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Sample records for acute intensive insulin

  1. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF

    PubMed Central

    Poulaki, Vassiliki; Qin, Wenying; Joussen, Antonia M.; Hurlbut, Peter; Wiegand, Stanley J.; Rudge, John; Yancopoulos, George D.; Adamis, Anthony P.

    2002-01-01

    Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1α (HIF-1α) levels and demonstrate increased HIF-1α–dependent binding to hypoxia-responsive elements in the VEGF promoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1α and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1α–mediated increase in retinal VEGF expression. Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1α–independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. PMID:11901189

  2. 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

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

    PubMed

    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 AS160(Ser588), 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.

  4. 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

  5. Intensive Insulin Therapy: Tight Blood Sugar Control

    MedlinePlus

    ... insulin therapy can help you achieve desired blood sugar control and what intensive insulin therapy requires of ... aggressive treatment approach designed to control your blood sugar levels. Intensive insulin therapy requires close monitoring of ...

  6. Intensive insulin therapy in the intensive cardiac care unit.

    PubMed

    Hasin, Tal; Eldor, Roy; Hammerman, Haim

    2006-01-01

    Treatment in the intensive cardiac care unit (ICCU) enables rigorous control of vital parameters such as heart rate, blood pressure, body temperature, oxygen saturation, serum electrolyte levels, urine output and many others. The importance of controlling the metabolic status of the acute cardiac patient and specifically the level of serum glucose was recently put in focus but is still underscored. This review aims to explain the rationale for providing intensive control of serum glucose levels in the ICCU, especially using intensive insulin therapy and summarizes the available clinical evidence suggesting its effectiveness.

  7. 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...

  8. 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

  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. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke

    PubMed Central

    Lioutas, Vasileios-Arsenios; Alfaro-Martinez, Freddy; Bedoya, Francisco; Chung, Chen-Chih; Pimentel, Daniela A.; Novak, Vera

    2016-01-01

    Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood–brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS. PMID:26040423

  11. Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver.

    PubMed

    Okamoto, Maristela Mitiko; Anhê, Gabriel Forato; Sabino-Silva, Robinson; Marques, Milano Felipe dos Santos Ferreira; Freitas, Helayne Soares; Mori, Rosana Cristina Tieko; Melo, Karla Fabiana S; Machado, Ubiratan Fabres

    2011-10-01

    Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM.

  12. Glycemic control in hospitalized patients not in intensive care: beyond sliding-scale insulin.

    PubMed

    Nau, Konrad C; Lorenzetti, Rosemarie C; Cucuzzella, Mark; Devine, Timothy; Kline, Jonathan

    2010-05-01

    Glycemic control in hospitalized patients who are not in intensive care remains unsatisfactory. Despite persistent expert recommendations urging its abandonment, the use of sliding-scale insulin remains pervasive in U.S. hospitals. Evidence for the effectiveness of sliding-scale insulin is lacking after more than 40 years of use. New physiologic subcutaneous insulin protocols use basal, nutritional, and correctional insulin. The initial total daily dose of subcutaneous insulin is calculated using a factor of 0.3 to 0.6 units per kg body weight, with one half given as long-acting insulin (the basal insulin dose), and the other one half divided daily over three meals as short-acting insulin doses (nutritional insulin doses). A correctional insulin dose provides a final insulin adjustment based on the preprandial glucose value. This correctional dose resembles a sliding scale, but is only a small fine-tuning of therapy, as opposed to traditional sliding-scale insulin alone. Insulin sensitivity, nutritional intake, and total daily dosing review can alter the physiologic insulin-dosing schedule. Prospective trials have demonstrated reductions in hyperglycemic measurements, hypoglycemia, and adjusted hospital length of stay when physiologic subcutaneous insulin protocols are used. Transitions in care require special considerations and attention to glycemic control medications. Changing the sliding-scale insulin culture requires a multidisciplinary effort to improve patient safety and outcomes.

  13. Current role of short-term intensive insulin strategies in newly diagnosed type 2 diabetes.

    PubMed

    Xu, Wen; Weng, Jianping

    2013-09-01

    Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by worsening insulin resistance and a decline in β-cell function. Achieving good glycemic control becomes more challenging as β-cell function continues to deteriorate throughout the disease process. The traditional management paradigm emphasizes a stepwise approach, and insulin has generally been reserved as a final armament. However, mounting evidence indicates that short-term intensive insulin therapy used in the early stages of type 2 diabetes could improve β-cell function, resulting in better glucose control and more extended glycemic remission than oral antidiabetic agents. Improvements in insulin sensitivity and lipid profile were also seen after the early initiation of short-term intensive insulin therapy. Thus, administering short-term intensive insulin therapy to patients with newly diagnosed T2DM has the potential to delay the natural process of this disease, and should be considered when clinicians initiate treatment. Although the early use of insulin is advocated by some guidelines, the optimal time to initiate insulin therapy is not clearly defined or easily recognized, and a pragmatic approach is lacking. Herein we summarize the current understanding of early intensive insulin therapy in patients with newly diagnosed T2DM, focusing on its clinical benefit and problems, as well as possible biological mechanisms of action, and discuss our perspective.

  14. Intensive Insulin Therapy is Associated with Reduced Infectious Complications in Burn Patients

    PubMed Central

    Hemmila, Mark R.; Taddonio, Michael A.; Arbabi, Saman; Maggio, Paul M.; Wahl, Wendy L.

    2013-01-01

    Background Intensive insulin therapy to control blood glucose levels has reduced mortality in surgical, but not medical intensive care unit (ICU) patients. Control of blood glucose levels has also been shown to reduce morbidity in surgical ICU patients. There is very little data for use of intensive insulin therapy in the burn patient population. We sought to evaluate our experience with intensive insulin therapy in burn injured ICU patients with regard to mortality, morbidity, and use of hospital resources. Study Design Burn patients admitted to our American College of Surgeons Level 1 verified Burn Center ICU from 7/1/2004 to 6/30/2006 were studied. An intensive insulin therapy protocol was initiated for ICU patients admitted starting 7/1/2005 with a blood glucose target of 100–140 mg/dL. The two groups of patients studied were control (7/1/2004 to 6/30/2005) and intensive insulin therapy (7/1/2005 to 6/30/2006). All glucose values for the hospitalization were analyzed. Univariate and multivariate analyses were performed. Results 152 ICU patients admitted with burn injury were available for study. No difference in mortality was evident between the control and intensive insulin therapy groups. After adjusting for patient risk, the intensive insulin therapy group was found to have a decreased rate of pneumonia, ventilator-associated pneumonia, and urinary tract infection. In patients with a maximum glucose value > 140 mg/dL, the risk for an infection was significantly increased (OR 11.3, 95% CI 4–32, p-value <0.001). Presence of a maximum glucose value > 140 mg/dL was associated with a sensitivity of 91% and specificity of 62% for an infectious complication. Conclusion Intensive insulin therapy for burn injured patients admitted to the ICU was associated with a reduced incidence of pneumonia, ventilator associated pneumonia, and urinary tract infection. Intensive insulin therapy did not result in a change in mortality or length of stay when adjusting for

  15. Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis

    PubMed Central

    DU, JUN-DONG; ZHENG, XI; HUANG, ZHI-QIANG; CAI, SHOU-WANG; TAN, JING-WANG; LI, ZHAN-LIANG; YAO, YONG-MING; JIAO, HUA-BO; YIN, HUI-NAN; ZHU, ZI-MAN

    2014-01-01

    The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments. PMID:24944612

  16. The effect of exercise-intensity on skeletal muscle stress kinase and insulin protein signaling

    PubMed Central

    Trewin, Adam; Levinger, Itamar; Shaw, Christopher S.; Stepto, Nigel K.

    2017-01-01

    Background Stress and mitogen activated protein kinase (SAPK) signaling play an important role in glucose homeostasis and the physiological adaptation to exercise. However, the effects of acute high-intensity interval exercise (HIIE) and sprint interval exercise (SIE) on activation of these signaling pathways are unclear. Methods Eight young and recreationally active adults performed a single cycling session of HIIE (5 x 4 minutes at 75% Wmax), SIE (4 x 30 second Wingate sprints), and continuous moderate-intensity exercise work-matched to HIIE (CMIE; 30 minutes at 50% of Wmax), separated by a minimum of 1 week. Skeletal muscle SAPK and insulin protein signaling were measured immediately, and 3 hours after exercise. Results SIE elicited greater skeletal muscle NF-κB p65 phosphorylation immediately after exercise (SIE: ~40%; HIIE: ~4%; CMIE; ~13%; p < 0.05) compared to HIIE and CMIE. AS160Ser588 phosphorylation decreased immediately after HIIE (~-27%; p < 0.05), and decreased to the greatest extent immediately after SIE (~-60%; p < 0.05). Skeletal muscle JNK (~42%; p < 0.05) and p38 MAPK (~171%; p < 0.05) phosphorylation increased, and skeletal muscle AktSer473 phosphorylation (~-32%; p < 0.05) decreased, to a similar extent immediately after all exercise protocols. AS160Ser588 phosphorylation was similar to baseline three hours after SIE (~-12%; p > 0.05), remained lower 3 hours after HIIE (~-34%; p < 0.05), and decreased 3 hours after CMIE (~-33%; p < 0.05). Conclusion Despite consisting of less total work than CMIE and HIIE, SIE proved to be an effective stimulus for the activation of stress protein kinase signaling pathways linked to exercise-mediated adaptation of skeletal muscle. Furthermore, post-exercise AS160Ser588 phosphorylation decreased in an exercise-intensity and post-exercise time-course dependent manner. PMID:28182793

  17. Acute effects of aerobic exercise intensity on arterial stiffness after glucose ingestion in young men.

    PubMed

    Kobayashi, Ryota; Hashimoto, Yuto; Hatakeyama, Hiroyuki; Okamoto, Takanobu

    2016-10-18

    Arterial stiffness increases after glucose ingestion. Acute low- and moderate-intensity aerobic exercise decreases arterial stiffness. However, the acute effects of 30 min of cycling at low- and moderate-intensity [25% (LE trial) and 65% (ME trial) peak oxygen uptake, respectively] on arterial stiffness at 30, 60 and 120 min of a postexercise glucose ingestion. Ten healthy young men (age, 22·4 ± 0·5 years) performed LE and ME trials on separate days in a randomized controlled crossover fashion. Carotid-femoral (aortic) pulse wave velocity (PWV), femoral-ankle (leg) PWV, carotid augmentation index (AIx) and carotid blood pressure (BP) (applanation tonometry), brachial and ankle BP (oscillometric device), heart rate (HR) (electrocardiography), blood glucose (UV-hexokinase method) and blood insulin (CLEIA method) levels were measured at before (baseline) and at 30, 60 and 120 min after the 75-g OGTT. Leg PWV, ankle pulse pressure and BG levels significantly increased from baseline after the 75-g OGTT in the LE trial (P<0·05), but not in the ME trial. Insulin levels and HR significantly increased from baseline after the 75-g OGTT in both trials (P<0·05). Aortic PWV, carotid AIx, brachial BP and carotid BP did not change from baseline after the 75-g OGTT in both trials. The present findings indicate that aerobic exercise at moderate intensity before glucose ingestion suppresses increases leg arterial stiffness after glucose ingestion.

  18. Performance of an Electronic Diary System for Intensive Insulin Management in Global Diabetes Clinical Trials

    PubMed Central

    Zhang, Shuyu; Mou, Jiani; Hackett, Andy P.; Raymond, Stephen A.; Chang, Annette M.

    2015-01-01

    Abstract Background: This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient–investigator interactions during intensive insulin management in diabetes clinical trials. Materials and Methods: We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report. Results: Patients (n=2,938) in 31 countries used e-diaries to transmit 2,439,087 blood glucose (BG) values, 96% of which were associated by the patient with a protocol time point during the 72-h response window. Of 208,192 hypoglycemia events captured, 96% had a BG value, and 95% had treatments and outcomes entered by patients within the 72-h window. Patients recorded administration of 1,964,477 insulin doses; 93% of basal insulin doses were adherent with the investigator prescription. Investigators adjusted 13 basal and 92 bolus insulin prescriptions per patient-year using the e-diary system. After 26 weeks of treatment and e-diary use in the combined study arms, hemoglobin A1c values decreased by 0.6% or 1.6% and fasting BG decreased by 7.8 or 28 mg/dL in patients with T1DM or T2DM, respectively. Conclusions: The e-diary system enabled comprehensive data collection and facilitated communication between investigators and patients for intensive insulin management in three global clinical trials testing basal insulins. PMID:25826466

  19. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

    PubMed

    Ott, Volker; Lehnert, Hendrik; Staub, Josefine; Wönne, Kathrin; Born, Jan; Hallschmid, Manfred

    2015-03-01

    Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia.

  20. Full Neurological Recovery after Extreme Hypoglycemia during Intensive Insulin Therapy: A Case Report

    PubMed Central

    Piot, Veerle M.; Verrijcken, Anton; Vanhoof, Marc; Mertens, Ilse; Soetens, Filiep

    2012-01-01

    Since 2000, there has been an ongoing debate regarding tightness of glycemic control in critically ill patients. An increased risk of hypoglycemia is observed in patients treated with an intensive insulin protocol targeting “normoglycemia,” probably accounting for a reduction of the overall benefit. Hypoglycemia is associated with neurological side effects and is found to be an independent predictor of mortality in most trials; however, long-term sequelae are rare if glucose is administered early. We describe a case of prolonged, extreme hypoglycemia in a critically ill patient treated according to an intensive insulin protocol who recovered without any neurological deficit at discharge. PMID:22920826

  1. 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.

  2. Two weeks of moderate intensity continuous training, but not high intensity interval training increases insulin-stimulated intestinal glucose uptake.

    PubMed

    Motiani, Kumail Kumar; Savolainen, Anna M; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A; Parkkola, Riitta; Kapanen, Jukka; Gronroos, Tove J; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-02-09

    Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy middle-aged sedentary men were randomized for two weeks of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [(18)F]FDG and [(18)F]FTHA. In addition, effects of HIIT and MICT on intestinal Glut2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (p=0.001) and whole-body insulin sensitivity (p=0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon [HIIT=0%; MICT=37%] (p=0.02 for time*training) and tended to increase in the jejunum [HIIT=-4%; MICT=13%] (p=0.08 for time*training). Fasting free fatty acid uptake decreased in the duodenum in both groups [HIIT=-6%; MICT=-48%] (p=0.001 time) and tended to decrease in the colon in the MICT group [HIIT=0%; MICT=-38%] (p=0.08 for time*training). In rats, both training groups had higher Glut2 and CD36 expression compared to control animals. This study shows that already two weeks of MICT enhances insulin-stimulated glucose uptake while both training modes reduce fasting free fatty acid uptake in the intestine in healthy middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism.

  3. Effects of acute and chronic psychological stress on isolated islets' insulin release.

    PubMed

    Zardooz, Homeira; Zahediasl, Saleh; Rostamkhani, Fatemeh; Farrokhi, Babak; Nasiraei, Shiva; Kazeminezhad, Behrang; Gholampour, Roohollah

    2012-01-01

    This study investigated the effects of acute and chronic psychological stress on glucose-stimulated insulin secretion from isolated pancreatic islets. Male Wistar rats were divided into two control and stressed groups; each further was allocated into fed and fasted groups. Stress was induced by communication box for one (acute), fifteen and thirty (chronic) days. After islet isolation, their number, size and insulin output were assessed. Plasma corticosterone level was determined. In fasted animals, acute stress increased basal and post stress plasma corticosterone level, while 30 days stress decreased it compared to day 1. In fed rats, acute stress increased only post stress plasma corticosterone concentration, however, after 15 days stress, it was decreased compared to day 1. Acute stress did not change insulin output; however, the insulin output was higher in the fed acutely stressed rats at 8.3 and 16.7 mM glucose than fasted ones. Chronic stress increased insulin output on day 15 in the fasted animals but decreased it on day 30 in the fed animals at 8.3 and 16.7 mM glucose. In the fasted control rats insulin output was lower than fed ones. In the chronic stressed rats insulin output at 8.3 and 16.7 mM glucose was higher in the fasted than fed rats. The number of islets increased in the fasted rats following 15 days stress. This study indicated that the response of the isolated islets from acute and chronically stressed rats are different and depends on the feeding status.

  4. Impact of acute psychological stress on cardiovascular risk factors in face of insulin resistance.

    PubMed

    Jones, Kristian T; Shelton, Richard C; Wan, Jun; Li, Li

    2016-11-01

    Individuals with insulin resistance (IR) are at greater risk for cardiovascular disease (CVD). Psychological stress may contribute to develop CVD in IR, although mechanisms are poorly understood. Our aim was to test the hypothesis that individuals with IR have enhanced emotional and physiological responses to acute psychological stress, leading to increased CVD risk. Sixty participants were enrolled into the study, and classified into IR group (n = 31) and insulin sensitive group (n = 29) according to the Quantitative insulin sensitivity check index, which was calculated based on an oral glucose tolerance test. The Trier social stress test, a standardized experimental stress paradigm, was performed on each participant, and emotional and physiological responses were examined. Blood was collected from each subject for insulin, cytokines, and cortisol measurements. Compared with the insulin-sensitive group, individuals with IR had significantly lower ratings of energy and calm, but higher fatigue levels in response to acute stressors. Individuals with IR also showed blunted heart rate reactivity following stress. In addition, the IR status was worsened by acute psychological stress as demonstrated by further increased insulin secretion. Furthermore, individuals with IR showed significantly increased levels of leptin and interleukin-6, but decreased levels of adiponectin, at baseline, stress test, and post-stress period. Our findings in individuals with IR under acute stress would allow a better understanding of the risks for developing CVD and to tailor the interventions for better outcomes.

  5. 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

  6. [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

  7. 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

  8. Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?

    PubMed Central

    Steil, Garry M.; Deiss, Dorothee; Shih, Judy; Buckingham, Bruce; Weinzimer, Stuart; Agus, Michael S.D.

    2009-01-01

    Objective Studies showing improved outcomes with tight glycemic control in the intensive care unit (ICU) have resulted in a substantial number of new insulin delivery algorithms being proposed. The present study highlights mechanisms used in the better-known approaches, examines what might be critical differences among them, and uses systems theory to characterize the conditions under which each can be expected to perform best. Methods Algorithm dose (ΔI/ΔG) and step (response to a persistent elevation in glucose) response curves were calculated for written instruction algorithms, developed at the Providence Heart and Vascular Institute (Portland [P] protocol), the University of Washington (UW), and Yale University (Y), together with similar curves for the Glucommander (GM) and proportional integral derivative (PID) computer algorithms. From the simulated curves, different mechanisms used to adjust insulin delivery were identified. Results All algorithms increased insulin delivery in response to persistent hyperglycemia, but the mechanism used altered the algorithm's sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it unchanged for the P protocol and PID algorithm. Conclusions The increase in insulin delivery in response to persistent hyperglycemia observed with all the algorithms can be expected to bring subjects who respond to insulin to targeted glucose ranges. However, because the PID and P protocols did not alter the insulin delivery response curves, these algorithms can be expected to take longer to achieve target glucose levels in individuals who are insulin resistant and/or are exposed to increased carbohydrate loads (e.g., glucose infusions). By contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin resistance such that the time to achieve target levels is unchanged if the time for insulin to act does not change. If the insulin resistance is accompanied by a longer time for insulin to act, the UW, Y

  9. 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

  10. 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

  11. Pubertal Changes of Insulin Sensitivity, Acute Insulin Response and β-Cell function in Overweight Latino Youth

    PubMed Central

    Kelly, Louise A.; Lane, Christianne J.; Weigensberg, Marc J.; Toledo-Corral, Claudia M; Goran, Michael I.

    2010-01-01

    Objective To examine changes in insulin sensitivity (SI), compensatory acute insulin response (AIR) and β-cell function/disposition index (DI) across puberty in overweight Latino boys and girls. Study design 253 Latino children followed annually for up to 5 years. Longitudinal modeling was used to examine changes in SI, AIR, DI and fasting and 2-hr glucose and insulin across Tanner stage. Results In boys, SI decreased in early puberty with a recovery by late puberty. The compensatory increase in AIR was appropriate in early maturation, but after Tanner 3, AIR declined by more than that predicted from the recovery in SI. For girls, SI decreased in early puberty and across all stages of maturation. In early maturation, there was an appropriate compensatory increase in AIR, but after Tanner 3 AIR decreased. Thus, DI deteriorated across puberty in boys and girls. Conclusions In overweight Hispanic youth, compensatory changes in insulin secretion fails after Tanner 3 in both sexes, indicating β-cell deterioration during this critical period of development, thus increasing risk for Type 2 diabetes. PMID:20888012

  12. Insulin in Acute Coronary Syndrome: a Narrative Review with Contemporary Perspectives.

    PubMed

    Nam, Michael C Y; Byrne, Christopher D; Kaski, Juan Carlos; Greaves, Kim

    2016-10-01

    The role of insulin in the treatment of acute coronary syndrome (ACS) has been widely studied over the past 100 years. The current indication for its use in this context is the treatment of hyperglycemia, irrespective of diabetes, which is associated with adverse outcome. Initial theories proposed that glucose was beneficial in the context of myocardial ischemia and insulin was required to enable glucose cell uptake. However, studies testing this hypothesis with routine insulin administration during ACS have produced disappointing results and research interest has therefore declined. We propose that the less well known but important vasodilator effect of insulin has been overlooked by some of these studies and warrants further consideration. Previous reports have shown that hyperinsulinemic euglycaemia improves myocardial blood flow reserve. With this in mind, this review considers the role of insulin in the context of ACS from the perspective of a vasodilator rather than a metabolic modulator. We discuss the importance of time to treatment, dosage of insulin administered, problems with hypoglycaemia and insulin resistance, and how they may have affected the outcomes of the major trials. Finally, we propose new study designs that allow determination of the optimal vasodilator conditions for the use of insulin as adjunctive pharmacotherapy during myocardial ischaemia.

  13. Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Polakof, Sergio; Skiba-Cassy, Sandrine; Choubert, Georges; Panserat, Stéphane

    2010-05-01

    The relative glucose intolerance of carnivorous fish species is often proposed to be a result of poor peripheral insulin action or possibly insulin resistance. In the present study, data from aortic cannulated rainbow trout receiving bovine insulin (75 mIU kg(-1)) injections show for the first time their ability to clear glucose in a very efficient manner. In another set of experiments, mRNA transcripts and protein phosphorylation status of proteins controlling glycaemia and glucose-related metabolism were studied during both acute and chronic treatment with bovine insulin. Our results show that fasted rainbow trout are well adapted at the molecular level to respond to increases in circulating insulin levels, and that this hormone is able to potentially improve glucose distribution and uptake by peripheral tissues. After acute insulin administration we found that to counter-regulate the insulin-induced hypoglycaemia, trout metabolism is strongly modified. This short-term, efficient response to hypoglycaemia includes a rapid, coordinated response involving the reorganization of muscle and liver metabolism. During chronic insulin treatment some of the functions traditionally attributed to insulin actions in mammals were observed, including increased mRNA levels of glucose transporters and glycogen storage (primarily in the muscle) as well as decreased mRNA levels of enzymes involved in de novo glucose production (in the liver). Finally, we show that the rainbow trout demonstrates most of the classic metabolic adjustments employed by mammals to efficiently utilize glucose in the appropriate insulin context.

  14. Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin.

    PubMed

    Descamps, Francis J; Van den Steen, Philippe E; Martens, Erik; Ballaux, Florence; Geboes, Karel; Opdenakker, Ghislain

    2003-05-01

    Genetic, endocrine, and environmental factors contribute to the development of diabetes. Much information has been gathered on the homeostasis mechanisms of glucose regulation by insulin-producing pancreatic beta cells. Here we demonstrate high expression levels of gelatinase B (matrix metalloproteinase-9, MMP-9) by neutrophils in acute pancreatitis and by ductular epithelial cells in chronic pancreatitis. Because gelatinase B processes cytokines and chemokines, we investigated whether and how gelatinase B cleaves insulin. Pure human neutrophil gelatinase B was found to destroy insulin by cleavage at 10 sites. Pancreatic islet and ductular cells are relatively spared in comparison with the complete destruction of acinar cells of the exocrine pancreas in chronic pancreatitis. High expression levels of gelatinase B are maintained in the immediate proximity of insulin-secreting beta cells. Consequently, diabetes may be worsened by enzymatic degradation of insulin by gelatinase B and by the consequent enhancement of the autoimmune process. Gelatinase B is diabetogenic in acute and chronic pancreatitis by cleaving insulin.

  15. 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

  16. Novel remodeling of the mouse heart mitochondrial proteome in response to acute insulin stimulation

    PubMed Central

    Pedersen, Brian A; Yazdi, Puya G; Taylor, Jared F; Khattab, Omar S; Chen, Yu-Han; Chen, Yumay; Wang, Ping H

    2015-01-01

    Mitochondrial dysfunction contributes to the pathophysiology of diabetic cardiomyopathy. The aim of this study was to investigate the acute changes in the mitochondrial proteome in response to insulin stimulation. Cardiac mitochondria from C57BL/6 mice after insulin stimulation were analyzed using two-dimensional fluorescence difference gel electrophoresis. MALDI-TOF MS/MS was utilized to identify differences. Two enzymes involved in metabolism and four structural proteins were identified. Succinyl-CoA ligase [ADP forming] subunit beta was identified as one of the differentially regulated proteins. Upon insulin stimulation, a relatively more acidic isoform of this protein was increased by 53% and its functional activity was decreased by ∼32%. This proteomic remodeling in response to insulin stimulation may play an important role in the normal and diabetic heart. PMID:26610654

  17. 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

  18. Hypocaloric enteral nutrition protects against hypoglycemia associated with intensive insulin therapy better than intravenous dextrose.

    PubMed

    Kauffmann, Rondi M; Hayes, Rachel M; VanLaeken, Amanda H; Norris, Patrick R; Diaz, Jose J; May, Addison K; Collier, Bryan R

    2014-11-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes.

  19. Hypocaloric Enteral Nutrition Protects Against Hypoglycemia Associated with Intensive Insulin Therapy Better Than Intravenous Dextrose

    PubMed Central

    Kauffmann, Rondi M.; Hayes, Rachel M.; Vanlaeken, Amanda H.; Norris, Patrick R.; Diaz, Jose J.; May, Addison K.; Collier, Bryan R.

    2015-01-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes. PMID:25347500

  20. 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

  1. Acute suppression of apo B secretion by insulin occurs independently of MTP.

    PubMed

    Sparks, Janet D; Chamberlain, Jeffrey M; O'Dell, Colleen; Khatun, Irani; Hussain, M Mahmood; Sparks, Charles E

    2011-03-11

    Secretion of apolipoprotein (apo) B-containing lipoproteins by the liver depends mainly upon apo B availability and microsomal triglyceride transfer protein (MTP) activity and is subject to insulin regulation. Hepatic MTP mRNA expression is negatively regulated by insulin which correlates with inhibition of apo B secretion suggesting that insulin might suppress apo B secretion through an MTP-dependent mechanism. To investigate this possibility, we examined the acute effect of insulin on hepatic MTP expression and activity levels in vivo utilizing apobec-1(-/-) mice. Insulin did not significantly alter hepatic MTP mRNA levels or lipid transfer activity 2h following injection, but suppressed expression of genes important in gluconeogenesis. To study the specific role of MTP, we expressed human MTP (hMTP) in primary rat hepatocytes using adenoviral gene transfer. Increased expression of hMTP resulted in a 47.6±17.9% increase in total apo B secreted. Incubation of hepatocytes with insulin suppressed apo B secretion by 50.1±10.8% in cells over-expressing hMTP and by 53.0±12.4% in control transfected hepatocytes. Results indicate that even under conditions of increased hepatic apo B secretion mediated by MTP, responsiveness of hepatocytes to insulin to suppress apo B secretion is maintained.

  2. Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle.

    PubMed

    Anderson, Marianne S; Thamotharan, M; Kao, Doris; Devaskar, Sherin U; Qiao, Liping; Friedman, Jacob E; Hay, William W

    2005-02-01

    To test the effects of acute fetal hyperinsulinemia on the pattern and time course of insulin signaling in ovine fetal skeletal muscle, we measured selected signal transduction proteins in the mitogenic, protein synthetic, and metabolic pathways in the skeletal muscle of normally growing fetal sheep in utero. In experiment 1, 4-h hyperinsulinemic-euglycemic clamps were conducted in anesthetized twin fetuses to produce selective fetal hyperinsulinemia-euglycemia in one twin and euinsulinemia-euglycemia in the other. Serial skeletal muscle biopsies were taken from each fetus during the clamp and assayed by Western blot for selected insulin signal transduction proteins. Tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and the p85 subunit of phosphatidylinositol 3-kinase doubled at 30 min and gradually returned to control values by 240 min. Phosphorylation of extracellular signal-regulated kinase 1,2 was increased fivefold through 120 min of insulin infusion and decreased to control concentration by 240 min. Protein kinase B phosphorylation doubled at 30 min and remained elevated throughout the study. Phosphorylation of p70 S6K increased fourfold at 30, 60, and 120 min. In the second experiment, a separate group of nonanesthetized singleton fetuses was clamped to intermediate and high hyperinsulinemic-euglycemic conditions for 1 h. GLUT4 increased fourfold in the plasma membrane at 1 h, and hindlimb glucose uptake increased significantly at the higher insulin concentration. These data demonstrate that an acute increase in fetal plasma insulin concentration stimulates a unique pattern of insulin signal transduction proteins in intact skeletal muscle, thereby increasing pathways for mRNA translation, glucose transport, and cell growth.

  3. Lactation Intensity and Postpartum Maternal Glucose Tolerance and Insulin Resistance in Women With Recent GDM

    PubMed Central

    Gunderson, Erica P.; Hedderson, Monique M.; Chiang, Vicky; Crites, Yvonne; Walton, David; Azevedo, Robert A.; Fox, Gary; Elmasian, Cathie; Young, Stephen; Salvador, Nora; Lum, Michael; Quesenberry, Charles P.; Lo, Joan C.; Sternfeld, Barbara; Ferrara, Assiamira; Selby, Joseph V.

    2012-01-01

    OBJECTIVE To examine the association between breastfeeding intensity in relation to maternal blood glucose and insulin and glucose intolerance based on the postpartum 2-h 75-g oral glucose tolerance test (OGTT) results at 6–9 weeks after a pregnancy with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We selected 522 participants enrolled into the Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT), a prospective observational cohort study of Kaiser Permanente Northern California members diagnosed with GDM using the 3-h 100-g OGTT by the Carpenter and Coustan criteria. Women were classified as normal, prediabetes, or diabetes according to American Diabetes Association criteria based on the postpartum 2-h 75-g OGTT results. RESULTS Compared with exclusive or mostly formula feeding (>17 oz formula per 24 h), exclusive breastfeeding and mostly breastfeeding (≤6 oz formula per 24 h) groups, respectively, had lower adjusted mean (95% CI) group differences in fasting plasma glucose (mg/dL) of −4.3 (−7.4 to −1.3) and −5.0 (−8.5 to −1.4), in fasting insulin (μU/mL) of −6.3 (−10.1 to −2.4) and −7.5 (−11.9 to −3.0), and in 2-h insulin of −21.4 (−41.0 to −1.7) and −36.5 (−59.3 to −13.7) (all P < 0.05). Exclusive or mostly breastfeeding groups had lower prevalence of diabetes or prediabetes (P = 0.02). CONCLUSIONS Higher intensity of lactation was associated with improved fasting glucose and lower insulin levels at 6–9 weeks’ postpartum. Lactation may have favorable effects on glucose metabolism and insulin sensitivity that may reduce diabetes risk after GDM pregnancy. PMID:22011407

  4. 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

  5. Alcohol acutely increases vascular reactivity together with insulin sensitivity in type 2 diabetic men.

    PubMed

    Schaller, G; Kretschmer, S; Gouya, G; Haider, D G; Mittermayer, F; Riedl, M; Wagner, O; Pacini, G; Wolzt, M; Ludvik, B

    2010-01-01

    Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1).microU (-1).ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1).microU (-1).ml (p<0.05), and FMD to +8.2+/-2.8% (p<0.05), while GTN-induced dilation remained unchanged. No relationship was detectable between the observed changes. We conclude that alcohol intake acutely increases endothelium-dependent brachial artery vasodilation in patients with type 2 diabetes together with insulin sensitivity. This acute effect might explain some beneficial effects of low alcohol consumption in epidemiological observations.

  6. Steroidogenic acute regulatory protein (StAR) overexpression reduces inflammation and insulin resistance in obese mice.

    PubMed

    Qiu, Yanyan; Sui, Xianxian; Cao, Shengxuan; Li, Xiaobo; Ning, Yanxia; Wang, Songmei; Yin, Lianhua; Zhi, Xiuling

    2017-04-12

    Steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol delivery protein, plays a beneficial role in hyperlipidemia, NAFLD and endothelial inflammation. Elevated circulating fatty acids and low grade inflammation are known as key risk factors of insulin resistance and type 2 diabetes. In the present study, C57BL/6J mice were fed with a HFD and infected with recombinant adenovirus expressing StAR by tail-vein injection. Intraperitoneal glucose/insulin tolerance test was performed to assess the insulin sensitivity. Morphological analysis and intramuscular lipid determination were used to illustrate the adipose hypertrophy and ectopic fat accumulation in skeletal muscle. The levels of inflammatory factor and nitric oxide were determined by ELISA and classic Griess reagent methods respectively. The fatty acids composition was analysis using gas chromatography -mass spectrometry (GC-MS). The expression of genes associated with inflammation and insulin resistance were determined by Western blotting and qPCR to elucidate the underlying mechanism.We demonstrated that StAR overexpression ameliorated insulin resistance and systemic inflammatory response with the reduction of adipose hypertrophy and intramuscular lipid in HFD fed mice. In addition, StAR overexpression increased serum unsaturated fatty acids and PPARγ expression in muscle and adipose tissue of obese mice. In conclusion, StAR may activate PPARγ by increasing unsaturated fatty acids, which leads to a protective role in systemic inflammation and insulin resistance in obese mice. This article is protected by copyright. All rights reserved.

  7. Potential beneficial mechanisms of insulin (glucose-potassium) in acute myocardial infarction

    PubMed Central

    van der Horst, I.C.C.; Zijlstra, F.

    2005-01-01

    In the time-span of almost a century, a large amount of experimental evidence has been accumulated that underlines the importance of glucose metabolism during ischaemia/reperfusion of the heart. As early as 1912, Goulston suggested that treatment with glucose could be beneficial in several heart diseases. The first experimental results on the mechanical effects of insulin and glucose in the isolated heart were reported by Visscher and Muller in 1926. In 1935, Evans and colleagues showed that the uptake of glucose is increased in the ischaemic myocardium. Almost 30 years later, Sodi-Pallares and colleagues suggested that metabolic interference during myocardial ischaemia with GIK infusion decreased electrocardiographic signs of ischaemia. They also showed that glucose-insulin-potassium (GIK) infusion resulted in a lower occurrence of arrhythmias. They attributed this effect mainly to the influx of potassium in ischaemic cardiomyocytes. In order to further stimulate potassium transport into the cell, insulin was administered. Consequently, the rise of intercellular calcium is curtailed by the influx of potassium and so the incidence of arrhythmias is reduced. However, systemic infusion of insulin stimulates the uptake of glucose in many celltypes, which may result in hypoglycaemic episodes. Consequently, it is not possible to administer potassium and insulin in high concentrations without adding glucose. Interventions in the glucose metabolism in the clinical arena, whether or not used to correct acute hyperglycaemia, encompass three potentially effective elements: glucose, insulin and potassium. PMID:25696497

  8. Update of acute kidney injury: intensive care nephrology

    PubMed Central

    Tsagalis, G

    2011-01-01

    Albeit the considerable progress that has been made both in our understanding of the pathophysiology of acute renal failure (ARF) and in its treatment (continuous renal replacement therapies), the morbidity of this complex syndrome remains unacceptably high. The current review focuses on recent developments concerning the definition of ARF, new strategies for the prevention and pharmacological treatment of specific causes of ARF, dialysis treatment in the intensive care setting and provides an update on critical care issues relevant to the clinical nephrologist. PMID:21897760

  9. Glycaemic control with modified intensive insulin injections (MII) using insulin pens and premixed insulin in children with type-1 diabetes: a randomized controlled trial.

    PubMed

    Soliman, Ashraf T; Omar, Magdi; Rizk, Mostafa M; El Awwa, Ahmad; AlGhobashy, Fatma M

    2006-08-01

    The objective of this study was to compare glycemic control and insulin dosage in children with type 1 diabetes treated by a modified intensified insulin therapy MII using insulin pens (and premixed and regular insulin) with those on conventional insulin therapy. This was a longitudinal, randomized controlled trial for 6 months or more. From a cohort of 125 children with previously diagnosed type-1 diabetes (more than a year after diagnosis) two groups were randomly selected Group AI (n=20) and Group B (n=20). Group AI children and 10 children with recently diagnosed type 1 diabetes (Group AII) were allocated to MII using regular insulin and premixed insulin (30/70 and 40/60 and 50/50). Group B patients continued their conventional insulin therapy for the whole period of the trial. The main outcome measures were glycemic control measured by mean blood glucose concentration and percentage of glycated haemoglobin and total daily insulin dose. Mean blood glucose concentrations before the three main meals, and at midnight, (148, 147, 179 and 127 mg/dl, respectively) were lower in children receiving intensified MII compared with those receiving conventional insulin therapy (192, 174, 194 and 179 mg/dl, respectively) (standardized mean difference 34+/-15 mg/dl), equivalent to a difference of 1.9+/-0.8 mmol/l. This improved control during MII was achieved with no change in the average daily insulin dose in group-AI. In group-AII insulin dose decreased significantly during their first 6 moths of treatment (honeymooning). Glycemic control is better during MII using insulin pens and premixed and regular insulin compared with conventional insulin therapy, without any significant change in insulin dose needed to achieve this level of control. The difference in glycemic control between the two methods is significant and could reduce the risk of micro-vascular complications.

  10. Effects of acute lipid overload on skeletal muscle insulin resistance, metabolic flexibility, and mitochondrial performance

    PubMed Central

    Coen, Paul M.; DiStefano, Giovanna; Chacon, Alexander C.; Helbling, Nicole L.; Desimone, Marisa E.; Stafanovic-Racic, Maja; Hames, Kazanna C.; Despines, Alex A.; Toledo, Frederico G. S.; Goodpaster, Bret H.

    2014-01-01

    We hypothesized that acute lipid-induced insulin resistance would be attenuated in high-oxidative muscle of lean trained (LT) endurance athletes due to their enhanced metabolic flexibility and mitochondrial capacity. Lean sedentary (LS), obese sedentary (OS), and LT participants completed two hyperinsulinemic euglycemic clamp studies with and without (glycerol control) the coinfusion of Intralipid. Metabolic flexibility was measured by indirect calorimetry as the oxidation of fatty acids and glucose during fasted and insulin-stimulated conditions, the latter with and without lipid oversupply. Muscle biopsies were obtained for mitochondrial and insulin-signaling studies. During hyperinsulinemia without lipid, glucose infusion rate (GIR) was lowest in OS due to lower rates of nonoxidative glucose disposal (NOGD), whereas state 4 respiration was increased in all groups. Lipid infusion reduced GIR similarly in all subjects and reduced state 4 respiration. However, in LT subjects, fat oxidation was higher with lipid oversupply, and although glucose oxidation was reduced, NOGD was better preserved compared with LS and OS subjects. Mitochondrial performance was positively associated with better NOGD and insulin sensitivity in both conditions. We conclude that enhanced mitochondrial performance with exercise is related to better metabolic flexibility and insulin sensitivity in response to lipid overload. PMID:25352435

  11. Adipokines, ghrelin and obesity-associated insulin resistance in nondiabetic patients with acute coronary syndrome.

    PubMed

    Barazzoni, Rocco; Aleksova, Aneta; Armellini, Ilaria; Cattin, Maria Rosa; Zanetti, Michela; Carriere, Cosimo; Giacca, Mauro; Dore, Franca; Guarnieri, Gianfranco; Sinagra, Gianfranco

    2012-12-01

    Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity-related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMA(IR))-insulin resistance index, plasma adiponectin, leptin, total (T-Ghrelin), acylated (Acyl-Ghrelin), and desacylated ghrelin (Desacyl-Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non-ACS, ACS patients had similar HOMA(IR) and plasma adipokines, but lower T- and Desacyl-Ghrelin and higher Acyl-Ghrelin. Obesity (BMI > 30) was associated with higher HOMA(IR), lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non-ACS subjects. In ACS (n = 60) HOMA(IR) remained associated negatively with adiponectin and positively with leptin independently of BMI and c-reactive protein (CRP) (P < 0.05). On the other hand, low T- and Desacyl-Ghrelin with high Acyl-Ghrelin characterized both obese and non-obese ACS patients and were not associated with HOMA(IR). In conclusion, in ACS patients, obesity and obesity-related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.

  12. Long-term efficacy of insulin glargine after switching from NPH insulin as intensive replacement of basal insulin in Japanese diabetes mellitus. Comparison of efficacy between type 1 and type 2 diabetes (JUN-LAN Study 1.2).

    PubMed

    Kanazawa, Yoshie; Igarashi, Yasuhiro; Komiya, Koji; Sakurai, Yuko; Shimizu, Tomoaki; Fujitani, Yoshio; Tanaka, Yasushi; Watada, Hirotaka; Kawamori, Ryuzo; Hirose, Takahisa

    2007-12-01

    To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA(1C). Mean HbA(1C) level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA(1C) level: type 1: baseline 8.9 +/- 2.6%, 18 months 7.8 +/- 1.5% (p<0.05), type 2: baseline 8.2 +/- 2.6%, 18 months 7.7 +/- 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA(1C) level at baseline exhibited more than 10% improvement in HbA(1C) level after switching both type 1 and type 2 diabetes. The HbA(1C) levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.

  13. Intensive insulin therapy for preventing postoperative infection in patients with traumatic brain injury

    PubMed Central

    Wang, Yan; Li, Jin-ping; Song, Ying-lun; Zhao, Qi-huang

    2017-01-01

    Abstract Objective: To assess the effect of intensive insulin therapy (IIT) for preventing postoperative infection in patients with traumatic brain injury (TBI). Methods: In total, 88 patients with TBI were randomly divided into 2 groups, 44 in each group. One group (group ITT) received IIT and the other group (group CIT) received conventional insulin therapy (CIT). This study was conducted between February 2013 and January 2016. Outcomes included infection rate, mortality, and neurological outcome (measured by the Glasgow Outcome Scale [GOS]). Results: A total of 81 patients completed the study. IIT showed greater efficacy than CIT, with a decreased infection rate in the IIT group compared to the CIT group (31.9% vs 52.3%, P = 0.03), and also a reduced duration of stay in intensive care unit (ICU) (IIT group, 4.5 ± 2.1 days vs CIT group, 5.7 ± 2.8 days, P = 0.02). In addition, a significant difference in scores on the GOS scale was observed between the 2 groups (P = 0.04). The mortality rates in hospital and at the 26-week follow-up were similar between the 2 groups. Conclusion: IIT leads to a reduced infection rate, shorter stays in ICU, and improved neurological outcome. PMID:28353579

  14. Acute effects of different diet compositions on skeletal muscle insulin signalling in obese individuals during caloric restriction

    PubMed Central

    Wang, Cecilia C.L.; Adochio, Rebecca L.; Leitner, J. Wayne; Abeyta, Ian M.; Draznin, Boris; Cornier, Marc-Andre

    2012-01-01

    Objective The cellular effects of restricting fat versus carbohydrate during a low-calorie diet are unclear. The aim of this study was to examine acute effects of energy and macronutrient restriction on skeletal muscle insulin signalling in obesity. Materials/Methods Eighteen obese individuals without diabetes underwent euglycemic-hyperinsulinemic clamp and skeletal muscle biopsy after: (a) 5 days of eucaloric diet (30% fat, 50% carbohydrate), and (b) 5 days of a 30% calorie-restricted diet, either low fat/high carbohydrate (LF/HC: 20% fat, 60% carbohydrate) or high-fat/low carbohydrate (HF/LC: 50% fat, 30% carbohydrate). Results Weight, body composition, and insulin sensitivity were similar between groups after eucaloric diet. Weight loss was similar between groups after hypocaloric diet, 1.3 ± 1.3 kg (p<0.0001 compared with eucaloric). Whole-body insulin sensitivity was unchanged after calorie restriction and similar between groups. However, ex vivo skeletal muscle insulin signalling differed depending on macronutrient composition of calorie-restricted diet. Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser 307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity. Conclusion Acute caloric restriction with a LF/HC diet alters skeletal muscle insulin signalling in a way that improves insulin sensitivity, while acute caloric restriction with a HF/LC diet induces changes compatible with insulin resistance. In both cases, ex vivo changes in skeletal muscle insulin signalling appear prior to changes in whole body insulin sensitivity. PMID:23174405

  15. Insulin

    MedlinePlus

    ... container that can be closed like a laundry detergent bottle. Check the expiration date on the insulin ... in a hard container like an empty laundry detergent bottle or a metal coffee can. Make sure ...

  16. Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage

    PubMed Central

    Xu, Qian; Wei, Yi-ting; Fan, Shuang-bo; Wang, Liang; Zhou, Xiao-ping

    2017-01-01

    Aim The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT. Methods Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m−2 min−1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. Results In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05). Conclusion Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment. PMID:28228657

  17. Malarial acute kidney injury in a paediatric intensive care unit.

    PubMed

    Kapoor, Kapil; Gupta, Shalu

    2012-10-01

    Acute kidney injury (AKI) is a serious complication of malaria which has a very high mortality rate. A retrospective analysis of medical record data of children treated for malarial AKI in a paediatric intensive care unit (PICU) was performed in order to evaluate the incidence, poor prognostic factors and outcome of AKI with malaria. Eighteen (48.6%) malarial patients had AKI (11 Plasmodium vivax positive, six P. falciparum positive and one mixed infection) with a male-to-female ratio of 1:2. The mean age was 75 ± 32 months (range, 1 month to 10 years). Oliguria was present in 61.1% and 55.5% required renal replacement therapy. Mortality was noted in 33.3% of patients and full recovery was achieved in 50% of patients. Oliguria, shock, central nervous system involvement, jaundice, disseminated intravascular coagulopathy and acute respiratory distress syndrome emerged as bad prognostic factors in simple univariate analysis. Malaria patients with and without AKI differ significantly in terms of shock, ventilator requirement, mortality and length of PICU stay.

  18. Clinical Impact of Sample Interference on Intensive Insulin Therapy in Severely Burned Patients: A Pilot Study

    PubMed Central

    Tran, Nam K.; Godwin, Zachary R.; Bockhold, Jennifer C.; Passerini, Anthony G.; Cheng, Julian; Ingemason, Morgan

    2013-01-01

    Objective Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). We evaluated the clinical impact of automatic correction of hematocrit and ascorbic acid interference for bedside glucose monitoring performance in critically ill burn patients. Methods The performance of two point-of-care glucose monitoring systems (GMS): (a) GMS1, an autocorrecting device, and (b) GMS2, a non-correcting device were compared. Sixty remnant arterial blood samples were collected in a prospective observational study to evaluate hematocrit and ascorbic acid effects on GMS1 vs. GMS2 accuracy paired against a plasma glucose reference. Next we enrolled 12 patients in a pilot randomized controlled trial (RCT). Patients were randomized 1:1 to receive IIT targeting a TGC interval of 111–151 mg/dL and guided by either GMS1 or GMS2. GMS bias, mean insulin rate, and glycemic variability were calculated. Results In the prospective study, GMS1 results were similar to plasma glucose results (mean bias: −0.75[4.0] mg/dL, n=60, P=0.214). GMS2 results significantly differed from paired plasma glucose results (mean bias: −5.66[18.7] mg/dL, n=60, P=0.048). Ascorbic acid therapy elicited significant GMS2 performance bias (29.2[27.2], P<0.001). RCT results reported lower mean bias (P<0.001), glycemic variability (P<0.05), mean insulin rate (P<0.001), and frequency of hypoglycemia (P<0.001) in the GMS1 group than the GMS2 group. Conclusions Anemia and high dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn patients. Automatic correction of confounding factors improves glycemic control. Further studies are warranted to determine outcomes associated with accurate glucose monitoring during IIT. PMID:23884048

  19. 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.

  20. Effect of intensive insulin therapy on first-phase insulin secretion in newly diagnosed type 2 diabetic patients with a family history of the disease

    PubMed Central

    LI, QING; WANG, LUAN; XIAO, LIN; WANG, ZHONGCHAO; WANG, FANG; YU, XIAOLONG; YAN, SHENGLI; WANG, YANGANG

    2015-01-01

    Intensive insulin treatment is known to improve β-cell function in the majority of patients with newly diagnosed type 2 diabetes mellitus (T2DM), and family history (FH) is known to be an important independent risk factor for T2DM. Thus, the aim of the present study was to investigate the difference in first-phase insulin secretion and the effect of intensive insulin therapy on the improvement of β-cell function between T2DM patients with and without a FH of diabetes. Patients with newly diagnosed T2DM and healthy controls were divided into groups according to their FH of diabetes. Improvement in β-cell function was evaluated with an arginine stimulation test after two weeks of continuous subcutaneous insulin infusion (CSII). Compared with the control group, the level of fasting insulin and the homeostasis model assessment of insulin resistance (HOMA2-IR) were higher in the DM group, while the homeostasis model assessment of β-cell insulin secretion (HOMA2-%β) and the first-phase peak ratio were lower (P<0.05). In addition, the first-phase peak ratio in the FH- control group was higher compared with that in the FH+ control group (P=0.023). Following CSII, all the patients achieved excellent blood glucose control in 6.2±3.6 days, without severe adverse effects. In the DM groups, the fasting insulin level and HOMA2-IR were lower, while the HOMA2-%β and first-phase peak ratio were higher, when compared with the values prior to treatment, particularly in the FH- DM group. The HOMA2-%β in the FH+ DM group was lower compared with the FH- DM group (P=0.027). Therefore, T2DM patients with and without a FH of the disease were shown to have a good response to CSII in the improvement of insulin resistance and β-cell function; however, the improvements were less significant in patients with a FH compared with patients without a FH of diabetes. PMID:25574243

  1. 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.

  2. Modeling of free fatty acid dynamics: insulin and nicotinic acid resistance under acute and chronic treatments.

    PubMed

    Andersson, Robert; Kroon, Tobias; Almquist, Joachim; Jirstrand, Mats; Oakes, Nicholas D; Evans, Neil D; Chappel, Michael J; Gabrielsson, Johan

    2017-02-21

    Nicotinic acid (NiAc) is a potent inhibitor of adipose tissue lipolysis. Acute administration results in a rapid reduction of plasma free fatty acid (FFA) concentrations. Sustained NiAc exposure is associated with tolerance development (drug resistance) and complete adaptation (FFA returning to pretreatment levels). We conducted a meta-analysis on a rich pre-clinical data set of the NiAc-FFA interaction to establish the acute and chronic exposure-response relations from a macro perspective. The data were analyzed using a nonlinear mixed-effects framework. We also developed a new turnover model that describes the adaptation seen in plasma FFA concentrations in lean Sprague-Dawley and obese Zucker rats following acute and chronic NiAc exposure. The adaptive mechanisms within the system were described using integral control systems and dynamic efficacies in the traditional [Formula: see text] model. Insulin was incorporated in parallel with NiAc as the main endogenous co-variate of FFA dynamics. The model captured profound insulin resistance and complete drug resistance in obese rats. The efficacy of NiAc as an inhibitor of FFA release went from 1 to approximately 0 during sustained exposure in obese rats. The potency of NiAc as an inhibitor of insulin and of FFA release was estimated to be 0.338 and 0.436 [Formula: see text], respectively, in obese rats. A range of dosing regimens was analyzed and predictions made for optimizing NiAc delivery to minimize FFA exposure. Given the exposure levels of the experiments, the importance of washout periods in-between NiAc infusions was illustrated. The washout periods should be [Formula: see text]2 h longer than the infusions in order to optimize 24 h lowering of FFA in rats. However, the predicted concentration-response relationships suggests that higher AUC reductions might be attained at lower NiAc exposures.

  3. Meal-induced insulin sensitization is preserved after acute olanzapine administration in female Sprague-Dawley rats.

    PubMed

    Kovács, Diána; Hegedűs, Csaba; Kiss, Rita; Sári, Réka; Németh, József; Szilvássy, Zoltán; Peitl, Barna

    2015-05-01

    Olanzapine, an atypical antipsychotic, can acutely induce fasting insulin resistance, but we do not know whether it is able to modulate the meal-induced insulin sensitization (MIS). Two main experimental groups (control and olanzapine-treated) were created with two subgroups (fasted and re-fed) within each. After oral vehicle/olanzapine administration, the first meal size and duration and the total amount of consumed food was recorded in conscious rats. Then, under anaesthesia, the carotid artery and jugular vein was prepared and cannulated to obtain samples for blood glucose and hormone determination as well as for insulin/glucose infusion, respectively. Basal insulin sensitivity and MIS was determined by homeostasis model assessment (HOMA) calculation and by rapid insulin sensitivity test, respectively. In fasted animals, olanzapine increased blood glucose and plasma insulin and reduced basal insulin sensitivity, but it failed to modify other hormone levels. Postprandial leptin and glucose-dependent insulinotropic polypeptide (GIP) levels increased, and ghrelin level decreased significantly (p < 0.05) both in vehicle- and olanzapine-treated groups, but plasma insulin increased only in vehicle-treated animals. Furthermore, decrement in ghrelin level was attenuated in olanzapine-treated animals compared to controls. There was no significant change in the first meal size and duration or in the total amount of food consumed. Olanzapine had no effect on the MIS. We demonstrated that olanzapine can induce insulin resistance without weight gain in healthy rats. Furthermore, the MIS was preserved after acute olanzapine treatment. The blunted postprandial ghrelin and insulin response could contribute to the effect of olanzapine on feeding behaviour. Pharmacological induction of MIS may improve the olanzapine-induced insulin resistance.

  4. Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy.

    PubMed

    McNay, Ewan C; Teske, Jennifer A; Kotz, Catherine M; Dunn-Meynell, Ambrose; Levin, Barry E; McCrimmon, Rory J; Sherwin, Robert S

    2013-01-15

    A major side effect of insulin treatment of diabetes is weight gain, which limits patient compliance and may pose additional health risks. Although the mechanisms responsible for this weight gain are poorly understood, it has been suggested that there may be a link to the incidence of recurrent episodes of hypoglycemia. Here we present a rodent model of marked weight gain associated with weekly insulin-induced hypoglycemic episodes in the absence of diabetes. Insulin treatment caused a significant increase in both body weight and fat mass, accompanied by reduced motor activity, lowered thermogenesis in response to a cold challenge, and reduced brown fat uncoupling protein mRNA. However, there was no effect of insulin treatment on total food intake nor on hypothalamic neuropeptide Y or proopiomelanocortin mRNA expression, and insulin-treated animals did not become insulin-resistant. Our results suggest that repeated iatrogenic hypoglycemia leads to weight gain, and that such weight gain is associated with a multifaceted deficit in metabolic regulation rather than to a chronic increase in caloric intake.

  5. 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.

  6. Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE).

    PubMed

    2017-03-30

    Objective To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment.Design Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial).Setting Eight secondary care centres in England and Scotland.Participants Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment ("dose adjustment for normal eating," DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections.Interventions Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years.Main outcome measures The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction.Results 317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the

  7. Acute exercise ameliorates differences in insulin resistance between physically active and sedentary overweight adults.

    PubMed

    Nelson, Rachael K; Horowitz, Jeffrey F

    2014-07-01

    Although regular exercise is associated with reduced cardiometabolic disease risk among overweight adults, it remains unclear whether much of the health benefits of exercise are derived from the most recent session(s) of exercise or if they are the result of adaptations stemming from weeks, months, or even years of training. The purpose of this study was to compare the effects of habitual and acute exercise on key markers of cardiometabolic disease risk in overweight adults. We compared insulin sensitivity index (ISI) using an oral glucose tolerance test, blood pressure (BP), blood lipids, and systemic inflammatory cytokines in 12 overweight to mildly obese adults (BMI: 27-34 kg/m(2)) who exercise regularly (EX; >2.5 h exercise per week) with a well-matched cohort of 12 nonexercisers (Non-EX). Baseline measurements in EX were performed exactly 3 days after exercise, whereas Non-EX remained sedentary. We repeated these measurements the day after a session of exercise in both groups. At baseline, ISI was significantly greater in EX versus Non-EX (3.1 ± 0.2 vs. 2.3 ± 0.2; p = 0.02), but BP, blood lipids, and plasma concentration of the systemic inflammatory cytokines we measured were not different between groups. Acute exercise increased ISI the next morning in Non-EX (2.3 ± 0.2 vs. 2.8 ± 0.3; p = 0.03) but not EX. As a result, ISI was similar between groups the morning after exercise. In summary, exercising regularly was accompanied by a persistent improvement in insulin sensitivity that lasted at least 3 days after exercise in overweight adults, but just one session of exercise increased insulin sensitivity among sedentary overweight adults to levels equivalent to the regular exercisers.

  8. Acute exercise ameliorates differences in insulin resistance between physically active and sedentary overweight adults

    PubMed Central

    Nelson, Rachael K.; Horowitz, Jeffrey F.

    2014-01-01

    Although regular exercise is associated with reduced cardiometabolic disease risk among overweight adults, it remains unclear whether much of the health benefits of exercise are derived from the most recent session(s) of exercise or if they are the result of adaptations stemming from weeks, months, or even years of training. The purpose of this study was to compare the effects of habitual and acute exercise on key markers of cardiometabolic disease risk in overweight adults. We compared insulin sensitivity index (ISI) using an oral glucose tolerance test, blood pressure (BP), blood lipids, and systemic inflammatory cytokines in 12 overweight to mildly obese adults (BMI: 27–34 kg/m2) who exercise regularly (EX; >2.5 h exercise per week) with a well-matched cohort of 12 nonexercisers (Non-EX). Baseline measurements in EX were performed exactly 3 days after exercise, whereas Non-EX remained sedentary. We repeated these measurements the day after a session of exercise in both groups. At baseline, ISI was significantly greater in EX versus Non-EX (3.1 ± 0.2 vs. 2.3 ± 0.2; p = 0.02), but BP, blood lipids, and plasma concentration of the systemic inflammatory cytokines we measured were not different between groups. Acute exercise increased ISI the next morning in Non-EX (2.3 ± 0.2 vs. 2.8 ± 0.3; p = 0.03) but not EX. As a result, ISI was similar between groups the morning after exercise. In summary, exercising regularly was accompanied by a persistent improvement in insulin sensitivity that lasted at least 3 days after exercise in overweight adults, but just one session of exercise increased insulin sensitivity among sedentary overweight adults to levels equivalent to the regular exercisers. PMID:24773370

  9. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise.

    PubMed

    Cartee, Gregory D

    2015-12-15

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24-48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise.

  10. Acute Treatment With XMetA Activates Hepatic Insulin Receptors and Lowers Blood Glucose in Normal Mice.

    PubMed

    Bedinger, Daniel H; Kieffer, Dorothy A; Goldfine, Ira D; Roell, Marina K; Adams, Sean H

    2015-09-01

    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 transport in cultured cells, and chronically reduced fasting blood glucose levels in mouse models of diabetes mellitus. Under acute dosing conditions, the large size of an IR-binding antibody like XMetA (∼ 150 kDa) could lead to a more rapid access into liver, an insulin sensitive tissue with well-fenestrated capillaries, when compared to other insulin sensitive tissues with non-fenestrated capillaries, such as muscle and adipose. Thus, in the present study we administered XMetA (10 mg/kg) and insulin (0.5 U/kg) via IV injection, and for 90 min compared their effects on blood glucose lowering and IR activation in three of the major insulin-sensitive tissues of the normal fasted mouse: liver, adipose, and muscle. Like insulin, XMetA lowered blood glucose levels, although the effect was less rapid. Insulin activated IR autophosphorylation and Akt phosphorylation in liver, fat, and muscle. In contrast, IR activation by XMetA was primarily observed in the liver. Both insulin and XMetA lowered β-hydroxybutyrate levels in plasma; however, only insulin reduced both non-esterified fatty acids (NEFA) and glycerol concentrations. These data indicate that, in normal mice, acute glucose regulation by XMetA is largely mediated by its action on the liver.

  11. Peers, Regulators, and Professions: The Influence of Organizations in Intensive Insulin Therapy Adoption

    PubMed Central

    Campion, Thomas R.; Gadd, Cynthia S.

    2011-01-01

    Following the landmark Leuven study in 2001, health care organizations implemented intensive insulin therapy (IIT) as the standard of care for critically ill patients. However, a recent meta-analysis showed no mortality benefit and an increased safety risk for patients treated with IIT. IIT affects labor and capital decisions related to nurses, physicians, pharmacists, managers, laboratory personnel, and informatics staff. The expenditure of labor and capital to provide IIT without corresponding outcome improvements suggests the adoption of IIT produces inefficiency in hospitals. In sociology and organizational studies, the tendency for organizations to become more similar without necessarily becoming more efficient is called institutional isomorphism. Institutional isomorphism examines the pressure organizations encounter from peers, regulators, and professions through mimetic, coercive, and normative mechanisms, respectively. To enhance their prospects of survival, organizations establish and maintain legitimacy by adopting socially acceptable approaches to work endorsed by successful peer organizations, regulatory agencies, and professional societies. In this paper, the authors describe how organizational influence—through the Leuven study, the Joint Commission, and professional organizations—played a role in the widespread adoption of IIT. Divergence from institutionalized forms may explain variation in IIT studies following Leuven. Healthcare researchers, practitioners, and managers should consider organizational influence when implementing large scale clinical activities. PMID:19369854

  12. 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.

  13. Intensive or conventional insulin therapy in type 2 diabetic patients? A population-based study on metabolic control and quality of life (The JEVIN-trial).

    PubMed

    Schiel, R; Müller, U A

    1999-01-01

    Long-term micro- and macrovascular complications cause major morbidity and mortality in patients with type 2 diabetes mellitus. Up to the present it is not clear whether intensified or conventional insulin treatment is more effective to keep blood glucose concentrations close to the normal range. In the present trial 90% (n = 117) of all insulin-treated type 2 diabetic patients aged 16 to 60 years and living in the city of Jena (100,247 inhabitants), Thuringia, Germany were examined. Fourty patients (34%) were on intensive insulin therapy (ICT, > or = 2 injections of normal- and > or = 1 injection of NPH-/mixed-insulin/day, > or = 1 insulin-dose adjustments/week, > or = 2 blood-glucose self-tests/day) and 77 patients (66%) were on conventional insulin therapy (CIT). Patients with ICT had more injections/d (4.3 +/- 0.7 vs CIT 2.4 +/- 0.7, p < 0.001), more insulin-dose adjustments/week < or = 11.5 +/- 8.2 vs 2.2 +/- 5.2, p < 0.001) and more blood-glucose self-tests/week (25.2 +/- 5.7 vs 9.6 +/- 8.8, p < 0.001). Patients with ICT had higher insulin doses (0.71 +/- 0.32 vs 0.47 +/- 0.2 IU/kg body wt/d, p < 0.001), were younger (50.5 +/-6.7 vs 54.0 +/- 5.9 years, p = 0.004) and they had a non-significant tendency to a better HbAlc (8.7 +/- 2.2 vs 9.2 +/- 2.0%, p = 0.23, HPLC, Diamat, normal range 4.4-5,9%). There was a negative correlation between HbAlc and the frequency of blood-glucose self-tests/week (r = -0.23, p = 0.019) and the number of insulin-dose adjustments/week (r = -0.33, p < 0.001). There were no differences between the groups as regards body-mass index (29.7 +/-4.9 vs 28.0 +/- 4.5 kg/m2, p = 0.06), diabetes duration (12.3 +/- 6.9 vs 12.2 +/- 7.5 years, p = 0.96), duration of insulin therapy (4.2 +/-3.5 versus 4.5 +/- 4.8 years, p = 0.67), incidence of acute complications (severe hypoglycaemia, diabetic coma), prevalence of retino-, nephro- and neuropathy (assessed according to Young et al.) and education or socio-economic factors. Also, in respect of

  14. Use of neutral protamine lispro (NPL) insulin in a patient affected by acute pancreatitis under parenteral nutrition.

    PubMed

    Fatati, G; Mirri, E; Papi, M; Coaccioli, S

    2011-01-01

    Hyperglycaemia is considered the main obstacle to the activation of a correct nutritional support, even in patients not affected by diabetes mellitus. The stress associated with the acute pathology stimulates controinsular hormones and causes modifications in the glucidic metabolism. Artificial nutrition (AN), both enteral and parenteral (PN), is considered one of the main causes of hyperglycaemia in hospitalized patients. ADI-AMD recommendations underline that a long-acting insulin analogues can be used on a stabilized patient supported with PN via peristaltic pump. In the following case report, a patient under PN was given, after a surgery for acute pancreatitis, an injectable suspension of lispro NPL insulin. Our case report shows that also NPL lispro insulin subcutaneously can be used in patients under PN who need an insulin treatment and who can use a constant-flow infusion pump. Thanks to initial observations on the use of NPL insulin lispro in patients under PN we can assume the importance of such an insulin in association with AN. Clin Ter 2011; 162(3):231-234.

  15. Metabolic control and educational status in children with type 1 diabetes: effects of a summer camp and intensive insulin treatment.

    PubMed

    Karagüzel, G; Bircan, I; Erişir, S; Bundak, R

    2005-12-01

    Our aim was to evaluate prospectively, in our diabetic patients, the impacts of a summer camp and intensive insulin treatment (IIT) on both metabolic control and disease-related educational level. Twenty-five patients participated in a 7-day-long summer camp. Before the camp, all patients were on therapy with short-acting human insulin (SAI) and intermediate-acting insulin (IAI) twice daily. On arrival, their insulin therapy regimen was changed by IIT including either SAI or rapid-acting insulin analogue (RAI) three times before meals supplemented by IAI at bedtime. Following the camp, all participants were given IIT with RAI plus IAI. Frequency of hypoglycaemia, insulin dose, body mass index (BMI) and glycohaemoglobin (HbA1c) levels were assessed at pre-camp and post-camp controls. To evaluate the effectiveness of camp-assisted education, all participants were regularly tested. We observed significant elevations in total daily dose of insulin and BMI at months 3 and 6 when compared with the pre-camp values but, by month 12, they were not significantly different from precamp values. The mean HbA(1c) level decreased significantly at months 6 and 12. Severe hypoglycaemic episodes and ketoacidosis were not detected during the camp and the following year. Significant improvements in knowledge about diabetes and self-management were determined at the end of the camp, after 6 and 12 months. Camp-assisted IIT with RAI improved metabolic control of diabetic children. Additionally, camp-assisted education has a positive effect on disease-related educational level and self-management.

  16. 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...

  17. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.

    PubMed

    de Laat, M A; Kyaw-Tanner, M T; Nourian, A R; McGowan, C M; Sillence, M N; Pollitt, C C

    2011-04-15

    Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n=4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n=4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6h (n=4), 12h (n=4), 24h (n=4) and 48 h (n=4), and in normal control horses (n=4). The only change in gene expression observed was an upregulation of MMP-9 (p<0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p<0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.

  18. Altered mitochondrial function after acute alteration of the endogenous insulin/glucagon ratio

    SciTech Connect

    Rohweder-Dunn, G.; Aprille, J.R.

    1986-05-01

    Mannoheptulose (MH) affects pancreatic Islet cells to cause a drop in serum insulin and a rise in glucagon. This effect peaks 1 hr after injection and results in a 3-fold increase in serum glucose. Here they examined whether metabolic functions of liver mitochondria (mito) are altered by this change in hormone status. Rats fed ad lib on 12 hr light/dark cycles were given MH (2g/kg) or vehicle i.p. during the first 2 hrs of the light cycle. Liver mito were isolated 1 hr later. Acid-extracts were assayed for ATP+ADP+AMP (nmol/mg prot). Citrulline synthesis and pyruvate carboxylation rates (nmol/min/mg prot) were assayed by following H(/sup 14/C)O/sub 3//sup -/ fixation in appropriate media. State 3 and 2,4-DNP-uncoupled respiratory rates (1/2 nmol O/sub 2//min/mg prot) were assayed polarographically with succinate. The effects of MH on mito are comparable to reported effects of glucagon injection. MH evokes acute reciprocal changes in insulin and glucagon that are highly reproducible. Thus, MH offers an interesting model for studying the effect of endogenous hormones on mito functions.

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

    PubMed Central

    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. PMID:25805973

  20. Validity of bedside blood glucose measurement in critically ill patients with intensive insulin therapy

    PubMed Central

    Mahmoodpoor, Ata; Hamishehkar, Hadi; Shadvar, Kamran; Sanaie, Sarvin; Iranpour, Afshin; Fattahi, Vahid

    2016-01-01

    Background and Aims: There have been variable results on the practice of tight glycemic control, and studies have demonstrated that point-of-care (POC) glucometers have variable accuracy. Glucometers must be accurate, and many variables can affect blood glucose levels. The purpose of this study was to determine the difference between blood glucose concentrations obtained from POC glucometers and laboratory results in critically ill patients with intensive insulin therapy. Materials and Methods: This was a descriptive study which enrolled 300 critically ill patients. Four samples of arterial blood were collected and analyzed at the bedside with the POC glucometer and also in the central laboratory to obtain the blood glucose level. To define the effect of various factors on this relation, we noted the levels of hemoglobin (Hb), PaO2, body temperature, bilirubin, history of drug usage, and sepsis. Results: There were not any significant differences between blood sugar levels using laboratory and glucometer methods of measurements. There was a good and significant correlation between glucose levels between two methods (r = 0.81, P < 0.001). Among evaluated factors (body temperature, bilirubin level, blood pressure, Hb level, PaO2, sepsis, and drugs) which added one by one in model, just drugs decreased the correlation more than others (r = 0.78). Conclusions: The results of POC glucometer differ from laboratory glucose concentrations, especially in critically ill patients with unstable hemodynamic status while receiving several drugs. This may raise the concern about using POC devices for tight glycemic control in critically ill patients. These results should be interpreted with caution because of the large variation of accuracy among different glucometer devices. PMID:27994380

  1. Vitamin E induces regular structure and stability of human insulin, more intense than vitamin D3.

    PubMed

    Soleymani, Hossein; Saboury, Ali A; Moosavi-Movahedi, Ali A; Rahmani, Fatemeh; Maleki, Javad; Yousefinejad, Saeid; Maghami, Parvaneh

    2016-12-01

    Changes in human environment and lifestyle over the last century have caused a dramatic increase in the occurrence of diabetes. Research of past decades illustrated that vitamin D and E have a key role in the improvement of diabetes by reducing oxidative stress, protein glycosylation, insulin resistance and also improving beta cell function. Binding properties and conformational changes of human insulin upon interaction with vitamins D3 and E (α-tocopherol) were investigated by spectroscopy, differential scanning calorimetry (DSC) and molecular dynamic simulation. Tyrosine fluorescence quenching studies indicates changes in the human insulin conformation in the presence of vitamins. Binding constants of vitamins D3 and E for human insulin were determined to be 2.7 and 1.5 (×10(-5)M(-1)) and the corresponding average numbers of binding sites were determined to be 1.3 and 1.2, respectively. Far- and near-UV circular dichroism studies showed that vitamin E can significantly change the secondary and tertiary structures of human insulin via an increase in the content of α-helix structure. Results of DSC showed that both vitamins D3 and E stabilize the structure of human insulin. Molecular dynamic simulation results indicated that vitamin D3 decreases the helical and strand structural contents of human insulin, but vitamin E stabilizes more regular secondary structures such as helical and strand structural contents as shown by experimental results.

  2. Short-term intensive insulin therapy at diagnosis in type 2 diabetes: plan for filling the gaps.

    PubMed

    Weng, Jianping; Retnakaran, Ravi; Ariachery C, Ammini; Ji, Linong; Meneghini, Luigi; Yang, Wenying; Woo, Jeong-Taek

    2015-09-01

    Short-term intensive insulin therapy is unique amongst therapies for type 2 diabetes because it offers the potential to preserve and improve beta-cell function without additional pharmacological treatment. On the basis of clinical experience and the promising results of a series of studies in newly diagnosed patients, mostly in Asian populations, an expert workshop was convened to assess the available evidence and the potential application of short-term intensive insulin therapy should it be advocated for inclusion in clinical practice. Participants included primary care physicians and endocrinologists. We endorse the concept of short-term intensive insulin therapy as an option for some patients with type 2 diabetes at the time of diagnosis and have identified the following six areas where additional knowledge could help clarify optimal use in clinical practice: (1) generalizability to primary care, (2) target population and biomarkers, (3) follow-up treatment, (4) education of patients and providers, (5) relevance of ethnicity, and (6) health economics.

  3. 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

  4. The intensive care medicine agenda on acute kidney injury.

    PubMed

    Pickkers, Peter; Ostermann, Marlies; Joannidis, Michael; Zarbock, Alexander; Hoste, Eric; Bellomo, Rinaldo; Prowle, John; Darmon, Michael; Bonventre, Joseph V; Forni, Lui; Bagshaw, Sean M; Schetz, Miet

    2017-01-30

    Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints.

  5. High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation

    PubMed Central

    Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

    2017-01-01

    Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21–5% FiO2, 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy. PMID:28255159

  6. 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)…

  7. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.

    PubMed

    Lewis, G F; Uffelman, K D; Szeto, L W; Weller, B; Steiner, G

    1995-01-01

    Changes in VLDL triglyceride and VLDL apo B production were determined semiquantitatively in healthy young men by examining the effect of altering plasma insulin and/or FFA levels on the change in the slopes of the specific activity of VLDL [3H]triglyceride glycerol or the 131I-VLDL apo B versus time curves. In one study (n = 8) insulin was infused for 5 h using the euglycemic hyperinsulinemic clamp technique. Plasma FFA levels declined by approximately 80% (0.52 +/- 0.01 to 0.11 +/- 0.02 mmol/liter), VLDL triglyceride production decreased by 66.7 +/- 4.2% (P = 0.0001) and VLDL apo B production decreased by 51.7 +/- 10.6% (P = 0.003). In a second study (n = 8) heparin and Intralipid (Baxter Corp., Toronto, Canada) were infused with insulin to prevent the insulin-mediated fall in plasma FFA levels. Plasma FFA increased approximately twofold (0.43 +/- 0.05 to 0.82 + 0.13 mmol/liter), VLDL triglyceride production decreased to a lesser extent than with insulin alone (P = 0.006) (-31.8 +/- 9.5%, decrease from baseline P = 0.03) and VLDL apo B production did not decrease significantly (-6.3 +/- 13.6%, P = NS). In a third study (n = 8) when heparin and Intralipid were infused without insulin, FFA levels rose approximately twofold (0.53 +/- 0.04 to 0.85 +/- 0.1 mmol/liter), VLDL triglyceride production increased by 180.1 +/- 45.7% (P = 0.008) and VLDL apo B production increased by 94.2 +/- 28.7% (P = 0.05). We confirm our previous observation that acute hyperinsulinemia suppresses VLDL triglyceride and VLDL apo B production in healthy humans. In addition, we have demonstrated that elevation of plasma FFA levels acutely stimulates VLDL production in vivo in healthy young males. Elevating plasma FFA during hyperinsulinemia attenuates but does not completely abolish the suppressive effect of insulin on VLDL production, at least with respect to VLDL triglycerides. Therefore, in normal individuals the acute inhibition of VLDL production by insulin in vivo is only partly due to

  8. A regular meal and insulin infusion regimen: its use in the treatment of acute-onset ketotic diabetes and in stabilization of poorly controlled established diabetic subjects.

    PubMed

    Davis, T M; Holman, R R; Eaton, P M; Turner, R C

    1982-01-01

    A simple regimen, consisting of a constant intravenous insulin infusion at either a basal, nocturnal rate or at a daytime rate matched by seven small, isocaloric meals taken every 2 h, has been applied to two clinical situations requiring optimal blood glucose control. In eight poorly controlled established diabetic subjects, quantitative estimates of daily insulin requirements were possible, with consequent improved control upon reinstitution of twice-daily subcutaneous insulin. In five acute-onset, ketotic diabetic subjects first treated by intravenous saline and low-dose intramuscular insulin, the regimen was used to achieve and maintain basal and postprandial normoglycemia. Ketonuria was abolished quickly in these patients, and falling insulin requirements and large doses of insulin were handled easily. In both clinical situations, subsequent subcutaneous insulin doses required little adjustment. The regimen is cheap, convenient to use, and widely applicable.

  9. Mobile telecare system for intensive insulin treatment and patient education. First applications for newly diagnosed type 1 diabetic patients.

    PubMed

    Ładyzyński, P; Wójcicki, J M; Krzymień, J; Foltyński, P; Migalska-Musiał, K; Tracz, M; Karnafel, W

    2006-11-01

    The aim of the work was to develop and to evaluate the clinical efficiency of a mobile telecare system implementing teleconsultations based on the continuous transmission of patient-collected data directly to the physician and to the clinic. The developed TeleMed system consists of the patients' and the diabetologist's mobile units, the diabetologist's clinic and home workstations and the clinical server. The evaluation of the system was performed on a group of 13 newly diagnosed type 1 diabetic patients, during a single-arm study with 3-days run-in period, including a one-day intensive educational program, and 3-week study period, when the intensive insulin treatment was conducted without visits of patients to the clinic. The MBG dropped from 7.2 +/- 1.7 mmol/L before the study to 6.1 +/- 1.0 mmol/L in the third week of the study (P = 0.02) and the J-index from 30.2+/-19.2 to 19.7+/-7.7 (P = 0.04). Hemoglobin A1c decreased from 11.8 +/- 3.3% to 8.6 +/- 1.2% (P = 0.0002) in one month. The total daily insulin dose declined from 39.9 +/- 8.5 U to 20.0 +/- 9.6 U (P = 0.000006). The number of hypoglycemia episodes per patient per day decreased by 66% (P = 0.08) and the number of hyperglycemia episodes was reduced by 47% (P < 0.0001). The TeleMed facilitates not only efficient realization of the intensive insulin treatment but also successful remote patient training and education. No formal patient satisfaction study was done. However, some of the findings indicate that the application of the developed system increases patient self-confidence and quality of life.

  10. Improved Glycemic Control in Intensively Treated Adult Subjects with Type 1 Diabetes Using Insulin Guidance Software

    PubMed Central

    Bookout, Tevin R.; McFann, Kim K.; Kelly, William C.; Beatson, Christie; Ellis, Samuel L.; Gutin, Raymond S.; Gottlieb, Peter A.

    2008-01-01

    Abstract Background Management of type 1 diabetes could be significantly improved with the availability of computerized insulin algorithms for home use. Methods This was a 1-year open label randomized control trial involving 123 adult subjects with type 1 diabetes (hemoglobin A1c values 7.5–11%) assigned to either the insulin guidance software (ACCU-CHEK® [Roche, Indianapolis, IN] Advisor) for personal data assistant (experimental group) or the control group. The primary aim of the study was to see if subjects using insulin dosing advisor software will improve glucose control over 1 year. The principal end point was an improvement in A1c at 6 and 12 months by ≥0.4%. Results Baseline demographics were similar in the two groups. Mean A1c was 8.54 ± 0.11% in the control group and 8.42 ± 0.11% (P = 0.4265) in the experimental group. The mean A1c was significantly lower from 3 to 12 months in the experimental group (P < 0.02). A1c reduction of ≥0.6% was maintained at 12 months in the experimental group. Also, a significantly higher number of subjects achieved A1c <7.5% in the experimental group from 3 to 9 months. Within target range glycemia (70–150 mg/dL) was higher in the experimental group at 3–9 months without any change in insulin dose or weight. Above target range glycemia was lower in the experimental group throughout the study. Frequency of testing per day was higher in the experimental group. Nocturnal hypoglycemia was not different between groups; however, the experimental group experienced more severe hypoglycemic events. Conclusions This is the first report that shows improved glycemic control can be maintained over 12 months in patients with type 1 diabetes by using Advisor with no change in insulin dose and weight. PMID:18715213

  11. A quantitative analysis of the effect of glucose-insulin-potassium in acute myocardial infarction

    PubMed Central

    Rasoul, S.; Svilaas, T.; Ottervanger, J-P.; Timmer, J.R.; van 't Hof, A.W.J.; Zijlstra, F.

    2006-01-01

    Objective To review the currently available data to investigate the clinical benefit of high- and low-dose glucose-insulin-potassium (GIK) in patients with ST-segment elevation acute myocardial infarction (STEMI). Design Quantitative analysis of all randomised trials on GIK in patients with STEMI. Electronic and manual searches for randomised controlled trials of GIK in STEMI were performed with regard to inclusion criteria, dose of GIK and additional use of reperfusion therapy, and a meta-analysis with the primary endpoint 30-day mortality was performed. Patients Data from 16 randomised trials, involving 26,273 patients, were included. Results Studies were conducted between 1962 and 2005. Overall, hospital mortality was 9.6% after GIK compared with 10.2% in controls (p=0.088). GIK infusion was not associated with an increase in major adverse events. Conclusion This quantitative analysis of GIK in patients with STEMI did not show a beneficial or detrimental effect of GIK infusion on 30-day mortality. GIK infusion should not be part of the standard therapy for patients with STEMI. PMID:25696550

  12. 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.

  13. Response of non-insulin-dependent diabetic patients to an intensive program of diet and exercise.

    PubMed

    Barnard, R J; Lattimore, L; Holly, R G; Cherny, S; Pritikin, N

    1982-01-01

    To assess the effectiveness of the Pritikin program of diet and exercise for treating patients with non-insulin-dependent diabetes mellitus (NIDDM), data were obtained from 60 patients who completed the 26-day residential program. Of the 23 patients who were taking oral hypoglycemic agents upon entry, all but 2 were off medication by the end of the program. Of the 17 patients who were taking insulin, all but 4 were off medication at discharge. Two of the four had their insulin reduced by 50% while the remaining two had no major change in their insulin dosage. Fasting blood glucose was reduced from 194.9 +/- 10.1 to 144.6 +/- 7.1 mg/dl. Serum cholesterol was reduced from 225.4 +/- 5.7 to 181.7 +/- 4.9 mg/dl while triglycerides were reduced from 283.7 +/- 28.8 to 186.2 +/- 11.6 mg/dl. The group as a whole lost an average of 4.3 kg/body wt and achieved 40.5% of their desired weight loss. Maximum work capacity increased from 5.6 +/- 0.3 to 7.9 +/- 0.4 METs, while daily walking increased from 11.7 +/- 2.4 to 102.8 +/- 4.8 min/day. The decrease in fasting glucose was not correlated with weight loss (r = 0.24), increase in walking time (r = 0.00), or increase in MET capacity (r = 0.05). We conclude that the total program is an effective means for treating NIDDM patients. We also feel that the high-complex-carbohydrate, high-fiber, low-fat diet is of primary importance.

  14. Acute high-intensity exercise with low energy expenditure reduced LDL-c and total cholesterol in men.

    PubMed

    Lira, Fabio S; Zanchi, Nelo E; Lima-Silva, Adriano E; Pires, Flávio O; Bertuzzi, Rômulo C; Santos, Ronaldo V; Caperuto, Erico C; Kiss, Maria A; Seelaender, Marília

    2009-09-01

    A reduction in LDL cholesterol and an increase in HDL cholesterol levels are clinically relevant parameters for the treatment of dyslipidaemia, and exercise is often recommended as an intervention. This study aimed to examine the effects of acute, high-intensity exercise ( approximately 90% VO(2max)) and varying carbohydrate levels (control, low and high) on the blood lipid profile. Six male subjects were distributed randomly into exercise groups, based on the carbohydrate diets (control, low and high) to which the subjects were restricted before each exercise session. The lipid profile (triglycerides, VLDL, HDL cholesterol, LDL cholesterol and total cholesterol) was determined at rest, and immediately and 1 h after exercise bouts. There were no changes in the time exhaustion (8.00 +/- 1.83; 7.82 +/- 2.66; and 9.09 +/- 3.51 min) and energy expenditure (496.0 +/- 224.8; 411.5 +/- 223.1; and 592.1 +/- 369.9 kJ) parameters with the three varying carbohydrate intake (control, low and high). Glucose and insulin levels did not show time-dependent changes under the different conditions (P > 0.05). Total cholesterol and LDL cholesterol were reduced after the exhaustion and 1 h recovery periods when compared with rest periods only in the control carbohydrate intake group (P < 0.05), although this relation failed when the diet was manipulated. These results indicate that acute, high-intensity exercise with low energy expenditure induces changes in the cholesterol profile, and that influences of carbohydrate level corresponding to these modifications fail when carbohydrate (low and high) intake is manipulated.

  15. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    PubMed

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

  16. REGULATION OF GLUCOSE AND INSULIN RELEASE FOLLOWING ACUTE AND REPEATED TREATMENT WITH THE SYNTHETIC GALANIN ANALOG NAX-5055

    PubMed Central

    Flynn, Sean P.; White, H. Steve

    2015-01-01

    The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems. However there is limited understanding of how individual galanin receptor (GalR1, 2, and 3) subtypes mediate the physiological activity of galanin in vivo. To address this issue we utilized NAX-5055 a systemically available, metabolically stable galanin analog. NAX-5055 displays a preference for GalR1 receptors and possesses potent anticonvulsant activity in vivo, suggesting that NAX-5055 engages central galanin receptors. To determine if NAX-5055 also modulates the activity of peripheral galanin receptors, we evaluated the effect of NAX-5055 on blood glucose and insulin levels in mice. Acute and repeated (once daily for four days) systemic administration of NAX-5055 (4 mg/kg) significantly increased blood glucose levels compared to vehicle treated mice. However, a hyperglycemic response was not observed following systemic administration of NAX-805-1 a scrambled analog of NAX-5055, with critical receptor binding residues, Trp2 and Tyr9, reversed. These results suggest chemical modifications independent of the galanin backbone of NAX-5055 are not responsible for the hyperglycemic response. The effect of NAX-5055 on glucose homeostasis was further evaluated with a glucose tolerance test (GTT). Mice administered either acute or repeated (once daily for four days) injections of NAX-5055 (4mg/kg) displayed impaired glucose handling and reduced insulin response to an acute glucose (1g/kg) challenge. Here we have shown that systemic administration of a centrally active GalR1-preferring galanin analog produces acute hyperglycemia and an inhibition of insulin release in vivo and that these effects are not attenuated with repeated administration. NAX-5055 thus provides a new pharmacological tool to further the understanding of function of both central and peripheral GalR1 receptors in vivo. PMID:25690510

  17. 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.

  18. 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…

  19. Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men.

    PubMed

    Boden, Guenther; Homko, Carol; Barrero, Carlos A; Stein, T Peter; Chen, Xinhua; Cheung, Peter; Fecchio, Chiara; Koller, Sarah; Merali, Salim

    2015-09-09

    Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known as the metabolic or insulin resistance syndrome. How obesity promotes insulin resistance remains incompletely understood. Plasma concentrations of free fatty acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and oxidative stress are all elevated in obesity and have been shown to induce insulin resistance. However, they may be late events that only develop after chronic excessive nutrient intake. The nature of the initial event that produces insulin resistance at the beginning of excess caloric intake and weight gain remains unknown. We show that feeding healthy men with ~6000 kcal/day of the common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 week produced a rapid weight gain of 3.5 kg and the rapid onset (after 2 to 3 days) of systemic and adipose tissue insulin resistance and oxidative stress but no inflammatory or ER stress. In adipose tissue, the oxidative stress resulted in extensive oxidation and carbonylation of numerous proteins, including carbonylation of GLUT4 near the glucose transport channel, which likely resulted in loss of GLUT4 activity. These results suggest that the initial event caused by overnutrition may be oxidative stress, which produces insulin resistance, at least in part, via carbonylation and oxidation-induced inactivation of GLUT4.

  20. Acute Effect of High-Intensity Eccentric Exercise on Vascular Endothelial Function in Young Men.

    PubMed

    Choi, Youngju; Akazawa, Nobuhiko; Zempo-Miyaki, Asako; Ra, Song-Gyu; Shiraki, Hitoshi; Ajisaka, Ryuichi; Maeda, Seiji

    2016-08-01

    Choi, Y, Akazawa, N, Zempo-Miyaki, A, Ra, S-G, Shiraki, H, Ajisaka, R, and Maeda, S. Acute effect of high-intensity eccentric exercise on vascular endothelial function in young men. J Strength Cond Res 30(8): 2279-2285, 2016-Increased central arterial stiffness is as an independent risk factor for cardiovascular disease. Evidence regarding the effects of high-intensity resistance exercise on vascular endothelial function and central arterial stiffness is conflicting. The purpose of this study was to examine the effects of acute high-intensity eccentric exercise on vascular endothelial function and central arterial stiffness. We evaluated the acute changes in endothelium-dependent flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and arterial stiffness after high-intensity eccentric exercise. Seven healthy, sedentary men (age, 24 ± 1 year) performed maximal eccentric elbow flexor exercise using their nondominant arm. Before and 45 minutes after eccentric exercise, carotid arterial compliance and brachial artery FMD and L-FMC in the nonexercised arm were measured. Carotid arterial compliance was significantly decreased, and β-stiffness index significantly increased after eccentric exercise. Brachial FMD was significantly reduced after eccentric exercise, whereas there was no significant difference in brachial L-FMC before and after eccentric exercise. A positive correlation was detected between change in arterial compliance and change in FMD (r = 0.779; p ≤ 0.05), and a negative correlation was detected between change in β-stiffness index and change in FMD (r = -0.891; p < 0.01) with eccentric exercise. In this study, acute high-intensity eccentric exercise increased central arterial stiffness; this increase was accompanied by a decrease in endothelial function caused by reduced endothelium-dependent vasodilation but not by a change in endothelium-dependent vasoconstriction.

  1. 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

  2. The intriguing effects of time to glycemic goal in newly diagnosed type 2 diabetes after short-term intensive insulin therapy.

    PubMed

    Cheng, Lin; Xu, Mingtong; Lin, Xiuhong; Tang, Juying; Qi, Yiqin; Wan, Yan; Pan, Xiaofang; Chen, Xiaoyun; Ren, Meng; Yan, Li

    2016-08-31

    Short-term intensive insulin therapy is effective for type 2 diabetes because it offers the potential to achieve excellent glycemic control and improve β-cell function. We observed that the time to glycemic goal (TGG) was adjustable. Original data of 138 newly diagnosed type 2 diabetic patients received intensive insulin therapy by continuous subcutaneous insulin infusion for 2-3 weeks were retrospectively collected. Subjects underwent an intravenous glucose tolerance test (IVGTT) and an oral glucose tolerance test (OGTT) pre and post treatment. The glycemic goal was achieved within 6 (4-8) days. Patients were divided into two groups by TGG above (TGG-slow) and below (TGG-fast) the median value. Patients in both groups had significantly better glycemic control. Compared with TGG-fast, TGG-slow required a few more total insulin and performed more improvement of HOMA-β and IVGTT-AUCIns, but less improvement of HOMA-IR and QUICKI. Multiple linear regression analysis revealed that TGG was always an explanatory variable for the changes (HOMA-β, IVGTT-AUCIns, HOMA-IR and QUICKI). The hypoglycemia prevalence was lower in TGG-slow (1.48% vs. 3.40%, P<0.01). Multivariate logistic regression analysis indicated that individuals in TGG-slow had a lower risk of hypoglycemia (adjusted OR, 0.700; 95% CI, 0.567-0.864; P<0.05). Multiple linear regression analysis confirmed that the ratio of the incremental insulin to glucose responses over the first 30 min during OGTT (ΔIns30/ΔG30), average insulin dose before achieving targets, initial insulin dose and LDL-c were independent predictors for TGG. It is intriguing to hypothesize that patients with fast time to glycemic goal benefit more in improving insulin sensitivity, but patients with slow time benefit more in improving β-cell function and reducing the risk of hypoglycemia.

  3. Acute effects of the different intensity of static stretching on flexibility and isometric muscle force.

    PubMed

    Kataura, Satoshi; Suzuki, Shigeyuki; Matsuo, Shingo; Hatano, Genki; Iwata, Masahiro; Yokoi, Kazuaki; Tsuchida, Wakako; Banno, Yasuhiro; Asai, Yuji

    2016-11-29

    In various fields, static stretching is commonly performed to improve flexibility, whereas the acute effects of different stretch intensities are unclear. Therefore, we investigated the acute effects of different stretch intensities on flexibility and muscle force. Eighteen healthy participants (nine men, nine women) performed 180-s static stretches of the right hamstrings at 80%, 100%, and 120% of maximum tolerable intensity without stretching pain, in random order. The following outcomes were assessed as markers of lower limb function and flexibility: static passive torque (SPT), range of motion (ROM), passive joint (muscle-tendon) stiffness, passive torque at onset of pain (PT), and isometric muscle force. SPT was significantly decreased after all stretching intensities (p < 0.05). Compared with before stretching at 100% and 120% intensity, ROM and PT were significantly increased after stretching (p < 0.05), and passive stiffness (p = 0.05) and isometric muscle force (p < 0.05) were significantly decreased. In addition, ROM was significantly greater after stretching at 100% and 120% than at 80%, and passive stiffness was significantly lower after 120% than after 80% (p < 0.05). However, all measurements except SPT were unchanged after 80% intensity. There was a weak positive correlation between the intensities of stretching and the relative change for SPT (p < 0.05), a moderate positive correlation with ROM (p < 0.05), and a moderate positive correlation with passive stiffness (p < 0.05). These results indicate that static stretching at greater intensity is more effective for increasing ROM and decreasing passive muscle-tendon stiffness.

  4. Feasibility and cost analysis of implementing high intensity aphasia clinics within a sub-acute setting.

    PubMed

    Wenke, Rachel; Lawrie, Melissa; Hobson, Tania; Comben, Wendy; Romano, Michelle; Ward, Elizabeth; Cardell, Elizabeth

    2014-06-01

    The current study explored the clinical feasibility and costs of embedding three different intensive service delivery models for aphasia treatment (computer, group therapy, and therapy with a speech pathology therapy assistant) within three sub-acute facilities. The study employed a two cohort comparison design, with the first cohort (n = 22) receiving the standard service of treatment currently offered. This treatment was delivered by a speech-language pathologist and involved on average 3 hours of treatment/week over 8 weeks. Participants in the second cohort (n = 31) received one of the three intensive treatment models providing up to 9 hours of therapy/week for 11 weeks. Organizational data was collected throughout treatment, with participant, caregiver, and clinician satisfaction with the intensive models also being measured. Participants completed the spoken language production sub-tests and the Disability Questionnaire of the Comprehensive Aphasia Test (CAT) pre- and post-treatment. All intensive models yielded high participant attendance, satisfaction, and significant improvements to the CAT sub-tests. The pro-rata cost of providing treatment per hour per client for the computer and group therapy models was found to be ˜ 30% cheaper compared to the standard service. The outcomes support the potential feasibility of embedding the different models into sub-acute facilities to enhance client access to intensive treatment for aphasia.

  5. Acute insulin responses to glucose and arginine as predictors of beta-cell secretory capacity in human islet transplantation.

    PubMed

    Rickels, Michael R; Naji, Ali; Teff, Karen L

    2007-11-27

    Islet transplantation for type 1 diabetes can enable the achievement of near-normal glycemic control without severe hypoglycemic episodes. How much an islet (beta-cell) graft may be contributing to glycemic control can be quantified by stimulatory tests of insulin (or C-peptide) secretion. Glucose-potentiation of arginine-induced insulin secretion provides a measure of functional beta-cell mass, the beta-cell secretory capacity, as either AIR(pot) or AIR(max), but requires conduct of a hyperglycemic clamp. We sought to determine whether acute insulin responses to intravenous glucose (AIR(glu)) or arginine (AIR(arg)) could predict beta-cell secretory capacity in islet recipients. AIR(arg) was a better predictor of both AIR(pot) and AIR(max) (n=10, r2=0.98, P<0.0001 and n=7, r2=0.97, P<0.0001) than was AIR(glu) (n=9, r2=0.78, P=0.002 and n=6, r2=0.76, P=0.02). Also, the measures of beta-cell secretory capacity were highly correlated (n=7, r2=0.98, P<0.0001). These results support the use of AIR(arg) as a surrogate indicator of beta-cell secretory capacity in islet transplantation.

  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.

  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. Pioglitazone acutely reduces insulin secretion and causes metabolic deceleration of the pancreatic beta-cell at submaximal glucose concentrations.

    PubMed

    Lamontagne, Julien; Pepin, Emilie; Peyot, Marie-Line; Joly, Erik; Ruderman, Neil B; Poitout, Vincent; Madiraju, S R Murthy; Nolan, Christopher J; Prentki, Marc

    2009-08-01

    Thiazolidinediones (TZDs) have beneficial effects on glucose homeostasis via enhancement of insulin sensitivity and preservation of beta-cell function. How TZDs preserve beta-cells is uncertain, but it might involve direct effects via both peroxisome proliferator-activated receptor-gamma-dependent and -independent pathways. To gain insight into the independent pathway(s), we assessed the effects of short-term (insulin secretion (GIIS), AMP-activated protein kinase (AMPK) activation, and beta-cell metabolism in INS 832/13 beta-cells and rat islets. Pio caused a right shift in the dose-dependence of GIIS, such that insulin release was reduced at intermediate glucose but unaffected at either basal or maximal glucose concentrations. This was associated in INS 832/13 cells with alterations in energy metabolism, characterized by reduced glucose oxidation, mitochondrial membrane polarization, and ATP levels. Pio caused AMPK phosphorylation and its action on GIIS was reversed by the AMPK inhibitor compound C. Pio also reduced palmitate esterification into complex lipids and inhibited lipolysis. As for insulin secretion, the alterations in beta-cell metabolic processes were mostly alleviated at elevated glucose. Similarly, the antidiabetic agents and AMPK activators metformin and berberine caused a right shift in the dose dependence of GIIS. In conclusion, Pio acutely reduces glucose oxidation, energy metabolism, and glycerolipid/fatty acid cycling of the beta-cell at intermediate glucose concentrations. We suggest that AMPK activation and the metabolic deceleration of the beta-cell caused by Pio contribute to its known effects to reduce hyperinsulinemia and preserve beta-cell function and act as an antidiabetic agent.

  9. Insulin Resistance and Risk Factors for Cardiovascular Disease in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Oeffinger, Kevin C.; Adams-Huet, Beverley; Victor, Ronald G.; Church, Timothy S.; Snell, Peter G.; Dunn, Andrea L.; Eshelman-Kent, Debra A.; Ross, Robert; Janiszewski, Peter M.; Turoff, Alicia J.; Brooks, Sandra; Vega, Gloria Lena

    2009-01-01

    Purpose To determine the prevalence of insulin resistance and other risk factors for cardiovascular disease (CVD) in young adult survivors of childhood acute lymphoblastic leukemia (ALL). Patients and Methods In this cross-sectional evaluation of 118 survivors of childhood ALL (median age, 23.0 years; range, 18 to 37 years), insulin resistance was estimated using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to 37-year-old individuals from the same region participating in the Dallas Heart Study (DHS, N = 782). ALL survivors were stratified by treatment with and without cranial radiotherapy (CRT). Results Female ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.6, 95% CI, 3.6 to 5.7; no CRT, mean 3.3, 95% CI, 2.8 to 3.8) in comparison with DHS women (mean 2.4, 95% CI, 2.2 to 2.7). Eighty percent of women treated with CRT had at least three of six CVD risk factors, and they were significantly more likely to have three or more risk factors compared with DHS women (odds ratio [OR], 5.96; 95% CI, 2.15 to 16.47). Male ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.0, 95% CI, 2.8 to 5.6; no CRT, mean 3.4, 95% CI, 2.9 to 3.9) in comparison with DHS men (mean 2.3, 95% CI, 2.1 to 2.6), but were not more likely to have multiple CVD risk factors. Conclusion ALL survivors had an increased prevalence of insulin resistance in comparison with a cohort of older individuals from the same community. Importantly, women treated with CRT seem to have an increased prevalence of multiple CVD risk factors, warranting close monitoring and risk-reducing strategies. PMID:19564534

  10. Mechanisms for independent and combined effects of calorie restriction and acute exercise on insulin-stimulated glucose uptake by skeletal muscle of old rats.

    PubMed

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

    2015-04-01

    Either calorie restriction [CR; consuming 60-65% of ad libitum (AL) intake] or acute exercise can independently improve insulin sensitivity in old age, but their combined effects on muscle insulin signaling and glucose uptake have previously been unknown. Accordingly, we assessed the independent and combined effects of CR (beginning at 14 wk old) and acute exercise (3-4 h postexercise) on insulin signaling and glucose uptake in insulin-stimulated epitrochlearis muscles from 30-mo-old rats. Either CR alone or exercise alone vs. AL sedentary controls induced greater insulin-stimulated glucose uptake. Combined CR and exercise vs. either treatment alone caused an additional increase in insulin-stimulated glucose uptake. Either CR or exercise alone vs. AL sedentary controls increased Akt Ser(473) and Akt Thr(308) phosphorylation. Combined CR and exercise further elevated Akt phosphorylation on both sites. CR alone, but not exercise alone, vs. AL sedentary controls significantly increased Akt substrate of 160 kDa (AS160) Ser(588) and Thr(642) phosphorylation. Combined CR and exercise did not further enhance AS160 phosphorylation. Exercise alone, but not CR alone, modestly increased GLUT4 abundance. Combined CR and exercise did not further elevate GLUT4 content. These results suggest that CR or acute exercise independently increases insulin-stimulated glucose uptake via overlapping (greater Akt phosphorylation) and distinct (greater AS160 phosphorylation for CR, greater GLUT4 for exercise) mechanisms. Our working hypothesis is that greater insulin-stimulated glucose uptake in the combined CR and exercise group vs. CR or exercise alone relies on greater Akt activation, leading to greater phosphorylation of one or more Akt substrates other than AS160.

  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. 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

  13. 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

  14. Acute interval exercise intensity does not affect appetite and nutrient preferences in overweight and obese males.

    PubMed

    Alkahtani, Shaea A; Byrne, Nuala M; Hills, Andrew P; King, Neil A

    2014-01-01

    This study investigated the influence of two different intensities of acute interval exercise on food preferences and appetite sensations in overweight and obese men. Twelve overweight/obese males (age=29.0±4.1 years; BMI =29.1±2.4 kg/m2) completed three exercise sessions: an initial graded exercise test, and two interval cycling sessions: moderate-(MIIT) and high-intensity (HIIT) interval exercise sessions on separate days in a counterbalanced order. The MIIT session involved cycling for 5-minute repetitions of alternate workloads 20% below and 20% above maximal fat oxidation. The HIIT session consisted of cycling for alternate bouts of 15 seconds at 85% VO2max and 15 seconds unloaded recovery. Appetite sensations and food preferences were measured immediately before and after the exercise sessions using the Visual Analogue Scale and the Liking & Wanting experimental procedure. Results indicated that liking significantly increased and wanting significantly decreased in all food categories after both MIIT and HIIT. There were no differences between MIIT and HIIT on the effect on appetite sensations and Liking & Wanting. In conclusion, manipulating the intensity of acute interval exercise did not affect appetite and nutrient preferences.

  15. 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.

  16. The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia.

    PubMed

    Holwerda, S W; Reynolds, L J; Restaino, R M; Credeur, D P; Leidy, H J; Thyfault, J P; Fadel, P J

    2015-12-15

    Reduced insulin sensitivity and impaired glycemic control are among the consequences of physical inactivity and have been associated with reduced cardiac baroreflex sensitivity (BRS). However, the effect of reduced insulin sensitivity and acute hyperglycemia following glucose consumption on cardiac BRS in young, healthy subjects has not been well characterized. We hypothesized that a reduction in insulin sensitivity via reductions in physical activity would reduce cardiac BRS at rest and following an oral glucose tolerance test (OGTT). Nine recreationally active men (23 ± 1 yr; >10,000 steps/day) underwent 5 days of reduced daily physical activity (RA5) by refraining from planned exercise and reducing daily steps (<5,000 steps/day). Spontaneous cardiac BRS (sequence technique) was compared at rest and for 120 min following an OGTT at baseline and after RA5. A substudy (n = 8) was also performed to independently investigate the influence of elevated insulin alone on cardiac BRS using a 120-min hyperinsulinemic-euglycemic clamp. Insulin sensitivity (Matsuda index) was significantly reduced following RA5 (BL 9.2 ± 1.3 vs. RA5 6.4 ± 1.1, P < 0.001). Resting cardiac BRS was unaffected by RA5 and significantly reduced during the OGTT similarly at baseline and RA5 (baseline 0 min, 28 ± 4 vs. 120 min, 18 ± 4; RA5 0 min, 28 ± 4 vs. 120 min, 21 ± 3 ms/mmHg). Spontaneous cardiac BRS was also reduced during the hyperinsulinemic-euglycemic clamp (P < 0.05). Collectively, these data demonstrate that acute elevations in plasma glucose and insulin can impair spontaneous cardiac BRS in young, healthy subjects, and that reductions in cardiac BRS following acute hyperglycemia are unaffected by reduced insulin sensitivity via short-term reductions in physical activity.

  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. Acute stress or systemic insulin injection increases flunitrazepam sensitive-GABAA receptor density in synaptosomes of chick forebrain: Modulation by systemic epinephrine.

    PubMed

    Cid, Mariana Paula; Arce, Augusto; Salvatierra, Nancy Alicia

    2008-03-01

    Interactions between acute stress and systemic insulin and epinephrine on GABAA receptor density in the forebrain were studied. Here, 10 day-old chicks were intraperitoneally injected with insulin, epinephrine or vehicle and then immediately stressed by partial water immersion for 15 min and killed by decapitation. Non-stressed controls were similarly injected, then returned to their rearing boxes for 15 min and then killed. Forebrains were dissected and GABAA receptor density was measured ex vivo in synaptosomes by 3[H]-flunitrazepam binding assay. In non-stressed chicks, insulin at 1.25, 2.50 and 5.00 IU/kg of body weight (non-hypoglycemic doses) increased Bmax by 33, 53 and 44% compared to saline, respectively. A similar increase of 41% was observed in receptor density after stress. However, the insulin effect was not additive to the stress-induced increase suggesting that both effects occur through similar mechanisms. In contrast, epinephrine, at 0.25 and 0.5 mg/kg did not induce any changes in Bmax in non-stressed chicks. Nevertheless, after stress these doses increased the receptor density by about 13 and 27%, respectively. Similarly, the same epinephrine doses co-administered with insulin (2.50 IU/kg), increased the receptor density by about 20% compared to insulin alone. These results suggest that systemic epinephrine, perhaps by evoking central norepinephrine release, modulates the increase in forebrain GABAA receptor binding induced by both insulin and stress.

  19. Acute pyelonephritis resulting in intense vascular blush during dynamic renal scintigraphy

    PubMed Central

    Joshi, Prathamesh; Deshpande, Sushil; Kulkarni, Mukta; Shetkar, Shubhangi

    2016-01-01

    A thirty-year-old male underwent Tc-99m diethylenetriaminepentaacetic acid renal scintigraphy for evaluation of gross hydronephrosis of left kidney. The perfusion phase revealed an intense vascular blush in left renal fossa. The uptake phase of scintigraphy revealed the absence of tracer uptake in left kidney. Contrast-enhanced computed tomography (CECT) was performed for evaluating the cause of vascular blush. CECT demonstrated features suggestive of acute pyelonephritis (APN) involving lower pole of the hydronephrotic left kidney, corresponding to the site of vascular blush seen on renal scintigraphy. The postnephrectomy specimen confirmed the diagnosis of APN suggested on CECT. PMID:26917903

  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. 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

  2. Senescence marker protein-30/gluconolactonase deletion worsens glucose tolerance through impairment of acute insulin secretion.

    PubMed

    Hasegawa, Goji; Yamasaki, Masahiro; Kadono, Mayuko; Tanaka, Muhei; Asano, Mai; Senmaru, Takafumi; Kondo, Yoshitaka; Fukui, Michiaki; Obayashi, Hiroshi; Maruyama, Naoki; Nakamura, Naoto; Ishigami, Akihito

    2010-02-01

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout (KO) mice treated with L-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wild-type (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in beta-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mm glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mm in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging.

  3. Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin

    PubMed Central

    Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R.; Obermayer-Pietsch, Barbara; Koehler, Gerd; Hofmann, Peter

    2015-01-01

    Introduction We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Material and Methods Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. Results BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Conclusion Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. Trial Registration ClinicalTrials.gov NCT02075567 http

  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. Role of TNF-α/TNFR1 in intense acute swimming-induced delayed onset muscle soreness in mice.

    PubMed

    Borghi, Sergio M; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Cardoso, Renato D R; Martins-Pinge, Marli C; Tatakihara, Roberto I; Cunha, Thiago M; Ferreira, Sergio H; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

    2014-04-10

    The injection of cytokines such as TNF-α induces muscle pain. Herein, it was addressed the role of endogenous TNF-α/TNFR1 signaling in intense acute swimming-induced muscle mechanical hyperalgesia in mice. Mice were exposed to water during 30 s (sham) or to a single session of 30-120 min of swimming. Intense acute swimming induced a dose-dependent (time of exercise-dependent) muscle mechanical hyperalgesia, which peaked after 24 h presenting characteristics of delayed onset muscle soreness (DOMS). The intense acute swimming (120 min)-induced muscle mechanical hyperalgesia was reduced in etanercept (soluble TNF receptor) treated and TNFR1 deficient ((-/-)) mice. TNF-α levels increased 2 and 4 h after intense acute swimming in soleus muscle (but not in gastrocnemius), and spinal cord, respectively. Exercise induced an increase of myeloperoxidase activity and decrease in reduced glutathione levels in an etanercept-sensitive and TNFR1-dependent manners in the soleus muscle, but not in the gastrocnemius muscle. Concluding, TNF-α/TNFR1 signaling mediates intense acute swimming-induced DOMS by an initial role in the soleus muscle followed by spinal cord, inducing muscle inflammatory hyperalgesia and oxidative stress. The knowledge of these mechanisms might contribute to improve the training of athletes, individuals with physical impairment and intense training such as military settings.

  6. 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.

  7. 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.

  8. Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer

    PubMed Central

    Drodge, C.S.; Boychak, O.; Patel, S.; Usmani, N.; Amanie, J.; Parliament, M.B.; Murtha, A.; Field, C.; Ghosh, S.; Pervez, N.

    2015-01-01

    Background Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. Methods Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. Results For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50–76 years). Disease was organ-confined (T1c–T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose–volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. Conclusions This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes. PMID:25908924

  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.

  11. Accuracy of roche accu-chek inform whole blood capillary, arterial, and venous glucose values in patients receiving intensive intravenous insulin therapy after cardiac surgery.

    PubMed

    Karon, Brad S; Gandhi, Gunjan Y; Nuttall, Gregory A; Bryant, Sandra C; Schaff, Hartzell V; McMahon, M Molly; Santrach, Paula J

    2007-06-01

    Intravenous insulin protocols are increasingly common in the intensive care unit to maintain normoglycemia. Little is known about the accuracy of point-of-care glucometers for measuring glucose in this patient population or the impact of sample source (capillary, arterial, or venous whole blood) on the accuracy of glucometer results. We compared capillary, arterial, and venous whole blood glucose values with laboratory plasma glucose values in 20 patients after cardiac surgery. All 4 samples (capillary, arterial, and venous whole blood and laboratory plasma glucose) were analyzed hourly for the first 5 hours during intravenous insulin therapy in the intensive care unit. There were no significant differences between median capillary whole blood (149 mg/dL [8.3 mmol/L]) and laboratory plasma (151 mg/dL [8.4 mmol/L]) glucose levels. The median arterial (161 mg/dL [8.9 mmol/L]) and venous (162 mg/dL [9.0 mmol/L]) whole blood glucose levels were significantly higher than the median laboratory plasma glucose level. Capillary whole blood glucose levels correlate most closely with laboratory plasma glucose levels in patients receiving intensive intravenous insulin therapy after cardiac surgery.

  12. 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

  13. Psychophysiological effects of music on acute recovery from high-intensity interval training.

    PubMed

    Jones, Leighton; Tiller, Nicholas B; Karageorghis, Costas I

    2017-03-01

    Numerous studies have examined the multifarious effects of music applied during exercise but few have assessed the efficacy of music as an aid to recovery. Music might facilitate physiological recovery via the entrainment of respiratory rhythms with music tempo. High-intensity exercise training is not typically associated with positive affective responses, and thus ways of assuaging negative affect warrant further exploration. This study assessed the psychophysiological effects of music on acute recovery and prevalence of entrainment in between bouts of high-intensity exercise. Thirteen male runners (Mage=20.2±1.9years; BMI=21.7±1.7; V̇O2 max=61.6±6.1mL·kg·min(-1)) completed three exercise sessions comprising 5×5-min bouts of high-intensity intervals interspersed with 3-min periods of passive recovery. During recovery, participants were administered positively-valenced music of a slow-tempo (55-65bpm), fast-tempo (125-135bpm), or a no-music control. A range of measures including affective responses, RPE, cardiorespiratory indices (gas exchange and pulmonary ventilation), and music tempo-respiratory entrainment were recorded during exercise and recovery. Fast-tempo, positively-valenced music resulted in higher Feeling Scale scores throughout recovery periods (p<0.01, ηp(2)=0.38). There were significant differences in HR during initial recovery periods (p<0.05, ηp(2)=0.16), but no other music-moderated differences in cardiorespiratory responses. In conclusion, fast-tempo, positively-valenced music applied during recovery periods engenders a more pleasant experience. However, there is limited evidence that music expedites cardiorespiratory recovery in between bouts of high-intensity exercise. These findings have implications for athletic training strategies and individuals seeking to make high-intensity exercise sessions more pleasant.

  14. The acute effect of moderate intensity aquatic exercise on coagulation factors in haemophiliacs.

    PubMed

    Beltrame, Luis Gustavo Normanton; Abreu, Laurinda; Almeida, Jussara; Boullosa, Daniel Alexandre

    2015-05-01

    The objective of this cross-sectional study was to analyse the acute effect of aquatic exercise on haemostasis in persons with haemophilia. Ten adult haemophiliacs (8 type A, 2 type B) familiarized with aquatic training performed a 20-min exercise session in a swimming pool at an intensity of ~70% maximum heart rate (HR). Blood samples were collected immediately after the training session. The haemostatic parameters selected for analyses were factor VIII (FVIII), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen. There were unclear effects of the exercise bout on FVIII and APTT, with a possibly beneficial effect on PT (-11·4%; 90% confidence interval: -26·1;3·3%), and a trivial change on fibrinogen levels. It was found an association between the mean rise in HR during exercise and the decrement in PT after exercise (r = 0·729; P = 0·026). The greater changes were observed in the patients diagnosed with a moderate level of haemophilia. It is concluded that a short bout of moderate intensity of aquatic exercise may have a positive influence on PT in adults with haemophilia with greater changes in those individuals exhibiting a greater rise in HR during exercise. This may be an important issue to the haemostatic control of haemophiliacs in clinical settings. Further studies are warranted for testing the influence of different aquatic exercise intensities on haemostasis.

  15. Acute effects of an ascending intensity squat protocol on vertical jump performance.

    PubMed

    Hirayama, Kuniaki

    2014-05-01

    The purpose of this study was to examine the acute effects of an ascending intensity squat protocol consisting of single-repetition exercises on subsequent vertical jump performance. Fourteen college weightlifters attended 2 testing sessions: squat (SQ) and control (CON) conditions. In the SQ condition, squat exercises with incremental loads (20% 1 repetition maximum [RM], 40% 1RM, 60% 1RM, 80% 1RM, and maximal isometric [MI] half-squat exercise) were performed with a time interval of 3 minutes after submaximal cycling and static stretching. Maximum vertical jump height was measured at the beginning of the session and after cycling, static stretching, and each squat exercise in the SQ condition. In the CON condition, vertical jump height was measured at the same times with the subject resting on a chair after cycling and stretching. Vertical jump height gradually increased after 60% 1RM, 80% 1RM, and MI half-squat exercises compared with baseline values (i.e., first trial of vertical jump), whereas no change was observed in the CON condition. These results suggest that an ascending intensity squat protocol consisting of single-repetition exercises of sufficient intensity can be useful for athletes who require high muscular power.

  16. Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis

    PubMed Central

    Honore, Patrick M.; Nguyen, H. Bryant; Gong, Michelle; Chawla, Lakhmir S.; Bagshaw, Sean M.; Artigas, Antonio; Shi, Jing; Joannes-Boyau, Olivier; Vincent, Jean-Louis

    2016-01-01

    Objectives: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. Method: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2–3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)2/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 results in patients with and without acute kidney injury and across nonrenal Sequential Organ Failure Assessment scores. Finally, we constructed a clinical model for acute kidney injury in this population and compared the performance of the model with and without tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. Results: We included 232 patients in the analysis and 40 (17%) developed acute kidney injury. We observed significantly higher urine tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with acute kidney injury than without acute kidney injury in both patients with low and high nonrenal Sequential Organ Failure Assessment scores (p < 0.001). The area under the receiver operating characteristic curve (95% CI) of tissue inhibitor of metalloproteinase-2 and insulin

  17. Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance.

    PubMed

    Qiu, Yanyan; Sui, Xianxian; Zhan, Yongkun; Xu, Chen; Li, Xiaobo; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR). StAR expression was also examined in pathology samples of patients with fatty liver by immunohistochemical staining. We found that the expression level of StAR was reduced in the livers obtained from fatty liver patients and NAFLD mice. Additionally, StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis due to the activation of farnesoid x receptor (FXR). StAR overexpression attenuated the impairment of insulin signaling in fatty liver. This protective role of StAR was owing to a reduction of intracellular diacylglycerol levels and the phosphorylation of PKCε. Furthermore, FXR inactivation reversed the observed beneficial effects of StAR. The present study revealed that StAR overexpression can reduce hepatic lipid accumulation, regulate glucose metabolism and attenuate insulin resistance through a mechanism involving the activation of FXR. Our study suggests that StAR may be a potential therapeutic target for NAFLD.

  18. The acute psychobiological impact of the intensive care experience on relatives

    PubMed Central

    Turner-Cobb, J.M.; Smith, P.C.; Ramchandani, P.; Begen, F.M.; Padkin, A.

    2016-01-01

    There is a growing awareness amongst critical care practitioners that the impact of intensive care medicine extends beyond the patient to include the psychological impact on close family members. Several studies have addressed the needs of relatives within the intensive care context but the psychobiological impact of the experience has largely been ignored. Such impact is important in respect to health and well-being of the relative, with potential to influence patient recovery. The current feasibility study aimed to examine the acute psychobiological impact of the intensive care experience on relatives. Using a mixed methods approach, quantitative and qualitative data were collected simultaneously. Six relatives of patients admitted to the intensive care unit (ICU) of a District General Hospital, were assessed within 48 h of admission. Qualitative data were provided from semi-structured interviews analysed using interpretative phenomenological analysis. Quantitative data were collected using a range of standardised self-report questionnaires measuring coping responses, emotion, trauma symptoms and social support, and through sampling of diurnal salivary cortisol as a biomarker of stress. Four themes were identified from interview: the ICU environment, emotional responses, family relationships and support. Questionnaires identified high levels of anxiety, depression and trauma symptoms; the most commonly utilised coping techniques were acceptance, seeking support through advice and information, and substance use. Social support emerged as a key factor with focused inner circle support relating to family and ICU staff. Depressed mood and avoidance were linked to greater mean cortisol levels across the day. Greater social network and coping via self-distraction were related to lower evening cortisol, indicating them as protective factors in the ICU context. The experience of ICU has a psychological and physiological impact on relatives, suggesting the importance of

  19. 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

  20. [Use of enoximone in patients with acute and subacute heart failure in the intensive care unit].

    PubMed

    Holubarsch, C; Pieske, B; Hasenfuss, G; Just, H

    1994-01-01

    The phosphodiesterase inhibitor enoximone has both vasodilating and positive inotropic pharmacological properties. The balance between vasodilation and positive inotropism may be different between the various types of heart failure as well as the various stages of heart failure. Therefore, we investigated the effect of intravenous application of enoximone (1 mg/kg body weight) in a cohort of patients (n = 10) suffering from acute or subacute heart failure mainly due to ischemia or hypoxia. All patients had high left ventricular filling pressure, low cardiac output and were pretreated with intravenous dobutamine. Enoximone increased cardiac output from 3.2 +/- 1.2 to 5.5 +/- 2.2 l/min, increased heart rate from 94 +/- 20 to 100 +/- 18 beats/min, decreased systemic peripheral resistance from 1770 +/- 861 to 931 +/- 340 dyn.sec.cm-5 and decreased pulmonary wedge pressure from 24 +/- 5 to 20 +/- 6 mmHg, significantly. However, systolic aortic pressure, systolic pulmonary pressure and right atrial pressure were not significantly altered. We conclude that in a selected group of patients enoximone-given intravenously and acutely in the intensive care unity-can induce beneficial effects on central hemodynamics without critical falls in perfusion pressure.

  1. [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.

  2. The bulldozer and the ballet dancer: aspects of nurses' caring approaches in acute psychiatric intensive care.

    PubMed

    Björkdahl, A; Palmstierna, T; Hansebo, G

    2010-08-01

    Demanding conditions in acute psychiatric wards inhibit provision of safe, therapeutic care and leave nurses torn between humanistic ideals and the harsh reality of their daily work. The aim of this study was to describe nurses' caring approaches within this context. Data were collected from interviews with nurses working in acute psychiatric intensive care. Data were analysed using qualitative analysis, based on interpretive description. Results revealed a caring-approach continuum on which two approaches formed the main themes: the bulldozer and the ballet dancer. The bulldozer approach functioned as a shield of power that protected the ward from chaos. The ballet dancer approach functioned as a means of initiating relationships with patients. When examining the data from a theoretical perspective of caring and uncaring encounters in nursing, the ballet dancer approach was consistent with a caring approach, while the bulldozer approach was more complex and somewhat aligned with uncaring approaches. Conclusions drawn from the study are that although the bulldozer approach involves a risk for uncaring and harming actions, it also brings a potential for caring. This potential needs to be further explored and nurses should be encouraged to reflect on how they integrate paternalistic nursing styles with person-centred care.

  3. T-1032, a cyclic GMP phosphodiesterase-5 inhibitor, acutely blocks physiologic insulin-mediated muscle haemodynamic effects and glucose uptake in vivo.

    PubMed

    Mahajan, Hema; Richards, Stephen M; Rattigan, Stephen; Clark, Michael G

    2003-12-01

    1. Cyclic GMP phosphodiesterase-5 inhibitors have been shown to alter blood flow in specific tissues by potentiating local NO-dependent vasodilatory mechanisms. Since the haemodynamic effects of physiologic insulin, particularly capillary recruitment, may be critical for muscle glucose uptake in vivo and are blocked by inhibitors of nitric oxide synthase, we have explored the acute effects of the specific cGMP phosphodiesterase-5 inhibitor T-1032 on physiologic insulin action in anaesthetized healthy rats in vivo. 2. Whole-body glucose infusion (GIR), femoral blood flow (FBF), hind leg vascular resistance (VR), hind leg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R'g), hind leg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, and muscle cGMP were determined. The experimental groups were T-1032 (10 microg min-1 kg-1) infused for 1 h before and during a euglycaemic insulin clamp (3 mU min-1 kg-1 x 2 h), T-1032 infused for 3 h with saline, T-1032 during a 2 h clamp, T-1032 with saline for 2 h, and a 2 h saline control. 3. Insulin increased GIR from zero to 13 mg min-1 kg-1, HGU from 0.1+/-0.01 to 0.43+/-0.05 micromol min-1, R'g and 1-MX, marginally increased FBF, and had no effect on blood pressure or heart rate. T-1032 alone had no effect on blood pressure, heart rate, FBF, VR, HGU, R'g or 1-MX, but increased muscle cGMP. T-1032 1 h before and during insulin completely blocked GIR (1 h), HGU (2 h), R'g (2 h), and 1-MX (2 h). T-1032 commenced with insulin had only partial blocking activity against insulin. 4. We conclude that T-1032 is a potent acutely acting inhibitor of the muscle effects of physiologic insulin on capillary recruitment and glucose uptake in vivo. These, together with inhibition of whole-body glucose infusion during insulin, may caution against the use of isoenzyme-5-specific cyclic GMP phosphodiesterase inhibitors as therapeutic agents.

  4. 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.

  5. A Single Session of Low-Intensity Exercise Is Sufficient to Enhance Insulin Sensitivity Into the Next Day in Obese Adults

    PubMed Central

    Newsom, Sean A.; Everett, Allison C.; Hinko, Alexander; Horowitz, Jeffrey F.

    2013-01-01

    OBJECTIVE The purpose of this study was to determine the effect of a relatively modest session of exercise on insulin sensitivity and fatty acid uptake the next day in obese adults. RESEARCH DESIGN AND METHODS Eleven sedentary obese adults (male/female: 3/8; BMI 37 ± 1 kg/m2; peak oxygen uptake [VO2peak] 20 ± 1 mL/kg/min) completed three experimental trials. On two of these occasions, subjects exercised to expend 350 kcal in the afternoon. These two exercise trials were identical except for the exercise intensity (50% VO2peak [EX50] and 65% VO2peak [EX65]) and the duration of exercise necessary to expend 350 kcal (EX50 = ∼70 min; EX65 = ∼55 min). Subjects also completed a control trial (CON), without exercise. The next morning, we measured insulin sensitivity (hyperinsulinemic-euglycemic clamp) and whole-body fatty acid uptake (palmitate rate of disappearance from plasma [Rd]). RESULTS Exercise increased insulin sensitivity the next day, but whereas the 35% improvement after EX50 compared with CON was statistically significant (P = 0.01), the 20% improvement after EX65 was not (P = 0.17). Despite nearly identical values between CON and EX65 (P = 0.88), systemic fatty acid uptake was lower after EX50 compared with EX65 (P = 0.02), but not quite significant compared with CON (P = 0.07). Importantly, the change in fatty acid uptake after exercise compared with CON was negatively correlated with the change in insulin sensitivity for all trials (r = −0.60, P = 0.003). CONCLUSIONS A relatively modest single session of exercise in obese adults improved insulin sensitivity the next day, and a reduction in systemic fatty acid uptake in the several hours after exercise may be important for this effect. PMID:23757424

  6. 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

  7. Acute Low-Volume High-Intensity Interval Exercise and Continuous Moderate-Intensity Exercise Elicit a Similar Improvement in 24-h Glycemic Control in Overweight and Obese Adults.

    PubMed

    Parker, Lewan; Shaw, Christopher S; Banting, Lauren; Levinger, Itamar; Hill, Karen M; McAinch, Andrew J; Stepto, Nigel K

    2016-01-01

    Background: Acute exercise reduces postprandial oxidative stress and glycemia; however, the effects of exercise intensity are unclear. We investigated the effect of acute low-volume high-intensity interval-exercise (LV-HIIE) and continuous moderate-intensity exercise (CMIE) on glycemic control and oxidative stress in overweight and obese, inactive adults. Methods: Twenty-seven adults were randomly allocated to perform a single session of LV-HIIE (9 females, 5 males; age: 30 ± 1 years; BMI: 29 ± 1 kg·m(-2); mean ± SEM) or CMIE (8 females, 5 males; age: 30 ± 2.0; BMI: 30 ± 2.0) 1 h after consumption of a standard breakfast. Plasma redox status, glucose and insulin were measured. Continuous glucose monitoring (CGM) was conducted during the 24-h period before (rest day) and after exercise (exercise day). Results: Plasma thiobarbituric acid reactive substances (TBARS; 29 ±13%, p < 0.01; mean percent change ±90% confidence limit), hydrogen peroxide (44 ± 16%, p < 0.01), catalase activity (50 ± 16%, p < 0.01), and superoxide dismutase activity (21 ± 6%, p < 0.01) significantly increased 1 h after breakfast (prior to exercise) compared to baseline. Exercise significantly decreased postprandial glycaemia in whole blood (-6 ± 5%, p < 0.01), irrespective of the exercise protocol. Only CMIE significantly decreased postprandial TBARS (CMIE: -33 ± 8%, p < 0.01; LV-HIIE: 11 ± 22%, p = 0.34) and hydrogen peroxide (CMIE: -25 ± 15%, p = 0.04; LV-HIIE: 7 ± 26%; p = 0.37). Acute exercise provided a similar significant improvement in 24-h average glucose levels (-5 ± 2%, p < 0.01), hyperglycemic excursions (-37 ± 60%, p < 0.01), peak glucose concentrations (-8 ± 4%, p < 0.01), and the 2-h postprandial glucose response to dinner (-9 ± 4%, p < 0.01), irrespective of the exercise protocol. Conclusion: Despite elevated postprandial oxidative stress compared to CMIE, LV-HIIE is an equally effective exercise mode for improving 24-h glycemic control in overweight and obese

  8. Acute Low-Volume High-Intensity Interval Exercise and Continuous Moderate-Intensity Exercise Elicit a Similar Improvement in 24-h Glycemic Control in Overweight and Obese Adults

    PubMed Central

    Parker, Lewan; Shaw, Christopher S.; Banting, Lauren; Levinger, Itamar; Hill, Karen M.; McAinch, Andrew J.; Stepto, Nigel K.

    2017-01-01

    Background: Acute exercise reduces postprandial oxidative stress and glycemia; however, the effects of exercise intensity are unclear. We investigated the effect of acute low-volume high-intensity interval-exercise (LV-HIIE) and continuous moderate-intensity exercise (CMIE) on glycemic control and oxidative stress in overweight and obese, inactive adults. Methods: Twenty-seven adults were randomly allocated to perform a single session of LV-HIIE (9 females, 5 males; age: 30 ± 1 years; BMI: 29 ± 1 kg·m−2; mean ± SEM) or CMIE (8 females, 5 males; age: 30 ± 2.0; BMI: 30 ± 2.0) 1 h after consumption of a standard breakfast. Plasma redox status, glucose and insulin were measured. Continuous glucose monitoring (CGM) was conducted during the 24-h period before (rest day) and after exercise (exercise day). Results: Plasma thiobarbituric acid reactive substances (TBARS; 29 ±13%, p < 0.01; mean percent change ±90% confidence limit), hydrogen peroxide (44 ± 16%, p < 0.01), catalase activity (50 ± 16%, p < 0.01), and superoxide dismutase activity (21 ± 6%, p < 0.01) significantly increased 1 h after breakfast (prior to exercise) compared to baseline. Exercise significantly decreased postprandial glycaemia in whole blood (−6 ± 5%, p < 0.01), irrespective of the exercise protocol. Only CMIE significantly decreased postprandial TBARS (CMIE: −33 ± 8%, p < 0.01; LV-HIIE: 11 ± 22%, p = 0.34) and hydrogen peroxide (CMIE: −25 ± 15%, p = 0.04; LV-HIIE: 7 ± 26%; p = 0.37). Acute exercise provided a similar significant improvement in 24-h average glucose levels (−5 ± 2%, p < 0.01), hyperglycemic excursions (−37 ± 60%, p < 0.01), peak glucose concentrations (−8 ± 4%, p < 0.01), and the 2-h postprandial glucose response to dinner (−9 ± 4%, p < 0.01), irrespective of the exercise protocol. Conclusion: Despite elevated postprandial oxidative stress compared to CMIE, LV-HIIE is an equally effective exercise mode for improving 24-h glycemic control in

  9. Acute tendon changes in intense CrossFit workout: an observational cohort study.

    PubMed

    Fisker, F Y; Kildegaard, S; Thygesen, M; Grosen, K; Pfeiffer-Jensen, M

    2016-10-07

    CrossFit is a fitness program that has become increasingly popular in the Western world, but as in other sports, the risk of injury is present. Only a few studies have addressed health benefits and injuries in CrossFit. It is known that chronically overloaded tendons will thicken and increase the risk of tendinopathy. However, it remains unknown whether acute overload caused by strenuous, high-intensity exercise will exert changes in tendons and if these changes can be detected and described by ultrasonography. The aim of this study is to evaluate the effects of acute overload on tendon thickness using ultrasonography. Standardized ultrasound measurements of the patella, Achilles, and plantaris tendons were performed before and after a specific workout in 34 healthy subjects. Significant increases were observed in patella tendon thickness before (M = 4.5, SD = 0.6) and after (M = 5.0, SD = 0.7) highly intense strenuous exercise, with an estimated mean differences of 0.47 mm (95% CI: 0.35-0.59 mm; P < 0.0001) and in Achilles tendon thickness before (M = 4.4, SD = 0.4) and after (M = 4.5, SD = 0.5) workout, with an estimated difference of 0.17 mm (95% CI: 0.04-0.29 mm; P < 0.01). However, there was no significant difference in fascia plantaris thickness before (M = 3.4, SD = 0.5) and after (M = 3.4, SD = 0.5) workout (P = 0.97). A significant increase in the thickness of the patellar and Achilles tendons was found in response to strenuous, highly intense CrossFit exercises. In order to understand the underlying mechanisms of the findings and possibly utilize this to gain a better understanding, further studies must be conducted.

  10. Impact of conditioning intensity and TBI on acute GVHD after hematopoietic cell transplantation.

    PubMed

    Nakasone, H; Fukuda, T; Kanda, J; Mori, T; Yano, S; Kobayashi, T; Miyamura, K; Eto, T; Kanamori, H; Iwato, K; Uchida, N; Mori, S; Nagamura-Inoue, T; Ichinohe, T; Atsuta, Y; Teshima, T; Murata, M

    2015-04-01

    The impact of the conditioning intensity and TBI on acute GVHD (aGVHD) is still a matter of debate. We analyzed 6848 adult recipients who received allogeneic hematopoietic cell transplants (HCT) between 2006 and 2011 in Japan. The subjects were divided into groups who had received myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), either with or without TBI. There was a significant difference in the incidence of aGVHD 2-4 among the different conditioning types: 39% in TBI-MAC, 35% in TBI-RIC and 32% in both no-TBI MAC and no-TBI-RIC (P<0.001). In a multivariate analysis, TBI-MAC, but not no-TBI MAC, was significantly associated with an increased risk of aGVHD 2-4 (hazard ratio (HR) 1.33, P<0.01), whereas TBI-RIC was associated with an increased risk of GVHD 3-4 (HR 1.36, P=0.048). TBI-MAC and TBI-RIC were significantly associated with skin and gastrointestinal aGVHD. Subgroup analyses demonstrated that not only TBI-MAC, but also TBI-RIC, was significantly associated with aGVHD 2-4 in older patients. Furthermore, high-dose TBI only had an adverse impact on aGVHD 2-4 in HLA-matched HCT. Impacts of intensity and TBI on aGVHD differ by patient backgrounds, and this difference should be considered to establish a risk-adapted strategy for the prevention of aGVHD.

  11. 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…

  12. Acute kidney injury in elderly intensive care patients from a developing country: clinical features and outcome

    PubMed Central

    Yokota, Laís Gabriela; Sampaio, Beatriz Motta; Rocha, Erica; Balbi, André Luís; Ponce, Daniela

    2017-01-01

    Aim The elderly are at high risk of acute kidney injury (AKI) because of structural and functional degeneration over time and with the aging of the population, the demand for intensive care unit (ICU) admission for older patients has risen recently. However, data from developing countries are scarce. This study aimed to describe the incidence of AKI in elderly patients admitted to ICU from a developing country, to determine the most frequent etiologies for renal impairment and identify its risk factors and outcome. Methods All patients admitted to the ICU at a Brazilian teaching hospital for 12 consecutive months were followed prospectively from the time of admission until ICU discharge. Elderly was defined as aged >60 years and AKI was defined according to the Kidney Disease Improving Global Outcomes 2012 criteria. Multivariable logistic regression was used to adjust confounding and selection bias. Results Two hundred elderly patients were included in the study. AKI incidence was 27% and the main etiology was sepsis (48.1%). At logistic regression, baseline creatinine (odds ratio [OR]=5.17, p<0.0001), Acute Physiology and Chronic Health Evaluation (APACHE) II (OR=1.20, p<0.0001), sepsis (OR=2.96, p<0.0001), and longer ICU stay (OR=1.68, p<0.0001) were associated with AKI in elderly patients. Baseline creatinine (OR=1.97, p=0.018), APACHE II (OR=1.29, p<0.0001), sepsis (OR=1.87, p<0.0001), and AKI severity (OR=2.57, p=0.027) were identified as predictors of death. Conclusion AKI was frequent in elderly patients admitted to ICU from a developing country, and it was identified as a risk factor for death. Sepsis was an important risk factor for both AKI and mortality, similar to developed countries and in younger populations. PMID:28210101

  13. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    PubMed

    Scott, Bart L; Pasquini, Marcelo C; Logan, Brent R; Wu, Juan; Devine, Steven M; Porter, David L; Maziarz, Richard T; Warlick, Erica D; Fernandez, Hugo F; Alyea, Edwin P; Hamadani, Mehdi; Bashey, Asad; Giralt, Sergio; Geller, Nancy L; Leifer, Eric; Le-Rademacher, Jennifer; Mendizabal, Adam M; Horowitz, Mary M; Deeg, H Joachim; Horwitz, Mitchell E

    2017-04-10

    Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P < .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, -0.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC ( P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC ( P < .01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

  14. Acute Responses To Resistance And High Intensity Interval Training In Adolescents.

    PubMed

    Harris, Nigel; Dulson, Deborah; Logan, Greig; Warbrick, Isaac; Merien, Fabrice; Lubans, David

    2016-08-16

    The purpose of this study was to compare the acute physiological responses within and between resistance training (RT) and high intensity interval training (HIIT) matched for time and with comparable effort, in a school setting. Seventeen early adolescents (12.9 ± 0.3 y) performed both RT (2-5 repetitions perceived short of failure at the end of each set) and HIIT (90% of age predicted maximum heart rate), equated for total work set and recovery period durations comprising of 12 'sets' of 30 s work followed by 30 s recovery (total session time 12 min). Variables of interest included oxygen consumption, set and session heart rate (HR) and rate of perceived exertion (RPE), and change in salivary cortisol (SC), salivary alpha amylase (SαA), and blood lactate (BL) from pre- to post-session. Analyses were conducted to determine responses within and between the two different protocols. For both RT and HIIT there were very large increases pre- to post-trial for SC and BL, and only BL increased greater in HIIT (9.1 ± 2.6 mmol·L) than RT (6.8 ± 3.3 mmol·L). Mean set HR for both RT (170 ± 9.1 bpm) and HIIT (179 ± 5.6 bpm) was at least 85% of HR maximum. VO2 over all 12 sets was greater for HIIT (33.8 ± 5.21 mL·kg·min) than RT (24.9 ± 3.23 mL·kg·min). Brief, repetitive, intermittent forays into high, but not supra-maximal intensity exercise utilising either RT or HIIT appeared to be a potent physiological stimulus in adolescents.

  15. 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

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

    PubMed Central

    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

    2017-01-01

    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 cm3) 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 within

  17. Increased insulin-stimulated glucose uptake in both leg and arm muscles after sprint interval and moderate intensity training in subjects with Type 2 Diabetes or Prediabetes.

    PubMed

    Sjöros, Tanja J; Heiskanen, Marja A; Motiani, Kumail K; Löyttyniemi, Eliisa; Eskelinen, Jari-Joonas; Virtanen, Kirsi A; Savisto, Nina J; Solin, Olof; Hannukainen, Jarna C; Kalliokoski, Kari K

    2017-03-13

    We investigated the effects of sprint interval (SIT) and moderate intensity continuous training (MICT) on glucose uptake (GU) during hyperinsulinemic euglycemic clamp and fatty acid uptake (FAU) at fasting state in thigh and arm muscles in subjects with type 2 diabetes (T2D) or prediabetes. Twenty-six patients (age 49, SD 4; 10 women) were randomly assigned into two groups: SIT (n=13), and MICT (n=13). The exercise in the SIT group consisted of 4-6 x 30 s of all-out cycling with 4 min recovery and in the MICT group 40-60 min cycling at 60% of VO2peak . Both groups completed six training sessions within two weeks. GU and FAU were measured before and after the intervention with positron emission tomography in thigh (quadriceps femoris, QF; and hamstrings) and upper arm (biceps and triceps brachii) muscles. Whole-body insulin-stimulated GU increased significantly by 25% in both groups and this was accompanied with significantly increased insulin-stimulated GU in all thigh and upper arm muscles and significantly increased FAU in QF. Within QF, insulin-stimulated GU improved more by SIT than MICT in rectus femoris (p=0.01), but not differently between the training modes in the other QF muscles. In individuals with T2D or prediabetes, both SIT and MICT training rapidly improve insulin-stimulated GU in whole body and in the thigh and arm muscles as well as FAU in the main working muscle QF. These findings highlight the underused potential of exercise in rapidly restoring the impaired skeletal muscle metabolism in subjects with impaired glucose metabolism. This article is protected by copyright. All rights reserved.

  18. [Dysphagia management of acute and long-term critically ill intensive care patients].

    PubMed

    Zielske, J; Bohne, S; Axer, H; Brunkhorst, F M; Guntinas-Lichius, O

    2014-10-01

    Dysphagia is a severe complication in critically ill patients and affects more than half the patients in an intensive care unit. Dysphagia also has a strong impact on morbidity and mortality. Risk factors for the development of dysphagia are neurological diseases, age >55-70 years, intubation >7 days and sepsis. With increasing numbers of long-term survivors chronic dysphagia is becoming an increasing problem. There is not much knowledge on the influence of specific diseases, including the direct impact of sepsis on the development of dysphagia. Fiberoptic evaluation of swallowing is a standardized tool for bedside evaluation, helping to plan swallowing training during the acute phase and to decrease the rate of chronic dysphagia. For evaluation of chronic dysphagia even more extensive diagnostic tools as well as several options of stepwise rehabilitation using restitution, compensation and adaption strategies for swallowing exist. Currently it seems that these options are not being sufficiently utilized. In general, there is a need for controlled clinical trials analyzing specific swallowing rehabilitation concepts for former critically ill patients and long-term survivors.

  19. Acute Cardiovascular and Hemodynamic Responses to Low Intensity Eccentric Resistance Exercise with Blood Flow Restriction

    PubMed Central

    Bazgir, Behzad; Rezazadeh Valojerdi, Mojtaba; Rajabi, Hamid; Fathi, Rouhollah; Ojaghi, Seyed Mojtaba; Emami Meybodi, Mohammad Kazem; Neto, Gabriel R.; Rahimi, Mostafa; Asgari, Alireza

    2016-01-01

    Background Recently it has been suggested that low intensity (LI) resistance exercise (RE) alone or in combination with blood flow restriction (BFR) can be applied for cardiovascular function improvement or rehabilitation. Objectives The aim of the present study was to investigate the acute effects of LI eccentric RE with and without BFR on heart rate (HR), rate pressure product (RPP), blood pressure (BP) parameters [systolic, diastolic, and mean arterial pressure (MAP)], oxygen saturation (SpO2) and rate of perceived exertion (RPE). Methods In a semi-experimental study 16 young adults (26.18 ± 3.67 years) volunteered and performed LI (30% maximum voluntary contraction) eccentric RE alone or combined with BFR. Results The results indicated that HR, RPP, and RPE increased significantly within both groups (P < 0.05); SBP and DBP increased significantly only with BFR (P < 0.05); MAP increased significantly during exercise without BFR (P < 0.05); and no change was observed in SpO2 in either groups (P > 0.05). Furthermore, studied parameters did not vary amongst different groups (P > 0.05). Conclusions It is concluded that LI eccentric RE with BFR positively regulated the hemodynamic and cardiovascular responses. Therefore, the eccentric RE combined with BFR seems to be a good option for future studies with the aim of time efficacy, since it alters these parameters within normal values. PMID:28144415

  20. 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

    2016-09-06

    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.

  1. 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.

  2. Exercise Intensity-Dependent Effects on Cognitive Control Function during and after Acute Treadmill Running in Young Healthy Adults

    PubMed Central

    Wohlwend, Martin; Olsen, Alexander; Håberg, Asta K.; Palmer, Helen S.

    2017-01-01

    The idea that physical activity differentially impacts upon performance of various cognitive tasks has recently gained increased interest. However, our current knowledge about how cognition is altered by acute physical activity is incomplete. To measure how different intensity levels of physical activity affect cognition during and after 1 bout of physical activity, 30 healthy, young participants were randomized to perform a not-X continuous performance test (CPT) during low (LI)- and moderate intensity (MI) running. The same participants were subsequently randomized to perform the not-X CPT post LI, MI, and high intensity (HI) running. In addition, exercise related mood changes were assessed through a self-report measure pre and post running at LI, MI, and HI. Results showed worsening of performance accuracy on the not-X CPT during one bout of moderate compared to low intensity running. Post running, there was a linear decrease in reaction time with increasing running intensity and no change in accuracy or mood. The decreased reaction times post HI running recovered back to baseline within 20 min. We conclude that accuracy is acutely deteriorated during the most straining physical activity while a transient intensity-dependent enhancement of cognitive control function is present following physical activity. PMID:28377735

  3. Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

    PubMed

    Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-04-01

    Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m(2)) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR (P < 0.05) were identified to HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P < 0.041). For diastolic blood pressure, significant differences were observed in the NR prevalence between the HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR

  4. 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

  5. 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.

  6. 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

  7. Fibre type-specific change in FXYD1 phosphorylation during acute intense exercise in humans.

    PubMed

    Thomassen, Martin; Murphy, Robyn M; Bangsbo, Jens

    2013-03-15

    The aim of the present study was to examine fibre type-specific Na(+)-K(+) pump subunit expression and exercise-induced alterations in phospholemman (FXYD1) phosphorylation in humans. Segments of human skeletal muscle fibres were dissected and fibre typed, and protein expression was determined by Western blotting. The protein expression of the Na(+)-K(+) pump α2 isoform was lower in type I than in type II fibres (0.63 ± 0.04 a.u. vs. 1.00 ± 0.07 a.u., P < 0.001), while protein expression of the Na(+)-K(+) pump α1 and β1 isoforms was not different. Protein expression of the ATP-dependent potassium channel Kir6.2 was higher in type I compared with type II fibres. In both type I (P < 0.01) and type II fibres (P < 0.001) the AB_FXYD1 signal was lower after exercise compared with rest, indicating an increase in unspecific FXYD1 phosphorylation. The FXYD1 serine 68 phosphorylation was higher (P < 0.001) after exercise compared with rest in type II fibres (1.90 ± 0.25 vs. 1.00 ± 0.08) and not changed in type I fibres. Total FXYD1 was not expressed in a fibre type-specific manner. Expression of phosphofructokinase was lower (P < 0.001) in type I than in type II fibres, whereas citrate synthase and 3-hydroxyacyl-CoA dehydrogenase were more abundant (P < 0.001) in type I fibres. In conclusion, FXYD1 phosphorylation at serine 68 increased after an acute bout of intense exercise in human type II fibres, while AB_FXYD1 signal intensity was lower in both type I and type II fibres, indicating fibre type-specific differences in FXYD1 phosphorylation on serine 63, serine 68 and threonine 69. This, together with the observation of a higher abundance of the Na(+)-K(+) pump α2 isoform protein in type II fibres, is likely to have importance for the exercise-induced human Na(+)-K(+) pump activity in the different fibre types.

  8. Fibre type-specific change in FXYD1 phosphorylation during acute intense exercise in humans

    PubMed Central

    Thomassen, Martin; Murphy, Robyn M; Bangsbo, Jens

    2013-01-01

    The aim of the present study was to examine fibre type-specific Na+–K+ pump subunit expression and exercise-induced alterations in phospholemman (FXYD1) phosphorylation in humans. Segments of human skeletal muscle fibres were dissected and fibre typed, and protein expression was determined by Western blotting. The protein expression of the Na+–K+ pump α2 isoform was lower in type I than in type II fibres (0.63 ± 0.04 a.u. vs. 1.00 ± 0.07 a.u., P < 0.001), while protein expression of the Na+–K+ pump α1 and β1 isoforms was not different. Protein expression of the ATP-dependent potassium channel Kir6.2 was higher in type I compared with type II fibres. In both type I (P < 0.01) and type II fibres (P < 0.001) the AB_FXYD1 signal was lower after exercise compared with rest, indicating an increase in unspecific FXYD1 phosphorylation. The FXYD1 serine 68 phosphorylation was higher (P < 0.001) after exercise compared with rest in type II fibres (1.90 ± 0.25 vs. 1.00 ± 0.08) and not changed in type I fibres. Total FXYD1 was not expressed in a fibre type-specific manner. Expression of phosphofructokinase was lower (P < 0.001) in type I than in type II fibres, whereas citrate synthase and 3-hydroxyacyl-CoA dehydrogenase were more abundant (P < 0.001) in type I fibres. In conclusion, FXYD1 phosphorylation at serine 68 increased after an acute bout of intense exercise in human type II fibres, while AB_FXYD1 signal intensity was lower in both type I and type II fibres, indicating fibre type-specific differences in FXYD1 phosphorylation on serine 63, serine 68 and threonine 69. This, together with the observation of a higher abundance of the Na+–K+ pump α2 isoform protein in type II fibres, is likely to have importance for the exercise-induced human Na+–K+ pump activity in the different fibre types. PMID:23359667

  9. Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation.

    PubMed

    Hirsch, Katie R; Smith-Ryan, Abbie E; Roelofs, Erica J; Trexler, Eric T; Mock, Meredith G

    2016-07-13

    To determine the effects of a mushroom blend containing Cordyceps militaris on high-intensity exercise after 1 and 3 weeks of supplementation. Twenty-eight individuals (Mean ± standard deviation [SD]; Age = 22.7 ± 4.1 yrs; Height = 175.4 ± 8.7 cm; Weight = 71.6 ± 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (%drop) were recorded during a 3 minute maximal cycle test with resistance at 4.5% body weight. Subjects consumed 4 g·d(-1) mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks. Exercise tests were separated by at least 48 hours and repeated following supplementation periods. One week of supplementation elicited no significant time × treatment interaction for VO2max (p = 0.364), VT (p = 0.514), TTE (p = 0.540), RPP (p = 0.134), AvgP (p = 0.398), or %drop (p = 0.823). After 3 weeks, VO2max significantly improved (p = 0.042) in MR (+4.8 ml·kg(-1)·min(-1)), but not PL (+0.9 ml·kg(-1)·min(-1)). Analysis of 95% confidence intervals revealed significant improvements in TTE after 1- (+28.1 s) and 3 weeks (+69.8 s) in MR, but not PL, with additional improvements in VO2max (+4.8 ml·kg(-1)·min(-1)) and VT (+0.7 l·min(-1)) after 3 weeks. Acute supplementation with a Cordyceps militaris containing mushroom blend may improve tolerance to high-intensity exercise; greater benefits may be elicited with consistent chronic supplementation.

  10. 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.

  11. Incidence of acute kidney injury in the neonatal intensive care unit.

    PubMed

    Youssef, Doaa; Abd-Elrahman, Hadeel; Shehab, Mohamed M; Abd-Elrheem, Mohamed

    2015-01-01

    The aim of this work is to study the incidence of acute kidney injury (AKI) in neonates admitted to the neonatal intensive care unit (NICU) over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children's Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN), serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.

  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. Novel Faces of Fibroblast Growth Factor 23 (FGF23): Iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury.

    PubMed

    Kanbay, Mehmet; Vervloet, Marc; Cozzolino, Mario; Siriopol, Dimitrie; Covic, Adrian; Goldsmith, David; Solak, Yalcin

    2017-03-01

    FGF23 is a hormone that appears as the core regulator of phosphate metabolism. Great deal of data has accumulated to demonstrate increased FGF23 secretion from the bone to compensate for even subtle increases in serum phosphorus long before intact PTH. However, recent evidence points to the fact that actions and interactions of FGF23 are not limited solely to phosphate metabolism. FGF23 may be implicated in iron metabolism and erythropoiesis, inflammation, insulin resistance, proteinuria, acute kidney injury and left ventricular hypertrophy. In this review, we will summarize latest experimental and clinical data examining impact of FGF23 on aforementioned pathophysiologic pathways/disorders.

  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. Vicious circle of acute radiation toxicities and weight loss predicts poor prognosis for nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

    PubMed Central

    Li, Guo; Jiang, Xiong-ying; Qiu, Bo; Shen, Lu-Jun; Chen, Chen; Xia, Yun-Fei

    2017-01-01

    Background: Weight loss during radiotherapy has been known as a negative prognostic factor for nasopharyngeal carcinoma (NPC) patients, but the factors related to weight loss during radiotherapy were not fully understood. Methods: A total of 322 newly diagnosed NPC patients receiving intensity modulated radiotherapy (IMRT) in Sun Yat-sen University Cancer Center between June 2002 and August 2006 were enrolled. Kaplan-Meier methods and log-rank test were applied for survival analysis; a multiple regression was used to identify the factors related to weight loss during radiotherapy. Results: The mean and median values of weight loss (%) during radiotherapy were 6.85% and 6.70%. NPC patients with critical weight loss (> 5.4%) have poorer overall survival (OS) and distant metastasis-free survival (DMFS) than the patients without critical weight loss (p = 0.002 and 0.021, respectively). Pre-radiotherapy weight, acute mucosal toxicity, acute pharynx and esophagus toxicity, and acute upper gastrointestinal toxicity were related to the weight loss during radiotherapy independently (p = 0.01, p < 0.001, p < 0.001, and p = 0.009, respectively). Conclusions: Acute radiation toxicities had significant and independent impact on weight loss during radiotherapy. The vicious circle of acute radiation toxicities and weight loss had bad effect on prognosis of NPC patients. PMID:28382146

  17. Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive care unit in critically ill acute trauma patients.

    PubMed

    Bartanusz, Viktor; Corneille, Michael G; Sordo, Salvador; Gildea, Marianne; Michalek, Joel E; Nair, Prakash V; Stewart, Ronald M; Jezova, Daniela

    2014-12-01

    Acute trauma patients represent a specific subgroup of the critically ill population due to sudden and dramatic changes in homeostasis and consequently extreme demands on the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Salivary cortisol is an accepted surrogate for serum free cortisol in the assessment of HPA axis function. The purpose of this study was (1) to establish the feasibility of salivary cortisol measurement in acute trauma patients in the neurosurgical-surgical intensive care unit (NSICU), and (2) to determine the diurnal pattern of salivary cortisol in the acute phase after injury. Saliva from 50 acute trauma patients was prospectively collected twice a day at 6AM and 4PM during the first week after injury in the NSICU. Mean PM cortisol concentrations were significantly higher in subjects versus controls (p<0.001). Subjects failed to develop the expected PM versus AM decrease in cortisol concentration seen in controls (p=0.005). Salivary cortisol did not vary significantly with baseline Glasgow Coma Scale (GCS), Injury Severity Score, sex, injury type, ethnicity, or age. When comparing mean AM and PM salivary cortisol by GCS severity category (GCS ⩽8 and GCS >8) the AM salivary cortisol was significantly higher in patients with GCS ⩽8 (p=0.002). The results show a loss of diurnal cortisol variation in acute trauma patient in the NSICU during the first week of hospitalization. Patients with severe brain injury had higher morning cortisol levels than those with mild/moderate brain injury.

  18. 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

  19. One-year mortality among Danish intensive care patients with acute kidney injury: a cohort study

    PubMed Central

    2012-01-01

    Introduction There are few studies on long-term mortality among intensive care unit (ICU) patients with acute kidney injury (AKI). We assessed the prevalence of AKI at ICU admission, its impact on mortality during one year of follow-up, and whether the influence of AKI varied in subgroups of ICU patients. Methods We identified all adults admitted to any ICU in Northern Denmark (approximately 1.15 million inhabitants) from 2005 through 2010 using population-based medical registries. AKI was defined at ICU admission based on the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) classification, using plasma creatinine changes. We included four severity levels: AKI-risk, AKI-injury, AKI-failure, and without AKI. We estimated cumulative mortality by the Kaplan-Meier method and hazard ratios (HRs) using a Cox model adjusted for potential confounders. We computed estimates for all ICU patients and for subgroups with different comorbidity levels, chronic kidney disease status, surgical status, primary hospital diagnosis, and treatment with mechanical ventilation or with inotropes/vasopressors. Results We identified 30,762 ICU patients, of which 4,793 (15.6%) had AKI at ICU admission. Thirty-day mortality was 35.5% for the AKI-risk group, 44.2% for the AKI-injury group, and 41.0% for the AKI-failure group, compared with 12.8% for patients without AKI. The corresponding adjusted HRs were 1.96 (95% confidence interval (CI) 1.80-2.13), 2.60 (95% CI 2.38 to 2.85) and 2.41 (95% CI 2.21 to 2.64), compared to patients without AKI. Among patients surviving 30 days (n = 25,539), 31- to 365 day mortality was 20.5% for the AKI-risk group, 23.8% for the AKI-injury group, and 23.2% for the AKI-failure group, compared with 10.7% for patients without AKI, corresponding to adjusted HRs of 1.33 (95% CI 1.17 to 1.51), 1.60 (95% CI 1.37 to1.87), and 1.64 (95% CI 1.42 to 1.90), respectively. The association between AKI and 30-day mortality was evident in

  20. 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.

  1. [Hospital management of acute respiratory failure: the role of the pulmonologist and of the respiratory intensive care unit].

    PubMed

    Scala, Raffaele

    2009-04-01

    Acute respiratory failure (ARF) is one of the most common and severe urgencies of the modern medicine which may require the application of mechanical ventilation and a careful monitoring of the patient's conditions. With the popularity of non-invasive ventilation and the interest of the pulmonologist for the care of the respiratory critical patient, in Italy there has been the spreading of Respiratory Intensive Care Units (RICU), which are as intermediate specialist structures in terms of intensity of care between the General Intensive Care Unit and the ordinary ward. In this article, the author analysed the cultural, scientific and organizational aspects of the central role played by the pulmonologist who's working in the RICU in the complex intra-hospital multi-disciplinary management of ARF.

  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.

  3. Conducting an acute intense interval exercise session during the Ramadan fasting month: what is the optimal time of the day?

    PubMed

    Aziz, Abdul Rashid; Chia, Michael Yong Hwa; Low, Chee Yong; Slater, Gary John; Png, Weileen; Teh, Kong Chuan

    2012-10-01

    This study examines the effects of Ramadan fasting on performance during an intense exercise session performed at three different times of the day, i.e., 08:00, 18:00, and 21:00 h. The purpose was to determine the optimal time of the day to perform an acute high-intensity interval exercise during the Ramadan fasting month. After familiarization, nine trained athletes performed six 30-s Wingate anaerobic test (WAnT) cycle bouts followed by a time-to-exhaustion (T(exh)) cycle on six separate randomized and counterbalanced occasions. The three time-of-day nonfasting (control, CON) exercise sessions were performed before the Ramadan month, and the three corresponding time-of-day Ramadan fasting (RAM) exercise sessions were performed during the Ramadan month. Note that the 21:00 h session during Ramadan month was conducted in the nonfasted state after the breaking of the day's fast. Total work (TW) completed during the six WAnT bouts was significantly lower during RAM compared to CON for the 08:00 and 18:00 h (p < .017; effect size [d] = .55 [small] and .39 [small], respectively) sessions, but not for the 21:00 h (p = .03, d = .18 [trivial]) session. The T(exh) cycle duration was significantly shorter during RAM than CON in the 18:00 (p < .017, d = .93 [moderate]) session, but not in the 08:00 (p = .03, d = .57 [small]) and 21:00 h (p = .96, d = .02 [trivial]) sessions. In conclusion, Ramadan fasting had a small to moderate, negative impact on quality of performance during an acute high-intensity exercise session, particularly during the period of the daytime fast. The optimal time to conduct an acute high-intensity exercise session during the Ramadan fasting month is in the evening, after the breaking of the day's fast.

  4. 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

  5. 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

  6. Insulin Therapy

    MedlinePlus

    ... 3 hours and lasts 12 to 16 hours.Long-acting insulin (such as insulin glargine and insulin detemir) ... hard to time their meals around regular insulin injections. Sometimes they end up eating too soon or ...

  7. 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.

  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. CARDIORESPIRATORY FITNESS MODULATES THE ACUTE FLOW-MEDIATED DILATION RESPONSE FOLLOWING HIGH-INTENSITY BUT NOT MODERATE-INTENSITY EXERCISE IN ELDERLY MEN.

    PubMed

    Bailey, Tom G; Perissiou, Maria; Windsor, Mark; Russell, Fraser D; Golledge, Jonathan; Green, Daniel J; Askew, Christopher D

    2017-02-16

    Impaired endothelial function is observed with ageing and with low cardiorespiratory fitness (VO2peak) whilst improvements in both are suggested to be reliant on higher-intensity exercise in the elderly. This may be due to the flow-mediated dilation (FMD) response to acute exercise of varying intensity. We examined the hypothesis that exercise-intensity alters the FMD response in healthy elderly adults, and would be modulated by VO2peak Forty-seven elderly men were stratified into lower- (VO2peak = 24.3±2.9 ml.kg(-1)min(-1), n=27) and higher-fit groups (VO2peak = 35.4±5.5 ml.kg(-1)min(-1), n=20) after a test of cycling peak power output (PPO). In randomised order, participants undertook 27 min moderate-intensity continuous (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO), or no-exercise control. Brachial FMD was assessed at rest, 10 and 60 min after exercise. In control, FMD reduced in both groups (P=0.05). FMD increased after MICE in both groups [increase of 0.86 % (95% CI, 0.17 to 1.56), P=0.01], and normalised after 60 min. In the lower-fit, FMD reduced after HIIE [reduction of 0.85 % (95% CI, 0.12 to 1.58), P=0.02), and remained decreased at 60 min (P=0.05). In the higher-fit FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52 % (95% CI, 0.41 to 2.62), P<0.01], which was correlated with VO2peak (r =0.41; P<0.01). Exercise-intensity alters the FMD response in elderly adults, and VO2peak modulates the FMD response following HIIE, but not MICE. The sustained decrease in FMD in the lower-fit may represent a signal for vascular adaptation or endothelial fatigue.

  10. Differential effects of differing intensities of acute exercise on speed and accuracy of cognition: a meta-analytical investigation.

    PubMed

    McMorris, Terry; Hale, Beverley J

    2012-12-01

    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<0.01) on cognition. Examination of the comparison between speed and accuracy dependent variables showed that speed accounted for most of the effect. For speed, moderate intensity exercise demonstrated a significantly larger mean effect size than those for low and high intensities. For speed of processing during moderate intensity exercise, central executive tasks showed a larger effect size than recall and alertness/attention tasks; and mean effect size for counterbalanced or randomized studies was significantly greater than for studies in which a pre-exercise followed by during or post-exercise protocol was used. There was no significant difference between mean effect sizes when testing took place post-exercise compared to during exercise for speed but accuracy studies demonstrated a significantly larger mean effect size post-exercise. It was concluded that increased arousal during moderate intensity exercise resulted in faster speed of processing. The very limited effect on accuracy may be due to the failure to choose tests which are complex enough to measure exercise-induced changes in accuracy of performance.

  11. Hormone responses to an acute bout of low intensity blood flow restricted resistance exercise in college-aged females.

    PubMed

    Kim, Eonho; Gregg, Lee D; Kim, Ldaeyeol; Sherk, Vanessa D; Bemben, Michael G; Bemben, Debra A

    2014-01-01

    The purpose of this study was to determine whether the acute hormone response to exercise differed between low intensity blood flow restricted resistance exercise and traditional high-intensity resistance exercise in college-aged women. A total of 13 healthy women (aged 18-25 yrs), who were taking oral contraceptives, volunteered for this randomized crossover study. Subjects performed a session of low intensity blood flow restricted resistance exercise (BFR) (20% of 1-RM, 1 set 30 reps, 2 sets 15 reps) and a session of traditional high intensity resistance exercise without blood flow restriction (HI) (3 sets of 10 repetitions at 80% of 1-RM) on separate days. Fasting serum cortisol and growth hormone (GH) and blood lactate responses were measured in the morning pre and post exercise sessions. GH (Change: HI: 6.34 ± 1.72; BFR: 4.22 ± 1.40 ng·mL(-1)) and cortisol (Change: HI: 4.46 ± 1.53; BFR: 8.10 ± 2.30 ug·dL(-1)) significantly (p < 0.05) increased immediately post exercise for both protocols compared to baseline and there were no significant differences between the protocols for these responses. In contrast, blood lactate levels (HI: 7.35 ± 0.45; BFR: 4.02 ± 0.33 mmol·L(-1)) and ratings of perceived exertion were significantly (p < 0.01) higher for the HI protocol. In conclusion, acute BFR restricted resistance exercise stimulated similar increases in anabolic and catabolic hormone responses in young women. Key PointsGrowth hormone and cortisol levels significantly increased after a single bout of low intensity blood flow restricted resistance exercise in young women.There were no significant differences in hormone responses between the low intensity blood flow restricted protocol and the traditional high intensity higher total workload protocol.Low intensity blood flow restricted resistance exercise provides a sufficient stimulus to elicit anabolic and catabolic hormone responses in young women.

  12. 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.

  13. Assessments of urine cofilin-1 in patients hospitalized in the intensive care units with acute kidney injury

    NASA Astrophysics Data System (ADS)

    Lee, Yi-Jang; Chao, Cheng-Han; Chang, Ying-Feng; Chou, Chien

    2013-02-01

    The actin depolymerizing factor (ADF)/cofilin protein family has been reported to be associated with ischemia induced renal disorders. Here we examine if cofilin-1 is associated with acute kidney injury (AKI). We exploited a 96-well based fiber-optic biosensor that uses conjugated gold nanoparticles and a sandwich immunoassay to detect the urine cofilin-1 level of AKI patients. The mean urine cofilin-1 level of the AKI patients was two-fold higher than that of healthy adults. The receiver operating characteristic (ROC) curve showed that cofilin-1 is a potential biomarker for discriminating AKI patients from healthy adults for intensive care patients.

  14. 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.

  15. 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...

  16. 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

  17. Activation of AMP-activated protein kinase, inhibition of pyruvate dehydrogenase activity, and redistribution of substrate partitioning mediate the acute insulin-sensitizing effects of troglitazone in skeletal muscle cells.

    PubMed

    Fediuc, S; Pimenta, A S; Gaidhu, M P; Ceddia, R B

    2008-05-01

    The aim of this study was to investigate the acute effects of troglitazone on several pathways of glucose and fatty acid (FA) partitioning and the molecular mechanisms involved in these processes in skeletal muscle. Exposure of L6 myotubes to troglitazone for 1 h significantly increased phosphorylation of AMPK and ACC, which was followed by approximately 30% and approximately 60% increases in palmitate oxidation and carnitine palmitoyl transferase-1 (CPT-1) activity, respectively. Troglitazone inhibited basal ( approximately 25%) and insulin-stimulated ( approximately 35%) palmitate uptake but significantly increased basal and insulin-stimulated glucose uptake by approximately 2.2- and 2.7-fold, respectively. Pharmacological inhibition of AMPK completely prevented the effects of troglitazone on palmitate oxidation and glucose uptake. Interestingly, even though troglitazone exerted an insulin sensitizing effect, it reduced basal and insulin-stimulated rates of glycogen synthesis, incorporation of glucose into lipids, and glucose oxidation to values corresponding to approximately 30%, approximately 60%, and 30% of the controls, respectively. These effects were accompanied by an increase in basal and insulin-stimulated phosphorylation of Akt(Thr308), Akt(Ser473), and GSK3alpha/beta. Troglitazone also powerfully suppressed pyruvate decarboxylation, which was followed by a significant increase in basal ( approximately 3.5-fold) and insulin-stimulated ( approximately 5.5-fold) rates of lactate production by muscle cells. In summary, we provide novel evidence that troglitazone exerts acute insulin sensitizing effects by increasing FA oxidation, reducing FA uptake, suppressing pyruvate dehydrogenase activity, and shifting glucose metabolism toward lactate production in muscle cells. These effects seem to be at least partially dependent on AMPK activation and may account for potential acute PPAR-gamma-independent anti-diabetic effects of thiazolidinediones in skeletal

  18. Acute confusion and unreal experiences in intensive care patients in relation to the ICU syndrome. Part II.

    PubMed

    Granberg, A; Engberg, I B; Lundberg, D

    1999-02-01

    The intensive care unit syndrome (ICU syndrome) is defined as an altered emotional state occurring in a highly stressful environment, which may manifest itself in various forms such as delirium, confusion, crazy dreams or unreal experiences. The purpose of this part of a study of patients' experiences is to describe and illuminate patients' experiences of acute confusion, disorientation, wakefulness, dreams and nightmares during and after their stay in the ICU. The data were obtained from 19 ventilated patients, who were interviewed twice and had stayed at least 36 hours in the ICU, the first interview being about one week after discharge from the ICU, and the second 4-8 weeks later. The hermeneutic approach used when interpreting and analysing the text from the interviews revealed that patients' experiences of unreal experiences were often associated with intense fear. Intense or continuous unbearable fear seems to result in frightening unreal experiences, which further increase the level of fear. Care actions or caring relationships with relatives or nurses can reduce this fear, which can help to prevent the occurrence and/or duration and intensity of the unreal experiences. Trust and confidence in nurses or significant others and feelings of self-control or trust in self-control seemed to reduce the risk of unreal experiences so that adverse stimuli might only trigger a mild confusion.

  19. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

    PubMed Central

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Socié, Gérard; Huynh, Anne; Reman, Oumédaly; Yakoub-Agha, Ibrahim; Furst, Sabine; Guillaume, Thierry; Tabrizi, Resa; Vigouroux, Stéphane; Peterlin, Pierre; El-Cheikh, Jean; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2017-01-01

    The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. PMID:27561720

  20. 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.

  1. 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

  2. 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

  3. 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

  4. Effect of postremission therapy before reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission.

    PubMed

    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

    2014-02-01

    The impact of pretransplant (hematopoietic cell transplantation [HCT]) cytarabine consolidation therapy on post-HCT outcomes has yet to be evaluated after reduced-intensity or nonmyeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia in first complete remission (CR1) reported to the Center for International Blood and Marrow Transplant Research who received a reduced-intensity or nonmyeloablative conditioning HCT from an HLA-identical sibling, HLA-matched unrelated donor, or umbilical cord blood donor from 2000 to 2010. We compared transplant outcomes based on exposure to cytarabine postremission consolidation. Three-year survival rates were 36% (95% confidence interval [CI], 29% to 43%) in the no consolidation arm and 42% (95% CI, 37% to 47%) in the cytarabine consolidation arm (P = .16). Disease-free survival was 34% (95% CI, 27% to 41%) and 41% (95% CI, 35% to 46%; P = .15), respectively. Three-year cumulative incidences of relapse were 37% (95% CI, 30% to 44%) and 38% (95% CI, 33% to 43%), respectively (P = .80). Multivariate regression confirmed no effect of consolidation on relapse, disease-free survival, and survival. Before reduced-intensity or nonmyeloablative conditioning 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 treatment-related mortality and is reasonable if required.

  5. 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

  6. Insulin Basics

    MedlinePlus

    ... long insulin continues to lower blood glucose. Insulin Strength All insulins come dissolved or suspended in liquids. The standard and most commonly used strength in the United States today is U-100, ...

  7. Idarubicin appears equivalent to dose-intense daunorubicin for remission induction in patients with acute myeloid leukemia.

    PubMed

    Trifilio, Steven; Zhou, Zheng; Mehta, Jayesh; Czerniak, Colleen; Pi, Judy; Greenberg, Deborah; Koslosky, Molly; Pantiru, Mihaela; Altman, Jessica

    2013-08-01

    Daunorubicin has historically been considered the anthracycline of choice at many cancer centers for the treatment of acute myeloid leukemia (AML). Drug shortages have required the substitution of daunorubicin with idarubicin. Randomized studies have shown idarubicin (10-12mg/m(2)) to be comparable or superior to standard dose daunorubicin (45-60mg/m(2)) for achieving complete remission (CR). Whether these results can be extrapolated to dose-intense daunorubicin (90mg/m(2)), recently shown to improve CR rates when compared to standard daunorubicin doses remains uncertain. This observational study was conducted at Northwestern Memorial Hospital (NMH) to compare CR rates. The results suggest idarubicin is equivalent to daunorubicin, and for some subsets of patients, idarubicin may have superior CR rates.

  8. Comorbidity, age and mortality among adults treated intensively for acute myeloid leukemia (AML)

    PubMed Central

    Tawfik, Bernard; Pardee, Timothy; Isom, Scott; Sliesoraitis, Sarunas; Winter, Allison; Lawrence, Julia; Powell, Bayard L.; Klepin, Heidi D.

    2015-01-01

    Introduction Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. Methods We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002–2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. Results In this series, 144 patients were ≥60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, p<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non diabetic patients, p =0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6–15.2) times. Discussion Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy. PMID:26527394

  9. Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles.

    PubMed

    Serizawa, Yasuhiro; Oshima, Rieko; Yoshida, Mitsuki; Sakon, Ichika; Kitani, Kazuto; Goto, Ayumi; Tsuda, Satoshi; Hayashi, Tatsuya

    2014-10-10

    Salicylate (SAL) has been recently implicated in the antidiabetic effect in humans. We assessed whether 5'-AMP-activated protein kinase (AMPK) in skeletal muscle is involved in the effect of SAL on glucose homeostasis. Rat fast-twitch epitrochlearis and slow-twitch soleus muscles were incubated in buffer containing SAL. Intracellular concentrations of SAL increased rapidly (<5 min) in both skeletal muscles, and the Thr(172) phosphorylation of the α subunit of AMPK increased in a dose- and time-dependent manner. SAL increased both AMPKα1 and AMPKα2 activities. These increases in enzyme activity were accompanied by an increase in the activity of 3-O-methyl-D-glucose transport, and decreases in ATP, phosphocreatine, and glycogen contents. SAL did not change the phosphorylation of insulin receptor signaling including insulin receptor substrate 1, Akt, and p70 ribosomal protein S6 kinase. These results suggest that SAL may be transported into skeletal muscle and may stimulate AMPK and glucose transport via energy deprivation in multiple muscle types. Skeletal muscle AMPK might be part of the mechanism responsible for the metabolic improvement induced by SAL.

  10. Incidence and recognition of acute respiratory distress syndrome in a UK intensive care unit

    PubMed Central

    Summers, Charlotte; Singh, Nanak R; Worpole, Linda; Simmonds, Rosalind; Babar, Judith; Condliffe, Alison M; Gunning, Kevin E; Johnston, Andrew J; Chilvers, Edwin R

    2016-01-01

    The reported incidence of ARDS is highly variable (2.5%–19% of intensive care unit (ICU) patients) and varies depending on study patient population used. We undertook a 6-month, prospective study to determine the incidence and outcome of ARDS in a UK adult University Hospital ICU. 344 patients were admitted during the study period, of these 43 (12.5%) were determined to have ARDS. Patients with ARDS had increased mortality at 28 days and 2 years post-diagnosis, and there was under-recognition of ARDS in both medical records and death certificattion. Our findings have implications for critical care resource planning. PMID:27552782

  11. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

    PubMed

    Hamaki, T; Kami, M; Kanda, Y; Yuji, K; Inamoto, Y; Kishi, Y; Nakai, K; Nakayama, I; Murashige, N; Abe, Y; Ueda, Y; Hino, M; Inoue, T; Ago, H; Hidaka, M; Hayashi, T; Yamane, T; Uoshima, N; Miyakoshi, S; Taniguchi, S

    2005-03-01

    Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

  12. Early Clinical Outcome of Acute Poisoning Cases Treated in Intensive Care Unit

    PubMed Central

    Sulaj, Zihni; Prifti, Edvin; Demiraj, Aurel; Strakosha, Arjana

    2015-01-01

    Introduction: A variety of factors have influenced the significant incidence of morbidity and mortality of acute poisoning and the timely recognition and properly management of critically ill poisoned patients is a key component. The aim of this study is to reveal the reasons for ICU admission of acutely poisoned patients, the main factors influencing the course and outcome of patients in relation with clinical approaches applied, available resources and infrastructure of treatment. Materials and Methods: This is a retrospective study based on most reachable variables extracted from patients’ medical records and ED registers of patients admitted at the medical ICU of “Mother Teresa” University Hospital in Tirana over two (2012-2013) years. Demography, time of exposure, etiology and circumstances of poisonings, assessment and treatment, reasons for ICU admission, course and outcome were duly obtained. Results: The number of ICU treated patients was 118, consisting in 47.4% (56) males and 52.5% (62) females which represented 10.2% of poisoned patients admitted during this two-year-period in ED and 9.2% of other etiology ICU admitted patients. Mean was 42.6 years for males, and 38 years for females. About 55.9% were urban residents and 44% rural ones. The elapsed time from toxic exposure to treatment initiation had varied between 2-6 hours, 44% arrived in the hospital <4 hours. The toxic exposures were intentional in 87.2% of cases, with a male:female ratio was 0.8:1. Agrochemicals such as Aluminum phosphide and organophosphates were involved in 77.1% of cases. Cardiovascular collapse and respiratory failure were the main clinical syndromes encountered. Mechanical ventilation was required in 31.4% of patients. The length of ICU stay was 2.73 (0.96) days and the mortality was 54.2%. Conclusion: This study evidenced that highly lethal toxicants used in poisoning acts such as agrochemicals, high rate of suicide, notwithstanding the infrastructure and resources

  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.

  14. Renal assist device and treatment of sepsis-induced acute kidney injury in intensive care units.

    PubMed

    Issa, Naim; Messer, Jennifer; Paganini, Emil P

    2007-01-01

    Acute kidney injury (AKI) is a frequent and serious complication of sepsis in ICU patients and is associated with a very high mortality. Despite the advent of sophisticated renal replacement therapies (RRT) employing high-dose hemofiltration and high-flux membranes, mortality and morbidity from sepsis-induced AKI remained high. Moreover, these dialytic modalities could not substitute for the important functions of renal tubular cells in decreasing sepsis-induced AKI biological dysregulations. The results from the in vitro and preclinical animal model studies were very intriguing and led to the development of a bioartificial kidney consisting of a renal tubule assist device containing human proximal tubular cells (RAD) added in tandem to a continuous venovenous hemofiltration circuit. The results from the phase I safety trial and the recent phase II clinical trial showed that the RAD not only can replace many of the indispensable biological kidney functions, but also modify the natural history of sepsis-induced AKI by ameliorating patient survival.

  15. Role of reduced-intensity conditioning allogeneic hematopoietic cell transplantation in older patients with de novo acute myeloid leukemia.

    PubMed

    Yamasaki, Satoshi; Hirakawa, Akihiro; Aoki, Jun; Uchida, Naoyuki; Fukuda, Takahiro; Ogawa, Hiroyasu; Ohashi, Kazuteru; Kondo, Tadakazu; Eto, Tetsuya; Kanamori, Heiwa; Okumura, Hirokazu; Iwato, Koji; Ichinohe, Tatsuo; Kanda, Junya; Onizuka, Makoto; Kuwatsuka, Yachiyo; Yanada, Masamitsu; Atsuta, Yoshiko; Takami, Akiyoshi; Yano, Shingo

    2017-02-01

    Reduced-intensity conditioning (RIC) regimens extend the therapeutic use of allogeneic hematopoietic cell transplantation (HCT) to older patients. The survival trend in 2325 patients aged >50 years presenting with de novo acute myeloid leukemia (AML) who underwent first reduced-intensity HCT (RIC-HCT) was assessed by retrospectively analyzing outcomes between 2000 and 2013. The annual number of RIC-HCTs in Japan was higher in the 2008-2013 period (n = 205/year [1229/6 years]) than in the 2000-2007 period (n = 137/year [1096/8 years]). Overall and disease-free survival were higher in the 2008-2013 period (P < 0.001) because of the improvement in transplant-related mortality (TRM). Survival regarding RIC-HCT for AML has improved over time, with an increased number of RIC-HCTs in patients with a Karnofsky performance status (KPS) ≥80. However, TRM remains high and the relapse rate has not improved over time. Multivariate analyses showed that a KPS ≥80 and complete remission at HCT were associated with less TRM and relapse, and better survival regardless of age ≥65 years. Accurate timing and prospective identification of patients at risk of TRM may aid the development of risk-adapted strategies for RIC-HCT in AML patients regardless of age.

  16. Treatment strategies and regimens of graduated intensity for childhood acute lymphoblastic leukemia in low-income countries: A proposal.

    PubMed

    Hunger, Stephen P; Sung, Lillian; Howard, Scott C

    2009-05-01

    Cure rates for children with acute lymphoblastic leukemia (ALL) are 80-85% in high-income countries (HICs) in North America and Western Europe. However, cure rates are much lower in many low-income countries (LICs), where most cases of ALL occur. Over the past several decades partnerships ("twinning") between HIC and LIC pediatric oncology programs have led to major improvements in outcome for children with ALL in some LICs, often by developing time and resource intensive relationships that allow LIC centers to treat children with regimens similar or identical to those used in HICs. However, the resources are not available in most LICs to allow immediate introduction of intensive ALL treatment regimens similar to those used in HICs. With these thoughts in mind, we present a proposal for a systematic and graduated approach to ALL diagnosis, risk classification, and treatment in LICs. We have based the strategy and the proposed regimens on those developed by the Children's Cancer Group (CCG) and Children's Oncology Group (COG) over the past several decades, beginning with a first level regimen similar to CCG therapy of the early 1980s and then layering on successive treatment intensifications proven effective in randomized clinical trials. Simple monitoring rules are included to help centers decide when they are ready to add new treatment components. This proposal provides a framework that LIC centers can use to provide effective ALL therapy, particularly in regions of the world where few children are currently being cured.

  17. 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.

  18. Acute high-intensity sound exposure alters responses of place cells in hippocampus.

    PubMed

    Goble, T J; Møller, A R; Thompson, L T

    2009-07-01

    Overstimulation is known to activate neural plasticity in the auditory nervous system causing changes in function and re-organization. It has been shown earlier that overstimulation using high-intensity noise or tones can induce signs of tinnitus. Here we show in studies in rats that overstimulation causes changes in the way place cells of the hippocampus respond as rats search for rewards in a spatial maze. In familiar environments, a subset of hippocampal pyramidal neurons, known as place cells, respond when the animal moves through specific locations but are relatively silent in others. This place-field activity (i.e. location-specific firing) is stable in a fixed environment. The present study shows that activation of neural plasticity through overstimulation by sound can alter the response of these place cells. Rats implanted with chronic drivable dorsal hippocampal tetrodes (four microelectrodes) were assessed for stable single-unit place-field responses that were extracted from multiunit responses using NeuroExplorer computer spike-sorting software. Rats then underwent either 30 min exposure to a 4 kHz tone at 104 dB SPL or a control period in the same sound chamber. The place-field activity was significantly altered after sound exposure showing that plastic changes induced by overstimulation are not limited to the auditory nervous system but extend to other parts of the CNS, in this case to the hippocampus, a brain region often studied in the context of plasticity.

  19. High prevalence of respiratory viral infections in patients hospitalized in an intensive care unit for acute respiratory infections as detected by nucleic acid-based assays.

    PubMed

    Legoff, Jérôme; Guérot, Emmanuel; Ndjoyi-Mbiguino, Angélique; Matta, Mathieu; Si-Mohamed, Ali; Gutmann, Laurent; Fagon, Jean-Yves; Bélec, Laurent

    2005-01-01

    Forty-seven bronchoalveolar lavages (BAL) were obtained from 41 patients with acute pneumonia attending an intensive care unit. By molecular diagnosis, 30% of total BAL and 63% of bacteria-negative BAL were positive for respiratory viruses. Molecular detection allows for high-rate detection of respiratory viral infections in adult patients suffering from severe pneumonia.

  20. High Prevalence of Respiratory Viral Infections in Patients Hospitalized in an Intensive Care Unit for Acute Respiratory Infections as Detected by Nucleic Acid-Based Assays

    PubMed Central

    Legoff, Jérôme; Guérot, Emmanuel; Ndjoyi-Mbiguino, Angélique; Matta, Mathieu; Si-Mohamed, Ali; Gutmann, Laurent; Fagon, Jean-Yves; Bélec, Laurent

    2005-01-01

    Forty-seven bronchoalveolar lavages (BAL) were obtained from 41 patients with acute pneumonia attending an intensive care unit. By molecular diagnosis, 30% of total BAL and 63% of bacteria-negative BAL were positive for respiratory viruses. Molecular detection allows for high-rate detection of respiratory viral infections in adult patients suffering from severe pneumonia. PMID:15635014

  1. 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

  2. Acute renal failure requiring renal replacement therapy in the intensive care unit: impact on prognostic assessment for shared decision making.

    PubMed

    Johnson, Robert F; Gustin, Jillian

    2011-07-01

    A 69-year-old female was receiving renal replacement therapy (RRT) for acute renal failure (ARF) in an intensive care unit (ICU). Consultation was requested from the palliative medicine service to facilitate a shared decision-making process regarding goals of care. Clinician responsibility in shared decision making includes the formulation and expression of a prognostic assessment providing the necessary perspective for a spokesperson to match patient values with treatment options. For this patient, ARF requiring RRT in the ICU was used as a focal point for preparing a prognostic assessment. A prognostic assessment should include the outcomes of most importance to a discussion of goals of care: mortality risk and survivor functional status, in this case including renal recovery. A systematic review of the literature was conducted to document published data regarding these outcomes for adult patients receiving RRT for ARF in the ICU. Forty-one studies met the inclusion criteria. The combined mean values for short-term mortality, long-term mortality, renal-function recovery of short-term survivors, and renal-function recovery of long-term survivors were 51.7%, 68.6%, 82.0%, and 88.4%, respectively. This case example illustrates a process for formulating and expressing a prognostic assessment for an ICU patient requiring RRT for ARF. Data from the literature review provide baseline information that requires adjustment to reflect specific patient circumstances. The nature of the acute primary process, comorbidities, and severity of illness are key modifiers. Finally, the prognostic assessment is expressed during a family meeting using recommended principles of communication.

  3. Patterns of "severe acute renal failure" in a referral center in Sudan: excluding intensive care and major surgery patients.

    PubMed

    Kaballo, Babikir G; Khogali, Mohamed S; Khalifa, Eman H; Khaiii, Eltahir A G; Ei-Hassan, Ahmed M; Abu-Aisha, Hasan

    2007-06-01

    Acute renal failure (ARF) is a common health problem worldwide. There is limited data on the pattern of ARF in Sudan. Moreover, glomerular diseases, which are a well-known cause of ARF, have not been accurately and adequately diagnosed previously. A retrospective study on the patterns of ARF was carried out in a general nephrology referral center in Sudan during the period from February 2003-February 2004. Patients from intensive care units with ARF and those who developed ARF after massive surgery were excluded from the study. Renal biopsy was performed when indicated and studied with light and immunofluorescent microscopy. Eighty-nine patients (57 (64%) cases were males and mean age was 39+/-19.4 years) fulfilled the criteria for the diagnosis of advanced renal failure requiring renal function replacement therapy. Acute tubular necrosis (ATN) was diagnosed in 50 (56%) patients; 33 (66%) ATN patients had renal failure as a complication of volume depletion, fulminant infections (particularly malaria and typhoid fever) or snakebites and 12 (13.4%) patients ingested paraphenylene-diamine (PPD) (hair/Henna dye) in suicidal attempts. Eight (9%) patients of the total study group had glomerular diseases and 11 (12.3%) had obstructive uropathy associated with ARF; the cause of ARF could not be determined in 17 (19%) patients. Fifty-three (60%) patients recovered their renal function, six (6.7%) patients progressed to chronic kidney disease (CKD), 16 (18%) died and 14 (16%) were lost to follow-up. In conclusion, patients with ARF associated with ATN had a favorable prognosis except when ATN was associated with PPD poisoning.

  4. 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.

  5. Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit – a homogeneous population?

    PubMed Central

    Santos, Wilson JQ; Zanetta, Dirce MT; Pires, Antonio C; Lobo, Suzana MA; Lima, Emerson Q; Burdmann, Emmanuel A

    2006-01-01

    Introduction Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. Method We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. Results Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]). Conclusion The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The

  6. 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.

  7. Diagnostic Value of Urine Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Acute Kidney Injury: A Meta-Analysis

    PubMed Central

    Su, Yuanyuan; Gong, Zhiyan; Wu, Yan; Tian, Yuan; Liao, Xiaohui

    2017-01-01

    Background Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) are both involved in renal tubular epithelial cell cycle arrest in acute kidney injury (AKI). Several recent studies showed that urine TIMP-2 times IGFBP7 ([TIMP-2]*[IGFBP7]) is a promising biomarker to predict AKI. Methods The aim of this meta-analysis was to assess the diagnostic value of urine [TIMP-2]*[IGFBP7] for early diagnosis of AKI. Relevant studies were retrieved from the PubMed, EMBASE, and Cochrane Library databases. The sensitivity and specificity were determined, and summary receiver operating characteristic (SROC) curves were constructed. Results Ten full-text prospective studies were included in this meta-analysis. The estimated sensitivity of urine [TIMP-2]*[IGFBP7] for the early diagnosis of AKI was 0.84 (95% CI = 0.80–0.88) and the specificity was 0.57 (95%CI = 0.55–0.60). The SROC analysis showed an area under the curve of 0.8813. Limitation The limited number of included studies, small sample size, unpublished negative results and language limitation might have affected the evaluation. Conclusion Urine [TIMP-2]*[IGFBP7] is a promising candidate for early detection of AKI, especially in ruling-out AKI. However, the potential of this biomarker should be validated in larger studies with a broader spectrum of clinical settings. PMID:28107490

  8. Insulin signaling and insulin resistance.

    PubMed

    Beale, Elmus G

    2013-01-01

    Insulin resistance or its sequelae may be the common etiology of maladies associated with metabolic syndrome (eg, 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.

  9. 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.

  10. Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure.

    PubMed

    Mokart, Djamel; Lambert, Jérôme; Schnell, David; Fouché, Louis; Rabbat, Antoine; Kouatchet, Achille; Lemiale, Virginie; Vincent, François; Lengliné, Etienne; Bruneel, Fabrice; Pene, Frederic; Chevret, Sylvie; Azoulay, Elie

    2013-08-01

    Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in patients with cancer. The aim of this study was to identify early predictors of death in patients with cancer admitted to the ICU for ARF who were not intubated at admission. We conducted analysis of a prospective randomized controlled trial including 219 patients with cancer with ARF in which day-28 mortality was a secondary endpoint. Mortality at day 28 was 31.1%. By multivariate analysis, independent predictors of day-28 mortality were: age (odds ratio [OR] 1.30/10 years, 95% confidence interval [CI] [1.01-1.68], p = 0.04), more than one line of chemotherapy (OR 2.14, 95% CI [1.08-4.21], p = 0.03), time between respiratory symptoms onset and ICU admission > 2 days (OR 2.50, 95% CI [1.25-5.02], p = 0.01), oxygen flow at admission (OR 1.07/L, 95% CI [1.00-1.14], p = 0.04) and extra-respiratory symptoms (OR 2.84, 95%CI [1.30-6.21], p = 0.01). After adjustment for the logistic organ dysfunction (LOD) score at admission, only time between respiratory symptoms onset and ICU admission > 2 days and LOD score were independently associated with day-28 mortality. Determinants of death include both factors non-amenable to change, and delay in ARF management. These results suggest that early intensive care management of patients with cancer with ARF may translate to better survival.

  11. 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.

  12. 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

  13. 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

  14. [Successful treatment with reduced-intensity cord blood transplantation for acute myeloid leukemia with complete tetraploidy (92, XXXX)].

    PubMed

    Iwasaki, Junko; Onozawa, Masahiro; Takahashi, Shojiro; Okada, Kohei; Takahata, Mutsumi; Shigematsu, Akio; Kahata, Kaoru; Kondo, Takeshi; Hashino, Satoshi; Imamura, Masahiro; Asaka, Masahiro

    2011-03-01

    A 56-year-old female was diagnosed with acute myeloid leukemia (FAB: AML-M1). G-banding karyotype of her bone marrow showed complete tetraploidy (92, XXXX [24/24]). Although she achieved complete remission (CR) after induction therapy and maintained CR during consolidation therapy, relapse occurred only 2 months after discharge. When the relapse occurred, bone marrow karyotypic analysis showed complete tetraploidy again. The patient received reduced-intensity cord blood transplantation (RI-CBT), which induced CR for the second time. The patient is currently alive 24 months after transplantation and there have not been any signs of recurrence to date. There have been a few reports of AML with near-tetraploidy, but cases of AML with complete tetraploidy are extremely rare. Tetraploid AML has been reported to have a poor prognosis and there have been very few cases maintaining CR over the long term after chemotherapy alone. This is the first case of complete tetraploid AML successfully treated by RI-CBT. The clinical course of this case suggests that hematopoietic stem cell transplantation during the first CR phase should be considered a treatment option for tetraploid AML.

  15. 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

  16. 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

  17. A randomized controlled trial of liraglutide versus insulin detemir plus sitagliptin: Effective switch from intensive insulin therapy to the once-daily injection in patients with well-controlled type 2 diabetes.

    PubMed

    Inoue, Yuichiro; Nakamura, Akinobu; Kondo, Yoshinobu; Hamano, Kumiko; Satoh, Shinobu; Terauchi, Yasuo

    2015-07-01

    This study aimed to compare the efficacy and safety of liraglutide versus insulin detemir plus sitagliptin in Japanese patients with type 2 diabetes treated with a basal-bolus insulin regimen. In this multicenter, open-label trial, 90 patients whose diabetes had been controlled well or moderately (glycated hemoglobin [HbA1c ] ≤ 7.3%) with basal-bolus insulin regimen were randomly assigned to a liraglutide group or a detemir group and were followed up for 24 weeks. The primary end point was HbA1c change from baseline to 24 weeks. Of the 90 enrolled patients, 82 completed this trial. At 24 weeks, the mean changes in HbA1c from baseline were 0.1% ± 0.9% versus 0.3% ± 0.8% in the liraglutide versus detemir groups, respectively (P = .46). The "overall" satisfaction score for the Diabetes Treatment Satisfaction Questionnaire changed from 25.2 ± 7.4 to 29.9 ± 5.3 (P < .001) and from 26.4 ± 6.1 to 28.3 ± 6.4 (P = .12) in the liraglutide and detemir groups, respectively. Although the mean change difference in HbA1c between both groups was not significant, switching from a basal-bolus insulin regimen to liraglutide once daily improved patient satisfaction levels without loss of glycemic control.

  18. Insulin Test

    MedlinePlus

    ... ovarian syndrome (PCOS) , prediabetes or heart disease , or metabolic syndrome . A health practitioner also may order insulin and ... such as appears in type 2 diabetes and metabolic syndrome Decreased insulin levels are seen with: Diabetes Hypopituitarism ...

  19. Insulin Signalling: The Inside Story.

    PubMed

    Posner, Barry I

    2017-02-01

    Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS). The peroxovanadium compounds (pVs) were discovered to activate the IRK in the absence of insulin and lead to a full insulin response. Thus, IRK activation is both necessary and sufficient for insulin signalling. Furthermore, this could be shown to occur with activation of only the endosomal IRK. The mechanism of pV action was shown to be the inhibition of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that the duration and intensity of insulin signalling are modulated within ENS by the recruitment of cellular substrates to ENS; intra-endosomal acidification, which promotes dissociation of insulin from the IRK; an endosomal acidic insulinase, which degrades intra-endosomal insulin; and IRK-associated PTPs, which dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of IRKs is central to insulin signalling and its regulation.

  20. Enhanced Medical Rehabilitation increases therapy intensity and engagement and improves functional outcomes in post-acute rehabilitation of older adults: a randomized controlled trial

    PubMed Central

    Lenze, Eric J.; Host, Helen H.; Hildebrand, Mary W.; Morrow-Howell, Nancy; Carpenter, Brian; Freedland, Kenneth E.; Baum, Carolyn A.; Dixon, David; Doré, Peter; Wendleton, Leah; Binder, Ellen F.

    2012-01-01

    Objectives For millions of disabled older adults each year, post-acute care in skilled nursing facilities (SNFs) is a brief window of opportunity to regain enough function to return home and live independently. Too often this goal is not achieved, possibly due to therapy that is inadequately intense or engaging. This study tested Enhanced Medical Rehabilitation, an intervention designed to increase patient engagement in, and intensity of, daily physical and occupational therapy sessions in post-acute care rehabilitation. Design Randomized controlled trial of Enhanced Medical Rehabilitation versus standard-of-care rehabilitation. Setting Post-acute care unit of a skilled nursing facility in St Louis, MO. Participants 26 older adults admitted from a hospital for post-acute rehabilitation. Intervention Based on models of motivation and behavior change, Enhanced Medical Rehabilitation is a set of behavioral skills for physical and occupational therapists (PT/OT) that increase patient engagement and intensity, with the goal of improving functional outcome, through: (1) a patient-directed, interactive approach, (2) increased rehabilitation intensity, and (3) frequent feedback to patients on their effort and progress. Measurements Therapy intensity: assessment of patient active time in therapy sessions. Therapy engagement: Rehabilitation Participation Scale. Functional and performance outcomes: Barthel Index, gait speed, and six-minute walk. Results Participants randomized to Enhanced Medical Rehabilitation had higher intensity therapy and were more engaged in their rehabilitation sessions; they had more improvement in gait speed (improving from 0.08 to 0.38 meter/sec vs. 0.08 to 0.22 in standard of care,p=0.003) and six-minute walk (from 73 to 266 feet vs. 40 to 94 feet in standard of care, p=0.026), with a trend for better improvement of Barthel Index (+43 points vs. 26 points in standard of care, p=0.087), compared to participants randomized to standard

  1. 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

  2. Frequency of and Risk Factors for Acute Kidney Injury Associated With Vancomycin Use in the Pediatric Intensive Care Unit

    PubMed Central

    Bresee, Lauren C.; Kraft, Timothy; Ross, B. Catherine; Dersch-Mills, Deonne

    2016-01-01

    BACKGROUND: Published information evaluating frequency of and risk factors for vancomycin-induced acute kidney injury (AKI) in the pediatric intensive care unit (PICU) population is conflicting. OBJECTIVES: The primary objective was to describe the proportion of our PICU patients who developed AKI with intravenous (IV) vancomycin. The secondary objective was to describe the associated potential risk factors. METHODS: Pediatric patients (0–18 years) who received their first IV vancomycin dose in the PICU were evaluated in this retrospective chart review. AKI was defined based on Pediatric-Modified RIFLE (pRIFLE) criteria. Patient demographics, vancomycin trough concentrations, concomitant nephrotoxins, and estimated creatinine clearance changes were analyzed. RESULTS: Of 265 patients included, the primary outcome of AKI (defined by meeting any pRIFLE criteria) occurred in 62 (23.4%) patients (48 category R, 11 category I, 3 category F). Patients who received vancomycin treatment for = 5 days were more likely to develop AKI (unadjusted odds ratio [uOR]: 2.52; 95% confidence interval [CI]: 1.11–5.73), as were patients with a maximum vancomycin trough level = 20 mg/L (OR: 2.99; 95% CI: 1.54–5.78) and patients on 1 (uOR: 2.29; 95% CI: 1.12–4.66) or more concurrent nephrotoxin (uOR: 3.11; 95% CI: 1.43–6.77). Among nephrotoxins, patients receiving furosemide concomitantly with vancomycin were more likely to develop AKI (uOR: 3.47; 95% CI: 1.92–6.27). After adjustment, only furosemide was a significant predictor of risk of AKI/AKI (adjusted OR: 3.52; 95% CI: 1.88–6.62). The study was limited by its retrospective and observational design, and confounding variables. CONCLUSIONS: Patients who were receiving vancomycin with concurrent furosemide were at highest risk of developing AKI. PMID:28018150

  3. 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

  4. Does breastfeeding reduce acute procedural pain in preterm infants in the neonatal intensive care unit? A randomized clinical trial.

    PubMed

    Holsti, Liisa; Oberlander, Timothy F; Brant, Rollin

    2011-11-01

    Managing acute procedural pain effectively in preterm infants in the neonatal intensive care unit remains a significant problem. The objectives of this study were to evaluate the efficacy of breastfeeding for reducing pain and to determine if breastfeeding skills were altered after this treatment. Fifty-seven infants born at 30-36 weeks gestational age were randomized to be breastfed (BF) or to be given a soother during blood collection. Changes in the Behavioral Indicators of Infant Pain (BIIP) and in mean heart rate (HR) across 3 phases of blood collection were measured. In the BF group, the Premature Infant Breastfeeding Behaviors (PIBBS) scale was scored before and 24 hours after blood collection. Longitudinal regression analysis was used to compare changes in Lance/squeeze and Recovery phases of blood collection between groups, with gestational age at birth, baseline BIIP scores, and mean HR included as covariates. Differences in PIBBS scores were assessed using a paired t-test. Relationships between PIBBS scores, BIIP scores, and HR were evaluated with Pearson correlations. No differences between treatment groups were found: BIIP (P=0.44, confidence interval [CI] -1.60-0.69); HR (P=0.73, CI -7.0-10.0). Infants in the BF group showed improved PIBBS scores after the treatment (P<0.01, CI -2.7 to -0.2). Lower BIIP scores during the Lance/squeeze were associated significantly with more mature sucking patterns (r=-0.39, P<0.05). Breastfeeding during blood collection did not reduce pain indices or interfere with the acquisition of breastfeeding skills. Exploratory analyses indicate there may be benefit for infants with mature breastfeeding abilities.

  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. Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes

    PubMed Central

    Eapen, Mary; Ahn, Kwang Woo; Appelbaum, Frederick R.; Ballen, Karen K.; Champlin, Richard E.; Cutler, Corey; Kan, Fangyu; Laughlin, Mary J.; Soiffer, Robert J.; Weisdorf, Daniel J.; Woolfrey, Anne; Wagner, John E.

    2012-01-01

    We report the relative efficacy of co-infusing 2 umbilical cord blood units (dUCB) compared with peripheral blood progenitor cells (PBPCs) from 8 of 8 or 7 of 8 HLA-matched unrelated donors. All patients received reduced-intensity conditioning (RIC) regimens. Four treatment groups were evaluated: 4-6 of 6 matched dUCB-TCF (n = 120; TCF = total body irradiation [TBI] 200 cGy + cyclophos-phamide + fludarabine), 4-6 of 6 matched dUCB-other (n = 40; alkylating agent + fludarabine ± TBI), and 8 of 8 (n = 313) and 7 of 8 HLA-matched PBPCs (n = 111). Compared with matched 8 of 8 PBPC transplantations, transplantation-related mortality (TRM), and overall mortality were similar after dUCB-TCF (relative risk [RR] 0.72, P = .72; RR 0.93, P = .60) but higher after dUCB-other RIC (hazard ratio [HR] 2.70, P = .0001; 1.79 P = .004). Compared with 7 of 8 PBPC transplantations, TRM (but not overall mortality) was lower after dUCB-TCF (RR 0.57, P = .04; RR 0.87 P = .41). The probabilities of survival after dUCB-TCF, dUCB-other RIC, and 8 of 8 PBPC and 7 of 8 PBPC transplantations were 38%, 19%, 44%, and 37%, respectively. With similar survival after 8 of 8, 7 of 8 matched PBPCs, and dUCB-TCF, these data support use of dUCB-TCF transplantation in adults with acute leukemia who may benefit from RIC transplantation urgently or lack a 7-8 of 8 unrelated donor. PMID:22496153

  7. Insulin-like growth factor-binding protein-2 levels in pediatric patients with growth hormone deficiency, eating disorders and acute lymphoblastic leukemia.

    PubMed

    Barrios, V; Buño, M; Pozo, J; Muñoz, M T; Argente, J

    2000-01-01

    Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) is altered in different diseases and might be used as an indication of its severity. The aims of our study were to investigate: (1) the developmental pattern of the serum IGFBP-2 concentration at birth and during childhood and adolescence; (2) whether the serum IGFBP-2 level could be a marker for the diagnosis and evolution of diseases where the growth hormone (GH)-IGF axis is altered, and (3) whether this binding protein shows a relationship with IGF-I, its free fraction, IGFBP-1 and -3. We report reference values for 55 normal full-term newborns and 221 normal children who were divided into 5 groups according to their Tanner stage. Serum levels were higher in newborns when compared with Tanner stages I-V (p < 0.001, ANOVA), with no further changes throughout development. Furthermore, we studied IGFBP-2 levels in 24 children with congenital GH deficiency (GHD), 26 with acute lymphoblastic leukemia (ALL), 75 obese children, and 60 girls with anorexia nervosa (AN) at diagnosis and during a follow-up period. IGFBP-2 at diagnosis was increased in GHD, ALL and AN, and decreased in obesity (p < 0.05, ANOVA). During the follow-up, IGFBP-2 concentrations tended to normalize. IGFBP-2 correlated positively with IGFBP-1 and negatively with IGF-I and IGFBP-3 in normal subjects and at diagnosis of the pathologies studied. Although IGFBP-2 functions are not well understood, these results suggest a possible role for this protein in diseases where the GH-IGF axis is altered.

  8. Effects of acute and subchronic treatments with fluoxetine and desipramine on the memory of fear in moderate and high-intensity contextual conditioning.

    PubMed

    Santos, Julia M; Martinez, Raquel C R; Brandão, Marcus L

    2006-08-07

    Selective serotonin and noradrenalin reuptake inhibitors such as fluoxetine and desipramine, respectively, are efficacious in the treatment of depression and chronic stress. Although they inhibit the reuptake of the biogenic monoamines soon after administration, therapeutic improvements occur only after 2 or 3 weeks. Freezing response and potentiated startle are common responses to moderate fear contextual conditioning. However, freezing but not startle is increased in rats that undergo intense fear conditioning. In this study, we evaluated the effects of acute and subchronic administration of fluoxetine and desipramine on these responses in testing sessions, as indices of fear in moderate and high fear conditioning. Fluoxetine did not show any significant effect on the moderate fear conditioning but reduced freezing and restored the startle response in rats under intense fear conditioning. In comparison, desipramine had no effect on the startle response when administered acutely or subchronically while freezing of the intense fear conditioning was reduced. Our findings indicate that intense contextual fear conditioning is sensitive to subchronic treatment with fluoxetine and resistant to desipramine. Fluoxetine appears to restore the serotoninergic function in brain areas recruited by intense contextual fear conditioning. These effects of fluoxetine may underlie its reported efficacy in the pharmacotherapy of panic disorders.

  9. Extreme hypertriglyceridemia managed with insulin.

    PubMed

    Thuzar, Moe; Shenoy, Vasant V; Malabu, Usman H; Schrale, Ryan; Sangla, Kunwarjit S

    2014-01-01

    Extreme hypertriglyceridemia can lead to acute pancreatitis and rapid lowering of serum triglycerides (TG) is necessary for preventing such life-threatening complications. However, there is no established consensus on the acute management of extreme hypertriglyceridemia. We retrospectively reviewed 10 cases of extreme hypertriglyceridemia with mean serum TG on presentation of 101.5 ± 23.4 mmol/L (8982 ± 2070 mg/dL) managed with insulin. Serum TG decreased by 87 ± 4% in 24 hours in those patients managed with intravenous insulin and fasting and 40 ± 8.4% in those managed with intravenous insulin alone (P = .0003). The clinical course was uncomplicated in all except 1 patient who subsequently developed a pancreatic pseudocyst. Thus, combination of intravenous insulin with fasting appears to be an effective, simple, and safe treatment strategy in immediate management of extreme hypertriglyceridemia.

  10. Insulin allergy.

    PubMed

    Ghazavi, Mohammad K; Johnston, Graham A

    2011-01-01

    Insulin reactions occur rarely but are of tremendous clinical importance. The first was reported in 1922 as a callus reaction at the injection site of insufficiently purified bovine insulin. Porcine insulin was subsequently found to be less allergenic than bovine insulin. Increasingly pure insulins have decreased the risk of adverse reactions, and the production of recombinant insulin with the same amino sequence as human insulin saw a large decrease in adverse reactions. Currently, the prevalence of allergic reactions to insulin products appears to be approximately 2%, and less than one-third of these events have been considered related to the insulin itself. Other reactions occur due to the preservatives added to insulin, including zinc, protamine, and meta-cresol. Allergic reactions can be type I or immunoglobulin E-mediated, type III or Arthus, and type IV or delayed-type hypersensitivity reactions. Type I reactions are the most common and can, rarely, cause anaphylaxis. In contrast, type IV reactions can occur after a delay of several days. Investigations include skin prick testing, patch testing, intradermal testing, and occasionally, skin biopsy.

  11. Potential for the Australian and New Zealand paediatric intensive care registry to enhance acute flaccid paralysis surveillance in Australia: a data-linkage study

    PubMed Central

    2013-01-01

    Background Australia uses acute flaccid paralysis (AFP) surveillance to monitor its polio-free status. The World Health Organization criterion for a sensitive AFP surveillance system is the annual detection of at least one non-polio AFP case per 100,000 children aged less than 15 years, a target Australia has not consistently achieved. Children exhibiting AFP are likely to be hospitalised and may be admitted to an intensive care unit. This provides a potential opportunity for active AFP surveillance. Methods A data-linkage study for the period from 1 January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by the Polio Expert Panel with 880 acute neurological presentations potentially compatible with AFP documented in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry. Results Forty-two (25%) AFP cases classified by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of these, nineteen (45%) cases were classified as Guillain-Barré syndrome on both registries. Ten additional Guillain-Barré syndrome cases recorded in the ANZPIC Registry were not notified to the national AFP surveillance system. Conclusions The identification of a further ten AFP cases supports inclusion of intensive care units in national AFP surveillance, particularly specialist paediatric intensive care units, to identify AFP cases that may not otherwise be reported to the national surveillance system. PMID:23964831

  12. A cross-over study of the acute effects of espresso coffee on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus.

    PubMed

    Krebs, Jeremy D; Parry-Strong, Amber; Weatherall, Mark; Carroll, Richard W; Downie, Michelle

    2012-09-01

    The objective was to determine the effect of a single dose of espresso caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus. Eighteen participants who were habitual coffee drinkers, were studied using a random-order cross-over design. After a fasting blood sample participants consumed either a double-shot black espresso coffee, decaffeinated coffee, or hot water. The main outcomes were area under the curve (AUC) glucose and insulin, and insulin sensitivity (Matsuda index) during a 75 g oral glucose tolerance test (OGTT) performed one hour later. Other outcomes were change in glucose and insulin and also the insulinogenic index (IGI) and disposition index (DI). AUC glucose was marginally different between beverages (P=.06) being greater following caffeinated coffee than water, mean difference 104 mmol/L/180 min (95% CI 0.1 to 198.1, P=.031), or decaffeinated coffee, mean difference 92.1 mmol/L/180 min (95% CI -1.9 to 186.1, P=.055). There was no difference in AUC insulin (P=.87) or insulin sensitivity (P=.47), nor in change in glucose or insulin over the hour following beverage consumption. There was a marginal difference in IGI between beverages (P=.097) with coffee having a lower incremental increase in insulin/glucose than water (P=.037) though no difference between coffee and decaffeinated coffee (P=.54) and no difference in DI (P=.23). Black espresso coffee in people with type 2 diabetes mellitus results in a marginally greater excursion of glucose during a following OGTT compared with water or decaffeinated coffee. This effect does not appear to be mediated by changes in insulin sensitivity.

  13. Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men.

    PubMed

    Chennaoui, Mounir; Drogou, Catherine; Sauvet, Fabien; Gomez-Merino, Danielle; Scofield, Denis E; Nindl, Bradley C

    2014-01-01

    Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (P<0.01 respectively), as well as TLR-4 (P<0.05), while IL-6 mRNA levels remained unchanged. Circulating concentrations of free IGF-I were decreased at D4 (P<0.001). One night of recovery was sufficient to restore basal expression levels for TNF-α, sTNF-R1, TLR-4 and circulating IGF-I. Changes in TLR-4 mRNA levels during the protocol correlated positively with those of TNF-α and sTNF-R1 (r=0.393 and r=0.490 respectively), and negatively with circulating free IGF-I (r=-0.494). In conclusion, 25 h of sleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.

  14. Insulin-Dependent Regulation of Insulin Receptor Concentrations: A Direct Demonstration in Cell Culture

    PubMed Central

    Gavin, James R.; Roth, Jesse; Neville, David M.; De Meyts, Pierre; Buell, Donald N.

    1974-01-01

    Chronic (5-16 hr) exposure of cultured human lymphocytes to 10-8 M insulin at 37° in vitro produced a decrease in insulin receptor concentrations unaccounted for by simple occupancy of sites; acute exposure (0-2 hr) was without effect. These results reproduced observations in vivo where chronic hyperinsulinemia (e.g., 10-8 M insulin in the circulation of obese insulinresistant hyperglycemic mice) is associated with a substantial reduction in the concentration of insulin receptors per cell, while acute hyperinsulinemia in vivo has no effect on receptor concentration. These data suggest a reciprocal relationship between insulin in the extracellular fluid and the concentration of insulin receptors per cell, which is mediated at the target cell itself by intracellular insulin-sensitive regulatory processes and directly affects target-cell sensitivity to hormone. PMID:4359334

  15. Acute effect of 3β-hidroxihop-22(29)ene on insulin secretion is mediated by GLP-1, potassium and calcium channels for the glucose homeostasis.

    PubMed

    Castro, Allisson Jhonatan Gomes; Cazarolli, Luisa Helena; de Carvalho, Francieli Kanumfre; da Luz, Gabrielle; Altenhofen, Delsi; dos Santos, Adair Roberto Soares; Pizzolatti, Moacir Geraldo; Silva, Fátima Regina Mena Barreto

    2015-06-01

    The effect of 3β-hidroxihop-22(29)ene (3-BHO) on insulin and glucagon-like peptide 1 (GLP-1) secretion as well as the mechanism of action of the compound in pancreatic islet on glucose homeostasis was investigated. The data from in vivo treatment show that 3-BHO significantly reduces the hyperglycemia by increasing the insulin and GLP-1 secretion, as well as by accumulating hepatic glycogen in hyperglycemic rats. In rat pancreatic β-cell, 3-BHO stimulates the glucose uptake, insulin vesicles translocation to the plasma membrane and thus the insulin secretion through the involvement of potassium channels (ATP- and Ca(2+)-dependent K(+) channels) and calcium channels (L-type voltage-dependent calcium channels (L-VDCC)). Furthermore, this study also provides evidence for a crosstalk between intracellular high calcium concentration, PKA and PKC in the signal transduction of 3-BHO to stimulate insulin secretion. In conclusion, 3-BHO diminishes glycaemia, stimulates GLP-1 secretion and potentiates insulin secretion and increase hepatic glycogen content. Moreover, this triterpene modulates calcium influx characterizing ATP-K(+), Ca(2+)-K(+) and L-VDCC channels-dependent pathways as well as PKA and PKC activity in pancreatic islets underlying the signaling of 3-BHO for the secretory activity and contribution on glucose homeostasis.

  16. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

    PubMed Central

    Ringdén, Olle; Shrestha, Smriti; da Silva, Gisela Tunes; Zhang, Mei-Jie; Dispenzieri, Angela; Remberger, Mats; Kamble, Rammurti; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Gupta, Vikas; Holmberg, Leona; Lazarus, Hillard; McCarthy, Philip; Meehan, Kenneth; Schouten, Harry; Milone, Gustavo A.; Lonial, Sagar; Hari, Parameswaran N

    2011-01-01

    We evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on relapse and survival after allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma (MM) using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005 following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (grades I–IV) was 42% (95% confidence interval (CI) 35 – 49%) and of chronic GVHD at five years was 59% (95% CI 49 – 69%), with 70% developing extensive chronic GVHD. In multivariate analysis, acute GVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42; p=0.016), whereas limited chronic GVHD significantly decreased the risk of myeloma relapse (RR=0.35, p=0.035) and was associated with superior event-free survival (RR=0.40, p=0.027). Acute GVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52; p=0.001). The reduction in relapse risk associated with chronic GVHD is consistent with a beneficial graft-versus-myeloma effect, but this did not translate into a survival advantage. PMID:21946381

  17. Acute administration of high doses of taurine does not substantially improve high-intensity running performance and the effect on maximal accumulated oxygen deficit is unclear.

    PubMed

    Milioni, Fabio; Malta, Elvis de Souza; Rocha, Leandro George Spinola do Amaral; Mesquita, Camila Angélica Asahi; de Freitas, Ellen Cristini; Zagatto, Alessandro Moura

    2016-05-01

    The aim of the present study was to investigate the effects of acute administration of taurine overload on time to exhaustion (TTE) of high-intensity running performance and alternative maximal accumulated oxygen deficit (MAODALT). The study design was a randomized, placebo-controlled, crossover design. Seventeen healthy male volunteers (age: 25 ± 6 years; maximal oxygen uptake: 50.5 ± 7.6 mL·kg(-1)·min(-1)) performed an incremental treadmill-running test until voluntary exhaustion to determine maximal oxygen uptake and exercise intensity at maximal oxygen uptake. Subsequently, participants completed randomly 2 bouts of supramaximal treadmill-running at 110% exercise intensity at maximal oxygen uptake until exhaustion (placebo (6 g dextrose) or taurine (6 g) supplementation), separated by 1 week. MAODALT was determined using a single supramaximal effort by summating the contribution of the phosphagen and glycolytic pathways. When comparing the results of the supramaximal trials (i.e., placebo and taurine conditions) no differences were observed for high-intensity running TTE (237.70 ± 66.00 and 277.30 ± 40.64 s; p = 0.44) and MAODALT (55.77 ± 8.22 and 55.06 ± 7.89 mL·kg(-1); p = 0.61), which seem to indicate trivial and unclear differences using the magnitude-based inferences approach, respectively. In conclusion, acute 6 g taurine supplementation before exercise did not substantially improve high-intensity running performance and showed an unclear effect on MAODALT.

  18. Inflammatory cytokine kinetics to single bouts of acute moderate and intense aerobic exercise in women with active and inactive systemic lupus erythematosus.

    PubMed

    Perandini, L A; Sales-de-Oliveira, D; Mello, Sbv; Camara, N O; Benatti, F B; Lima, F R; Borba, E; Bonfa, E; Roschel, H; Sá-Pinto, A L; Gualano, B

    2015-01-01

    The aim of this study was to evaluate changes in the cytokines INF-γ, IL-10, IL-6, TNF-α and soluble TNF receptors (sTNFR1 and sTNFR2) in response to single bouts of acute moderate and intense exercise in systemic lupus erythematosus women with active (SLE(ACTIVE)) and inactive (SLE(INACTIVE)) disease. Twelve SLE(INACTIVE) women (age: 35.3 ± 5.7 yrs; BMI: 25.6±3.4 kg/m2), eleven SLE(ACTIVE) women (age: 30.4 ± 4.5 yrs; BMI: 26.1±4.8 kg/m2), and 10 age- and BMI-matched healthy control women (HC) performed 30 minutes of acute moderate (~50% of VO(2)peak) and intense (~70% of VO(2)peak) exercise bout. Cytokines and soluble TNF receptors were assessed at baseline, immediately after, every 30 minutes up to three hours, and 24 hours after both acute exercise bouts. In response to acute moderate exercise, cytokines and soluble TNF receptors levels remained unchanged in all groups (P>0.05), except for a reduction in IL-6 levels in the SLE(ACTIVE) group at the 60th and 180th minutes of recovery (P<0.05), and a reduction in sTNFR1 levels in the HC group at the 90th, 120th, 150th, 180th minutes of recovery (P<0.05). The SLE(INACTIVE) group showed higher levels of TNF-α, sTNFR1, and sTNFR2 at all time points when compared with the HC group (P<0.05). Also, the SLE(ACTIVE) group showed higher levels of IL-6 at the 60th minute of recovery (P<0.05) when compared with the HC group. After intense exercise, sTNFR1 levels were reduced at the 150th (P=0.041) and 180th (P=0.034) minutes of recovery in the SLE(INACTIVE) group, whereas the other cytokines and sTNFR2 levels remained unchanged (P>0.05). In the HC group, IL-10, TNF-α, sTNFR1, and sTNFR2 levels did not change, whilst INF-γ levels decreased (P=0.05) and IL-6 levels increased immediately after the exercise (P=0.028), returning to baseline levels 24 hours later (P > 0.05). When compared with the HC group, the SLE(INACTIVE) group showed higher levels of TNF-α and sTNFR2 in all time points, and higher levels of sTNFR1 at

  19. Early use of insulin in type 2 diabetes.

    PubMed

    Eldor, Roy; Stern, Erwin; Milicevic, Zvonko; Raz, Itamar

    2005-06-01

    Type 2 diabetes is a disease characterised by peripheral insulin resistance, as well as by pancreatic beta cell dysfunction. This process is in part due to elevated blood glucose and free fatty acids--termed glucolipotoxicity. The traditional pathway of treating type 2 diabetes in a stepwise manner, beginning with life style modifications and continuing with oral hypoglycaemic agents leads to a protracted period of unnecessary hyperglycaemia. A new approach, targeted at alleviating the deleterious effects of hyperglycaemia and elevated free fatty acids by acutely lowering both with intensive insulin therapy, has yielded prolonged remissions in therapy in which only diet was necessary to maintain normoglycaemia. This new approach, its rationale, benefits and misgivings are discussed in this review.

  20. 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

  1. Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance

    PubMed Central

    Lin, Po-Ju; Borer, Katarina T.

    2016-01-01

    Background Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states. Methods Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR). Results The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia. Conclusions Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals

  2. 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.

  3. 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.

  4. Reactive oxygen species levels and DNA fragmentation on astrocytes in primary culture after acute exposure to low intensity microwave electromagnetic field.

    PubMed

    Campisi, Agata; Gulino, Marisa; Acquaviva, Rosaria; Bellia, Paolo; Raciti, Giuseppina; Grasso, Rosaria; Musumeci, Francesco; Vanella, Angelo; Triglia, Antonio

    2010-03-31

    The exposure of primary rat neocortical astroglial cell cultures to acute electromagnetic fields (EMF) in the microwave range was studied. Differentiated astroglial cell cultures at 14 days in vitro were exposed for 5, 10, or 20min to either 900MHz continuous waves or 900MHz waves modulated in amplitude at 50Hz using a sinusoidal waveform and 100% modulation index. The strength of the electric field (rms value) at the sample position was 10V/m. No change in cellular viability evaluated by MTT test and lactate dehydrogenase release was observed. A significant increase in ROS levels and DNA fragmentation was found only after exposure of the astrocytes to modulated EMF for 20min. No evident effects were detected when shorter time intervals or continuous waves were used. The irradiation conditions allowed the exclusion of any possible thermal effect. Our data demonstrate, for the first time, that even acute exposure to low intensity EMF induces ROS production and DNA fragmentation in astrocytes in primary cultures, which also represent the principal target of modulated EMF. Our findings also suggest the hypothesis that the effects could be due to hyperstimulation of the glutamate receptors, which play a crucial role in acute and chronic brain damage. Furthermore, the results show the importance of the amplitude modulation in the interaction between EMF and neocortical astrocytes.

  5. 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

  6. 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

  7. Examining Factors That Impact Inpatient Management of Diabetes and the Role of Insulin Pen Devices.

    PubMed

    Smallwood, Chelsea; Lamarche, Danièle; Chevrier, Annie

    2017-02-01

    Insulin administration in the acute care setting is an integral component of inpatient diabetes management. Although some institutions have moved to insulin pen devices, many acute care settings continue to employ the vial and syringe method of insulin administration. The aim of this study was to evaluate the impact of insulin pen implementation in the acute care setting on patients, healthcare workers and health resource utilization. A review of published literature, including guidelines, was conducted to identify how insulin pen devices in the acute care setting may impact inpatient diabetes management. Previously published studies have revealed that insulin pen devices have the potential to improve inpatient management through better glycemic control, increased adherence and improved self-management education. Furthermore, insulin pen devices may result in cost savings and improved safety for healthcare workers. There are benefits to the use of insulin pen devices in acute care and, as such, their implementation should be considered.

  8. Acute lung injury and acute respiratory distress syndrome requiring tracheal intubation and mechanical ventilation in the intensive care unit: impact on managing uncertainty for patient-centered communication.

    PubMed

    Johnson, Robert F; Gustin, Jillian

    2013-09-01

    A case of acute lung injury (ALI) progressing to acute respiratory distress syndrome (ARDS) requiring tracheal intubation and mechanical ventilation (ETMV) is presented. The palliative medicine service was asked to address concerns expressed by the patient's spouse reflecting uncertainty regarding outcome expectations. Acknowledging and confronting the uncertainties of a critical illness is an essential component of patient-centered communication. Addressing and managing uncertainty for the case scenario requires consideration of both short- and long-term outcomes including mortality, ventilator independence, and adverse effects on quality of life for survivors. In this paper, ALI/ARDS requiring ETMV in the ICU was used as a focal point for preparing a prognostic assessment incorporating these issues. This assessment was based on a review of recently published literature regarding mortality and ventilator independence of survivors for adult patients receiving ETMV for ALI/ARDS in the ICU. In the studies reviewed, long-term survival reported at 60 days to 1 year was 50-73% with greater than 84% of the survivors in each study breathing independently. Selected articles discussing outcomes other than mortality or recovery of respiratory function, particularly quality of life implications for ALI/ARDS survivors, were also reviewed. A case of of ALI/ARDS requiring ETMV in the ICU is used to illustrate the situation of an incapacitated critically ill patient where the outcome is uncertain. Patient-centered communication should acknowledge and address this uncertainty. Managing uncertainty consists of effectively expressing a carefully formulated prognostic assessment and using sound communication principles to alleviate the distress associated with the uncertain outcome probabilities.

  9. 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...

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

    ClinicalTrials.gov

    2017-01-25

    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

  11. Chronic and acute inspiratory muscle loading augment the effect of a 6-week interval program on tolerance of high-intensity intermittent bouts of running.

    PubMed

    Tong, Tom K; Fu, Frank H; Eston, Roger; Chung, Pak-Kwong; Quach, Binh; Lu, Kui

    2010-11-01

    This study examined the hypothesis that chronic (training) and acute (warm-up) loaded ventilatory activities applied to the inspiratory muscles (IM) in an integrated manner would augment the training volume of an interval running program. This in turn would result in additional improvement in the maximum performance of the Yo-Yo intermittent recovery test in comparison with interval training alone. Eighteen male nonprofessional athletes were allocated to either an inspiratory muscle loading (IML) group or control group. Both groups participated in a 6-week interval running program consisting of 3-4 workouts (1-3 sets of various repetitions of selected distance [100-2,400 m] per workout) per week. For the IML group, 4-week IM training (30 inspiratory efforts at 50% maximal static inspiratory pressure [P0] per set, 2 sets·d-1, 6 d·wk-1) was applied before the interval program. Specific IM warm-up (2 sets of 30 inspiratory efforts at 40% P0) was performed before each workout of the program. For the control group, neither IML was applied. In comparison with the control group, the interval training volume as indicated by the repeatability of running bouts at high intensity was approximately 27% greater in the IML group. Greater increase in the maximum performance of the Yo-Yo test (control: 16.9 ± 5.5%; IML: 30.7 ± 4.7% baseline value) was also observed after training. The enhanced exercise performance was partly attributable to the greater reductions in the sensation of breathlessness and whole-body metabolic stress during the Yo-Yo test. These findings show that the combination of chronic and acute IML into a high-intensity interval running program is a beneficial training strategy for enhancing the tolerance to high-intensity intermittent bouts of running.

  12. 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

  13. The evaluation of sequential platelet counts has prognostic value for acute kidney injury patients requiring dialysis in the intensive care setting

    PubMed Central

    Valente, Carla; Soares, Márcio; Rocha, Eduardo; Cardoso, Lucio; Maccariello, Elizabeth

    2013-01-01

    OBJECTIVE: To evaluate the prognostic value of platelet counts in acute kidney injury patients requiring renal replacement therapy. METHODS: This prospective cohort study was performed in three tertiary-care hospitals. Platelet counts were obtained upon admission to the intensive care unit and during the first week of renal replacement therapy on days 1, 3, 5 and 7. The outcome of interest was the hospital mortality rate. With the aim of minimizing individual variation, we analyzed the relative platelet counts on days 3, 5, 7 and at the point of the largest variation during the first week of renal replacement therapy. Logistic regression analysis was used to test the prognostic value of the platelet counts. RESULTS: The study included 274 patients. The hospital mortality rate was 62%. The survivors had significantly higher platelet counts upon admission to the intensive care unit compared to the non-survivors [175.5×103/mm3 (108.5–259×103/mm3) vs. 148×103/mm3 (80−141×103/mm3)] and during the first week of renal replacement therapy. The relative platelet count reductions were significantly associated with a higher hospital mortality rate compared with the platelet count increases (70% vs. 44% at the nadir, respectively). A relative platelet count reduction >60% was significantly associated with a worse outcome (mortality rate = 82.6%). Relative platelet count variations and the percentage of reduction were independent risk factors of hospital mortality during the first week of renal replacement therapy. CONCLUSION: Platelet counts upon admission to the intensive care unit and at the beginning of renal replacement therapy as well as sequential platelet count evaluation have prognostic value in acute kidney injury patients requiring renal replacement therapy. PMID:23778497

  14. Nitrosative stress and pathogenesis of insulin resistance.

    PubMed

    Kaneki, Masao; Shimizu, Nobuyuki; Yamada, Daisuke; Chang, Kyungho

    2007-03-01

    Insulin resistance is a major causative factor for type 2 diabetes and is associated with increased risk of cardiovascular disease. Despite intense investigation for a number of years, molecular mechanisms underlying insulin resistance remain to be determined. Recently, chronic inflammation has been highlighted as a culprit for obesity-induced insulin resistance. Nonetheless, upstream regulators and downstream effectors of chronic inflammation in insulin resistance remain unclarified. Inducible nitric oxide synthase (iNOS), a mediator of inflammation, has emerged as an important player in insulin resistance. Obesity is associated with increased iNOS expression in insulin-sensitive tissues in rodents and humans. Inhibition of iNOS ameliorates obesity-induced insulin resistance. However, molecular mechanisms by which iNOS mediates insulin resistance remain largely unknown. Protein S-nitrosylation, a covalent attachment of NO moiety to thiol sulfhydryls, has emerged as a major mediator of a broad array of NO actions. S-nitrosylation is elevated in patients with type 2 diabetes, and increased S-nitrosylation of insulin signaling molecules, including insulin receptor, insulin receptor substrate-1, and Akt/PKB, has been shown in skeletal muscle of obese, diabetic mice. Akt/PKB is reversibly inactivated by S-nitrosylation. Based on these findings, S-nitrosylation has recently been proposed to play an important role in the pathogenesis of insulin resistance.

  15. Comparison of Reduced-Intensity and Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: A Meta-Analysis

    PubMed Central

    Ismail, Nor-Azimah; Mohd-Idris, Mohd-Razif; Jamaluddin, Fariza Wan; Tumian, NorRafeah; Sze-Wei, Ernie Yap; Muhammad, Norasiah; Nai, Ming Lai

    2014-01-01

    Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2–6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2–6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT. PMID:25072307

  16. APACHE III Outcome Prediction in Patients Admitted to the Intensive Care Unit with Sepsis Associated Acute Lung Injury

    PubMed Central

    Chen, Lin

    2015-01-01

    Background and objective Acute Physiology and Chronic Health Evaluation (APACHE) III score has been widely used for prediction of clinical outcomes in mixed critically ill patients. However, it has not been validated in patients with sepsis-associated acute lung injury (ALI). The aim of the study was to explore the calibration and predictive value of APACHE III in patients with sepsis-associated ALI. Method The study was a secondary analysis of a prospective randomized controlled trial investigating the efficacy of rosuvastatin in sepsis-associated ALI (Statins for Acutely Injured Lungs from Sepsis, SAILS). The study population was sepsis-related ALI patients. The primary outcome of the current study was the same as in the original trial, 60-day in-hospital mortality, defined as death before hospital discharge, censored 60 days after enrollment. Discrimination of APACHE III was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with its 95% CI. Hosmer-Lemeshow goodness-of-fit statistic was used to assess the calibration of APACHE III. The Brier score was reported to represent the overall performance of APACHE III in predicting outcome. Main results A total of 745 patients were included in the study, including 540 survivors and 205 non-survivors. Non-survivors were significantly older than survivors (59.71±16.17 vs 52.00±15.92 years, p<0.001). The primary causes of ALI were also different between survivors and non-survivors (p = 0.017). Survivors were more likely to have the cause of sepsis than non-survivors (21.2% vs. 15.1%). APACHE III score was higher in non-survivors than in survivors (106.72±27.30 vs. 88.42±26.86; p<0.001). Discrimination of APACHE III to predict mortality in ALI patients was moderate with an AUC of 0.68 (95% confidence interval: 0.64–0.73). Conclusion this study for the first time validated the discrimination of APACHE III in sepsis associated ALI patients. The result shows that APACHE III

  17. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin.

    PubMed

    Reiter, Chad E N; Wu, Xiaohua; Sandirasegarane, Lakshman; Nakamura, Makoto; Gilbert, Kirk A; Singh, Ravi S J; Fort, Patrice E; Antonetti, David A; Gardner, Thomas W

    2006-04-01

    Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

  18. Insulin Lispro Injection

    MedlinePlus

    ... unless it is used in an external insulin pump. In patients with type 2 diabetes, insulin lispro ... also can be used with an external insulin pump. Before using insulin lispro in a pump system, ...

  19. Understanding the continuous renal replacement therapy circuit for acute renal failure support: a quality issue in the intensive care unit.

    PubMed

    Boyle, Martin; Baldwin, Ian

    2010-01-01

    Delivery of renal replacement therapy is now a core competency of intensive care nursing. The safe and effective delivery of this form of therapy is a quality issue for intensive care, requiring an understanding of the principles underlying therapy and the functioning of machines used. Continuous hemofiltration, first described in 1977, used a system where blood flowed from arterial to venous cannulas through a small-volume, low-resistance, and high-flux filter. Monitoring of these early systems was limited, and without a machine interface, less nursing expertise was required. Current continuous renal replacement therapy machines offer user-friendly interfaces, cassette-style circuits, and comprehensive circuit diagnostics and monitoring. Although these machines conceal complexity behind a user-friendly interface, it remains important that nurses have sufficient knowledge for their use and the ability to compare and contrast circuit setups and functions for optimal and efficient treatment.

  20. 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

  1. 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.

  2. Predicting changes in high-intensity intermittent running performance with acute responses to short jump rope workouts in children.

    PubMed

    Buchheit, Martin; Rabbani, Alireza; Beigi, Hamid Taghi

    2014-09-01

    The aims of the present study were to 1) examine whether individual HR and RPE responses to a jump rope workout could be used to predict changes in high-intensity intermittent running performance in young athletes, and 2) examine the effect of using different methods to determine a smallest worthwhile change (SWC) on the interpretation of group-average and individual changes in the variables. Before and after an 8-week high-intensity training program, 13 children athletes (10.6 ± 0.9 yr) performed a high-intensity running test (30-15 Intermittent Fitness Test, VIFT) and three jump rope workouts, where HR and RPE were collected. The SWC was defined as either 1/5(th) of the between-subjects standard deviation or the variable typical error (CV). After training, the large ~9% improvement in VIFT was very likely, irrespective of the SWC. Standardized changes were greater for RPE (very likely-to-almost certain, ~30-60% changes, ~4-16 times >SWC) than for HR (likely-to-very likely, ~2-6% changes, ~1-6 times >SWC) responses. Using the CV as the SWC lead to the smallest and greatest changes for HR and RPE, respectively. The predictive value for individual performance changes tended to be better for HR (74-92%) than RPE (69%), and greater when using the CV as the SWC. The predictive value for no-performance change was low for both measures (<26%). Substantial decreases in HR and RPE responses to short jump rope workouts can predict substantial improvements in high-intensity running performance at the individual level. Using the CV of test measures as the SWC might be the better option. Key pointsDecreased HR and RPE responses to short jump rope workouts can be confidently used to track improvements in high-intensity intermittent running performance in children familiarized with this exercise mode. Rope jumping is a particularly convenient exercise, since it can be performed in a restricted space and allows the testing of a large number of athletes simultaneously

  3. 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.

  4. 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.

  5. Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

    PubMed Central

    2012-01-01

    Background Our purpose was to report acute gastrointestinal (GI) and genitourinary (GU) toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT) with a daily endorectal water-filled balloon (ERBH2O), and assess associations with planning parameters and pretreatment clinical characteristics. Methods The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERBH2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0) were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Results Mean age was 68 (range 51–88). Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV) rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps < 0.05). Maximum acute GU toxicity was grade 0, 1, and 2 for 17%, 41%, and 42% of patients, respectively. Infield bladder V20 (P = 0.03) and pretreatment International Prostate Symptom Scale (IPSS) (P = 0.003) were associated with grade 2 GU toxicity. Conclusion Prostate IG-IMRT using a daily ERBH2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities. PMID:22621764

  6. Characterization of acute graft-versus-host disease following reduced-intensity stem-cell transplantation from an HLA-identical related donor.

    PubMed

    Murashige, Naoko; Kami, Masahiro; Mori, Shin-ichiro; Katayama, Yuta; Kobayashi, Kazuhiko; Onishi, Yasushi; Hori, Akiko; Kishi, Yukiko; Hamaki, Tamae; Tajima, Kinuko; Kanda, Yoshinobu; Tanosaki, Ryuji; Takaue, Yoichi

    2008-08-01

    To investigate clinical features of acute graft-versus-host disease (GVHD) following reduced intensity stem-cell transplantation (RIST), we retrospectively investigated medical records of 65 patients with hematologic malignancies who underwent RIST from a matched related donor. Preparative regimen comprised fludarabine 30 mg/m(2) (n = 53) or cladribine 0.11 mg/kg (n = 12) for 6 days plus busulfan 4 mg/kg for 2 days. Twelve patients received rabbit antithymocyte globulin 2.5 mg/kg/day for 2-4 consecutive days. Grade II to IV acute GVHD was diagnosed in 36 patients (55%). Its median onset was day 58 (range, 17-109), while it was bimodal, peaking day 15-29 (early-onset GVHD, n = 18) and day 75-89 days (late-onset GVHD, n = 18). Variables that were more common in early-onset GVHD than late-onset GVHD included skin rash (89% vs. 61%) and noninfectious fevers (33% vs. 11%). Desaturation, pulmonary infiltrates and hyperbilirubinemia (>2.0 mg/dL) were more common in late-onset GVHD (6% vs. 22%, 0% vs. 17%, and 6% vs. 33%, respectively). All of the patients with early-onset GVHD given corticosteroid responded to it, while 5 of the 18 patients with late-onset GVHD failed to respond it. Patients with either early-onset or late-onset GVHD tended to have better progression-free survival (PFS) than those without it; however, there was no significant difference in PFS between patients with early-onset GVHD and those with late-onset GVHD. This study suggests that several etiologies might have contributed to the development of acute GVHD following RIST.

  7. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

    PubMed

    Kobayashi, Kazuhiko; Kami, Masahiro; Murashige, Naoko; Kusumi, Eiji; Kishi, Yukiko; Hamaki, Tamae; Hori, Akiko; Matsumura, Tomoko; Yuji, Koichiro; Masuo, Shigeru; Mori, Shinichiro; Miyakoshi, Shigesaburo; Tanosaki, Ryuji; Mitamura, Tadayuki; Takaue, Yoichi; Taniguchi, Shuichi

    2005-06-01

    The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

  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. 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

  10. Allogeneic stem cell transplantation after reduced-intensity conditioning for acute myeloid leukaemia: impact of chronic graft-versus-host disease.

    PubMed

    Valcárcel, David; Martino, Rodrigo; Piñana, Jose L; Sierra, Jorge

    2009-06-01

    The antineoplastic effect of allogeneic stem cell transplantation after reduced-intensity conditioning (RIC) relies on the graft-versus-tumour (GvT) reaction. GvT is closely linked to the development of graft-versus-host disease (GvHD). The incidence of acute GvHD after RIC seems lower than after myeloablative conditioning (MAC), whereas the incidence of chronic GvHD after RIC seems similar to after MAC. The results of RIC for acute myeloid leukaemia show a non-relapse mortality of approximately 15% at one year, a relapse incidence of approximately 40% after a median of 4-6 months, translating into overall and disease-free survival rates of 40-60%. The factors associated with improved outcome in most studies are the stage of the disease at transplantation, age and the development of chronic GvHD (and thus GvT). In a recent report, chronic GvHD was the most important factor associated with prolonged survival. Future efforts should be directed at aiming to decrease relapse rates. For this purpose, an adequate identification of high-risk patients, close monitoring of minimal residual disease after the procedure, and the use of antineoplastic drugs or immunotherapy may be of help.

  11. Outcome of patients with acute kidney injury in severe sepsis and septic shock treated with early goal-directed therapy in an intensive care unit.

    PubMed

    Ahmed, Wasim; Memon, Javed I; Rehmani, Rifat; Al Juhaiman, Abdulmajeed

    2014-05-01

    Acute kidney injury (AKI) in the intensive care unit (ICU) is commonly caused by severe sepsis and septic shock. There is limited data regarding the incidence and outcomes of patients developing AKI treated with early goal-directed therapy (EGDT). Our aim was to observe the incidence and outcomes of patients with AKI in severe sepsis and septic shock, treated with EGDT as compared with historic controls. Study subjects included all adults admitted to the ICU with a diagnosis of severe sepsis and septic shock prior to (historic controls) and after introduction of EGDT (intervention group). Two groups were compared for incidence of AKI, length of ICU and hospital stay, incidence and requirement for renal replacement therapy, serum creatinine at discharge, maximum RIFLE (Risk, injury, failure, loss, end stage) in each group and 28-day mortality. Two groups were well matched for age, sex, (April 16, 2014) and acute physiological and chronic health evaluation (APACHE) II scores. We found no significant difference in the incidence of AKI (51% vs. 46%). There was no statistical difference in any of the above outcomes, including 28-day mortality in historic controls versus patients treated with EGDT. Septic AKI is a complex syndrome. The incidence and outcomes have not improved despite advances in sepsis management and EGDT. Very early detection of septic AKI and targeted therapies may improve outcomes.

  12. 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.

  13. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes.

    PubMed

    Martino, Rodrigo; Caballero, María Dolores; Pérez-Simón, José Antonio; Simón, José Antonio Pérez; Canals, Carmen; Solano, Carlos; Urbano-Ispízua, Alvaro; Bargay, Joan; Léon, Angel; Sarrá, Josep; Sanz, Guillermo F; Moraleda, José María; Brunet, Salut; San Miguel, Jesús; Sierra, Jorge

    2002-09-15

    We report the results of a prospective study of a reduced-intensity conditioning (RIC) regimen followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling in 37 patients with acute myeloid leukemia (AML; n = 17) or myelodysplastic syndrome (MDS; n = 20). The median age was 57 years, and 22 (59%) were beyond the early phase of their disease. The incidence of grade II to IV acute graft-versus-host disease (GVHD) was 19% (5% grade III-IV), and the 1-year incidence of chronic extensive GVHD was 46%. With a median follow-up of 297 days (355 days in 24 survivors), the 1-year probability of transplant-related mortality was 5%, and the 1-year progression-free survival was 66%. The 1-year incidence of disease progression in patients with and without GVHD was 13% (95% CI, 4%-34%) and 58% (95% CI, 36%-96%), respectively (P =.008). These results suggest that a graft-versus-leukemia effect plays a crucial role in reducing the risk of relapse after a RIC allograft in AML and MDS.

  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. Sequential chemotherapy followed by reduced-intensity conditioning and allogeneic haematopoietic stem cell transplantation in adult patients with relapse or refractory acute myeloid leukaemia: a survey from the Acute Leukaemia Working Party of EBMT.

    PubMed

    Ringdén, Olle; Labopin, Myriam; Schmid, Christoph; Sadeghi, Behnam; Polge, Emmanuelle; Tischer, Johanna; Ganser, Arnold; Michallet, Mauricette; Kanz, Lothar; Schwerdtfeger, Rainer; Nagler, Arnon; Mohty, Mohamad

    2017-02-01

    This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%. The 3-year probability of non-relapse mortality (NRM) was 25·9%, that of relapse was 48·5%, that of GVHD-free and relapse-free survival (GRFS) was 17·8% and that of leukaemia-free survival (LFS) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II-IV [hazard ratio (HR) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti-T-cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti-T-cell antibodies seems promising in patients with refractory AML.

  16. The effect of stress-inducible extracellular Hsp72 on human neutrophil chemotaxis: a role during acute intense exercise.

    PubMed

    Ortega, Eduardo; Hinchado, M D; Martín-Cordero, L; Asea, A

    2009-05-01

    We studied the physiological role of the 72 kDa extracellular heat shock protein (Hsp72, a stress-inducible protein) in modulating neutrophil chemotaxis during a single bout of intense exercise performed by sedentary women, together with various cell mechanisms potentially involved in the modulation. For each volunteer, we evaluated neutrophil chemotaxis and serum Hsp72 concentration before and immediately after a single bout of exercise (1 h on a cycle ergometer at 70% VO(2) max), and 24 h later. Both parameters were found to be stimulated by the exercise, and had returned to basal values 24 h later. In vitro, there was a dose-dependent increase in chemotaxis when neutrophils were incubated both with physiological Hsp72 concentrations and with a 100 x greater concentration. The chemotaxis was greater when the neutrophils were incubated with the post-exercise Hsp72 concentration than with the basal concentration, suggesting a physiological role for this protein in the context of the stimulation of neutrophil chemotaxis by intense exercise. The 100 x Hsp72 concentration stimulated chemotaxis even more strongly. In addition, Hsp72 was found to have chemoattractant and chemokinetic effects on the neutrophils at physiological concentrations, with these effects being significantly greater with the post-exercise than with the basal Hsp72 concentration. The Hsp72-induced stimulation of neutrophil chemotaxis disappeared when the toll-like receptor 2 (TLR-2) was blocked, and phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and nuclear transcription factor kappa B (NF-kappaB) were also found to be involved in the signaling process. No changes were observed, however, in neutrophil intracellular calcium levels in response to Hsp72. In conclusion, physiological concentrations of the stress protein Hsp72 stimulate human neutrophil chemotaxis through TLR-2 with its cofactor CD14, involving ERK, NF-kappaB, and PI3K, but not iCa(2 + ), as

  17. 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.…

  18. 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.

  19. The Effect of an Electronic SBAR Communication Tool on Documentation of Acute Events in the Pediatric Intensive Care Unit.

    PubMed

    Panesar, Rahul S; Albert, Ben; Messina, Catherine; Parker, Margaret

    2016-01-01

    The Situation, Background, Assessment, Recommendation (SBAR) handoff tool is designed to improve communication. The effects of integrating an electronic medical record (EMR) with a SBAR template are unclear. The research team hypothesizes that an electronic SBAR template improves documentation and communication between nurses and physicians. In all, 84 patient events were recorded from 542 admissions to the pediatric intensive care unit. Three time periods were studied: (a) paper documentation only, (b) electronic documentation, and (c) electronic documentation with an SBAR template. Documentation quality was assessed using a 4-point scoring system. The frequency of event notes increased progressively during the 3 study periods. Mean quality scores improved significantly from paper documentation to EMR free-text notes and to electronic SBAR-template notes, as did nurse and attending physician notification. The implementation of an electronic SBAR note is associated with more complete documentation and increased frequency of documentation of communication among nurses and physicians.

  20. Intensity-dependent and sex-specific alterations in hepatic triglyceride metabolism in mice following acute exercise.

    PubMed

    Tuazon, Marc A; McConnell, Taylor R; Wilson, Gabriel J; Anthony, Tracy G; Henderson, Gregory C

    2015-01-01

    Precise regulation of hepatic triglyceride (TG) metabolism and secretion is critical for health, and exercise could play a significant role. We compared one session of high-intensity interval exercise (HIIE) vs. continuous exercise (CE) on hepatic TG metabolism. Female and male mice were assigned to CE, HIIE, or sedentary control (CON). HIIE was a 30-min session of 30-s running intervals (30 m/min) interspersed with 60-s walking periods (5 m/min). CE was a distance- and duration-matched run at 13.8 m/min. Hepatic content of TG and TG secretion rates, as well as expression of relevant genes/proteins, were measured at 3 h (day 1) and 28 h (day 2) postexercise. On day 1, hepatic [TG] in CE and HIIE were both elevated vs. CON in both sexes with an approximately twofold greater elevation in HIIE vs. CE in females. In both sexes, hepatic perilipin 2 (PLIN2) protein on day 1 was increased significantly by both exercise types with a significantly greater increase with HIIE than CE, whereas the increase in mRNA reached significance only after HIIE. On day 2 in both sexes the increases in hepatic TG and PLIN2 with exercise declined toward CON levels. Only HIIE on day 2 resulted in reduced hepatic TG secretion by ∼20% in females with no effect in males. Neither exercise modality altered AMPK signaling or microsomal triglyceride transfer protein expression. Females exhibited higher hepatic TG secretion than males in association with different expression levels of related metabolic enzymes. These intensity-dependent and sex-specific alterations following exercise may have implications for sex-based exercise prescription.

  1. 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 ...

  2. Incidence and outcome of osteonecrosis in children and adolescents after intensive therapy for acute lymphoblastic leukemia (ALL).

    PubMed

    Padhye, Bhavna; Dalla-Pozza, Luciano; Little, David; Munns, Craig

    2016-05-01

    Osteonecrosis (ON), a significant complication following treatment of acute lymphoblastic leukemia (ALL), has a profound impact on quality of life of ALL survivors. We studied incidence and outcome of ON in patients treated on or according to Australian and New Zealand Children's Haematology/ Oncology Group (ANZCHOG) study 8 at The Children's Hospital at Westmead. The study involved retrospective chart review of the patients. ON was defined by development of symptoms and confirmed by magnetic resonance imaging. From 2002-2011, 251 patients (143M, 108F, 59 Standard Risk (SR), 159 Medium Risk (MR) 5 High Risk (HR), and 28 Very high risk (VHR)) were treated according to study 8. Eighteen (7M, 11F, 2 SR, 12 MR, 4 VHR) patients developed ON (7.2%). Median age at diagnosis was 13.05 years(4.3-16.7). Incidence of ON in patients > 10 years at diagnosis was 29%. Six out of 18 patients developed ON after allogeneic stem cell transplantation. Median time from diagnosis to the development of ON following chemotherapy for ALL was 1.15 years (range 0.25-2.12). Most patients were treated with intravenous Zoledronic acid. At last follow-up, three patients had undergone arthroplasty, two patients were symptom free, and the remaining 13 patients reported persistent pain with activity. A majority of patients with ON of the hips had radiological progression. Overall, 7% of patients with ALL developed ON. Age >10 years was the most important risk factor. At last follow-up, 70% of patients had persistent symptoms. Although Zoledronic acid improved pain, most patients with ON of the hips had radiological progression.

  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. Acute effects of high-intensity intermittent training on kinematics and foot strike patterns in endurance runners.

    PubMed

    Latorre-Román, P Á; García Pinillos, F; Bujalance-Moreno, P; Soto-Hermoso, V M

    2016-08-11

    The main purpose of this study was to evaluate running kinematic characteristics and foot strike patterns (FSP) during early and late stages of actual and common high-intensity intermittent training (HIIT): 5 × 2000 m with 120-s recovery between runs. Thirteen healthy, elite, highly trained male endurance runners participated in this study. They each had a personal record in the half-marathon of 70 ± 2.24 min, and each had a minimum experience of 4 years of training and competition. Heart rate (HR) and rate of perceived exertion (RPE) were monitored during HIIT. High levels of exhaustion were reached by the athletes during HIIT (HRpeak: 174.30 bpm; RPE: 17.23). There was a significant increase of HRpeak and RPE during HIIT; nevertheless, time for each run remained unchanged. A within-protocol paired t-test (first vs. last run) revealed no significant changes (P ≥ 0.05) in kinematics variables and FSP variables during HIIT. There were no substantial changes on kinematics and FSP characteristics in endurance runners after fatigue induced by a HIIT. Only the minimum ankle alignment showed a significant change. The author suggests that these results might be due to both the high athletic level of participants and their experience in HIIT.

  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.

  6. Insulin Oedema in Newly Diagnosed Type 1 Diabetes Mellitus

    PubMed Central

    Çetinkaya, Semra; Yılmaz Ağladıoğlu, Sebahat; Peltek Kendirici, Havva Nur; Bilgili, Hatice; Yıldırım, Nurdan; Aycan, Zehra

    2010-01-01

    Despite the essential role of insulin in the management of patients with insulin deficiency, insulin use can lead to adverse effects such as hypoglycaemia and weight gain. Rarely, crucial fluid retention can occur with insulin therapy, resulting in an oedematous condition. Peripheral or generalised oedema is an extremely rare complication of insulin therapy in the absence of heart, liver or renal involvement. It has been reported in newly diagnosed type 1 diabetes, in poorly controlled type 2 diabetes following the initiation of insulin therapy, and in underweight patients on large doses of insulin. The oedema occurs shortly after the initiation of intensive insulin therapy. We describe two adolescent girls with newly diagnosed type 1 diabetes, who presented with oedema of the lower extremities approximately one week after the initiation of insulin treatment; other causes of oedema were excluded. Spontaneous recovery was observed in both patients. Conflict of interest:None declared. PMID:21274337

  7. Profile and outcome of patients with acute toxicity admitted in intensive care unit: Experiences from a major corporate hospital in urban India

    PubMed Central

    Singh, Omender; Javeri, Yash; Juneja, Deven; Gupta, Manish; Singh, Gurpreet; Dang, Rohit

    2011-01-01

    Background and Aim: There is scarcity of data from the Indian subcontinent regarding the profile and outcome of patients presenting with acute poisoning admitted to intensive care units (ICU). We undertook this retrospective analysis to assess the course and outcome of such patients admitted in an ICU of a tertiary care private hospital. Methods: We analyzed data from 138 patients admitted to ICU with acute poisoning between July 2006 and March 2009. Data regarding type of poisoning, time of presentation, reason for ICU admission, ICU course and outcome were obtained. Results: Seventy (50.7%) patients were males and majority (47.8%) of admissions were from age group 21 to 30 years. The most common agents were benzodiazepines, 41/138 (29.7%), followed by alcohol, 34/138 (24.63%) and opioids, 10/138 (7.2%). Thirty-two (23%) consumed two or more agents. Commonest mode of toxicity was suicidal (78.3%) and the route of exposure was mainly oral (97.8%). The highest incidence of toxicity was due to drugs (46.3%) followed by household agents (13%). Organ failure was present in 67 patients (48.5%). During their ICU course, dialysis was required in four, inotropic support in 14 and ventilator support in 13 patients. ICU mortality was 3/138 (2.8%). All deaths were due to aluminium phosphide poisoning. Conclusions: The present data give an insight into epidemiology of poisoning and represents a trend in urban India. The spectrum differs as we cater to urban middle and upper class. There is an increasing variety and complexity of toxins, with substance abuse attributing to significant number of cases. PMID:22013253

  8. Decreased nonrelapse mortality after unrelated cord blood transplantation for acute myeloid leukemia using reduced-intensity conditioning: a prospective phase II multicenter trial.

    PubMed

    Rio, Bernard; Chevret, Sylvie; Vigouroux, Stéphane; Chevallier, Patrice; Fürst, Sabine; Sirvent, Anne; Bay, Jacques-Olivier; Socié, Gérard; Ceballos, Patrice; Huynh, Anne; Cornillon, Jérôme; Françoise, Sylvie; Legrand, Faezeh; Yakoub-Agha, Ibrahim; Michel, Gérard; Maillard, Natacha; Margueritte, Geneviève; Maury, Sébastien; Uzunov, Madalina; Bulabois, Claude Eric; Michallet, Mauricette; Clement, Laurence; Dauriac, Charles; Bilger, Karin; Gluckman, Eliane; Ruggeri, Annalisa; Buzyn, Agnès; Nguyen, Stéphanie; Simon, Tabassome; Milpied, Nöel; Rocha, Vanderson

    2015-03-01

    A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m(2)). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 10(7)/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (<3.4 × 10(7)/kg; P = .001) were associated with increased NRM, and use of 2 or more induction courses to obtain CR1 was associated with increased relapse incidence (P = .04). Leukemia-free survival (LFS) at 2 years was 35%, and the only factor associated with decreased LFS was secondary AML (P = .04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high-risk AML. (EUDRACT 2006-005901-67).

  9. Increasing Patient Acceptance and Adherence Toward Insulin.

    PubMed

    Riddle, Matthew; Peters, Anne; Funnell, Martha

    2016-10-01

    Because of the progressive nature of type 2 diabetes mellitus (T2DM), the majority of patients will need insulin to achieve and maintain glycemic control. By maintaining glycemic control, patients will avoid acute osmotic symptoms of hyperglycemia, instability in plasma glucose (PG) over time, and prevent or delay the development of diabetes complications without adversely affecting quality of life. Despite recommendations for initiating insulin therapy, both patient and health system barriers stand in the way. To develop confidence in individualizing patient therapy and maximize outcomes for patients with T2DM, healthcare practitioners (HCPs) were updated on recommendations and clinical evidence supporting when to initiate insulin therapy, strategies for overcoming provider and patient barriers for initiating insulin therapy, and the safety and efficacy of current and emerging insulin therapy and delivery technology for patients with T2DM.

  10. [Insulin-like growth factor 1 and the key markers of proteolysis during the acute period of readaptation of the muscle atrophied as a result of unloading].

    PubMed

    Kachaeva, E V; Turtikova, O V; Leĭnsoo, T A; Shenkman, B S

    2010-01-01

    It has been shown that, after prolonged disuse, the accumulation of muscle mass and the recovery of soleus fibers volume are caused by water accumulation rather than protein synthesis intensification. At the same time, expression rate of the main markers of the activity of ubiquitin-proteasome system remained increased on the 3rd day of reloading and decreased to the control by the 7th day. Both the quantity of the insulin-like growth factor 1 and the number of satellite cells fused with muscle fibers and of myonuclei began to increase only on the 7th day of reloading. The data obtained evidenced a significant inertness of the postural muscle during its adaptation to the load (normal gravity) after prolonged disuse.

  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 Central

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

    2010-01-01

    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. PMID:20176121

  13. Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome.

    PubMed

    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

    2014-09-01

    Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation 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/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 10(6) CD34(+)/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P = .001), overall mortality (HR, 1.48; P = .008), and lower neutrophil (odds ratio [OR], .76; P = .03) and platelet (OR, .76; P = .03) recovery. PBPC from unrelated donors with CD34(+) dose < 6 × 10(6) CD34(+)/kg was also associated with higher nonrelapse (HR, 1.38; P = .02) and overall mortality (HR, 1.20; P = .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(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.

  14. 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 ...

  15. Predictive Performance of the Simplified Acute Physiology Score (SAPS) II and the Initial Sequential Organ Failure Assessment (SOFA) Score in Acutely Ill Intensive Care Patients: Post-Hoc Analyses of the SUP-ICU Inception Cohort Study

    PubMed Central

    Møller, Morten Hylander; Krag, Mette; Perner, Anders; Hjortrup, Peter Buhl

    2016-01-01

    Purpose Severity scores including the Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA) score are used in intensive care units (ICUs) to assess disease severity, predict mortality and in research. We aimed to assess the predictive performance of SAPS II and the initial SOFA score for in-hospital and 90-day mortality in a contemporary international cohort. Methods This was a post-hoc study of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) inception cohort study, which included acutely ill adults from ICUs across 11 countries (n = 1034). We compared the discrimination of SAPS II and initial SOFA scores, compared the discrimination of SAPS II in our cohort with the original cohort, assessed the calibration of SAPS II customised to our cohort, and compared the discrimination for 90-day mortality vs. in-hospital mortality for both scores. Discrimination was evaluated using areas under the receiver operating characteristics curves (AUROC). Calibration was evaluated using Hosmer-Lemeshow’s goodness-of-fit Ĉ-statistic. Results AUROC for in-hospital mortality was 0.80 (95% confidence interval (CI) 0.77–0.83) for SAPS II and 0.73 (95% CI 0.69–0.76) for initial SOFA score (P<0.001 for the comparison). Calibration of the customised SAPS II for predicting in-hospital mortality was adequate (P = 0.60). Discrimination of SAPS II was reduced compared with the original SAPS II validation sample (AUROC 0.80 vs. 0.86; P = 0.001). AUROC for 90-day mortality was 0.79 (95% CI 0.76–0.82; P = 0.74 for comparison with in-hospital mortality) for SAPS II and 0.71 (95% CI 0.68–0.75; P = 0.66 for comparison with in-hospital mortality) for the initial SOFA score. Conclusions The predictive performance of SAPS II was similar for in-hospital and 90-day mortality and superior to that of the initial SOFA score, but SAPS II’s performance has decreased over time. Use of a contemporary severity score with improved predictive

  16. 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

  17. Quantitative measurements of relative fluid-attenuated inversion recovery (FLAIR) signal intensities in acute stroke for the prediction of time from symptom onset

    PubMed Central

    Cheng, Bastian; Brinkmann, Mathias; Forkert, Nils D; Treszl, Andras; Ebinger, Martin; Köhrmann, Martin; Wu, Ona; Kang, Dong-Wha; Liebeskind, David S; Tourdias, Thomas; Singer, Oliver C; Christensen, Soren; Luby, Marie; Warach, Steven; Fiehler, Jens; Fiebach, Jochen B; Gerloff, Christian; Thomalla, Götz

    2013-01-01

    In acute stroke magnetic resonance imaging, a ‘mismatch' between visibility of an ischemic lesion on diffusion-weighted imaging (DWI) and missing corresponding parenchymal hyperintensities on fluid-attenuated inversion recovery (FLAIR) data sets was shown to identify patients with time from symptom onset ≤4.5 hours with high specificity. However, moderate sensitivity and suboptimal interpreter agreement are limitations of a visual rating of FLAIR lesion visibility. We tested refined image analysis methods in patients included in the previously published PREFLAIR study using refined visual analysis and quantitative measurements of relative FLAIR signal intensity (rSI) from a three-dimensional, segmented stroke lesion volume. A total of 399 patients were included. The rSI of FLAIR lesions showed a moderate correlation with time from symptom onset (r=0.382, P<0.001). A FLAIR rSI threshold of <1.0721 predicted symptom onset ≤4.5 hours with slightly increased specificity (0.85 versus 0.78) but also slightly decreased sensitivity (0.47 versus 0.58) as compared with visual analysis. Refined visual analysis differentiating between ‘subtle' and ‘obvious' FLAIR hyperintensities and classification and regression tree algorithms combining information from visual and quantitative analysis also did not improve diagnostic accuracy. Our results raise doubts whether the prediction of stroke onset time by visual image judgment can be improved by quantitative rSI measurements. PMID:23047272

  18. Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats.

    PubMed

    Jessen, Lene; Clegg, Deborah J; Bouman, Stephan D

    2010-01-01

    Insulin detemir is a novel human insulin analog that does not show the usual propensity for weight gain in diabetic patients. We speculated that this beneficial effect could be due to insulin detemir exerting stronger anorectic effects within the brain than other insulins. To study the central effects of regular human insulin and insulin detemir on food intake, the present study was undertaken. We used acute intracerebroventricular insulin injections to compare food intake and body weight in rats fed ad libitum. Contrary to previously published data, we found that neither regular human insulin (8 or 32 mU) nor insulin detemir (1,290 pmol) reduced food intake in this model. Melanotan-II was also injected intracerebroventricularly as a positive control, and significantly reduced food intake and body weight, suggesting that our intracerebroventricular model is able to show anorectic effects. A series of experiments was therefore conducted in which different set-ups were tested to investigate which factors would be required to produce the reported anorectic effect of intracerebroventricular insulin. Although we varied rat strain, stereotactic coordinates, formulations of insulin and vehicle, dose, volume, and time of injection, the anorectic effect of intracerebroventricular insulin could not be replicated. Therefore, we suggest that acute intracerebroventricularly injected insulin does not robustly inhibit food intake in rats. Based on our results, the acute intracerebroventricular injection procedure may not be a preferred method for studying the central anorectic effects of insulin in rats. Instead, administrations over time or locally in hypothalamic nuclei might be recommended.

  19. 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

  20. 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.

  1. Previtellogenic oocyte growth in salmon: relationships among body growth, plasma insulin-like growth factor-1, estradiol-17beta, follicle-stimulating hormone and expression of ovarian genes for insulin-like growth factors, steroidogenic-acute regulatory protein and receptors for gonadotropins, growth hormone, and somatolactin.

    PubMed

    Campbell, B; Dickey, J; Beckman, B; Young, G; Pierce, A; Fukada, H; Swanson, P

    2006-07-01

    Body growth during critical periods is known to be an important factor in determining the age of maturity and fecundity in fish. However, the endocrine mechanisms controlling oogenesis in fish and the effects of growth on this process are poorly understood. In this study interactions between the growth and reproductive systems were examined by monitoring changes in various components of the FSH-ovary axis, plasma insulin-like growth factor 1 (Igf1), and ovarian gene expression in relation to body and previtellogenic oocyte growth in coho salmon. Samples were collected from females during two hypothesized critical periods when growth influences maturation in this species. Body growth during the fall-spring months was strongly related to the degree of oocyte development, with larger fish possessing more advanced oocytes than smaller, slower growing fish. The accumulation of cortical alveoli in the oocytes was associated with increases in plasma and pituitary FSH, plasma estradiol-17beta, and ovarian steroidogenic acute regulatory protein (star) gene expression, whereas ovarian transcripts for growth hormone receptor and somatolactin receptor decreased. As oocytes accumulated lipid droplets, a general increase occurred in plasma Igf1 and components of the FSH-ovary axis, including plasma FSH, estradiol-17beta, and ovarian mRNAs for gonadotropin receptors, star, igf1, and igf2. A consistent positive relationship between plasma Igf1, estradiol-17beta, and pituitary FSH during growth in the spring suggests that these factors are important links in the mechanism by which body growth influences the rate of oocyte development.

  2. [Intensified insulin treatment is cost-effective].

    PubMed

    Reichard, P; Alm, C; Andersson, E; Wärn, I; Rosenqvist, U

    1999-01-20

    Both the Diabetes Control and Complications Trial (DCCT) in USA/Canada, and Stockholm Diabetes Intervention Study (SDIS) showed intensified insulin treatment and reduced glycaemia to prevent complications in patients with insulin-dependent (type I) diabetes mellitus. In the DCCT, the intensified treatment was considered cost-effective. In the SDIS, investigation of the direct increase in costs due to the intensified insulin treatment showed the saving in direct costs due to the reduction in photocoagulation requirements, and in the prevalence of renal insufficiency and of amputation, to correspond to 10 years' intensive insulin treatment. Thus, as intensified insulin treatment in type I diabetes reduces direct suffering at a low cost, it may be regarded as 'evidence-based' and mandatory.

  3. 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

  4. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.

    PubMed

    Schlenk, Richard F; Lübbert, Michael; Benner, Axel; Lamparter, Alexander; Krauter, Jürgen; Herr, Wolfgang; Martin, Hans; Salih, Helmut R; Kündgen, Andrea; Horst, Heinz-A; Brossart, Peter; Götze, Katharina; Nachbaur, David; Wattad, Mohammed; Köhne, Claus-Henning; Fiedler, Walter; Bentz, Martin; Wulf, Gerald; Held, Gerhard; Hertenstein, Bernd; Salwender, Hans; Gaidzik, Verena I; Schlegelberger, Brigitte; Weber, Daniela; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut

    2016-12-01

    The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m(2), days 6-8; 15 mg/m(2), days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).

  5. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial

    PubMed Central

    Ribera, Josep-Maria; Oriol, Albert; González, Marcos; Vidriales, Belén; Brunet, Salut; Esteve, Jordi; del Potro, Eloy; Rivas, Concepción; Moreno, Maria-José; Tormo, Mar; Martín-Reina, Victoria; Sarrá, Josep; Parody, Ricardo; de Oteyza, Jaime Pérez; Bureo, Encarna; Bernal, Maria-Teresa

    2010-01-01

    Background Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph+ ALL. Design and Methods This was a phase II study of patients with newly diagnosed Ph+ ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease. Results Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively. Conclusions These results confirm that imatinib is an effective first-line treatment for adult Ph+ ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post

  6. Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients.

    PubMed

    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

    2013-08-01

    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.

  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. 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

  9. 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

  10. 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

    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

    2014-05-15

    The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care 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 benefits. Here we report 1-year outcomes. Prespecified 1-year end points 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). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.

  11. PROXIMITY TO DELIVERY ALTERS INSULIN SENSITIVITY AND GLUCOSE METABOLISM IN PREGNANT MICE

    PubMed Central

    Musial, Barbara; Fernandez-Twinn, Denise S.; Vaughan, Owen R.; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

    2016-01-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and utilisation, and insulin sensitivity using acute insulin administration and hyperinsulinaemic-euglycaemic clamps with 3H-glucose infusion. Whole body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinaemia, insulin-resistant endogenous glucose production and downregulation of several proteins in hepatic and skeletal muscle insulin signalling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19 with restoration of NP insulin concentrations, improved hepatic insulin sensitivity and increased abundance of hepatic insulin signalling proteins. At D16, insulin resistance at whole body, tissue and molecular levels will favour fetal glucose acquisition while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice with implications for human and other species. PMID:26740602

  12. Insulin use in NIDDM.

    PubMed

    Genuth, S

    1990-12-01

    The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms

  13. 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.

  14. 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

  15. 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

  16. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome.

    PubMed

    Mawad, Raya; Gooley, Ted A; Rajendran, Joseph G; Fisher, Darrell R; Gopal, Ajay K; Shields, Andrew T; Sandmaier, Brenda M; Sorror, Mohamed L; Deeg, Hans Joachim; Storb, Rainer; Green, Damian J; Maloney, David G; Appelbaum, Frederick R; Press, Oliver W; Pagel, John M

    2014-09-01

    We treated patients under age 50 years with iodine-131 ((131)I)-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 to 1561 mCi of (131)I, 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), 1 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 nonrelapse mortality were observed in the first year after transplantation. However, 2 patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplantation, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-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.

  17. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    PubMed

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli.

  18. 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)…

  19. 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

  20. 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.

  1. Insulin during pregnancy, labour and delivery.

    PubMed

    de Valk, Harold W; Visser, Gerard H A

    2011-02-01

    subcutaneous insulin administration (CSII (insulin pump)) over intensive insulin injection therapy (multiple-dose insulin (MDI)) on any maternal or foeto-neonatal end point. However, group sizes were far too small to allow assessment of superiority and issues such as manageability of the disease and quality of life were never assessed. These two issues are of major importance to patients. The first trimester is often the period of most hypoglycaemic events, and insulin therapy should be especially closely monitored and adjusted in this period. After midterm, insulin requirements increase. Continuous glucose monitoring can offer better insights into the glycaemic profile than self-monitoring of blood glucose levels by the patients but the place of these new monitoring techniques has yet to be established more clearly. Insulin therapy during labour means short-acting insulin adjusted to achieve glucose levels between 4 and 8 mmol l(-1) to prevent neonatal hypoglycaemia as much as possible. After delivery, glycaemic control must be relaxed to prevent hypoglycaemia, especially in women who breastfeed.

  2. Diabetes and Insulin

    MedlinePlus

    ... you have. There are three main types of diabetes: • Type 1 occurs when the pancreas stops making insulin. It ... but may occur later in life. People with type 1 diabetes need insulin to survive. Treatment includes changes in ...

  3. 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 ...

  4. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  5. All about Insulin Resistance

    MedlinePlus

    Toolkit No. 2 All About Insulin Resistance Insulin resistance is a condition that raises your risk for type 2 diabetes and heart disease. ... Diabetes Association, Inc. 1/15 Toolkit No. 2: All About Insulin Resistance continued J Order the smallest ...

  6. Chronic insulin effects on insulin signalling and GLUT4 endocytosis are reversed by metformin.

    PubMed Central

    Pryor, P R; Liu, S C; Clark, A E; Yang, J; Holman, G D; Tosh, D

    2000-01-01

    Decreases in insulin-responsive glucose transport and associated levels of cell surface GLUT4 occur in rat adipocytes maintained in culture for 20 h under hyperinsulinaemic and hyperglycaemic conditions. We have investigated whether this defect is due to reduced signalling from the insulin receptor, GLUT4 expression or impaired GLUT4 trafficking. The effects of chronic insulin treatment on glucose transport and GLUT4 trafficking were ameliorated by inclusion of metformin in the culture medium. In comparison with the ic insulin treatment attenuated changes in signalling processes leading to glucose transport. These included insulin receptor tyrosine phosphorylation, phosphoinositide 3-kinase activity and Akt activity, which were all reduced by 60-70%. Inclusion of metformin in the culture medium prevented the effects of the chronic insulin treatment on these signalling processes. In comparison with cells maintained in culture without insulin, the total expression of GLUT4 protein was not significantly altered by chronic insulin treatment, although the level of GLUT1 expression was increased. Trafficking rate constants for wortmannin-induced cell-surface loss of GLUT4 and GLUT1 were assessed by 2-N-4-(1-azi-2, 2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannose-4-yloxy)-2-propyla min e (ATB-BMPA) photolabelling. In comparison with cells acutely treated with insulin, chronic insulin treatment resulted in a doubling of the rate constants for GLUT4 endocytosis. These results suggest that the GLUT4 endocytosis process is very sensitive to the perturbations in signalling that occur under hyperinsulinaemic and hyperglycaemic conditions, and that the resulting elevation of endocytosis accounts for the reduced levels of net GLUT4 translocation observed. PMID:10794717

  7. 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

  8. Insulin-Dependent Activation of MCH Neurons Impairs Locomotor Activity and Insulin Sensitivity in Obesity.

    PubMed

    Hausen, A Christine; Ruud, Johan; Jiang, Hong; Hess, Simon; Varbanov, Hristo; Kloppenburg, Peter; Brüning, Jens C

    2016-12-06

    Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions. Similarly, obesity promotes PI3 kinase signaling in these neurons, and this response is abrogated in IR(ΔMCH) mice. In turn, acute chemogenetic activation of MCH neurons impairs locomotor activity but not insulin sensitivity. Collectively, our experiments reveal an insulin-dependent activation of MCH neurons in obesity, which contributes via distinct mechanisms to the manifestation of impaired locomotor activity and insulin resistance.

  9. Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myélodysplasies.

    PubMed

    Ades, Lionel; Prebet, Thomas; Stamatoullas, Aspasia; Recher, Christian; Guieze, Romain; Raffoux, Emmanuel; Bouabdallah, Krimo; Hunault, Mathilde; Wattel, Eric; Stalnikiewicz, Laure; Toma, Andrea; Dombret, Hervé; Vey, Norbert; Sebert, Marie; Gardin, Claude; Chaffaut, Cendrine; Chevret, Sylvie; Fenaux, Pierre

    2017-04-01

    Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within a complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with intensive chemotherapy in a phase II study. Treatment consisted of daunorubicin (45 mg/m(2)/day, days 1-3 in cohort 1, escalated to 60 mg/m(2)/day, days 1-3 in cohorts 2 and 3) combined with cytosine arabinoside (200 mg/m(2)/day, days 1-7) and lenalidomide (10 mg/day, days 1-21 in cohorts 1 and 2, escalated to 25 mg/day, days 1-21 in cohort 3). Eighty-two patients with 5q deletion were enrolled, including 62 with acute myeloblastic leukemia, 62/79 (78%) of whom had a complex karyotype (median 7 cytogenetic abnormalities, all but 2 of them monosomal) and three had unknown karyotypes. Thirty-eight patients (46%) achieved complete remission and the overall response rate was 58.5%. Among the 62 patients with a complex karyotype, 27 achieved complete remission (44%) and 21 had cytogenetic responses. A lower response rate was observed in patients with acute myeloblastic leukemia but other pretreatment factors, including cytogenetic complexity and treatment cohort, did not significantly influence response. Fifteen patients underwent allogeneic stem cell transplantation, including 11 patients in first remission. The 1-year cumulative incidence of relapse was 64.6% and the median overall survival was 8.2 months. By comparison with conventional intensive chemotherapy, the treatment protocol we used appeared to produce higher hematologic and cytogenetic complete remission rates in patients with very poor cytogenetics, but response duration was short in this very poor risk population, highlighting the need for better post-induction strategies. Clinical trial registry number: NCT00885508.

  10. Percutaneous catheter-based intracoronary infusion of insulin--a dose finding study in the porcine model.

    PubMed

    Slettom, Grete; Jonassen, Anne K; Tuseth, Vegard; Pettersen, Reidar J; Larsen, Terje H; Seifert, Reinhard; Nordrehaug, Jan E

    2011-06-01

    Insulin given at immediate reperfusion reduces myocardial infarct size in the in vitro and the ex vivo rat heart. In vivo, insulin may cause hypoglycaemia, hypokalaemia and elevation of catecholamines, potentially harmful during an acute myocardial infarction. The purpose of this study was to evaluate tolerance and safety of intracoronary insulin infusions in a porcine model applying percutaneous intervention techniques.

  11. 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…

  12. 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

  13. [Insulin producing cells as therapy in diabetes mellitus].

    PubMed

    Schnedl, W J; Hohmeier, H E; Newgard, C B

    1996-01-01

    Even with intensive insulin therapy it is impossible to reach physiological blood glucose levels in insulin-dependent diabetes mellitus. Because of the high costs and technical problems involved in islet cell transplantation broad applicability of this therapy seems uncertain. An alternative approach is the development of molecular-engineered insulin-producing clonal cell lines. The main interest is in rodent insulinoma cell lines and neuroendocrine AtT-20ins cells. This paper reviews the current knowledge about glucose-stimulated insulin secretion and the problems that have to be solved before these cells can be used for therapy in diabetes mellitus.

  14. Diabetic ketoacidosis: Treatment in the intensive care unit or general medical/surgical ward?

    PubMed Central

    Mendez, Yamely; Surani, Salim; Varon, Joseph

    2017-01-01

    Diabetic ketoacidosis (DKA) is defined as an acute metabolic disorder, which is characterized by an increased presence of circulating ketones, and the development of ketoacidosis in the presence of hyperglycemia. This syndrome occurs as a result of insulin deficiency. Patients can be dramatically ill, however, with aggressive treatment, most patients recover rapidly. Despite being a low-risk condition, the development of acidosis, is one of the admission criteria to the intensive care unit (ICU) for these patients, in order to provide close monitoring, and recognize complications that could result from the use of aggressive therapy, such as continuous infusions if insulin. In some institutions, DKA is treated in the emergency department and general medical/surgical wards to avoid ICU overcrowding. PMID:28265341

  15. Inhaled human insulin.

    PubMed

    Strack, Thomas R

    2006-04-01

    The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human

  16. [Acute quadriplegia after diabetic ketoacidosis].

    PubMed

    Mihalik, Zoltán; Arányi, Zsuzsanna; Siska, Eva; Nyulasi, Tibor; Pénzes, István

    2003-11-02

    A 36-year-old female was admitted to the intensive care unit after resuscitation diagnosed with diabetic ketoacidotic coma, which was the first manifestation of her diabetes mellitus. It may have been provoked by pulmonary or gastrointestinal coinfection. Five days following admission the patient regained consciousness and homeostasis returned to normal. One week after the stabilization of her cardiopulmonary state, weaning from the respirator turned out to be unsuccessful: flaccid tetraparesis developed with rapid muscle atrophy and absence of deep tendon reflexes. The sensory system and cranial nerves remained intact. Electrophysiological studies and muscle biopsy showed serious acute illness myopathy with mild demyelination owing probably to the latent diabetes. The course of acute quadriplegia was fluctuating and correlated mainly with the activity of the systemic inflammatory response syndrome mechanisms. Myopathy might have been aggravated by using high-dose glucocorticoid therapy. The patient's general condition improved quickly as a result of full recovery from sepsis, discontinuation of glucocorticoids and normoglicaemia maintained by subcutan insulin substitution. Eight months after admission almost full neuromuscular restitution was achieved showing the reversibility of this grave illness.

  17. Basal insulin: beyond glycemia.

    PubMed

    Niswender, Kevin D

    2011-07-01

    Insulin is a pleiotropic hormone with numerous effects at the cellular, tissue, and organismal levels. Clinicians are familiar with physiological effects of insulin on carbohydrate metabolism, including stimulation of glucose uptake in skeletal muscle and the suppression of glucose production from the liver. Other metabolic effects of insulin include inhibiting the release of free fatty acids from adipose tissue and stimulating the incorporation of amino acids into proteins. Indeed, every organ in the body, including the brain, is a target for insulin action. Insulin resistance, typically defined with respect to glucose metabolism, is a condition in which normal levels of insulin do not trigger the signal for glucose disposition. The effects of insulin resistance and impaired insulin signaling have profound pathophysiologic effects, such as hyperglycemia-induced tissue damage, hypertension, dyslipidemia, metabolic syndrome, and cardiovascular and renal disease. An integrated view of insulin action in all of these tissues may yield improved therapeutic insight and possibly even illuminate new therapeutic opportunities. With the increase in the number of patients diagnosed with prediabetes and diabetes, an updated understanding of the disease and the pharmacologic armamentarium used to treat it is needed to improve outcomes. To help expand the clinical care provider's perspective, this article will provide a provocative discussion about the pathophysiology of diabetes, the role of insulin and insulin resistance, and the clinical efficacy potential of insulin. Understanding the cellular and molecular mechanisms underlying the effects of insulin and how these translate into clinical consequences beyond glycemia will assist primary care physicians in the care of their patients with diabetes and metabolic syndrome.

  18. Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data

    PubMed Central

    Andreassi, Alice; Salvioni, Michela; Pelliccione, Fiore; Mantellassi, Gianna; Banderali, Giuseppe

    2016-01-01

    Myoinositol and D-chiro inositol, which are inositol isomers, have been shown to possess insulin-mimetic properties and to improve insulin resistance, especially in women with polycystic ovary syndrome. However, it has not been determined if this relationship exists also in children. Based on these previous findings, we hypothesized that inositol could be effective in improving insulin sensitivity in children with insulin resistance. To evaluate this hypothesis, we administered both inositol formulations before carrying out an oral glucose tolerance test (OGTT) in a group of obese insulin-resistant male children with high basal insulin levels and compared the values obtained with an OGTT previously conducted without inositol, in the same group, with unchanged BMI. Our results confirm that myoinositol and D-chiro inositol acutely reduce insulin increase after glucose intake mainly in children with high basal insulin level. PMID:27882052

  19. Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes.

    PubMed

    Dardano, Angela; Bianchi, Cristina; Del Prato, Stefano; Miccoli, Roberto

    2014-01-01

    Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients' preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal-bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients' viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients.

  20. 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.

  1. High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003–2007

    PubMed Central

    Kozlowski, Piotr; Åström, Maria; Ahlberg, Lucia; Bernell, Per; Hulegårdh, Erik; Hägglund, Hans; Karlsson, Karin; Markuszewska-Kuczymska, Alicja; Tomaszewska-Toporska, Beata; Smedmyr, Bengt; Hallböök, Helene

    2012-01-01

    Background A minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission. Design and Methods Between 2003–2007, 76 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt’s leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated. Results Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13–32) and 15% (95% CI: 7–24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2–8.3) after relapse, whereas all patients over 35 years old at diagnosis have died. Conclusions Allogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis. PMID:22511497

  2. 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.

  3. Sodium retention by insulin may depend on decreased plasma potassium.

    PubMed

    Friedberg, C E; Koomans, H A; Bijlsma, J A; Rabelink, T J; Dorhout Mees, E J

    1991-02-01

    Evidence is accumulating that insulin is a hypertensive factor in humans. The involved mechanism may be its sodium-retaining effect. We examined whether insulin causes sodium retention through a direct action on the kidney, as is generally assumed, or indirectly through hypokalemia. Insulin was infused (euglycemic clamp technique) with and without potassium infusion to prevent hypokalemia in six healthy subjects. Without potassium infusion, insulin caused a marked decrease in plasma potassium (-0.75 mmol/L), and decreased urinary sodium and potassium excretions by, approximately 38% and 65%, respectively. Simultaneous potassium infusion largely prevented the decrease in plasma potassium, as well as the decrease in urinary sodium and potassium excretions. These data suggest that the acute antinatriuretic effect of insulin may be largely mediated in an indirect way, ie, through hypokalemia.

  4. 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

  5. Adipokines and insulin action

    PubMed Central

    Knights, Alexander J; Funnell, Alister PW; Pearson, Richard CM; Crossley, Merlin; Bell-Anderson, Kim S

    2014-01-01

    Obesity is a major public health concern and a strong risk factor for insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The last two decades have seen a reconsideration of the role of white adipose tissue (WAT) in whole body metabolism and insulin action. Adipose tissue-derived cytokines and hormones, or adipokines, are likely mediators of metabolic function and dysfunction. While several adipokines have been associated with obese and insulin-resistant phenotypes, a select group has been linked with insulin sensitivity, namely leptin, adiponectin, and more recently, adipolin. What is known about these insulin-sensitizing molecules and their effects in healthy and insulin resistant states is the subject of this review. There remains a significant amount of research to do to fully elucidate the mechanisms of action of these adipokines for development of therapeutics in metabolic disease. PMID:24719781

  6. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    PubMed Central

    Valla, Vasiliki

    2010-01-01

    Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. PMID:20589066

  7. Immunologic insulin resistance.

    PubMed

    Davidson, J K; DeBra, D W

    1978-03-01

    The efficacy of sulfated beef insulin for plasma glucose control in 35 patients with immunologic insulin resistance was studied. Patients were on a mean dose of 550 U./day (range 200--2,000) of U-500 regular beef insulin. Mean maximum 125I-insulin-binding capacity was 191 mU./ml. serum (range 13--1,080). Mean in vivo half-life (T 1/2) of 125I-regular beef insulin was 614 minutes (range 114--1,300), as against a mean T 1/2 of 13.9 minutes (range 11.8--16.5) in normal controls. Treatment was successful in 34 patients and unsuccessful in one with lipoatrophic diabetes. The mean initial dose of sulfated insulin was 89 U./day (range 15--400) and at three months was 66 U./day (range 20--400). Twenty-eight patients who responded and survived have been on sulfated insulin for a mean of 39 months (range 2-66) and are on a mean dose of 25 U./day (range 0--100). The mean maximum binding capacity fell to 9 mU./ml. (range 0--34) during therapy (p less than 0.01). Mean 125I-insulin T 1/2 fell from 614 to 249 minutes after sulfated insulin therapy (p less than 0.001). A comparative study of 15 patients on consecutive days showed a 35 sulfated insulin T 1/2 of 60 minutes (range 15--94) and a mean 125I-regular insulin T 1/2 of 246 minutes (range 62--560, p less than 0.001). These results indicate that sulfated insulin is less antigenic than regular beef insulin and combines less avidly with human antibodies to regular beef insulin. The response to sulfated insulin therapy was significantly better than the response reported by other investigators to pork insulin or to steroid therapy in similar patients.

  8. Insulin resistance and atherosclerosis

    PubMed Central

    Semenkovich, Clay F.

    2006-01-01

    Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent findings suggest that insulin resistance and atherosclerosis could represent independent and ultimately maladaptive responses to the disruption of cellular homeostasis caused by the excess delivery of fuel. PMID:16823479

  9. 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.

  10. Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response

    PubMed Central

    Kodama, Keiichi; Tojjar, Damon; Yamada, Satoru; Toda, Kyoko; Patel, Chirag J.; Butte, Atul J.

    2013-01-01

    OBJECTIVE Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response. RESEARCH DESIGN AND METHODS We identified studies that measured the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance. RESULTS We found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable. CONCLUSIONS Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset. PMID:23704681

  11. 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

  12. Molecular and functional resistance to insulin in hypothalamus of rats exposed to cold.

    PubMed

    Torsoni, Márcio A; Carvalheira, José B; Pereira-Da-Silva, Márcio; de Carvalho-Filho, Marco A; Saad, Mário J A; Velloso, Lício A

    2003-07-01

    Insulin and leptin act in the hypothalamus, providing robust anorexigenic signals. The exposure of homeothermic animals to a cold environment leads to increased feeding, accompanied by sustained low levels of insulin and leptin. In the present study, the initial and intermediate steps of the insulin-signaling cascade were evaluated in the hypothalamus of cold-exposed Wistar rats. By immunohistochemistry, most insulin receptor (IR) and insulin receptor substrate-2 (IRS-2) immunoreactivity localized to the arcuate nucleus. Basal levels of tyrosine phosphorylation of IR and IRS-2 were increased in cold-exposed rats compared with rats maintained at room temperature. However, after an acute, peripheral infusion of exogenous insulin, significantly lower increases of IR and IRS-2 tyrosine phosphorylation were detected in the hypothalamus of cold-exposed rats. Insulin-induced association of p85/phosphatidylinositol 3-kinase with IRS-2, Ser473 phosphorylation of Akt, and tyrosine phosphorylation of ERK was significantly reduced in the hypothalamus of cold-exposed rats. To test the hypothesis of functional impairment of insulin signaling in the hypothalamus, intracerebroventricularly cannulated rats were acutely treated with insulin, and food ingestion was measured over a period of 12 h. Cold-exposed animals presented a significantly lower insulin-induced reduction in food consumption compared with animals maintained at room temperature. Hence, the present studies reveal that animals exposed to cold are resistant, both at the molecular and the functional level, to the actions of insulin in the hypothalamus.

  13. 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.

  14. Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick

    PubMed Central

    Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank

    2012-01-01

    Purpose Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Methods Chicks were treated with either +7 D, −7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-AktThr308, and anti-phospho-Erk1/2(Thr202/Tyr204) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Results Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens–treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor

  15. Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome.

    PubMed

    Bernal, Teresa; Diez-Campelo, María; Godoy, Vicky; Rojas, Silvia; Colado, Enrique; Alcoceba, Miguel; González, Marcos; Vidriales, Belén; Sánchez-Guijo, Fermín M; López-Corral, Lucía; Luño, Elisa; del Cañizo, Consuelo

    2014-05-01

    We evaluated the impact of detection of minimal residual disease by flow cytometry (FCMRD) and CD3 chimerism in relapse in a cohort of 87 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing stem cell transplantation. Patients with a positive FCMRD at day +100 after transplantation showed higher relapse rates and worse overall survival. In multivariate analysis, a positive FCMRD after transplantation was a significant predictor of relapse. Mixed chimerism showed a trend to statistical signification. We conclude that FCMRD at day 100 after SCT is the best predictor of relapse after SCT in patients with aggressive myeloid malignancies.

  16. 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

  17. Fatal hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine.

    PubMed

    Madsen, Kristian Roerbaek

    2014-01-08

    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.

  18. Effects of glucosamine infusion on insulin secretion and insulin action in humans.

    PubMed

    Monauni, T; Zenti, M G; Cretti, A; Daniels, M C; Targher, G; Caruso, B; Caputo, M; McClain, D; Del Prato, S; Giaccari, A; Muggeo, M; Bonora, E; Bonadonna, R C

    2000-06-01

    Glucose toxicity (i.e., glucose-induced reduction in insulin secretion and action) may be mediated by an increased flux through the hexosamine-phosphate pathway. Glucosamine (GlcN) is widely used to accelerate the hexosamine pathway flux, independently of glucose. We tested the hypothesis that GlcN can affect insulin secretion and/or action in humans. In 10 healthy subjects, we sequentially performed an intravenous glucose (plus [2-3H]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 micromol x min(-1) x kg(-1)) or high (5 micromol x min(-1) x kg(-1) [n = 5]) GlcN infusion. Beta-cell secretion, insulin (SI*-IVGTT), and glucose (SG*) action on glucose utilization during the IVGTT were measured according to minimal models of insulin secretion and action. Infusion of GlcN did not affect readily releasable insulin levels, glucose-stimulated insulin secretion (GSIS), or the time constant of secretion, but it increased both the glucose threshold of GSIS (delta approximately 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (delta approximately 0.3-0.5 mmol/l, P < 0.05-0.02). GlcN did not change glucose utilization or intracellular metabolism (glucose oxidation and glucose storage were measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in SI*-IVGTT (delta approximately 30%, P < 0.02) and in SG* (delta approximately 40%, P < 0.05). Thus, in humans, acute GlcN infusion recapitulates some metabolic features of human diabetes. It remains to be determined whether acceleration of the hexosamine pathway can cause insulin resistance at euglycemia in humans.

  19. 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

  20. Effect of an Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: A Preliminary Study.

    PubMed

    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.

  1. 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.

  2. [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.

  3. 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

  4. Insulin delivery by injection in children and adolescents with diabetes.

    PubMed

    Hanas, Ragnar; de Beaufort, Carine; Hoey, Hilary; Anderson, Barbara

    2011-08-01

    Type 1 diabetes is treated with insulin, which has traditionally been delivered by vial and syringe. However, for many patients, dosing inaccuracy, pain, anxiety, inconvenience, and social acceptability present barriers to this method of administration (1-5). This has contributed to the increased popularity of alternative insulin delivery systems, including pen delivery devices (4, 6). Evidence suggests that discreet devices, such as insulin pens, facilitate adherence to intensive insulin therapy regimens, help improve lifestyle flexibility, and reduce injection pain compared with the conventional syringe-based regimens, as shown in studies in adults and adolescents (7). In addition, compared with the vial and syringe method of insulin administration, pens may provide more accurate dosing - which is particularly important in children - thereby improving short-term blood glucose control and potentially improving long-term outcomes (5, 8). Children, in particular, may benefit from insulin pens that are simple to use as adherence issues may be more evident in this patient group (9). Pens for insulin delivery in children with type 1 diabetes have been used for a long time in Europe, and have recently gained in popularity in many other places around the world (4, 10). Furthermore, the conventional vial and syringe method of insulin delivery is beginning to be considered as obsolete (11). Moreover, there is a continued drive to improve insulin pen technology, to refine and enhance the functionality and usability of these pens. However, despite recent advances in pen design and function, the selection of pens available especially for children is limited.

  5. 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.

  6. Ozone (O3): A Potential Contributor to Metabolic Syndrome through Altered Insulin Signaling

    EPA Science Inventory

    Air pollutants have been associated with diabetes and metabolic syndrome, but the mechanisms remain to be elucidated. We hypothesized that acute O3 exposure will produce metabolic impairments through endoplasmic reticular stress (ER) stress and altered insulin signaling in liver,...

  7. Acute Effects of Energy Deficit Induced by Moderate-Intensity Exercise or Energy-Intake Restriction on Postprandial Lipemia in Healthy Girls.

    PubMed

    Thackray, Alice Emily; Barrett, Laura Ann; Tolfrey, Keith

    2015-05-01

    Eleven healthy girls (mean ± SD: age 12.1 ± 0.6 years) completed three 2-day conditions in a counterbalanced, crossover design. On day 1, participants either walked at 60 (2)% peak oxygen uptake (energy deficit 1.55[0.20] MJ), restricted food energy intake (energy deficit 1.51[0.25] MJ) or rested. On day 2, capillary blood samples were taken at predetermined intervals throughout the 6.5 hr postprandial period before, and following, the ingestion of standardized breakfast and lunch meals. Fasting plasma triacylglycerol concentrations (TAG) was 29% and 13% lower than rest control in moderate-intensity exercise (effect size [ES] = 1.39, p = .01) and energy-intake restriction (ES = 0.57, p = .02) respectively; moderate-intensity exercise was 19% lower than energy-intake restriction (ES = 0.82, p = .06). The moderate-intensity exercise total area under the TAG versus time curve was 21% and 13% lower than rest control (ES = 0.71, p = .004) and energy-intake restriction (ES = 0.39, p = .06) respectively; energy-intake restriction was marginally lower than rest control (-10%; ES = 0.32, p = .12). An exercise-induced energy deficit elicited a greater reduction in fasting plasma TAG with a trend for a larger attenuation in postprandial plasma TAG than an isoenergetic diet-induced energy deficit in healthy girls.

  8. The effect of acute exercise on GLUT4 levels in peripheral blood mononuclear cells of sled dogs.

    PubMed

    Schnurr, Theresia M; Reynolds, Arleigh J; Komac, Alyssa M; Duffy, Lawrence K; Dunlap, Kriya L

    2015-07-01

    Using sled dogs as exercise model, our objectives of this study were to 1) assess the effects of one acute bout of high-intensity exercise on surface GLUT4 concentrations on easily accessible peripheral blood mononuclear cells (PBMC) and 2) compare our findings with published research on exercise induced GLUT4 in skeletal muscle. During the exercise bout, dogs ran 5 miles at approximately 90% of VO2 max. PMBC were collected before exercise (baseline), immediately after exercise and after 24h recovery.GLUT4 was measured via ELISA. Acute exercise resulted in a significant increase on surface GLUT4 content on PBMC. GLUT4 was increased significantly immediately after exercise (~ 50%; p<0.05) and reduced slightly by 24h post-exercise as compared to baseline (~ 22%; p>0.05). An effect of acute exercise on GLUT4 levels translocated to the cell membrane was observed, with GLUT4 levels not yet returned to baseline after 24h post-exercise. In conclusion, the present investigation demonstrated that acute high-intensity exercise increased GLUT4 content at the surface of PBMC of sled dogs as it has been reported in skeletal muscle in other species. Our findings underline the potential use of peripheral blood mononuclear cell GLUT4 protein content as minimally invasive proxy to investigate relationships between insulin sensitivity, insulin resistance, GLUT4 expression and glucose metabolism.

  9. Chromium and insulin resistance.

    PubMed

    Anderson, Richard A

    2003-12-01

    Insulin resistance leads to the inability of insulin to control the utilization and storage of glucose. It is associated initially with elevated levels of circulating insulin followed by glucose intolerance which may progress to type 2 diabetes, hyperlipidaemia, hypertension, obesity and cardiovascular diseases. While the causes of these diseases are multifactorial, one nutrient that is associated with all of these abnormalities is Cr. In the presence of Cr, in a biologically active form, much lower levels of insulin are required. Modern diets, which are often high in refined carbohydrates, are not only low in Cr, but lead to enhanced Cr losses. In response to the consumption of refined carbohydrates, there is a rapid rise in blood sugar leading to elevations in insulin that cause a mobilization of Cr. Once mobilized, Cr is not reabsorbed but lost via the urine leading to decreased Cr stores. Several studies involving both human subjects and experimental animals have reported improvements in insulin sensitivity, blood glucose, insulin, lipids, haemoglobin A1c, lean body mass and related variables in response to improved Cr nutrition. However, not all studies have reported beneficial effects associated with improved Cr nutrition. Well-controlled human studies are needed to document an unequivocal effect of Cr on insulin sensitivity in human subjects. Studies need to involve a significant number of subjects with insulin resistance, glucose intolerance or early stages of diabetes, who have not been taking supplements containing Cr for at least 4 months, and involve at least 400 to 600 microg supplemental Cr daily or more. Studies should be at least 4 months to document sustained effects of supplemental Cr on insulin resistance and related variables. Cr is a nutrient and not a therapeutic agent and therefore will only be of benefit to those whose problems are due to suboptimal intake of Cr.

  10. Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes

    PubMed Central

    Belfort-DeAguiar, Renata D.; Naik, Sarita; Hwang, Janice; Szepietowska, Barbara

    2015-01-01

    OBJECTIVE Hypoglycemia is one of the major factors limiting implementation of tight glycemic control in patients with type 1 diabetes and is associated with increased morbidity and mortality during intensive insulin treatment. β-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled β-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established. RESEARCH DESIGN AND METHODS Seven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 μg), a highly specific β-2 AR agonist, or a placebo during a hyperinsulinemic-hypoglycemic clamp study to evaluate its capacity to antagonize the effect of insulin. In a second set of studies, five subjects with type 1 diabetes received inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia. RESULTS During a hyperinsulinemic-hypoglycemic clamp, compared with placebo, inhaled formoterol decreased the glucose infusion rate required to maintain plasma glucose at a target level by 45–50% (P < 0.05). There was no significant effect on glucagon, epinephrine, cortisol, or growth hormone release (P = NS). Furthermore, in volunteers with type 1 diabetes 1 h after increasing basal insulin delivery twofold, glucose levels dropped to 58 ± 5 mg/dL, whereas hypoglycemia was prevented by inhaled formoterol (P < 0.001). CONCLUSIONS Inhalation of the β-2 AR–specific agonist formoterol may be useful in the prevention or treatment of acute hypoglycemia and thus may help patients with type 1 diabetes achieve optimal glucose control more safely. PMID:26153273

  11. Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy.

    PubMed

    Scheiner, Gary; Boyer, Bret A

    2005-07-01

    Establishment of appropriate basal insulin levels is an essential component of intensive insulin therapy. While the existence of a "dawn phenomenon" is widely recognized, the present study sought to establish whether diurnal basal insulin patterns exist in Type-1 diabetes, and whether these patterns vary by age and gender. Participant data was drawn from 322 Type-1 insulin pump users treated at a private diabetes education practice in suburban Philadelphia. All participants completed a battery of fasting tests designed to match basal insulin levels to endogenous glucose production and insulin sensitivity. Analysis of resultant basal patterns revealed significant differences between juvenile (age < or =20) and adult (age >20) basal insulin patterns. The younger group exhibited a more pronounced and sustained night-time peak; the older group exhibiting a briefer and less pronounced early-morning peak. Lower overall basal insulin requirements were found in the youngest (age < or =10) and oldest (age >60) groups. No noteworthy gender differences were found. Results can serve as a guide for clinicians when initiating and fine-tuning patients who utilize basal/bolus insulin therapy.

  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. 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.

  14. Individualizing insulin therapy in the management of type 2 diabetes.

    PubMed

    Moghissi, Etie; King, Allen B

    2014-10-01

    It is recognized that reducing hyperglycemia early on in disease progression has long-term benefits for patients with diabetes. Insulin therapy has greater potential to reduce hyperglycemia than other therapies; however, there is often a significant delay in insulin initiation and intensification. Insulin replacement therapy in type 2 diabetes should no longer be viewed as the treatment of last resort. With the development of modern insulin analogs, the field has evolved. Large clinical trials have improved our understanding of the potential benefits and risks associated with intensive glycemic control in different patient populations and highlighted the need for individualization of glycemic targets and treatment strategies. Current treatment guidelines recognize the important role of insulin therapy both early on and throughout the progression of type 2 diabetes.

  15. Physical activity, insulin action, and diabetes prevention and control.

    PubMed

    Colberg, Sheri R

    2007-08-01

    Control of blood glucose levels in individuals with diabetes mellitus (DM) is directly affected by the balance between insulin and glucose-raising endocrine hormones, along with other metabolic factors, including fuel use and availability, exercise intensity and duration, training status, and visceral fat levels, all of which can impact the effect of physical activity on insulin action in diabetic or prediabetic individuals. Current research suggests that type 2 DM can be prevented and controlled with increased physical activity, largely through improvements in the muscles' sensitivity to insulin that are affected by changes in both glucose and fat metabolism. In addition, abnormal insulin action in the body is associated with a host of other health conditions, including cardiovascular disease and hypertension, which can be better controlled when their associations are fully understood. This article discusses the importance of varying types of physical activity on insulin action to enhance metabolic control and how they can be undertaken safely by all diabetic individuals.

  16. Specific Newborn Individualized Developmental Care and Assessment Program Movements Are Associated With Acute Pain in Preterm Infants in the Neonatal Intensive Care Unit

    PubMed Central

    Grunau, Ruth E.; Oberlander, Tim F.; Whitfield, Michael F.

    2005-01-01

    Objective. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) is widely used in neonatal intensive care units and comprises 85 discrete infant behaviors, some of which may communicate infant distress. The objective of this study was to identify developmentally relevant movements indicative of pain in preterm infants. Methods. Forty-four preterm infants were assessed at 32 weeks' gestational age (GA) during 3 phases (baseline, lance/squeeze, and recovery) of routine blood collection in the neonatal intensive care unit. The NIDCAP and Neonatal Facial Coding System (NFCS) were coded from separate continuous bedside video recordings; mean heart rate (mHR) was derived from digitally sampled continuous electrographic recordings. Analysis of variance (phase × gender) with Bonferroni corrections was used to compare differences in NIDCAP, NFCS, and mHR. Pearson correlations were used to examine relationships between the NIDCAP and infant background characteristics. Results. NFCS and mHR increased significantly to lance/squeeze. Eight NIDCAP behaviors also increased significantly to lance/squeeze. Another 5 NIDCAP behaviors decreased significantly to lance/squeeze. Infants who had lower GA at birth, had been sicker, had experienced more painful procedures, or had greater morphine exposure showed increased hand movements indicative of increased distress. Conclusions. Of the 85 NIDCAP behaviors, a subset of 8 NIDCAP movements were associated with pain. Particularly for infants who are born at early GAs, addition of these movements to commonly used measures may improve the accuracy of pain assessment. PMID:15231909

  17. 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.

  18. Infliximab and insulin resistance.

    PubMed

    Ursini, Francesco; Naty, Saverio; Grembiale, Rosa Daniela

    2010-06-01

    Insulin resistance is the most important pathophysiologic feature of obesity, type 2 diabetes mellitus and prediabetic states. TNF-alpha, a proinflammatory cytokine, plays a pivotal role in the pathogenesis of inflammation-associated insulin resistance during the course of rheumatic diseases. Therapies aimed at neutralizing TNF-alpha, such as the monoclonal antibody infliximab, represent a novel approach for the treatment of rheumatic diseases and allow to obtain significant results in terms of control of the inflammatory process. In this article we reviewed the scientific evidence published in the literature about a potential role of TNF-alpha blockade in improving insulin resistance in non-diabetic rheumatic patients.

  19. 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

  20. Pre-treatment with oral hydroxyurea prior to intensive chemotherapy improves early survival of patients with high hyperleukocytosis in acute myeloid leukemia.

    PubMed

    Mamez, Anne-Claire; Raffoux, Emmanuel; Chevret, Sylvie; Lemiale, Virginie; Boissel, Nicolas; Canet, Emmanuel; Schlemmer, Benoît; Dombret, Hervé; Azoulay, Elie; Lengliné, Etienne

    2016-10-01

    Acute myeloid leukemia with high white blood cell count (WBC) is a medical emergency. A reduction of tumor burden with hydroxyurea may prevent life-threatening complications induced by straight chemotherapy. To evaluate this strategy, we reviewed medical charts of adult patients admitted to our institution from 1997 to 2011 with non-promyelocytic AML and WBC over 50 G/L. One hundred and sixty patients were included with a median WBC of 120 G/L (range 50-450), 107 patients received hydroxyurea prior to chemotherapy, and 53 received emergency induction chemotherapy (CT). Hospital mortality was lower for patients treated with hydroxyurea (34% versus 19%, p = 0.047) even after adjusting for age (p < 0.01) and initial WBC count (p = 0.02). No evidence of any difference between treatment groups in terms of WBC decline kinetics and disease free survival (p = 0.87) was found. Oral hydroxyurea prior to chemotherapy seems a safe and efficient strategy to reduce early death of hyperleukocytic AML patients.

  1. Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.

    PubMed

    Polidori, David C; Bergman, Richard N; Chung, Stephanie T; Sumner, Anne E

    2016-06-01

    Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance.

  2. Improved outcome in acute myeloid leukemia patients enrolled in clinical trials: A national population-based cohort study of Danish intensive chemotherapy patients

    PubMed Central

    Østgård, Lene Sofie Granfeldt; Nørgaard, Mette; Sengeløv, Henrik; Medeiros, Bruno C.; Kjeldsen, Lars; Overgaard, Ulrik Malthe; Severinsen, Marianne Tang; Marcher, Claus Werenberg; Jensen, Morten Krogh; Nørgaard, Jan Maxwell

    2016-01-01

    Clinical trials are critical to improve AML treatment. It remains, however, unclear if clinical trial participation per se affects prognosis and to what extent the patients selected for trials differ from those of patients receiving intensive therapy off-trial. We conducted a population-based cohort study of newly diagnosed Danish AML patients treated with intensive chemotherapy between 2000–2013. We estimated accrual rates and compared characteristics, complete remission (CR) rates, and relative risks (RRs) of death at 90-day, 1-year, and 3-years in clinical trial patients to patients treated off-trial. Of 867 patients, 58.3% (n = 504) were included in a clinical trial. Accrual rates were similar across age groups (p = 0.55). Patients with poor performance status, comorbidity, therapy-related and secondary AML were less likely to be enrolled in trials. CR rates were 80.2% in trial-patients versus 68.6% in patients treated off- trial. Also, trial-patients had superior survival at 1-year; 72%, vs. 54% (adjusted RR of death 1.28(CI = 1.06–1.54)), and at 3 years; 45% vs. 29% (adjusted RR 1.14(CI = 1.03–1.26)) compared to patients treated off-trial. Despite high accrual rates, patients enrolled in clinical trials had a favorable prognostic profile and a better survival than patients treated off-trial. In conclusion, all trial results should be extrapolated with caution and population-based studies of “real world patients” have a prominent role in examining the prognosis of AML. PMID:27732947

  3. Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study.

    PubMed

    Bergfelt, Emma; Kozlowski, Piotr; Ahlberg, Lucia; Hulegårdh, Erik; Hägglund, Hans; Karlsson, Karin; Markuszewska-Kuczymska, Alicja; Tomaszewska-Toporska, Beata; Smedmyr, Bengt; Åström, Maria; Amini, Rose-Marie; Hallböök, Heléne

    2015-04-01

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status ≥2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

  4. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies.

    PubMed

    Oosterveld, Margriet; Suciu, Stefan; Muus, Petra; Germing, Ulrich; Delforge, Michel; Belhabri, Amin; Aul, Carlo; Selleslag, Dominik; Ferrant, Augustin; Marie, Jean-Pierre; Amadori, Sergio; Jehn, Ulrich; Mandelli, Franco; Hess, Uwe; Hellström-Lindberg, Eva; Cakmak-Wollgast, Songuel; Vignetti, Marco; Labar, Boris; Willemze, Roel; de Witte, Theo

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-specific prognostic factors and to develop prognostic scores for both patient groups. A total of 692 patients in the EORTC/GIMEMA AML-10 study and 289 patients in the CRIANT study received identical remission-induction and consolidation treatment. Estimated 5-year survival rate was 34 % in the AML-10 versus 27 % in the CRIANT study, and estimated disease-free survival was 40 % versus 28 %, respectively. In multivariate analysis, cytogenetic characteristics, white blood count, and age appeared prognostic for survival in both studies. French-American-British (FAB) subtype and performance status were prognostic in the AML-10 study only, whereas number of cytopenias and duration of antecedent hematologic disorder >6 months were prognostic in the CRIANT study only. The prognostic scores distinguish three groups with a 5-year survival rate of 54, 38, and 19 % in the AML-10 study versus 69, 37, and 5 % in the CRIANT study. The prognostic value of these scores has been validated on two external series. The new scoring systems form a practical tool to predict the outcome of individual MDS and AML patients treated with intensive antileukemic therapy.

  5. Lilly lecture 1995. Glucose transport: pivotal step in insulin action.

    PubMed

    Kahn, B B

    1996-11-01

    The effect of insulin to acutely stimulate glucose uptake into muscle and adipose tissue is essential for normal glucose homeostasis. The GLUT4 glucose transporter is a major mediator of this action, and insulin recruits GLUT4 from an intracellular pool to the plasma membrane. An important pathologic feature of obesity, NIDDM, and to a lesser extent IDDM is resistance to insulin-stimulated glucose uptake. Investigations of the mechanisms have revealed tissue-specific regulation of GLUT4 with decreased gene expression in adipose cells but not in skeletal muscle. This has led to the hypothesis that alterations in the trafficking of the GLUT4 vesicle or in the exposure or activation of the GLUT4 transporter may cause insulin resistance in skeletal muscle in obesity and diabetes. Exercise training increases GLUT4 expression in muscle in association with enhanced glucose tolerance in vivo. Transgenic mice have been created to investigate other approaches to improve insulin action on glucose transport. Overexpression of GLUT4 in adipocytes of transgenic mice increases the proportion of GLUT4 on the plasma membrane and enhances insulin sensitivity in vivo. Altering insulin signaling by overexpressing p21ras in adipocytes of transgenic mice results in increased GLUT4 on the plasma membrane in the absence of insulin and increases insulin sensitivity in vitro and in vivo. Thus, glucose transport is a pivotal step in whole-body insulin action. Strategies to increase the number of GLUT4 transporters that are functionally inserted in the plasma membrane in muscle and adipocytes may lead to new therapies to treat or prevent NIDDM.

  6. Insulin Regulates the Activity of the High-Affinity Choline Transporter CHT

    PubMed Central

    Fishwick, Katherine J.; Rylett, R. Jane

    2015-01-01

    Studies in humans and animal models show that neuronal insulin resistance increases the risk of developing Alzheimer’s Disease (AD), and that insulin treatment may promote memory function. Cholinergic neurons play a critical role in cognitive and attentional processing and their dysfunction early in AD pathology may promote the progression of AD pathology. Synthesis and release of the neurotransmitter acetylcholine (ACh) is closely linked to the activity of the high-affinity choline transporter protein (CHT), but the impact of insulin receptor signaling and neuronal insulin resistance on these aspects of cholinergic function are unknown. In this study, we used differentiated SH-SY5Y cells stably-expressing CHT proteins to study the effect of insulin signaling on CHT activity and function. We find that choline uptake activity measured after acute addition of 20 nM insulin is significantly lower in cells that were grown for 24 h in media containing insulin compared to cells grown in the absence of insulin. This coincides with loss of ability to increase phospho-Protein Kinase B (PKB)/Akt levels in response to acute insulin stimulation in the chronic insulin-treated cells. Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3-kinase) in cells significantly lowers phospho-PKB/Akt levels and decreases choline uptake activity. We show total internal reflection microscopy (TIRF) imaging of the dynamic movement of CHT proteins in live cells in response to depolarization and drug treatments. These data show that acute exposure of depolarized cells to insulin is coupled to transiently increased levels of CHT proteins at the cell surface, and that this is attenuated by chronic insulin exposure. Moreover, prolonged inhibition of PI3-kinase results in enhanced levels of CHT proteins at the cell surface by decreasing their rate of internalization. PMID:26161852

  7. Insulin Resistance and Prediabetes

    MedlinePlus

    ... especially sleep apnea; and cigarette smoking. Does sleep matter? Yes. Studies show that untreated sleep problems, especially ... a severe form of insulin resistance may have dark patches of skin, usually on the back of ...

  8. 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.

  9. Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial

    PubMed Central

    Needham, Dale M; Colantuoni, Elizabeth; Dinglas, Victor D; Hough, Catherine L; Wozniak, Amy W; Jackson, James C; Morris, Peter E; Mendez-Tellez, Pedro A; Ely, E Wesley; Hopkins, Ramona O

    2016-01-01

    Summary Background Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge. Preclinical and observational studies suggest that the use of statins might reduce delirium in intensive care. We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a randomised controlled trial. Methods We did this ancillary study within the SAILS trial, a randomised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome. This study was done at 35 hospitals in the USA. Patients were randomly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin (40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care, study day 28, or death) or placebo. Patients and investigators were masked to treatment assignment. Delirium was assessed with the validated Confusion Assessment Method for intensive care. Cognitive function was assessed with tests for executive function, language, verbal reasoning and concept formation, and working, immediate, and delayed memory. We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1·5 SDs below norms. The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months. This trial is registered with ClinicalTrials.gov (NCT00979121 and NCT00719446). Findings 272 patients were assessed for delirium daily in intensive care. The mean proportion of days with delirium was 34% (SD 30%) in the rosuvastatin group versus 31% (29%) in the placebo group; hazard ratio 1·14, 95% CI 0·92–1·41, p=0·22. At 6

  10. Stress hyperglycemia, insulin treatment, and innate immune cells.

    PubMed

    Xiu, Fangming; Stanojcic, Mile; Diao, Li; Jeschke, Marc G

    2014-01-01

    Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

  11. 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.

  12. Acute effects of prolonged intermittent low-intensity isometric warm-up schemes on jump, sprint, and agility performance in collegiate soccer players

    PubMed Central

    Pojskić, H; Babajić, F; Užičanin, E; Muratović, M; Tomljanović, M

    2015-01-01

    The aim of the present study was to compare the effects of different warm-up interventions on jump, sprint and agility performance in collegiate soccer players. Twenty-one healthy male college soccer players (age: 20.14 ± 1.65 years; body height: 179.9 ± 8.34 cm; body mass: 74.4 ± 13.0 kg; % body fat: 9.45 ± 4.8) participated in the study. Subjects underwent four different randomized warm-up protocols separated by at least 48 hours. The warm-up schemes were: 1. no conditioning contraction protocol (NCC); 2. dynamic stretching (DS); 3. prolonged intermittent low-intensity isometric exercise (ST); and, 4. ST with an additional external load equal to 30% of body weight (ST + 30% BW). All interventions were preceded by a general warm-up. Results from one-way repeated measures ANOVA demonstrated a significant difference in countermovement jump (CMJ) at F(3,60) = 10.2, ηρ2 = 0.337, p < 0.01. Post hoc analysis revealed a significant difference in CMJ performance in DS when compared to NCC and ST + 30% BW. No significant difference in CMJ was observed between DS and ST. CMJ scores in NCC, ST, and ST + 30% BW were non-significant. There was a significant difference in speed; F(3, 60) = 6.61, ηρ2 = 0.248, p < 0.01. Post hoc analysis revealed significantly better time in DS than NCC and ST. However, no difference in speed was observed between DS and ST + 30% BW. Similarly, speed was similar in NCC, ST and ST + 30% BW. A significant difference in agility performance was also observed; F(3, 60) = 24.1, ηρ2= 0.546, p < 0.01. Post hoc analysis revealed significantly greater performance gains in DS than NCC. No significant difference in agility was observed in DS, ST and ST + 30% BW. In conclusion, a prolonged intermittent low-intensity isometric protocol using bodyweight only showed similar benefits with dynamic stretching in countermovement jump performance. When the same isometric condition with additional load equal to 30% of bodyweight was applied, effects in speed

  13. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning.

    PubMed

    Ho, Aloysius Y L; Pagliuca, Antonio; Kenyon, Michelle; Parker, Jane E; Mijovic, Aleksandar; Devereux, Stephen; Mufti, Ghulam J

    2004-09-15

    Reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) has improved the accessibility of transplantation in patients previously ineligible. We report the results of allografting following conditioning with fludarabine, busulphan, and alemtuzumab in 62 patients with myelodysplastic syndromes (MDSs) (matched sibling donors [24] or volunteer unrelated donors [VUDs, 38]). The median age for sibling recipients was 56 years (range, 41-70 years) and for VUD recipients, 52 years (range, 22-65 years), with a median follow-up (survivors) of 524 days (range, 93-1392 days) and 420 days (range, 53-1495 days), respectively. The nonrelapse mortality (NRM) at days 100, 200, and 360 was 0%, 5%, and 5%, respectively, for siblings and 11%, 17%, and 21%, respectively, for VUD. The overall survival at one year was 73% for siblings and 71% for VUDs, with a disease-free survival (DFS) of 61% and 59%, respectively. The prognostic significance of the International Prognostic Scoring System (IPSS) was preserved. Of recipients, 86% achieved full-donor chimerism. The cumulative incidence at day 100 of grades III to IV graft-versus-host disease (GVHD) for VUD recipients was 9% and for sibling recipients, 0%. There were 26 patients (16 sibling and 10 VUD) who received donor lymphocyte infusion (DLI) at a median of 273 days (range, 126-1323 days). RIC allogeneic HSCT using this protocol appears to be safe and permits durable donor engraftment. Longer follow-up is required to confirm any potential survival advantage.

  14. Mouse models of insulin resistance.

    PubMed

    Hribal, Marta Letizia; Oriente, Francesco; Accili, Domenico

    2002-05-01

    The hallmarks of type 2 diabetes are impaired insulin action in peripheral tissues and decreased pancreatic beta-cell function. Classically, the two defects have been viewed as separate entities, with insulin resistance arising primarily from impaired insulin-dependent glucose uptake in skeletal muscle, and beta-cell dysfunction arising from impaired coupling of glucose sensing to insulin secretion. Targeted mutagenesis and transgenesis involving components of the insulin action pathway have changed our understanding of these phenomena. It appears that the role of insulin signaling in the pathogenesis of type 2 diabetes has been overestimated in classic insulin target tissues, such as skeletal muscle, whereas it has been overlooked in liver, pancreatic beta-cells, and brain, which had been thought not to be primary insulin targets. We review recent progress and try to reconcile areas of apparent controversy surrounding insulin signaling in skeletal muscle and pancreatic beta-cells.

  15. II - Insulin processing in mitochondria.

    PubMed

    Camberos, María Del Carmen; Pérez, Adriana A; Passicot, Gisel A; Martucci, Lucía C; Wanderley, María I; Udrisar, Daniel P; Cresto, Juan C

    2016-10-01

    Our objective was to know how insulin is processing in mitochondria; if IDE is the only participant in mitochondrial insulin degradation and the role of insulin degradation on IDE accumulation in mitoplasts. Mitochondria and its fractions were isolated as described by Greenwalt. IDE was purified and detected in immunoblot with specific antibodies. High insulin degradation was obtained through addition to rat's diet of 25 g/rat of apple and 10 g/rat of hard-boiled eggs, 3 days a week. Mitochondrial insulin degradation was assayed with 5 % TCA, insulin antibody or Sephadex G50 chromatography. Degradation was also assayed 60 min at 37 °C in mitochondrial fractions (IMS and Mx) with diet or not and without IDE. Degradation in fractions precipitated with ammonium sulfates (60-80 %) were studied after mitochondrial insulin incubation (1 ng. insulin during 15 min, at 30 °C) or with addition of 2.5 mM ATP. Supplementary diet increased insulin degradation. High insulin did not increase mitoplasts accumulation and did not decrease mitochondrial degradation. High insulin and inhibition of degradation evidence insulin competition for a putative transport system. Mitochondrial incubation with insulin increased IDE in matrix as observed in immunoblot. ATP decreased degradation in Mx and increased it in IMS. Chromatography of IMS demonstrated an ATP-dependent protease that degraded insulin, similar to described by Sitte et al. Mitochondria participate in insulin degradation and the diet increased it. High insulin did not accomplish mitochondrial decrease of degradation or its accumulation in mitoplasts. Mitochondrial incubation with insulin increased IDE in matrix. ATP suggested being a regulator of mitochondrial insulin degradation.

  16. 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)

  17. 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.

  18. 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

  19. 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.

  20. Insulin and diet-induced changes in the ubiquitin-modified proteome of rat liver

    PubMed Central

    Shtein, Harrison C.; Nguyen, Thinh Q.; Suryana, Eurwin; Poronnik, Philip; Cooney, Gregory J.; Saunders, Darren N.

    2017-01-01

    Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions. KEGG pathway analysis of these proteins identified enrichment of metabolic pathways, TCA cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and carbon metabolism, with similar pathways altered by diet and insulin resistance. Thus, the rat liver ubiquitome is sensitive to diet and insulin stimulation and this is perturbed in insulin resistance. PMID:28329008

  1. Insulin signaling genes modulate nicotine-induced behavioral responses in C. elegans

    PubMed Central

    Wescott, Seth A.; Ronan, Elizabeth A.; Xu, X.Z. Shawn

    2015-01-01

    Insulin signaling has been suggested to modulate nicotine dependence, but the underlying genetic evidence has been lacking. Here, we used the nematode, C. elegans, to investigate whether genetic alterations in the insulin signaling pathway affect behavioral responses to nicotine. To do so, we challenged drug-naïve C. elegans with an acute dose of nicotine [100 μM] while recording changes in their locomotion speed. While 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, revealing a genetic link between nicotine behavior and insulin signaling. PMID:26317299

  2. Insulin-releasing and insulin-like activity of Agaricus campestris (mushroom).

    PubMed

    Gray, A M; Flatt, P R

    1998-05-01

    Agaricus campestris (mushroom) has been documented as a traditional treatment for diabetes. Here the administration of mushroom in the diet (62.5 g/kg) and drinking water (2.5 g/l) countered the hyperglycaemia of streptozotocin-diabetic mice. An aqueous extract of mushroom (1 mg/ml) stimulated 2-deoxyglucose transport (2.0-fold), glucose oxidation (1.5-fold) and incorporation of glucose into glycogen (1.8-fold) in mouse abdominal muscle. In acute 20 min tests, 0.25-1 mg/ml aqueous extract of mushroom evoked a stepwise 3.5- to 4.6-fold stimulation of insulin secretion from the BRIN-BD11 pancreatic B-cell line. This effect was abolished by 0.5 mM diazoxide and prior exposure to extract did not affect subsequent stimulation of insulin secretion by 10 mM L-alanine, thereby negating a detrimental effect on cell viability. The effect of extract was potentiated by 16.7 mM glucose, L-alanine (10 mM) and IBMX (1 mM), and a depolarising concentration of KCl (25 mM) did not augment the insulin-releasing activity of mushroom. Activity of the extract was found to be heat stable, acetone soluble and unaltered by exposure to alkali, but decreased with exposure to acid. Dialysis to remove components with molecular mass < 2000 Da caused a 40% reduction in activity. Sequential extraction with solvents revealed insulin-releasing activity to be greatest in polar fractions. Lack of haemagglutinin activity with extract activity indicated that activity was unlikely to be due to a lectin-mediated event. These results demonstrate the presence of antihyperglycaemic, insulin-releasing and insulin-like activity in A. campestris.

  3. Insulin Aspart (rDNA Origin) Injection

    MedlinePlus

    ... unless it is used in an external insulin pump. In patients with type 2 diabetes, insulin aspart ... also can be used with an external insulin pump. Before using insulin aspart in a pump system, ...

  4. Short-term in vivo inhibition of insulin receptor substrate-1 expression leads to insulin resistance, hyperinsulinemia, and increased adiposity.

    PubMed

    Araújo, Eliana P; De Souza, Cláudio T; Gasparetti, Alessandra L; Ueno, Mirian; Boschero, Antonio C; Saad, Mário J A; Velloso, Lício A

    2005-03-01

    Insulin receptor substrate-1 (IRS-1) has an important role as an early intermediary between the insulin and IGF receptors and downstream molecules that participate in insulin and IGF-I signal transduction. Here we employed an antisense oligonucleotide (IRS-1AS) to inhibit whole-body expression of IRS-1 in vivo and evaluate the consequences of short-term inhibition of IRS-1 in Wistar rats. Four days of treatment with IRS-1AS reduced the expression of IRS-1 by 80, 75, and 65% (P < 0.05) in liver, skeletal muscle, and adipose tissue, respectively. This was accompanied by a 40% (P < 0.05) reduction in the constant of glucose decay during an insulin tolerance test, a 78% (P < 0.05) reduction in glucose consumption during a hyperinsulinemic-euglycemic clamp, and a 90% (P < 0.05) increase in basal plasma insulin level. The metabolic effects produced by IRS-1AS were accompanied by a significant reduction in insulin-induced [Ser (473)] Akt phosphorylation in liver (85%, P < 0.05), skeletal muscle (40%, P < 0.05), and adipose tissue (85%, P < 0.05) and a significant reduction in insulin-induced tyrosine phosphorylation of ERK in liver (20%, P < 0.05) and skeletal muscle (30%, P < 0.05). However,