-15

    Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet.

  6. Insulin

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The manipulation of organic materials--cells, tissues, and even living organisms--offers many exciting possibilities for the future from organic computers to improved aquaculture. Commercial researchers are using the microgravity environment to produce large near perfect protein crystals Research on insulin has yielded crystals that far surpass the quality of insulin crystals grown on the ground. Using these crystals industry partners are working to develop new and improved treatments for diabetes. Other researchers are exploring the possibility of producing antibiotics using plant cell cultures which could lead to both orbital production and the improvement of ground-based antibiotic production.

  7. Intensive insulin treatment increases donor site wound protein synthesis in burn patients

    PubMed Central

    Tuvdendorj, Demidmaa; Zhang, Xiao-Jun; Chinkes, David L.; Aarsland, Asle; Kulp, Gabriela A.; Jeschke, Marc G.; Herndon, David N.

    2013-01-01

    Background In the treatment of burns, patients’ own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is routinely used to treat hyperglycemia after injury. We investigated whether intensive insulin treatment (INS) increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA). Methods FSR of the donor site wound protein was measured in pediatric patients randomized to control (CNT) (n = 13) and INS (n = 10) treatments. Depending on the postoperative day when the tracer study was done studies were divided into “Early” (days < 5) and “Late” (days >=5) periods. Results FSR of the donor site wound protein was greater in the INS group at the “Early” period of wound healing (CNT vs. INS, 8.2±3.8 vs. 13.1±6.9 %/day, p: < 0.05); but not at the “Late” (CNT vs. INS, 19.7±4.6 vs. 16.6±4.0 %/day, p > 0.05). Despite these differences LOS/TBSA was not decreased in the INS group. Correlation analyses demonstrated that independently of the treatment regimen FSR positively correlated (p < 0.05) with time post creation of the donor site and negatively correlated (p < 0.05) with LOS/TBSA. Conclusions Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independently of the treatment regimen. PMID:21236451

  8. Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training.

    PubMed

    DiPietro, Loretta; Dziura, James; Yeckel, Catherine W; Neufer, P Darrell

    2006-01-01

    Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant. Healthy older (73 +/- 10 yr) women (N = 25) who were inactive, but not obese, were randomized into one of three training programs (9-mo duration): 1) high-intensity [80% peak aerobic capacity (V(O2)peak); T(H)] aerobic training; 2) moderate-intensity (65% V(O2)peak; T(M)) aerobic training; or 3) low-intensity (stretching) placebo control (50% V(O2)peak); C(TB)). Importantly, exercise volume (300 kcal/session) was held constant for subjects in both the T(H) and the T(M) groups. V(O2)peak was determined by using a graded exercise challenge on a treadmill. Total body fat and lean mass were determined with dual-energy X-ray absorptiometry. The rate of insulin-stimulated glucose utilization as well as the suppression of lipolysis were determined approximately 72 h after the final exercise bout by using a two-step euglycemic-hyperinsulinemic clamp. We observed improved glucose utilization at the higher insulin dose with training, but these improvements were statistically significant only in the T(H) (21%; P = 0.02) compared with the T(M) (16%; P = 0.17) and C(TB) (8%; P = 0.37) groups and were observed without changes in either body composition or V(O2)peak. Likewise in the T(H) group, we detected a significant improvement in insulin-stimulated suppression (%) of adipose tissue lipolysis at the low-insulin dose (38-55%, P < 0.05). Our findings suggest that long-term higher intensity exercise training provides more enduring benefits to insulin action compared with moderate- or low-intensity exercise, likely due to greater transient effects.

  9. Short term response of insulin, glucose, growth hormone and corticosterone to acute vibration in rats.

    NASA Technical Reports Server (NTRS)

    Dolkas, C. B.; Leon, H. A.; Chackerian, M.

    1971-01-01

    Study carried out to obtain some notion of the initial phasing and interactive effects among some hormones known to be responsive to vibration stress. Sprague-Dawley derived rats were exposed to the acute effects of confinement and confinement with lateral (plus or minus G sub y) vibration. The coincident monitoring of glucose, insulin, growth hormone, and corticosterone plasma levels, during and immediately subsequent to exposure to brief low level vibration, exhibits the effects of inhibition of insulin release by epinephrine. The ability of insulin (IRI) to return rapidly to basal levels, from appreciably depressed levels during vibration, in the face of elevated levels of glucose is also shown. Corticosterone responds with almost equal rapidity, but in opposite phase to the IRI. The immuno-assayable growth hormone (IGH) dropped from a basal level of 32 ng/ml to 7.3 ng/ml immediately subsequent to vibration and remained at essentially that level throughout the experiment (60 min). Whether these levels represent a real fall in the rat or whether they merely follow the immuno-logically deficient form is still in question.

  10. Effects of intensive dietary treatment on insulin-stimulated skeletal muscle glycogen synthase activation and insulin secretion in newly presenting type 2 diabetic patients.

    PubMed

    Johnson, A B; Argyraki, M; Thow, J C; Broughton, D; Jones, I R; Taylor, R

    1990-06-01

    Ten newly presenting, untreated, Europid Type 2 diabetic patients were studied before and after 8 weeks treatment with intensive diet alone. Nine normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, prior to and during a 240-min insulin infusion (100 mU kg-1 h-1). Fasting blood glucose decreased from 12.1 +/- 0.9 (+/- SE) to 9.2 +/- 0.8 mmol l-1 (p less than 0.01), but there was no change in fasting insulin concentrations, 9.9 +/- 2.3 vs 9.3 +/- 2.1 mU l-1. Fractional GS activity did not increase in the Type 2 diabetic patients during the insulin infusion either at presentation (change -1.5 +/- 1.9%) or after treatment (change +0.9 +/- 1.8%), and was markedly decreased compared with the control subjects (change +14.5 +/- 2.8%, both p less than 0.001). Glucose requirement during the clamp was decreased in the Type 2 diabetic patients at presentation (2.2 +/- 0.7 vs 7.3 +/- 0.6 mg kg-1 min-1, p less than 0.001), and despite improvement following dietary treatment to 3.3 +/- 0.6 mg kg-1 min-1 (p less than 0.01) remained lower than in the control subjects (p less than 0.001). Fasting plasma non-esterified fatty acid (NEFA) concentrations were elevated at presentation (p less than 0.05), and failed to suppress normally during the insulin infusion. After treatment fasting NEFA concentrations decreased (p less than 0.05) and suppressed normally (p less than 0.05). Insulin secretion was assessed following an intravenous bolus of glucose (0.5 g kg-1) at euglycaemia before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy.

    PubMed

    Carta, Q; Meriggi, E; Trossarelli, G F; Catella, G; Dal Molin, V; Menato, G; Gagliardi, L; Massobrio, M; Vitelli, A

    1986-06-01

    Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women.

  12. Redesigning an intensive insulin service for patients with type 1 diabetes: a patient consultation exercise

    PubMed Central

    Ozcan, Seyda; Rogers, Helen; Choudhary, Pratik; Amiel, Stephanie A; Cox, Alison; Forbes, Angus

    2013-01-01

    Context Providing effective support for patients in using insulin effectively is essential for good diabetes care. For that support to be effective it must reflect and attend to the needs of patients. Purpose To explore the perspectives of adult type 1 diabetes patients on their current diabetes care in order to generate ideas for creating a new patient centered intensive insulin clinic. Methods A multi-method approach was used, comprising: an observational exercise of current clinical care; three focus groups (n = 17); and a survey of service users (n = 419) to test the ideas generated from the observational exercise and focus groups (rating 1 to 5 in terms of importance). The ideas generated by the multi-method approach were organized thematically and mapped onto the Chronic Care Model (CCM). Results The themes and preferences for service redesign in relation to CCM components were: health care organization, there was an interest in having enhanced systems for sharing clinical information; self-management support, patients would like more flexible and easy to access resources and more help with diabetes technology and psychosocial support; delivery system design and clinical information systems, the need for greater integration of care and better use of clinic time; productive relationships, participants would like more continuity; access to health professionals, patient involvement and care planning. The findings from the patient survey indicate high preferences for most of the areas for service enhancement identified in the focus groups and observational exercise. Clinical feedback and professional continuity (median = 5, interquartile range = 1) were the most highly rated. Conclusion The patient consultation process had generated important ideas on how the clinical team and service can improve the care provided. Key areas for service development were: a stronger emphasis of collaborative care planning; improved patient choice in the use of health technology

  13. A physical map at 1p31 encompassing the acute insulin response locus and the leptin receptor

    SciTech Connect

    Thompson, D.B.; Sutherland, J.; Apel, W.; Ossowski, V.

    1997-01-15

    Recently, we reported genetic linkage in Pima Indians between the acute insulin response to an intravenous glucose challenge and the short tandem repeat marker D1S198, indicative of a genetic element in this region that controls the phenotypic variation in the first phase of insulin secretion. As a first step to isolating the gene responsible for the acute insulin response, we have constructed a yeast artificial chromosome (YAC) contig map that spans the DNA microsatellites D1S438 through D1S464. The contig comprises 34 YACs on which we have mapped 44 ends of the genomic DNA inserts from the 34 YACs, 13 short tandem repeats, eight expressed sequence tags, and six genes. In addition, we have used this contig to construct a physical map encompassing approximately 9 Mb of DNA in this region. 21 refs., 2 figs.

  14. Acute handling disturbance modulates plasma insulin-like growth factor binding proteins in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of acute stressor exposure on proximal (growth hormone; GH) and distal (insulin-like growth factor-I; IGF-I and IGF-binding proteins) components of the somatotropic axis are poorly understood in finfish. We exposed rainbow trout (Oncorhynchus mykiss) to a 5-minute handling disturbance to...

  15. The effects of acute exercise on serum adiponectin and resistin levels and their relation to insulin sensitivity in overweight males.

    PubMed

    Jamurtas, A Z; Theocharis, V; Koukoulis, G; Stakias, N; Fatouros, I G; Kouretas, D; Koutedakis, Y

    2006-05-01

    The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson's correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (microg ml(-1)) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml(-1)) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity.

  16. The Effect of Glucose-Insulin-Potassium on Cardiac Ultrastructure Following Acute Experimental Coronary Occlusion

    PubMed Central

    Sybers, H. D.; Maroko, P. R.; Ashraf, M.; Libby, P.; Braunwald, E.

    1973-01-01

    The effects of glucose-insulin-potassium (GIK) on cardiac ultrastructure following acute experimental coronary occlusion were studied in dogs. Epicardial ST segment elevations at multiple sites on the anterior surface of the left ventricle 15 minutes after ligation of the left anterior descending coronary artery were used to predict infarct development. Biopsies removed from sites of known ST segment elevation were examined with the electron microscope, and the degree of injury was correlated with the ST segment elevation. The animals receiving GIK showed significantly less necrosis than was seen in dogs with occlusion alone at corresponding levels of ST segment elevation. Other evidence suggesting a beneficial effect of GIK was the presence of a fibrillar material in several biopsies from the treated animals, which may indicate the regeneration of myofilaments. ImagesFig 3Fig 4Fig 8Fig 9Fig 5Fig 6Fig 10Fig 7p[417]-aFig 1Fig 2 PMID:4570076

  17. Insulin signaling is acutely required for long-term memory in Drosophila.

    PubMed

    Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

    2015-01-01

    Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

  18. Calculation of the intake of three intense sweeteners in young insulin-dependent diabetics.

    PubMed

    Garnier-Sagne, I; Leblanc, J C; Verger, P

    2001-07-01

    In 1994, European Directive 94/35/CE authorised the use as food additives of five intense sweeteners for which Acceptable Daily Intakes (ADI) were established. The same directive stipulated that member states should organise a monitoring system to determine the consumption of these substances. Diabetic children are normally considered to constitute a group with a high consumption of sweeteners (European Commission, 1998. Report on Methodology for the Monitoring of Food Additives Intake across the European Union. Report of the Scientific Cooperation, Task 4.2 SCOOP/INT/REPORT/2. European Commission Directorate General III, Brussels.). A stepwise approach to the food additive intake in the general population had shown that three of the five authorised intense sweeteners (aspartame, saccharin and acesulfame K) are used at particularly high levels in sugar-free foods and are also very commonly utilised as table-top sweeteners. This paper presents the results of a food intake survey conducted in a group of French, insulin-dependent children in 1997, aimed at estimating the Theoretical Maximum Daily Intake (TMDI) for these three sweeteners and comparing this with the relevant ADI values. A 5-day diary questionnaire was used to estimate the intake of sugar-free, artificially sweetened foods and table-top sweeteners. When assessing the intake of each additive, all sugar-free products were assumed to be sweetened using a single sweetener at its maximum authorised level. This study was performed in five age groups, and based on the mean and 97.5th percentile of the distribution of consumption, demonstrated that it was unlikely that total exposure could rise above the ADI.

  19. Acute effects of 17 β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats.

    PubMed

    Alonso, Ana; González-Pardo, Héctor; Garrido, Pablo; Conejo, Nélida M; Llaneza, Plácido; Díaz, Fernando; Del Rey, Carmen González; González, Celestino

    2010-12-01

    Aging is characterized by decline in metabolic function and insulin resistance, and both seem to be in the basis of neurodegenerative diseases and cognitive dysfunction. Estrogens prevent age-related changes, and phytoestrogens influence learning and memory. Our hypothesis was that estradiol and genistein, using rapid-action mechanisms, are able to modify insulin sensitivity, process of learning, and spatial memory. Young and aged ovariectomized rats received acute treatment with estradiol or genistein. Aged animals were more insulin-resistant than young. In each age, estradiol and genistein-treated animals were less insulin-resistant than the others, except in the case of young animals treated with high doses of genistein. In aged rats, no differences between groups were found in spatial memory test, showing a poor performance in the water maze task. However, young females treated with estradiol or high doses of genistein performed well in spatial memory task like the control group. Only rats treated with high doses of genistein showed an optimal spatial memory similar to the control group. Conversely, acute treatment with high doses of phytoestrogens improved spatial memory consolidation only in young rats, supporting the critical period hypothesis for the beneficial effects of estrogens on memory. Therefore, genistein treatment seems to be suitable treatment in aged rats in order to prevent insulin resistance but not memory decline associated with aging. Acute genistein treatment is not effective to restore insulin resistance associated to the early loss of ovarian function, although it can be useful to improve memory deficits in this condition. PMID:20467821

  20. Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

    PubMed Central

    2013-01-01

    It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. PMID:23442260

  1. [Psychological aspects of remission induced by intensive insulin therapy in type I diabetes. A retrospective study of 44 patients].

    PubMed

    Ziegler, O; Kolopp, M; Kahn, J P; Floquet, B; Goudot, C; Beyel, P; Drouin, P; Debry, G

    1991-01-01

    The psychological consequences of induced remission of type 1 diabetes, have not yet been investigated thoroughly. We studied the psychological status of 44 patients (16 women, 28 men), age 21 years +/- 8 months (mean +/- SD), whose remission lasted 12 +/- 9 months. Patients' psychological reactions were analyzed retrospectively, using a 20 items standardized questionnaire, investigating 3 successive periods: 1) initial intensive insulin therapy; 2) remission; 3) permanent insulin therapy. 8% of the subjects only considered the remission phase useless, whereas 49% expressed a positive appraisal. Hope was predominant feeling, 25% of the patients believing in a completed recovery of diabetes. Perceived therapeutic constraints were, in decreasing order: regimen, way of life's regularity, self monitoring of blood glucose. When starting permanent insulin therapy, opposite answers were given: 49% negative feelings, 33% positive feelings and 18% ambivalent feelings. During this period, insulin injections represented the major therapeutic constraint, followed by self monitoring of blood glucose. To summarize, induced remission does not appear to be psychologically harmful and is considered useful by a large majority of patients. Effective psychological support has to be offered to help those patients to cope with their irrational hopes of healing and to dampen their deception at the end of the remission period. PMID:1752345

  2. The Effect of Vigorous Intensity Acute Exercise on Executive Function

    ERIC Educational Resources Information Center

    Phillips, David Spencer

    2012-01-01

    The effect of physical activity (PA) and consequent influence on cognition within adult seniors has been widely published. However, there is a paucity of causal research relating PA and cognition to schoolchildren within an authentic setting. Also, little is known about the required intensity and dosage of PA to effect executive function (EF)…

  3. Altered insulin response to an acute bout of exercise in pediatric obesity.

    PubMed

    Tran, Brian D; Leu, Szu-Yun; Oliver, Stacy; Graf, Scott; Vigil, Diana; Galassetti, Pietro

    2014-11-01

    Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more pronounced in the half of Ob children with higher basal insulin (Ob-H). In all groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations. PMID:24723046

  4. The effect of differing intensities of acute cycling on preadolescent academic achievement.

    PubMed

    Duncan, Michael; Johnson, Andrew

    2014-01-01

    The present study examined the effects of differing intensity levels of acute exercise on preadolescent academic ability. In a repeated measures design, 18 preadolescent participants (mean age±S.D.= 9.8±1.4 years: 9 male and 9 female) completed the Wide Range Achievement Test (WRAT 4) following 20 minutes of rest, 20-minutes on a cycling ergometer at 50% maximal heart rate reserve (HRR), and 20-minutes on a cycling ergometer at 75% HRR on separate days. Exercise was found to improve spelling irrespective of intensity level. Moderate levels of exercise improved reading although the effect of high levels of intensity is less clear. Both intensity levels impaired arithmetic, whilst sentence comprehension was unaffected. These findings further support the past research that indicates acute bouts of exercise can selectively improve cognition in preadolescent children. However, the present study finds no support for the notion that increasing the intensity of exercise accentuates benefits. PMID:23724796

  5. Effects of insulin-like growth factor-1 on B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Yamada, Hiroyuki; Iijima, Kazutoshi; Tomita, Osamu; Taguchi, Tomoko; Miharu, Masashi; Kobayashi, Kenichiro; Okita, Hajime; Saito, Masahiro; Shimizu, Toshiaki; Kiyokawa, Nobutaka

    2013-01-01

    Insulin-like growth factor-1 (IGF-1) is known to be a major growth factor with effects on various cell types, including hematopoietic cells, as well as neoplasms, and is regulated by IGF-binding proteins (IGFBPs). In this study, we investigated the effects of IGF-1 on B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. When the expression of IGF-1R in clinical samples of BCP-ALL was examined, five of thirty-two cases showed IGF-1R expression, whereas IGF-1R was expressed in most BCP-ALL cell lines. We observed that IGF-1 enhanced the proliferation of BCP-ALL cell lines that can be partially inhibited by IGFBP-1, -3, and -4, but not other IGFBPs. IGF-1 also partially inhibited dexamethasone-induced apoptosis, but not apoptosis mediated by VP-16 and irradiation. Interestingly, the proliferative effect of IGF-1 was partially blocked by inhibitors of MAPK and AKT, whereas the inhibition of dexamethasone-induced apoptosis was completely blocked by both inhibitors. Our data indicate that IGF-1 is involved in cell proliferation and apoptosis regulation in BCP-ALL cells. Since some BCP-ALL cases express IGF-1R, it appears to be a plausible target for prognostic evaluation and may represent a new therapeutic strategy.

  6. Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men1

    PubMed Central

    Shannon, Chris E; Nixon, Aline V; Greenhaff, Paul L; Stephens, Francis B

    2016-01-01

    Background: Increasing skeletal muscle carnitine content represents an appealing intervention in conditions of perturbed lipid metabolism such as obesity and type 2 diabetes but requires chronic l-carnitine feeding on a daily basis in a high-carbohydrate beverage. Objective: We investigated whether whey protein ingestion could reduce the carbohydrate load required to stimulate insulin-mediated muscle carnitine accretion. Design: Seven healthy men [mean ± SD age: 24 ± 5 y; body mass index (in kg/m2): 23 ± 3] ingested 80 g carbohydrate, 40 g carbohydrate + 40 g protein, or control (flavored water) beverages 60 min after the ingestion of 4.5 g l-carnitine tartrate (3 g l-carnitine; 0.1% 2[H]3-l-carnitine). Serum insulin concentration, net forearm carnitine balance (NCB; arterialized-venous and venous plasma carnitine difference × brachial artery flow), and carnitine disappearance (Rd) and appearance (Ra) rates were determined at 20-min intervals for 180 min. Results: Serum insulin and plasma flow areas under the curve (AUCs) were similarly elevated by carbohydrate [4.5 ± 0.8 U/L · min (P < 0.01) and 0.5 ± 0.6 L (P < 0.05), respectively] and carbohydrate+protein [3.8 ± 0.6 U/L · min (P < 0.01) and 0.4 ± 0.6 L (P = 0.05), respectively] consumption, respectively, compared with the control visit (0.04 ± 0.1 U/L · min and −0.5 ± 0.2 L). Plasma carnitine AUC was greater after carbohydrate+protein consumption (3.5 ± 0.5 mmol/L · min) than after control and carbohydrate visits [2.1 ± 0.2 mmol/L · min (P < 0.05) and 1.9 ± 0.3 mmol/L · min (P < 0.01), respectively]. NCB AUC with carbohydrate (4.1 ± 3.1 μmol) was greater than during control and carbohydrate-protein visits (−8.6 ± 3.0 and −14.6 ± 6.4 μmol, respectively; P < 0.05), as was Rd AUC after carbohydrate (35.7 ± 25.2 μmol) compared with control and carbohydrate consumption [19.7 ± 15.5 μmol (P = 0.07) and 14.8 ± 9.6 μmol (P < 0.05), respectively]. Conclusions: The insulin

  7. Intense adrenal enhancement in patients with acute pancreatitis and early organ failure.

    PubMed

    Bollen, T L; van Santvoort, H C; Besselink, M G H; van Ramshorst, B; van Es, H W; Gooszen, H G

    2007-10-01

    Intense adrenal enhancement has previously been reported in patients with hypovolemic and septic shock. The purpose of this study was to assess whether this computed tomography (CT) finding is also observed in patients presenting with severe acute pancreatitis and early organ failure. A retrospective analysis of a prospectively collected database was performed. Out of 38 consecutive patients with predicted severe acute pancreatitis, 3 patients showed intense bilateral adrenal enhancement on early CT. All patients had early multiple organ failure and subsequently died. In two cases, pathologic correlation was obtained. Intense adrenal enhancement may be a new prognostic indicator in patients with acute pancreatitis, particularly when organ failure is present at the time of CT examination. Further studies are necessary to confirm this observation.

  8. Achilles tendon biomechanics in response to acute intense exercise.

    PubMed

    Joseph, Michael F; Lillie, Kurtis R; Bergeron, Daniel J; Cota, Kevin C; Yoon, Joseph S; Kraemer, William J; Denegar, Craig R

    2014-05-01

    Achilles tendinopathy is a common disorder and is more prevalent in men. Although differences in tendon mechanics between men and women have been reported, understanding of tendon mechanics in young active people is limited. Moreover, there is limited understanding of changes in tendon mechanics in response to acute exercise. Our purpose was to compare Achilles tendon mechanics in active young adult men and women at rest and after light and strenuous activity in the form of repeated jumping with an added load. Participants consisted of 17 men and 14 women (18-30 years) who were classified as being at least moderately physically active as defined by the International Physical Activity Questionnaire. Tendon force/elongation measures were obtained during an isometric plantarflexion contraction on an isokinetic dynamometer with simultaneous ultrasound imaging of the Achilles tendon approximate to the soleus myotendinous junction. Data were collected at rest, after a 10-minute treadmill walk, and after a fatigue protocol of 100 toe jumps performed in a Smith machine, with a load equaling 20% of body mass. We found greater tendon elongation, decreased stiffness, and lower Young's modulus only in women after the jumping exercise. Force and stress were not different between groups but decreased subsequent to the jumping exercise bout. In general, women had greater elongation and strain, less stiffness, and a lower Young's modulus during plantarflexor contraction. These data demonstrate differences in tendon mechanics between men and women and suggest a potential protective mechanism explaining the lower incidence of Achilles tendinopathy in women.

  9. Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects.

    PubMed

    Fisher, B M; Quin, J D; Rumley, A; Lennie, S E; Small, M; MacCuish, A C; Lowe, G D

    1991-05-01

    1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.

  10. Sustainability of lifestyle changes following an intensive lifestyle intervention in insulin resistant adults: Follow-up at 2-years.

    PubMed

    Dale, Kelly S; Mann, Jim I; McAuley, Kirsten A; Williams, Sheila M; Farmer, Victoria L

    2009-01-01

    The objective of this study was to determine whether overweight insulin resistant individuals who lost weight and improved cardiovascular risk factors during a 4-month lifestyle intervention could sustain these lifestyle changes in the long-term. Seventy-nine insulin resistant adults were randomised to a control group or either a modest or intensive lifestyle intervention group for 4-months. Thereafter the two intervention groups were combined and all participants were followed-up at 8, 12 and 24 months. Anthropometry, blood pressure, fasting glucose, lipids, insulin and aerobic fitness were measured and dietary intake was assessed. An interview was conducted to determine factors which participants perceived facilitated or hindered maintenance of healthy lifestyle habits. Seventy-two (91.1%), sixty-nine (87.3%) and sixty-two (78.5%) participants were retained at 8, 12 and 24-month respectively. At 4-months the adjusted difference in weight between the modest and control groups was -3.4 kg (95% CI -5.4, -1.3) p=0.002 and intensive and control groups was -4.7 kg (-6.9, -2.4) p=0.0001 respectively. At 2-years there were no significant differences for weight when the initial 3 groups were compared or when the combined intervention group was compared with the control group. At 2-years, 64% of participants reported that more frequent follow-up would have helped them to maintain healthy lifestyle habits. Even intensive counselling for 4-months with 4-monthly and then yearly monitoring were not enough for maintaining lifestyle changes sufficient to sustain weight loss. More frequent monitoring for an indefinite period was perceived by two-thirds of participants as necessary for them to maintain their initial lifestyle changes.

  11. Insulin resistance, hyperglycemia, glucosuria, and galactosuria in intensively milk-fed calves: dependency on age and effects of high lactose intake.

    PubMed

    Hugi, D; Bruckmaier, R M; Blum, J W

    1997-02-01

    Calves intensively fed milk replacers frequently develop postprandial insulin resistance, characterized by excessively elevated plasma insulin concentrations, hyperglycemia, and glucosuria. To test the hypothesis that insulin secretion and insulin-dependent dependent glucose metabolism are modified by age and carbohydrate intake, 20 male calves (Simmental x Red Holstein) were fed a milk replacer containing 290 and 423 g lactose/kg DM from 60-70 to 190-200 kg BW. Responses of insulin and glucose to milk replacer intake and orally administered glucose and pre- and postprandial glucose responses to i.v. infused glucose and i.v. injected insulin were tested at 75-105 and 160-200 kg BW. Urine was collected during 24h to determine glucose, galactose, dopamine, noradrenaline, and creatinine excretion. Insulin resistance, hyperinsulinemia, hyperglycemia, glucosuria, and galactosuria developed with increasing age and occurred primarily postprandially. High lactose intake enhanced postprandial hyperglycemia but did not significantly increase glucosuria, galactosuria, and hyperinsulinemia. Based on urinary excretion of dopamine and noradrenaline there was a marked age-dependent increase in the activity of the sympathetic nervous system, which was not modified by lactose intake. high feeding intensity and lactose intake, excessive hyperinsulinemia per se and enhanced activity of the sympathetic nervous system possibly contributed to the development of insulin resistance. Glucose-dependent insulinotropic polypeptide, growth hormone and cortisol concentrations, and iron intake were low and comparable in both groups and therefore were etiologically not involved in the development of insulin resistance. Increasing circulating concentrations of insulin-like growth factor I during growth may have in part allowed high growth rates in the presence of insulin resistance.

  12. Acute effects of intense interval training on running mechanics.

    PubMed

    Collins, M H; Pearsall, D J; Zavorsky, G S; Bateni, H; Turcotte, R A; Montgomery, D L

    2000-02-01

    The aims of this study were to determine if there are significant kinematic changes in running pattern after intense interval workouts, whether duration of recovery affects running kinematics, and whether changes in running economy are related to changes in running kinematics. Seven highly trained male endurance runners (VO2max = 72.3+/-3.3 ml x kg(-1) x min(-1); mean +/- s) performed three interval running workouts of 10 x 400 m at a speed of 5.94+/-0.19 m x s(-1) (356+/-11.2 m x min(-1)) with a minimum of 4 days recovery between runs. Recovery of 60, 120 or 180 s between each 400 m repetition was assigned at random. Before and after each workout, running economy and several kinematic variables were measured at speeds of 3.33 and 4.47 m x s(-1) (200 and 268 m x min(-1)). Speed was found to have a significant effect on shank angle, knee velocity and stride length (P < 0.05). Correlations between changes pre- and post-test for VO2 (ml x kg(-1) x min(-1)) and several kinematic variables were not significant (P > 0.05) at both speeds. In general, duration of recovery was not found to adversely affect running economy or the kinematic variables assessed, possibly because of intra-individual adaptations to fatigue.

  13. Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury

    PubMed Central

    2008-01-01

    BACKGROUND The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P = 0.47). There was no significant difference between the two groups in the duration of renalreplacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal

  14. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

    PubMed

    Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

    2015-11-01

    The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (-0.92 mmol L(-1), -1.22 to -0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results.

  15. Association of Hyperglycemia, Glucocorticoids, and Insulin Use with Morbidity and Mortality in the Pediatric Intensive Care Unit

    PubMed Central

    Wintergerst, Kupper A; Foster, Michael B; Sullivan, Janice E; Woods, Charles R

    2012-01-01

    Background Studies of pediatric intensive care unit (PICU) patients have shown a significant association of morbidity and mortality with hyperglycemia. We retrospectively evaluated the degree of hyperglycemia as well as its correlation with glucocorticoid and insulin use and assessed its association with hospital length of stay (LOS) and mortality. This study preceded the initiation of a standard glycemic control protocol. Methods We examined medical records at Kosair Children's Hospital for all PICU admissions from 2008 of patients without diabetes mellitus. Critical illness hyperglycemia (CIH) was defined by having three or more peak glucose values greater than thresholds of 110, 140, 180, and 200 mg/dl. These patients were evaluated for glucocorticoid, insulin use, and outcome measures. Results We evaluated the eligible 1173 admissions, where 10.5% of these patients reached the highest threshold (200 mg/dl) of CIH. Glucocorticoids were used in 43% of these patients, with dexamethasone being the most common (58%). There was a significant correlation between glucocorticoids and higher peak glucose values, where 81% of the patients who were above the 200 mg/dl cutoff level were treated with glucocorticoids. Only 36.8% in that group were also treated with insulin. Patients at the 200 mg/dl cutoff had the highest median PICU and total hospital length of stays (4 and 10 days, respectfully). Mortality was associated with increasing glucose levels, reaching 18.7% among patients above the 200 mg/dl cutoff. Conclusion Hyperglycemia was prevalent in the PICU and was associated with increased morbidity, as characterized by increased LOS and increased mortality. Glucocorticoid use was prevalent among patients exhibiting hyperglycemia. Insulin use was uncommon. PMID:22401317

  16. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

    PubMed

    Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

    2015-11-01

    The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (-0.92 mmol L(-1), -1.22 to -0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results. PMID:26481101

  17. The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue.

    PubMed

    Vidal, H; Auboeuf, D; De Vos, P; Staels, B; Riou, J P; Auwerx, J; Laville, M

    1996-07-15

    The regulation of ob gene expression in abdominal subcutaneous adipose tissue was investigated using a reverse transcription-competitive PCR method to quantify the mRNA level of leptin. Leptin mRNA level was highly correlated with the body mass index of 26 subjects (12 lean, 7 non-insulin-dependent diabetic, and 7 obese patients). The effect of fasting on ob gene expression was investigated in 10 subjects maintained on a hypocaloric diet (1045 KJ/d) for 5 d. While their metabolic parameters significantly changed (decrease in insulinemia, glycemia, and resting metabolic rate and increase in plasma ketone bodies), the caloric restriction did not modify the leptin mRNA level in the adipose tissue. To verify whether insulin regulates ob gene expression, six lean subjects underwent a 3-h euglycemic hyperinsulinemic (846 +/- 138 pmol/liter) clamp. Leptin and Glut 4 mRNA levels were quantified in adipose tissue biopsies taken before and at the end of the clamp. Insulin infusion produced a significant threefold increase in Glut 4 mRNA while leptin mRNA was not affected. It is concluded that ob gene expression is not acutely regulated by insulin or by metabolic factors related to fasting in human abdominal subcutaneous adipose tissue. PMID:8755631

  18. Effect of acute cold exposure and insulin hypoglycemia on plasma thyrotropin levels by IRMA in healthy young males.

    PubMed

    Vigas, M; Martino, E; Bukovská, M; Langer, P

    1988-12-01

    Thyrotropin (TSH) levels in plasma were estimated with the aid of immunoradiometric assay in two groups of healthy male subjects aged 21-22 years in two experiments: 1. acute (30 min) exposure to 4 degrees C in a cold room; 2. insulin (0.01 U per kg i.v.) hypoglycemia at room temperature and at 55 degrees C. Immediately after cold exposure a decrease of TSH level was found (P less than 0.01), while no changes were observed during 30 min exposure. After insulin injection a significant decrease (P less than 0.05 to less than 0.001) of TSH level was found at 45 to 120 min irrespectively of the ambient temperature. In addition, increased levels of noradrenaline and decreased levels of growth hormone after cold exposure are presented. PMID:3243203

  19. Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle.

    PubMed

    Laville, M; Auboeuf, D; Khalfallah, Y; Vega, N; Riou, J P; Vidal, H

    1996-07-01

    We have investigated the acute regulation by insulin of the mRNA levels of nine genes involved in insulin action, in muscle biopsies obtained before and at the end of a 3-h euglycemic hyperinsulinemic clamp. Using reverse transcription-competitive PCR, we have measured the mRNAs encoding the two insulin receptor variants, the insulin receptor substrate-1, the p85alpha subunit of phosphatidylinositol-3-kinase, Ras associated to diabetes (Rad), the glucose transporter Glut 4, glycogen synthase, 6-phosphofructo-l-kinase, lipoprotein lipase, and the hormone-sensitive lipase. Insulin infusion induced a significant increase in the mRNA level of Glut 4 (+56 +/- 13%), Rad (+96 +/- 25%), the p85alpha subunit of phosphatidylinositol-3-kinase (+92 +/- 18%) and a decrease in the lipoprotein lipase mRNA level (-49 +/- 5%), while the abundance of the other mRNAs was unaffected. The relative expression of the two insulin receptor variants was not modified. These results demonstrate an acute coordinated regulation by insulin of the expression of genes coding key proteins involved in its action in human skeletal muscle and suggest that Rad and the p85alpha regulatory subunit of phosphatidylinositol-3-kinase can be added to the list of the genes controlled by insulin. PMID:8690802

  20. Decline in Executive Control during Acute Bouts of Exercise as a Function of Exercise Intensity and Fitness Level

    ERIC Educational Resources Information Center

    Labelle, Veronique; Bosquet, Laurent; Mekary, Said; Bherer, Louis

    2013-01-01

    Studies on the effects of acute bouts of cardiovascular exercise on cognitive performances show contradictory findings due to methodological differences (e.g., exercise intensity, cognitive function assessed, participants' aerobic fitness level, etc.). The present study assessed the acute effect of exercise intensity on cognition while controlling…

  1. Patterns and Predictors of Intensive Statin Therapy among Patients with Diabetes Mellitus after Acute Myocardial Infarction

    PubMed Central

    Abdallah, Mouin S.; Kosiborod, Mikhail; Tang, Fengming; Karrowni, Wassef Y.; Maddox, Thomas M.; McGuire, Darren K.; Spertus, John A.; Arnold, Suzanne V.

    2014-01-01

    Intensive statin therapy is a central component of secondary prevention after acute myocardial infarction (AMI), particularly among high-risk patients, such as those with diabetes mellitus (DM). However, the frequency and predictors of intensive statin therapy use after AMI among patients with DM have not been described. We examined patterns of intensive statin therapy use (defined as a statin with expected LDL-C lowering of >50%) at discharge among AMI patients with known DM enrolled in a 24-site US registry. Predictors of intensive statin therapy use were evaluated using multivariable hierarchical Poisson regression models. Among 1300 patients with DM after AMI, 22% were prescribed intensive statin therapy at hospital discharge. In multivariable models, ST-elevation AMI (RR 1.48, 95% CI 1.29–1.70), insurance for medications (RR 1.28, 95% CI 1.00–1.63) and higher LDL-C levels (RR 1.05 per 1 mg/dL, 95% CI 1.02–1.07) were independent predictors of intensive statin therapy whereas higher GRACE scores were associated with lower rates of intensive statin therapy (RR 0.94 per 10 points; 95% CI 0.91–0.98). In conclusion, only 1 in 5 patients with DM were prescribed intensive statin therapy at discharge after an AMI. Predictors of intensive statin therapy use suggest important opportunities to improve quality of care in this patient population. PMID:24560324

  2. Insulin Signaling and Glucose Uptake in the Soleus Muscle of 30-Month-Old Rats After Calorie Restriction With or Without Acute Exercise.

    PubMed

    Wang, Haiyan; Sharma, Naveen; Arias, Edward B; Cartee, Gregory D

    2016-03-01

    Exercise and calorie restriction (CR) can each improve insulin sensitivity in older individuals, but benefits of combining these treatments on skeletal muscle insulin signaling and glucose uptake are poorly understood, especially in predominantly slow-twitch muscles (eg, soleus). Accordingly, our purpose was to determine independent and combined effects of prior acute exercise and CR (beginning at 14 weeks old) on insulin signaling and glucose uptake in insulin-stimulated soleus muscles of 30-month-old rats. CR alone (but not exercise alone) versus ad libitum sedentary controls induced greater insulin-stimulated glucose uptake. There was a main effect of diet (CR > ad libitum) for insulin-stimulated Akt(Ser473) and Akt(Thr308) phosphorylation. CR alone versus ad libitum sedentary increased Akt substrate of 160 kDa (AS160) Ser(588) phosphorylation and TBC1D1 Thr(596), but not AS160 Thr(642) phosphorylation or abundance of GLUT4, GLUT1, or hexokinase II proteins. Combined CR and exercise versus CR alone did not further increase insulin-stimulated glucose uptake although phosphorylation of Akt(Ser473), Akt(Thr308), TBC1D1(Thr596), and AMPK(Thr172) for the combined group exceeded values for CR and/or exercise alone. These results revealed that although the soleus was highly responsive to a CR-induced enhancement of insulin-stimulated glucose uptake, the exercise protocol did not elevate insulin-stimulated glucose uptake, either alone or when combined with CR.

  3. Treatment of acute pancreatitis with mexidol and low-intensity laser radiation

    NASA Astrophysics Data System (ADS)

    Parzyan, G. R.; Geinits, A. V.

    2001-04-01

    This article presents the results of treatment of 54 patients with acute pancreatitis. The patients were divided into two groups according to the method of treatment. The control group (26 patients) received a conventional therapy, whereas the experimental group (28 patients) received mexidol in combination with the intravenous laser irradiation of blood. Clinical and laboratory tests confirmed a high efficiency of the combined therapy based on the administration of mexidol antioxidant and low-intensity (lambda) equals 0.63 micrometers diode laser irradiation of blood. This therapeutic technique produced an influence on the basic pathogenetic mechanisms of acute pancreatitis. The application of this method of treatment improved the course and prognosis of acute pancreatitis.

  4. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies

    PubMed Central

    Pettit, Kristen; Odenike, Olatoyosi

    2015-01-01

    Although acute myeloid leukemia (AML) is primarily a disease of older adults (age ≥60 years), the optimal treatment for older adults remains largely undefined. Intensive chemotherapy is rarely beneficial for frail older adults or those with poor-risk disease, but criteria that define fitness and/or appropriateness for intensive chemotherapy remain to be standardized. Evaluation of disease-related and patient-specific factors in the context of clinical decision making has therefore been largely subjective. A uniform approach to identify those patients most likely to benefit from intensive therapies is needed. Here, we review currently available objective measures to define older adults with AML who are ineligible for intensive chemotherapy, and discuss promising investigational approaches. PMID:26697412

  5. Signal Intensity of Superb Microvascular Imaging Correlates with the Severity of Acute Cholecystitis

    PubMed Central

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    Evaluation of the severity of acute cholecystitis is critical for the management of this condition. Superb microvascular imaging (SMI) enables the assessment of slow blood flow of small vessels without any contrast medium. An 84-year-old man visited our hospital with right upper abdominal pain. Computed tomography and abdominal ultrasonography showed a slight thickening of the gallbladder. White blood cell count and C-reactive protein levels were elevated. He was diagnosed with acute cholecystitis and treated conservatively with antibiotics. Two days later, his condition worsened and percutaneous transhepatic gallbladder drainage (PTGBD) was performed. The patient recovered and was discharged, and his drainage was withdrawn 7 days later. On admission, color-coded SMI (cSMI) showed pulsatory signals on the slightly thickened gallbladder wall. On the day of PTGBD, the intensity of the signal on cSMI had increased. Once the patient was cured, no further signal was observed on the gallbladder wall with either cSMI or mSMI. In conclusion, the strong pulsatory signal correlated with the severity of acute cholecystitis observed with cSMI and mSMI. Illustrating the signal intensity is useful for the evaluation of the severity of acute cholecystitis. PMID:27721732

  6. Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

    PubMed

    Couturier, Karine; Hininger, Isabelle; Poulet, Laurent; Anderson, Richard A; Roussel, Anne-Marie; Canini, Frédéric; Batandier, Cécile

    2016-02-01

    Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3β and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions. PMID:26878796

  7. Transient Increase in Homocysteine but Not Hyperhomocysteinemia during Acute Exercise at Different Intensities in Sedentary Individuals

    PubMed Central

    Iglesias-Gutiérrez, Eduardo; Egan, Brendan; Díaz-Martínez, Ángel Enrique; Peñalvo, José Luis; González-Medina, Antonio; Martínez-Camblor, Pablo; O’Gorman, Donal J.; Úbeda, Natalia

    2012-01-01

    Considering that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the purpose of this study was to determine the kinetics of serum homocysteine (tHcy) and the vitamins involved in its metabolism (folates, B12, and B6) in response to acute exercise at different intensities. Eight sedentary males (18–27 yr) took part in the study. Subjects were required to complete two isocaloric (400 kcal) acute exercise trials on separate occasions at 40% (low intensity, LI) and 80% VO2peak (high intensity, HI). Blood samples were drawn at different points before (pre4 and pre0 h), during (exer10, exer20, exer30, exer45, and exer60 min), and after exercise (post0, post3, and post19 h). Dietary, genetic, and lifestyle factors were controlled. Maximum tHcy occurred during exercise, both at LI (8.6 (8.0–10.1) µmol/L, 9.3% increase from pre0) and HI (9.4 (8.2–10.6) µmol/L, 25.7% increase from pre0), coinciding with an accumulated energy expenditure independent of the exercise intensity. From this point onwards tHcy declined until the cessation of exercise and continued descending. At post19, tHcy was not different from pre-exercise values. No values of hyperhomocysteinemia were observed at any sampling point and intensity. In conclusion, acute exercise in sedentary individuals, even at HI, shows no negative effect on tHcy when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate, since no hyperhomocysteinemia has been observed and basal concentrations were recovered in less than 24 h. This could be relevant for further informing healthy exercise recommendations. PMID:23236449

  8. Nicotinic acetylcholine receptors in glucose homeostasis: the acute hyperglycemic and chronic insulin-sensitive effects of nicotine suggest dual opposing roles of the receptors in male mice.

    PubMed

    Vu, Christine U; Siddiqui, Jawed A; Wadensweiler, Paul; Gayen, Jiaur R; Avolio, Ennio; Bandyopadhyay, Gautam K; Biswas, Nilima; Chi, Nai-Wen; O'Connor, Daniel T; Mahata, Sushil K

    2014-10-01

    Cigarette smoking causes insulin resistance. However, nicotine induces anti-inflammation and improves glucose tolerance in insulin-resistant animal models. Here, we determined the effects of nicotine on glucose metabolism in insulin-sensitive C57BL/J6 mice. Acute nicotine administration (30 min) caused fasting hyperglycemia and lowered insulin sensitivity acutely, which depended on the activation of nicotinic-acetylcholine receptors (nAChRs) and correlated with increased catecholamine secretion, nitric oxide (NO) production, and glycogenolysis. Chlorisondamine, an inhibitor of nAChRs, reduced acute nicotine-induced hyperglycemia. qRT-PCR analysis revealed that the liver and muscle express predominantly β4 > α10 > α3 > α7 and β4 > α10 > β1 > α1 mRNA for nAChR subunits respectively, whereas the adrenal gland expresses β4 > α3 > α7 > α10 mRNA. Chronic nicotine treatment significantly suppressed expression of α3-nAChR (predominant peripheral α-subunit) in liver. Whereas acute nicotine treatment raised plasma norepinephrine (NE) and epinephrine (Epi) levels, chronic nicotine exposure raised only Epi. Acute nicotine treatment raised both basal and glucose-stimulated insulin secretion (GSIS). After chronic nicotine treatment, basal insulin level was elevated, but GSIS after acute saline or nicotine treatment was blunted. Chronic nicotine exposure caused an increased buildup of NO in plasma and liver, leading to decreased glycogen storage, along with a concomitant suppression of Pepck and G6Pase mRNA, thus preventing hyperglycemia. The insulin-sensitizing effect of chronic nicotine was independent of weight loss. Chronic nicotine treatment enhanced PI-3-kinase activities and increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation in an nAChR-dependent manner coupled with decreased cAMP response element-binding protein (CREB) phosphorylation. The latter effects caused suppression of Pepck and G6Pase gene expression. Thus, nicotine causes both

  9. Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury

    PubMed Central

    Lu, Haiyan; Huang, Danping; Saederup, Noah; Charo, Israel F.; Ransohoff, Richard M.; Zhou, Lan

    2011-01-01

    CC chemokine receptor 2 (CCR2) is essential to acute skeletal muscle injury repair. We studied the subpopulation of inflammatory cells recruited via CCR2 signaling and their cellular functions with respect to muscle regeneration. Mobilization of monocytes/macrophages (MOs/MPs), but not lymphocytes or neutrophils, was impaired from bone marrow to blood and from blood to injured muscle in Ccr2−/− mice. While the Ly-6C+ but not the Ly-6C− subset of MOs/MPs was significantly reduced in blood, both subsets were drastically reduced in injured muscle of Ccr2−/− mice. Expression of insulin-like growth factor-1 (IGF-I) was markedly up-regulated in injured muscle of wild-type but not Ccr2−/− mice. IGF-I was strongly expressed by macrophages within injured muscle, more prominently by the Ly-6C− subset. A single injection of IGF-I, but not PBS, into injured muscle to replace IGF-I remarkably improved muscle regeneration in Ccr2−/− mice. CCR2 was not detected in myogenic cells or capillary endothelial cells in injured muscle to suggest its direct involvement in muscle regeneration or angiogenesis. We conclude that CCR2 is essential to acute skeletal muscle injury repair primarily by recruiting Ly-6C+ MOs/MPs. Within injured muscle, these cells conduct phagocytosis, contribute to accumulation of intramuscular Ly-6C− macrophages, and produce a high level of IGF-I to promote muscle regeneration.—Lu, H., Huang, D., Saederupm, N., Charo, I. F., Ransohoff, R. M., Zhou, L. Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury. PMID:20889618

  10. Muscle Activation During Exercise in Severe Acute Hypoxia: Role of Absolute and Relative Intensity

    PubMed Central

    Torres-Peralta, Rafael; Losa-Reyna, José; González-Izal, Miriam; Perez-Suarez, Ismael; Calle-Herrero, Jaime; Izquierdo, Mikel

    2014-01-01

    Abstract Torres-Peralta, Rafael, José Losa-Reyna, Miriam González-Izal, Ismael Perez-Suarez, Jaime Calle-Herrero, Mikel Izquierdo, and José A.L. Calbet. Muscle activation during exercise in severe acute hypoxia: Role of absolute and relative intensity. High Alt Med Biol 15:472–482, 2014.—The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIo2=0.21, two tests) or hypoxic gas (FIo2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak Vo2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIo2. No significant FIo2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIo2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIo2. PMID:25225839

  11. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    PubMed

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state.

  12. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    PubMed

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state. PMID:26112241

  13. High-intensity telemedicine-enhanced acute care for older adults: an innovative healthcare delivery model.

    PubMed

    Shah, Manish N; Gillespie, Suzanne M; Wood, Nancy; Wasserman, Erin B; Nelson, Dallas L; Dozier, Ann; McConnochie, Kenneth M

    2013-11-01

    Accessing timely acute medical care is a challenge for older adults. This article describes an innovative healthcare model that uses high-intensity telemedicine services to provide rapid acute care for older adults without requiring them to leave their senior living community (SLC) residences. This program, based in a primary care geriatrics practice that cares for SLC residents, is designed to offer acute care through telemedicine for complaints that are felt to need attention before the next available outpatient visit but not to require emergency department (ED) resources. This option gives residents access to care in their residence. Measures used to evaluate the program include successful completion of telemedicine visits, satisfaction of residents and caregivers with telemedicine care, and site of care that would have been recommended had telemedicine been unavailable. During the first 2 years of the program's operation, 281 of 301 requested telemedicine visits were completed successfully. Twelve residents were sent to an ED for care after the telemedicine visit. Ninety-four percent of residents reported being satisfied or very satisfied with telemedicine care. Had telemedicine not been available, residents would have been sent to an ED (48.1%) or urgent care center (27.0%) or been scheduled for an outpatient visit (24.4%). The project demonstrated that high-intensity telemedicine services for acute illnesses are feasible and acceptable and can provide definitive care without requiring ED or urgent care use. Continuation of the program will require evaluation demonstrating equal or better resident-level outcomes and the development of sustainable business models.

  14. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles

    PubMed Central

    Costantino, N. S.; Blackburn, H. L.; Engler, R. J. M.; Kashani, M.; Vernalis, M. N.

    2016-01-01

    Summary Objective Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type‐2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction. Methods Subjects with diagnosed type‐2 diabetes, CAD or significant risk factors participated in one of two clinical lifestyle modification interventions: (i) intensive non‐randomized programme with a strict vegetarian diet (n = 90 participants, 90 matched controls) or (ii) moderate randomized trial following a Mediterranean‐style diet (n = 89 subjects, 58 controls). On‐treatment and intention‐to‐treat analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic risk factors in intervention participants and controls in both programmes. Results In the on‐treatment analysis, both interventions led to weight loss: [−8.9% (95% CI, −10.3 to −7.4), intensive programme; −2.8% (95% CI, −3.8 to −1.9), moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [−13.3% (95% CI, −18.2 to −8.3), intensive; −8.8% (95% CI, −12.9 to −4.7), moderate; adjusted P < 0.01] compared with respective controls. Of the six lipoprotein parameters comprising LPIR, only large very‐low‐density lipoprotein particle concentrations decreased significantly in participants compared with controls in both programmes [−26.3% (95% CI, −43.0 to −9.6), intensive; −14.2% (95% CI, −27.4 to −1.0), moderate; P < 0.05]. Intention‐to‐treat analysis confirmed and strengthened the primary results. Conclusion A stringent lifestyle modification intervention with a vegetarian diet and a moderate lifestyle modification intervention following a Mediterranean diet were both effective for improving IR defined by the

  15. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles

    PubMed Central

    Costantino, N. S.; Blackburn, H. L.; Engler, R. J. M.; Kashani, M.; Vernalis, M. N.

    2016-01-01

    Summary Objective Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type‐2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction. Methods Subjects with diagnosed type‐2 diabetes, CAD or significant risk factors participated in one of two clinical lifestyle modification interventions: (i) intensive non‐randomized programme with a strict vegetarian diet (n = 90 participants, 90 matched controls) or (ii) moderate randomized trial following a Mediterranean‐style diet (n = 89 subjects, 58 controls). On‐treatment and intention‐to‐treat analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic risk factors in intervention participants and controls in both programmes. Results In the on‐treatment analysis, both interventions led to weight loss: [−8.9% (95% CI, −10.3 to −7.4), intensive programme; −2.8% (95% CI, −3.8 to −1.9), moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [−13.3% (95% CI, −18.2 to −8.3), intensive; −8.8% (95% CI, −12.9 to −4.7), moderate; adjusted P < 0.01] compared with respective controls. Of the six lipoprotein parameters comprising LPIR, only large very‐low‐density lipoprotein particle concentrations decreased significantly in participants compared with controls in both programmes [−26.3% (95% CI, −43.0 to −9.6), intensive; −14.2% (95% CI, −27.4 to −1.0), moderate; P < 0.05]. Intention‐to‐treat analysis confirmed and strengthened the primary results. Conclusion A stringent lifestyle modification intervention with a vegetarian diet and a moderate lifestyle modification intervention following a Mediterranean diet were both effective for improving IR defined by the

  16. Acute kidney injury on admission to the intensive care unit: where to go from here?

    PubMed

    Ostermann, Marlies

    2008-01-01

    Acute kidney injury (AKI) is a common problem, especially in critically ill patients. In Critical Care, Kolhe and colleagues report that 6.3% of 276,731 patients in 170 intensive care units (ICUs) in the UK had evidence of severe AKI within the first 24 hours of admission to ICU. ICU and hospital mortality as well as length of stay in hospital were significantly increased. In light of this serious burden on individuals and the health system in general, the following commentary discusses the current state of knowledge of AKI in ICU and calls for more attention to preventive strategies.

  17. Similar Responses of Circulating MicroRNAs to Acute High-Intensity Interval Exercise and Vigorous-Intensity Continuous Exercise.

    PubMed

    Cui, Shu F; Wang, Cheng; Yin, Xin; Tian, Dong; Lu, Qiu J; Zhang, Chen Y; Chen, Xi; Ma, Ji Z

    2016-01-01

    High-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P < 0.05), and there was only a significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while no significant differences were observed for other muscle-related miRNAs between both exercises (P > 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P < 0.05) in both exercises compared to rest. However, no significant differences were found between both exercises (P > 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used

  18. Similar Responses of Circulating MicroRNAs to Acute High-Intensity Interval Exercise and Vigorous-Intensity Continuous Exercise

    PubMed Central

    Cui, Shu F.; Wang, Cheng; Yin, Xin; Tian, Dong; Lu, Qiu J.; Zhang, Chen Y.; Chen, Xi; Ma, Ji Z.

    2016-01-01

    High-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P < 0.05), and there was only a significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while no significant differences were observed for other muscle-related miRNAs between both exercises (P > 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P < 0.05) in both exercises compared to rest. However, no significant differences were found between both exercises (P > 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used

  19. Similar Responses of Circulating MicroRNAs to Acute High-Intensity Interval Exercise and Vigorous-Intensity Continuous Exercise.

    PubMed

    Cui, Shu F; Wang, Cheng; Yin, Xin; Tian, Dong; Lu, Qiu J; Zhang, Chen Y; Chen, Xi; Ma, Ji Z

    2016-01-01

    High-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P < 0.05), and there was only a significant reduction in miR-1 level for HIIE compared to VICE (P < 0.05), while no significant differences were observed for other muscle-related miRNAs between both exercises (P > 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P < 0.05) in both exercises compared to rest. However, no significant differences were found between both exercises (P > 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used

  20. Acute Exercise and Motor Memory Consolidation: The Role of Exercise Intensity

    PubMed Central

    Geertsen, Svend S.; Christiansen, Lasse; Ritz, Christian; Roig, Marc

    2016-01-01

    A single bout of high intensity aerobic exercise (~90% VO2peak) was previously demonstrated to amplify off-line gains in skill level during the consolidation phase of procedural memory. High intensity exercise is not always a viable option for many patient groups or in a rehabilitation setting where low to moderate intensities may be more suitable. The aim of this study was to investigate the role of intensity in mediating the effects of acute cardiovascular exercise on motor skill learning. We investigated the effects of different exercise intensities on the retention (performance score) of a visuomotor accuracy tracking task. Thirty six healthy male subjects were randomly assigned to one of three groups that performed either a single bout of aerobic exercise at 20 min post motor skill learning at 45% (EX45), 90% (EX90) maximal power output (Wmax) or rested (CON). Randomization was stratified to ensure that the groups were matched for relative peak oxygen consumption (ml O2/min/kg) and baseline score in the tracking task. Retention tests were carried out at 1 (R1) and 7 days (R7) post motor skill learning. At R1, changes in performance scores were greater for EX90 compared to CON (p<0.001) and EX45 (p = 0.011). The EX45 and EX90 groups demonstrated a greater change in performance score at R7 compared to the CON group (p = 0.003 and p<0.001, respectively). The change in performance score for EX90 at R7 was also greater than EX45 (p = 0.049). We suggest that exercise intensity plays an important role in modulating the effects that a single bout of cardiovascular exercise has on the consolidation phase following motor skill learning. There appears to be a dose-response relationship in favour of higher intensity exercise in order to augment off-line effects and strengthen procedural memory. PMID:27454423

  1. Acute Exercise and Motor Memory Consolidation: The Role of Exercise Intensity.

    PubMed

    Thomas, Richard; Johnsen, Line K; Geertsen, Svend S; Christiansen, Lasse; Ritz, Christian; Roig, Marc; Lundbye-Jensen, Jesper

    2016-01-01

    A single bout of high intensity aerobic exercise (~90% VO2peak) was previously demonstrated to amplify off-line gains in skill level during the consolidation phase of procedural memory. High intensity exercise is not always a viable option for many patient groups or in a rehabilitation setting where low to moderate intensities may be more suitable. The aim of this study was to investigate the role of intensity in mediating the effects of acute cardiovascular exercise on motor skill learning. We investigated the effects of different exercise intensities on the retention (performance score) of a visuomotor accuracy tracking task. Thirty six healthy male subjects were randomly assigned to one of three groups that performed either a single bout of aerobic exercise at 20 min post motor skill learning at 45% (EX45), 90% (EX90) maximal power output (Wmax) or rested (CON). Randomization was stratified to ensure that the groups were matched for relative peak oxygen consumption (ml O2/min/kg) and baseline score in the tracking task. Retention tests were carried out at 1 (R1) and 7 days (R7) post motor skill learning. At R1, changes in performance scores were greater for EX90 compared to CON (p<0.001) and EX45 (p = 0.011). The EX45 and EX90 groups demonstrated a greater change in performance score at R7 compared to the CON group (p = 0.003 and p<0.001, respectively). The change in performance score for EX90 at R7 was also greater than EX45 (p = 0.049). We suggest that exercise intensity plays an important role in modulating the effects that a single bout of cardiovascular exercise has on the consolidation phase following motor skill learning. There appears to be a dose-response relationship in favour of higher intensity exercise in order to augment off-line effects and strengthen procedural memory. PMID:27454423

  2. Acute Exercise and Motor Memory Consolidation: The Role of Exercise Intensity.

    PubMed

    Thomas, Richard; Johnsen, Line K; Geertsen, Svend S; Christiansen, Lasse; Ritz, Christian; Roig, Marc; Lundbye-Jensen, Jesper

    2016-01-01

    A single bout of high intensity aerobic exercise (~90% VO2peak) was previously demonstrated to amplify off-line gains in skill level during the consolidation phase of procedural memory. High intensity exercise is not always a viable option for many patient groups or in a rehabilitation setting where low to moderate intensities may be more suitable. The aim of this study was to investigate the role of intensity in mediating the effects of acute cardiovascular exercise on motor skill learning. We investigated the effects of different exercise intensities on the retention (performance score) of a visuomotor accuracy tracking task. Thirty six healthy male subjects were randomly assigned to one of three groups that performed either a single bout of aerobic exercise at 20 min post motor skill learning at 45% (EX45), 90% (EX90) maximal power output (Wmax) or rested (CON). Randomization was stratified to ensure that the groups were matched for relative peak oxygen consumption (ml O2/min/kg) and baseline score in the tracking task. Retention tests were carried out at 1 (R1) and 7 days (R7) post motor skill learning. At R1, changes in performance scores were greater for EX90 compared to CON (p<0.001) and EX45 (p = 0.011). The EX45 and EX90 groups demonstrated a greater change in performance score at R7 compared to the CON group (p = 0.003 and p<0.001, respectively). The change in performance score for EX90 at R7 was also greater than EX45 (p = 0.049). We suggest that exercise intensity plays an important role in modulating the effects that a single bout of cardiovascular exercise has on the consolidation phase following motor skill learning. There appears to be a dose-response relationship in favour of higher intensity exercise in order to augment off-line effects and strengthen procedural memory.

  3. How to regulate the acute physiological response to "aerobic" high-intensity interval exercise.

    PubMed

    Tschakert, Gerhard; Kroepfl, Julia; Mueller, Alexander; Moser, Othmar; Groeschl, Werner; Hofmann, Peter

    2015-03-01

    The acute physiological processes during "aerobic" high-intensity interval exercise (HIIE) and their regulation are inadequately studied. The main goal of this study was to investigate the acute metabolic and cardiorespiratory response to long and short HIIE compared to continuous exercise (CE) as well as its regulation and predictability. Six healthy well-trained sport students (5 males, 1 female; age: 25.7 ± 3.1 years; height: 1.80 ± 0.04 m; weight: 76.7 ± 6.4 kg; VO2max: 4.33 ± 0.7 l·min(-1)) performed a maximal incremental exercise test (IET) and subsequently three different exercise sessions matched for mean load (Pmean) and exercise duration (28 min): 1) long HIIE with submaximal peak workloads (Ppeak = power output at 95 % of maximum heart rate), peak workload durations (tpeak) of 4 min, and recovery durations (trec) of 3 min, 2) short HIIE with Ppeak according to the maximum power output (Pmax) from IET, tpeak of 20 s, and individually calculated trec (26.7 ± 13.4 s), and 3) CE with a target workload (Ptarget) equating to Pmean of HIIE. In short HIIE, mean lactate (Lamean) (5.22 ± 1.41 mmol·l(-1)), peak La (7.14 ± 2.48 mmol·l(-1)), and peak heart rate (HRpeak) (181.00 ± 6.66 b·min(-1)) were significantly lower compared to long HIIE (Lamean: 9.83 ± 2.78 mmol·l(-1); Lapeak: 12.37 ± 4.17 mmol·l(-1), HRpeak: 187.67 ± 5.72 b·min(-1)). No significant differences in any parameters were found between short HIIE and CE despite considerably higher peak workloads in short HIIE. The acute metabolic and peak cardiorespiratory demand during "aerobic" short HIIE was significantly lower compared to long HIIE and regulable via Pmean. Consequently, short HIIE allows a consciously aimed triggering of specific and desired or required acute physiological responses. Key pointsHigh-intensity interval exercise (HIIE) with short peak workload durations (tpeak) induce a lower acute metabolic and peak cardiorespiratory response compared to intervals with long tpeak

  4. Acute effects of moderate intensity aerobic exercise on affective withdrawal symptoms and cravings among women smokers.

    PubMed

    Williams, David M; Dunsiger, Shira; Whiteley, Jessica A; Ussher, Michael H; Ciccolo, Joseph T; Jennings, Ernestine G

    2011-08-01

    A growing number of laboratory studies have shown that acute bouts of aerobic exercise favorably impact affect and cravings among smokers. However, randomized trials have generally shown exercise to have no favorable effect on smoking cessation or withdrawal symptoms during quit attempts. The purpose of the present study was to explore this apparent contradiction by assessing acute changes in affect and cravings immediately prior to and following each exercise and contact control session during an eight-week smoking cessation trial. Sixty previously low-active, healthy, female smokers were randomized to an eight-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either three sessions/week of moderate intensity aerobic exercise or contact control. Findings revealed a favorable impact of exercise on acute changes in positive activated affect (i.e., energy), negative deactivated affect (i.e., tiredness), and cigarette cravings relative to contact control. However, effects dissipated from session to session. Results suggest that aerobic exercise has potential as a smoking cessation treatment, but that it must be engaged in frequently and consistently over time in order to derive benefits. Thus, it is not surprising that previous randomized controlled trials-in which adherence to exercise programs has generally been poor-have been unsuccessful in showing effects of aerobic exercise on smoking cessation outcomes.

  5. Effect of Opuntia humifusa supplementation and acute exercise on insulin sensitivity and associations with PPAR-γ and PGC-1α protein expression in skeletal muscle of rats.

    PubMed

    Kang, Junyong; Lee, Junghun; Kwon, Daekeun; Song, Youngju

    2013-03-28

    This study examined whether Opuntia humifusa (O. humifusa), which is a member of the Cactaceae family, supplementation and acute swimming exercise affect insulin sensitivity and associations with PPAR-γ and PGC-1α protein expression in rats. Thirty-two rats were randomly divided into four groups (HS: high fat diet sedentary group, n = 8; HE: high fat diet acute exercise group, n = 8; OS: 5% O. humifusa supplemented high fat diet sedentary group, n = 8; OE: 5% O. humifusa supplemented high fat diet acute exercise group, n = 8). Rats in the HE and OE swam for 120 min. before being sacrificed. Our results indicated that serum glucose level, fasting insulin level and homeostasis model assessment of insulin resistance (HOMA-IR) in OS were significantly lower compared to those of the HS (p < 0.01, p < 0.05, p < 0.05). In addition, PPAR-γ protein expression in the OS and OE was significantly higher than that of the HS and HE, respectively (p < 0.05, p < 0.01). PGC-1α and GLUT-4 protein expressions in the OS were significantly higher compared to those of the HS (p < 0.05, p < 0.05). From these results, O. humifusa supplementation might play an important role for improving insulin sensitivity through elevation of PPAR-γ, PGC-1α, and GLUT-4 protein expression in rat skeletal muscle.

  6. Effect of Opuntia humifusa Supplementation and Acute Exercise on Insulin Sensitivity and Associations with PPAR-γ and PGC-1α Protein Expression in Skeletal Muscle of Rats

    PubMed Central

    Kang, Junyong; Lee, Junghun; Kwon, Daekeun; Song, Youngju

    2013-01-01

    This study examined whether Opuntia humifusa (O. humifusa), which is a member of the Cactaceae family, supplementation and acute swimming exercise affect insulin sensitivity and associations with PPAR-γ and PGC-1α protein expression in rats. Thirty-two rats were randomly divided into four groups (HS: high fat diet sedentary group, n = 8; HE: high fat diet acute exercise group, n = 8; OS: 5% O. humifusa supplemented high fat diet sedentary group, n = 8; OE: 5% O. humifusa supplemented high fat diet acute exercise group, n = 8). Rats in the HE and OE swam for 120 min. before being sacrificed. Our results indicated that serum glucose level, fasting insulin level and homeostasis model assessment of insulin resistance (HOMA-IR) in OS were significantly lower compared to those of the HS (p < 0.01, p < 0.05, p < 0.05). In addition, PPAR-γ protein expression in the OS and OE was significantly higher than that of the HS and HE, respectively (p < 0.05, p < 0.01). PGC-1α and GLUT-4 protein expressions in the OS were significantly higher compared to those of the HS (p < 0.05, p < 0.05). From these results, O. humifusa supplementation might play an important role for improving insulin sensitivity through elevation of PPAR-γ, PGC-1α, and GLUT-4 protein expression in rat skeletal muscle. PMID:23538842

  7. Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic beta-cells.

    PubMed

    Eto, Kazuhiro; Yamashita, Tokuyuki; Hirose, Kenzo; Tsubamoto, Yoshiharu; Ainscow, Edward K; Rutter, Guy A; Kimura, Satoshi; Noda, Mitsuhiko; Iino, Masamitsu; Kadowaki, Takashi

    2003-08-01

    We studied acute changes of secretory vesicle pH in pancreatic beta-cells with a fluorescent pH indicator, lysosensor green DND-189. Fluorescence was decreased by 0.66 +/- 0.10% at 149 +/- 16 s with 22.2 mM glucose stimulation, indicating that vesicular pH was alkalinized by approximately 0.016 unit. Glucose-responsive pH increase was observed when cytosolic Ca2+ influx was blocked but disappeared when an inhibitor of glycolysis or mitochondrial ATP synthase was present. Glutamate dimethyl ester (GME), a plasma membrane-permeable analog of glutamate, potentiated glucose-stimulated insulin secretion at 5 mM without changing cellular ATP content or cytosolic Ca2+ concentration ([Ca2+]). Application of GME at basal glucose concentration decreased DND-189 fluorescence by 0.83 +/- 0.19% at 38 +/- 2 s. These results indicated that the acutely alkalinizing effect of glucose on beta-cell secretory vesicle pH was dependent on glucose metabolism but independent of modulations of cytosolic [Ca2+]. Moreover, glutamate derived from glucose may be one of the mediators of this alkalinizing effect of glucose, which may have potential relevance to the alteration of secretory function by glutamate.

  8. Acute Citrulline-Malate Supplementation and High-Intensity Cycling Performance.

    PubMed

    Cunniffe, Brian; Papageorgiou, Maria; OʼBrien, Barbara; Davies, Nathan A; Grimble, George K; Cardinale, Marco

    2016-09-01

    Cunniffe, B, Papageorgiou, M, O'Brien, B, Davies, NA, Grimble, GK, and Cardinale, M. Acute citrulline-malate supplementation and high-intensity cycling performance. J Strength Cond Res 30(9): 2638-2647, 2016-Dietary L-citrulline-malate (CM) consumption has been suggested to improve skeletal muscle metabolism and contractile efficiency, which would be expected to predispose exercising individuals to greater fatigue resistance. The purpose of this study was to examine the effects of CM supplementation on acid-base balance and high-intensity exercise performance. In a double-blind, placebo-controlled, crossover study, 10 well-trained males consumed either 12 g of CM (in 400 ml) or lemon sugar-free cordial (placebo [PL]) 60 minutes before completion of 2 exercise trials. Each trial consisted of subjects performing 10 (×15 seconds) maximal cycle sprints (with 30-second rest intervals) followed by 5 minutes recovery before completing a cycle time-to-exhaustion test (TTE) at 100% of individual peak power (PP). Significant increases in plasma concentrations of citrulline (8.8-fold), ornithine (3.9-fold), and glutamine (1.3-fold) were observed 60 minutes after supplementation in the CM trial only (p ≤ 0.05) and none of the subjects experienced gastrointestinal side-effects during testing. Significantly higher exercise heart rates were observed in CM condition (vs. PL) although no between trial differences in performance related variables (TTE: [120 ± 61 seconds CM vs. 113 ± 50 seconds PL]), PP or mean power, ([power fatigue index: 36 ± 16% CM vs. 28 ± 18% PL]), subjective rating of perceived exertion or measures of acid-base balance (pH, lactate, bicarbonate, base-excess) were observed (p > 0.05). This study demonstrated that acute supplementation of 12 g CM does not provide acute ergogenic benefits using the protocol implemented in this study in well-trained males. PMID:26808848

  9. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  10. Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation.

    PubMed

    Johnson, Ariel M; Kurti, Stephanie P; Smith, Joshua R; Rosenkranz, Sara K; Harms, Craig A

    2016-03-01

    A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men. PMID:26872295

  11. Acute inhibition of central c-Jun N-terminal kinase restores hypothalamic insulin signalling and alleviates glucose intolerance in diabetic mice.

    PubMed

    Benzler, J; Ganjam, G K; Legler, K; Stöhr, S; Krüger, M; Steger, J; Tups, A

    2013-05-01

    The hypothalamus has been identified as a main insulin target tissue for regulating normal body weight and glucose metabolism. Recent observations suggest that c-Jun-N-terminal kinase (JNK)-signalling plays a crucial role in the development of obesity and insulin resistance because neuronal JNK-1 ablation in the mouse prevented high-fat diet-induced obesity (DIO) and increased energy expenditure, as well as insulin sensitivity. In the present study, we investigated whether central JNK inhibition is associated with sensitisation of hypothalamic insulin signalling in mice fed a high-fat diet for 3 weeks and in leptin-deficient mice. We determined whether i.c.v. injection of a pharmacological JNK-inhibitor (SP600125) improved impaired glucose homeostasis. By immunohistochemistry, we first observed that JNK activity was increased in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH) in both mouse models, relative to normoglycaemic controls. This suggests that up-regulation of JNK in these regions is associated with glucose intolerance and obesity, independent of leptin levels. Acute i.c.v. injection of SP600125 ameliorated glucose tolerance within 30 min in both leptin-deficient and DIO mice. Given the acute nature of i.c.v. injections, these effects cannot be attributed to changes in food intake or energy balance. In a hypothalamic cell line, and in the ARC and VMH of leptin-deficient mice, JNK inhibition by SP600125 consistently improved impaired insulin signalling. This was determined by a reduction of phospho-insulin receptor substrate-1 [IRS-1(Ser612)] protein in a hypothalamic cell line and a decline in the number of pIRS-1(Ser612) immunoreactive cells in the ARC and VMH. Serine 612 phosphorylation of IRS-1 is assumed to negatively regulate insulin signalling. In leptin-deficient mice, in both nuclei, central inhibition of JNK increased the number of cells immunoreactive for phospho-Akt (Ser473) and phospho-GSK-3β (Ser9), which are important

  12. Relationship of glucose values to sliding scale insulin (correctional insulin) dose delivery and meal time in acute care patients with diabetes mellitus.

    PubMed

    Trotter, Barbara; Conaway, Mark R; Burns, Suzanne M

    2013-01-01

    Findings of this study suggest the traditional sliding scale insulin (SSI) method does not improve target glucose values among adult medical inpatients. Timing of blood glucose (BC) measurement does affect the required SSI dose. BC measurement and insulin dose administration should be accomplished immediately prior to mealtime. PMID:23802496

  13. Fungal infection intensity and zoospore output of Atelopus zeteki, a potential acute chytrid supershedder.

    PubMed

    Direnzo, Graziella V; Langhammer, Penny F; Zamudio, Kelly R; Lips, Karen R

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially as they relate to

  14. Fungal Infection Intensity and Zoospore Output of Atelopus zeteki, a Potential Acute Chytrid Supershedder

    PubMed Central

    DiRenzo, Graziella V.; Langhammer, Penny F.; Zamudio, Kelly R.; Lips, Karen R.

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially

  15. Impaired nutritional status during intensive chemotherapy in Russian and Norwegian cohorts with acute myeloid leukemia.

    PubMed

    Iversen, Per Ole; Ukrainchenko, Ekaterina; Afanasyev, Boris; Hulbekkmo, Kristin; Choukah, Amal; Gulbrandsen, Nina; Wisløff, Finn; Tangen, Jon-Magnus

    2008-10-01

    Intensive chemotherapy is mandatory in curative treatment of acute myeloid leukemia (AML), but whether the nutritional status deteriorates during treatment, is unknown. We therefore prospectively examined anthropometric and biochemical nutritional markers during intensive chemotherapy in 26 Russian and 19 Norwegian AML patients during 9 months from diagnosis. Although the body mass index remained unchanged in both cohorts, hand grip strength and triceps skinfold thickness declined (P<0.05) during treatment before normalisation at study end. We detected a similar significant, temporary decrease in albumin, transferrin, testosterone and gonadotrophins in both cohorts. Although the fat-soluble vitamins D and E also displayed such a pattern, vitamin A dropped and remained low throughout the study in both cohorts. The Russian patients reported lower global quality of life, more symptoms and more financial concern than the Norwegians. Our data suggest a catabolic metabolism during intensive chemotherapy for AML, leading to impaired nutritional status, hypofunction of the pituitary-gonadal axis and decreased health-related quality of life.

  16. Are Intensive Care Factors Associated with Depressive Symptoms Six Months after Acute Lung Injury?

    PubMed Central

    Dowdy, David W.; Bienvenu, O. Joseph; Dinglas, Victor D.; Mendez-Tellez, Pedro A.; Sevransky, Jonathan; Shanholtz, Carl; Needham, Dale M.

    2009-01-01

    Objective To evaluate intensive care-related factors as predictors of depressive symptoms 6 months after acute lung injury (ALI) Design Prospective cohort study Setting Thirteen intensive care units (ICUs) in 4 hospitals in Baltimore, MD Patients Consecutive ALI survivors (n = 160; 71% from medical ICUs) screened for depressive symptoms at six months post-ALI Interventions None Measurements and Main Results We prospectively measured 12 features of critical illness and ICU care and used multivariable regression to evaluate associations with depressive symptoms as measured by the Hospital Anxiety and Depression (HAD) depression score. The prevalence of a positive screening for depression (score ≥8) at 6 months post-ALI was 26%. Depressive symptoms were significantly associated with surgical (versus medical or trauma) ICU admission (relative risk [RR] 2.2, 95% confidence interval [CI] 1.1 – 4.2), maximum daily Sequential Organ Failure Assessment score of >10 (RR 2.1, 95% CI 1.1 – 3.5), and mean daily ICU benzodiazepine dose of ≥75mg of midazolam-equivalent (RR 2.1, 95% CI 1.1 – 3.5). Conclusions Depressive symptoms at 6 months post-ALI are common and potentially associated with ICU-related factors. Mechanisms by which critical illness and intensive care management associate with depressive symptoms merit further investigation. PMID:19357507

  17. An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.

    PubMed

    Rivas, Eric; Newmire, Dan E; Crandall, Craig G; Hooper, Philip L; Ben-Ezra, Vic

    2016-07-01

    Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, P<0.01; 5.3±0.4% HbA1c, P<0.01) participated. Using a randomized design, subjects underwent either a whole body passive hyperthermia treatment via head-out hot water immersion (1h resting in 39.4±0.4°C water) that increased internal temperature above baseline by ∆1.6±0.4°C or a control resting condition. Twenty-four hours post treatments, a 75g OGTT was administered to evaluate changes in plasma glucose, insulin, C-peptide, and leptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg·fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals. PMID:27264884

  18. Hyperglycemia, acute insulin resistance, and renal dysfunction in the early phase of ST-elevation myocardial infarction without previously known diabetes: impact on long-term prognosis.

    PubMed

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; Attanà, Paola; Mattesini, Alessio; Nesti, Martina; Gensini, Gian Franco

    2014-11-01

    We evaluated the relationship between admission renal function (as assessed by estimated glomerular filtration rate (eGFR)), hyperglycemia, and acute insulin resistance, indicated by the homeostatic model assessment (HOMA) index, and their impact on long-term prognosis in 825 consecutive patients with ST-elevation myocardial infarction (STEMI) without previously known diabetes who underwent primary percutaneous coronary intervention (PCI). Admission eGFR showed a significant indirect correlation with admission glycemia (Spearman's ρ -0.23, P < 0.001) and insulin values (Spearman's ρ -0.11, P = 0.002). The incidence of patients with admission glycemia ≥140 mg/dl was significantly higher in patients with eGFR <60 ml/min/m(2) (P < 0.001) as well as the incidence of HOMA positivity (P = 0.002). According to our data, a relationship between renal function and glucose values and acute insulin resistance in the early phase of STEMI was detectable, since a significant, indirect correlation between eGFR, insulin values, and glycemia was observed. Patients with renal dysfunction (eGFR <60 ml/min/1.73 m(2)) exhibited higher glucose values and a higher incidence of acute insulin resistance (as assessed by HOMA index) than those with normal renal function (eGFR ≥60 ml/min/1.73 m(2)). The prognostic role of glucose values for 1-year mortality was confined to patients with eGFR ≥60 ml/min/m(2), who represent the large part of our population and are thought to be at lower risk. In these patients, an independent relationship between 1-year mortality and glucose values was detectable not only for admission glycemia but also for glucose values measured at discharge.

  19. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    ClinicalTrials.gov

    2015-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  20. Computerised treatment of anomia in acute aphasia: treatment intensity and training size.

    PubMed

    Laganaro, Marina; Di Pietro, Marie; Schnider, Armin

    2006-12-01

    In this study we analysed the outcome of computer-assisted therapy (CAT) for anomia on eight acute aphasic patients. Since therapy for anomia generally leads to an item-specific effect, the aim of the present study was to investigate whether it is possible to enhance recovery from anomia by increasing the number of treated items. Two periods of five daily written-naming CAT sessions were compared: In one period the CAT included one set of 48 words (single list) and in the other period a double list of 96 items was treated. Seven out of eight patients improved in naming performance for treated items. Overall gains were superior after practising the double list, despite fewer item repetitions. These results suggest that the size of the effect of therapy for anomia depends more on the number of treated items than on the number of repetitions per item. The integration of these results within the framework of studies on intensity is discussed.

  1. Decline in executive control during acute bouts of exercise as a function of exercise intensity and fitness level.

    PubMed

    Labelle, Véronique; Bosquet, Laurent; Mekary, Saïd; Bherer, Louis

    2013-02-01

    Studies on the effects of acute bouts of cardiovascular exercise on cognitive performances show contradictory findings due to methodological differences (e.g., exercise intensity, cognitive function assessed, participants' aerobic fitness level, etc.). The present study assessed the acute effect of exercise intensity on cognition while controlling for key methodological confounds. Thirty-seven participants (M(age)=23. 8 years; SD=2.6) completed a computerized modified-Stroop task (involving denomination, inhibition and switching conditions) while pedalling at 40%, 60% and 80% of their peak power output (PPO). Results showed that in the switching condition of the task, error rates increased as a function of exercise intensity (from 60% to 80% of PPO) in all participants and that lower fit individuals showed increased reaction time variability. This suggests that acute bouts of cardiovascular exercise can momentarily alter executive control and increase performance instability in lower fit individuals. PMID:23146780

  2. Evaluating acute pain intensity relief: challenges when using an 11-point numerical rating scale.

    PubMed

    Chauny, Jean-Marc; Paquet, Jean; Lavigne, Gilles; Marquis, Martin; Daoust, Raoul

    2016-02-01

    Percentage of pain intensity difference (PercentPID) is a recognized way of evaluating pain relief with an 11-point numerical rating scale (NRS) but is not without flaws. A new metric, the slope of relative pain intensity difference (SlopePID), which consists in dividing PercentPID by the time between 2 pain measurements, is proposed. This study aims to validate SlopePID with 3 measures of subjective pain relief: a 5-category relief scale (not, a little, moderate, very, complete), a 2-category relief question ("I'm relieved," "I'm not relieved"), and a single-item question, "Wanting other medication to treat pain?" (Yes/No). This prospective cohort study included 361 patients in the emergency department who had an initial acute pain NRS > 3 and a pain intensity assessment within 90 minutes after analgesic administration. Mean age was 50.2 years (SD = 19.3) and 59% were women. Area under the curves of receiver operating characteristic curves analyses revealed similar discriminative power for PercentPID (0.83; 95% confidence interval [CI], 0.79-0.88) and SlopePID (0.82; 95% CI, 0.77-0.86). Considering the "very" category from the 5-category relief scale as a substantial relief, the average cutoff for substantial relief was a decrease of 64% (95% CI, 59-69) for PercentPID and of 49% per hour (95% CI, 44-54) for SlopePID. However, when a cutoff criterion of 50% was used as a measure of pain relief for an individual patient, PercentPID underestimated pain-relieved patients by 12.1% (P < 0.05) compared with the SlopePID measurement, when pain intensity at baseline was an odd number compared with an even number (32.9% vs 45.0%, respectively). SlopePID should be used instead of PercentPID as a metric to evaluate acute pain relief on a 0 to 10 NRS.

  3. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  4. `An observational report of intensive robotic and manual gait training in sub-acute stroke

    PubMed Central

    2012-01-01

    Background The use of automated electromechanical devices for gait training in neurological patients is increasing, yet the functional outcomes of well-defined training programs using these devices and the characteristics of patients that would most benefit are seldom reported in the literature. In an observational study of functional outcomes, we aimed to provide a benchmark for expected change in gait function in early stroke patients, from an intensive inpatient rehabilitation program including both robotic and manual gait training. Methods We followed 103 sub-acute stroke patients who met the clinical inclusion criteria for Body Weight Supported Robotic Gait Training (BWSRGT). Patients completed an intensive 8-week gait-training program comprising robotic gait training (weeks 0-4) followed by manual gait training (weeks 4-8). A change in clinical function was determined by the following assessments taken at 0, 4 and 8 weeks (baseline, mid-point and end-point respectively): Functional Ambulatory Categories (FAC), 10 m Walking Test (10 MWT), and Tinetti Gait and Balance Scales. Results Over half of the patients made a clinically meaningful improvement on the Tinetti Gait Scale (> 3 points) and Tinetti Balance Scale (> 5 points), while over 80% of the patients increased at least 1 point on the FAC scale (0-5) and improved walking speed by more than 0.2 m/s. Patients responded positively in gait function regardless of variables gender, age, aetiology (hemorrhagic/ischemic), and affected hemisphere. The most robust and significant change was observed for patients in the FAC categories two and three. The therapy was well tolerated and no patients withdrew for factors related to the type or intensity of training. Conclusions Eight-weeks of intensive rehabilitation including robotic and manual gait training was well tolerated by early stroke patients, and was associated with significant gains in function. Patients with mid-level gait dysfunction showed the most robust

  5. [Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

    PubMed

    Scheer, U; Schellong, G; Riehm, H

    1979-03-01

    Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

  6. Patients with Acute Myeloid Leukemia Admitted to Intensive Care Units: Outcome Analysis and Risk Prediction

    PubMed Central

    Braess, Jan; Thudium, Johannes; Schmid, Christoph; Kochanek, Matthias; Kreuzer, Karl-Anton; Lebiedz, Pia; Görlich, Dennis; Gerth, Hans U.; Rohde, Christian; Kessler, Torsten; Müller-Tidow, Carsten; Stelljes, Matthias; Büchner, Thomas; Schlimok, Günter; Hallek, Michael; Waltenberger, Johannes; Hiddemann, Wolfgang; Berdel, Wolfgang E.; Heilmeier, Bernhard; Krug, Utz

    2016-01-01

    Background This retrospective, multicenter study aimed to reveal risk predictors for mortality in the intensive care unit (ICU) as well as survival after ICU discharge in patients with acute myeloid leukemia (AML) requiring treatment in the ICU. Methods and Results Multivariate analysis of data for 187 adults with AML treated in the ICU in one institution revealed the following as independent prognostic factors for death in the ICU: arterial oxygen partial pressure below 72 mmHg, active AML and systemic inflammatory response syndrome upon ICU admission, and need for hemodialysis and mechanical ventilation in the ICU. Based on these variables, we developed an ICU mortality score and validated the score in an independent cohort of 264 patients treated in the ICU in three additional tertiary hospitals. Compared with the Simplified Acute Physiology Score (SAPS) II, the Logistic Organ Dysfunction (LOD) score, and the Sequential Organ Failure Assessment (SOFA) score, our score yielded a better prediction of ICU mortality in the receiver operator characteristics (ROC) analysis (AUC = 0.913 vs. AUC = 0.710 [SAPS II], AUC = 0.708 [LOD], and 0.770 [SOFA] in the training cohort; AUC = 0.841 for the developed score vs. AUC = 0.730 [SAPSII], AUC = 0.773 [LOD], and 0.783 [SOFA] in the validation cohort). Factors predicting decreased survival after ICU discharge were as follows: relapse or refractory disease, previous allogeneic stem cell transplantation, time between hospital admission and ICU admission, time spent in ICU, impaired diuresis, Glasgow Coma Scale <8 and hematocrit of ≥25% at ICU admission. Based on these factors, an ICU survival score was created and used for risk stratification into three risk groups. This stratification discriminated distinct survival rates after ICU discharge. Conclusions Our data emphasize that although individual risks differ widely depending on the patient and disease status, a substantial portion of critically ill patients with AML benefit

  7. [Intensive glycemia control in the first day of the acute cerebral blood flow disturbance in patients with diabetes mellitus type 2].

    PubMed

    Grigorian, I G; Gustov, A V; Strongin, L G; Beliaeva, N G

    2012-01-01

    Forty-seven patients with cerebral stroke and diabetes mellitus type 2 were included in the study. To maintain the target values of glycemia on the level 7.8-10.2 mmol/l, patients of the main group received the continuous intravenous infusion of insulin and patients of the control group received frequent (every 3h) subcutaneous injections of insulin during the first 24 h after the acute cerebral blood flow disturbance. The results obtained have shown that continuous intravenous insulin infusion reduces the risk of hypoglycemia, accelerates positive neurologic dynamics, reduces terms of hospitalization and decreases mortality in patients with diabetes mellitus type 2.

  8. Does weather affect daily pain intensity levels in patients with acute low back pain? A prospective cohort study.

    PubMed

    Duong, Vicky; Maher, Chris G; Steffens, Daniel; Li, Qiang; Hancock, Mark J

    2016-05-01

    The aim of this study was to investigate the influence of various weather parameters on pain intensity levels in patients with acute low back pain (LBP). We performed a secondary analysis using data from the PACE trial that evaluated paracetamol (acetaminophen) in the treatment of acute LBP. Data on 1604 patients with LBP were included in the analysis. Weather parameters (precipitation, temperature, relative humidity, and air pressure) were obtained from the Australian Bureau of Meteorology. Pain intensity was assessed daily on a 0-10 numerical pain rating scale over a 2-week period. A generalised estimating equation analysis was used to examine the relationship between daily pain intensity levels and weather in three different time epochs (current day, previous day, and change between previous and current days). A second model was adjusted for important back pain prognostic factors. The analysis did not show any association between weather and pain intensity levels in patients with acute LBP in each of the time epochs. There was no change in strength of association after the model was adjusted for prognostic factors. Contrary to common belief, the results demonstrated that the weather parameters of precipitation, temperature, relative humidity, and air pressure did not influence the intensity of pain reported by patients during an episode of acute LBP.

  9. Does weather affect daily pain intensity levels in patients with acute low back pain? A prospective cohort study.

    PubMed

    Duong, Vicky; Maher, Chris G; Steffens, Daniel; Li, Qiang; Hancock, Mark J

    2016-05-01

    The aim of this study was to investigate the influence of various weather parameters on pain intensity levels in patients with acute low back pain (LBP). We performed a secondary analysis using data from the PACE trial that evaluated paracetamol (acetaminophen) in the treatment of acute LBP. Data on 1604 patients with LBP were included in the analysis. Weather parameters (precipitation, temperature, relative humidity, and air pressure) were obtained from the Australian Bureau of Meteorology. Pain intensity was assessed daily on a 0-10 numerical pain rating scale over a 2-week period. A generalised estimating equation analysis was used to examine the relationship between daily pain intensity levels and weather in three different time epochs (current day, previous day, and change between previous and current days). A second model was adjusted for important back pain prognostic factors. The analysis did not show any association between weather and pain intensity levels in patients with acute LBP in each of the time epochs. There was no change in strength of association after the model was adjusted for prognostic factors. Contrary to common belief, the results demonstrated that the weather parameters of precipitation, temperature, relative humidity, and air pressure did not influence the intensity of pain reported by patients during an episode of acute LBP. PMID:26759130

  10. Regional anesthesia for management of acute pain in the intensive care unit.

    PubMed

    De Pinto, Mario; Dagal, Armagan; O'Donnell, Brendan; Stogicza, Agnes; Chiu, Sheila; Edwards, William Thomas

    2015-01-01

    Pain is a major problem for Intensive Care Unit (ICU) patients. Despite numerous improvements it is estimated that as many as 70% of the patients experience moderate-to-severe postoperative pain during their stay in the ICU. Effective pain management means not only decreasing pain intensity, but also reducing the opioids' side effects. Minimizing nausea, vomiting, urinary retention, and sedation may indeed facilitate patient recovery and it is likely to shorten the ICU and hospital stay. Adequate postoperative and post-trauma pain management is also crucial for the achievement of effective rehabilitation. Furthermore, recent studies suggest that effective acute pain management may be helpful in reducing the development of chronic pain. When used appropriately, and in combination with other treatment modalities, regional analgesia techniques (neuraxial and peripheral nerve blocks) have the potential to reduce or eliminate the physiological stress response to surgery and trauma, decreasing the possibility of surgical complications and improving the outcomes. Also they may reduce the total amount of opioid analgesics necessary to achieve adequate pain control and the development of potentially dangerous side effects. PMID:26557482

  11. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia

    PubMed Central

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T.; Bhatt, Vijaya Raj

    2016-01-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials. PMID:27247754

  12. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    PubMed

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

  13. Exposure of fish to high-intensity sonar does not induce acute pathology.

    PubMed

    Kane, A S; Song, J; Halvorsen, M B; Miller, D L; Salierno, J D; Wysocki, L E; Zeddies, D; Popper, A N

    2010-05-01

    This study investigated immediate effects of intense sound exposure associated with low-frequency (170-320 Hz) or with mid-frequency (2.8-3.8 kHz) sonars on caged rainbow trout Oncorhynchus mykiss, channel catfish Ictalurus punctatus and hybrid sunfish Lepomis sp. in Seneca Lake, New York, U.S.A. This study focused on potential effects on inner ear tissues using scanning electron microscopy and on non-auditory tissues using gross and histopathology. Fishes were exposed to low-frequency sounds for 324 or 628 s with a received peak signal level of 193 dB re 1 microPa (root mean square, rms) or to mid-frequency sounds for 15 s with a received peak signal level of 210 dB re 1 microPa (rms). Although a variety of clinical observations from various tissues and organ systems were described, no exposure-related pathologies were observed. This study represents the first investigation of the effects of high-intensity sonar on fish tissues in vivo. Data from this study indicate that exposure to low and midfrequency sonars, as described in this report, might not have acute effects on fish tissues.

  14. Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations.

    PubMed

    Cochran, Andrew J R; Percival, Michael E; Tricarico, Steven; Little, Jonathan P; Cermak, Naomi; Gillen, Jenna B; Tarnopolsky, Mark A; Gibala, Martin J

    2014-05-01

    High-intensity interval training (HIIT) performed in an 'all-out' manner (e.g. repeated Wingate tests) is a time-efficient strategy to induce skeletal muscle remodelling towards a more oxidative phenotype. A fundamental question that remains unclear, however, is whether the intermittent or 'pulsed' nature of the stimulus is critical to the adaptive response. In study 1, we examined whether the activation of signalling cascades linked to mitochondrial biogenesis was dependent on the manner in which an acute high-intensity exercise stimulus was applied. Subjects performed either four 30 s Wingate tests interspersed with 4 min of rest (INT) or a bout of continuous exercise (CONT) that was matched for total work (67 ± 7 kJ) and which required ∼4 min to complete as fast as possible. Both protocols elicited similar increases in markers of adenosine monophosphate-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase activation, as well as Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression (main effects for time, P ≤ 0.05). In study 2, we determined whether 6 weeks of the CONT protocol (3 days per week) would increase skeletal muscle mitochondrial content to a similar extent to what we have previously reported after 6 weeks of INT. Despite similar acute signalling responses to the CONT and INT protocols, training with CONT did not increase the maximal activity or protein content of a range of mitochondrial markers. However, peak oxygen uptake was higher after CONT training (from 45.7 ± 5.4 to 48.3 ± 6.5 ml kg(-1) min(-1); P < 0.05) and 250 kJ time trial performance was improved (from 26:32 ± 4:48 to 23:55 ± 4:16 min:s; P < 0.001) in our recreationally active participants. We conclude that the intermittent nature of the stimulus is important for maximizing skeletal muscle adaptations to low-volume, all-out HIIT. Despite the lack of skeletal muscle mitochondrial adaptations

  15. Differential Effects of Differing Intensities of Acute Exercise on Speed and Accuracy of Cognition: A Meta-Analytical Investigation

    ERIC Educational Resources Information Center

    McMorris, Terry; Hale, Beverley J.

    2012-01-01

    The primary purpose of this study was to examine, using meta-analytical techniques, the differential effects of differing intensities of acute exercise on speed and accuracy of cognition. Overall, exercise demonstrated a small, significant mean effect size (g = 0.14, p less than 0.01) on cognition. Examination of the comparison between speed and…

  16. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT

    PubMed Central

    Sengsayadeth, Salyka; Savani, Bipin N.; Blaise, Didier; Malard, Florent; Nagler, Arnon; Mohty, Mohamad

    2015-01-01

    Acute myeloid leukemia is the most common indication for an allogeneic hematopoietic cell transplant. The introduction of reduced intensity conditioning has expanded the recipient pool for transplantation, which has importantly made transplant an option for the more commonly affected older age groups. Reduced intensity conditioning allogeneic transplantation is currently the standard of care for patients with intermediate or high-risk acute myeloid leukemia and is now most often employed in older patients and those with medical comorbidities. Despite being curative for a significant proportion of patients, post-transplant relapse remains a challenge in the reduced intensity conditioning setting. Herein we discuss the studies that demonstrate the feasibility of reduced intensity conditioning allogeneic transplants, compare the outcomes of reduced intensity conditioning versus chemotherapy and conventional myeloablative conditioning regimens, describe the optimal donor and stem cell source, and consider the impact of post-remission consolidation, comorbidities, center experience, and more intensive (reduced toxicity conditioning) regimens on outcomes. Additionally, we discuss the need for further prospective studies to optimize transplant outcomes. PMID:26130513

  17. The glucoregulatory response to high-intensity aerobic exercise following training in rats with insulin-treated type 1 diabetes mellitus.

    PubMed

    McDonald, Matthew W; Murray, Michael R; Grise, Kenneth N; Olver, T Dylan; Dey, Adwitia; Shoemaker, J Kevin; Noble, Earl G; Melling, C W James

    2016-06-01

    An acute bout of exercise elicits a rapid, potentially deleterious, reduction in blood glucose in patients with type 1 diabetes mellitus (T1DM). In the current study, we examined whether a 10-week aerobic training program could alleviate the rapid exercise-associated reduction in blood glucose through changes in the glucoregulatory hormonal response or increased hepatic glycogen storage in an insulin-treated rat model of T1DM. Thirty-two male Sprague-Dawley rats were divided evenly into 4 groups: non-T1DM sedentary (C) (n = 8), non-T1DM exercised (CX) (n = 8), T1DM sedentary (D) (n = 8), and T1DM exercised (DX) (n = 8). Exercise training consisted of treadmill running for 5 days/week (1 h, 27 m/min, 6% grade) for 10 weeks. T1DM was induced by multiple streptozotocin injections (20 mg/kg) followed by implantation of subcutaneous insulin pellets. At week 1, an acute exercise bout led to a significant reduction in blood glucose in DX (p < 0.05), whereas CX exhibited an increase in blood glucose (p < 0.05). During acute exercise, serum epinephrine was increased in both DX and CX (p < 0.05), whereas serum glucagon was increased during recovery only in CX (p < 0.01). Following aerobic training in DX, the exercise-mediated reduction in blood glucose remained; however, serum glucagon increased to the same extent as in CX (p < 0.05). DX exhibited significantly less hepatic glycogen (p < 0.001) despite elevations in glycogenic proteins in the liver (p < 0.05). Elevated serum epinephrine and decreased hepatic adrenergic receptor expression were also evident in DX (p < 0.05). In summary, despite aerobic training in DX, abrupt blood glucose reductions and hepatic glycogen deficiencies were evident. These data suggest that sympathetic overactivity may contribute to deficiencies in hepatic glycogen storage. PMID:27175938

  18. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage.

    PubMed

    Qureshi, Adnan I; Palesch, Yuko Y; Barsan, William G; Hanley, Daniel F; Hsu, Chung Y; Martin, Renee L; Moy, Claudia S; Silbergleit, Robert; Steiner, Thorsten; Suarez, Jose I; Toyoda, Kazunori; Wang, Yongjun; Yamamoto, Haruko; Yoon, Byung-Woo

    2016-09-15

    Background Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage. Methods We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments. Results Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events

  19. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage.

    PubMed

    Qureshi, Adnan I; Palesch, Yuko Y; Barsan, William G; Hanley, Daniel F; Hsu, Chung Y; Martin, Renee L; Moy, Claudia S; Silbergleit, Robert; Steiner, Thorsten; Suarez, Jose I; Toyoda, Kazunori; Wang, Yongjun; Yamamoto, Haruko; Yoon, Byung-Woo

    2016-09-15

    Background Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage. Methods We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments. Results Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events

  20. A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia.

    PubMed

    Russell, N H; Kjeldsen, L; Craddock, C; Pagliuca, A; Yin, J A; Clark, R E; Howman, A; Hills, R K; Burnett, A K

    2015-07-01

    Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35-44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50-0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01-2.21), P=0.04) due to lower NRM (34 vs 14%, P=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57-0.97), P=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35-44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (P=0.3).

  1. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    PubMed

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-01

    Acute exercise can positively impact cognition. The present study examined the effect of acute high-intensity aerobic exercise on prefrontal-dependent cognitive performance and brain-derived neurotrophic factor (BDNF). Fifty-eight young adults were randomly assigned to one of two experimental groups: (a) an acute bout of high-intensity exercise (n=29) or (b) a non-exercise control (n=29). Participants in the exercise group improved performance on inhibitory control in Stroop interference and on cognitive flexibility in Trail Making Test (TMT) Part-B compared with participants in the control group and increased BDNF immediately after exercise. There was a significant relationship between BDNF and TMT Part-B on the pre-post change following exercise. These findings provide support for the association between improved prefrontal-dependent cognitive performance and increased BDNF in response to acute exercise. We conclude that the changes in BDNF concentration may be partially responsible for prefrontal-dependent cognitive functioning following an acute bout of exercise. PMID:27450438

  2. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    PubMed

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-01

    Acute exercise can positively impact cognition. The present study examined the effect of acute high-intensity aerobic exercise on prefrontal-dependent cognitive performance and brain-derived neurotrophic factor (BDNF). Fifty-eight young adults were randomly assigned to one of two experimental groups: (a) an acute bout of high-intensity exercise (n=29) or (b) a non-exercise control (n=29). Participants in the exercise group improved performance on inhibitory control in Stroop interference and on cognitive flexibility in Trail Making Test (TMT) Part-B compared with participants in the control group and increased BDNF immediately after exercise. There was a significant relationship between BDNF and TMT Part-B on the pre-post change following exercise. These findings provide support for the association between improved prefrontal-dependent cognitive performance and increased BDNF in response to acute exercise. We conclude that the changes in BDNF concentration may be partially responsible for prefrontal-dependent cognitive functioning following an acute bout of exercise.

  3. Acute molecular responses to concurrent resistance and high-intensity interval exercise in untrained skeletal muscle.

    PubMed

    Pugh, Jamie K; Faulkner, Steve H; Jackson, Andrew P; King, James A; Nimmo, Myra A

    2015-04-01

    Concurrent training involving resistance and endurance exercise may augment the benefits of single-mode training for the purpose of improving health. However, muscle adaptations, associated with resistance exercise, may be blunted by a subsequent bout of endurance exercise, via molecular interference. High-intensity interval training (HIIT), generating similar adaptations to endurance exercise, may offer an alternative exercise mode to traditional endurance exercise. This study examined the influence of an acute HIIT session on the molecular responses following resistance exercise in untrained skeletal muscle. Ten male participants performed resistance exercise (4 × 8 leg extensions, 70% 1RM, (RE)) or RE followed by HIIT (10 × 1 min at 90% HRmax, (RE+HIIT)). Muscle biopsies were collected from the vastus lateralis before, 2 and 6 h post-RE to determine intramuscular protein phosphorylation and mRNA responses. Phosphorylation of Akt (Ser(473)) decreased at 6 h in both trials (P < 0.05). Phosphorylation of mTOR (Ser(2448)) was higher in RE+HIIT (P < 0.05). All PGC-1α mRNA variants increased at 2 h in RE+HIIT with PGC-1α and PGC-1α-ex1b remaining elevated at 6 h, whereas RE-induced increases at 2 and 6 h for PGC-1α-ex1b only (P < 0.05). Myostatin expression decreased at 2 and 6 h in both trials (P < 0.05). MuRF-1 was elevated in RE+HIIT versus RE at 2 and 6 h (P < 0.05). Atrogin-1 was lower at 2 h, with FOXO3A downregulated at 6 h (P < 0.05). These data do not support the existence of an acute interference effect on protein signaling and mRNA expression, and suggest that HIIT may be an alternative to endurance exercise when performed after resistance exercise in the same training session to optimize adaptations.

  4. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF.

    PubMed

    Adibzadeh, F; van Rhoon, G C; Verduijn, G M; Naus-Postema, N C; Paulides, M M

    2016-01-21

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg(-1)) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients' feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R (2) =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature simulations as a

  5. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

  6. Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume.

    PubMed

    Cullen, Tom; Thomas, Andrew W; Webb, Richard; Hughes, Michael G

    2016-08-01

    Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise. PMID:27377137

  7. Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume.

    PubMed

    Cullen, Tom; Thomas, Andrew W; Webb, Richard; Hughes, Michael G

    2016-08-01

    Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise.

  8. Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: Effects of fat composition and gender

    PubMed Central

    Newens, K.J.; Thompson, A.K.; Jackson, K.G.; Williams, C.M.

    2015-01-01

    Background and aims We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. Methods and results Thirty adults (mean age 27.8 y, BMI 23.2 kg/m2) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60 and 390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P = 0.027) whilst SFA + LC n-3 PUFA improved FMD at 240 min (P = 0.003). In males, insulin infusion attenuated the increase in FMD with SFA + LC n-3 PUFA (P = 0.049), with SI 10% greater with SFA + LC n-3 PUFA than SFA (P = 0.041). Conclusion This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. This trial was registered at clinical trials.gov as NCT01351324 on 6th May 2011. PMID:25921849

  9. Six-month survival and quality of life of intensive care patients with acute kidney injury

    PubMed Central

    2013-01-01

    Introduction Acute kidney injury (AKI) has high incidence among the critically ill and associates with dismal outcome. Not only the long-term survival, but also the quality of life (QOL) of patients with AKI is relevant due to substantial burden of care regarding these patients. We aimed to study the long-term outcome and QOL of patients with AKI treated in intensive care units. Methods We conducted a predefined six-month follow-up of adult intensive care unit (ICU) patients from the prospective, observational, multi-centre FINNAKI study. We evaluated the QOL of survivors with the EuroQol (EQ-5D) questionnaire. We included all participating sites with at least 70% rate of QOL measurements in the analysis. Results Of the 1,568 study patients, 635 (40.5%, 95% confidence interval (CI) 38.0-43.0%) had AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Of the 635 AKI patients, 224 (35.3%), as compared to 154/933 (16.5%) patients without AKI, died within six months. Of the 1,190 survivors, 959 (80.6%) answered the EQ-5D questionnaire at six months. The QOL (median with Interquartile range, IQR) measured with the EQ-5D index and compared to age- and sex-matched general population was: 0.676 (0.520-1.00) versus 0.826 (0.812-0.859) for AKI patients, and 0.690 (0.533-1.00) versus 0.845 (0.812-0.882) for patients without AKI (P <0.001 in both). The EQ-5D at the time of ICU admission was available for 774 (80.7%) of the six-month respondents. We detected a mean increase of 0.017 for non-AKI and of 0.024 for AKI patients in the EQ-5D index (P = 0.728). The EQ-5D visual analogue scores (median with IQR) of patients with AKI (70 (50–83)) and patients without AKI (75 (60–87)) were not different from the age- and sex-matched general population (69 (68–73) and 70 (68–77)). Conclusions The health-related quality of life of patients with and without AKI was already lower on ICU admission than that of the age- and sex-matched general

  10. Acute Transfusion Reactions (ATRs) in Intensive Care Unit (ICU): A Retrospective Study

    PubMed Central

    Kumar, Rajesh; Gupta, Manvi; Gupta, Varun; Kaur, Amarjit; Gupta, Sonia

    2014-01-01

    Background: Blood transfusion is a frequent and integral part of critical care. Although life saving, it can occasionally be unsafe and result in a spectrum of adverse events. Acute transfusion reactions (ATRs) are probably under diagnosed in critically ill patients due to confusion of the symptoms with the underlying disease. Aim: To analyze the incidence and spectrum of ATRs occuring in critically ill patients. Materials and Methods: This was a retrospective review conducted from 1st April 2011 till 31st March 2013. The ATRs related to the administration of blood components in the patients admitted in various Intensive Care Units (ICUs) were recorded, analyzed and classified on the basis of their clinical features and laboratory tests. Results: During the study period 98651 blood components were issued. Out of these 21971 were issued to various ICUs. A total of 225 transfusion reactions were reported from the various critical care departments during this period. The most frequent were Febrile Non Hemolytic Transfusion Reactions (FNHTR) 136 (60.4%), allergic reactions 70 (31.2%), hemolytic reactions 1(0.4%) and non specific reactions 18 (8%). The incidence of ATRs in our study was found to be 1.09% in adult ICUs and 0.36% in pediatric ICUs. Conclusions: Blood transfusion is a vital therapeutic procedure with a potential risk to already critical patients. So a strict vigilance has to be kept and each transfusion has to be monitored carefully with prompt recognition and treatment of ATRs. A rational use of these products considering their deleterious effects can decrease transfusion related morbidity and mortality in the critically ill patients. PMID:24701502

  11. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  12. High-intensity interval training attenuates the exercise-induced increase in plasma IL-6 in response to acute exercise.

    PubMed

    Croft, Louise; Bartlett, Jonathan D; MacLaren, Don P M; Reilly, Thomas; Evans, Louise; Mattey, Derek L; Nixon, Nicola B; Drust, Barry; Morton, James P

    2009-12-01

    This aims of this study were to investigate the effects of carbohydrate availability during endurance training on the plasma interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha response to a subsequent acute bout of high-intensity interval exercise. Three groups of recreationally active males performed 6 weeks of high-intensity interval running. Groups 1 (LOW+GLU) and 2 (LOW+PLA) trained twice per day, 2 days per week, and consumed a 6.4% glucose or placebo solution, respectively, before every second training session and at regular intervals throughout exercise. Group 3 (NORM) trained once per day, 4 days per week, and consumed no beverage during training. Each group performed 50 min of high-intensity interval running at the same absolute workloads before and after training. Muscle glycogen utilization in the gastrocnemius muscle during acute exercise was reduced (p < 0.05) in all groups following training, although this was not affected by training condition. Plasma IL-6 concentration increased (p < 0.05) after acute exercise in all groups before and after training. Furthermore, the magnitude of increase was reduced (p < 0.05) following training. This training-induced attenuation in plasma IL-6 increase was similar among groups. Plasma IL-8 concentration increased (p < 0.05) after acute exercise in all groups, although the magnitude of increase was not affected (p > 0.05) by training. Acute exercise did not increase (p > 0.05) plasma TNF-alpha when undertaken before or after training. Data demonstrate that the exercise-induced increase in plasma IL-6 concentration in response to customary exercise is attenuated by previous exercise training, and that this attenuation appears to occur independent of carbohydrate availability during training.

  13. Influence of acute high-intensity aerobic interval exercise bout on selective attention and short-term memory tasks.

    PubMed

    Alves, Christiano R R; Tessaro, Victor H; Teixeira, Luis A C; Murakava, Karina; Roschel, Hamilton; Gualano, Bruno; Takito, Monica Y

    2014-02-01

    Acute moderate intensity continuous aerobic exercise can improve specific cognitive functions, such as short-term memory and selective attention. Moreover, high-intensity interval training (HIT) has been recently proposed as a time-efficient alternative to traditional cardiorespiratory exercise. However, considering previous speculations that the exercise intensity affects cognition in a U-shaped fashion, it was hypothesized that a HIT session may impair cognitive performance. Therefore, this study assessed the effects of an acute HIT session on selective attention and short-term memory tasks. 22 healthy middle-aged individuals (M age = 53.7 yr.) engaged in both (1) a HIT session, 10 1 min. cycling bouts at the intensity corresponding to 80% of the reserve heart rate interspersed by 1 min. active pauses cycling at 60% of the reserve heart rate and (2) a control session, consisting of an active condition with low-intensity active stretching exercise. Before and after each experimental session, cognitive performance was assessed by the Victoria Version of the Stroop test (a selective attention test) and the Digit Span test (a short-term memory test). Following the HIT session, the time to complete the Stroop "Color word" test was significantly lower when compared with that of the control session. The performances in the other subtasks of the Stroop test as well as in the Digit Span test were not significantly different. A HIT session can improve cognitive function.

  14. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes

    PubMed Central

    Kramer, Caroline K; Zinman, Bernard; Choi, Haysook; Retnakaran, Ravi

    2016-01-01

    Objective In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2–4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to 1 year in some patients. However, little is known about the predictors of such a sustained remission. Methods We evaluated data from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM. Results At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function (Insulin Secretion-Sensitivity Index-2) (p=0.01) that was then sustained across 48 weeks post-IIT (p=0.006). On logistic regression analyses, however, shorter duration of diabetes supplanted baseline A1c (p=0.24) and β-cell function (p=0.19) as an independent predictor of remission (p=0.04). In particular, diabetes duration <2 years predicted persistence of remission (p=0.006). Conclusions The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. Trial registration number ClinicalTrials.Gov NCT01270789; Post-results. PMID:27547422

  15. Acute, intermediate intensity exercise, and speed and accuracy in working memory tasks: a meta-analytical comparison of effects.

    PubMed

    McMorris, Terry; Sproule, John; Turner, Anthony; Hale, Beverley J

    2011-03-01

    The purpose of this study was to compare, using meta-analytic techniques, the effect of acute, intermediate intensity exercise on the speed and accuracy of performance of working memory tasks. It was hypothesized that acute, intermediate intensity exercise would have a significant beneficial effect on response time and that effect sizes for response time and accuracy data would differ significantly. Random-effects meta-analysis showed a significant, beneficial effect size for response time, g=-1.41 (p<0.001) but a significant detrimental effect size, g=0.40 (p<0.01), for accuracy. There was a significant difference between effect sizes (Z(diff)=3.85, p<0.001). It was concluded that acute, intermediate intensity exercise has a strong beneficial effect on speed of response in working memory tasks but a low to moderate, detrimental one on accuracy. There was no support for a speed-accuracy trade-off. It was argued that exercise-induced increases in brain concentrations of catecholamines result in faster processing but increases in neural noise may negatively affect accuracy.

  16. Men and Women Exhibit Similar Acute Hypotensive Responses After Low, Moderate, or High-Intensity Plyometric Training.

    PubMed

    Ramírez-Campillo, Rodrigo; Abad-Colil, Felipe; Vera, Maritza; Andrade, David C; Caniuqueo, Alexis; Martínez-Salazar, Cristian; Nakamura, Fábio Y; Arazi, Hamid; Cerda-Kohler, Hugo; Izquierdo, Mikel; Alonso-Martínez, Alicia M

    2016-01-01

    The aim of this study was to compare the acute effects of low-, moderate-, high-, and combined-intensity plyometric training on heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and rate-pressure product (RPP) cardiovascular responses in male and female normotensive subjects. Fifteen (8 women) physically active normotensive subjects participated in this study (age 23.5 ± 2.6 years, body mass index 23.8 ± 2.3 kg · m(-2)). Using a randomized crossover design, trials were conducted with rest intervals of at least 48 hours. Each trial comprised 120 jumps, using boxes of 20, 30, and 40 cm for low, moderate, and high intensity, respectively. For combined intensity, the 3 height boxes were combined. Measurements were taken before and after (i.e., every 10 minutes for a period of 90 minutes) each trial. When data responses of men and women were combined, a mean reduction in SBP, DBP, and RPP was observed after all plyometric intensities. No significant differences were observed pre- or postexercise (at any time point) for HR, SBP, DBP, or RPP when low-, moderate-, high-, or combined-intensity trials were compared. No significant differences were observed between male and female subjects, except for a higher SBP reduction in women (-12%) compared with men (-7%) after high-intensity trial. Although there were minor differences across postexercise time points, collectively, the data demonstrated that all plyometric training intensities can induce an acute postexercise hypotensive effect in young normotensive male and female subjects. PMID:26691407

  17. The acute impact of ingestion of sourdough and whole-grain breads on blood glucose, insulin, and incretins in overweight and obese men.

    PubMed

    Mofidi, Anita; Ferraro, Zachary M; Stewart, Katherine A; Tulk, Hilary M F; Robinson, Lindsay E; Duncan, Alison M; Graham, Terry E

    2012-01-01

    Consumption of whole-grain and sourdough breads is associated with improved glucose homeostasis. We examined the impact of commercial breads on biomarkers of glucose homeostasis in subjects at risk for glucose intolerance. In a randomized, crossover study, overweight or obese males ingested 11-grain, sprouted-grain, 12-grain, sourdough, or white bread on different occasions, matched for available carbohydrate (50 g) in part 1 (n = 12) and bread mass (107 g) in part 2 (n = 11), and blood glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were determined for 3 h. In part 1, glucose response for sprouted-grain was lower than 11-grain, sourdough, and white breads. Insulin area under the curve (AUC) for sourdough and white was lower than 11-grain and sprouted-grain breads. GLP-1 response to sourdough was lower than all breads. In part 2, glucose and insulin AUC for sourdough was greater than 11-grain, sprouted-grain, and 12-grain breads. Sprouted-grain bread improved glycemia by lowering glucose response and increasing GLP-1 response. In overweight and obese men, the glycemic response to sprouted grain bread was reduced in both parts 1 and 2 while the other whole-grain test breads did not improve metabolic responses in the acute postprandial state.

  18. A single acute dose of pinitol from a naturally-occurring food ingredient decreases hyperglycaemia and circulating insulin levels in healthy subjects.

    PubMed

    Hernández-Mijares, Antonio; Bañuls, Celia; Peris, Jose E; Monzó, Nuria; Jover, Ana; Bellod, Lorena; Victor, Victor M; Rocha, Milagros

    2013-11-15

    A limited amount of research suggests that oral ingestion of pinitol (3-O-methyl-d-chiro-inositol) positively influences glucose tolerance in humans. This study assessed the effects of different doses of pinitol supplementation on glucose tolerance, insulin sensitivity and plasma pinitol concentrations. Thirty healthy subjects underwent two one-day trials in which they consumed a nutritive beverage (Fruit Up®) containing 2.5, 4.0 or 6.0g of pinitol and a corresponding placebo equivalent in both energy and carbohydrates. Blood samples were collected frequently over the 240-min test period. The pinitol-enriched beverage reduced serum glucose and insulin at 45 and 60min, but only at a dose of 6.0g. Plasma pinitol concentrations, maximum concentration and AUC increased according to the dose administered. The results show that a single dose of pinitol from a naturally-occurring food ingredient at the highest dose administered acutely influences indices of whole-body glucose tolerance and insulin sensitivity in healthy subjects.

  19. Autocrine insulin-like growth factor-I signaling promotes growth and survival of human acute myeloid leukemia cells via the phosphoinositide 3-kinase/Akt pathway.

    PubMed

    Doepfner, K T; Spertini, O; Arcaro, A

    2007-09-01

    Insulin-like growth factor (IGF) signaling plays an important role in various human cancers. Therefore, the role of insulin-like growth factor I (IGF-I) signaling in growth and survival of acute myeloid leukemia (AML) cells was investigated. Expression of the IGF-I receptor (IGF-IR) and its ligand IGF-I were detected in a panel of human AML blasts and cell lines. IGF-I and insulin promoted the growth of human AML blasts in vitro and activated the phosphoinositide 3-kinase (PI3K)/Akt and the extracellular signal-regulated kinase (Erk) pathways. IGF-I-stimulated growth of AML blasts was blocked by an inhibitor of the PI3K/Akt pathway. Moreover, downregulation of the class Ia PI3K isoforms p110beta and p110delta by RNA interference impaired IGF-I-stimulated Akt activation, cell growth and survival in AML cells. Proliferation of a panel of AML cell lines and blasts isolated from patients with AML was inhibited by the IGF-IR kinase inhibitor NVP-AEW541 or by an IGF-IR neutralizing antibody. In addition to its antiproliferative effects, NVP-AEW541 sensitized primary AML blasts and cell lines to etoposide-induced apoptosis. Together, our data describe a novel role for autocrine IGF-I signaling in the growth and survival of primary AML cells. IGF-IR inhibitors in combination with chemotherapeutic agents may represent a novel approach to target human AML.

  20. Insulin and Insulin Resistance

    PubMed Central

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  1. Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial

    PubMed Central

    2011-01-01

    Background Prolonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate (CHO) drinks 2 hours before surgery. Our hypothesis is that the addition of whey protein to a CHO-based drink not only reduces the inflammatory response but also diminish insulin resistance. Methods Seventeen patients scheduled to cholecystectomy or inguinal herniorraphy were randomized and given 474 ml and 237 ml of water (CO group) or a drink containing CHO and milk whey protein (CHO-P group) respectively, 6 and 3 hours before operation. Blood samples were collected before surgery and 24 hours afterwards for biochemical assays. The endpoints of the study were the insulin resistance (IR), the prognostic inflammatory and nutritional index (PINI) and the C-reactive protein (CRP)/albumin ratio. A 5% level for significance was established. Results There were no anesthetic or postoperative complications. The post-operative IR was lower in the CHO-P group when compared with the CO group (2.75 ± 0.72 vs 5.74 ± 1.16; p = 0.03). There was no difference between the two groups in relation to the PINI. The CHO-P group showed a decrease in the both CRP elevation and CRP/albumin ratio (p < 0.05). The proportion of patients who showed CRP/albumin ratio considered normal was significantly greater (p < 0.05) in the CHO-P group (87.5%) than in the CO group (33.3%). Conclusions Shortening the pre-operative fasting using CHO and whey protein is safe and reduces insulin resistance and postoperative acute phase response in elective moderate operations. Trial registration ClinicalTrail.gov NCT01354249 PMID:21668975

  2. The time-frame of acute resistance exercise effects on football skill performance: the impact of exercise intensity.

    PubMed

    Draganidis, Dimitrios; Chatzinikolaou, Athanasios; Jamurtas, Athanasios Z; Carlos Barbero, Jose; Tsoukas, Dimitrios; Theodorou, Apostolos Spyridon; Margonis, Konstantinos; Michailidis, Yannis; Avloniti, Alexandra; Theodorou, Anastasios; Kambas, Antonis; Fatouros, Ioannis

    2013-01-01

    The purpose of this study was to determine the recovery rate of football skill performance following resistance exercise of moderate or high intensity. Ten elite football players participated in three different trials: control, low-intensity resistance exercise (4 sets, 8-10 repetitions/set, 65-70% 1 repetition maximum [1RM]) and high-intensity resistance exercise (4 sets, 4-6 repetitions/set, 85-90% 1RM) in a counterbalanced manner. In each experimental condition, participants were evaluated pre, post, and at 24, 48, 72 h post exercise time points. Football skill performance was assessed through the Loughborough Soccer Passing Test, long passing, dribbling, shooting and heading. Delayed onset muscle soreness, knee joint range of motion, and muscle strength (1RM) in squat were considered as muscle damage markers. Blood samples analysed for creatine kinase activity, C-reactive protein, and leukocyte count. Passing and shooting performance declined (P < 0.05) post-exercise following resistance exercise. Strength declined post-exercise following high-intensity resistance exercise. Both trials induced only a mild muscle damage and inflammatory response in an intensity-dependent manner. These results indicate that football skill performance is minimally affected by acute resistance exercise independent of intensity suggesting that elite players may be able to participate in a football practice or match after only 24 h following a strength training session. PMID:23301779

  3. The time-frame of acute resistance exercise effects on football skill performance: the impact of exercise intensity.

    PubMed

    Draganidis, Dimitrios; Chatzinikolaou, Athanasios; Jamurtas, Athanasios Z; Carlos Barbero, Jose; Tsoukas, Dimitrios; Theodorou, Apostolos Spyridon; Margonis, Konstantinos; Michailidis, Yannis; Avloniti, Alexandra; Theodorou, Anastasios; Kambas, Antonis; Fatouros, Ioannis

    2013-01-01

    The purpose of this study was to determine the recovery rate of football skill performance following resistance exercise of moderate or high intensity. Ten elite football players participated in three different trials: control, low-intensity resistance exercise (4 sets, 8-10 repetitions/set, 65-70% 1 repetition maximum [1RM]) and high-intensity resistance exercise (4 sets, 4-6 repetitions/set, 85-90% 1RM) in a counterbalanced manner. In each experimental condition, participants were evaluated pre, post, and at 24, 48, 72 h post exercise time points. Football skill performance was assessed through the Loughborough Soccer Passing Test, long passing, dribbling, shooting and heading. Delayed onset muscle soreness, knee joint range of motion, and muscle strength (1RM) in squat were considered as muscle damage markers. Blood samples analysed for creatine kinase activity, C-reactive protein, and leukocyte count. Passing and shooting performance declined (P < 0.05) post-exercise following resistance exercise. Strength declined post-exercise following high-intensity resistance exercise. Both trials induced only a mild muscle damage and inflammatory response in an intensity-dependent manner. These results indicate that football skill performance is minimally affected by acute resistance exercise independent of intensity suggesting that elite players may be able to participate in a football practice or match after only 24 h following a strength training session.

  4. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    PubMed

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. PMID:27346646

  5. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    PubMed

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance.

  6. Similar Anti-Inflammatory Acute Responses from Moderate-Intensity Continuous and High-Intensity Intermittent Exercise

    PubMed Central

    Cabral-Santos, Carolina; Gerosa-Neto, José; Inoue, Daniela Sayuri; Panissa, Valéria Leme Gonçalves; Gobbo, Luís Alberto; Zagatto, Alessandro Moura; Campos, Eduardo Zapaterra; Lira, Fábio Santos

    2015-01-01

    The purpose of this study was to compare the effect of high-intensity intermittent exercise (HIIE) versus volume matched steady state exercise (SSE) on inflammatory and metabolic responses. Eight physically active male subjects completed two experimental sessions, a 5-km run on a treadmill either continuously (70% vVO2max) or intermittently (1:1 min at vVO2max). Blood samples were collected at rest, immediately, 30 and 60 minutes after the exercise session. Blood was analyzed for glucose, non-ester fatty acid (NEFA), uric acid, lactate, cortisol, and cytokines (IL-6, IL-10 and TNF-α) levels. The lactate levels exhibited higher values immediately post-exercise than at rest (HIIE 1.34 ± 0.24 to 7.11 ± 2.85, and SSE 1.35 ± 0.14 to 4.06±1.60 mmol·L-1, p < 0.05), but HIIE promoted higher values than SSE (p < 0.05); the NEFA levels were higher immediately post-exercise than at rest only in the SSE condition (0.71 ± 0.04 to 0.82±0.09 mEq/L, respectively, p < 0.05), yet, SSE promoted higher values than HIIE immediately after exercise (HIIE 0.72±0.03 vs SSE 0.82±0.09 mEq·L-1, p < 0.05). Glucose and uric acid levels did not show changes under the different conditions (p > 0.05). Cortisol, IL-6, IL-10 and TNF-α levels showed time-dependent changes under the different conditions (p < 0.05), however, the area under the curve of TNF-α in the SSE were higher than HIIE (p < 0.05), and the area under the curve of IL-6 in the HIIE showed higher values than SSE (p < 0.05). In addition, both exercise conditions promote increased IL-10 levels and IL-10/TNF-α ratio (p < 0.05). In conclusion, our results demonstrated that both exercise protocols, when volume is matched, promote similar inflammatory responses, leading to an anti-inflammatory status; however, the metabolic responses are different. Key points Metabolic contribution of both exercise, HIIE and SSE, was different. Both protocols leading to an anti-inflammatory status. HIIE induce a higher energy expenditure take

  7. Changes in the hormone (ACTH, insulin,epinephrine) content of immune cells in children having acute lymphocytic leukemia (ALL).

    PubMed

    Pállinger, Eva; Kovács, Gábor; Horváth, Zsuzsanna; Müller, Judit; Csaba, György

    2013-12-01

    Immune cells synthesize, store and secrete hormones, the level of which changes in ALL. In previous experiments the level of histamine, serotonin and triiodothyronine (T3)was studied, while at present that of ACTH, insulin and epinephrine, using flow cytometric analysis for the determination of cell subsets and detection of hormone content. The measurements were done in children at the time of diagnosis. ACTH was significantly elevated in each T cell subsets (total T, Th, Tc, activated T), while B and NK cells were not touched. The alterations in the insulin content (decrease in Tc and activated T cells) were uncertain, and NK cells contained significantly less insulin. The disease did not influence the cells' epinephrine content. There is not clear explanation for the importance of changes in the cells' hormone content, however, it is discussed in the text.

  8. Experience with a Simplified Computer Based Intensive Care Monitoring System in the Management of Acutely Ill Surgical Patients

    PubMed Central

    Hadley, H. Roger; Rutherford, Harold G.; Smith, Louis L.; Briggs, Burton A.; Neilsen, Ivan R.; Rau, Richard

    1979-01-01

    The need exists for a simplified and ecomonical computer based monitoring system for critically ill surgical patients. Such a system would enjoy widespread use in surgical intensive care units in regional, as well as larger community hospitals. We have assembled such a system which provides digital readout of the usual physiologic parameters, and also provide computer storage of accumulated data for review and evaluation of patient care. The computer provides graphic and digital display and digital printout for subsequent inclusion in the patient records. Most frequent indications for this system include the development of acute respiratory insufficiency or acute circulatory failure due to invasive sepsis and/or severe arteriosclerotic cardiovascular disease. Information most beneficial in patient care included measurement of cardiac output;alveolar arterial oxygen gradient. ImagesFigure 1Figure 5Figure 9Figure 11

  9. The contribution of temperature, exposure intensity and visible light to the inhibitory effect of irradiation on acute chlamydial infection.

    PubMed

    Marti, Hanna; Blenn, Christian; Borel, Nicole

    2015-12-01

    Water-filtered infrared A (wIRA) is radiation with a spectrum ranging from 780 to 1400 nm. Chlamydiaceae are obligate intracellular bacteria associated with various diseases in both animals and humans. A recent in vitro study demonstrated that wIRA combined with visible light (wIRA/VIS) has potential as a non-chemical method for the treatment of chlamydial infections without adversely affecting the cell viability. The aim of this study was to investigate the influence of various factors on the effect of wIRA/VIS on acute chlamydial infection, namely the impact of temperature, exposure intensity and infectious dose (multiplicity of infection) as well as the efficacy of the visible light component.We demonstrate that non-thermal effects contribute to the inhibition of acute chlamydial infection. Visible light enhances the inhibitory effect of wIRA on extracellular bacteria (elementary bodies or EBs).Moreover, the inhibitory effect of wIRA/VIS following treatment of EBs prior to infection correlated with increased irradiation intensity. The infectivity of mature chlamydial inclusions was significantly reduced upon wIRA/VIS exposure at all irradiation intensities investigated, suggesting the contribution of host cell factors to the anti-chlamydial effect of wIRA/VIS in the late stage of the developmental cycle. The effect of irradiation was not influenced by the infectious dose.

  10. SAPS 3, APACHE IV or GRACE: which score to choose for acute coronary syndrome patients in intensive care units?

    PubMed

    Nassar Junior, Antonio Paulo; Mocelin, Amilcar Oshiro; Andrade, Fabio Moreira; Brauer, Leonardo; Giannini, Fabio Poianas; Nunes, Andre Luiz Baptiston; Dias, Carlos Augusto

    2013-01-01

    CONTEXT AND OBJECTIVE Acute coronary syndromes (ACS) are a common cause of intensive care unit (ICU) admission. Specific prognostic scores have been developed and validated for ACS patients and, among them, GRACE (Global Registry of Acute Coronary Events) has had the best performance. However, intensive care clinicians generally use prognostic scores developed from heterogeneous populations of critically ill patients, such as APACHE IV (Acute Physiologic and Chronic Health Evaluation IV) and SAPS 3 (Simplified Acute Physiology Score 3). The aim of this study was to evaluate and compare the performance of these three scores in a non-selected population of ACS cases. DESIGN AND SETTING Retrospective observational study to evaluate three prognostic scores in a population of ACS patients admitted to three general ICUs in private hospitals in São Paulo. METHODS All patients with ACS admitted from July 2008 to December 2009 were considered for inclusion in the study. Score calibration and discrimination were evaluated in relation to predicting hospital mortality. RESULTS A total of 1065 patients were included. The calibration was appropriate for APACHE IV and GRACE but not for SAPS 3. The discrimination was very good for all scores (area under curve of 0.862 for GRACE, 0.860 for APACHE IV and 0.804 for SAPS 3). CONCLUSIONS In this population of ACS patients admitted to ICUs, GRACE and APACHE IV were adequately calibrated, but SAPS 3 was not. All three scores had very good discrimination. GRACE and APACHE IV may be used for predicting mortality risk among ACS patients.

  11. The influence of acute intense exercise on exogenous spatial attention depends on physical fitness level.

    PubMed

    Llorens, Francesc; Sanabria, Daniel; Huertas, Florentino

    2015-01-01

    We investigated the effect of a previous bout of intense exercise on exogenous spatial attention. In Experiment 1, a group of participants performed an exogenous spatial task at rest (without prior effort), immediately after intense exercise, and after recovering from an intense exercise. The analyses revealed that the typical "facilitation effect" (i.e., faster reaction times on cued than on uncued trials) immediately after exercise was positively correlated with participants' fitness level. In Experiment 2, a high-fit and a low-fit group performed the same task at rest (without prior effort) and immediately after an intense exercise. Results revealed that, after the bout of exercise, only low-fit participants showed reduced attentional effects compared to the rest condition. We argue that the normal functioning of exogenous attention was influenced by intense effort, affecting low-fit participants to a larger extent than to high-fit participants. As a consequence, target processing was prioritized over irrelevant stimuli.

  12. Acute treatment with XMetA activates hepatic insulin receptors and lowers blood glucose in normal mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been proposed that monoclonal antibodies may become therapeutics for metabolic diseases such as diabetes mellitus. We have previously characterized an allosteric monoclonal antibody to the human insulin receptor (IR), XMetA, that activated metabolic signaling leading to enhanced glucose tran...

  13. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  14. Insulin, insulin analogues and diabetic retinopathy.

    PubMed

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  15. Acute Cocoa Supplementation Increases Postprandial HDL Cholesterol and Insulin in Obese Adults with Type 2 Diabetes after Consumption of a High-Fat Breakfast123

    PubMed Central

    Basu, Arpita; Betts, Nancy M; Leyva, Misti J; Fu, Dongxu; Aston, Christopher E; Lyons, Timothy J

    2015-01-01

    Background: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function. Objective: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food–style meal. Methods: Adults with T2D [n = 18; age (mean ± SE): 56 ± 3 y; BMI (in kg/m2): 35.3 ± 2.0; 14 women; 4 men] were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols; <0.1 mg flavanols) with a high-fat fast-food–style breakfast [766 kcal, 50 g fat (59% energy)] in a crossover trial. After an overnight fast (10–12 h), participants consumed the breakfast with cocoa or placebo, and blood sample collection [glucose, insulin, lipids, and high-sensitivity C-reactive protein (hsCRP)] and vascular measurements were conducted at 0.5, 1, 2, 4, and 6 h postprandially on each study day. Insulin resistance was evaluated by homeostasis model assessment. Results: Over the 6-h study, and specifically at 1 and 4 h, cocoa increased HDL cholesterol vs. placebo (overall Δ: 1.5 ± 0.8 mg/dL; P ≤ 0.01) but had no effect on total and LDL cholesterol, triglycerides, glucose, and hsCRP. Cocoa increased serum insulin concentrations overall (Δ: 5.2 ± 3.2 mU/L; P < 0.05) and specifically at 4 h but had no overall effects on insulin resistance (except at 4 h, P < 0.05), systolic or diastolic blood pressure, or small artery elasticity. However, large artery elasticity was overall lower after cocoa vs. placebo (Δ: −1.6 ± 0.7 mL/mm Hg; P < 0.05), with the difference significant only at 2 h. Conclusion: Acute cocoa supplementation showed no clear overall benefit in T2D patients after a high-fat fast-food–style meal challenge

  16. Are intensive lipid-lowering regimens an optimal economic strategy in patients with ACS? An acute and chronic perspective.

    PubMed

    Ara, Roberta; Rafia, Rachid; Ward, Sue E; Wierzbicki, Anthony S; Reynolds, Tim M; Rees, Angie; Pandor, Abdullah

    2009-10-01

    A literature review was conducted to identify studies exploring the cost-effectiveness of intensive lipid-lowering regimens compared with a generic low-dose statin for individuals with acute coronary syndrome. Three papers matched the inclusion criteria. All used a Markov model to represent the long-term clinical pathway; two were set in the UK and one was in the USA. While there were substantial differences in the effectiveness data, the definitions of the health states and the numbers of events predicted, all authors found that the intensive regimen was a cost-effective alternative compared with a generic lower dose statin. If the cost of atorvastatin reduces from GBP 368 pounds to 90 pounds per annum when the patent expires in 2011, atorvastatin 80 mg/day would be the most optimal treatment for this patient group. Simvastatin 80 mg/day should not be considered an alternative owing to an adverse safety profile and limited additional benefits.

  17. Influence of age, previous health status, and severity of acute illness on outcome from intensive care.

    PubMed

    Le Gall, J R; Brun-Buisson, C; Trunet, P; Latournerie, J; Chantereau, S; Rapin, M

    1982-09-01

    Age, previous health status (HS), and severity of acute illness were assessed prospectively on 228 unselected patients admitted over 1 yr to the multidisciplinary ICU, to determine their influence on outcome. One hundred and fifty patients (66%) were discharged from the ICU, but the survival rate fell to 50% at 6 months, and was similar after 1 yr (49%). Over a 6-month period, there was improved HS in survivors which gradually leveled off. Compared to prior HS, the final HS was worsened in 37% of survivors. Three factors were important predictors of late survival: age under 50, good previous HS, and less than two visceral failures. We conclude that evaluation of ICU outcome should provide information on 6-month survival and HS and include important variables as age, previous HS, and severity of acute illness. PMID:7105766

  18. Granulomatous Insulitis as a Cause of Acute-Onset Insulin-Dependent Diabetes Mellitus in a Patient With a Pancreatic Endocrine Carcinoma.

    PubMed

    Saab, Jad; Qin, Lihui; Jessurun, Jose

    2016-10-01

    Autoimmune destruction of β cells is the cause of most cases of type 1 diabetes mellitus. Lymphocytic insulitis has been documented in the early phases of this disease as well as in recurrent diabetes after pancreas transplantation and in certain viral infections. We report a unique case of granulomatous insulitis in a patient with an endocrine tumor of the pancreas that clinically manifested as acute-onset insulin-dependent diabetes mellitus. Granulomata were present in islets with complete disappearance of β cells, as well as in the primary tumor, metastases, and lymph nodes. We postulate that these granulomata represent a sarcoid-like reaction to the tumor with secondary injury to nonneoplastic endocrine cells through a mechanism of molecular mimicry.

  19. Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulin-like growth factor 1 responses to acute resistance exercise.

    PubMed

    Youl Kang, Ho; Hwan Kim, Seung; Jun Lee, Woen; Byrne, Heidi K

    2002-05-01

    Ginseng, an herbal plant, has been ingested by many athletes in Oriental regions of the world in order to improve stamina and to facilitate rapid recovery from injuries. However, adequate investigation has not been conducted to examine the ergogenic effects of ginseng. To examine the effects of ginseng supplements on hormonal status following acute resistance exercise, eight male college students were randomly given water (control; CON) or 20 g of ginseng root extract (GIN) treatment immediately after a standardized exercise bout. Venous blood samples were drawn before and immediately after exercise and at 4 time points during a 2-hour recovery period. Human growth hormone, testosterone, cortisol, and insulin-like growth factor 1 (IGF-1) levels were determined by radioimmunoassay. The responses of plasma hormones following ginseng consumption were not significant between CON and GIN treatments during the 2-hour recovery period. These results do not support the use of ginseng to promote an anabolic hormonal status following resistance exercise.

  20. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    PubMed Central

    Kim, Yeon Joo; Park, Jin-hong; Yun, In-Ha; Kim, Young Seok

    2016-01-01

    Purpose To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings. Methods Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy. Results Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses. Conclusion Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages. PMID:27022287

  1. The acute effects of four protein meals on insulin, glucose, appetite and energy intake in lean men.

    PubMed

    Pal, Sebely; Ellis, Vanessa

    2010-10-01

    Different dietary proteins vary in their ability to influence satiety and reduce food intake. The present study compared the effects of four protein meals, whey, tuna, turkey and egg albumin, on postprandial glucose and insulin concentrations as well as on appetite measures and energy intake in twenty-two lean, healthy men. This was a randomised, cross-over design study where participants consumed four liquid test meals on separate occasions followed by the collection of regular blood samples (fasting, +30, 60, 90, 120, 180 and 240 min). They were then offered a buffet meal 4 h later. The blood glucose response after the consumption of the test meal, as an incremental area under the curve (AUC), was significantly lower with the whey meal than with the turkey (P < 0.023) and egg (P < 0.001) meals, but it was not lower than with the tuna meal (P < 0.34). The AUC blood insulin after the consumption of the test meal was significantly higher with the whey meal than with the tuna, turkey and egg meals (all P < 0.001). The AUC rating of hunger was significantly lower with the whey meal than with the tuna (P < 0.033), turkey (P < 0.001) and egg (P < 0.001) meals. Mean energy intake at the ad libitum meal was significantly lower (P < 0.001) with the whey meal than with the tuna, egg and turkey meals. There was a strong relationship between self-rated appetite, postprandial insulin response and energy intake at lunch. Whey protein meal produced a greater insulin response, reduced appetite and decreased ad libitum energy intake at a subsequent meal compared with the other protein meals, indicating a potential for appetite suppression and weight loss in overweight or obese individuals.

  2. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  3. Acute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study.

    PubMed

    Tschakert, Gerhard; Kroepfl, Julia M; Mueller, Alexander; Harpf, Hanns; Harpf, Leonhard; Traninger, Heimo; Wallner-Liebmann, Sandra; Stojakovic, Tatjana; Scharnagl, Hubert; Meinitzer, Andreas; Pichlhoefer, Patriz; Hofmann, Peter

    2016-03-01

    Despite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn't show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. Key pointsHigh-intensity interval exercise (HIIE

  4. Acute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study

    PubMed Central

    Tschakert, Gerhard; Kroepfl, Julia M.; Mueller, Alexander; Harpf, Hanns; Harpf, Leonhard; Traninger, Heimo; Wallner-Liebmann, Sandra; Stojakovic, Tatjana; Scharnagl, Hubert; Meinitzer, Andreas; Pichlhoefer, Patriz; Hofmann, Peter

    2016-01-01

    Despite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn’t show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. Key points High-intensity interval exercise (HIIE

  5. Greater impact of acute high-intensity interval exercise on post-exercise executive function compared to moderate-intensity continuous exercise.

    PubMed

    Tsukamoto, Hayato; Suga, Tadashi; Takenaka, Saki; Tanaka, Daichi; Takeuchi, Tatsuya; Hamaoka, Takafumi; Isaka, Tadao; Hashimoto, Takeshi

    2016-03-01

    Aerobic moderate-intensity continuous exercise (MCE) can improve executive function (EF) acutely, potentially through the activation of both physiological and psychological factors. Recently, high-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than MCE. Factors for EF improvement can potentially be more enhanced by HIIE than by MCE; but the effects of HIIE on EF remain unknown. Therefore, we aimed to examine to what extent HIIE impacts post-exercise EF immediately after exercise and during post-exercise recovery, compared with traditional MCE. Twelve healthy male subjects performed cycle ergometer exercise based on either HIIE or MCE protocols in a randomized and counterbalanced order. The HIIE protocol consisted of four 4-min bouts at 90% of peak VO2 with 3-min active recovery at 60% of peak VO2. A volume-matched MCE protocol was applied at 60% of peak VO2. To evaluate EF, a color-words Stroop task was performed pre- and post-exercise. Improvement in EF immediately after exercise was the same for the HIIE and MCE protocols. However, the improvement of EF by HIIE was sustained during 30 min of post-exercise recovery, during which MCE returned to the pre-exercise level. The EF response in the post-exercise recovery was associated with changes in physiological and psychological responses. The present findings showed that HIIE and MCE were capable of improving EF. Moreover, HIIE could prolong improvement in EF during post-exercise recovery. For the first time, we suggest that HIIE may be more effective strategy than MCE for improving EF.

  6. Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

    PubMed

    Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

    2013-11-12

    Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain.

  7. Insulin therapy in children and adolescents with type 1 diabetes.

    PubMed

    Malik, Faisal S; Taplin, Craig E

    2014-04-01

    Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of exogenous insulin. The primary goal of treatment of T1DM in children and adolescents is to maintain near-normoglycemia through intensive insulin therapy, avoid acute complications, and prevent long-term microvascular and macrovascular complications, while facilitating as close to a normal life as possible. Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM. To achieve target glycemic control, the best therapeutic option for patients with T1DM is basal-bolus therapy either with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many formulations of insulin are available to help simulate endogenous insulin secretion as closely as possible in an effort to eliminate the symptoms and complications of hyperglycemia, while minimizing the risk of hypoglycemia secondary to therapy. When using MDI, basal insulin requirements are given as an injection of long- or intermediate-acting insulin analogs, while meal-related glucose excursions are controlled with bolus injections of rapid-acting insulin analogs. Alternatively, CSII can be used, which provides a 24-h preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses, eliminating the need for periodic injections. Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation. Current therapies still do not match the endogenous insulin profile of pancreatic β-cells, and all still pose risks of suboptimal control, hypoglycemia, and ketosis in children and adolescents. The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose and/or a continuous glucose monitoring system

  8. The insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 induces apoptosis in acute myeloid leukemia cells exhibiting autocrine insulin-like growth factor-I secretion.

    PubMed

    Tazzari, P L; Tabellini, G; Bortul, R; Papa, V; Evangelisti, C; Grafone, T; Martinelli, G; McCubrey, J A; Martelli, A M

    2007-05-01

    Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) have been implicated in the pathophysiology of many human cancers, including those of hematopoietic lineage. We investigated the therapeutic potential of the novel IGF-IR tyrosine kinase activity inhibitor, NVP-AEW541, on human acute myeloid leukemia (AML) cells. NVP-AEW541 was tested on a HL60 cell subclone, which is dependent on autocrine secretion of IGF-I for survival and drug resistance, as well as primary drug resistant leukemia cells. NVP-AEW541 treatment (24 h) induced dephosphorylation of IGF-IR. NVP-AEW541 also caused Akt dephosphorylation and changes in the expression of key regulatory proteins of the cell cycle. At longer incubation times (48 h), NVP-AEW541-induced apoptotic cell death, as demonstrated by caspase-3 cleavage. Apoptosis was accompanied by decreased expression of anti-apoptotic proteins. NVP-AEW541 enhanced sensitivity of HL60 cells to either cytarabine or etoposide. Moreover, NVP-AEW541 reduced the clonogenic capacity of AML CD34(+) cells cultured in the presence of IGF-I. Chemoresistant AML blasts displayed enhanced IGF-I secretion, and were sensitized to etoposide-induced apoptosis by NVP-AEW541. Our findings indicate that NVP-AEW541 might be a promising therapeutic agent for the treatment of those AML cases characterized by IGF-I autocrine secretion.

  9. Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

    SciTech Connect

    Fonteyne, Valerie Villeirs, Geert; Speleers, Bruno; Neve, Wilfried de; Wagter, Carlos de; Lumen, Nicolas; Meerleer, Gert de

    2008-11-01

    Purpose: To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. Methods and Materials: Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. Results: The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. Conclusion: The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

  10. Community-acquired pneumonia and survival of critically ill acute exacerbation of COPD patients in respiratory intensive care units

    PubMed Central

    Lu, Zhiwei; Cheng, Yusheng; Tu, Xiongwen; Chen, Liang; Chen, Hu; Yang, Jian; Wang, Jinyan; Zhang, Liqin

    2016-01-01

    Purpose The aim of this study was to appraise the effect of community-acquired pneumonia (CAP) on inhospital mortality in critically ill acute exacerbation of COPD (AECOPD) patients admitted to a respiratory intensive care unit. Patients and methods A retrospective observational study was performed. Consecutive critically ill AECOPD patients receiving treatment in a respiratory intensive care unit were reviewed from September 1, 2012, to August 31, 2015. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed by Mann–Whitney U-test. Kaplan–Meier analysis was used to assess the association of CAP with survival of critically ill AECOPD patients for univariate analysis. Cox’s proportional hazards regression model was performed to identify risk factors for multivariate analysis. Results A total of 80 consecutive eligible individuals were reviewed. These included 38 patients with CAP and 42 patients without CAP. Patients with CAP had a higher inhospital rate of mortality than patients without CAP (42% vs 33.3%, P<0.05). Kaplan–Meier survival analysis showed that patients with CAP had a worse survival rate than patients without CAP (P<0.05). Clinical characteristics, including Acute Physiology and Chronic Health Evaluation II (APACHE II) score, C-reactive protein, and CAP, were found to be closely associated with survival of AECOPD individuals. Further multivariate Cox regression analysis confirmed that CAP and APACHE II were independent risk factors for inhospital mortality in critically ill AECOPD patients (CAP: hazard ratio, 5.29; 95% CI, 1.50–18.47, P<0.01 and APACHE II: hazard ratio, 1.20; 95% CI, 1.06–1.37, P<0.01). Conclusion CAP may be an independent risk factor for higher inhospital mortality in critically ill AECOPD patients. PMID:27563239

  11. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers

    PubMed Central

    Sheets, Erin S.; Bujarski, Spencer; Leventhal, Adam M.; Ray, Lara A.

    2015-01-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers’ subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d = 0.55), along with more intense negative emotion (d = 0.97) and greater negative emotion variability (d = 0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not. PMID:25885662

  12. The Effects of Acute Intense Physical Exercise on Postural Stability in Children With Cerebral Palsy.

    PubMed

    Leineweber, Matthew J; Wyss, Dominik; Dufour, Sophie-Krystale; Gane, Claire; Zabjek, Karl; Bouyer, Laurent J; Maltais, Désirée B; Voisin, Julien I; Andrysek, Jan

    2016-07-01

    This study evaluated the effects of intense physical exercise on postural stability of children with cerebral palsy (CP). Center of pressure (CoP) was measured in 9 typically developing (TD) children and 8 with CP before and after a maximal aerobic shuttle-run test (SRT) using a single force plate. Anteroposterior and mediolateral sway velocities, sway area, and sway regularity were calculated from the CoP data and compared between pre- and postexercise levels and between groups. Children with CP demonstrated significantly higher pre-SRT CoP velocities than TD children in the sagittal (18.6 ± 7.6 vs. 6.75 1.78 m/s) and frontal planes (15.4 ± 5.3 vs. 8.04 ± 1.51 m/s). Post-SRT, CoP velocities significantly increased for children with CP in the sagittal plane (27.0 ± 1.2 m/s), with near-significant increases in the frontal plane (25.0 ± 1.5m/s). Similarly, children with CP evidenced larger sway areas than the TD children both pre- and postexercise. The diminished postural stability in children with CP after short but intense physical exercise may have important implications including increased risk of falls and injury. PMID:27623610

  13. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers.

    PubMed

    Sheets, Erin S; Bujarski, Spencer; Leventhal, Adam M; Ray, Lara A

    2015-08-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers' subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d=0.55), along with more intense negative emotion (d=0.97) and greater negative emotion variability (d=0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not. PMID:25885662

  14. Emotion differentiation and intensity during acute tobacco abstinence: A comparison of heavy and light smokers.

    PubMed

    Sheets, Erin S; Bujarski, Spencer; Leventhal, Adam M; Ray, Lara A

    2015-08-01

    The ability to recognize and label discrete emotions, termed emotion differentiation, is particularly pertinent to overall emotion regulation abilities. Patterns of deficient emotion differentiation have been associated with mood and anxiety disorders but have yet to be examined in relation to nicotine dependence. This study employed ecological momentary assessment to examine smokers' subjective experience of discrete emotions during 24-h of forced tobacco abstinence. Thirty daily smokers rated their emotions up to 23 times over the 24-hour period, and smoking abstinence was biologically verified. From these data, we computed individual difference measures of emotion differentiation, overall emotion intensity, and emotional variability. As hypothesized, heavy smokers reported poorer negative emotion differentiation than light smokers (d=0.55), along with more intense negative emotion (d=0.97) and greater negative emotion variability (d=0.97). No differences were observed in positive emotion differentiation. Across the sample, poorer negative emotion differentiation was associated with greater endorsement of psychological motives to smoke, including negative and positive reinforcement motives, while positive emotion differentiation was not.

  15. Effects of intensive gait-oriented physiotherapy during early acute phase of stroke.

    PubMed

    Peurala, Sinikka H; Airaksinen, Olavi; Jäkälä, Pekka; Tarkka, Ina M; Sivenius, Juhani

    2007-01-01

    We assessed the effects and strenuousness of intensive gait-oriented inpatient rehabilitation initiated very early after stroke. Therapy content and interrater reliability of the assessments were also analyzed. Of 22 patients, 19 (average 8.0 d poststroke) completed the study. Before rehabilitation, 13 patients were unable to walk or needed two assistants to walk and 6 patients needed one assistant. Patients spent a daily maximum of 1 h therapy time to obtain 20 min of walking. Additional physiotherapy was also provided during the 3 wk therapy period. Seven structured motor tests were recorded before and after rehabilitation and at 6 months postrehabilitation, and perceived exertion was followed during physiotherapy. After rehabilitation, 16 patients could walk unassisted and 3 needed one assistant to walk. Mean +/- standard deviation exercise walking distance was 10,784 +/- 4,446 m and exercise was ranked as slightly strenuous. After 3 wk, the patients' 10 m walking time, ankle spasticity, lower-limb muscle force, and motor scale scores improved (p < 0.05). The early intensive rehabilitation was well tolerated and only three patients dropped out. Improved motor abilities were seen in all stroke patients.

  16. Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

    PubMed

    Ichai, Carole; Vinsonneau, Christophe; Souweine, Bertrand; Armando, Fabien; Canet, Emmanuel; Clec'h, Christophe; Constantin, Jean-Michel; Darmon, Michaël; Duranteau, Jacques; Gaillot, Théophille; Garnier, Arnaud; Jacob, Laurent; Joannes-Boyau, Olivier; Juillard, Laurent; Journois, Didier; Lautrette, Alexandre; Muller, Laurent; Legrand, Matthieu; Lerolle, Nicolas; Rimmelé, Thomas; Rondeau, Eric; Tamion, Fabienne; Walrave, Yannick; Velly, Lionel

    2016-12-01

    Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall. PMID:27230984

  17. Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

    PubMed

    Ichai, Carole; Vinsonneau, Christophe; Souweine, Bertrand; Armando, Fabien; Canet, Emmanuel; Clec'h, Christophe; Constantin, Jean-Michel; Darmon, Michaël; Duranteau, Jacques; Gaillot, Théophille; Garnier, Arnaud; Jacob, Laurent; Joannes-Boyau, Olivier; Juillard, Laurent; Journois, Didier; Lautrette, Alexandre; Muller, Laurent; Legrand, Matthieu; Lerolle, Nicolas; Rimmelé, Thomas; Rondeau, Eric; Tamion, Fabienne; Walrave, Yannick; Velly, Lionel

    2016-12-01

    Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall.

  18. Pathophysiology of insulin secretion.

    PubMed

    Scheen, A J

    2004-02-01

    Defects in pancreatic islet beta-cell function play a major role in the development of diabetes mellitus. Type 1 diabetes is caused by a more or less rapid destruction of pancreatic beta cells, and the autoimmune process begins years before the beta-cell destruction becomes complete, thereby providing a window of opportunity for intervention. During the preclinical period and early after diagnosis, much of the insulin deficiency may be the result of functional inhibition of insulin secretion that may be at least partially and transiently reversible. Type 2 diabetes is characterized by a progressive loss of beta-cell function throughout the course of the disease. The pattern of loss is an initial (probably of genetic origin) defect in acute or first-phase insulin secretion, followed by a decreasing maximal capacity of insulin secretion. Last, a defective steady-state and basal insulin secretion develops, leading to almost complete beta-cell failure requiring insulin treatment. Because of the reciprocal relation between insulin secretion and insulin sensitivity, valid representation of beta-cell function requires interpretation of insulin responses in the context of the prevailing degree of insulin sensitivity. This appropriate approach highlights defects in insulin secretion at the various stages of the natural history of type 2 diabetes and already present in individuals at risk to develop the disease. To date none of the available therapies can stop the progressive beta-cell defect and the progression of the metabolic disorder. The better understanding of the pathophysiology of the disease should lead to the development of new strategies to preserve beta-cell function in both type 1 and type 2 diabetes mellitus.

  19. Intensive Glycemic Control in Cardiac Surgery.

    PubMed

    Tsai, Lillian L; Jensen, Hanna A; Thourani, Vinod H

    2016-04-01

    Hyperglycemia has been found to be associated with increased morbidity and mortality in surgical patients, yet, the optimal glucose management strategy during the perioperative setting remains undetermined. While much has been published about hyperglycemia and cardiac surgery, most studies have used widely varying definitions of hyperglycemia, methods of insulin administration, and the timing of therapy. This has only allowed investigators to make general conclusions in this challenging clinical scenario. This review will introduce the basic pathophysiology of hyperglycemia in the cardiac surgery setting, describe the main clinical consequences of operative hyperglycemia, and take the reader through the published material of intensive and conservative glucose management. Overall, it seems that intensive control has modest benefits with adverse effects often outweighing these advantages. However, some studies have indicated differing results for certain patient subgroups, such as non-diabetics with acute operative hyperglycemia. Future studies should focus on distinguishing which patient populations, if any, would optimally benefit from intensive insulin therapy. PMID:26879308

  20. Central hemodynamic responses during acute high-intensity interval exercise and moderate continuous exercise in patients with heart failure.

    PubMed

    Gayda, Mathieu; Normandin, Eve; Meyer, Philippe; Juneau, Martin; Haykowsky, Mark; Nigam, Anil

    2012-12-01

    The aim of this study was to compare the acute hemodynamic responses during high-intensity intermittent exercise (HIIE) session compared with moderate-intensity continuous exercise (MICE) session in patients with heart failure and reduced ejection fraction (HFREF). Thirteen patients with HFREF (age, 59 ± 6 years; left ventricular ejection fraction, 27% ± 6%; New York Heart Association class I to III) were randomly assigned to a single session of HIIE (2 × 8 min) corresponding to 30 s at 100% of peak power output (PPO) and 30 s passive recovery intervals or to a MICE (22 min) at 60% of PPO. Gas exchange and central hemodynamic parameters (cardiac bioimpedance) were measured continuously during exercise. Oxygen uptake, stroke volume (SV), cardiac output (CO), and arterio-venous difference (C(a-v)O(2)) were compared. Mean oxygen uptake and ventilation were lower during HIIE vs. MICE. CO, SV, and C(a-v)O(2)) were not different between MICE and HIIE. Optimized HIIE was well tolerated (similar perceived exertion) and no significant ventricular arrhythmias and (or) abnormal blood pressure responses occurred during HIEE session. Compared with MICE, optimized HIIE elicited similar central hemodynamic and C(a-v)O(2) responses in HFREF patients with lower oxygen uptake and ventilation. HIIE may be an efficient exercise training modality in patients with HFREF.

  1. Dissociation of Increases in PGC-1α and Its Regulators from Exercise Intensity and Muscle Activation Following Acute Exercise

    PubMed Central

    Hankinson, Paul B.; Simpson, Craig A.; Little, Jonathan P.; Graham, Ryan B.; Gurd, Brendon J.

    2013-01-01

    Muscle activation as well as changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) following high-intensity interval exercise (HIIE) were examined in young healthy men (n  = 8; age, 21.9±2.2 yrs; VO2peak, 53.1±6.4 ml/min/kg; peak work rate, 317±23.5 watts). On each of 3 visits HIIE was performed on a cycle ergometer at a target intensity of 73, 100, or 133% of peak work rate. Muscle biopsies were taken at rest and three hours after each exercise condition. Total work was not different between conditions (∼730 kJ) while average power output (73%, 237±21; 100%, 323±26; 133%, 384±35 watts) and EMG derived muscle activation (73%, 1262±605; 100%, 2089±737; 133%, 3029±1206 total integrated EMG per interval) increased in an intensity dependent fashion. PGC-1α mRNA was elevated after all three conditions (p<0.05), with a greater increase observed following the 100% condition (∼9 fold, p<0.05) compared to both the 73 and 133% conditions (∼4 fold). When expressed relative to muscle activation, the increase in PGC-1α mRNA for the 133% condition was less than that for the 73 and 100% conditions (p<0.05). SIRT1 mRNA was also elevated after all three conditions (∼1.4 fold, p<0.05), with no difference between conditions. These findings suggest that intensity-dependent increases in PGC-1α mRNA following submaximal exercise are largely due to increases in muscle recruitment. As well, the blunted response of PGC-1α mRNA expression following supramaximal exercise may indicate that signalling mediated activation of PGC-1α may also be blunted. We also indentify that increases in PDK4, SIRT1, and RIP140 mRNA following acute exercise are dissociated from exercise intensity and muscle activation, while increases in EGR1 are augmented with supramaximal HIIE (p<0.05). PMID:23951207

  2. Breast Intensity-Modulated Radiation Therapy Reduces Time Spent With Acute Dermatitis for Women of All Breast Sizes During Radiation

    SciTech Connect

    Freedman, Gary M. Li Tianyu; Nicolaou, Nicos; Chen Yan; Ma, Charlie C.-M.; Anderson, Penny R.

    2009-07-01

    Purpose: To study the time spent with radiation-induced dermatitis during a course of radiation therapy for breast cancer in women treated with conventional or intensity-modulated radiation therapy (IMRT). Methods and Materials: The study population consisted of 804 consecutive women with early-stage breast cancer treated with breast-conserving surgery and radiation from 2001 to 2006. All patients were treated with whole-breast radiation followed by a boost to the tumor bed. Whole-breast radiation consisted of conventional wedged photon tangents (n = 405) earlier in the study period and mostly of photon IMRT (n = 399) in later years. All patients had acute dermatitis graded each week of treatment. Results: The breakdown of the cases of maximum acute dermatitis by grade was as follows: 3%, Grade 0; 34%, Grade 1; 61%, Grade 2; and 2%, Grade 3. The breakdown of cases of maximum toxicity by technique was as follows: 48%, Grade 0/1, and 52%, Grade 2/3, for IMRT; and 25%, Grade 0/1, and 75%, Grade 2/3, for conventional radiation therapy (p < 0.0001). The IMRT patients spent 82% of weeks during treatment with Grade 0/1 dermatitis and 18% with Grade 2/3 dermatitis, compared with 29% and 71% of patients, respectively, treated with conventional radiation (p < 0.0001). Furthermore, the time spent with Grade 2/3 toxicity was decreased in IMRT patients with small (p = 0.0015), medium (p < 0.0001), and large (p < 0.0001) breasts. Conclusions: Breast IMRT is associated with a significant decrease both in the time spent during treatment with Grade 2/3 dermatitis and in the maximum severity of dermatitis compared with that associated with conventional radiation, regardless of breast size.

  3. Acute Poisonings Admitted to a Tertiary Level Intensive Care Unit in Northern India: Patient Profile and Outcomes

    PubMed Central

    Mathai, Ashu Sara; Pannu, Aman; Arora, Rohit

    2015-01-01

    Background Poisoning is becoming a real health care burden for developing countries like India. An improved knowledge of the patterns of poisonings, as well as the clinical course and outcomes of these cases can help to formulate better preventive and management strategies. Aim To study the demographic and clinical profiles of patients admitted to the ICU with acute poisoning and to study the factors that predict their mortality. Materials and Methods Retrospective two years (September 1, 2010 to August 31, 2012) study of all consecutive patients admitted to the Intensive Care Unit (ICU) with acute poisoning at a tertiary care hospital in Northern India. Results Out of the 67 patients admitted to the ICU during the study period, the majority were young (median age 29 years) males (69%) who had consumed poison intentionally. Pesticides were the most commonly employed poison, notably organophosphorus compounds (22 patients, 32.8%) and aluminium phosphide (14 patients, 20.9%). While the overall mortality from all poisonings was low (18%), aluminium phosphide was highly toxic, with a mortality rate of 35%. The factors at ICU admission that were found to be associated with a significant risk of death were, high APACHE II and SOFA scores (p =0.0001 and p=0.006, respectively), as well as the need for mechanical ventilation and drugs for vasoactive support (p=0.012 and p= 0.0001, respectively). Conclusion Use of pesticides for intentional poisoning continues to be rampant in Northern India, with many patients presenting in a critical condition to tertiary level hospitals. Pesticide regulations laws, educational awareness, counseling and poison information centers will help to curtail this public health problem. PMID:26557594

  4. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure.

    PubMed

    Kornhauser, Carlos; Dubey, Luis-Antonio; Garay, M-Eugenia; Pérez-Luque, Elva-Leticia; Malacara, Juan-Manuel; Vargas-Origel, Arturo

    2002-05-01

    Acute renal failure (ARF) in neonates may occur after renal ischemia. Growth factors participate in the tubular regeneration process. Insulin-like growth factor-1 (IGF-1) is produced in the kidney during the recovery phase of ARF. Tumor necrosis factor-alpha (TNFalpha) may play a role in renal apoptosis. We examined serum and urinary IGF-1 and TNFalpha in neonates with or without ARF after asphyxia, in order to assess their possible use as markers of renal damage and recovery. We studied 20 full-term asphyxiated neonates, 10 with ARF and 10 without ARF, and compared them with 13 normal newborns for 7 days after birth. Blood urea, creatinine, pH, base deficit, and serum and urine IGF-1 and TNFalpha were assessed. Neonates with ARF had more-severe acidosis than patients without ARF. All patients had lower serum IGF-1 values immediately after birth than control children. Serum IGF-1 remained low in the ARF patients. The initial urinary IGF-1 was higher in all patients compared with control newborns, and remained elevated for the rest of the study only in the ARF neonates. Serum and urinary TNFalpha concentrations were similar for all healthy and diseased neonates. Measurement of serum and urinary IGF-1 levels in ARF neonates might be of additional value for clinical assessment of ARF.

  5. Fibre-Specific Responses to Endurance and Low Volume High Intensity Interval Training: Striking Similarities in Acute and Chronic Adaptation

    PubMed Central

    Scribbans, Trisha D.; Edgett, Brittany A.; Vorobej, Kira; Mitchell, Andrew S.; Joanisse, Sophie D.; Matusiak, Jennifer B. L.; Parise, Gianni; Quadrilatero, Joe; Gurd, Brendon J.

    2014-01-01

    The current study involved the completion of two distinct experiments. Experiment 1 compared fibre specific and whole muscle responses to acute bouts of either low-volume high-intensity interval training (LV-HIT) or moderate-intensity continuous endurance exercise (END) in a randomized crossover design. Experiment 2 examined the impact of a six-week training intervention (END or LV-HIT; 4 days/week), on whole body and skeletal muscle fibre specific markers of aerobic and anaerobic capacity. Six recreationally active men (Age: 20.7±3.8 yrs; VO2peak: 51.9±5.1 mL/kg/min) reported to the lab on two separate occasions for experiment 1. Following a muscle biopsy taken in a fasted state, participants completed an acute bout of each exercise protocol (LV-HIT: 8, 20-second intervals at ∼170% of VO2peak separated by 10 seconds of rest; END: 30 minutes at ∼65% of VO2peak), immediately followed by a muscle biopsy. Glycogen content of type I and IIA fibres was significantly (p<0.05) reduced, while p-ACC was significantly increased (p<0.05) following both protocols. Nineteen recreationally active males (n = 16) and females (n = 3) were VO2peak-matched and assigned to either the LV-HIT (n = 10; 21±2 yrs) or END (n = 9; 20.7±3.8 yrs) group for experiment 2. After 6 weeks, both training protocols induced comparable increases in aerobic capacity (END: Pre: 48.3±6.0, Mid: 51.8±6.0, Post: 55.0±6.3 mL/kg/min LV-HIT: Pre: 47.9±8.1, Mid: 50.4±7.4, Post: 54.7±7.6 mL/kg/min), fibre-type specific oxidative and glycolytic capacity, glycogen and IMTG stores, and whole-muscle capillary density. Interestingly, only LV-HIT induced greater improvements in anaerobic performance and estimated whole-muscle glycolytic capacity. These results suggest that 30 minutes of END exercise at ∼65% VO2peak or 4 minutes of LV-HIT at ∼170% VO2peak induce comparable changes in the intra-myocellular environment (glycogen content and signaling activation); correspondingly, training

  6. Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function

    PubMed Central

    2014-01-01

    Background Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). Methods In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices. Results IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026). Conclusion IR assessed by the HOMA index during the

  7. Effects of carbohydrate ingestion on acute leukocyte, cortisol, and interleukin-6 response in high-intensity long-distance running.

    PubMed

    Ihalainen, Johanna K; Vuorimaa, Timo; Puurtinen, Risto; Hämäläinen, Ismo; Mero, Antti A

    2014-10-01

    The purpose of this study was to investigate the effect of ingestion of fluids with different carbohydrate concentrations (0, 1.5, and 7%) on the acute immune stress responses after high-intensity long-distance running. Continuous 18- to 20-km run was performed at 75% of maximal oxygen uptake with carbohydrate supplementation (CHO7%, 7% carbohydrate solution) and low-carbohydrate supplementation (lowCHO1.5%, 1.5% carbohydrate solution) in a randomized, double-blind, placebo (PLA) controlled design. Seven recreational runners (4 men and 3 women) completed all 3 trials. Blood was collected at baseline (PRE) and immediately after the run (POST). The running task induced significant (p ≤ 0.05) increases in leukocyte (white blood cells), neutrophil, and interleukin-6 (IL-6) counts in every trial. There was a significant (p ≤ 0.05) increase in cortisol with PLA and lowCHO1.5% but not with CHO7%. Increase in total leukocyte and neutrophil concentration was significantly lower with CHO7% compared with PLA (p ≤ 0.05). Postexercise IL-6 levels were significantly elevated when compared with baseline in all conditions (p ≤ 0.05). Interleukin-6 (IL-6) concentrations did not differ significantly between trials. LowCHO1.5% sport drink did not significantly differ from PLA in measured variables, which indicated that the amount and rate of carbohydrate ingestion (15 g, 10 g·h) in low-carbohydrate sport drink was not enough to significantly protect from the stress induced by high-intensity long-distance running, whereas the ingestion of CHO7% (45 g·h) blunted the significant cortisol response and significantly decreased the leukocyte response.

  8. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia.

    PubMed

    Chalandon, Yves; Thomas, Xavier; Hayette, Sandrine; Cayuela, Jean-Michel; Abbal, Claire; Huguet, Françoise; Raffoux, Emmanuel; Leguay, Thibaut; Rousselot, Philippe; Lepretre, Stéphane; Escoffre-Barbe, Martine; Maury, Sébastien; Berthon, Céline; Tavernier, Emmanuelle; Lambert, Jean-François; Lafage-Pochitaloff, Marina; Lhéritier, Véronique; Chevret, Sylvie; Ifrah, Norbert; Dombret, Hervé

    2015-06-11

    In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678. PMID:25878120

  9. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia.

    PubMed

    Chalandon, Yves; Thomas, Xavier; Hayette, Sandrine; Cayuela, Jean-Michel; Abbal, Claire; Huguet, Françoise; Raffoux, Emmanuel; Leguay, Thibaut; Rousselot, Philippe; Lepretre, Stéphane; Escoffre-Barbe, Martine; Maury, Sébastien; Berthon, Céline; Tavernier, Emmanuelle; Lambert, Jean-François; Lafage-Pochitaloff, Marina; Lhéritier, Véronique; Chevret, Sylvie; Ifrah, Norbert; Dombret, Hervé

    2015-06-11

    In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678.

  10. Does adherence to treatment mediate the relationship between patients' treatment outcome expectancies and the outcomes of pain intensity and recovery from acute low back pain?

    PubMed

    Haanstra, Tsjitske M; Kamper, Steven J; Williams, Christopher M; Spriensma, Alette S; Lin, Chung-Wei Christine; Maher, Christopher G; de Vet, Henrica C W; Ostelo, Raymond W J G

    2015-08-01

    It is believed that patients' expectancies about the effectiveness of treatment influence their treatment outcomes, but the working mechanism is rarely studied in patients with low back pain. Theoretical models suggest that adherence to treatment may be an important pathway. The aim of this study was to assess the mediating role of adherence to treatment in the relationship between expectancies and the outcomes of recovery and pain intensity in patients with acute low back pain. This study used data from a randomized placebo-controlled trial of paracetamol for acute low back pain. Expectancies were measured with the Credibility Expectancy Questionnaire. Adherence was measured with a medication diary. Pain intensity was recorded daily in a diary on a 0 to 10 pain scale, and recovery was defined as the first of 7 consecutive days scoring 0 or 1 on a 6-point pain scale. Cox regression (dependent variable: recovery) and linear mixed-model analyses (dependent variable: daily pain intensity scores) were performed. The "difference in coefficients" approach was used to establish mediation. A total of 1573 participants were included in current analyses. There was a small but highly significant relationship between expectancies and outcomes; 3.3% of the relationship between expectancies and recovery and 14.2% of the relationship between expectancies and pain intensity were mediated by adherence to treatment. This study does not convincingly support the theory that adherence is a key pathway in the relationship between treatment outcome expectancies and recovery and pain intensity in this acute low back pain population.

  11. Comparison of acute physiology and chronic health evaluation II and acute physiology and chronic health evaluation IV to predict intensive care unit mortality

    PubMed Central

    Parajuli, Bashu Dev; Shrestha, Gentle S.; Pradhan, Bishwas; Amatya, Roshana

    2015-01-01

    Context: Clinical assessment of severity of illness is an essential component of medical practice to predict the outcome of critically ill-patient. Acute Physiology and Chronic Health Evaluation (APACHE) model is one of the widely used scoring systems. Aims: This study was designed to evaluate the Performance of APACHE II and IV scoring systems in our Intensive Care Unit (ICU). Settings and Design: A prospective study in 6 bedded ICU, including 76 patients all above 15 years. Subjects and Methods: APACHE II and APACHE IV scores were calculated based on the worst values in the first 24 h of admission. All enrolled patients were followed, and outcome was recorded as survivors or nonsurvivors. Statistical Analysis Used: SPSS version 17. Results: The mean APACHE score was significantly higher among nonsurvivors than survivors (P < 0.005). Discrimination for APACHE II and APACHE IV was fair with area under receiver operating characteristic curve of 0.73 and 0.79 respectively. The cut-off point with best Youden index for APACHE II was 17 and for APACHE IV was 85. Above cut-off point, mortality was higher for both models (P < 0.005). Hosmer–Lemeshow Chi-square coefficient test showed better calibration for APACHE II than APACHE IV. A positive correlation was seen between the models with Spearman's correlation coefficient of 0.748 (P < 0.01). Conclusions: Discrimination was better for APACHE IV than APACHE II model however Calibration was better for APACHE II than APACHE IV model in our study. There was good correlation between the two models observed in our study. PMID:25722550

  12. Insulin Signaling And Insulin Resistance

    PubMed Central

    Beale, Elmus G.

    2013-01-01

    Insulin resistance or its sequelae may be the common etiology of maladies associated with metabolic syndrome (e.g., hypertension, type 2 diabetes, atherosclerosis, heart attack, stroke and kidney failure). It is thus important to understand those factors that affect insulin sensitivity. This review stems from the surprising discovery that interference with angiotensin signaling improves insulin sensitivity and it provides a general overview of insulin action and factors that control insulin sensitivity. PMID:23111650

  13. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

    PubMed Central

    Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  14. Reduced intensity conditioning followed by peripheral blood stem cell transplantation for adult patients with high-risk acute lymphoblastic leukemia

    PubMed Central

    Stein, Anthony S.; Palmer, Joycelynne M.; O'Donnell, Margaret R.; Kogut, Neil M.; Spielberger, Ricardo T.; Slovak, Marilyn L.; Tsai, Ni-Chun; Senitzer, David; Snyder, David S.; Thomas, Sandra H.; J.Forman, Stephen

    2009-01-01

    Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT), however it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine/melphalan prior to allogeneic peripheral blood stem cell transplant between 6/14/02 and 6/15/07 at City of Hope. Indications for the RIC regimen were: 1) age 50 or older (42%), 2) compromised organ function (54%), or 3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival and disease-free survival at two years was 61.5%. Relapse incidence was 21.1% and non-relapse mortality was 21.5% at two years. cGVHD developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant. PMID:19822300

  15. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice.

    PubMed

    Borghi, Sergio M; Pinho-Ribeiro, Felipe A; Fattori, Victor; Bussmann, Allan J C; Vignoli, Josiane A; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  16. Effect of low-intensity focused ultrasound on the middle ear in a mouse model of acute otitis media.

    PubMed

    Noda, Kanako; Hirano, Takashi; Noda, Kenji; Kodama, Satoru; Ichimiya, Issei; Suzuki, Masashi

    2013-03-01

    We hypothesized that low-intensity focused ultrasound (LIFU) increases vessel permeability and antibacterial drug activity in the mouse middle ear. We determined appropriate settings by applying LIFU to mouse ears with the external auditory canal filled with normal saline and performed histologic and immunohistologic examination. Acute otitis media was induced in mice with nontypable Haemophilus influenzae, and they were given ampicillin (50, 10, or 2 mg/kg) intraperitoneally once daily for 3 days with or without LIFU (1.0 W/cm(2), 20% duty cycle, 30 s). In the LIFU(+) groups receiving the 2- and 10-mg/kg doses, viable bacteria counts, number of inflammatory cells and IL-1β and TNF-α levels in middle ear effusion were significantly lower than in the LIFU(-) groups on the same doses. Severity of AOM also tended to be reduced more in the LIFU(+) groups than in the LIFU(-) groups. LIFU application with antibiotics may be effective for middle ear infection. PMID:23312959

  17. Effect of post remission therapy prior to reduced intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission

    PubMed Central

    Warlick, Erica D.; Paulson, Kristjan; Brazauskas, Ruta; Zhong, Xiaobo; Miller, Alan M.; Camitta, Bruce M.; George, Biju; Savani, Bipin N.; Ustun, Celalettin; Marks, David I.; Waller, Edmund K.; Baron, Frédéric; Freytes, César O.; Socie, Gérard; Akpek, Gorgun; Schouten, Harry C.; Lazarus, Hillard M.; Horwitz, Edwin M.; Koreth, John; Cahn, Jean-Yves; Bornhauser, Martin; Seftel, Matthew; Cairo, Mitchell S.; Laughlin, Mary J.; Sabloff, Mitchell; Ringdén, Olle; Gale, Robert Peter; Kamble, Rammurti T.; Vij, Ravi; Gergis, Usama; Mathews, Vikram; Saber, Wael; Chen, Yi-Bin; Liesveld, Jane L.; Cutler, Corey S.; Ghobadi, Armin; Uy, Geoffrey L.; Eapen, Mary; Weisdorf, Daniel J.; Litzow, Mark R.

    2013-01-01

    The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia (AML) in first complete remission (CR1) reported to the CIBMTR who received a RIC or NMA HCT from an HLA-identical sibling, HLA-matched unrelated donor (URD), or umbilical cord blood (UCB) donor in 2000–2010. We compared transplant outcomes based on exposure to cytarabine post remission consolidation. Three year survival rates were 36% (29–43%, 95% CI) in the no consolidation arm and 42% (37–47%, 95% CI) in the cytarabine consolidation arm (p=0.16). Disease free survival was 34% (27–41%, 95% CI) and 41% (35–46%, 95% CI) (p=0.15), respectively. Three year cumulative incidences of relapse were 37% (30–44%, 95% CI) and 38% (33–43%, 95% CI), respectively (p=0.80). Multivariate regression confirmed no effect of consolidation on relapse, DFS and survival. Prior to RIC/NMA HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant TRM and is reasonable if required. PMID:24184335

  18. Effect of low-intensity focused ultrasound on the middle ear in a mouse model of acute otitis media.

    PubMed

    Noda, Kanako; Hirano, Takashi; Noda, Kenji; Kodama, Satoru; Ichimiya, Issei; Suzuki, Masashi

    2013-03-01

    We hypothesized that low-intensity focused ultrasound (LIFU) increases vessel permeability and antibacterial drug activity in the mouse middle ear. We determined appropriate settings by applying LIFU to mouse ears with the external auditory canal filled with normal saline and performed histologic and immunohistologic examination. Acute otitis media was induced in mice with nontypable Haemophilus influenzae, and they were given ampicillin (50, 10, or 2 mg/kg) intraperitoneally once daily for 3 days with or without LIFU (1.0 W/cm(2), 20% duty cycle, 30 s). In the LIFU(+) groups receiving the 2- and 10-mg/kg doses, viable bacteria counts, number of inflammatory cells and IL-1β and TNF-α levels in middle ear effusion were significantly lower than in the LIFU(-) groups on the same doses. Severity of AOM also tended to be reduced more in the LIFU(+) groups than in the LIFU(-) groups. LIFU application with antibiotics may be effective for middle ear infection.

  19. A comparison of Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II and Acute Physiology and Chronic Health Evaluation III scoring system in predicting mortality and length of stay at surgical intensive care unit

    PubMed Central

    Gilani, Mahryar Taghavi; Razavi, Majid; Azad, Azadeh Mokhtari

    2014-01-01

    Background: In critically ill patients, several scoring systems have been developed over the last three decades. The Acute Physiology and Chronic Health Evaluation (APACHE) and the Simplified Acute Physiology Score (SAPS) are the most widely used scoring systems in the intensive care unit (ICU). The aim of this study was to assess the prognostic accuracy of SAPS II and APACHE II and APACHE III scoring systems in predicting short-term hospital mortality of surgical ICU patients. Materials and Methods: Prospectively collected data from 202 patients admitted to Mashhad University Hospital postoperative ICU were analyzed. Calibration was estimated using the Hosmer-Lemeshow goodness-of-fit test. Discrimination was evaluated by using the receiver operating characteristic (ROC) curves and area under a ROC curve (AUC). Result: Two hundred and two patients admitted on post-surgical ICU were evaluated. The mean SAPS II, APACHE II, and APACHE III scores for survivors were found to be significantly lower than of non-survivors. The calibration was best for APACHE II score. Discrimination was excellent for APACHE II (AUC: 0.828) score and acceptable for APACHE III (AUC: 0.782) and SAPS II (AUC: 0.778) scores. Conclusion: APACHE II provided better discrimination than APACHE III and SAPS II calibration was good at APACHE II and poor at APACHE III and SAPS II. Use of APACHE II was excellent in this post-surgical ICU. PMID:24791049

  20. Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome.

    PubMed

    Johansson, Julia; Feng, Yi; Shao, Ruijin; Lönn, Malin; Billig, Håkan; Stener-Victorin, Elisabet

    2010-10-01

    Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20-25 min five times/wk for 4-5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity. PMID:20663984

  1. Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins.

    PubMed

    Miller, L L

    1976-01-01

    The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.

  2. Acute Kidney Injury Treated with Dialysis outside the Intensive Care Unit: A Retrospective Observational Single-Center Study

    PubMed Central

    Sprenger-Mähr, Hannelore; Zitt, Emanuel; Lhotta, Karl

    2016-01-01

    Introduction The number of patients suffering from acute kidney injury requiring dialysis (AKI-D) is increasing. Whereas causes and outcome of AKI-D in the intensive care unit (ICU) are described extensively, few data exist about AKI-D patients treated outside the ICU. Aim of this study was to identify the causes of AKI-D, determine in-depth the comorbid conditions and outcome of this particular patient group and identify possibilities for its prevention. Methods We retrospectively studied all AKI-D patients treated outside the ICU in a single nephrology referral center between January 2010 and June 2015. Data on comorbid conditions, renal function and drug therapy prior to AKI-D, and possible causal events were collected. Patients were grouped into those with renal hypoperfusion as the predominant cause of AKI-D (hemodynamic group) and those with other causes (non-hemodynamic group). Results During 66 months 128 patients (57% male, mean age 69.3 years) were treated. AKI-D was community-acquired in 70.3%. The most frequent comorbidities were hypertension (62.5%), chronic kidney disease (CKD) (58.9%), coronary artery disease (CAD) (46.1%), diabetes (35.9%) and heart failure (34.1%). Most patients were prescribed diuretics (61.7%) and inhibitors of the renin-angiotensin-aldosterone system (RASI) (57.8%); 46.1% had a combination of both. In the 88 patients with hemodynamic AKI-D (68.8%) the most frequent initiating events were diarrhea (39.8%), infections (17.0%) and acute heart failure (13.6%). In the 40 patients with non-hemodynamic AKI-D (31.2%) interstitial nephritis (n = 15) was the prominent diagnosis. Patients with hemodynamic AKI-D were older (72.6 vs. 62.1 years, p = 0.001), suffered more often from CKD (68.2% vs. 33.3%, p = 0.003), CAD (54.5% vs. 27.5%, p = 0.004) and diabetes (42.0% vs. 22.5%, p = 0.033), and were more frequently on diuretics (75.0% vs. 32.5%, p<0.001), RASI (67.0% vs. 37.5%, p = 0.002) or their combination (58.0% vs. 20.0%, p<0

  3. The role of exercise intensity in the bone metabolic response to an acute bout of weight-bearing exercise.

    PubMed

    Scott, Jonathan P R; Sale, Craig; Greeves, Julie P; Casey, Anna; Dutton, John; Fraser, William D

    2011-02-01

    We compared the effects of exercise intensity (EI) on bone metabolism during and for 4 days after acute, weight-bearing endurance exercise. Ten males [mean ± SD maximum oxygen uptake (Vo(2max)): 56.2 ± 8.1 ml·min(-1)·kg(-1)] completed three counterbalanced 8-day trials. Following three control days, on day 4, subjects completed 60 min of running at 55%, 65%, and 75% Vo(2max). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH(2)-terminal propeptides of procollagen type 1 (P1NP), osteocalcin (OC), bone-alkaline phosphatase (ALP)], osteoprotegerin (OPG), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate (PO(4)), and cortisol were measured during and for 3 h after exercise and on four follow-up days (FU1-FU4). At 75% Vo(2max), β-CTX was not significantly increased from baseline by exercise but was higher compared with 55% (17-19%, P < 0.01) and 65% (11-13%, P < 0.05) Vo(2max) in the first hour postexercise. Concentrations were decreased from baseline in all three groups by 39-42% (P < 0.001) at 3 h postexercise but not thereafter. P1NP increased (P < 0.001) during exercise only, while bone-ALP was increased (P < 0.01) at FU3 and FU4, but neither were affected by EI. PTH and cortisol increased (P < 0.001) with exercise at 75% Vo(2max) only and were higher (P < 0.05) than at 55% and 65% Vo(2max) during and immediately after exercise. The increases (P < 0.001) in OPG, ACa, and PO(4) with exercise were not affected by EI. Increasing EI from 55% to 75% Vo(2max) during 60 min of running resulted in higher β-CTX concentrations in the first hour postexercise but had no effect on bone formation markers. Increased bone-ALP concentrations at 3 and 4 days postexercise suggest a beneficial effect of this type of exercise on bone mineralization. The increase in OPG was not influenced by exercise intensity, whereas PTH was increased at 75% Vo(2max) only, which cannot be fully explained by changes in

  4. Simplified Acute Physiology Score II as Predictor of Mortality in Intensive Care Units: A Decision Curve Analysis

    PubMed Central

    Allyn, Jérôme; Ferdynus, Cyril; Bohrer, Michel; Dalban, Cécile; Valance, Dorothée; Allou, Nicolas

    2016-01-01

    Background End-of-life decision-making in Intensive care Units (ICUs) is difficult. The main problems encountered are the lack of a reliable prediction score for death and the fact that the opinion of patients is rarely taken into consideration. The Decision Curve Analysis (DCA) is a recent method developed to evaluate the prediction models and which takes into account the wishes of patients (or surrogates) to expose themselves to the risk of obtaining a false result. Our objective was to evaluate the clinical usefulness, with DCA, of the Simplified Acute Physiology Score II (SAPS II) to predict ICU mortality. Methods We conducted a retrospective cohort study from January 2011 to September 2015, in a medical-surgical 23-bed ICU at University Hospital. Performances of the SAPS II, a modified SAPS II (without AGE), and age to predict ICU mortality, were measured by a Receiver Operating Characteristic (ROC) analysis and DCA. Results Among the 4.370 patients admitted, 23.3% died in the ICU. Mean (standard deviation) age was 56.8 (16.7) years, and median (first-third quartile) SAPS II was 48 (34–65). Areas under ROC curves were 0.828 (0.813–0.843) for SAPS II, 0.814 (0.798–0.829) for modified SAPS II and of 0.627 (0.608–0.646) for age. DCA showed a net benefit whatever the probability threshold, especially under 0.5. Conclusion DCA shows the benefits of the SAPS II to predict ICU mortality, especially when the probability threshold is low. Complementary studies are needed to define the exact role that the SAPS II can play in end-of-life decision-making in ICUs. PMID:27741304

  5. Changes in mechanisms proposed to mediate fat loss following an acute bout of high-intensity interval and endurance exercise.

    PubMed

    Williams, Cameron B; Zelt, Jason G E; Castellani, Laura N; Little, Jonathan P; Jung, Mary E; Wright, David C; Tschakovsky, Michael E; Gurd, Brendon J

    2013-12-01

    The purpose of this study was to investigate the acute effects of endurance exercise (END; 65% V̇O2peak for 60 min) and high-intensity interval exercise (HIE; four 30 s Wingates separated by 4.5 min of active rest) on cardiorespiratory, hormonal, and subjective appetite measures that may account for the previously reported superior fat loss with low volume HIE compared with END. Recreationally active males (n = 18) completed END, HIE, and control (CON) protocols. On each test day, cardiorespiratory measures including oxygen uptake (V̇O2), respiratory exchange ratio (RER), and heart rate were recorded and blood samples were obtained at baseline (BSL), 60 min after exercise, and 180 min after exercise (equivalent times for CON). Subjective measures of appetite (hunger, fullness, nausea, and prospective consumption) were assessed using visual analogue scales, administered at BSL, 0, 60, 120, and 180 min after exercise. No significant differences in excess postexercise oxygen consumption (EPOC) were observed between conditions. RER was significantly (P < 0.05) depressed in HIE compared with CON at 60 min after exercise, yet estimates of total fat oxidation over CON were not different between HIE and END. No differences in plasma adiponectin concentrations between protocols or time points were present. Epinephrine and norepinephrine were significantly (P < 0.05) elevated immediately after exercise in HIE compared with CON. Several subjective measures of appetite were significantly (P < 0.05) depressed immediately following HIE. Our data indicate that increases in EPOC or fat oxidation following HIE appear unlikely to contribute to the reported superior fat loss compared with END.

  6. Acute effect of high-intensity aerobic exercise performed on treadmill and cycle ergometer on strength performance.

    PubMed

    Panissa, Valéria L G; Tricoli, Valmor A A; Julio, Ursula F; Ribeiro, Natalia; de Azevedo Neto, Raymundo M A; Carmo, Everton C; Franchini, Emerson

    2015-04-01

    Concurrent training (i.e., combination of endurance with strength training) may result in negative interference on strength performance. Moreover, there are indications that the magnitude of this interference is dependent on endurance exercise mode. Thus, this study aimed to verify the acute effects of previous running and cycling on strength endurance performance. After the determination of the maximum intensity reached (Imax) during treadmill running and cycle ergometer pedaling and half-squat maximum strength (1 repetition maximum [1RM]), 10 physically active men were submitted to 3 experimental conditions: control condition (S) comprised of 4 sets of maximum repetitions at 80% 1RM, intermittent running (RS), and cycling (CS) conditions (15 × 1 minute:1 minute in the Imax) followed by the strength exercise (S). Maximum number of repetitions (MNR), total session volume (TV), and vastus lateralis electromyographic signal (VLRMS) were analyzed. It was observed that MNR and TV performed in set 1 in the S condition was superior to that performed in set 1 in the RS (p < 0.001) and CS (p < 0.001) conditions; and set 2 in the S condition was superior to set 2 only in the CS for the MNR (p = 0.032) and TV (p = 0.012). For the VLRMS, there was a main effect for repetition, with higher values in the last repetition compared with the second one (p < 0.01). In conclusion, an aerobic exercise bout before strength exercise impairs the subsequent strength endurance performance. In addition, the magnitude of the interference effect was higher after the aerobic cycling exercise.

  7. Acute effect of high-intensity aerobic exercise performed on treadmill and cycle ergometer on strength performance.

    PubMed

    Panissa, Valéria L G; Tricoli, Valmor A A; Julio, Ursula F; Ribeiro, Natalia; de Azevedo Neto, Raymundo M A; Carmo, Everton C; Franchini, Emerson

    2015-04-01

    Concurrent training (i.e., combination of endurance with strength training) may result in negative interference on strength performance. Moreover, there are indications that the magnitude of this interference is dependent on endurance exercise mode. Thus, this study aimed to verify the acute effects of previous running and cycling on strength endurance performance. After the determination of the maximum intensity reached (Imax) during treadmill running and cycle ergometer pedaling and half-squat maximum strength (1 repetition maximum [1RM]), 10 physically active men were submitted to 3 experimental conditions: control condition (S) comprised of 4 sets of maximum repetitions at 80% 1RM, intermittent running (RS), and cycling (CS) conditions (15 × 1 minute:1 minute in the Imax) followed by the strength exercise (S). Maximum number of repetitions (MNR), total session volume (TV), and vastus lateralis electromyographic signal (VLRMS) were analyzed. It was observed that MNR and TV performed in set 1 in the S condition was superior to that performed in set 1 in the RS (p < 0.001) and CS (p < 0.001) conditions; and set 2 in the S condition was superior to set 2 only in the CS for the MNR (p = 0.032) and TV (p = 0.012). For the VLRMS, there was a main effect for repetition, with higher values in the last repetition compared with the second one (p < 0.01). In conclusion, an aerobic exercise bout before strength exercise impairs the subsequent strength endurance performance. In addition, the magnitude of the interference effect was higher after the aerobic cycling exercise. PMID:25259468

  8. Intensive rearing of male calves during the first three weeks of life has long-term effects on number of islets of Langerhans and insulin stained area in the pancreas.

    PubMed

    Prokop, L; Kaske, M; Maccari, P; Lucius, R; Kunz, H-J; Wiedemann, S

    2015-03-01

    Permanent effects of early postnatal nutrition on the development and function of tissues and organs have been previously demonstrated primarily in humans and rodents. The objective of this study in calves was to analyze the impact of rearing conditions during the first 3 wk of life on morphology of insulin-producing pancreatic β-cells. Forty-two male Holstein calves were raised during the first 3 wk of life either intensively (intensively reared [INT]; ad libitum milk feeding and individual hutches; = 21) or according to an established restrictive rearing protocol (4 L milk/d) during wk 1 in hutches and 720 g/d milk replacer (MR) from d 8 to 21 in group pens (restrictively reared [CON]; = 21). Thereafter, all calves were housed and fed under comparable conditions. Birth weight and weekly BW up to wk 10 were recorded. Plasma glucose, insulin, IGF-1, and GH levels were assessed in wk 1, 2, 3, and 10 of life. Slaughtering took place after 8 mo and pancreatic tissue from the medium body (corpus pancreatic) was removed. The number of islets of Langerhans and the insulin stained area were examined histologically. Total milk intake of INT calves was nearly double the intake in CON calves in the first 3 wk of life ( < 0.01). Daily starter intake during wk 4 to 10 of life did not differ between groups ( = 0.24). During the first 3 wk, the ADG were up to 9 times higher in INT calves compared to CON calves ( < 0.01), yet BW at time of slaughter did not differ ( = 0.18). Intensive rearing led to increased plasma glucose, insulin, and IGF-1 concentrations after 3 wk of life compared with rearing to the established standard protocol (all < 0.05), whereas GH was lower in INT calves during the second week of life. At time of slaughter, the mean number of islets of Langerhans was higher in INT calves compared to CON calves (9.1 ± 0.3 vs. 7.8 ± 0.3; < 0.01). Also, the total insulin stained area per photograph was higher in INT calves compared to CON calves (107,180 ± 4,987 vs

  9. Minimal Intensity Physical Activity (Standing and Walking) of Longer Duration Improves Insulin Action and Plasma Lipids More than Shorter Periods of Moderate to Vigorous Exercise (Cycling) in Sedentary Subjects When Energy Expenditure Is Comparable

    PubMed Central

    Duvivier, Bernard M. F. M.; Schaper, Nicolaas C.; Bremers, Michelle A.; van Crombrugge, Glenn; Menheere, Paul P. C. A.; Kars, Marleen; Savelberg, Hans H. C. M.

    2013-01-01

    Background Epidemiological studies suggest that excessive sitting time is associated with increased health risk, independent of the performance of exercise. We hypothesized that a daily bout of exercise cannot compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids. Methodology/Principal Findings Eighteen healthy subjects, age 21±2 year, BMI 22.6±2.6 kgm−2 followed randomly three physical activity regimes for four days. Participants were instructed to sit 14 hr/day (sitting regime); to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr (exercise regime); to substitute 6 hrs sitting with 4 hr walking and 2 hr standing (minimal intensity physical activity (PA) regime). The sitting and exercise regime had comparable numbers of sitting hours; the exercise and minimal intensity PA regime had the same daily energy expenditure. PA was assessed continuously by an activity monitor (ActivPAL) and a diary. Measurements of insulin sensitivity (oral glucose tolerance test, OGTT) and plasma lipids were performed in the fasting state, the morning after the 4 days of each regime. In the sitting regime, daily energy expenditure was about 500 kcal lower than in both other regimes. Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml, respectively. Triglycerides, non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise. Conclusions One hour of daily physical exercise cannot compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting. Reducing inactivity by increasing the time spent walking/standing is more effective than one hour of

  10. [Novel insulins].

    PubMed

    Eriksson, Johan G; Laine, Merja K

    2016-01-01

    Novel insulins have entered the market during recent years. The ultra-long acting insulins, insulin degludek and insulin glargine, the latter having a strength of 300 U/ml, exhibit a steady and predictable action curve. Studies have indicated that significantly fewer hypoglycemiae occur when using degludek in patients with either type 1 or type 2 diabetes, whereas similar evidence about glargine (300 U/mI) has been obtained in the treatment of type 2 diabetes. The long duration of action of both insulins brings long-needed flexibility to.their dosing. PMID:27089618

  11. Insulin: pancreatic secretion and adipocyte regulation.

    PubMed

    Baumgard, L H; Hausman, G J; Sanz Fernandez, M V

    2016-01-01

    Insulin is the primary acute anabolic coordinator of nutrient partitioning. Hyperglycemia is the main stimulant of insulin secretion, but other nutrients such as specific amino acids, fatty acids, and ketoacids can potentiate pancreatic insulin release. Incretins are intestinal hormones with insulinotropic activity and are secreted in response to food ingestion, thus integrating diet chemical composition with the regulation of insulin release. In addition, prolactin is required for proper islet development, and it stimulates β-cell proliferation. Counterintuitively, bacterial components appear to signal insulin secretion. In vivo lipopolysaccharide infusion acutely increases circulating insulin, which is paradoxical as endotoxemia is a potent catabolic condition. Insulin is a potent anabolic orchestrator of nutrient partitioning, and this is particularly true in adipocytes. Insulin dictates lipid accretion in a dose-dependent manner during preadipocyte development in adipose tissue-derived stromal vascular cell culture. However, in vivo studies focused on insulin's role in regulating adipose tissue metabolism from growing, and market weight pigs are sometimes inconsistent, and this variability appears to be animal, age and depot dependent. Additionally, porcine adipose tissue synthesizes and secretes a number of adipokines (leptin, adiponectin, and so forth) that directly or indirectly influence insulin action. Therefore, because insulin has an enormous impact on agriculturally important phenotypes, it is critical to have a better understanding of how insulin homeostasis is governed.

  12. Plasma insulin-like peptide 3 concentrations are acutely regulated by luteinizing hormone in pubertal Japanese Black beef bulls.

    PubMed

    Hannan, M A; Fukami, Y; Kawate, N; Sakase, M; Fukushima, M; Pathirana, I N; Büllesbach, E E; Inaba, T; Tamada, H

    2015-12-01

    Insulin-like peptide 3 (INSL3) is a major secretory product of testicular Leydig cells. The mechanism of acute regulation of INSL3 secretion is still unknown. The present study was undertaken in pubertal beef bulls to (1) determine the temporal relationship of pulsatile secretion among LH, INSL3, and testosterone and (2) monitor acute regulation of INSL3 secretion by LH using GnRH analogue and hCG. Blood samples were collected from Japanese Black beef bulls (N = 6) at 15-minute intervals for 8 hours. Moreover, blood samples were collected at -0.5, 0, 1, 2, 3, 4, 5, and 6 hours after GnRH treatment and -0.5, 0, 2, 4, and 8 hours on the day of treatment (Day 0), and Days 1, 2, 4, 8, and 12 after hCG treatment. Concentrations of LH, INSL3, and testosterone determined by EIAs indicated that secretion in the general circulation was pulsatile. The frequency of LH, INSL3, and testosterone pulses was 4.7 ± 0.9, 3.8 ± 0.2, and 1.0 ± 0.0, respectively, during the 8-hour period. Seventy percent of these INSL3 pulses peaked within 1 hour after a peak of an LH pulse had occurred. The mean increase (peak per basal concentration) of testosterone pulses was higher (P < 0.001) than that of INSL3 pulses. After GnRH treatment, LH concentrations increased (P < 0.01) dramatically 1 hour after treatment and remained high (P < 0.05) until the end of sampling, whereas an elevated (P < 0.05) INSL3 concentration occurred at 1, 2, 5, and 6 hours after treatment. Testosterone concentrations increased (P < 0.01) 1 hour after the treatment and remained high until the end of sampling. After hCG treatment, an increase of INSL3 concentration occurred at 2 and 4 hours, and Days 2, 4, and 8 after treatment (P < 0.05), whereas in case of testosterone, concentrations remained high (P < 0.01) until Day 8 after treatment. The increase (maximum per pretreatment concentration) of INSL3 concentrations after injecting GnRH or hCG was much lower (P < 0.001) than that of

  13. The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

    SciTech Connect

    Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

    2011-02-01

    Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm{sup 3}, respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm{sup 3}) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm{sup 3} increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

  14. Does adherence to treatment mediate the relationship between patients' treatment outcome expectancies and the outcomes of pain intensity and recovery from acute low back pain?

    PubMed

    Haanstra, Tsjitske M; Kamper, Steven J; Williams, Christopher M; Spriensma, Alette S; Lin, Chung-Wei Christine; Maher, Christopher G; de Vet, Henrica C W; Ostelo, Raymond W J G

    2015-08-01

    It is believed that patients' expectancies about the effectiveness of treatment influence their treatment outcomes, but the working mechanism is rarely studied in patients with low back pain. Theoretical models suggest that adherence to treatment may be an important pathway. The aim of this study was to assess the mediating role of adherence to treatment in the relationship between expectancies and the outcomes of recovery and pain intensity in patients with acute low back pain. This study used data from a randomized placebo-controlled trial of paracetamol for acute low back pain. Expectancies were measured with the Credibility Expectancy Questionnaire. Adherence was measured with a medication diary. Pain intensity was recorded daily in a diary on a 0 to 10 pain scale, and recovery was defined as the first of 7 consecutive days scoring 0 or 1 on a 6-point pain scale. Cox regression (dependent variable: recovery) and linear mixed-model analyses (dependent variable: daily pain intensity scores) were performed. The "difference in coefficients" approach was used to establish mediation. A total of 1573 participants were included in current analyses. There was a small but highly significant relationship between expectancies and outcomes; 3.3% of the relationship between expectancies and recovery and 14.2% of the relationship between expectancies and pain intensity were mediated by adherence to treatment. This study does not convincingly support the theory that adherence is a key pathway in the relationship between treatment outcome expectancies and recovery and pain intensity in this acute low back pain population. PMID:25906348

  15. Biosimilar Insulins

    PubMed Central

    Hompesch, Marcus

    2014-01-01

    Until now most of the insulin used in developed countries has been manufactured and distributed by a small number of multinational companies. Beyond the established insulin manufacturers, a number of new players have developed insulin manufacturing capacities based on modern biotechnological methods. Because the patents for many of the approved insulin formulations have expired or are going to expire soon, these not yet established companies are increasingly interested in seeking market approval for their insulin products as biosimilar insulins (BI) in highly regulated markets like the EU and the United States. Differences in the manufacturing process (none of the insulin manufacturing procedures are 100% identical) can lead to insulins that to some extent may differ from the originator insulin. The key questions are if subtle differences in the structure of the insulins, purity, and so on are clinically relevant and may result in different biological effects. The aim of this article is to introduce and discuss basic aspects that may be of relevance with regard to BI. PMID:24876530

  16. Urinary Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) • Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Predicts Adverse Outcome in Pediatric Acute Kidney Injury

    PubMed Central

    Westhoff, Jens H.; Tönshoff, Burkhard; Waldherr, Sina; Pöschl, Johannes; Teufel, Ulrike; Westhoff, Timm H.; Fichtner, Alexander

    2015-01-01

    Background The G1 cell cycle inhibitors tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as promising biomarkers for the prediction of adverse outcomes including renal replacement therapy (RRT) and mortality in critically ill adult patients who develop acute kidney injury (AKI). However, the prognostic value of urinary TIMP-2 and IGFBP7 in neonatal and pediatric AKI for adverse outcome has not been investigated yet. Methods The product of the urinary concentration of TIMP-2 and IGFBP7 ([TIMP-2]•[IGFBP7]) was assessed by a commercially available immunoassay (NephroCheck™) in a prospective cohort study in 133 subjects aged 0–18 years including 46 patients with established AKI according to pRIFLE criteria, 27 patients without AKI (non-AKI group I) and 60 apparently healthy neonates and children (non-AKI group II). AKI etiologies were: dehydration/hypovolemia (n = 7), hemodynamic instability (n = 7), perinatal asphyxia (n = 9), septic shock (n = 7), typical hemolytic-uremic syndrome (HUS; n = 5), interstitial nephritis (n = 5), vasculitis (n = 4), nephrotoxic injury (n = 1) and renal vein thrombosis (n = 1). Results When AKI patients were classified into pRIFLE criteria, 6/46 (13%) patients fulfilled the criteria for the category “Risk”, 13/46 (28%) for “Injury”, 26/46 (57%) for “Failure” and 1/46 (2%) for “Loss”. Patients in the “Failure” stage had a median 3.7-fold higher urinary [TIMP-2]•[IGFBP7] compared to non-AKI subjects (P<0.001). When analyzed for AKI etiology, highest [TIMP-2]•[IGFBP7] values were found in patients with septic shock (P<0.001 vs. non-AKI I+II). Receiver operating characteristic (ROC) curve analyses in the AKI group revealed good performance of [TIMP-2]•[IGFBP7] in predicting 30-day (area under the curve (AUC) 0.79; 95% CI, 0.61–0.97) and 3-month mortality (AUC 0.84; 95% CI, 0.67–0.99) and moderate performance in predicting RRT

  17. Insulin-glycerolipid mediators and gene expression

    SciTech Connect

    Standaert, M.L.; Pollet, R.J. )

    1988-06-01

    Insulin is an anabolic polypeptide hormone with pleiotrophic effects. During the decades since the initial description by Banting and Best, the acute effects of insulin have been widely studied with particular focus on the mechanism or mechanisms of insulin activation of hexose transport and regulation of metabolic enzyme activity. However, recently there has been a major expansion of investigation to include insulin regulation of gene expression with multiple insulin-sensitive specific mRNAs now reported. In this review, we explore the involvement of insulin-induced changes in plasma membrane glycerolipid metabolism in the transmembrane signaling process required for insulin regulation of mRNA levels. Insulin increase diacylglycerol levels in insulin-responsive cells, and synthetic diacylglycerols or their phorbol ester diacylglycerol analogs, such as 4{beta}, 9{alpha}, 12{beta}, 13{alpha}, 20-pentahydroxytiglia-1,6-dien-3-one 12{beta}-myristate 13-acetate (TPA), mimic insulin regulation of ornithine decarboxylase mRNA, c-fos mRNA, and phosphoenolpyruvate carboxykinase mRNA levels. This suggests that insulin regulation of specific mRNA levels may be mediated by insulin-induced changes in phospholipid metabolism and that diacylglycerol may play a pivotal role in insulin regulation of gene expression.

  18. Insulin oedema.

    PubMed Central

    Evans, D. J.; Pritchard-Jones, K.; Trotman-Dickenson, B.

    1986-01-01

    A 35 year old markedly underweight woman presented with uncontrolled diabetes. Following insulin therapy she developed gross fluid retention with extensive peripheral oedema, bilateral pleural effusions and weight gain of 18.8 kg in 22 days, accompanied by a fall in plasma albumin. She responded well to treatment with diuretics and salt-poor albumin, losing 10.3 kg in 6 days without recurrence of oedema. Severe insulin oedema is an uncommon complication of insulin therapy and may be due to effects of insulin on both vascular permeability and the renal tubule. Images Figure 2 PMID:3529068

  19. [Intensified insulin therapy and insulin micro-pumps during pregnancy].

    PubMed

    Galuppi, V

    1994-06-01

    Before conception and during pregnancy in diabetic patients, every possible effort should be made in order to obtain a good, if not perfect, metabolic control and to warrant maternal and fetal health. Multiple daily injections are required to achieve a very strict glucose regulation in pregnant patients with insulin-dependent diabetes mellitus. The most usual intensive insulin administration patterns require 3 premeal doses of short-acting insulin and 1 (at bedtime) or 2 (one in the morning and one at bedtime) injections of intermediate or slow-acting insulin. As an alternative choice, insulin pumps allow a continuous subcutaneous infusion with short-acting insulin according to a basal rate which cover the insulin need during the night and between meals. Premeal and presnack surges of insulin are administrated by the patient herself. Home glucose monitoring must be used to adjust insulin doses. Target glucose levels every diabetic pregnant woman should try to achieve are lower than in non-pregnant women: fasting glycaemia should be below 100 mg/dl, 1 hour post-prandial value below 140 mg/dl and 2 hour post-prandial level below 120 mg/dl. The stricter the control and treatment goals are, the more frequently hypoglycaemia may occur. Hypoglycaemia may be harmful especially for patients with severe diabetic complications and may affect the fetus. Therefore, every pregnant diabetic woman should receive individualized treatment and glycaemic goals according to her clinical features, her compliance and her social and cultural background.

  20. Intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation: an interview study

    PubMed Central

    Kvangarsnes, Marit; Torheim, Henny; Hole, Torstein; Öhlund, Lennart S

    2013-01-01

    Aim To report a study conducted to explore intensive care unit nurses’ perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation. Background An acute exacerbation is a life-threatening situation, which patients often consider to be extremely frightening. Healthcare personnel exercise considerable power in this situation, which challenges general professional notions of patient participation. Design Critical discourse analysis. Methods In the autumn of 2009, three focus group interviews with experienced intensive care nurses were conducted at two hospitals in western Norway. Two groups had six participants each, and one group had five (N = 17). The transcribed interviews were analysed by means of critical discourse analysis. Findings The intensive care nurses said that an exacerbation is often an extreme situation in which healthcare personnel are exercising a high degree of control and power over patients. Patient participation during exacerbation often takes the form of non-involvement. The participating nurses attached great importance to taking a sensitive approach when meeting patients. The nurses experienced challenging ethical dilemmas. Conclusion This study shows that patient participation should not be understood in universal terms, but rather in relation to a specific setting and the interactions that occur in this setting. Healthcare personnel must develop skill, understanding, and competence to meet these challenging ethical dilemmas. A collaborative inter-professional approach between physicians and nurses is needed to meet the patients’ demand for involvement. PMID:22512673

  1. Treatment of hyperglycaemia in patients with acute stroke.

    PubMed

    Castilla-Guerra, L; Fernández-Moreno, M C; Hewitt, J

    2016-03-01

    The proportion of diabetic patients who are hospitalised for stroke has been increasing in recent years, currently reaching almost a third of all cases of stroke. In addition, about half of patients with acute stroke present hyperglycaemia in the first hours of the stroke. Although hyperglycaemia in the acute phase of stroke is associated with a poor prognosis, its treatment is currently a topic of debate. There is no evidence that the adminstration of intravenous insulin to these patients offers benefits in terms of the evolution of the stroke. New studies in development, such as the SHINE study (Stroke Hyperglycemia Insulin Network Effort), may contribute to clarifying the role of intensive control of glycaemia during the acute phase of the stroke. Ultimately, patients who have presented with stroke should be screened for diabetes. PMID:26189890

  2. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT

    PubMed Central

    Savani, Bipin N.; Labopin, Myriam; Kröger, Nicolaus; Finke, Jürgen; Ehninger, Gerhard; Niederwieser, Dietger; Schwerdtfeger, Rainer; Bunjes, Donald; Glass, Bertram; Socié, Gerard; Ljungman, Per; Craddock, Charles; Baron, Frédéric; Ciceri, Fabio; Gorin, Norbert Claude; Esteve, Jordi; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

    2016-01-01

    The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs

  3. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    SciTech Connect

    Mikell, John L.; Waller, Edmund K.; Switchenko, Jeffrey M.; Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael; Hall, William A.; Langston, Amelia A.; Esiashvili, Natia; Khoury, H. Jean; Khan, Mohammad K.

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  4. Effect of insulin on renal calcium transport

    SciTech Connect

    Gollaher, C.J.

    1985-01-01

    The author has investigated both the indirect effect of insulin parathyroid hormone (PTH) activity, and the direct effect of insulin on renal calcium transport. The indirect study was performed by comparing calcium excretion in sham-operated and parathyroidectomized rats infused with the insulin secretagogue, arginine. Arginine infusion increased urinary calcium excretion in both groups. Therefore, it is concluded that neither PTH activity nor secretion is involved in this response. The direct effects of insulin were investigated by exposing rat kidney slices in vitro to varying concentrations of insulin and performing a kinetic analysis to interpret insulin's effect on calcium transport through cellular compartments. Steady state calcium transport through the plasma membrane, cytosol and mitochondria were compared in the presence and absence of insulin. Insulin had no effect on any calcium pool size or exchange rate. The direct effect of insulin was also studied in an acute experiment, which simulates conditions where insulin levels are raised rapidly as in the case with protein or glucose consumption. Under these conditions insulin treatment caused a rapid, but transient increase in /sup 45/Ca efflux from rat kidney slices. This pattern is usually indicative of a stimulation of calcium efflux across the plasma membrane. Finally, insulin caused a slight decrease in slice chemical calcium concentration.

  5. Acute Myosin Heavy Chain Isoform mRNA Expression in Response to Two Resistance Exercise Intensities With Equal Volume Load in Resistance-Trained Men.

    PubMed

    Schwarz, Neil A; Spillane, Mike B; McKinley, Sarah K; Andre, Thomas L; Gann, Joshua J; Willoughby, Darryn S

    2015-08-01

    The purpose of this study was to determine if resistance exercise intensity, in the context of equal volume load, differentially affected myosin heavy chain (MHC) isoform messenger RNA (mRNA) expression in resistance-trained men. In a crossover, uniform-balanced design, 10 male participants (23.7 ± 2.8 years, 178.8 ± 5.9 cm, 85.9 ± 9.2 kg) completed 2 lower-body resistance exercise sessions of different intensities with equal volume load. For the higher-intensity exercise session, participants performed 5 sets of 6 repetitions at 80% of 1 repetition maximum (1RM). For the lower-intensity exercise session, participants performed 3 sets of 16 repetitions at 50% of 1RM. Muscle samples from the vastus lateralis were acquired before exercise (PRE), 45 minutes postexercise (45MINPE), 3 hours postexercise (3HRPE), 24 hours postexercise (24HRPE), and 48 hours postexercise (48HRPE). Statistical analyses of mRNA expression were performed using separate 2 × 5 two-way repeated-measures analyses of variance for each criterion variable (p ≤ 0.05). There were no statistically significant interactions between intensity and time. Likewise, there were no significant differences between exercise intensity in MHC expression. Expression of mRNA for all MHC isoforms decreased at all postexercise time points, except 3HRPE (p = 0.051), compared with PRE following both exercise bouts (p ≤ 0.05). The results of this study found no difference in mRNA expression of MHC isoforms as a function of resistance exercise intensity. In addition, in contrast to results found in previous studies of untrained men, MHC mRNA expression seems to decrease in response to acute resistance exercise in previously resistance-trained men.

  6. Reduced acute toxicity and improved efficacy from intensity-modulated proton therapy (IMPT) for the management of head and neck cancer.

    PubMed

    McKeever, Matthew R; Sio, Terence T; Gunn, G Brandon; Holliday, Emma B; Blanchard, Pierre; Kies, Merrill S; Weber, Randal S; Frank, Steven J

    2016-08-01

    Cancers in the head and neck area are usually close to several critical organ structures. Traditional external-beam photon radiation therapy unavoidably exposes these structures to significant doses of radiation, which can lead to serious acute and chronic toxicity. Intensity-modulated proton therapy (IMPT), however, has dosimetric advantages that allow it to deposit high doses within the target while largely sparing surrounding structures. Because of this advantage, IMPT has the potential to improve both tumor control and toxicity. To determine the degree to which IMPT can reduce toxicity and improve tumor control, more randomized trials are needed that directly compare IMPT with intensity-modulated photon therapy. Here we examine the existing evidence on the efficacy and toxicity of IMPT for treating cancers at several anatomic subsites of the head and neck. We also report on the ability of IMPT to reduce malnutrition, and gastrostomy tube dependence and improve patient-reported outcomes (PROs). PMID:27506808

  7. Insulin therapy and exercise.

    PubMed

    Kourtoglou, Georgios I

    2011-08-01

    Medical nutrition therapy and physical exercise are the cornerstones of the diabetes management. Patients with type 1 DM always need exogenous insulin administration, recently available in the form of insulin analogs. In type 2 DM, characterized by increased insulin resistance and progressive decline of the beta-cell function, various antidiabetic medications are used. Most of the subjects with type 2 DM will finally need insulin. The main site of insulin action is the skeletal muscle, while the liver is the main site of glucose storage in the form of glycogen. With the modern diabetes therapies it is possible to rapidly reach and maintain normoglycemia in both types of DM but with the cost of higher incidence of hypoglycemia, especially related to exercise. Regular physical exercise causes a lot of beneficial effects in healthy as well as diabetic subjects of all age groups. In type 1 DM physical exercise is a fundamental element for both physical and mental development. In type 2 DM it has a main role in diabetes control. The increased hepatic glucose production and the increased muscular glucose uptake during exercise are closely interrelated in all exercise intensities. In diabetes mellitus there is a disturbed energy substrate use during exercise leading to either hypo- or hyperglycemia. The influence of low or moderate intensity aerobic exercise on diabetes control has been well studied. The inappropriately high insulinemia combined with the low glucose levels can lead to severe hypoglycemia if proper measures are not taken. Prolonged exercise can also predispose to decreased glucose counter regulation. It is better for the type 1 diabetic subject to postpone the exercise session in very high (>300 mg/dl) or very low (<70 mg/dl) BG levels. Every insulin treated subject is recommended to be checked for any existing diabetic complication before the start of every exercise program. Glucose measurement with glucose meters or sometimes with Continuous Glucose

  8. The devil is in the detail: Acute Guillain–Barré syndrome camouflaged as neurosarcoidosis in a critically ill patient admitted to an Intensive Care Unit

    PubMed Central

    Sarada, Pooja Prathapan; Sundararajan, Krishnaswamy

    2016-01-01

    Guillain–Barré syndrome (GBS) is an acute demyelinating polyneuropathy, usually evoked by antecedent infection. Sarcoidosis is a multisystem chronic granulomatous disorder with neurological involvement occurring in a minority. We present a case of a 43-year-old Caucasian man who presented with acute ascending polyradiculoneuropathy with a recent diagnosis of pulmonary sarcoidosis. The absence of acute flaccid paralysis excluded a clinical diagnosis of GBS in the first instance. Subsequently, a rapid onset of proximal weakness with multi-organ failure led to the diagnosis of GBS, which necessitated intravenous immunoglobulin and plasmapheresis to which the patient responded adequately, and he was subsequently discharged home. Neurosarcoidosis often masquerades as other disorders, leading to a diagnostic dilemma; also, the occurrence of a GBS-like clinical phenotype secondary to neurosarcoidosis may make diagnosing coexisting GBS a therapeutic challenge. This article not only serves to exemplify the rare association of neurosarcoidosis with GBS but also highlights the need for a high index of clinical suspicion for GBS and accurate history taking in any patient who may present with rapidly progressing weakness to an Intensive Care Unit. PMID:27303139

  9. Using high-intensity care management to integrate acute and long-term care services: substitute for large scale system reform?

    PubMed

    Applebaum, Robert; Straker, Jane; Mehdizadeh, Shahla; Warshaw, Gregg; Gothelf, Elizabeth

    2002-01-01

    This study evaluates a demonstration that used high intensity care management to improve integration between the acute and long-term care service systems. The demonstration intervention included the use of clinical nurse care manager, supervised by a geriatrician, to supplement an existing in-home care management system. Chronically disabled home care clients age 60 and over were randomly assigned (N = 308) to receive enhanced clinical services plus traditional care management, or to the control group, to receive the normal care management services provided. Treatment group members were expected to experience lower use of hospitals and nursing homes and lower overall health and long-term care costs. Research subjects were followed for up to 18 months using Medicare records and mortality data. A subsample (N = 150) also received in-person interviews to cover a range of health and social outcomes anticipated as a result of the intervention. Although there was some variation in health use and cost across treatment and control groups over the 18 month time period, the overall conclusion is that there were no differences between groups on any of the outcome variables examined. Efforts to integrate the acute and long-term care systems have proven to be difficult. This intervention, which attempted to create integration through high intensity care managers, but without financial or regulatory incentives, was simply unable to create enough change in the care system to produce significant change for the clients served.

  10. The Amsterdam Studies of Acute Psychiatry - II (ASAP-II): a comparative study of psychiatric intensive care units in the Netherlands

    PubMed Central

    Koppelmans, Vincent; Schoevers, Robert; van Wijk, Cecile Gijsbers; Mulder, Wijnand; Hornbach, Annett; Barkhof, Emile; Klaassen, André; van Egmond, Marieke; van Venrooij, Janine; Bijpost, Yan; Nusselder, Hans; van Herrewaarden, Marjan; Maksimovic, Igor; Achilles, Alexander; Dekker, Jack

    2009-01-01

    Background The number of patients in whom mental illness progresses to stages in which acute, and often forced treatment is warranted, is on the increase across Europe. As a consequence, more patients are involuntarily admitted to Psychiatric Intensive Care Units (PICU). From several studies and reports it has become evident that important dissimilarities exist between PICU's. The current study seeks to describe organisational as well as clinical and patient related factors across ten PICU's in and outside the Amsterdam region, adjusted for or stratified by level of urbanization. Method/Design This paper describes the design of the Amsterdam Studies of Acute Psychiatry II (ASAP-II). This study is a prospective observational cohort study comparing PICU's in and outside the Amsterdam region on various patient characteristics, treatment aspects and recovery related variables. Dissimilarities were measured by means of collecting standardized forms which were filled out in the framework of care as usual, by means of questionnaires filled out by mental health care professionals and by means of extracting data from patient files for every consecutive patient admitted at participating PICU's during a specific time period. Urbanization levels for every PICU were calculated conform procedures as proposed by the Dutch Central Bureau for Statistics (CBS). Discussion The current study may provide a deeper understanding of the differences between psychiatric intensive care units that can be used to promote best practice and benchmarking procedures, and thus improve the standard of care. PMID:19725981

  11. Insulin sensitivity and lipid profile of eutrophic individuals after acute intake of fresh orange juice in comparison to the commercial-pasteurized orange juice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrus flavonoids from orange juice (OJ) have shown hypolipidemic, hypotension, and anti-inflammatory properties. However, the extraction and commercial pasteurization of OJ can influence its nutritional composition in comparison to the fresh squeezed OJ. We evaluated the insulin sensitivity, and th...

  12. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2016-01-19

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  13. Insulin Test

    MedlinePlus

    ... people with type 2 diabetes , polycystic ovarian syndrome (PCOS) , prediabetes or heart disease , or metabolic syndrome . A ... resistance), especially in obese individuals and those with PCOS . This test involves an IV-infusion of insulin, ...

  14. Modeling phasic insulin release: immediate and time-dependent effects of glucose.

    PubMed

    Nesher, Rafael; Cerasi, Erol

    2002-02-01

    The cellular and molecular mechanisms of insulin secretion are being intensively investigated, yet most researchers are seemingly unaware of the complexity of the dynamic regulation of the secretion. In this article, we summarize studies of the physiology of insulin secretion performed over several decades. The insulin response of perifused islets of rats, perfused rat pancreas, or that of a human, to a square-wave glucose stimulus is biphasic, a transient first-phase response of 4- to 10-min duration followed by a gradual rise in secretion rates (second-phase response). Several hypotheses have been proposed to account for the phasic nature of insulin secretion; they are briefly discussed in this review. We have favored the hypothesis that nutrient stimulators such as glucose, in addition to a primary and almost immediate secretory signal, with time induce both stimulatory and inhibitory messages in the beta-cell, and those messages modulate the primary insulinogenic signal. Indeed, studies in the rat pancreas and in humans have demonstrated that short stimulations with glucose generate a state of refractoriness of the insulin secretion, which we have termed time-dependent inhibition (TDI). Nonnutrient secretagogues such as arginine induce strong TDI independent of the duration of stimulation. Once the agent is removed, TDI persists for a considerable period. In contrast, prolonged stimulations with glucose (and other nutrients) lead to the amplification of the insulin response to subsequent stimuli; this can be demonstrated in the perfused rat pancreas, in perifused islets from several rodents, and in humans. We have termed this stimulatory signal time-dependent potentiation (TDP). The generation of TDP requires higher glucose concentrations and prolonged stimulation; the effect is retained for some time after cessation of the stimulus. Of major interest is the observation that, while the acute insulin response to glucose is severely reduced in glucose

  15. Microdialysis based monitoring of subcutaneous interstitial and venous blood glucose in Type 1 diabetic subjects by mid-infrared spectrometry for intensive insulin therapy

    NASA Astrophysics Data System (ADS)

    Heise, H. Michael; Kondepati, Venkata Radhakrishna; Damm, Uwe; Licht, Michael; Feichtner, Franz; Mader, Julia Katharina; Ellmerer, Martin

    2008-02-01

    Implementing strict glycemic control can reduce the risk of serious complications in both diabetic and critically ill patients. For this purpose, many different blood glucose monitoring techniques and insulin infusion strategies have been tested towards the realization of an artificial pancreas under closed loop control. In contrast to competing subcutaneously implanted electrochemical biosensors, microdialysis based systems for sampling body fluids from either the interstitial adipose tissue compartment or from venous blood have been developed, which allow an ex-vivo glucose monitoring by mid-infrared spectrometry. For the first option, a commercially available, subcutaneously inserted CMA 60 microdialysis catheter has been used routinely. The vascular body interface includes a double-lumen venous catheter in combination with whole blood dilution using a heparin solution. The diluted whole blood is transported to a flow-through dialysis cell, where the harvesting of analytes across the microdialysis membrane takes place at high recovery rates. The dialysate is continuously transported to the IR-sensor. Ex-vivo measurements were conducted on type-1 diabetic subjects lasting up to 28 hours. Experiments have shown excellent agreement between the sensor readout and the reference blood glucose concentration values. The simultaneous assessment of dialysis recovery rates renders a reliable quantification of whole blood concentrations of glucose and metabolites (urea, lactate etc) after taking blood dilution into account. Our results from transmission spectrometry indicate, that the developed bed-side device enables reliable long-term glucose monitoring with reagent- and calibration-free operation.

  16. Investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in breast cancer women under chemotherapy

    PubMed Central

    Matourypour, Pegah; Vanaki, Zohreh; Zare, Zahra; Mehrzad, Valiolah; Dehghan, Mojtaba; Ranjbaran, Mehdi

    2016-01-01

    Background: Nausea and vomiting are the worst and the most prevalent complications experienced by 70–80% of patients. Complementary treatments including therapeutic touch are cost-effective and low-risk, independent nursing interventions. Present research aims at investigating the effect of therapeutic touch on the intensity of acute chemotherapy-induced vomiting in these patients. Materials and Methods: As a single-blind, randomized clinical trial, the present research was carried out on women with breast cancer undergoing chemotherapy in Isfahan, Iran. The subjects were divided into three groups of control, placebo, and intervention. The intervention was applied to each patient once for 20 min on the aura (human energy field) focusing on solar chakra. Data gathering instruments included demographic questionnaire and acute vomiting intensity scale. Results: There was a significant difference among the three groups (and also after the intervention) (P < 0.0001). Paired comparisons among the groups using Mann–Whitney test showed that there was a statistically significant difference between the control group and the intervention group and between the control group and the placebo group (P < 0.0001). However, there was no significant difference between the placebo and intervention groups (P = 0.07). Conclusions: Therapeutic touch was effective in reducing vomiting in the intervention group. However, the patients experienced lower-intensity vomiting which may be because of presence of a therapist and probably the reduced anxiety related to an additional intervention. So, further research is recommended considering the placebo group and employing another person in addition to the therapist, who is not skilled for this technique. PMID:27186202

  17. Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

    PubMed

    Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J

    2015-02-28

    There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity. PMID:25661189

  18. Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

    PubMed

    Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J

    2015-02-28

    There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

  19. Heat stress acutely activates insulin-independent glucose transport and 5′-AMP-activated protein kinase prior to an increase in HSP72 protein in rat skeletal muscle

    PubMed Central

    Goto, Ayumi; Egawa, Tatsuro; Sakon, Ichika; Oshima, Rieko; Ito, Kanata; Serizawa, Yasuhiro; Sekine, Keiichi; Tsuda, Satoshi; Goto, Katsumasa; Hayashi, Tatsuya

    2015-01-01

    Heat stress (HS) stimulates heat shock protein (HSP) 72 mRNA expression, and the period after an increase in HSP72 protein is characterized by enhanced glucose metabolism in skeletal muscle. We have hypothesized that, prior to an increase in the level of HSP72 protein, HS activates glucose metabolism by acutely stimulating 5′-AMP-activated protein kinase (AMPK). Rat epitrochlearis muscle was isolated and incubated either with or without HS (42°C) for 10 and 30 min. HS for 30 min led to an increase in the level of Hspa1a and Hspa1b mRNA but did not change the amount of HSP72 protein. However, HS for both 10 and 30 min led to a significant increase in the rate of 3-O-methyl-d-glucose (3MG) transport, and the stimulatory effect of 3MG transport was completely blocked by cytochalasin B. HS-stimulated 3MG transport was also inhibited by dorsomorphin but not by wortmannin. HS led to a decrease in the concentration of ATP, phosphocreatine, and glycogen, to an increase in the level of phosphorylation of AMPKα Thr172, and to an increase in the activity of both AMPKα1 and AMPKα2. HS did not affect the phosphorylation status of insulin receptor signaling or Ca2+/calmodulin-dependent protein kinase II. These results suggest that HS acts as a rapid stimulator of insulin-independent glucose transport, at least in part by stimulating AMPK via decreased energy status. Although further research is warranted, heat treatment of skeletal muscle might be a promising method to promote glucose metabolism acutely. PMID:26542263

  20. Acute GVHD is a strong predictor of full donor CD3+ T cell chimerism after reduced intensity conditioning allogeneic stem cell transplantation.

    PubMed

    El-Cheikh, Jean; Vazquez, Alberto; Crocchiolo, Roberto; Furst, Sabine; Calmels, Boris; Castagna, Luca; Lemarie, Claude; Granata, Angela; Ladaique, Patrick; Oudin, Claire; Faucher, Catherine; Chabannon, Christian; Blaise, Didier

    2012-12-01

    The monitoring of chimerism is a standard procedure to assess engraftment and achievement of full donor lymphoid cells after reduced intensity conditioning (RIC) stem cell transplantation (Allo-SCT). However, there is no consensus on when and how often to monitor post-transplant chimerism. We retrospectively analyzed our experience regarding the impact of acute graft versus host disease (GVHD) for the prediction of allograft chimerism. One-hundred-and-fifteen patients transplanted between 2001 and 2010 were identified. This group included 57 females and 58 males with a median age of 50 years (range: 26-68). Patients evaluated in this study were adult patients with hematologic malignancies, who received transplants from an HLA-matched sibling donor or matched unrelated donor (MUD) at allele level so-called 10/10, and received the RIC regimen including fludarabine/busulfan and anti-thymoglobulin (ATG). Mixed T-cell chimerism was defined as between 5 and 94% recipient cells, and full chimerism was defined as the presence of more than 95% donor T-cell chimerism (TCC). Full donor TCC was achieved in 93 patients (81%) at a median of 77 days (range: 30-120) post-transplant. The cumulative incidence of Grade 2-4 GVHD in our population was 25% (95% CI 17-34). The analysis of the population of patients with acute GVHD grade ≥2 showed that at day 120 after Allo-SCT they all had a total full donor TCC. On the other hand, 78 (68%) patients without acute GVHD grade ≥2 presented with mixed chimerism (p = 0.002) on day 120 post-transplant. Interestingly, patients who received ATG 5 mg/kg obtained a higher probability of complete chimerism compared with those receiving 2.5 mg/kg (p = 0.03). In conclusion, our study demonstrates that acute GVHD was predictive of full donor TCC after RIC Allo-SCT. Therefore, our data may challenge the concept of the frequent or close monitoring of donor chimerism in some patients with ongoing acute GVHD. However, chimerism testing could represent

  1. Isoprene emission aids recovery of photosynthetic performance in transgenic Nicotiana tabacum following high intensity acute UV-B exposure.

    PubMed

    Centritto, Mauro; Haworth, Matthew; Marino, Giovanni; Pallozzi, Emanuele; Tsonev, Tsonko; Velikova, Violeta; Nogues, Isabel; Loreto, Francesco

    2014-09-01

    Isoprene emission by terrestrial plants is believed to play a role in mitigating the effects of abiotic stress on photosynthesis. Ultraviolet-B light (UV-B) induces damage to the photosynthetic apparatus of plants, but the role of isoprene in UV-B tolerance is poorly understood. To investigate this putative protective role, we exposed non-emitting (NE) control and transgenic isoprene emitting (IE) Nicotiana tabacum (tobacco) plants to high intensity UV-B exposure. Methanol emissions increased with UV-B intensity, indicating oxidative damage. However, isoprene emission was unaffected during exposure to UV-B radiation, but declined in the 48 h following UV-B treatment at the highest UV-B intensities of 9 and 15 Wm(-2). Photosynthesis and the performance of photosystem II (PSII) declined to similar extents in IE and NE plants following UV-B exposure, suggesting that isoprene emission did not ameliorate the immediate impact of UV-B on photosynthesis. However, after the stress, photosynthesis and PSII recovered in IE plants, which maintained isoprene formation, but not in NE plants. Recovery of IE plants was also associated with elevated antioxidant levels and cycling; suggesting that both isoprene formation and antioxidant systems contributed to reinstating the integrity and functionality of cellular membranes and photosynthesis following exposure to excessive levels of UV-B radiation.

  2. Diabetes and Insulin

    MedlinePlus

    ... years, but may eventually need insulin to maintain glucose control. What are the different types of insulin? Different ... glulisine • Short-acting: regular human insulin Basal insulin. Controls blood glucose levels between meals and throughout the night. This ...

  3. Severe Acute Asthma Exacerbation in Children: A Stepwise Approach for Escalating Therapy in a Pediatric Intensive Care Unit

    PubMed Central

    Nievas, I. Federico Fernandez; Anand, Kanwaljeet J. S.

    2013-01-01

    OBJECTIVES An increasing prevalence of pediatric asthma has led to increasing burdens of critical illness in children with severe acute asthma exacerbations, often leading to respiratory distress, progressive hypoxia, and respiratory failure. We review the definitions, epidemiology, pathophysiology, and clinical manifestations of severe acute asthma, with a view to developing an evidence-based, stepwise approach for escalating therapy in these patients. METHODS Subject headings related to asthma, status asthmaticus, critical asthma, and drug therapy were used in a MEDLINE search (1980–2012), supplemented by a manual search of personal files, references cited in the reviewed articles, and treatment algorithms developed within Le Bonheur Children's Hospital. RESULTS Patients with asthma require continuous monitoring of their cardiorespiratory status via noninvasive or invasive devices, with serial clinical examinations, objective scoring of asthma severity (using an objective pediatric asthma score), and appropriate diagnostic tests. All patients are treated with β-agonists, ipratropium, and steroids (intravenous preferable over oral preparations). Patients with worsening clinical status should be progressively treated with continuous β-agonists, intravenous magnesium, helium-oxygen mixtures, intravenous terbutaline and/or aminophylline, coupled with high-flow oxygen and non-invasive ventilation to limit the work of breathing, hypoxemia, and possibly hypercarbia. Sedation with low-dose ketamine (with or without benzodiazepines) infusions may allow better toleration of non-invasive ventilation and may also prepare the patient for tracheal intubation and mechanical ventilation, if indicated by a worsening clinical status. CONCLUSIONS Severe asthma can be a devastating illness in children, but most patients can be managed by using serial objective assessments and the stepwise clinical approach outlined herein. Following multidisciplinary education and training, this

  4. Insulin therapies: Current and future trends at dawn

    PubMed Central

    Yaturu, Subhashini

    2013-01-01

    Insulin is a key player in the control of hyperglycemia for type 1 diabetes patients and selective individuals in patients of type 2 diabetes. Insulin delivery systems that are currently available for the administration of insulin include insulin syringes, insulin infusion pumps, jet injectors and pens. The traditional and most predictable method for the administration of insulin is by subcutaneous injections. The major drawback of current forms of insulin therapy is their invasive nature. To decrease the suffering, the use of supersonic injectors, infusion pumps, sharp needles and pens has been adopted. Such invasive and intensive techniques have spurred the search for alternative, more acceptable methods for administering insulin. Several non-invasive approaches for insulin delivery are being pursued. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral and pulmonary routes. This review focuses on the new concepts that are being explored for use in future. PMID:23493823

  5. Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety- and depressive-like behaviors in rats.

    PubMed

    Otsuka, Tomomi; Nishii, Ayu; Amemiya, Seiichiro; Kubota, Natsuko; Nishijima, Takeshi; Kita, Ichiro

    2016-02-01

    Accumulating evidence suggests that physical exercise can reduce and prevent the incidence of stress-related psychiatric disorders, including depression and anxiety. Activation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is implicated in antidepressant/anxiolytic properties. In addition, the incidence and symptoms of these disorders may involve dysregulation of the hypothalamic-pituitary-adrenal axis that is initiated by corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Thus, it is possible that physical exercise produces its antidepressant/anxiolytic effects by affecting these neuronal activities. However, the effects of acute physical exercise at different intensities on these neuronal activation and behavioral changes are still unclear. Here, we examined the activities of 5-HT neurons in the DRN and CRF neurons in the PVN during 30 min of treadmill running at different speeds (high speed, 25 m/min; low speed, 15m/min; control, only sitting on the treadmill) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed the elevated plus maze test and the forced swim test to assess anxiety- and depressive-like behaviors, respectively. Acute treadmill running at low speed, but not high speed, significantly increased c-Fos expression in 5-HT neurons in the DRN compared to the control, whereas high-speed running significantly enhanced c-Fos expression in CRF neurons in the PVN compared with the control and low-speed running. Furthermore, low-speed running resulted in decreased anxiety- and depressive-like behaviors compared with high-speed running. These results suggest that acute physical exercise with mild and low stress can efficiently induce optimal neuronal activation that is involved in the antidepressant/anxiolytic effects.

  6. A Comparison of Acute and Chronic Toxicity for Men With Low-Risk Prostate Cancer Treated With Intensity-Modulated Radiation Therapy or {sup 125}I Permanent Implant

    SciTech Connect

    Eade, Thomas N.; Horwitz, Eric M. Ruth, Karen; Buyyounouski, Mark K.; D'Ambrosio, David J.; Feigenberg, Steven J.; Chen, David Y.T.; Pollack, Alan

    2008-06-01

    Purpose: To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and {sup 125}I transperineal permanent prostate seed implant ({sup 125}I) for patients with low-risk prostate cancer. Methods and Materials: Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 {sup 125}I patients). Median follow-up was 43 months for IMRT and 48 months for {sup 125}I. The IMRT prescription dose ranged from 74-78 Gy, and {sup 125}I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml). Results: Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for {sup 125}I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for {sup 125}I (p = 0.09). Conclusions: The IMRT and {sup 125}I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

  7. Association Between Bone Marrow Dosimetric Parameters and Acute Hematologic Toxicity in Anal Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Mell, Loren K. Schomas, David A.; Salama, Joseph K.; Devisetty, Kiran; Aydogan, Bulent; Miller, Robert C.; Jani, Ashesh B.; Kindler, Hedy L.; Roeske, John C.; Chmura, Steven J.

    2008-04-01

    Purpose: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V{sub 10} and PBM-V{sub 20}) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. Methods and Materials: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. Results: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V{sub 5}, V{sub 10}, V{sub 15}, and V{sub 20} were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V{sub 10}, V{sub 15}, and V{sub 20} (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). Conclusion: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.

  8. Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children

    PubMed Central

    Kilian, Yvonne; Wehmeier, Udo F.; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

    2016-01-01

    Aim: The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children. Methods:Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min−1·kg−1 peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90–95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA. Results: HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30′, 60′, 180′) and HVT (d3, 0′, 60′). Conclusion: Results of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues. PMID:27014090

  9. Higher Dose of Mycophenolate Mofetil Reduces Acute Graft-Versus-Host Disease in Reduced Intensity Conditioning Double Umbilical Cord Blood Transplantation

    PubMed Central

    Bejanyan, Nelli; Rogosheske, John; DeFor, Todd; Lazaryan, Aleksandr; Esbaum, Kelli; Holtan, Shernan; Arora, Mukta; MacMillan, Margaret L.; Weisdorf, Daniel; Jacobson, Pamala; Wagner, John; Brunstein, Claudio G.

    2016-01-01

    Mycophenolate mofetil (MMF) is frequently used in hematopoietic cell transplantation (HCT) for graft-versus-host disease (GVHD) prophylaxis and to facilitate engraftment. We previously reported that a higher level of mycophenolic acid can be achieved with an MMF dose of 3 g/day as compared to 2g/day. Here, we retrospectively compared clinical outcomes of reduced intensity conditioning (RIC) double umbilical cord blood (dUCB) HCT recipients receiving cyclosporine A with MMF 2g (n=93) vs. 3g (n=175) daily. Multiple regression analysis adjusted for ATG in the conditioning revealed that MMF 3g/day led to a 49% relative risk reduction in grade II–IV acute GVHD rate (RR=0.51, 95%CI 0.36–0.72; p<0.01). However, the higher MMF dose was not protective for chronic GVHD. Additionally, MMF dose was not an independent predictor of neutrophil engraftment, treatment-related mortality at 6 months, or 2-year post-transplant disease relapse, disease-free survival, or overall survival. Higher MMF dose did not increase risk of infectious complications and infection-related mortality was similar for both MMF doses. Our data indicate that MMF 3g/day reduces the risk of acute GVHD without affecting other clinical outcomes and should be used for GVHD prophylaxis after RIC dUCBT. PMID:25655791

  10. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

    PubMed

    Brissot, Eolia; Cahu, Xavier; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Peterlin, Pierre; Le Bourgeois, Amandine; Harousseau, Jean-Luc; Milpied, Noel; Bene, Marie-Christine; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

    2015-04-01

    In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.

  11. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

    PubMed

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

    2016-03-01

    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  12. High Frequency Migraine Is Associated with Lower Acute Pain Sensitivity and Abnormal Insula Activity Related to Migraine Pain Intensity, Attack Frequency, and Pain Catastrophizing

    PubMed Central

    Mathur, Vani A.; Moayedi, Massieh; Keaser, Michael L.; Khan, Shariq A.; Hubbard, Catherine S.; Goyal, Madhav; Seminowicz, David A.

    2016-01-01

    Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful), we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds nor in pre-scan pain ratings to mildly painful thermal stimuli, patients did have aberrant suprathreshold nociceptive processing. Brain imaging showed that, compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain vs. mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS); bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA) and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula, associated with indices

  13. Ten-day decitabine as initial therapy for newly diagnosed patients with acute myeloid leukemia unfit for intensive chemotherapy.

    PubMed

    Bhatnagar, Bhavana; Duong, Vu H; Gourdin, Theodore S; Tidwell, Michael L; Chen, Ching; Ning, Yi; Emadi, Ashkan; Sausville, Edward A; Baer, Maria R

    2014-07-01

    We retrospectively reviewed outcomes in 45 previously untreated patients with acute myeloid leukemia (AML) considered unfit for chemotherapy who were treated with 10-day courses of decitabine 20 mg/m(2) daily outside of a clinical trial, with no cut-offs for organ function or performance status (PS). Nineteen had Eastern Cooperative Group performance status (ECOG PS) ≥ 2, and 39 had ≥ 2 comorbidities. Fourteen patients (31%) achieved complete remission (CR) and five (11%) CR with incomplete count recovery, for an overall response rate of 42%, after a median of 2 (range, 1-4) courses. The only pretreatment characteristic that differed significantly between responders and non-responders was percent marrow blasts (median 42% vs. 65%; p = 0.01). Median overall survival was 9.0 months; it was 19.4 and 2.3 months for responders and non-responders, respectively (p < 0.001). Thus 10-day decitabine therapy has efficacy in patients with AML considered unfit for chemotherapy, and may serve as a backbone for the addition of other novel agents. PMID:24144313

  14. Characterizing the affective responses to an acute bout of moderate-intensity exercise among outpatients with schizophrenia.

    PubMed

    Duncan, Markus J; Faulkner, Guy; Remington, Gary; Arbour-Nicitopoulos, Kelly

    2016-03-30

    In addition to offering many physical health benefits, exercise may help improve mental health among individuals with schizophrenia through regulating affect. Therefore, the purpose of this study is to characterize affective responses experienced before, during and after a 10-min bout of exercise versus passive sitting among individuals with schizophrenia. A randomized crossover design compared affect related to feelings of pleasure and arousal at baseline, 6-min into the task, immediately post-task, and 10min post-task to sitting. Thirty participants enroled in the study; 28 participants completed the study. Separate mixed model analyses of variance were conducted for pleasure and arousal, with test order as the between-subject factor, and time and task as within-subject factors. For pleasure, a significant main effect for time and a time x task interaction effect emerged. Post-hoc Bonferroni corrected t-tests (α=.0125) revealed significant differences between pleasure at baseline and both immediately post-task and 10min post-task. No other main effects or interactions emerged. Individuals with schizophrenia derive acute feelings of pleasure from exercise. Thus, exercise may provide a method of regulating affect to improve mental health. Future studies should examine the links between affective responses to health behaviours such as long-term adherence to exercise within this population.

  15. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    PubMed

    Marshall, G M; Dalla Pozza, L; Sutton, R; Ng, A; de Groot-Kruseman, H A; van der Velden, V H; Venn, N C; van den Berg, H; de Bont, E S J M; Maarten Egeler, R; Hoogerbrugge, P M; Kaspers, G J L; Bierings, M B; van der Schoot, E; van Dongen, J; Law, T; Cross, S; Mueller, H; de Haas, V; Haber, M; Révész, T; Alvaro, F; Suppiah, R; Norris, M D; Pieters, R

    2013-07-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)-Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.

  16. SOCS-3 is involved in the downregulation of the acute insulin-like effects of growth hormone in rat adipocytes by inhibition of Jak2/IRS-1 signaling.

    PubMed

    Ridderstråle, M; Amstrup, J; Hilton, D J; Billestrup, N; Tornqvist, H

    2003-03-01

    One of the long-term effects of growth hormone (GH) in adipocytes is to maintain a state of refractoriness to insulin-like effects, a refractoriness which otherwise declines within a few hours of GH starvation. Here, we examined differences in GH signaling and the possible role for the recently identified family of suppressors of cytokine signaling (SOCS) proteins in the transition between the refractory and the responsive states in rat adipocytes. The ability of GH to stimulate lipogenesis and tyrosine phosphorylation of the GH receptor (GHR), Janus kinase 2 (Jak2), insulin receptor substrate-1 (IRS-1) and -2 (IRS-2) was greatly reduced in refractory as compared to responsive primary rat adipocytes. However, phosphorylation of Signal Transducer and Activator of Transcription 5 (Stat5) was not affected. SOCS-3 and CIS mRNA levels were significantly higher in refractory compared to responsive cells and could be induced by GH, whereas the level of SOCS-2 mRNA was unchanged. With overexpression of GHR, Jak2 and IRS-1 along with each of these SOCS proteins in human A293 cells, we could demonstrate that both SOCS-1 and SOCS-3 completely inhibited the GH-stimulated tyrosine phosphorylation of IRS-1, whereas SOCS-2 and CIS did not. Our data suggest that GH induces refractoriness to the insulin-like effects in a negative-feedback manner by inhibiting GH-induced GHR/Jak2/IRS-1/IRS-2 phosphorylation through upregulation of SOCS-3, which almost completely blocks Jak2 activation.

  17. Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year-old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT).

    PubMed

    Poiré, Xavier; Labopin, Myriam; Cornelissen, Jan J; Volin, Liisa; Richard Espiga, Carlos; Veelken, J Hendrik; Milpied, Noël; Cahn, Jean-Yves; Yacoub-Agha, Ibrahim; van Imhoff, Gustaaf W; Michallet, Mauricette; Michaux, Lucienne; Nagler, Arnon; Mohty, Mohamad

    2015-08-01

    Acute myeloid leukemia with monosomal karyotype (MK AML) carries a very poor prognosis, even after allogeneic stem cell transplantation (SCT). However, SCT remains the only curative option in this high-risk population. Because myeloablative conditioning regimen (MAC) is associated with less relapse, we hypothesized that more intensive conditioning regimen might be beneficial for MK AML patients. We reviewed 303 patients over age 45 diagnosed with either de novo or secondary MK AML. One hundred and five patients received a MAC and 198 a reduced-intensity conditioning (RIC). The median age at SCT was 57-year-old, significantly lower in the MAC (53-year-old) than in the RIC group (59-year-old). The median follow-up was 42 months (range, 3 - 156 months). The 3-year overall survival (OS), leukemia-free survival (LFS), and relapse rate (RR) were not significantly different between both groups with overall values of 34%, 29%, and 51%, respectively. On the contrary, the 3-year nonrelapse mortality (NRM) was significantly higher in MAC recipients (28%) compared with RIC patients (16%, P = 0.004). The incidence of Grades II to IV acute graft-versus-host disease (GvHD) was significantly higher after a MAC (30.5%) than after a RIC (19.3%, P = 0.02). That of chronic GvHD was comparable between both groups (35%) and did not impact on LFS. Interestingly, within our MK AML cohort, hypodiploidy was significantly associated with worse outcomes. Due to reduced toxicity and comparable OS, LFS, and RR, RIC appears as a good transplant option in the very high-risk population, including older patients, diagnosed with MK AML.

  18. Insulin Injection

    MedlinePlus

    ... to control blood sugar in people who have type 1 diabetes (condition in which the body does not make insulin and therefore cannot control the amount of sugar in the blood) or in people who have type 2 diabetes (condition in which the blood sugar ...

  19. What Are the Safety Considerations for Insulin Control for Athletes?

    ERIC Educational Resources Information Center

    McDaniel, Larry W.; Olson, Sara; Gaudet, Laura; Jackson, Allen

    2010-01-01

    Athletes diagnosed with diabetes may have difficulty with their blood sugar levels fluctuating during intense exercise. Considerations for athletes with insulin concerns may range anywhere from exercise rehabilitation to the use of an automatic insulin pump. The automatic insulin pump is a small battery-operated device about the size of a pager.…

  20. Incidence and risk factors for Central Nervous System thrombosis in paediatric acute lymphoblastic leukaemia during intensive asparaginase treatment: a single-centre cohort study.

    PubMed

    Duarte, Ximo; Esteves, Susana; Neto, Ana M; Pereira, Filomena

    2016-07-01

    Central Nervous System (CNS) thrombosis is a complication of acute lymphoblastic leukaemia (ALL) treatment that is potentially associated with significant morbidity and neurological sequelae. Its presumably multifactorial aetiology is poorly characterized. We conducted a single-centre, retrospective cohort study on 346 ALL paediatric patients (1-16 years old) treated with asparaginase intensive Dana Farber Cancer Institute (DFCI) protocols from 1998 to 2011. The incidence, risk factors and outcome of CNS thrombosis were evaluated. CNS thrombosis occurred in 3·8% (13/346) of the patients (95% confidence interval 2·0-6·3%). Twelve events were diagnosed during intensification, all of which resolved within 2 weeks without neurological sequelae or significant impact in survival. Obesity (body mass index above 95th percentile) and asparaginase formulation were the only factors associated with CNS thrombosis, with an increase in the odds of event in obese patients [odds ratio (OR) = 3·37; P = 0·064] and a reduction in patients receiving Erwinia asparaginase (OR = 0·12; P = 0·018). No association could be demonstrated for age, gender, DFCI risk-group, ALL phenotype, steroid or doxorubicin use, central venous line use or CNS radiotherapy. CNS thrombosis is a rare but manageable adverse event without significant sequelae or detrimental effects in survival. Increased awareness is recommended in obese patients particularly during intensive asparaginase use. PMID:27018199

  1. Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Pître, M; Nadeau, A; Bachelard, H

    1996-10-01

    The insulin-mediated vasodilator effect has been proposed as an important physiological determinant of insulin action on glucose disposal in normotensive humans. The present study was designed to further examine the acute regional hemodynamic effects of insulin in different vascular beds and to explore the relationships between insulin vascular effects and insulin sensitivity during euglycemic hyperinsulinemic clamps in conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and regional blood flows. In WKY rats, the euglycemic infusion of insulin (4 and 16 mU.kg-1.min-1) causes vasodilations in renal and hindquarter vascular beds but no changes in mean blood pressure, heart rate, or superior mesenteric vascular conductance. In contrast, in SHR, the same doses of insulin produce vasoconstrictions in superior mesenteric and hindquarter vascular beds and, at high doses, increase blood pressure. Moreover, at the lower dose of insulin tested, we found a reduction in the insulin sensitivity index in the SHR compared with the WKY rats. The present findings provide further evidence for an association between insulin sensitivity and insulin-mediated hemodynamic responses.

  2. Anti-insulin antibody test

    MedlinePlus

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

  3. Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

    ClinicalTrials.gov

    2016-10-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  4. Efficacy of acute caffeine ingestion for short-term high-intensity exercise performance: a systematic review.

    PubMed

    Astorino, Todd A; Roberson, Daniel W

    2010-01-01

    Caffeine is the most widely used drug in the world, commonly ingested in coffee, tea, soda, and energy drinks. Its ability to enhance muscular work has been apparent since the early 1900s. Caffeine typically increases endurance performance; however, efficacy of caffeine ingestion for short-term high-intensity exercise is equivocal, which may be explained by discrepancies in exercise protocols, dosing, and subjects' training status and habitual caffeine intake found across studies. The primary aim of this review is to critically examine studies that have tested caffeine's ability to augment performance during exercise dependent on nonoxidative metabolism such as sprinting, team sports, and resistance training. A review of the literature revealed 29 studies that measured alterations in short-term performance after caffeine ingestion. Each study was critically analyzed using the Physiotherapy Evidence Database (PEDro) scale. The mean PEDro score was 7.76 +/- 0.87. Eleven of 17 studies revealed significant improvements in team sports exercise and power-based sports with caffeine ingestion, yet these effects were more common in elite athletes who do not regularly ingest caffeine. Six of 11 studies revealed significant benefits of caffeine for resistance training. Some studies show decreased performance with caffeine ingestion when repeated bouts are completed. The exact mechanism explaining the ergogenic effect of caffeine for short-term exercise is unknown.

  5. Efficacy of acute caffeine ingestion for short-term high-intensity exercise performance: a systematic review.

    PubMed

    Astorino, Todd A; Roberson, Daniel W

    2010-01-01

    Caffeine is the most widely used drug in the world, commonly ingested in coffee, tea, soda, and energy drinks. Its ability to enhance muscular work has been apparent since the early 1900s. Caffeine typically increases endurance performance; however, efficacy of caffeine ingestion for short-term high-intensity exercise is equivocal, which may be explained by discrepancies in exercise protocols, dosing, and subjects' training status and habitual caffeine intake found across studies. The primary aim of this review is to critically examine studies that have tested caffeine's ability to augment performance during exercise dependent on nonoxidative metabolism such as sprinting, team sports, and resistance training. A review of the literature revealed 29 studies that measured alterations in short-term performance after caffeine ingestion. Each study was critically analyzed using the Physiotherapy Evidence Database (PEDro) scale. The mean PEDro score was 7.76 +/- 0.87. Eleven of 17 studies revealed significant improvements in team sports exercise and power-based sports with caffeine ingestion, yet these effects were more common in elite athletes who do not regularly ingest caffeine. Six of 11 studies revealed significant benefits of caffeine for resistance training. Some studies show decreased performance with caffeine ingestion when repeated bouts are completed. The exact mechanism explaining the ergogenic effect of caffeine for short-term exercise is unknown. PMID:19924012

  6. Sliding scale insulin use: myth or insanity?

    PubMed

    Umpierrez, Guillermo E; Palacio, Andres; Smiley, Dawn

    2007-07-01

    Inpatient hyperglycemia in people with or without diabetes is associated with an increased risk of complications and mortality, a longer hospital stay, a higher admission rate to the intensive care unit, and higher hospitalization costs. Despite increasing evidence that supports intensive glycemic control in hospitalized patients, blood glucose control continues to be challenging, and sliding scale insulin coverage, a practice associated with limited therapeutic success, continues to be the most frequent insulin regimen in hospitalized patients. Sliding scale insulin has been in use for more than 80 years without much evidence to support its use as the standard of care. Several studies have revealed evidence of poor glycemic control and deleterious effects in sliding scale insulin use. To understand its wide use and acceptance, we reviewed the origin, advantages, and disadvantages of sliding scale insulin in the inpatient setting.

  7. Adding sprints to continuous exercise at the intensity that maximises fat oxidation: implications for acute energy balance and enjoyment.

    PubMed

    Crisp, Nicole A; Fournier, Paul A; Licari, Melissa K; Braham, Rebecca; Guelfi, Kym J

    2012-09-01

    The objective was to examine the effect of adding sprints to continuous exercise at the intensity that maximises fat oxidation (Fat(max)) on energy expenditure, substrate oxidation, enjoyment and post-exercise energy intake in boys. Nine overweight and nine normal weight boys (8-12 years) attended the laboratory on three mornings. First, body anthropometrics, peak aerobic capacity and Fat(max) were assessed. On the remaining two sessions, resting metabolic rate was determined before participants completed 30 min of either continuous cycling at Fat(max) (MOD) or sprint interval exercise consisting of continuous cycling at Fat(max) interspersed with four-second maximal sprints every two minutes (SI). Energy expenditure and substrate oxidation were measured during exercise and for 30 min post-exercise, while participants completed a modified Physical Activity Enjoyment Scale (PACES). This was followed by a buffet-like breakfast to measure post-exercise energy intake. Fat oxidation rate was similar between groups and protocols (P>0.05). Both groups expended more energy with SI compared to MOD, resulting from increased carbohydrate oxidation (P<0.05), which was not compensated by increased energy intake. Participants indicated that they preferred SI more than MOD, although there was no significant difference in PACES score between the protocols (P>0.05). In summary, the addition of short sprints to continuous exercise at Fat(max) increased energy expenditure without compromising fat oxidation or stimulating increased post-exercise energy intake. The boys preferred SI and did not perceive it to be any harder than MOD, indicating that sprint interval exercise should be considered in exercise prescription for this population.

  8. The acute impact of ingestion of breads of varying composition on blood glucose, insulin and incretins following first and second meals.

    PubMed

    Najjar, Anita Mofidi; Parsons, Patricia M; Duncan, Alison M; Robinson, Lindsay E; Yada, Rickey Y; Graham, Terry E

    2009-02-01

    Structural characteristics and baking conditions influence the metabolic responses to carbohydrate-containing foods. We hypothesized that consumption of whole wheat or sourdough breads would have a favourable effect on biomarkers of glucose homeostasis after first and second meals, compared with those for white bread. Ten overweight volunteers consumed 50 g available carbohydrate of each of the four breads (white, whole wheat, sourdough, whole wheat barley) followed 3 h later by a standard second meal. Blood was sampled for 3 h following bread ingestion and a further 2 h after the second meal for determination of glucose, insulin, paracetamol (indirect marker of gastric emptying), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Glucose and GLP-1 responses to sourdough bread were lower (P < 0.05) than whole wheat and whole wheat barley breads. Glucose area under the curve (AUC) for sourdough bread was lower than those for whole wheat (P < 0.005) and whole wheat barley (P < 0.03) breads for the entire study. GIP AUC after sourdough bread ingestion was lower compared to white (P < 0.004) and whole wheat barley (P < 0.002) breads following the second meal. There were no significant differences in insulin and paracetamol concentrations among the test breads. Ultra-fine grind whole wheat breads did not result in postprandial responses that were lower than those of white bread, but sourdough bread resulted in lower glucose and GLP-1 responses compared to those of these whole wheat breads following both meals.

  9. Insulin-dependent (type I) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Insulin-dependent (type I) diabetes mellitus is a chronic disease characterized by hyperglycemia, impaired metabolism and storage of important nutrients, evidence of autoimmunity, and long-term vascular and neurologic complications. Insulin secretory function is limited. Cell membrane binding is not primarily involved. The goal of treatment is to relieve symptoms and to achieve blood glucose levels as close to normal as possible without severe hypoglycemia. However, even with education and self-monitoring of the blood glucose level, attaining recommended target values (plasma glucose level less than 8.0 mmol/L before main meals for adults) remains difficult. Human insulin offers no advantage in glycemic control but is important in the management and prevention of immune-related clinical problems (e.g., injection-site lipoatrophy, insulin resistance and allergy) associated with the use of beef or pork insulin. Therapy with one or two injections per day of mixed short-acting or intermediate-acting insulin preparations is a compromise between convenience and the potential for achieving target plasma glucose levels. Intensive insulin therapy with multiple daily injections or continuous infusion with an insulin pump improves mean glycated hemoglobin levels; however, it increases rates of severe hypoglycemia and has not been shown to decrease the incidence of clinically significant renal, retinal or neurologic dysfunction. Future prospects include automated techniques of insulin delivery, immunosuppression to preserve endogenous insulin secretion and islet transplantation. PMID:1933705

  10. Insulin pumps.

    PubMed

    Pickup, J

    2010-02-01

    Insulin pump therapy is now more than 30 years old, and is an established part of the routine care of selected people with type 1 diabetes. Nevertheless, there are still significant areas of concern, particularly how pumps compare with modern injection therapy, whether the increasingly sophisticated pump technologies like onboard calculators and facility for computer download offer any real benefit, and whether we have a consensus on the clinical indications. The following papers offer some insight into these and other current questions.

  11. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    SciTech Connect

    Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2012-05-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I-III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade {>=}2 GI toxicity and the volume of bowel receiving {>=}45 Gy (V{sub 45}) using the logistic model. Results: Twenty-three patients (46%) had Grade {>=}2 GI toxicity. The mean (SD) V{sub 45} was 143 mL (99). The mean V{sub 45} values for patients with and without Grade {>=}2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V{sub 45} >150 mL. The proportion of patients with Grade {>=}2 GI toxicity with and without V{sub 45} >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and {gamma} were 161 mL (95% confidence interval [CI] 60-399) and 0.31 (95% CI 0.04-0.63), respectively. On multivariable logistic regression, increased V{sub 45} was associated with an increased odds of Grade {>=}2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04-4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V{sub 45} is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V{sub 45} could reduce the risk of Grade {>=}2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  12. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance.

    PubMed

    McNay, Ewan C; Ong, Cecilia T; McCrimmon, Rory J; Cresswell, James; Bogan, Jonathan S; Sherwin, Robert S

    2010-05-01

    Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.

  13. Low CD34 Dose is Associated with Poor Survival after Reduced Intensity Conditioning Allogeneic Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

    PubMed Central

    Törlén, Johan; Ringdén, Olle; Le Rademacher, Jennifer; Batiwalla, Minoo; Chen, Junfang; Erkers, Tom; Ho, Vincent; Kebriaei, Partow; Keever-Taylor, Carolyn; Kindwall-Keller, Tamila; Lazarus, Hillard M.; Laughlin, Mary J.; Lill, Michael; O’Brien, Tracey; Perales, Miguel-Angel; Rocha, Vanderson; Savani, Bipin N.; Szwajcer, David; Valcarcel, David; Eapen, Mary

    2014-01-01

    Reduced intensity conditioning/non-myeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34+ dose to be important for transplant-outcome using myeloablative conditioning. The role of CD34+ dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced intensity conditioning/non-myeloablative HCT. We studied 1,054 patients aged 45–75 years, with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) transplanted between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 106 CD34+/kg were associated with higher non-relapse mortality (HR 2.03, p=0.001), overall mortality (HR 1.48, p=0.008), and lower neutrophil (OR 0.76, p=0.03) and platelet (OR 0.76, p=0.03) recovery. PBPC from unrelated donors with CD34+ dose <6 × 106 CD34+/kg were also associated with higher non-relapse (HR 1.38, p=0.02) and overall mortality (HR 1.20, p=0.05). In contrast to reports after myeloablative HCT, CD34+ dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34+ dose >4 × 106 CD34+/kg and >6 × 106 CD34+/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively. PMID:24892261

  14. Reversible laminar signal intensity in deep cortical gray matter in T1-weighted images and FLAIR after mild acute hyperammonemic hepatic encephalopathy.

    PubMed

    Treusch, N A; van de Loo, S; Hattingen, E

    2012-12-01

    Soporific acute hyperammonemic hepatic encephalopathy (aHE) can induce considerable changes in cerebral white and gray matter. This report describes a patient in the subacute phase of aHE grade I without disturbed consciousness and with reversible fine laminar cortical involvement on magnetic resonance imaging (MRI). The 59-year-old patient had esophageal varices bleeding due to primary biliary cirrhosis (ammonium blood level: 140 mmoL/L) and presented with sensory Jacksonian seizures, dysarthria, and increased drowsiness and fatigue. MRI revealed patchy hyperintense (T2-weighted, T2w) white-matter lesions and bilateral signal intensities in the striatum (T1w). During a rise of ammonium blood level to 220 mmoL/L, the patient had increased drowsiness, persistent dysarthria and mild temporary hemiparesis without loss of consciousness. Two weeks later, the patient was asymptomatic and blood ammonium level had reverted to normal value. MRI at that time revealed bihemispheric fine laminar subcortical hyperintensities on T2w and fluid-attenuated inversion recovery (FLAIR) imaging, and partially on T1w sequences, with no swelling or restricted diffusion; the hyperintensities were fully reversible a month later. Such a distinct cortical signal increase not only on T2w images, but also on T1w, in a patient after a mild form of aHE is a new MR finding.

  15. Giving an insulin injection

    MedlinePlus

    ... want. Put the needle into and through the rubber top of the insulin bottle. Push the plunger ... longer-acting insulin. Put the needle into the rubber top of that insulin bottle. Push the plunger ...

  16. Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

    PubMed Central

    El-Naga, Reem N.; Mahran, Yasmen F.

    2016-01-01

    Nephrotoxicity associated with the clinical use of the anticancer drug cisplatin is a limiting problem. Thus, searching for new protective measures is required. Indole-3-carbinol is a powerful anti-oxidant, anti-inflammatory and anti-tumor agent. The present study aimed to investigate the potential protective effect of indole-3-carbinol against cisplatin-induced acute nephrotoxicity in rats. Rats were pre-treated with 20 mg/kg indole-3-carbinol orally before giving cisplatin (7 mg/kg). Cisplatin-induced acute nephrotoxicity was demonstrated where relative kidney weight, BUN and serum creatinine were significantly increased. Increased oxidative stress was evident in cisplatin group where GSH and SOD tissue levels were significantly depleted. Also, lipid peroxidation and NOX-1 were increased as compared to the control. Additionally, renal expression of pro-inflammatory mediators was induced by cisplatin. Cisplatin-induced cell death was shown by increased caspase-3 and decreased expression of EGF, IGF-1 and IGF-1 receptor. Nephrotoxicity, oxidative stress, inflammation and apoptotic effects induced by cisplatin were significantly ameliorated by indole-3-carbinol pre-treatment. Besides, the role of CGRP in cisplatin-induced nephrotoxicity was explored. Furthermore, cisplatin cytotoxic activity was significantly enhanced by indole-3-carbinol pre-treatment in vitro. In conclusion, indole-3-carbinol provides protection against cisplatin-induced nephrotoxicity. Also, reduced expression of CGRP may play a role in the pathogenesis of cisplatin-induced renal injury. PMID:27417335

  17. Clinical utility of insulin and insulin analogs

    PubMed Central

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  18. [Inhaled insulin, new perspective for insulin therapy].

    PubMed

    Radermecker, R P; Sélam, J L

    2005-01-01

    Since the discovery of insulin and its use in diabetes care, patients, physicians and nurses dream of another way of insulin administration than the subcutaneous injections actually used. Different types of insulin administration have been evaluated and, particularly, that using the pulmonary route. The use of this alternative method to deliver insulin may result in improved patient compliance, facilitate intensified therapies and avoid the delay of initiating insulin administration because patient's reluctance. The different insulin pulmonary delivering devices actually studied will be presented. Preliminary data comparing this way of administration and the subcutaneous injection of human regular insulin are good, but sufficient data comparing inhaled insulin with the new short-acting insulin analogues are not yet available. Among various difficulties of the pulmonary insulin delivery, the finding of an effective promoter, capable of increasing the bioavailability of insulin, is a crucial issue. The cost of such insulin administration might also be a problem. Finally, careful studies concerning the safety of this kind of administration, particularly potential long-term pulmonary toxicity, are mandatory. Nevertheless, inhaled insulin is an attractive topic in which most important pharmaceutical companies are currently involved.

  19. Massive insulin overdose managed by monitoring daily insulin levels.

    PubMed

    Mork, Tyler A; Killeen, Colin T; Patel, Neel K; Dohnal, James M; Karydes, Harry C; Leikin, Jerrold B

    2011-09-01

    We present a case of a significant insulin overdose that was managed by monitoring daily plasma insulin levels. A 39-year-old male with poorly controlled diabetes mellitus presented to the Emergency Department via emergency medical services after an attempted suicide by insulin overdose. In the attempted suicide, he injected 800 U of insulin lispro and 3800 U of insulin glargine subcutaneously over several parts of his abdomen. The patient was conscious upon arrival to the emergency department. His vital parameters were within normal range. The abdominal examination, in particular, was nonfocal and showed no evidence of hematomas. He was awake, alert, conversant, tearful, and without any focal deficits. An infusion of 10% dextrose was begun at 100 mL/h with hourly blood glucose (BG) checks. The patient was transferred to the intensive care unit where his BG began to decrease and fluctuate between 50 and 80 mg/dL, and the rate of 10% dextrose was increased to 200 mL/h where it was maintained for the next 48 hours. The initial plasma insulin level was found to be 3712.6 uU/mL (reference range 2.6-31.1 uU/mL). At 10 hours, this had decreased to 1582.1 uU/ml. On five occasions, supplemental dextrose was needed when the BG was <70 mg/dL. Thirty-four hours after admission, the plasma insulin level was 724.8 uU/mL. Fifty-eight hours after admission, the plasma insulin level was 321.2 uU/mL, and the 10% dextrose infusion was changed to 5% dextrose solution at 200 mL/h. The plasma insulin levels continued to fall daily to 112.7 uU/mL at 80 hours and to 30.4 uU/mL at 108 hours. He was transferred to an inpatient psychiatric facility 109 hours after initial presentation. Monitoring daily plasma insulin levels and adjusting treatment on a day-to-day basis in terms of basal glucose infusions provides fewer opportunities for episodic hypoglycemia. Furthermore, it was easier to predict daily glucose requirements and eventual medical clearance based on the plasma levels.

  20. Study Design for the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care) Trial: A Double-blind Randomized Controlled Trial of Intravenous Glucose, Insulin, and Potassium (GIK) for Acute Coronary Syndromes in Emergency Medical Services

    PubMed Central

    Selker, Harry P.; Beshansky, Joni R.; Griffith, John L.; D’Agostino, Ralph B.; Massaro, Joseph M.; Udelson, James E.; Rashba, Eric J.; Ruthazer, Robin; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves D.; Atkins, James M.; Sayah, Assaad J.; Aufderheide, Tom P.; Rackley, Charles E.; Opie, Lionel H.; Lambrew, Costas T.; Cobb, Leonard A.; MacLeod, Bruce A.; Ingwall, Joanne S.; Zalenski, Robert J.; Apstein, Carl S.

    2014-01-01

    Background Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris (UAP) to acute myocardial infarction (AMI), and MI size. However, trials of hospital administration of IV GIK to patients with ST elevation MI (STEMI) have generally not shown favorable effects, possibly due to the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies. Objective The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK 1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and 2) administered in prehospital emergency medical service (EMS) settings, rather than later, in hospitals, following emergency department evaluation. Design IMMEDIATE was an EMS-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the US which enrolled 911 participants. Eligible were patients age 30 or older for whom a paramedic performed a 12-lead electrocardiogram (ECG)to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based ACI-TIPI (acute cardiac ischemia time-insensitive predictive instrument) indicated a > 75% probability of ACS, and/or the TPI (thrombolytic predictive instrument) indicated presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Pre-specified were the primary endpoint of progression of ACS to infarction, and as major secondary endpoints

  1. Concentrated insulins: the new basal insulins

    PubMed Central

    Lamos, Elizabeth M; Younk, Lisa M; Davis, Stephen N

    2016-01-01

    Introduction Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered This review highlights the published reports of the pharmacokinetic (PK) and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration. PMID:27022271

  2. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    SciTech Connect

    Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van; Heemsbergen, Wilma D.

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  3. [Interest of ambulatory simplified acute physiology score (ASAPS) applied to patients admitted in an intensive care unit of an infectious diseases unit in Dakar].

    PubMed

    Dia, N M; Diallo, I; Manga, N M; Diop, S A; Fortes-Deguenonvo, L; Lakhe, N A; Ka, D; Seydi, M; Diop, B M; Sow, P S

    2015-08-01

    The evaluation of patients by a scale of gravity allows a better categorization of patients admitted in intensive care unit (ICU). Our study had for objective to estimate interest of Ambulatory Simplified Acute Physiologic Score (ASAPS) applied to patients admitted in ICU of infectious diseases department of FANN hospital. It was about a descriptive and analytical retrospective study, made from the data found in patients' files admitted into the USI infectious diseases department of FANN hospital in Dakar, from January 1(st), 2009 till December 31st, 2009.The data of 354 patients' files were analyzed. The sex-ratio was 1.77 with an average age of 37.6 years ± 19.4 years old [5-94 years]. The majority of the patients were unemployed paid (39.6%). The most frequent failures were the following ones: neurological (80.5%), cardio-respiratory (16.7%). The average duration of stay was 6.2 days ± 8.2 days going of less than 24 hours to more than 10 weeks. The deaths arose much more at night (53.1%) than in the daytime (46.9%) and the strongest rate of death was recorded in January (61.5%), most low in October (26.7%). The global mortality was 48.3%. The rate of lethality according to the highest main diagnosis was allocated to the AIDS (80.5%). The average ambulatory simplified acute physiology score was 5.3 ± 3.6 with extremes of 0 and 18. The deaths in our series increased with this index (p = 0.000005). The female patients had a rate of lethality higher than that of the men people, 55.5% against 44.2% (p = 0.03). In spite of a predictive score of a high survival (ASAPS < 8), certain number of patients died (n = 105) that is 61.4% of the deaths. The metabolic disturbances, hyperleukocytosis or leukopenia when realised, the presence of a chronic disease, seemed also to influence this lethality. ASAPS only, although interesting, would not good estimate the gravity of patients, where from the necessity thus of a minimum biological balance sheet. It seems better adapted

  4. Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission.

    PubMed

    Magenau, John M; Braun, Thomas; Reddy, Pavan; Parkin, Brian; Pawarode, Attaphol; Mineishi, Shin; Choi, Sung; Levine, John; Li, Yumeng; Yanik, Gregory; Kitko, Carrie; Churay, Tracey; Frame, David; Riwes, Mary Mansour; Harris, Andrew; Bixby, Dale; Couriel, Daniel R; Goldstein, Steven C

    2015-06-01

    The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34-0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.

  5. Initial Sequential Organ Failure Assessment score versus Simplified Acute Physiology score to analyze multiple organ dysfunction in infectious diseases in Intensive Care Unit

    PubMed Central

    Nair, Remyasri; Bhandary, Nithish M.; D’Souza, Ashton D.

    2016-01-01

    Aims: To investigate initial Sequential Organ Failure Assessment (SOFA) score of patients in Intensive Care Unit (ICU), who were diagnosed with infectious disease, as an indicator of multiple organ dysfunction and to examine if initial SOFA score is a better mortality predictor compared to Simplified Acute Physiology Score (SAPS). Materials and Methods: Hospital-based study done in medical ICU, from June to September 2014 with a sample size of 48. Patients aged 18 years and above, diagnosed with infectious disease were included. Patients with history of chronic illness (renal/hepatic/pulmonary/  cardiovascular), diabetes, hypertension, chronic obstructive pulmonary disease, heart disease, those on immunosuppressive therapy/chemoradiotherapy for malignancy and patients in immunocompromised state were excluded. Blood investigations were obtained. Six organ dysfunctions were assessed using initial SOFA score and graded from 0 to 4. SAPS was calculated as the sum of points assigned to each of the 17 variables (12 physiological, age, type of admission, and three underlying diseases). The outcome measure was survival status at ICU discharge. Results: We categorized infectious diseases into dengue fever, leptospirosis, malaria, respiratory tract infections, and others which included undiagnosed febrile illness, meningitis, urinary tract infection and gastroenteritis. Initial SOFA score was both sensitive and specific; SAPS lacked sensitivity. We found no significant association between age and survival status. Both SAPS and initial SOFA score were found to be statistically significant as mortality predictors. There is significant association of initial SOFA score in analyzing organ dysfunction in infectious diseases (P < 0.001). SAPS showed no statistical significance. There was statistically significant (P = 0.015) percentage of nonsurvivors with moderate and severe dysfunction, based on SOFA score. Nonsurvivors had higher SAPS but was not statistically significant (P

  6. Cost of acute renal replacement therapy in the intensive care unit: results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Study

    PubMed Central

    2010-01-01

    Introduction Severe acute kidney injury (AKI) can be treated with either continuous renal replacement therapy (CRRT) or intermittent renal replacement therapy (IRRT). Limited evidence from existing studies does not support an outcome advantage of one modality versus the other, and most centers around the word use both modalities according to patient needs. However, cost estimates involve multiple factors that may not be generalizable to other sites, and, to date, only single-center cost studies have been performed. The aim of this study was to estimate the cost difference between CRRT and IRRT in the intensive care unit (ICU). Methods We performed a post hoc analysis of a prospective observational study among 53 centers from 23 countries, from September 2000 to December 2001. We estimated costs based on staffing, as well as dialysate and replacement fluid, anticoagulation and extracorporeal circuit. Results We found that the theoretic range of costs were from $3,629.80/day more with CRRT to $378.60/day more with IRRT. The median difference in cost between CRRT and IRRT was $289.60 (IQR 830.8-116.8) per day (greater with CRRT). Costs also varied greatly by region. Reducing replacement fluid volumes in CRRT to ≤ 25 ml/min (approximately 25 ml/kg/hr) would result in $67.20/day (23.2%) mean savings. Conclusions Cost considerations with RRT are important and vary substantially among centers. We identified the relative impact of four cost domains (nurse staffing, fluid, anticoagulation, and extracorporeal circuit) on overall cost differences, and hospitals can look to these areas to reduce costs associated with RRT. PMID:20346163

  7. Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients

    PubMed Central

    Dalboni, M A; Quinto, B M R; Grabulosa, C C; Narciso, R; Monte, J C; Durão, M; Rizzo, L; Cendoroglo, M; Santos, O P; Batista, M C

    2013-01-01

    Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of −308 G < A tumour necrosis factor (TNF)-α, −174 G > C interleukin (IL)-6 and −1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case–control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16–4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19–12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients. PMID:23607333

  8. Acute effects of a thermogenic nutritional supplement on energy expenditure and cardiovascular function at rest, during low-intensity exercise, and recovery from exercise.

    PubMed

    Ryan, Eric D; Beck, Travis W; Herda, Trent J; Smith, Abbie E; Walter, Ashley A; Stout, Jeffrey R; Cramer, Joel T

    2009-05-01

    The purpose of present study was to examine the acute effects of a thermogenic nutritional supplement on energy expenditure (EE) and cardiovascular function at rest, during low-intensity exercise, and recovery from exercise. Twenty-eight healthy sedentary participants (mean +/- SD; age, 22.3 +/- 1.9 years; body mass index, 24.0 +/- 3.7) volunteered for this randomized, double-blinded, placebo-controlled, crossover study. Each experimental trial was divided into 4 phases: (a) 30 minutes of initial resting, followed by the placebo or thermogenic nutritional supplementation, (b) 50 minutes of postsupplementation resting, (c) 60 minutes of treadmill walking (3.2-4.8 km x h), and (d) 50 minutes of postexercise recovery. Gas exchange variables measured by indirect calorimetry and heart rate (HR) were recorded during all 4 phases, blood pressure was only measured at rest, and rating of perceived exertion (RPE) was only recorded during exercise. EE and oxygen consumption rate (Vo2) were greater for the supplement than the placebo at 50 minutes after supplementation. Also, during the postsupplementation period, diastolic blood pressure (DBP) was higher at all time periods, whereas the respiratory exchange ratio (RER) was higher at 20 and 30 minutes for the supplement. During exercise, only Vo2 and minute ventilation (VE) were greater for the supplement than the placebo, with HR being less than the placebo at 20 minutes for the men. Postexercise EE, Vo2, systolic blood pressure (SBP), DBP, and HR (men only) at 10, 20, 30, and 50 minutes were greater for the supplement than the placebo. These findings indicated that the thermogenic nutritional supplement increased resting EE and exercise Vo2 with only minimal effects on blood pressure and HR and no meaningful effects on RER or RPE. These results suggested that the combination of thermogenic ingredients in this nutritional supplement may be useful to help maintain a negative caloric balance but may not influence substrate use

  9. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    PubMed Central

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  10. Survival pattern in patients with acute organophosphate poisoning on mechanical ventilation: A retrospective intensive care unit-based study in a tertiary care teaching hospital

    PubMed Central

    Ahmed, Syed M; Das, Bikramjit; Nadeem, Abu; Samal, Rajiv K

    2014-01-01

    Background and Aims: Organophosphorus (OP) compound poisoning is one of the most common poisonings in India. The aim of the study was to study the outcomes and predictors of mortality in patients with acute OP poisoning requiring mechanical ventilation. Methods: A retrospective study was conducted in the intensive care unit and 117 patients were included. Diagnosis was performed from the history taken either from the patient or from the patient's relatives. Demographic data, month of the year, mode of poisoning, common age group, duration of mechanical ventilation, time of starting pralidoxime (PAM), and mortality were recorded. Chi square test, Pearson correlation test, and multivariate binary logistic regression analysis was used. Data are presented as mean ± SD. Results: 91.86% (79/86) of cases were suicidal and remaining cases were accidental. Duration of mechanical ventilation varied from less than 48 hours to more than 7 days. Mortality rate was 33.3%, 7.2%, and 100% in those who required mechanical ventilation for more than 7 days, 5 to 7 days, and 2 to 4 days, respectively. Lag time was less than 6 hrs in 13 patients and all of them survived. 17.1% and 28.1% patients died in whom PAM was started 6 to 12 hrs and 13 to 24 hrs after poisoning, respectively. There was statistically significant positive correlation between lag time of starting of PAM with duration of mechanical ventilation and total dose of PAM (P < 0.0001). None of the predictors age, lag time, severity of poisoning, and duration of ventilation were independent predictors of death. Overall mortality rate was 18.6%. Conclusion: Mortality from OP compound poisoning is directly proportionate to the severity of poisoning, delay in starting PAM, and duration of mechanical ventilation. Death is not dependent on a single factor, rather contributory to these factors working simultaneously. PMID:24700893

  11. Radiolabeled Anti-CD45 Antibody with Reduced-Intensity Conditioning and Allogeneic Transplantation for Younger Patients with Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    PubMed Central

    Mawad, Raya; Gooley, Ted A.; Rajendran, Joseph G.; Fisher, Darrell R.; Gopal, Ajay K.; Shields, Andrew T.; Sandmaier, Brenda M.; Sorror, Mohamed L.; Deeg, H. Joachim; Storb, Rainer; Green, Damian J.; Maloney, David G.; Appelbaum, Frederick R.; Press, Oliver W.; Pagel, John M.

    2014-01-01

    We treated patients under age 50 years with 131I-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332–1,561 mCi of 131I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed Grade II graft-versus-host disease (GVHD), one patient developed Grade III GVHD, and no patients developed Grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of non-relapse mortality were observed in the first year after transplant. However, two patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplant, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using 131I-anti-CD45 antibody in addition to standard reduced intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse. PMID:24858425

  12. Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia.

    PubMed

    Aoki, Jun; Kanamori, Heiwa; Tanaka, Masatsugu; Yamasaki, Satoshi; Fukuda, Takahiro; Ogawa, Hiroyasu; Iwato, Koji; Ohashi, Kazuteru; Okumura, Hirokazu; Onizuka, Makoto; Maesako, Yoshitomo; Teshima, Takanori; Kobayashi, Naoki; Morishima, Yasuo; Hirokawa, Makoto; Atsuta, Yoshiko; Yano, Shingo; Takami, Akiyoshi

    2016-03-01

    Previous studies have repeatedly reported that increasing age is a significant risk factor for worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) among patients with acute myeloid leukemia (AML). However, more recent studies reported conflicting results regarding the association between age and outcomes in elderly patients. Therefore, we conducted a large-scale, nationwide retrospective study to examine the impact of age on outcomes of allo-HSCT with reduced intensity conditioning (RIC) for AML patients who were older than 50 years. Of the 757 patients, 89 patients (11.8%) were 50-54, 249 patients (32.9%) were 55-59, 301 patients (39.8%) were 60-64 and 118 patients (15.6%) were ≥65 years old. The 3-year overall survival (OS) (47.8, 45.2, 37.9, and 36.6% for patients aged 50-54, 55-59, 60-64, and ≥65 years, respectively, P = 0.24) and nonrelapse mortality (NRM) (24.0, 22.8, 29.2, and 27.6% for patients aged 50-54, 55-59, 60-64, and ≥65 years, respectively, P = 0.49) were not significantly different among the four age groups. Multivariate analysis revealed that increased age had no significant effect on OS or NRM after adjusting for covariates. These results suggested that advanced patient age is not a contraindication for RIC allo-HSCT in elderly AML patients. PMID:26663096

  13. Impact of cyclosporine levels on the development of acute graft versus host disease after reduced intensity conditioning allogeneic stem cell transplantation.

    PubMed

    García Cadenas, Irene; Valcarcel, David; Martino, Rodrigo; Piñana, J L; Barba, Pere; Novelli, Silvana; Esquirol, Albert; Garrido, Ana; Saavedra, Silvana; Granell, Miquel; Moreno, Carol; Briones, Javier; Brunet, Salut; Sierra, Jorge

    2014-01-01

    We analyze the impact of cyclosporine (CsA) levels in the development of acute graft-versus-host disease (aGVHD) after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC). We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10-444), 219 (54-656), 253 (53-910) and 224 (30-699) ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2-4 aGVHD for a cumulative incidence of 45% (95% CI 34-50%) at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P = 0.02) and development of grade 2-4 aGVHD (HR: 2.5, P < 0.01), while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P = 0.06). These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.

  14. [Effect of acute hypoxia on the intensity of free radical processes in the basal nuclei of the brain, and the rat behaviour in the open field test under conditions of altered photoperiod].

    PubMed

    Sopova, I Iu; Zamorskiĭ, I I

    2011-03-01

    The effect of acute hypoxia on the intensity of free radical processes in the basal nuclei (the nucleus caudatus, globus pallidus. nucleus accumbens. amygdaloid complex) of the brain, and the rat behaviour in the open field test has been studied under conditions of altered photoperiod. It has been shown that constant darkness levels the effect of acute hypoxia on the intensity of lipid peroxidation, preserves the activity of superoxide dismutase and catalase at a higher level, lowers the activity of glutathione peroxidase. Under light, the sensitivity of basal nuclei neurons to acute hypoxia is enhanced, the latter being reflected in intensification of lipid peroxidation at the expense of increased formation of dien conjugates. The activity of catalase at that considerably exceeds the level of even intact rats in all the structures. It has been established that an altered photoperiod modulates the effect of acute hypoxia on the parameters of rat's activity in the open field, the character of their change depending on the nature of a photophase change.

  15. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials.

    PubMed

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S; Reddy-Luthmoodoo, Medini; Natoli, Alaina K; Owen, Neville; Dunstan, David W; Kingwell, Bronwyn A

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  16. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials

    PubMed Central

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S.; Reddy-Luthmoodoo, Medini; Natoli, Alaina K.; Owen, Neville; Dunstan, David W.; Kingwell, Bronwyn A.

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  17. Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin.

    PubMed

    Begg, Denovan P; May, Aaron A; Mul, Joram D; Liu, Min; D'Alessio, David A; Seeley, Randy J; Woods, Stephen C

    2015-07-01

    Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake. PMID:25667307

  18. Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin

    PubMed Central

    Begg, Denovan P.; May, Aaron A.; Mul, Joram D.; Liu, Min; D’Alessio, David A.; Seeley, Randy J.

    2015-01-01

    Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake. PMID:25667307

  19. Sustained Treatment with Insulin Detemir in Mice Alters Brain Activity and Locomotion

    PubMed Central

    Sartorius, Tina; Hennige, Anita M.; Fritsche, Andreas; Häring, Hans-Ulrich

    2016-01-01

    Aims Recent studies have identified unique brain effects of insulin detemir (Levemir®). Due to its pharmacologic properties, insulin detemir may reach higher concentrations in the brain than regular insulin. This might explain the observed increased brain stimulation after acute insulin detemir application but it remained unclear whether chronic insulin detemir treatment causes alterations in brain activity as a consequence of overstimulation. Methods In mice, we examined insulin detemir’s prolonged brain exposure by continuous subcutaneous (s.c.) application using either micro-osmotic pumps or daily s.c. injections and performed continuous radiotelemetric electrocorticography and locomotion recordings. Results Acute intracerebroventricular injection of insulin detemir activated cortical and locomotor activity significantly more than regular insulin in equimolar doses (0.94 and 5.63 mU in total), suggesting an enhanced acute impact on brain networks. However, given continuously s.c., insulin detemir significantly reduced cortical activity (theta: 21.3±6.1% vs. 73.0±8.1%, P<0.001) and failed to maintain locomotion, while regular insulin resulted in an increase of both parameters. Conclusions The data suggest that permanently-increased insulin detemir levels in the brain convert its hyperstimulatory effects and finally mediate impairments in brain activity and locomotion. This observation might be considered when human studies with insulin detemir are designed to target the brain in order to optimize treatment regimens. PMID:27589235

  20. Effect of acupressure with valerian oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome in a cardiac intensive care unit.

    PubMed

    Bagheri-Nesami, Masoumeh; Gorji, Mohammad Ali Heidari; Rezaie, Somayeh; Pouresmail, Zahra; Cherati, Jamshid Yazdani

    2015-10-01

    The purpose of this three-group double-blind clinical trial study was to investigate the effect of acupressure ( zhǐ yā) with valerian ( xié cǎo) oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome (ACS) in a coronary intensive care unit (CCU). This study was conducted on 90 patients with ACS in Mazandaran Heart Center (Sari, Iran) during 2013. The patients were randomly assigned to one of three groups. Patients in the acupressure with valerian oil 2.5% group (i.e., valerian acupressure group) received bilateral acupoint ( xué wèi) massage with two drops of valerian oil for 2 minutes for three nights; including every point this treatment lasted in total 18 minutes. Patients in the acupressure group received massage at the same points with the same technique but without valerian oil. Patients in the control group received massage at points that were 1-1.5 cm from the main points using the same technique and for the same length of time. The quality and quantity of the patients' sleep was measured by the St. Mary's Hospital Sleep Questionnaire (SMHSQ). After the intervention, there was a significant difference between sleep quality and sleep quantity in the patients in the valerian acupressure group and the acupressure group, compared to the control group (p < 0.05). Patients that received acupressure with valerian oil experienced improved sleep quality; however, this difference was not statistically significant in comparison to the acupressure only group. Acupressure at the ear spirit gate ( shén mén), hand Shenmen, glabella ( yìn táng), Wind Pool ( fēng chí), and Gushing Spring ( yǒng quán) acupoints can have therapeutic effects and may improve the quality and quantity of sleep in patients with ACS. Using these techniques in combination with herbal medicines such valerian oil can have a greater impact on improving sleep and reducing waking during the night. PMID:26587395

  1. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    SciTech Connect

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T.

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

  2. Different characteristics associated with intensive care unit transfer from the medical ward between patients with acute exacerbations of chronic obstructive pulmonary disease with and without pneumonia

    PubMed Central

    Shin, Hong-Joon; Park, Cheol-Kyu; Kim, Tae-Ok; Ban, Hee-Jung; Oh, In-Jae; Kim, Yu-Il; Kwon, Yong-Soo; Kim, Young-Chul

    2016-01-01

    Background The rate of hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is increasing. Few studies have examined the clinical, laboratory and treatment differences between patients in general wards and those who need transfer to an intensive care unit (ICU). Methods We retrospectively reviewed clinical, laboratory, and treatment characteristics of 374 patients who were initially admitted to the general ward at Chonnam National University Hospital in South Korea due to AECOPD (pneumonic, 194; non-pneumonic, 180) between January 2008 and March 2015. Of these patients, 325 were managed at the medical ward during their hospitalization period (ward group), and 49 required ICU transfer (ICU group). We compared the clinical, laboratory, and treatment characteristics associated with ICU transfer between patients with AECOPD with and without pneumonia. Results Male patients were 86.5% in the ward group and 79.6% in the ICU group. High glucose levels [median 154.5 mg/dL, interquartile range (IQR) 126.8–218.3 in ICU group vs. median 133.0, IQR 109.8–160.3 in ward group], high pneumonia severity index scores (median 100.5, IQR 85.5–118.5 vs. median 86.0, IQR 75.0–103.5), low albumin levels (median 2.9 g/dL, IQR 2.6–3.6 vs. median 3.4, IQR 3.0–3.7), and anemia (73.3% vs. 43.3%) independently increased the risk of ICU transfer in the pneumonic AECOPD group. High PaCO2 levels (median 53.1 mmHg in ICU group, IQR 38.5–84.6 vs. median 39.7, IQR 34.2–48.6 in ward group) independently increased the risk of ICU transfer in the non-pneumonic AECOPD group. Treatment with systemic corticosteroids (≥30 mg of daily prednisolone) during hospitalization in the medical ward independently reduced the risk of ICU transfer in both groups. Conclusions The characteristics associated with ICU transfer differed between the pneumonic and non-pneumonic AECOPD groups, and systemic corticosteroids use was associated with lower rate of ICU

  3. Effect of acupressure with valerian oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome in a cardiac intensive care unit

    PubMed Central

    Bagheri-Nesami, Masoumeh; Gorji, Mohammad Ali Heidari; Rezaie, Somayeh; Pouresmail, Zahra; Cherati, Jamshid Yazdani

    2015-01-01

    The purpose of this three-group double-blind clinical trial study was to investigate the effect of acupressure (指壓 zhǐ yā) with valerian (纈草 xié cǎo) oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome (ACS) in a coronary intensive care unit (CCU). This study was conducted on 90 patients with ACS in Mazandaran Heart Center (Sari, Iran) during 2013. The patients were randomly assigned to one of three groups. Patients in the acupressure with valerian oil 2.5% group (i.e., valerian acupressure group) received bilateral acupoint (穴位 xué wèi) massage with two drops of valerian oil for 2 minutes for three nights; including every point this treatment lasted in total 18 minutes. Patients in the acupressure group received massage at the same points with the same technique but without valerian oil. Patients in the control group received massage at points that were 1–1.5 cm from the main points using the same technique and for the same length of time. The quality and quantity of the patients' sleep was measured by the St. Mary's Hospital Sleep Questionnaire (SMHSQ). After the intervention, there was a significant difference between sleep quality and sleep quantity in the patients in the valerian acupressure group and the acupressure group, compared to the control group (p < 0.05). Patients that received acupressure with valerian oil experienced improved sleep quality; however, this difference was not statistically significant in comparison to the acupressure only group. Acupressure at the ear spirit gate (神門 shén mén), hand Shenmen, glabella (印堂 yìn táng), Wind Pool (風池 fēng chí), and Gushing Spring (湧泉 yǒng quán) acupoints can have therapeutic effects and may improve the quality and quantity of sleep in patients with ACS. Using these techniques in combination with herbal medicines such valerian oil can have a greater impact on improving sleep and reducing waking during the night. PMID:26587395

  4. Effect of acupressure with valerian oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome in a cardiac intensive care unit.

    PubMed

    Bagheri-Nesami, Masoumeh; Gorji, Mohammad Ali Heidari; Rezaie, Somayeh; Pouresmail, Zahra; Cherati, Jamshid Yazdani

    2015-10-01

    The purpose of this three-group double-blind clinical trial study was to investigate the effect of acupressure ( zhǐ yā) with valerian ( xié cǎo) oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome (ACS) in a coronary intensive care unit (CCU). This study was conducted on 90 patients with ACS in Mazandaran Heart Center (Sari, Iran) during 2013. The patients were randomly assigned to one of three groups. Patients in the acupressure with valerian oil 2.5% group (i.e., valerian acupressure group) received bilateral acupoint ( xué wèi) massage with two drops of valerian oil for 2 minutes for three nights; including every point this treatment lasted in total 18 minutes. Patients in the acupressure group received massage at the same points with the same technique but without valerian oil. Patients in the control group received massage at points that were 1-1.5 cm from the main points using the same technique and for the same length of time. The quality and quantity of the patients' sleep was measured by the St. Mary's Hospital Sleep Questionnaire (SMHSQ). After the intervention, there was a significant difference between sleep quality and sleep quantity in the patients in the valerian acupressure group and the acupressure group, compared to the control group (p < 0.05). Patients that received acupressure with valerian oil experienced improved sleep quality; however, this difference was not statistically significant in comparison to the acupressure only group. Acupressure at the ear spirit gate ( shén mén), hand Shenmen, glabella ( yìn táng), Wind Pool ( fēng chí), and Gushing Spring ( yǒng quán) acupoints can have therapeutic effects and may improve the quality and quantity of sleep in patients with ACS. Using these techniques in combination with herbal medicines such valerian oil can have a greater impact on improving sleep and reducing waking during the night.

  5. A Randomized, Rater-Blinded, Parallel Trial of Intensive Speech Therapy in Sub-Acute Post-Stroke Aphasia: The SP-I-R-IT Study

    ERIC Educational Resources Information Center

    Martins, Isabel Pavao; Leal, Gabriela; Fonseca, Isabel; Farrajota, Luisa; Aguiar, Marta; Fonseca, Jose; Lauterbach, Martin; Goncalves, Luis; Cary, M. Carmo; Ferreira, Joaquim J.; Ferro, Jose M.

    2013-01-01

    Background: There is conflicting evidence regarding the benefits of intensive speech and language therapy (SLT), particularly because intensity is often confounded with total SLT provided. Aims: A two-centre, randomized, rater-blinded, parallel study was conducted to compare the efficacy of 100 h of SLT in a regular (RT) versus intensive (IT)…

  6. Misadventures in insulin therapy: are you at risk?

    PubMed Central

    Grissinger, Matthew; Lease, Michael

    2003-01-01

    About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

  7. Misadventures in insulin therapy: are you at risk?

    PubMed

    Grissinger, Matthew; Lease, Michael

    2003-02-01

    About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

  8. RIFLE-based data collection/management system applied to a prospective cohort multicenter Italian study on the epidemiology of acute kidney injury in the intensive care unit.

    PubMed

    Garzotto, Francesco; Piccinni, Pasquale; Cruz, Dinna; Gramaticopolo, Silvia; Dal Santo, Marzia; Aneloni, Giovanni; Kim, Jeong Chul; Rocco, Monica; Alessandri, Elisa; Giunta, Francesco; Michetti, Vincenzo; Iannuzzi, Michele; Belluomo Anello, Clara; Brienza, Nicola; Carlini, Mauro; Pelaia, Paolo; Gabbanelli, Vincenzo; Ronco, Claudio

    2011-01-01

    The epidemiology of acute kidney injury (AKI) has been difficult to explore in the past, due to different definitions across various studies. Nevertheless, this is a very important topic today in light of the high morbidity and mortality of critically ill patients presenting renal dysfunction during their stay in the intensive care unit (ICU). The case mix has changed over the years, and AKI is a common problem in critically ill patients often requiring renal replacement therapy (RRT). The RIFLE and AKIN initiatives have provided a unifying definition for AKI, making possible large retrospective studies in different countries. The present study aims at validating a unified web-based data collection and data management tool based on the most recent AKI definition/classification system. The interactive database is designed to elucidate the epidemiology of AKI in a critically ill population. As a test, we performed a prospective observational multicenter study designed to prospectively evaluate all incident admissions in ten ICUs in Italy and the relevant epidemiology of AKI. Thus, a simple user-friendly web-based data collection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts. We enrolled 601 consecutive incident patients into the study; 25 patients with end-stage renal disease were excluded, leaving 576 patients for analysis. The median age was 66 (IQR 53-76) years, 59.4% were male, while median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation II scores were 43 (IQR 35-54) and 18 (IQR 13-24), respectively. The most common diagnostic categories for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular (12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 (IQR 3-14) days. Of 576 patients, 246 patients (42.7%) had AKI within 24 h of ICU admission, while 133 developed new AKI

  9. Influence of Acute and Chronic Exercise on Glucose Uptake

    PubMed Central

    Röhling, Martin; Herder, Christian; Stemper, Theodor; Müssig, Karsten

    2016-01-01

    Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role. PMID:27069930

  10. Executive function and endocrinological responses to acute resistance exercise

    PubMed Central

    Tsai, Chia-Liang; Wang, Chun-Hao; Pan, Chien-Yu; Chen, Fu-Chen; Huang, Tsang-Hai; Chou, Feng-Ying

    2014-01-01

    This study had the following two aims: First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles) on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI) exercise group, moderate-intensity (MI) exercise group, and non-exercise-intervention (NEI) group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 min of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 min after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological) performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude) performance. The findings suggest the beneficial effects of acute RE on executive functioning could be due to

  11. Insulin Human Inhalation

    MedlinePlus

    ... insulin and therefore cannot control the amount of sugar in the blood). It is also used in ... normally and, therefore, cannot control the amount of sugar in the blood) who need insulin to control ...

  12. Insulin Lispro Injection

    MedlinePlus

    ... insulin and therefore cannot control the amount of sugar in the blood). It is also used to ... normally and therefore cannot control the amount of sugar in the blood) who need insulin to control ...

  13. Insulin pump (image)

    MedlinePlus

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  14. High-mix insulins

    PubMed Central

    Kalra, Sanjay; Farooqi, Mohammad Hamed; El-Houni, Ali E.

    2015-01-01

    Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use. PMID:26425485

  15. Adherence to Insulin Therapy.

    PubMed

    Sarbacker, G Blair; Urteaga, Elizabeth M

    2016-08-01

    IN BRIEF Six million people with diabetes use insulin either alone or in combination with an oral medication. Many barriers exist that lead to poor adherence with insulin. However, there is an underwhelming amount of data on interventions to address these barriers and improve insulin adherence. Until pharmacological advancements create easier, more acceptable insulin regimens, it is imperative to involve patients in shared decision-making. PMID:27574371

  16. Plasminogen activator inhibitor 1 and insulin levels in various insulin resistance states.

    PubMed

    Scelles, V; Raccah, D; Alessi, M C; Vialle, J M; Juhan-Vague, I; Vague, P

    1992-01-01

    Among obese insulin resistant subjects plasminogen activator inhibitor 1 (PAI 1) levels are closely associated with fasting insulin levels in cross sectional as well as intervention studies. Insulin concentration by itself does not seem to modulate PAI 1 levels at least in acute conditions. PAI 1 levels could be more directly related to the insulin resistant state than to hyperinsulinaemia. To elucidate further this phenomenon we compared insulin, triglyceride and PAI 1 levels in twenty control subjects and in three groups of patients presenting insulin resistance 14 obese subjects, 6 patients with Cushing disease and 7 with acromegaly. None of the tested subjects was diabetic. Fasting insulin levels were elevated in obese (21.4 +/- 8.0) hypercortisolic (20.3 +/- 11.0) and acromegalic patients (16.1 +/- 5.0) compared to controls (9.2 +/- 3.0 microU/ml, m +/- SD). PAI activity and PAI 1 antigen levels were elevated in the obese group only (34.3 +/- 13.0 for PAI 1 activity) and not in the others: 10.2 +/- 10.0, 7.0 +/- 4.6 I U/l for hypercortisolic and acromegalic patients respectively (normal controls 9.7 +/- 5.4). Triglyceride levels were also elevated among obese subjects 2.2 +/- 1.3 vs 1.1 +/- 0.4 mM/l in the controls; they were slightly higher than normal but not significantly in the hypercortisolic (1.5 +/- 0.6) and acromegalic (1.43 +/- 0.6 mM/l) patients. The mechanism of insulin resistance is different in the three conditions studied here. This may explain why elevated PAI 1 concentration are restricted to the common form of insulin resistance as seen in obese subjects. Therefore insulin resistant state per se is not associated with elevated PAI 1 levels.

  17. Insulin therapy in pregnancy.

    PubMed

    Kalra, Sanjay; Jawad, Fatema

    2016-09-01

    Insulin is the mainstay of pharmacotherapy in pregnancy complicated by diabetes. This review covers the various insulin regimes and preparations, explaining how to use them, and decide appropriate doses in pregnancy. It approaches insulin treatment from a patient - centred, as well as physician and obstetrician friendly viewpoint, providing pragmatic guidance for management of diabetes in pregnancy. PMID:27582152

  18. [Perspectives in the treatment of type 2 diabetes. Role of insulin therapy?].

    PubMed

    Bringer, J; Renard, E; Galtier Dereure, F; Jaffiol, C

    1994-01-01

    Independently of its initial mechanism, Type 2 diabetes associates in various degrees disorders in insulin sensibility and secretion. The dissociated insulin resistance among tissues explains the predictable imperfection of insulin therapy in this disease due to frequent weight increase and the potential risks of insulin on atherogenesis raised on the basis of experimental studies. All diabetic subjects are not equally insulin resistant and do not have the same insulin secretory capacity evaluated in practice by means of the response of insulin or C peptide plasma levels to various secreting agents. Intensity and duration of hyperglycaemia, muscular mass, physical activity and way of life, age, weight and fat patterning, the presence of complications, acceptance, education feasibility and compliance are essential in selecting towards insulin therapy. Meanwhile, as the results of the prospective studies in progress become available, it seems that insulin should be restricted to the smallest useful dosage possible and that weight change should be carefully checked within the weeks following initiation of insulin. The future of insulin therapy in Type 2 diabetes requires (1) better selection of patients showing a demonstrated beneficial effect of insulin, (2) the association of insulin with new molecules capable of reducing its dosage and preventing its deleterious effects, (3) a change in the mode of insulin administration, with an appropriate balance between comfort and efficacy, (4) change in the insulin structure towards analogues or compounds related to insulin but with less perverted effects.

  19. One-Year Outcomes of Out-of-Hospital Administration of Intravenous Glucose, Insulin, and Potassium (GIK) in Patients with Suspected Acute Coronary Syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care] Trial)

    PubMed Central

    Selker, Harry P.; Udelson, James E.; Massaro, Joseph M.; Ruthazer, Robin; D’Agostino, Ralph B.; Griffith, John L.; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M.; Atkins, James M.; Aufderheide, Tom P.; Sayah, Assaad J.; Pirrallo, Ronald G.; Levy, Michael K.; Richards, Michael E.; Braude, Darren A.; Doyle, Delanor D.; Frascone, Ralph J.; Kosiak, Donald J.; Leaming, James M.; Van Gelder, Carin M.; Walter, Gert-Paul; Wayne, Marvin A.; Woolard, Robert H.; Beshansky, Joni R.

    2014-01-01

    The IMMEDIATE Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefit. Here we report 1-year outcomes. Pre-specified 1-year endpoints of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality, and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Among 871 participants randomized to GIK vs. placebo, respectively, death occurred within 1 year in 11.6% vs. 13.5% (unadjusted hazard ratio [HR] 0.83; 95% CI 0.57, 1.23, P=0.36). The composite of cardiac arrest or 1-year mortality was 12.8% vs. 17.0% (HR 0.71; 95% CI 0.50, 1.02, P=0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% vs. 17.2% (HR 0.98; 95% CI 0.70, 1.37, P=0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% vs. 20.4% (HR 0.85; 95% CI 0.62, 1.16, P=0.30). Among patients presenting with suspected ST elevation myocardial infarction (STEMI), hazard ratios for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33, 1.27, P=0.21); 0.52 (95% CI 0.30, 0.92, P=0.03); 0.63 (95% CI 0.35, 1.16, P=0.14); and 0.51 (95% CI 0.30, 0.87, P=0.01). Among patients with suspected ACS, serious endpoints generally were lower with GIK than placebo, but the differences were not statistically significant. However, among those with STEMI, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced. PMID:24792735

  20. Sodium-retaining effect of insulin in diabetes

    PubMed Central

    Manhiani, M. Marlina

    2012-01-01

    Insulin has long been hypothesized to cause sodium retention, potentially of enough magnitude to contribute to hypertension in obesity, metabolic syndrome, and Type II diabetes. There is an abundance of supportive evidence from correlational analyses in humans, acute insulin infusion studies in humans and animals, and chronic insulin infusion studies in rats. However, the absence of hypertension in human insulinoma patients, and negative results for sodium-retaining or blood pressure effects of chronic insulin infusion in a whole series of dog studies, strongly refute the insulin hypothesis. We recently questioned whether the euglycemic, hyperinsulinemia model used for most insulin infusion studies, including the previous chronic dog studies, was the most appropriate model to test the renal actions of insulin in obesity, metabolic syndrome, and Type II diabetes. In those circumstances, hyperinsulinemia coexists with hyperglycemia. Therefore, we tested the sodium-retaining effect of insulin in chronically instrumented, alloxan-treated diabetic dogs. We used 24 h/day intravenous insulin infusion to regulate plasma insulin concentration. Induction of diabetes (∼400 mg/dl) caused sustained natriuresis and diuresis. However, if we clamped insulin at baseline, control levels, i.e., prevented it from decreasing, then the sustained natriuresis and diuresis were completely reversed, despite the same level of hyperglycemia. We also found that 24 h/day intrarenal insulin infusion had the same effect in diabetic dogs but had no sodium-retaining action in normal dogs. This new evidence that insulin has a sodium-retaining effect during hyperglycemia may have implications for maintaining sodium balance in uncontrolled Type II diabetes. PMID:23034715

  1. Oral Insulin Reloaded

    PubMed Central

    Heinemann, Lutz; Plum-Mörschel, Leona

    2014-01-01

    Optimal coverage of insulin needs is the paramount aim of insulin replacement therapy in patients with diabetes mellitus. To apply insulin without breaking the skin barrier by a needle and/or to allow a more physiological provision of insulin are the main reasons triggering the continuous search for alternative routes of insulin administration. Despite numerous attempts over the past 9 decades to develop an insulin pill, no insulin for oral dosing is commercially available. By way of a structured approach, we aim to provide a systematic update on the most recent developments toward an orally available insulin formulation with a clear focus on data from clinical-experimental and clinical studies. Thirteen companies that claim to be working on oral insulin formulations were identified. However, only 6 of these companies published new clinical trial results within the past 5 years. Interestingly, these clinical data reports make up a mere 4% of the considerably high total number of publications on the development of oral insulin formulations within this time period. While this picture clearly reflects the rising research interest in orally bioavailable insulin formulations, it also highlights the fact that the lion’s share of research efforts is still allocated to the preclinical stages. PMID:24876606

  2. Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

    PubMed

    Haffner, S M; D'Agostino, R; Saad, M F; Rewers, M; Mykkänen, L; Selby, J; Howard, G; Savage, P J; Hamman, R F; Wagenknecht, L E

    1996-06-01

    The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non

  3. Insulin-derived amyloidosis

    PubMed Central

    Gupta, Yashdeep; Singla, Gaurav; Singla, Rajiv

    2015-01-01

    Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms “insulin amyloidosis”. Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014. PMID:25593849

  4. Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

    ERIC Educational Resources Information Center

    Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

    2002-01-01

    Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

  5. Preserved Na/HCO3 cotransporter sensitivity to insulin may promote hypertension in metabolic syndrome.

    PubMed

    Nakamura, Motonobu; Yamazaki, Osamu; Shirai, Ayumi; Horita, Shoko; Satoh, Nobuhiko; Suzuki, Masashi; Hamasaki, Yoshifumi; Noiri, Eisei; Kume, Haruki; Enomoto, Yutaka; Homma, Yukio; Seki, George

    2015-03-01

    Hyperinsulinemia can contribute to hypertension through effects on sodium transport. To test whether the stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in insulin resistance, we compared the effects of insulin on abdominal adipocytes and proximal tubules in rats and humans. Insulin markedly stimulated the sodium-bicarbonate cotransporter (NBCe1) activity in isolated proximal tubules through the phosphoinositide 3-kinase (PI3-K) pathway. Gene silencing in rats showed that while insulin receptor substrate (IRS)1 mediates the insulin effect on glucose uptake into adipocytes, IRS2 mediates the insulin effect on proximal tubule transport. The stimulatory effect of insulin on glucose uptake into adipocytes was severely reduced, but its stimulatory effect on NBCe1 activity was completely preserved in insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats and patients with insulin resistance. Despite widespread reduction of IRS1 and IRS2 expression in insulin-sensitive tissues, IRS2 expression in the kidney cortex was exceptionally preserved in both OLETF rats and patients with insulin resistance. Unlike liver, acute insulin injection failed to change the expression levels of IRS2 and sterol regulatory element-binding protein 1 in rat kidney cortex, indicating that regulatory mechanisms of IRS2 expression are distinct in liver and kidney. Thus, preserved stimulation of proximal tubule transport through the insulin/IRS2/PI3-K pathway may play an important role in the pathogenesis of hypertension associated with metabolic syndrome.

  6. [The electroretinogram parameters and the state of the cornea in the rabbit following acute exposure of the eye to UV-radiation of different intensities].

    PubMed

    Belousov, V V; Gramenitskiĭ, A E

    1991-01-01

    The purpose of this study was to investigate wave amplitudes and latencies of electroretinograms (ERG) and to examine the eye cornea of rabbits a month after their eye UV-B-irradiation with a biologically effective dose of 1.3 kJ/m2 at three intensities of 1.62, 0.567 or 0.157 W/m2. It was demonstrated that ERG a- and b-waves decreased significantly 7-20 days after irradiation while latencies remained unchanged. It was also found that during this time period ERG wave amplitudes were dependent on the intensity: at higher intensities amplitudes of both waves diminished to a greater extent. After irradiation with a peak intensity photokeratoconjunctivitis was more severe and prolonged; however, the effect of irradiation with two other intensities was very similar. In view of the fact that the highest intensity of UV-B-radiation was comparable with that beyond the Earth's atmosphere while the lowest intensity was close to that near the Earth's surface, the above findings can be used to solve space biology problems and to assess potential effects of the ozone layer destruction on the eye.

  7. [Treating diabetes with an insulin pump].

    PubMed

    Pantalone, Létitia; Lambert, Angélique

    2016-01-01

    The use of an insulin pump in the treatment of diabetes in children has constantly increased over the last 15 years. This intensive form of treatment results in better glycaemic control, the disappearance of severe hypoglycaemic episodes and greater comfort. The quality of life of the patients and their family is thereby vastly improved. PMID:26776687

  8. BDNF, IGF-I, Glucose and Insulin during Continuous and Interval Exercise in Type 1 Diabetes.

    PubMed

    Tonoli, C; Heyman, E; Roelands, B; Buyse, L; Piacentini, F; Berthoin, S; Bailey, S; Pattyn, N; Meeusen, R

    2015-11-01

    Type 1 diabetes (T1D) can have a significant impact on brain function, mostly ascribed to episodes of hypoglycemia and chronic hyperglycemia. Exercise has positive effects on acute and chronic glycemic control in T1D, and has beneficial effects on cognitive function by increasing neurotrophins such as BDNF and IGF-I in non-diabetic humans. The present study examines the effects of different types of exercise intensities on neurotrophins in T1D. 10 participants with type 1 diabetes were evaluated in 3 sessions: high-intensity exercise (10×[60 s 90%Wmax, 60 s 50 W]), continuous exercise (22 min, 70% VO2 max) and a control session. Blood glucose, serum free insulin, serum BDNF and IGF-I were assessed pre/post all the trials and after recovery. Blood glucose significantly decreased after both exercise intensities and BDNF levels increased, with a dose-response effect for exercise intensity on BDNF. IGF-I changed over time, but without a difference between the different exercise protocols. Both exercise intensities change neurotrophins in T1D, but also exhibit a dose response effect for BDNF. The intensity-dependent findings may aid in designing exercise prescriptions for maintaining or improving neurological health in T1D, but both types of exercise can be implemented.

  9. Second reduced intensity conditioning allogeneic transplant as a rescue strategy for acute leukaemia patients who relapse after an initial RIC allogeneic transplantation: analysis of risk factors and treatment outcomes.

    PubMed

    Vrhovac, R; Labopin, M; Ciceri, F; Finke, J; Holler, E; Tischer, J; Lioure, B; Gribben, J; Kanz, L; Blaise, D; Dreger, P; Held, G; Arnold, R; Nagler, A; Mohty, M

    2016-02-01

    Limited therapeutic options are available after relapse of acute leukaemia following first reduced intensity conditioning haematopoietic stem cell transplantation (RIC1). A retrospective study on European Society for Blood and Marrow Transplantation (EBMT) registry data was performed on 234 adult patients with acute leukaemia who received a second RIC transplantation (RIC2) from 2000 to 2012 as a salvage treatment for relapse following RIC1. At the time of RIC2, 167 patients (71.4%) had relapsed or refractory disease, 49 (20.9%) were in second CR and 18 (7.7%) in third or higher CR. With a median follow-up of 21 (1.5-79) months after RIC2, 51 patients are still alive. At 2 years, the cumulative incidence of non-relapse mortality (NRM), relapse incidence (RI), leukaemia-free survival (LFS) and overall survival (OS) were 22.4% (95% confidence interval (CI): 17-28.4), 63.9% (56.7-70.1), 14.6% (8.8-18.5) and 20.5% (14.9-26.1), respectively. In patients with acute myelogenous, biphenotypic and undifferentiated leukaemia (representing 89.8% of all patients), duration of remission following RIC1 >225 days, presence of CR at RIC2, patient's Karnofsky performance status >80 at RIC2 and non-myeloablative conditioning were found to be the strongest predictors of patients' favourable outcome.

  10. [Comparative analysis of application of highly intensive laser irradiation and electrocoagulation during laparoscopic cholecystectomy performed for destructive forms of an acute calculous cholecystitis].

    PubMed

    Nichitayio, M Yu; Bazyak, A M; Klochan, V V; Grusha, P K; Goman, A V

    2015-02-01

    Comparative analysis of results of the laser diode (the wave length 940 nm) and elec- trocoagulation application while performing laparoscopic cholecystectomy was con- ducted. For an acute calculous cholecystitis 52 patients were operated, in whom instead of electrocoagulation the laser was applied, provide for reduction of thermal impact on tissues, the complications absence, reduction of the patients stationary treatment duration postoperatively from (5.2 ± 1.2) to (4.9 ± 0.6) days.

  11. Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

    PubMed

    Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

    2015-10-01

    The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.

  12. Biosimilar Insulin and Costs

    PubMed Central

    Heinemann, Lutz

    2015-01-01

    The costs for insulin treatment are high, and the steady increase in the number of patients with diabetes on insulin presents a true challenge to health care systems. Therefore, all measures to lower these costs are welcomed by patients, physicians, and health care providers. The market introduction of biosimilar insulins presents an option to lower treatment costs as biosimilars are usually offered at a lower price than the originator product. However, the assumption that a drastic reduction in insulin prices will take place, as was observed with many generic drugs, is most probably not realistic. As the first biosimilar insulin has now been approved in the EU, this commentary discusses a number of aspects that are relevant when it comes to the potential cost reduction we will see with the use of biosimilar insulins. PMID:26350722

  13. RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

    SciTech Connect

    Kachnic, Lisa A.; Winter, Kathryn; Myerson, Robert J.; Goodyear, Michael D.; Willins, John; Esthappan, Jacqueline; Haddock, Michael G.; Rotman, Marvin; Parikh, Parag J.; Safran, Howard; Willett, Christopher G.

    2013-05-01

    Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

  14. Tea enhances insulin activity.

    PubMed

    Anderson, Richard A; Polansky, Marilyn M

    2002-11-20

    The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity. The objective of this study was to determine the insulin-enhancing properties of tea and its components. Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay. Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia senensis, were all shown to increase insulin activity. High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate. For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds. Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins. Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities. Addition of lemon to the tea did not affect the insulin-potentiating activity. Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90%. Nondairy creamers and soy milk also decreased the insulin-enhancing activity. These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate. PMID:12428980

  15. Fatal hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine

    PubMed Central

    Madsen, Kristian Roerbaek

    2014-01-01

    A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure within 36 h from initial presentation. While second-generation antipsychotics are well known to be causally linked to diabetes and hyperlipidaemia, this is to my knowledge the first-described case of a fatal triad of extreme hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine. Clinicians should be aware of this rare clinical presentation since rapid progression to multiorgan failure can occur. Early supportive therapy should be initiated. Lactescent serum and ketoacidosis in severe acute pancreatitis should not be overlooked—initiate insulin therapy and possibly plasmapheresis in case of extreme hypertriglyceridaemia. PMID:24403385

  16. Insulin Signaling in Insulin Resistance States and Cancer: A Modeling Analysis

    PubMed Central

    Bertuzzi, Alessandro; Conte, Federica; Mingrone, Geltrude; Papa, Federico; Salinari, Serenella

    2016-01-01

    Insulin resistance is the common denominator of several diseases including type 2 diabetes and cancer, and investigating the mechanisms responsible for insulin signaling impairment is of primary importance. A mathematical model of the insulin signaling network (ISN) is proposed and used to investigate the dose-response curves of components of this network. Experimental data of C2C12 myoblasts with phosphatase and tensin homologue (PTEN) suppressed and data of L6 myotubes with induced insulin resistance have been analyzed by the model. We focused particularly on single and double Akt phosphorylation and pointed out insulin signaling changes related to insulin resistance. Moreover, a new characterization of the upstream signaling of the mammalian target of rapamycin complex 2 (mTORC2) is presented. As it is widely recognized that ISN proteins have a crucial role also in cell proliferation and death, the ISN model was linked to a cell population model and applied to data of a cell line of acute myeloid leukemia treated with a mammalian target of rapamycin inhibitor with antitumor activity. The analysis revealed simple relationships among the concentrations of ISN proteins and the parameters of the cell population model that characterize cell cycle progression and cell death. PMID:27149630

  17. The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity.

    PubMed

    Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta; Raman, Amitha; Bornholdt, Jette; Boyd, Mette; Toft, Eva; Qvist, Veronica; Näslund, Erik; Thorell, Anders; Andersson, Daniel P; Dahlman, Ingrid; Gao, Hui; Sandelin, Albin; Daub, Carsten O; Arner, Peter

    2016-08-30

    Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates that differences in the acute transcriptional response to insulin are primarily driven by obesity per se, challenging the notion of healthy obese adipose tissue, at least in severe obesity. PMID:27545890

  18. The effect of oral metformin on insulin sensitivity in insulin-resistant ponies.

    PubMed

    Tinworth, Kellie D; Boston, Ray C; Harris, Patricia A; Sillence, Martin N; Raidal, Sharanne L; Noble, Glenys K

    2012-01-01

    Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15 mg/kg bodyweight (BW), orally, twice-daily, for 21 days to the metformin-treated group. The control group received a placebo. A FSIGT was conducted before and after treatment. The Minimal Model of glucose and insulin dynamics rendered indices describing SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and the disposition index (DI). The body condition score (BCS), BW and cresty neck score (CNS) were also assessed. There was no significant change in SI, Sg, AIRg, DI, BW, BCS or CNS in response to metformin, or over time in the control group. There were no measurable benefits of metformin on SI, consistent with recent work showing that the bioavailability of metformin in horses is poor, and chronic dosing may not achieve therapeutic blood concentrations. Alternatively, metformin may only be effective in obese ponies losing weight or with hyperglycaemia.

  19. Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

    SciTech Connect

    Kachnic, Lisa A.; Tsai, Henry K.; Coen, John J.; Blaszkowsky, Lawrence S.; Hartshorn, Kevan; Kwak, Eunice L.; Willins, John D.; Ryan, David P.; Hong, Theodore S.

    2012-01-01

    Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs {<=}3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.

  20. Dogs infected with the blood trypomastigote form of Trypanosoma cruzi display an increase expression of cytokines and chemokines plus an intense cardiac parasitism during acute infection.

    PubMed

    de Souza, Sheler Martins; Vieira, Paula Melo de Abreu; Roatt, Bruno Mendes; Reis, Levi Eduardo Soares; da Silva Fonseca, Kátia; Nogueira, Nívia Carolina; Reis, Alexandre Barbosa; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2014-03-01

    The recent increase in immigration of people from areas endemic for Chagas disease (Trypanosoma cruzi) to the United States and Europe has raised concerns about the transmission via blood transfusion and organ transplants in these countries. Infection by these pathways occurs through blood trypomastigotes (BT), and these forms of T. cruzi are completely distinct of metacyclic trypomastigotes (MT), released by triatomine vector, in relation to parasite-host interaction. Thus, research comparing infection with these different infective forms is important for explaining the potential impacts on the disease course. Here, we investigated tissue parasitism and relative mRNA expression of cytokines, chemokines, and chemokine receptors in the heart during acute infection by MT or BT forms in dogs. BT-infected dogs presented a higher cardiac parasitism, increased relative mRNA expression of pro-inflammatory and immunomodulatory cytokines and of the chemokines CCL3/MIP-1α, CCL5/RANTES, and the chemokine receptor CCR5 during the acute phase of infection, as compared to MT-infected dogs. These results suggest that infection with BT forms may lead to an increased immune response, as revealed by the cytokines ratio, but this kind of immune response was not able to control the cardiac parasitism. Infection with the MT form presented an increase in the relative mRNA expression of IL-12p40 as compared to that of IL-10 or TGF-β1. Correlation analysis showed increased relative mRNA expression of IFN-γ as well as IL-10, which may be an immunomodulatory response, as well as an increase in the correlation of CCL5/RANTES and its CCR5 receptor. Our findings revealed a difference between inoculum sources of T. cruzi, as vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase, which may influence immunopathological aspects of Chagas disease.

  1. [Clinical-microbiological evaluation of the efficacy of combined use of chitosan, low intensity laser radiation and photosensitizer in treatment of patients with acute suppurative maxillofacial periostitis].

    PubMed

    Shomina, S A; Bogatov, V V; Chervinets, V M

    2005-01-01

    Results are presented on treatment of 68 patients with acute suppurative periostitis of maxillofacial region. After surgical interventions in patients of the study group (48 patients) the wounds were cleansed by 1% chitosan on 0.2% HC1 in combination with methylene blue and irradiated by IR laser beam. The wounds healed in 2-3 days. In the control group (20 patients) for wound dressing chlorhexidine as a standard procedure was used, length of the healing process was 5-6 days. After combined treatment the number of microflora in the wound was reduced and microflora did not show the signs of pathogenicity.

  2. Effect of an Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: A Preliminary Study

    PubMed Central

    GREENWALD, SAMANTHA; SEGER, EDWARD; NICHOLS, DAVID; RAY, ANDREW D.; RIDEOUT, TODD C.; GOSSELIN, LUC E.

    2016-01-01

    Impaired glucose tolerance can have significant health consequences. The purposes of this preliminary study were to examine whether a single session of kettlebell exercise improves acute post-exercise glucose tolerance in sedentary individuals, and whether it was as effective as high-intensity interval running. Six sedentary male subjects underwent a two-hour oral glucose tolerance test following three different conditions: 1) control (no exercise); 2) kettlebell exercise (2 sets of 7 exercises, 15 repetitions per exercise with 30 seconds rest between each exercise); or 3) high-intensity interval running (10 one-minute intervals at a workload corresponding to 90% VO2max interspersed with one-minute active recovery periods). Blood glucose and insulin levels were measured before (0 minutes), and 60 and 120 minutes after glucose ingestion. Both kettlebell and high-intensity interval running exercise significantly lowered blood glucose 60 minutes after glucose ingestion compared with control. However, there was no significant difference in blood glucose between the two exercise conditions at any time point. In addition, there were no significant differences in insulin concentration between high intensity interval running, kettlebell, and control conditions at all time points. Results indicate that an acute bout of kettlebell exercise is as effective as high intensity interval running at improving glucose tolerance in sedentary young men. PMID:27766136

  3. Adipocyte Metrnl Antagonizes Insulin Resistance Through PPARγ Signaling.

    PubMed

    Li, Zhi-Yong; Song, Jie; Zheng, Si-Li; Fan, Mao-Bing; Guan, Yun-Feng; Qu, Yi; Xu, Jian; Wang, Pei; Miao, Chao-Yu

    2015-12-01

    Adipokines play important roles in metabolic homeostasis and disease. We have recently identified a novel adipokine Metrnl, also known as Subfatin, for its high expression in subcutaneous fat. Here, we demonstrate a prodifferentiation action of Metrnl in white adipocytes. Adipocyte-specific knockout of Metrnl exacerbates insulin resistance induced by high-fat diet (HFD), whereas adipocyte-specific transgenic overexpression of Metrnl prevents insulin resistance induced by HFD or leptin deletion. Body weight and adipose content are not changed by adipocyte Metrnl. Consistently, no correlation is found between serum Metrnl level and BMI in humans. Metrnl promotes white adipocyte differentiation, expandability, and lipid metabolism and inhibits adipose inflammation to form functional fat, which contributes to its activity against insulin resistance. The insulin sensitization of Metrnl is blocked by PPARγ inhibitors or knockdown. However, Metrnl does not drive white adipose browning. Acute intravenous injection of recombinant Metrnl has no hypoglycemic effect, and 1-week intravenous administration of Metrnl is unable to rescue insulin resistance exacerbated by adipocyte Metrnl deficiency. Our results suggest adipocyte Metrnl controls insulin sensitivity at least via its local autocrine/paracrine action through the PPARγ pathway. Adipocyte Metrnl is an inherent insulin sensitizer and may become a therapeutic target for insulin resistance. PMID:26307585

  4. [Cardiovascular effects of insulin therapy: from pharmacology to clinical trials].

    PubMed

    Mannucci, Edoardo

    2016-03-01

    Insulin has direct effects on vascular walls which, depending on experimental models, can be either predominantly antiatherogenic or proatherogenic. In observational studies, insulin therapy is usually associated with an increase in the incidence of major cardiovascular events. However, this result is probably determined by the effect of confounders. In clinical trials performed in the acute phase of coronary syndromes, the benefits observed with insulin therapy are probably due to the improvement of glycemic control, rather than to direct effects of insulin on the cardiovascular system. In long-term trials for primary or secondary prevention such as UKPDS and ORIGIN insulin has no relevant effects on major cardiovascular events beyond those determined by the improvement of metabolic control. On the other hand, severe hypoglycemia, which is a possible side effect of insulin therapy, is associated with a worse prognosis of cardiovascular disease. The availability of new long-acting insulin analogs, which reduce the incidence of hypoglycemia for similar levels of glycemic control, makes insulin therapy easier and potentially safer for the cardiovascular system.

  5. Importance of transcapillary insulin transport on insulin action in vivo

    SciTech Connect

    Yang, Y.J.

    1989-01-01

    The relationship between transcapillary insulin transport and insulin action was examined in normal conscious dogs. Plasma and thoracic duct lymph insulin, and insulin action were simultaneously measured during euglycemic clamps and intravenous glucose tolerance tests. During the clamps, while {sup 14}C-inulin reached an equilibrium, steady-state (ss) plasma insulin was higher than lymph and the ratio of 3:2 was maintained during basal, activation and deactivation phases: 18 {+-} 2 vs. 12 {+-} 1, 51 {+-} 2 vs. 32 {+-} 1, and 18 {+-} 3 vs. 13 {+-} 1 {mu}U/ml. In addition, it took longer for lymph insulin to reach ss than plasma insulin during activation and deactivation: 11 {+-} 2 vs. 31 {+-} 5 and 8 {+-} 2 vs. 32 {+-} 6 min. During IVGTT, plasma insulin peaked within 5 {+-} 2 min; lymph insulin rose slowly to a lower peak. The significant gradient and delay between plasma and lymph insulin concentrations suggest a restricted transcapillary insulin transport.

  6. Acute response of peripheral CCr5 chemoreceptor and NK cells in individuals submitted to a single session of low-intensity strength exercise with blood flow restriction.

    PubMed

    Dorneles, Gilson Pires; Colato, Alana Schraiber; Galvão, Simone Lunelli; Ramis, Thiago Rozales; Ribeiro, Jerri Luiz; Romão, Pedro Roosevelt; Peres, Alessandra

    2016-07-01

    The purpose of this study was to compare the peripheral expression of natural killers and CCR5 in a session of low-intensity strength training with vascular occlusion and in high-intensity training. Young males were randomized into session groups of a high-intensity strength training (HI) and a session group of low-intensity strength training with vascular occlusion (LI-BFR). The exercise session consisted in knee extension and bicep curl in 80% 1RM (HI) and 30% 1RM (LI-BFR) with equalized volumes. Blood collection was made before, immediately after and 24 h after each training session. Immunophenotyping was carried out through CD195+ (CCR5) e CD3-CD16+CD56+ (NK) in peripheral blood and analysed by flow cytometry and presented in frequency (%). Peripheral frequency of NK cells showed no significant difference in LI-BFR group in time effect, while a gradual reduction of NK cells was identified in HI group in before-24 h postexercise and after-24 h postexercise comparison. However, significant differences have been found in relative change of NK cells immediately after exercise between sessions. In addition, HI and LI-BFR groups showed a significant reduction in the cells expressed CCR5 during 24 h postsession compared to the postsession, but CCR5 also differed when comparing before-24 h after session in the HI group. No differences were observed amongst the groups. LIO induced CCR5 response similar to the HI session, while the NK cells remained in similar frequency during the studied moments in LI-BFR, but not in HI group, suggesting that local hypoxia created by the blood flow restriction was able to prevent a change in the frequency of peripheral cells and a possible immunosuppression.

  7. Review of Insulin and its Analogues in Diabetes Mellitus

    PubMed Central

    Mane, Krishnappa; Chaluvaraju, KC; Niranjan, MS; Zaranappa, TR; Manjuthej, TR

    2012-01-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin’s, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  8. Protein Crystal Bovine Insulin

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The comparison of protein crystal, Bovine Insulin space-grown (left) and earth-grown (right). Facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  9. Insulin Resistance of Puberty.

    PubMed

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity. PMID:27179965

  10. Insulin and glucose regulation.

    PubMed

    Ralston, Sarah L

    2002-08-01

    Abnormally high or low blood glucose and insulin concentrations after standardized glucose tolerance tests can reflect disorders such as pituitary dysfunction, polysaccharide storage myopathies, and other clinical disorders. Glucose and insulin responses, however, are modified by the diet to which the animal has adapted, time since it was last fed, and what it was fed. Body fat (obesity), fitness level, physiologic status, and stress also alter glucose and insulin metabolism. Therefore, it is important to consider these factors when evaluating glucose and insulin tests, especially if only one sample it taken. This article describes the factors affecting glucose and insulin metabolism in horses and how they might influence the interpretation of standardized tests of glucose tolerance.

  11. Direct Demonstration of Separate Receptors for Growth and Metabolic Activities of Insulin and Multiplication-stimulating Activity (an Insulinlike Growth Factor) Using Antibodies to the Insulin Receptor

    PubMed Central

    King, George L.; Kahn, C. Ronald; Rechler, Matthew M.; Nissley, S. Peter

    1980-01-01

    Insulin and such insulinlike growth factors as multiplication stimulating activity (MSA) are related polypeptides that have common biological activities. Both insulin and MSA produce acute metabolic responses (stimulation of glucose oxidation in isolated fat cells) as well as growth effects (stimulation of [3H]thymidine incorporation into DNA in cultured fibroblasts). In addition, most cells have separate receptors for insulin and insulinlike growth factors, and both peptides have weaker affinity for each other's specific receptors than for their own. To determine, therefore, whether these effects are mediated by receptors for insulin, insulinlike growth factors, or both, we have selectively blocked insulin receptors with a specific antagonist, namely Fab fragments derived from naturally occurring antibodies to the insulin receptor. In rat adipocytes, 10 μg/ml of antireceptor Fab inhibited insulin binding by 90%, whereas it inhibited MSA binding <5%. The anti-insulin receptor Fab is without intrinsic biological activity, but acts as a competitive inhibitor of insulin receptors. Blockade of insulin receptors with Fab fragments produced a 30-fold rightward shift in the dose response for stimulation of glucose oxidation by both insulin and MSA. The dose-response curves for stimulation of oxidation by vitamin K5 and spermine, agents that stimulate glucose oxidation through noninsulin receptor pathways, were not affected by the blockade of insulin receptors with Fab antibody fragments. These data suggest that this acute metabolic effect of both insulin and MSA is mediated via the insulin receptor. In cultured human fibroblasts, 10 μg/ml of Fab inhibited insulin binding by 90% and MSA binding by 15%. In fibroblasts, however, blockade of the insulin receptor did not alter the dose response for stimulation of thymidine incorporation into DNA by either insulin or MSA. Furthermore, intact antireceptor antibody immunoglobulin (Ig)G, which produces multiple other insulinlike

  12. Prevalence of acute post-operative pain in patients in adult age-group undergoing inpatient abdominal surgery and correlation of intensity of pain and satisfaction with analgesic management: A cross-sectional single institute-based study

    PubMed Central

    Singh, Prashant Kumar; Saikia, Priyam; Lahakar, Mangala

    2016-01-01

    Background and Aims: Considering the paucity of regional data, this study was designed to investigate the prevalence of post-operative pain and determine if there exists any correlation between the intensity of post-operative pain and patient's level of satisfaction with their pain management after inpatient abdominal surgery at an academic tertiary care government centre. Methods: Pain intensity was measured in 120 patients with numeric rating scale at the fifth post-operative hour, second and third post-operative day. A questionnaire was used to measure the level of satisfaction with nurse's and doctor's response to their pain and overall pain management. Results: The prevalence of post-operative pain was 84.17%, 92.5% and 96.66% at the fifth post-operative hour, second and third post-operative day, respectively. Less number of patients experienced severe intensity pain on the third post-operative day (P = 0.00046), whereas the number of patients experiencing mild pain increased (P < 0.000) compared to the fifth post-operative hour. The number of patients with complete analgesia decreased on the third post-operative day (P = 0.001 compared to fifth post-operative day). The Spearman correlation coefficient between pain score on the third post-operative day and level of satisfaction with nurse's response, doctor's response to pain and the overall pain management was − 0.0218 (P = 0.8107), 0.1307 (P = 0.1553) and 0.0743 (P = 0.4195), respectively. Conclusion: There is a high prevalence of acute post-operative pain in patients undergoing inpatient abdominal surgery at our institute. There is a weak correlation between the intensity of pain and level of satisfaction with pain management. PMID:27761037

  13. Cardiovascular manifestations of insulin resistance.

    PubMed

    Chahwala, Veer; Arora, Rohit

    2009-01-01

    Data from the Centers for Disease Control and Prevention indicate that the prevalence of diabetes is increasing steadily and is coupled with a rise in obesity. Studies such as the Nurses' Health Study show that even slight glucose abnormalities, namely insulin resistance, increase the risk of myocardial infarctions, strokes, other cardiovascular disease, and mortality. Insulin resistance was found to accelerate atherosclerosis, inflammation, the onset of diabetes, cardiovascular disease, obesity, hypertension, chronic kidney disease, and dyslipidemia. Adiponectin was found to have potent antiinflammatory and antiatherosclerotic effects. Similarly, studies indicate that peroxisome proliferators-activated receptor agonists have the potential to treat obesity, diabetes, and atherosclerosis. From a preventive standpoint, it was shown that intensive glucose control reduces long-term cardiovascular risk. This intensive control approach included the use of thiazolidinediones (TZDs; troglitazone, pioglitazone, and rosiglitazone), which were demonstrated to have vascular and nonglycemic effects beyond glucose-lowering. A drawback of using TZDs is peripheral fluid retention. The DREAM study showed that participants with impaired fasting glucose or impaired glucose tolerance who are free from cardiovascular disease benefited significantly from taking 8 mg rosiglitazone per day. The ADOPT study provided evidence that rosiglitazone is more efficient at controlling glycemic loss and maintaining low glycosylated hemoglobin levels than metformin and glyburide. Data from the CHICAGO study indicate that the progression of carotid artery intima-media thickness, a marker of atherosclerosis and a surrogate end point for cardiovascular disease, was slowed more with pioglitazone than glimepiride in a racially diverse population of men and women with diabetes mellitus type 2. Overall, investigators have shifted from a focus on hyperglycemia to a multifactorial approach to risk management

  14. Fibroblast Growth Factor 21 Improves Insulin Sensitivity and Synergizes with Insulin in Human Adipose Stem Cell-Derived (hASC) Adipocytes

    PubMed Central

    Lee, Darwin V.; Li, Dongmei; Yan, Qingyun; Zhu, Yimin; Goodwin, Bryan; Calle, Roberto; Brenner, Martin B.; Talukdar, Saswata

    2014-01-01

    Fibroblast growth factor 21 (FGF21) has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC) adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway. PMID:25365322

  15. Role of O-GlcNAcylation in nutritional sensing, insulin resistance and in mediating the benefits of exercise.

    PubMed

    Myslicki, Jason P; Belke, Darrell D; Shearer, Jane

    2014-11-01

    The purpose of this review is to highlight the role of O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification in metabolic disease states and to summarize current knowledge of how exercise affects this important post-translational signalling pathway. O-GlcNAc modification is an intracellular tool capable of integrating energy supply with demand. The accumulation of excess energy associated with obesity and insulin resistance is mediated, in part, by the hexosamine biosynthetic pathway (HBP), which results in the O-GlcNAcylation of a myriad of proteins, thereby affecting their respective function, stability, and localization. Insulin resistance is related to the excessive O-GlcNAcylation of key metabolic proteins causing a chronic blunting of insulin signalling pathways and precipitating the accompanying pathologies, such as heart and kidney disease. Lifestyle modifications such as diet and exercise also modify the pathway. Exercise is a front-line and cost-effective therapeutic approach for insulin resistance, and recent work shows that the intervention can alter O-GlcNAc gene expression, signalling, and protein modification. However, there is currently no consensus on the effect of frequency, intensity, type, and duration of exercise on O-GlcNAc modification, the HBP, and its related enzymes. On one end of the spectrum, mild, prolonged swim training reduces O-GlcNAcylation, while on the other end, higher intensity treadmill running increases cardiac protein O-GlcNAc modification. Clearly, a balance between acute and chronic stress of exercise is needed to reap the benefits of the intervention on O-GlcNAc signalling. PMID:25203141

  16. Role of O-GlcNAcylation in nutritional sensing, insulin resistance and in mediating the benefits of exercise.

    PubMed

    Myslicki, Jason P; Belke, Darrell D; Shearer, Jane

    2014-11-01

    The purpose of this review is to highlight the role of O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification in metabolic disease states and to summarize current knowledge of how exercise affects this important post-translational signalling pathway. O-GlcNAc modification is an intracellular tool capable of integrating energy supply with demand. The accumulation of excess energy associated with obesity and insulin resistance is mediated, in part, by the hexosamine biosynthetic pathway (HBP), which results in the O-GlcNAcylation of a myriad of proteins, thereby affecting their respective function, stability, and localization. Insulin resistance is related to the excessive O-GlcNAcylation of key metabolic proteins causing a chronic blunting of insulin signalling pathways and precipitating the accompanying pathologies, such as heart and kidney disease. Lifestyle modifications such as diet and exercise also modify the pathway. Exercise is a front-line and cost-effective therapeutic approach for insulin resistance, and recent work shows that the intervention can alter O-GlcNAc gene expression, signalling, and protein modification. However, there is currently no consensus on the effect of frequency, intensity, type, and duration of exercise on O-GlcNAc modification, the HBP, and its related enzymes. On one end of the spectrum, mild, prolonged swim training reduces O-GlcNAcylation, while on the other end, higher intensity treadmill running increases cardiac protein O-GlcNAc modification. Clearly, a balance between acute and chronic stress of exercise is needed to reap the benefits of the intervention on O-GlcNAc signalling.

  17. Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats.

    PubMed

    Eskens, Bart J M; Mooij, Hans L; Cleutjens, Jack P M; Roos, Jozef M A; Cobelens, Johanna E; Vink, Hans; Vanteeffelen, Jurgen W G E

    2013-01-01

    It has been demonstrated that insulin-mediated recruitment of microvascular blood volume is associated with insulin sensitivity. We hypothesize that insulin rapidly stimulates penetration of red blood cells (RBC) and plasma into the glycocalyx and thereby promotes insulin-mediated glucose uptake by increasing intracapillary blood volume. Experiments were performed in rats; the role of the glycocalyx was assessed by enzymatic degradation using a bolus of hyaluronidase. First, the effect of insulin on glycocalyx accessibility was assessed by measuring the depth of penetration of RBCs into the glycocalyx in microvessels of the gastrocnemius muscle with Sidestream Dark-field imaging. Secondly, peripheral insulin sensitivity was determined using intravenous insulin tolerance tests (IVITT). In addition, in a smaller set of experiments, intravital microscopy of capillary hemodynamics in cremaster muscle and histological analysis of the distribution of fluorescently labeled 40 kDa dextrans (D40) in hindlimb muscle was used to evaluate insulin-mediated increases in capillary blood volume. Insulin increased glycocalyx penetration of RBCs by 0.34±0.44 µm (P<0.05) within 10 minutes, and this effect of insulin was greatly impaired in hyaluronidase treated rats. Further, hyaluronidase treated rats showed a 35±25% reduction in whole-body insulin-mediated glucose disposal compared to control rats. Insulin-mediated increases in capillary blood volume were reflected by a rapid increase in capillary tube hematocrit from 21.1±10.1% to 29.0±9.8% (P<0.05), and an increase in D40 intensity in individual capillaries of 134±138% compared to baseline at the end of the IVITT. These effects of insulin were virtually abolished in hyaluronidase treated animals. In conclusion, insulin rapidly increases glycocalyx accessibility for circulating blood in muscle, and this is associated with an increased blood volume in individual capillaries. Hyaluronidase treatment of the glycocalyx abolishes

  18. [Insulin and physical exercise].

    PubMed

    Louis-Sylvestre, J

    1987-04-01

    Secretion of some pituitary hormones and sympatho-adrenal activity increase very early during exercise. Sympathetic activation is of major importance in cardiovascular adaptation, thermoregulation, etc. Furthermore among the hormonal consequences of such activation those related to insulin are capital. In animal and human subjects basal insulin level decrease during prolonged and progressive exercise. With habitual exercise, both basal and stimulated insulin levels are reduced. It seems that the reduced basal level could be due to alpha-adrenergic inhibition of the islets of Langerhans, while the reduced stimulated response could be the consequence of increased clearance. In trained subjects, in spite of reduced insulin secretion tolerance to glucose is normal due to increased sensitivity to insulin. Sensitivity to insulin is particularly enhanced at the muscular tissue level; it is accompanied by increased hexokinase and glycogen synthetase activity. As a consequence glucose uptake remains optimal at the muscular level. In the liver, both insulin sensitivity and glucokinase activity are reduced, so that glucose is spared and the muscular glycogen store can be restored. At the adipocyte level, metabolic adaptations are such that triglyceride turnover is greatly increased, favouring fuel supply and resaturation of stores.

  19. [Alleged suicide by insulin].

    PubMed

    Birngruber, Christoph G; Krüll, Ralf; Dettmeyer, Reinhard; Verhoff, Marcel A

    2015-01-01

    A 26-year-old man, who was on probation, was found dead in his home by his mother. Insulin vials and 2 insulin pens, which the man's stepfather (an insulin-dependent diabetic) had been missing for over a week, were found next to the deceased. The circumstances suggested suicide by an injected insulin overdose. At the time of the autopsy, the corpse showed already marked signs of autolysis. Clinical chemical tests confirmed the injection of insulin, but indicated hyperglycemia at the time of death. Toxicological analyses revealed that the man had consumed amphetamine, cannabinoids, and tramadol in the recent past. Histological examination finally revealed extensive bronchopneumonia as the cause of death. The most plausible explanation for the results of the autopsy and the additional examinations was an injection of insulin as a failed attempt of self-treatment. It is conceivable that the man had discovered by a rapid test that he was a diabetic, but had decided not to go to a doctor to avoid disclosure of parole violation due to continued drug abuse. He may have misinterpreted the symptoms caused by his worsening bronchitis and the developing bronchopneumonia as symptoms of a diabetic metabolic status and may have felt compelled to treat himself with insulin. PMID:26419091

  20. Tagging insulin in microgravity

    NASA Technical Reports Server (NTRS)

    Dobeck, Michael; Nelson, Ronald S.

    1992-01-01

    Knowing the exact subcellular sites of action of insulin in the body has the potential to give basic science investigators a basis from which a cause and cure for this disease can be approached. The goal of this project is to create a test reagent that can be used to visualize these subcellular sites. The unique microgravity environment of the Shuttle will allow the creation of a reagent that has the possibility of elucidating the subcellular sites of action of insulin. Several techniques have been used in an attempt to isolate the sites of action of items such as insulin. One of these is autoradiography in which the test item is obtained from animals fed radioactive materials. What is clearly needed is to visualize individual insulin molecules at their sites of action. The insulin tagging process to be used on G-399 involves the conjugation of insulin molecules with ferritin molecules to create a reagent that will be used back on Earth in an attempt to elucidate the sites of action of insulin.

  1. Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP): an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients

    PubMed Central

    Vellinga, Namkje A. R.; Boerma, E. Christiaan; Koopmans, Matty; Donati, Abele; Dubin, Arnaldo; Shapiro, Nathan I.; Pearse, Rupert M.; Bakker, Jan; Ince, Can

    2012-01-01

    Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill. PMID:22666566

  2. Frequency of TGF-β and IFN-γ Genotype as Risk Factors for Acute Kidney Injury and Death in Intensive Care Unit Patients

    PubMed Central

    Grabulosa, Caren Cristina; Batista, Marcelo Costa; Cendoroglo, Miguel; Quinto, Beata Marie Redublo; Monte, Julio Cesar; Durão, Marcelino; Rizzo, Luiz Vicente; Santos, Oscar Fernando Pavão; Dalboni, Maria Aparecida

    2014-01-01

    Genetic variations in TGF-β and IFN-γ may interfere with proinflammatory cytokine production and, consequently, may be involved with inflammatory diseases, as acute kidney injury (AKI). We considered that genetic polymorphisms of these cytokines may have a crucial role in the outcome of critically ill patients. To investigate whether the genetic polymorphisms of rs1800470 (codon 10 T/C), rs1800471 (codon 25 C/G) from the TGF-β, and rs2430561 (+874 T/A) from IFN-γ may be a risk factor for ICU patients to the development of AKI and/or death. In a prospective nested case-control study, were included 139 ICU patients who developed AKI, 164 ICU patients without AKI, and 244 healthy individuals. We observed a higher frequency to T/A genotype for IFN-γ (intermediate producer phenotype) and higher frequency of TT GG and TC GG genotype (high producer) for TGF-β polymorphism in overall population. However, these polymorphisms have not been shown as a predictor of risk for AKI and death. We found an increased prevalence of high and intermediate producer phenotypes from TGF-β and IFN-γ, respectively, in patients in ICU setting. However, the studied genetic polymorphism of the TGF-β and IFN-γ was not associated as a risk factor for AKI or death in our population. PMID:25147823

  3. Insulin and the law.

    PubMed

    Marks, Vincent

    2015-11-01

    Hypoglycaemia, if it can be proved, may be used as a defence against almost any criminal charge provided it can be established that the perpetrator was in a state of neuroglycopenic (hypoglycaemic) automatism at the time of the offence. Hypoglycaemia produced by exogenous insulin can also be used as a suicidal or homicidal weapon. This paper discusses some of the pitfalls confronting the investigator of suspected insulin misuse including problems arising from the increasing prevalence of insulin analogues and the unreliability of immunoassays for their detection and measurement in the forensic context. PMID:26092979

  4. Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and mini-methotrexate (Tac/Sir/Mtx) as Acute GVHD Prophylaxis after Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation

    PubMed Central

    Ho, Vincent T.; Aldridge, Julie; Kim, Haesook T.; Cutler, Corey; Koreth, John; Armand, Philippe; Antin, Joseph H.; Soiffer, Robert J.; Alyea, Edwin P.

    2009-01-01

    Previous studies have shown that the addition of sirolimus to tacrolimus/mini-methotrexate (tac/sir/mtx) as GVHD prophylaxis produces low rates of acute GVHD after reduced intensity (RIC) allogeneic SCT. To assess whether the post transplant methotrexate can be safely eliminated altogether, we conducted a prospective clinical trial testing the combination of tacrolimus and silrolimus (tac/sir) alone as GVHD prophylaxis after RIC SCT from matched related donors. We compare the results with patients who received tac/sir/mtx as GVHD prophylaxis after RIC SCT from matched related donors in a previous prospective study. Patients on both trials received fludarabine 30 mg/m2/d IV and intravenous busulfan 0.8 mg/kg/d IV from day −5 through day −2 as conditioning, followed by transplantation of unmanipulated filgrastim mobilized peripheral blood stem cells. Both cohorts received tacrolimus and sirolimus orally starting on day-3, with doses adjusted to achieve trough serum levels of 5–10 ng/ml and 3–12 ng/ml, respectively. The tac/sir/mtx cohort received additional mini-methotrexate (5 mg/m2 IV) on day +1,3,6. Filgrastim 5 mcg/kg SC QD was started on day +1 until neutrophil engraftment. Twenty nine patients were transplanted on tac/sir, and 46 were transplanted on tac/sir/mtx. The two groups were balanced in age, gender, and disease characteristics. Engraftment was brisk and donor chimerism after transplant was robust in both groups. The cumulative incidence of grade II–IV acute GVHD were similar, 17% vs 11% for the tac/sir and tac/sir/mtx cohorts, respectively (p=0.46). There was also no difference in cumulative incidence of extensive chronic GVHD, treatment related mortality, disease relapse, or survival. The GVHD prophylaxis combination of tacrolimus and sirolimus is well tolerated, and is associated with a low incidence of acute GVHD in matched related donor RIC transplantation. The omission of mini-methotrexate from the tacrolimus and sirolimus GVHD

  5. Insulin inhalation: NN 1998.

    PubMed

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  6. Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.

    PubMed

    Vigouroux, Stéphane; Tabrizi, Reza; Melot, Cyril; Coiffard, Joelle; Lafarge, Xavier; Marit, Gérald; Bouabdallah, Krimo; Pigneux, Arnaud; Leguay, Thibaut; Dilhuydy, Marie-Sarah; Schmitt, Anna; Boiron, Jean-Michel; Milpied, Noël

    2011-01-01

    Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.

  7. Pilot Study of Nelarabine in Combination With Intensive Chemotherapy in High-Risk T-Cell Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

    PubMed Central

    Dunsmore, Kimberly P.; Devidas, Meenakshi; Linda, Stephen B.; Borowitz, Michael J.; Winick, Naomi; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce M.

    2012-01-01

    Purpose Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86–based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL). Patients and Methods In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m2 once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1% at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m2 once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m2 once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]). Results The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42% with v 81% without nelarabine). Five-year event-free survival (EFS) rates were 73% for 11 stage one SER patients and 67% for 22 stage two SER patients treated with nelarabine versus 69% for 16 stage one RER patients treated without nelarabine and 74% for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73% versus 69% for those treated without nelarabine (n = 16). Conclusion Addition of nelarabine to a BFM 86–based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly. PMID:22734022

  8. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Patients Treated With Intensity-Modulated Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal

    SciTech Connect

    Bazan, Jose G.; Luxton, Gary; Mok, Edward C.; Koong, Albert C.; Chang, Daniel T.

    2012-11-01

    Purpose: To identify dosimetric parameters that correlate with acute hematologic toxicity (HT) in patients with squamous cell carcinoma of the anal canal treated with definitive chemoradiotherapy (CRT). Methods and Materials: We analyzed 33 patients receiving CRT. Pelvic bone (PBM) was contoured for each patient and divided into subsites: ilium, lower pelvis (LP), and lumbosacral spine (LSS). The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. Endpoints included grade {>=}3 HT (HT3+) and hematologic event (HE), defined as any grade {>=}2 HT with a modification in chemotherapy dose. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression was used to test associations between HT and dosimetric/clinical parameters. Results: Nine patients experienced HT3+ and 15 patients experienced HE. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.175, n = 1, and TD{sub 50} = 32 Gy. With this model, mean PBM doses of 25 Gy, 27.5 Gy, and 31 Gy result in a 10%, 20%, and 40% risk of HT3+, respectively. Compared with patients with mean PBM dose of <30 Gy, patients with mean PBM dose {>=}30 Gy had a 14-fold increase in the odds of developing HT3+ (p = 0.005). Several low-dose radiation parameters (i.e., PBM-V10) were associated with the development of HT3+ and HE. No association was found with the ilium, LP, or clinical factors. Conclusions: LKB modeling confirms the expectation that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Low-dose radiation to the PBM was also associated with clinically significant HT. Keeping the mean PBM dose <22.5 Gy and <25 Gy is associated with a 5% and 10% risk of HT, respectively.

  9. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves.

    PubMed

    Kamal, M M; Van Eetvelde, M; Bogaert, H; Hostens, M; Vandaele, L; Shamsuddin, M; Opsomer, G

    2015-09-01

    The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves. Birth weight and gestational age of the calves at delivery were determined. On the next day, heart girth, wither height and diagonal length of both the calves and their dams were measured. Parity, body condition score and age at calving were recorded for all dams. For the cows, days open before last gestation, lactation length (LL), length of dry period (DP) and calving interval were also calculated. The magnitude and shape of the lactation curve both quantified using the MilkBot model based on monthly milk weights, were used to calculate the amount of milk produced during gestation. Using the same procedure, cumulative milk production from conception to drying off (MGEST) was calculated. A blood sample was collected from all calves (n=481; 169 born to heifers and 312 born to cows) at least 5 h after a milk meal on day 3 of life to measure basal glucose and insulin levels. In addition, an intravenous glucose-stimulated insulin secretion test was performed in a subset of the calves (n=316). After descriptive analysis, generalized linear mixed models were used to identify factors that were significantly associated with the major insulin traits (Insb, basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR, acute insulin response; DI, disposition index) of the newborn calves. The overall average birth weight of the calves was 42.7 ± 5.92 kg. The insulin traits were significantly associated with gender and season of birth when data of all calves were analyzed. In addition, the insulin traits in calves born to cows were significantly associated with MGEST, DP and LL. The Insb was estimated to be higher in calves born to the cows having passed a higher MGEST (P=0.076) and longer DP (P=0.034). The

  10. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves.

    PubMed

    Kamal, M M; Van Eetvelde, M; Bogaert, H; Hostens, M; Vandaele, L; Shamsuddin, M; Opsomer, G

    2015-09-01

    The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves. Birth weight and gestational age of the calves at delivery were determined. On the next day, heart girth, wither height and diagonal length of both the calves and their dams were measured. Parity, body condition score and age at calving were recorded for all dams. For the cows, days open before last gestation, lactation length (LL), length of dry period (DP) and calving interval were also calculated. The magnitude and shape of the lactation curve both quantified using the MilkBot model based on monthly milk weights, were used to calculate the amount of milk produced during gestation. Using the same procedure, cumulative milk production from conception to drying off (MGEST) was calculated. A blood sample was collected from all calves (n=481; 169 born to heifers and 312 born to cows) at least 5 h after a milk meal on day 3 of life to measure basal glucose and insulin levels. In addition, an intravenous glucose-stimulated insulin secretion test was performed in a subset of the calves (n=316). After descriptive analysis, generalized linear mixed models were used to identify factors that were significantly associated with the major insulin traits (Insb, basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR, acute insulin response; DI, disposition index) of the newborn calves. The overall average birth weight of the calves was 42.7 ± 5.92 kg. The insulin traits were significantly associated with gender and season of birth when data of all calves were analyzed. In addition, the insulin traits in calves born to cows were significantly associated with MGEST, DP and LL. The Insb was estimated to be higher in calves born to the cows having passed a higher MGEST (P=0.076) and longer DP (P=0.034). The

  11. Insulin Delivery System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    When Programmable Implantable Medication System (PIMS) is implanted in human body, it delivers precise programmed amounts of insulin over long periods of time. Mini-Med Technologies has been refining the Technologies since initial development at APL. The size of a hockey puck, and encased in titanium shell, PIMS holds about 2 1/2 teaspoons of insulin at a programmed basal rate. If a change in measured blood sugar level dictates a different dose, the patient can vary the amount of insulin delivered by holding a small radio transceiver over the implanted system and dialing in a specific program held in the PIMS computer memory. Insulin refills are accomplished approximately 4 times a year by hypodermic needle.

  12. All about Insulin Resistance

    MedlinePlus

    ... news is that cutting calories, being active, and losing weight can reverse insulin resistance and lower your ... you’ll lose weight. Studies have shown that losing even 7% of your weight, may help. For ...

  13. [Estimation of different models of insulin therapy in noninsulin-dependent diabetes mellitus].

    PubMed

    Trznadel-Morawska, I; Małecki, M; Sieradzki, J

    1997-01-01

    The aim of the study was to find out which model of insulin therapy in patients with noninsulin-dependent diabetes mellitus with secondary inefficacy of sulphonylurea is most effective for glycemia normalization, inhibition of late complications, prevention of atherosclerosis and better quality of life. In 27 patients aged 40-70 years with a history of diabetes over 3 years, BMI < 30, treated with maximal doses of Euclamine we applied 4 therapeutic models: 1) intensive insulin therapy (M1), 2) two injections of three insulins (M2), 3) Euclamin 20 mg + intermediate insulin (M3), 4) Euclamine 20 mg + intermediate insulin (M4). The study lasted 3 months whereas education was carried out within the first two weeks. The following parameters were evaluated: beta cell reserve (glibenclamide test), peptide C level, HbA1C concentration, glycemia profile, lipids, creatinine level. Foci of infection were eradicated. It was found out that: 1) all models of insulin therapy, produced near normoglycemia, 2) the model of intensive insulin therapy does not generate hyperinsulinism in face of body weight loss and improved lipid profile, 3) the model of intensive insulin therapy shows long-term efficacy in the absence of effects when assessing fasting glycemia state (HbA1C, Schilchtkrull's index, lipid indices), 4) the model combining Euclamine with intermediate insulin is on intermediate step leading to another form of insulin therapy. PMID:9380804

  14. Failure of Homeostatic Model Assessment of Insulin Resistance to Detect Marked Diet-Induced Insulin Resistance in Dogs

    PubMed Central

    Ader, Marilyn; Stefanovski, Darko; Richey, Joyce M.; Kim, Stella P.; Kolka, Cathryn M.; Ionut, Viorica; Kabir, Morvarid; Bergman, Richard N.

    2014-01-01

    Accurate quantification of insulin resistance is essential for determining efficacy of treatments to reduce diabetes risk. Gold-standard methods to assess resistance are available (e.g., hyperinsulinemic clamp or minimal model), but surrogate indices based solely on fasting values have attractive simplicity. One such surrogate, the homeostatic model assessment of insulin resistance (HOMA-IR), is widely applied despite known inaccuracies in characterizing resistance across groups. Of greater significance is whether HOMA-IR can detect changes in insulin sensitivity induced by an intervention. We tested the ability of HOMA-IR to detect high-fat diet–induced insulin resistance in 36 healthy canines using clamp and minimal model analysis of the intravenous glucose tolerance test (IVGTT) to document progression of resistance. The influence of pancreatic function on HOMA-IR accuracy was assessed using the acute insulin response during the IVGTT (AIRG). Diet-induced resistance was confirmed by both clamp and minimal model (P < 0.0001), and measures were correlated with each other (P = 0.001). In striking contrast, HOMA-IR ([fasting insulin (μU/mL) × fasting glucose (mmol)]/22.5) did not detect reduced sensitivity induced by fat feeding (P = 0.22). In fact, 13 of 36 animals showed an artifactual decrease in HOMA-IR (i.e., increased sensitivity). The ability of HOMA-IR to detect diet-induced resistance was particularly limited under conditions when insulin secretory function (AIRG) is less than robust. In conclusion, HOMA-IR is of limited utility for detecting diet-induced deterioration of insulin sensitivity quantified by glucose clamp or minimal model. Caution should be exercised when using HOMA-IR to detect insulin resistance when pancreatic function is compromised. It is necessary to use other accurate indices to detect longitudinal changes in insulin resistance with any confidence. PMID:24353184

  15. Effect of insulin on LHRH release by perifused hypothalamic fragments.

    PubMed

    Arias, P; Rodríguez, M; Szwarcfarb, B; Sinay, I R; Moguilevsky, J A

    1992-09-01

    Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle's, pH 7.4, gassed with 95% O2/5% CO2, flow rate 50 microliters/min). When glucose was absent (in the presence of insulin 10 mU/l), LHRH release was reduced, peak levels being < 5 pg/100 microliters. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 microliters (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/l) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/100 microliters (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH release.

  16. Insulin signaling and addiction

    PubMed Central

    Daws, Lynette C.; Avison, Malcolm J.; Robertson, Sabrina D.; Niswender, Kevin D.; Galli, Aurelio; Saunders, Christine

    2012-01-01

    Across species, the brain evolved to respond to natural rewards such as food and sex. These physiological responses are important for survival, reproduction and evolutionary processes. It is no surprise, therefore, that many of the neural circuits and signaling pathways supporting reward processes are conserved from Caenorhabditis elegans to Drosophilae, to rats, monkeys and humans. The central role of dopamine (DA) in encoding reward and in attaching salience to external environmental cues is well recognized. Less widely recognized is the role of reporters of the “internal environment”, particularly insulin, in the modulation of reward. Insulin has traditionally been considered an important signaling molecule in regulating energy homeostasis and feeding behavior rather than a major component of neural reward circuits. However, research over recent decades has revealed that DA and insulin systems do not operate in isolation from each other, but instead, work together to orchestrate both the motivation to engage in consummatory behavior and to calibrate the associated level of reward. Insulin signaling has been found to regulate DA neurotransmission and to affect the ability of drugs that target the DA system to exert their neurochemical and behavioral effects. Given that many abused drugs target the DA system, the elucidation of how dopaminergic, as well as other brain reward systems, are regulated by insulin will create opportunities to develop therapies for drug and potentially food addiction. Moreover, a more complete understanding of the relationship between DA neurotransmission and insulin may help to uncover etiological bases for “food addiction” and the growing epidemic of obesity. This review focuses on the role of insulin signaling in regulating DA homeostasis and DA signaling, and the potential impact of impaired insulin signaling in obesity and psychostimulant abuse. PMID:21420985

  17. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  18. The Use of Session RPE to Monitor the Intensity of Weight Training in Older Women: Acute Responses to Eccentric, Concentric, and Dynamic Exercises

    PubMed Central

    Ferreira, Sandro S.; Krinski, Kleverton; Alves, Ragami C.; Benites, Mariana L.; Redkva, Paulo E.; Elsangedy, Hassan M.; Buzzachera, Cosme F.; Souza-Junior, Tácito P.; da Silva, Sergio G.

    2014-01-01

    The rating of perceived exertion (RPE) is ability to detect and interpret organic sensations while performing exercises. This method has been used to measure the level of effort that is felt during weight-training at a given intensity. The purpose of this investigation was to compare session RPE values with those of traditional RPE measurements for different weight-training muscle actions, performed together or separately. Fourteen women with no former weight-training experience were recruited for the investigation. All participants completed five sessions of exercise: familiarization, maximum force, concentric-only (CONC-only), eccentric-only (ECC-only), and dynamic (DYN = CONC + ECC). The traditional RPE method was measured after each series of exercises, and the session RPE was measured 30 min after the end of the training session. The statistical analyses used were the paired t-test, one-way analysis of variance, and repeated measures analysis of variance. Significant differences between traditional RPE and session RPE for DYN, CONC, and ECC exercises were not found. This investigation demonstrated that session RPE is similar to traditional RPE in terms of weight-training involving concentric, eccentric, or dynamic muscle exercises, and that it can be used to prescribe and monitor weight-training sessions in older subjects. PMID:24834354

  19. Moving toward the ideal insulin for insulin pumps.

    PubMed

    Cengiz, Eda; Bode, Bruce; Van Name, Michelle; Tamborlane, William V

    2016-01-01

    Advances in insulin formulations have been important for diabetes management and achieving optimal glycemic control. Rapid-acting insulin analogs provide a faster time-action profile than regular insulin and are approved for use in pumps. However, the need remains for therapy to deliver a more physiologic insulin profile. New insulin formulations and delivery methods are in development, with the aim of accelerating insulin absorption to accomplish ultra-fast-acting insulin time-action profiles. Furthermore, the integration of continuous glucose monitoring with insulin pump therapy enables on-going adjustment of insulin delivery to optimize glycemic control throughout the day and night. These technological and pharmacological advances are likely to facilitate the development of closed-loop pump systems (i.e., artificial pancreas), and improve glycemic control and quality of life for patients with diabetes. PMID:26560137

  20. Purification and functional characterization of pancreatic insulin from camel (Camelus dromedarius)

    PubMed Central

    Elamin, Babiker A.; Al-Maleki, Abdulmajeed; Ismael, Mohammad A.; Ayoub, Mohammed Akli

    2014-01-01

    Large-scale production of insulin still represents the key step in helping diabetic patients throughout the world. Many species and approaches have been used for the production of insulin. In this study, we purified and characterized for the first time pancreatic insulin from the Arabian camel (Camelus dromedarius) using a modified acid-alcohol extraction method. After extraction insulin was purified using a one-step gel filtration on a Sephadex G-50 column leading to a purification yield of 80 mg/kg (20%) of camel pancreas. The purity of camel insulin was assessed by SDS–PAGE and HPLC using insulin from human, bovine and porcine as standards. Molecular weight was determined for purified camel insulin as 5800 Daltons and its amino acid composition is similar to that known for other species. The functional characterization of purified crude camel insulin was demonstrated in vitro by positive competition by radioimmunoassay and in vivo showing camel insulin inducing acute hypoglycaemia in mice. Together, our study reports for the first time the successful purification of functional insulin from camel pancreas with similar properties compared to other insulin species. This is of great interest given that the camel represents considerable economic worth in many countries. PMID:25473366

  1. Effects of Prior Intensive Insulin Therapy and Risk Factors on Visual Quality-of-Life in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort

    PubMed Central

    Gubitosi-Klug, Rose A.; Sun, Wanjie; Cleary, Patricia A.; Braffett, Barbara H.; Aiello, Lloyd Paul; Das, Arup; Tamborlane, William; Klein, Ronald

    2016-01-01

    Importance Preservation of visual acuity in patients with diabetes is critical to preserve VQOL. Interventions to improve glycemic control through early intensive treatment of diabetes reduce rates of severe retinopathy and preserve VA. Objective To assess the effect of prior intensive treatment and risk factors on visual quality of life (VQOL) in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) cohort. Design Randomized controlled clinical trial followed by an observational follow-up study. Setting 28 institutions across the United States and Canada. Participants 1184 DCCT/EDIC participants with type 1 diabetes completed the National Eye Institute (NEI) Visual Functioning Questionnaire (VFQ) during EDIC years 17-20, up to thirty years after the start of the DCCT. Main Outcome Measures The 25-item NEI-VFQ was administered. Visual acuity (VA) was measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol and the presence and severity of retinopathy and macular edema were detected by masked grading of stereoscopic color fundus photographs using the ETDRS retinopathy severity scheme. The composite VQOL and subscales were scored on a scale of 0 to 100 corresponding to poor to excellent function, respectively. Quantile regression was used to assess the treatment/risk factor effect on median QOL score, owing to the ordinal scoring and a skewed distribution. Results The overall average VQOL for DCCT/EDIC participants with a 30 year duration of diabetes was high (median 91.7, interquartile (IQR), 89.7-96.9). After adjustment for gender, age, HbA1c, and retinopathy level at DCCT baseline, the former intensive (INT) treatment group had a significant, albeit modest, improvement in overall VQOL compared to the former conventional (CONV) diabetes treatment group (median difference −1.0 [−1.7, −0.3], p=0.0058). This beneficial treatment effect was fully attributed to the prior

  2. Signal intensity of MR-images of thigh muscles following acute open- and closed chain kinetic knee extensor exercise - index of muscle use.

    PubMed

    Enocson, A G; Berg, H E; Vargas, R; Jenner, G; Tesch, P A

    2005-07-01

    Exercise-induced shifts in signal intensity (SI) of magnetic resonance (MR) images were examined to assess indirectly muscle use in closed- and open-chain knee extensor exercises. Eight men performed five sets of 8-12 repetitions in the leg press (LP) and the seated knee extension (KE) exercises at 50, 75 and 100%, respectively of the 5 x 10 repetition maximum (RM) load. Prior to exercise and after each load setting, images of the thigh were obtained. The increase in SI (Delta SI) of the quadriceps at 100% load was greater (P < 0.05) after KE (32.1 +/- 9.0%) than after LP (21.9 +/- 9.2%). Regardless of load, the four individual muscles of the quadriceps showed similar changes in SI after LP. The three vastii muscles showed comparable increases in SI after KE. M. rectus femoris showed greater (P < 0.05) Delta SI than the vastii muscles at 100%. Neither exercise produced increase in SI of mm. semimembranosus, semitendinosus, gracilis or biceps femoris. Mm. adductor magnus and longus showed increased (13.3 +/- 6.5%; P < 0.05) SI after LP, but not after KE, at 100% load. The present data also infer greater involvement of the quadriceps muscle in the open-chain knee extension than in the closed-chain leg press exercise. The results of the current investigation also indicate similar over-all use among the three vastii muscles in LP and KE, but differential m. rectus femoris use between the two exercises. This report extends the merits of the MR imaging technique as an aid to study individual muscle involvement in a particular exercise task. PMID:15918061

  3. Insulin pump therapy in pregnancy.

    PubMed

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience. PMID:27582150

  4. A Treatment Planning and Acute Toxicity Comparison of Two Pelvic Nodal Volume Delineation Techniques and Delivery Comparison of Intensity-Modulated Radiotherapy Versus Volumetric Modulated Arc Therapy for Hypofractionated High-Risk Prostate Cancer Radiotherapy

    SciTech Connect

    Myrehaug, Sten; Chan, Gordon; Craig, Tim; Weinberg, Vivian; Cheng, Chun; Roach, Mack; Cheung, Patrick; Sahgal, Arjun

    2012-03-15

    Purpose: To perform a comparison of two pelvic lymph node volume delineation strategies used in intensity-modulated radiotherapy (IMRT) for high risk prostate cancer and to determine the role of volumetric modulated arc therapy (VMAT). Methods and Materials: Eighteen consecutive patients accrued to an ongoing clinical trial were identified according to either the nodal contouring strategy as described based on lymphotropic nanoparticle-enhanced magnetic resonance imaging technology (9 patients) or the current Radiation Therapy Oncology Group (RTOG) consensus guidelines (9 patients). Radiation consisted of 45 Gy to prostate, seminal vesicles, and lymph nodes, with a simultaneous integrated boost to the prostate alone, to a total dose of 67.5 Gy delivered in 25 fractions. Prospective acute genitourinary and gastrointestinal toxicities were compared at baseline, during radiotherapy, and 3 months after radiotherapy. Each patient was retrospectively replanned using the opposite method of nodal contouring, and plans were normalized for dosimetric comparison. VMAT plans were also generated according to the RTOG method for comparison. Results: RTOG plans resulted in a significantly lower rate of genitourinary frequency 3 months after treatment. The dosimetric comparison showed that the RTOG plans resulted in both favorable planning target volume (PTV) coverage and lower organs at risk (OARs) and integral (ID) doses. VMAT required two to three arcs to achieve adequate treatment plans, we did not observe consistent dosimetric benefits to either the PTV or the OARs, and a higher ID was observed. However, treatment times were significantly shorter with VMAT. Conclusion: The RTOG guidelines for pelvic nodal volume delineation results in favorable dosimetry and acceptable acute toxicities for both the target and OARs. We are unable to conclude that VMAT provides a benefit compared with IMRT.

  5. Influence of anti-insulin antibodies on insulin immunoassays in the autoimmune insulin syndrome.

    PubMed

    Casesnoves, A; Mauri, M; Dominguez, J R; Alfayate, R; Picó, A M

    1998-11-01

    The autoimmune insulin syndrome (AIS) is a rare, benign syndrome characterized by hyperinsulinaemia and hypoglycaemia associated with the presence of autoantibodies to insulin in patients who have not been treated with insulin. We report here the case of a 52-year-old patient with recurrent attacks of severe postprandial hypoglycaemia and we also present the effect of anti-insulin antibodies on insulin immunoassays. The patient was submitted to the following diagnostic tests: 5-h oral glucose tolerance test (OGTT), a prolonged 72-h fast and an insulin tolerance test (ITT). Serum glucose, total and free insulin, C-peptide, proinsulin, insulin antibodies and other autoantibodies were measured. Insulin concentrations were measured by two methods: a double antibody radioimmunoassay (RIA) and an immunoradiometric assay (IRMA). Insulin concentration measured by RIA was extremely high in the OGTT and 72-h fast. In contrast, insulin concentrations measured by IRMA were between 120 and 888 pmol/L in the OGTT and between 37 and 133 pmol/L during the 72-h fast. Fasting free-insulin concentrations measured by RIA were between 2224 and 2669 pmol/L, whereas free-insulin concentrations measured by IRMA ranged between 93 and 237 pmol/L. Total insulin concentrations measured by RIA and IRMA were 57,615 and 94,021 pmol/L, respectively. The C-peptide concentrations were moderately high in the three tests. Serum insulin antibody concentrations were extremely high (62-71%), compared with less than 3% in normal serum samples. In conclusion, the high insulin concentrations measured by RIA were caused by insulin autoantibodies. However, insulin concentrations measured by IRMA were not influenced by them. We conclude that IRMA is the more accurate method for measuring insulin concentrations in such cases.

  6. Insulin-producing cells.

    PubMed

    Schroeder, Insa S; Kania, Gabriela; Blyszczuk, Przemyslaw; Wobus, Anna M

    2006-01-01

    Embryonic stem (ES) cells offer great potential for cell replacement and tissue engineering therapies because of their almost unlimited proliferation capacity and the potential to differentiate into cellular derivatives of all three primary germ layers. This chapter describes a strategy for the in vitro differentiation of mouse ES cells into insulin-producing cells. The three-step protocol does not select for nestin-expressing cells as performed in previous differentiation systems. It includes (1) the spontaneous differentiation of ES cells via embryoid bodies and (2) the formation of progenitor cells of all three primary germ layers (multilineage progenitors) followed by (3) directed differentiation into the pancreatic lineage. The application of growth and extracellular matrix factors, including laminin, nicotinamide, and insulin, leads to the development of committed pancreatic progenitors, which subsequently differentiate into islet-like clusters that release insulin in response to glucose. During differentiation, transcript levels of pancreas-specific transcription factors (i.e., Pdx1, Pax4) and of genes specific for early and mature beta cells, including insulin, islet amyloid pancreatic peptide, somatostatin, and glucagon, are upregulated. C-peptide/insulin-positive islet-like clusters are formed, which release insulin in response to high glucose concentrations at terminal stages. The differentiated cells reveal functional properties with respect to voltage-activated Na+ and ATP-modulated K+ channels and normalize blood glucose levels in streptozotocin-treated diabetic mice. In conclusion, we demonstrate the efficient differentiation of murine ES cells into insulin-producing cells, which may help in the future to establish ES cell-based therapies in diabetes mellitus.

  7. Insulin resistance in young, lean male subjects with essential hypertension.

    PubMed

    Penesova, A; Cizmarova, E; Belan, V; Blazicek, P; Imrich, R; Vlcek, M; Vigas, M; Selko, D; Koska, J; Radikova, Z

    2011-06-01

    Impaired insulin action, frequently found in essential hypertension (HT), is modified by other factors, such as higher age, accumulation of body fat, dyslipidaemia, impaired glucose metabolism and endothelial dysfunction. In addition, antihypertensive and insulin-sensitizing medication itself may significantly affect cardiovascular and metabolic milieu. The aim of this study was to assess insulin sensitivity, acute insulin response, lipidaemic status and the adipokines' concentrations with regard to abdominal fat distribution in young, lean male subjects with treatment-naïve essential HT and in matched healthy normotensive (NT) subjects. We studied 27 HT patients (age: 19.9±0.6 years; body mass index (BMI): 22.9±0.5 kg m(-2)) and 15 NT controls (age: 22.3±1.0 years; BMI: 23.7±0.6 kg m(-2)). The subjects underwent an oral and an intravenous glucose tolerance test (OGTT, IVGTT) on separate days in random order. Higher fasting insulin (P<0.001), non-esterified fatty acids (P<0.05) and plasminogen activator inhibitor factor 1 concentrations (P<0.05) were found in HT patients when compared with NT patients. Despite comparable anthropometric parameters and body fat distribution assessed by magnetic resonance imaging in both groups, newly diagnosed untreated young hypertensive male subjects showed decreased insulin sensitivity, augmented insulin response to both oral and intravenous glucose load (P<0.01; P<0.05 respectively) and 'higher still normal' 2-h plasma glucose levels during OGTT. Untreated, young, lean hypertensive male subjects, with distribution of abdominal adipose tissue and lipid profile comparable with their healthy NT matched counterparts, showed considerable signs of insulin resistance and hyperinsulinaemia. We hypothesize that insulin resistance is the initial feature, which is influenced by several environmental factors, and HT is one of their common consequences. PMID:20631738

  8. Effects of food restriction and insulin treatment on (Ca2+ + Mg2+)-ATPase response to insulin in kidney basolateral membranes of noninsulin-dependent diabetic rats.

    PubMed

    Levy, J; Grunberger, G; Karl, I; Gavin, J R

    1990-01-01

    Insulin increases (Ca2+ + Mg2+)-ATPase activity in cell membranes of normal rats but fails to do so in membranes of non-insulin-dependent diabetic (NIDD) rats. The loss of regulatory effect of the hormone on the enzyme might contribute to the insulin resistance observed in the NIDD animals. To further test this hypothesis, the effects of insulin treatment and acute food restriction on the ability of insulin to regulate the ATPase activity in kidney basolateral membranes (BLM) of NIDD rats were studied. Although insulin levels in NIDD and control rats were similar, plasma glucose was higher in the NIDD rats (18.3 +/- 1.5 v 19.3 +/- 1.7 microU/mL and 236 +/- 32 v 145 +/- 3 mg/dL, respectively). Insulin treatment (2 U/100 g), which increased plasma insulin in the NIDD rats (47.8 +/- 11.5 microU/mL; P less than .05), did not decrease their glucose (221 +/- 25 mg/dL). Higher insulin dose (4 U/100 g) decreased glucose level in the NIDD rats (73 +/- 3 mg/dL; P less than .001) but increased their plasma insulin 10-fold (202.5 +/- 52.5 microU/mL). Acute food restriction decreased glucose levels in the NIDD rats to levels seen in controls (135 +/- 3 mg/dL), while their insulin decreased by half (8.5 +/- 1.0 microU/mL; P less than .05). Basal (Ca2+ + Mg2+)-ATPase activity in BLM of all diabetic rats was higher than in controls (P less than .05). None of the treatments reversed this defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2136760

  9. Insulin signaling genes modulate nicotine-induced behavioral responses in Caenorhabditis elegans.

    PubMed

    Wescott, Seth A; Ronan, Elizabeth A; Xu, X Z Shawn

    2016-02-01

    Insulin signaling has been suggested to modulate nicotine dependence, but the underlying genetic evidence has been lacking. Here, we used the nematode, Caenorhabditis elegans, to investigate whether genetic alterations in the insulin signaling pathway affect behavioral responses to nicotine. For this, we challenged drug-naive C. elegans with an acute dose of nicotine (100 μmol/l) while recording changes in their locomotion speed. Although nicotine treatment stimulated locomotion speed in wild-type C. elegans, the same treatment reduced locomotion speed in mutants defective in insulin signaling. This phenotype could be suppressed by mutations in daf-16, a gene encoding a FOXO transcription factor that acts downstream of insulin signaling. Our data suggest that insulin signaling genes, daf-2, age-1, pdk-1, akt-1, and akt-2, modulate behavioral responses to nicotine in C. elegans, indicating a genetic link between nicotine behavior and insulin signaling.

  10. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    SciTech Connect

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  11. Disturbed Eating Behavior and Omission of Insulin in Adolescents Receiving Intensified Insulin Treatment

    PubMed Central

    Wisting, Line; Frøisland, Dag Helge; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

    2013-01-01

    OBJECTIVE To establish the prevalence of disturbed eating behavior (DEB) and insulin omission among adolescents with type 1 diabetes using intensive insulin treatment in a nationwide population-based study. RESEARCH DESIGN AND METHODS The Diabetes Eating Problem Survey–Revised (DEPS-R) is a diabetes-specific screening tool for DEB. Clinical data and HbA1c were obtained from the Norwegian Childhood Diabetes Registry. RESULTS A total of 770 children and adolescents 11–19 years of age with type 1 diabetes completed the DEPS-R. A total of 27.7% of the females and 8.6% of the males scored above the DEPS-R cutoff. Participants scoring above the cutoff had significantly higher HbA1c (9.2% [77 mmol/mol]; SD, 1.6) than participants scoring below the cutoff (8.4% [68 mmol/mol]; SD, 1.3; P < 0.001). The prevalence of DEB increased significantly with age and weight, from 7.2% in the underweight group to 32.7% in the obese group, and from 8.1% in the youngest age-group (11–13 years) to 38.1% in the oldest age-group (17–19 years). A total of 31.6% of the participants reported insulin restriction and 6.9% reported insulin omission after overeating. Patients reporting insulin restriction had significantly higher HbA1c (9.0% [75 mmol/mol]; SD, 1.7) than nonrestrictors (8.3% [67 mmol/mol]; SD, 1.2; P < 0.001). CONCLUSIONS One-fourth of girls with type 1 diabetes scored above the cutoff for DEB and one-third reported skipping their insulin dose entirely at least occasionally after overeating. Both DEB and insulin restriction were associated with poorer metabolic control, which may increase the risk of serious late diabetes complications. PMID:23963896

  12. New Insulins and New Aspects in Insulin Delivery.

    PubMed

    Woo, Vincent C

    2015-08-01

    The major abnormality in both type 1 and type 2 diabetes is insulin deficiency. The methods of replacing insulin have improved throughout the decades, but hypoglycemia is still the limiting factor for many individuals with diabetes, and it prevents them from achieving ideal glycemic targets. New insulin and newer delivery systems are being developed that can improve some of the limitations of current insulins or make the delivery of insulins more acceptable for some patients. Extending the duration of action of basal insulins and shortening the peak of fast-acting insulins may have advantages for individuals with diabetes. Different delivery systems may make insulin more acceptable to patients and may have other advantages, which may aid in attaining better glycemic control.

  13. New Insulins and New Aspects in Insulin Delivery.

    PubMed

    Woo, Vincent C

    2015-08-01

    The major abnormality in both type 1 and type 2 diabetes is insulin deficiency. The methods of replacing insulin have improved throughout the decades, but hypoglycemia is still the limiting factor for many individuals with diabetes, and it prevents them from achieving ideal glycemic targets. New insulin and newer delivery systems are being developed that can improve some of the limitations of current insulins or make the delivery of insulins more acceptable for some patients. Extending the duration of action of basal insulins and shortening the peak of fast-acting insulins may have advantages for individuals with diabetes. Different delivery systems may make insulin more acceptable to patients and may have other advantages, which may aid in attaining better glycemic control. PMID:26233724

  14. Molecular Mechanisms of Insulin Secretion and Insulin Action.

    ERIC Educational Resources Information Center

    Flatt, Peter R.; Bailey, Clifford J.

    1991-01-01

    Information and current ideas on the factors regulating insulin secretion, the mechanisms underlying the secretion and biological actions of insulin, and the main characteristics of diabetes mellitus are presented. (Author)

  15. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

    PubMed Central

    Czerw, Tomasz; Labopin, Myriam; Schmid, Christoph; Cornelissen, Jan J.; Chevallier, Patrice; Blaise, Didier; Kuball, Jürgen; Vigouroux, Stephane; Garban, Frédéric; Lioure, Bruno; Fegueux, Nathalie; Clement, Laurence; Sandstedt, Anna; Maertens, Johan; Guillerm, Gaëlle; Bordessoule, Dominique

    2016-01-01

    Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 × 10^6/kg and >8.25 × 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes. PMID:27036034

  16. Analysis of alternatives for insulinizing patients to achieve glycemic control and avoid accompanying risks of hypoglycemia

    PubMed Central

    GAO, JIALIN; XIONG, QIANYIN; MIAO, JUN; ZHANG, YAO; XIA, LIBING; LU, MEIQIN; ZHANG, BINHUA; CHEN, YUEPING; ZHANG, ANSU; YU, CUI; WANG, LI-ZHUO

    2015-01-01

    The aims of the present study were to explore the efficacy of glycemic control and the risks of hypoglycemia with different methods of insulin therapy, and to provide reference data for the clinical treatment of diabetes. In this retrospective study, hospitalized patients diagnosed with type 2 diabetes between March and December 2014, in the Department of Endocrinology in the First Affiliated Hospital of Wannan Medical College, were divided into three groups, including an intensive insulin analogue therapy group, a premixed insulin analogue treatment group and a premixed human insulin therapy group. The efficacy of glycemic control and the incidence of hypoglycemia were determined in each of the insulin treatment groups. Compared with the other treatment groups, the intensive insulin analogue therapy group was associated with superior blood glucose control, shorter time to reach standard insulin regimen, shorter hospitalization time, fewer fluctuations in blood glucose levels and lower insulin dosage on discharge from hospital. However, this treatment was also associated with a high risk of hypoglycemia. In conclusion, when combined with the effective prevention of hypoglycemia and appropriate nursing care (especially in hospital care), intensive insulin analogue therapy may provide the greatest benefit to patients. PMID:26137223

  17. The doripenem serum concentrations in intensive care patients suffering from acute kidney injury, sepsis, and multi organ dysfunction syndrome undergoing continuous renal replacement therapy slow low-efficiency dialysis.

    PubMed

    Wieczorek, Andrzej; Tokarz, Andrzej; Gaszynski, Wojciech; Gaszynski, Tomasz

    2014-01-01

    Doripenem is a novel wide-spectrum antibiotic, and a derivate of carbapenems. It is an ideal antibiotic for treatment of serious nosocomial infections and severe sepsis for its exceptionally high efficiency and broad antibacterial spectrum of action. Doripenem is eliminated mainly by the kidneys. In cases of acute kidney injury, dosing of doripenem depends on creatinine clearance and requires adjustments. Doripenem is eliminated during hemodialysis because its molecular weight is 300-400 Da. The aim of this study was to establish the impact of continuous renal replacement therapy (CRRT) slow low-efficiency dialysis (SLED) on doripenem serum concentrations in a population of intensive-therapy patients with life-threatening infections and severe sepsis. Ten patients were enrolled in this observational study. Twelve blood samples were collected during the first administration of doripenem in a 1-hour continuous infusion while CRRT SLED was provided. Fluid chromatography was used for measurement of the concentration of doripenem in serum. In all collected samples, concentration of doripenem was above the minimum inhibition concentration of this antibiotic. Based on these results, we can draw the conclusion that doripenem concentration is above the minimum inhibition concentration throughout all of CRRT. The dosing pattern proposed by the manufacturer can be used in patients receiving CRRT SLED without necessary modifications.

  18. Insulin C-peptide test

    MedlinePlus

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  19. The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study

    PubMed Central

    Sale, Michèle M; Hsu, Fang-Chi; Palmer, Nicholette D; Gordon, Candace J; Keene, Keith L; Borgerink, Hermina M; Sharma, Arun J; Bergman, Richard N; Taylor, Kent D; Saad, Mohammed F; Norris, Jill M

    2007-01-01

    Background Variants of uncoupling protein genes UCP1 and UCP2 have been associated with a range of traits. We wished to evaluate contributions of known UCP1 and UCP2 variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. Methods We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach. Results UCP1 A-3826G was associated with AIRg in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although UCP1 expression is reported to be restricted to adipose tissue, RT-PCR indicated that UCP1 is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. UCP2 A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and UCP2 G-866A with waist-to-hip ratio in AA (P = 0.016). Conclusion This study suggests a functional variant of UCP1 contributes to the variance of AIRg in an AA population; the plausibility of this unexpected association is supported by the novel finding that UCP1 is expressed in islets. PMID:17397545

  20. The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis.

    PubMed

    Deng, Hu-Ping; Chai, Jia-Ke

    2009-10-01

    Insulin resistance, hyperglycemia, inflammatory disorders and immune dysfunction cause high morbidity and mortality in patients with severe trauma, burn injuries, or sepsis. Many studies have shown that intensive insulin therapy can combat insulin resistance, decrease blood glucose levels, and induce anabolic processes, thus, decreasing morbidity and mortality. Moreover, in recent years, it has been proven that insulin can attenuate systemic inflammatory responses and modulate the proliferation, apoptosis, differentiation and immune functions of certain immune cells, especially monocytes/macrophages, neutrophils, and T cells associated with severe trauma, burn injury, or sepsis. This effect of insulin may expand our understanding of intensive insulin therapy in critically ill patients. This review attempts to summarize studies on the modulatory effects and mechanisms of insulin therapy on systemic inflammation and immune cells in severe trauma, burn injury and sepsis, and further propose some questions for future studies.

  1. Uptake and efficacy of a systematic intensive smoking cessation intervention using motivational interviewing for smokers hospitalised for an acute coronary syndrome: a multicentre before–after study with parallel group comparisons

    PubMed Central

    Auer, Reto; Gencer, Baris; Tango, Rodrigo; Nanchen, David; Matter, Christian M; Lüscher, Thomas Felix; Windecker, Stephan; Mach, François; Cornuz, Jacques; Humair, Jean-Paul; Rodondi, Nicolas

    2016-01-01

    Objectives To compare the efficacy of a proactive approach with a reactive approach to offer intensive smoking cessation intervention using motivational interviewing (MI). Design Before–after comparison in 2 academic hospitals with parallel comparisons in 2 control hospitals. Setting Academic hospitals in Switzerland. Participants Smokers hospitalised for an acute coronary syndrome (ACS). Intervention In the intervention hospitals during the intervention phase, a resident physician trained in MI systematically offered counselling to all smokers admitted for ACS, followed by 4 telephone counselling sessions over 2 months by a nurse trained in MI. In the observation phase, the in-hospital intervention was offered only to patients whose clinicians requested a smoking cessation intervention. In the control hospitals, no intensive smoking cessation intervention was offered. Primary and secondary outcomes The primary outcome was 1 week smoking abstinence (point prevalence) at 12 months. Secondary outcomes were the number of smokers who received the in-hospital smoking cessation intervention and the duration of the intervention. Results In the intervention centres during the intervention phase, 87% of smokers (N=193/225) received a smoking cessation intervention compared to 22% in the observational phase (p<0.001). Median duration of counselling was 50 min. During the intervention phase, 78% received a phone follow-up for a median total duration of 42 min in 4 sessions. Prescription of nicotine replacement therapy at discharge increased from 18% to 58% in the intervention phase (risk ratio (RR): 3.3 (95% CI 2.4 to 4.3; p≤0.001). Smoking cessation at 12-month increased from 43% to 51% comparing the observation and intervention phases (RR=1.20, 95% CI 0.98 to 1.46; p=0.08; 97% with outcome assessment). In the control hospitals, the RR for quitting was 1.02 (95% CI 0.84 to 1.25; p=0.8, 92% with outcome assessment). Conclusions A proactive strategy offering

  2. Insulin tolerance in laminitic ponies.

    PubMed Central

    Coffman, J R; Colles, C M

    1983-01-01

    Sensitivity to insulin was assessed in ponies episodically affected with chronic laminitis by measurement of blood glucose and arterial blood pressure during insulin tolerance tests. In terms of blood glucose values, laminitic ponies were significantly less sensitive to insulin than controls. Conversely, a post-insulin decline in diastolic, systolic and mean blood pressure values was significantly greater in laminitic ponies than in controls. PMID:6357412

  3. Oral Insulin and Buccal Insulin: A Critical Reappraisal

    PubMed Central

    Heinemann, Lutz; Jacques, Yves

    2009-01-01

    Despite the availability of modern insulin injection devices with needles that are so sharp and thin that practically no injection pain takes place, it is still the dream of patients with diabetes to, for example, swallow a tablet with insulin. This is not associated with any pain and would allow more discretion. Therefore, availability of oral insulin would not only ease insulin therapy, it would certainly increase compliance. However, despite numerous attempts to develop such a “tablet” in the past 85 years, still no oral insulin is commercially available. Buccal insulin is currently in the last stages of clinical development by one company and might become available in the United States and Europe in the coming years (it is already on the market in some other countries). The aim of this review is to critically describe the different approaches that are currently under development. Optimal coverage of prandial insulin requirements is the aim with both routes of insulin administration (at least with most approaches). The speed of onset of metabolic effect seen with some oral insulin approaches is rapid, but absorption appears to be lower when the tablet is taken immediately prior to a meal. With all approaches, considerable amounts of insulin have to be applied in order to induce therapeutically relevant increases in the metabolic effect because of the low relative biopotency of buccal insulin. Unfortunately, the number of publications about clinical–experimental and clinical studies is surprisingly low. In addition, there is no study published in which the variability of the metabolic effect induced (with and without a meal) was studied adequately. In summary, after the failure of inhaled insulin, oral insulin and buccal insulin are hot candidates to come to the market as the next alternative routes of insulin administration. PMID:20144297

  4. Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle.

    PubMed

    Sacramento, Joana F; Ribeiro, Maria J; Yubero, Sara; Melo, Bernardete F; Obeso, Ana; Guarino, Maria P; Gonzalez, Constancio; Conde, Silvia V

    2015-04-01

    Caffeine, a non-selective adenosine antagonist, has distinct effects on insulin sensitivity when applied acutely or chronically. Herein, we investigated the involvement of adenosine receptors on insulin resistance induced by single-dose caffeine administration. Additionally, the mechanism behind adenosine receptor-mediated caffeine effects in skeletal muscle was assessed. The effect of the administration of caffeine, 8-cycle-1,3-dipropylxanthine (DPCPX, A1 antagonist), 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261, A2A antagonist) and 8-(4-{[(4-cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754, A2B antagonist) on whole-body insulin sensitivity was tested. Skeletal muscle Glut4,5'-AMP activated protein kinase (AMPK) and adenosine receptor protein expression were also assessed. The effect of A1 and A2B adenosine agonists on skeletal muscle glucose uptake was evaluated in vitro. Sodium nitroprussiate (SNP, 10nM), a nitric oxide (NO) donor, was used to evaluate the effect of NO on insulin resistance induced by adenosine antagonists. Acute caffeine decreased insulin sensitivity in a concentration dependent manner (Emax=55.54±5.37%, IC50=11.61nM), an effect that was mediated by A1 and A2B adenosine receptors. Additionally, acute caffeine administration significantly decreased Glut4, but not AMPK expression, in skeletal muscle. We found that A1, but not A2B agonists increased glucose uptake in skeletal muscle. SNP partially reversed DPCPX and MRS1754 induced-insulin resistance. Our results suggest that insulin resistance induced by acute caffeine administration is mediated by A1 and A2B adenosine receptors. Both Glut4 and NO seem to be downstream effectors involved in insulin resistance induced by acute caffeine.

  5. Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle.

    PubMed

    Sacramento, Joana F; Ribeiro, Maria J; Yubero, Sara; Melo, Bernardete F; Obeso, Ana; Guarino, Maria P; Gonzalez, Constancio; Conde, Silvia V

    2015-04-01

    Caffeine, a non-selective adenosine antagonist, has distinct effects on insulin sensitivity when applied acutely or chronically. Herein, we investigated the involvement of adenosine receptors on insulin resistance induced by single-dose caffeine administration. Additionally, the mechanism behind adenosine receptor-mediated caffeine effects in skeletal muscle was assessed. The effect of the administration of caffeine, 8-cycle-1,3-dipropylxanthine (DPCPX, A1 antagonist), 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261, A2A antagonist) and 8-(4-{[(4-cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754, A2B antagonist) on whole-body insulin sensitivity was tested. Skeletal muscle Glut4,5'-AMP activated protein kinase (AMPK) and adenosine receptor protein expression were also assessed. The effect of A1 and A2B adenosine agonists on skeletal muscle glucose uptake was evaluated in vitro. Sodium nitroprussiate (SNP, 10nM), a nitric oxide (NO) donor, was used to evaluate the effect of NO on insulin resistance induced by adenosine antagonists. Acute caffeine decreased insulin sensitivity in a concentration dependent manner (Emax=55.54±5.37%, IC50=11.61nM), an effect that was mediated by A1 and A2B adenosine receptors. Additionally, acute caffeine administration significantly decreased Glut4, but not AMPK expression, in skeletal muscle. We found that A1, but not A2B agonists increased glucose uptake in skeletal muscle. SNP partially reversed DPCPX and MRS1754 induced-insulin resistance. Our results suggest that insulin resistance induced by acute caffeine administration is mediated by A1 and A2B adenosine receptors. Both Glut4 and NO seem to be downstream effectors involved in insulin resistance induced by acute caffeine. PMID:25661425

  6. Insulin Resistance in Alzheimer's Disease

    PubMed Central

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  7. Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus.

    PubMed

    Ivy, J L

    1997-11-01

    the insulin response to a glucose challenge without affecting glucose tolerance, and to increase the rate of glucose clearance during a euglycaemic clamp. Muscle glucose uptake is equal to the product of the arteriovenous glucose difference and the rate of glucose delivery or muscle blood flow. While it has been known for many years that insulin will accelerate blood glucose extraction by insulin-sensitive peripheral tissues, recent evidence suggests that it can also acutely vasodilate skeletal muscle and increase muscle blood flow in a dose-dependent manner. A reduced ability of insulin to stimulate muscle blood flow is a characteristic of insulin-resistant obese individuals and individuals with NIDDM. Exercise training, however, has been found to help alleviate this problem, and substantially improve the control of insulin over blood glucose. Improvements in insulin resistance and glucose tolerance with exercise training are highly related to an increased skeletal muscle insulin action. This increased insulin action is associated with an increase in the insulin-regulatable glucose transporters, GLUT4, and enzymes responsible for the phosphorylation, storage and oxidation of glucose. Changes in muscle morphology may also be important following training. With exercise training there is an increase in the conversion of fast twitch glycolytic IIb fibres to fast twitch oxidative IIa fibres, as well as an increase in capillary density. IIa fibres have a greater capillary density and are more insulin-sensitive and -responsive than IIb fibres. Evidence has been provided that morphological changes in muscle, particularly the capillary density of the muscle, are associated with changes in fasting insulin levels and glucose tolerance. Furthermore, significant correlations between glucose clearance, muscle capillary density and fibre type have been found in humans during a euglycaemic clamp. Exercise training may also improve control over hepatic glucose production by increasin

  8. Intravenously injected insulin-like growth factor (IGF) I/IGF binding protein-3 complex exerts insulin-like effects in hypophysectomized, but not in normal rats.

    PubMed

    Zapf, J; Hauri, C; Futo, E; Hussain, M; Rutishauser, J; Maack, C A; Froesch, E R

    1995-01-01

    Insulin-like growth factor (IGF) circulates in blood in two large molecular mass forms of 150 and 40 kD. Under normal conditions, most of the IGF is bound to the 150-kD complex by which it is retained in the circulation and therefore unable to exert acute insulin-like actions. The aim of this study was to answer the question whether or not IGF in the 40-kD complex is bioavailable to insulin target tissues and thus can cause acute insulin-like effects in vivo. Intravenously injected 1:1 molar recombinant human (rh) IGF I/rhIGF binding protein (BP)-3 complex lowered blood glucose and stimulated glycogen synthesis in diaphragm of hypophysectomized, but not of normal rats. The serum half-lives of the two components of the complex were similar to each other, but considerably shorter in hypox than in normal rats. On neutral gel filtration of serum both components of the injected complex appeared predominantly in the 150-kD region in normal rats. In hypox rats which lack the 150-kD complex they were found in the 40-kD region and disappeared rapidly from the circulation. We conclude that in the absence of the 150-kD complex, IGF associated with the 40-kD complex can rapidly leave the vascular compartment, reach insulin or type 1 IGF receptors and exert acute insulin-like effects. PMID:7529258

  9. Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review

    PubMed Central

    Molnár, Gergő A.; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István

    2016-01-01

    Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2nd and 3rd days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + ortho-tyrosine)/para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases. PMID:26785996

  10. DPP-4 inhibitor des-F-sitagliptin treatment increased insulin exocytosis from db/db mice {beta} cells

    SciTech Connect

    Nagamatsu, Shinya; Ohara-Imaizumi, Mica; Nakamichi, Yoko; Aoyagi, Kyota; Nishiwaki, Chiyono

    2011-09-09

    Highlights: {yields} Anti-diabetic new drug, DPP-4 inhibitor, can affect the insulin exocytosis. {yields} DPP-4 inhibitor treatment altered syntaxin 1 expression. {yields} Treatment of db/db mice with DPP-4 inhibitor increased insulin release. -- Abstract: Incretin promotes insulin secretion acutely. Recently, orally-administered DPP-4 inhibitors represent a new class of anti-hyperglycemic agents. Indeed, inhibitors of dipeptidyl peptidase-IV (DPP-4), sitagliptin, has just begun to be widely used as therapeutics for type 2 diabetes. However, the effects of sitagliptin-treatment on insulin exocytosis from single {beta}-cells are yet unknown. We therefore investigated how sitagliptin-treatment in db/db mice affects insulin exocytosis by treating db/db mice with des-F-sitagliptin for 2 weeks. Perfusion studies showed that 2 weeks-sitagliptin treatment potentiated insulin secretion. We then analyzed insulin granule motion and SNARE protein, syntaxin 1, by TIRF imaging system. TIRF imaging of insulin exocytosis showed the increased number of docked insulin granules and increased fusion events from them during first-phase release. In accord with insulin exocytosis data, des-F-sitagliptin-treatment increased the number of syntaxin 1 clusters on the plasma membrane. Thus, our data demonstrated that 2-weeks des-F-sitagliptin-treatment increased the fusion events of insulin granules, probably via increased number of docked insulin granules and that of syntaxin 1 clusters.

  11. The effects of acute and chronic stress on diabetes control.

    PubMed

    Marcovecchio, M Loredana; Chiarelli, Francesco

    2012-10-23

    Stress is an important contributor to pathological conditions in humans. Hormonal changes that occur during acute and chronic stress situations can affect glucose homeostasis in both healthy people and in those with diabetes. Several studies have reported a negative effect of acute stress on maintenance of blood glucose concentrations in patients with type 1 and type 2 diabetes. The effect of stress on glycemic control in people with diabetes may be related to a direct effect of stress hormones on blood glucose levels and an indirect effect of stress on patient behaviors related to diabetes treatment and monitoring and meal and exercise plans. In contrast, there is no clear evidence that stressful life events promote the development of diabetes in children or in adults. Stress hyperglycemia, the development of hyperglycemia during acute illness, represents another interesting connection between the stress system and glucose homeostasis. A large body of evidence supports an association between stress hyperglycemia and increased morbidity and mortality in critically ill patients. Interestingly, there is some evidence supporting a beneficial effect of insulin in reducing morbidity and mortality in patients admitted to intensive care units. Finally, stress can influence the development of type 2 diabetes indirectly by promoting obesity and metabolic syndrome. PMID:23092890

  12. Insulin resistance in the liver: Deficiency or excess of insulin?

    PubMed Central

    Bazotte, Roberto B; Silva, Lorena G; Schiavon, Fabiana PM

    2014-01-01

    In insulin-resistant states (obesity, pre-diabetes, and type 2 diabetes), hepatic production of glucose and lipid synthesis are heightened in concert, implying that insulin deficiency and insulin excess coexists in this setting. The fact that insulin may be inadequate or excessive at any one point in differing organs and tissues has many biologic ramifications. In this context the concept of metabolic compartmentalization in the liver is offered herein as one perspective of this paradox. In particular, we focus on the hypothesis that insulin resistance accentuates differences in periportal and perivenous hepatocytes, namely periportal glucose production and perivenous lipid synthesis. Subsequently, excessive production of glucose and accumulation of lipids could be expected in the livers of patients with obesity and insulin resistance. Overall, in this review, we provide our integrative perspective regarding how excessive production of glucose in periportal hepatocytes and accumulation of lipids in perivenous hepatocytes interact in insulin resistant states. PMID:25486190

  13. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  14. New Insulin Delivery Recommendations.

    PubMed

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. PMID:27594187

  15. [Insulin therapy of diabetes].

    PubMed

    Lechleitner, Monika; Roden, Michael; Weitgasser, Raimund; Ludvik, Bernhard; Fasching, Peter; Hoppichler, Friedrich; Kautzky-Willer, Alexandra; Schernthaner, Guntram; Prager, Rudolf; Wascher, Thomas C

    2016-04-01

    Hyperglycemia contributes to morbidity and mortality in patients with diabetes. Thus, reaching treatment targets with regard to control of glycemia is a central goal in the therapy of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of insulin according to current scientific evidence and clinical studies. PMID:27052221

  16. New Insulin Delivery Recommendations.

    PubMed

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.

  17. Insulin Resistance and Prediabetes

    MedlinePlus

    ... to be used in most health care providers' offices. The clamp is a research tool used by scientists to learn more about glucose metabolism. Research has shown that if blood tests indicate prediabetes, insulin ... care provider's office or commercial facility and sending the sample to ...

  18. New method of preoxygenation for orotracheal intubation in patients with hypoxaemic acute respiratory failure in the intensive care unit, non-invasive ventilation combined with apnoeic oxygenation by high flow nasal oxygen: the randomised OPTINIV study protocol

    PubMed Central

    Jaber, Samir; Molinari, Nicolas; De Jong, Audrey

    2016-01-01

    Introduction Tracheal intubation in the intensive care unit (ICU) is associated with severe life-threatening complications including severe hypoxaemia. Preoxygenation before intubation has been recommended in order to decrease such complications. Non-invasive ventilation (NIV)-assisted preoxygenation allows increased oxygen saturation during the intubation procedure, by applying a positive end-expiratory pressure (PEEP) to prevent alveolar derecruitment. However, the NIV mask has to be taken off after preoxygenation to allow the passage of the tube through the mouth. The patient with hypoxaemia does not receive oxygen during this period, at risk of major hypoxaemia. High-flow nasal cannula oxygen therapy (HFNC) has a potential for apnoeic oxygenation during the apnoea period following the preoxygenation with NIV. Whether application of HFNC combined with NIV is more effective at reducing oxygen desaturation during the intubation procedure compared with NIV alone for preoxygenation in patients with hypoxaemia in the ICU with acute respiratory failure remains to be established. Methods and analysis The HFNC combined to NIV for decreasing oxygen desaturation during the intubation procedure in patients with hypoxaemia in the ICU (OPTINIV) trial is an investigator-initiated monocentre randomised controlled two-arm trial with assessor-blinded outcome assessment. The OPTINIV trial randomises 50 patients with hypoxaemia requiring orotracheal intubation for acute respiratory failure to receive NIV (pressure support=10, PEEP=5, fractional inspired oxygen (FiO2)=100%) combined with HFNC (flow=60 L/min, FiO2=100%, interventional group) or NIV alone (reference group) for preoxygenation. The primary outcome is lowest oxygen saturation during the intubation procedure. Secondary outcomes are intubation-related complications, quality of preoxygenation and ICU mortality. Ethics and dissemination The study project has been approved by the appropriate ethics committee (CPP Sud

  19. TOR-centric view on insulin resistance and diabetic complications: perspective for endocrinologists and gerontologists

    PubMed Central

    Blagosklonny, M V

    2013-01-01

    This article is addressed to endocrinologists treating patients with diabetic complications as well as to basic scientists studying an elusive link between diseases and aging. It answers some challenging questions. What is the link between insulin resistance (IR), cellular aging and diseases? Why complications such as retinopathy may paradoxically precede the onset of type II diabetes. Why intensive insulin therapy may initially worsen retinopathy. How nutrient- and insulin-sensing mammalian target of rapamycin (mTOR) pathway can drive insulin resistance and diabetic complications. And how rapamycin, at rational doses and schedules, may prevent IR, retinopathy, nephropathy and beta-cell failure, without causing side effects. PMID:24336084

  20. Evidence against extrapancreatic insulin synthesis.

    PubMed Central

    Eng, J; Yalow, R S

    1981-01-01

    Labeled and unlabeled insulin in acid/ethanol tissue extracts can be concentrated up to 100-fold by using a hydrophobic adsorption technique. After adsorption to and elution from an octadecylsilyl silica column, insulin is recovered in yields greater than 75%. By using this method of concentration, insulin in brain tissues of three of four fed rats and one rabbit was found to be less than 20% of plasma concentration. The kidney is the only extrapancreatic organ in which insulin is observed to be markedly above plasma levels. Porcine-insulin-like material was not detectable in guinea pig tissues (less than 0.02 ng/g). It is concluded that insulin is not synthesized in brain or other extrapancreatic tissues and that other mammalian insulins are not found in guinea pig tissues. PMID:6270683

  1. Insulin degludec for diabetes mellitus.

    PubMed

    2013-07-01

    Over the last few years there has been a s