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Sample records for acute hyperglycemia worsens

  1. Hyperglycemia, Acute Ischemic Stroke and Thrombolytic Therapy

    Science.gov (United States)

    Bruno, Askiel; Fagan, Susan C.; Ergul, Adviye

    2014-01-01

    Ischemic stroke is a leading cause of disability and is considered now the 4th leading cause of death. Many clinical trials have shown that stroke patients with acute elevation in blood glucose at onset of stroke suffer worse functional outcomes, longer in-hospital stay and higher mortality rates. The only therapeutic hope for these patients is the rapid restoration of blood flow to the ischemic tissue through intravenous administration of the only currently proven effective therapy, tissue plasminogen activator (tPA). However, even this option is associated with the increased risk of intracerebral hemorrhage. Nonetheless, the underlying mechanisms through which hyperglycemia (HG) and tPA worsen the neurovascular injury after stroke are not fully understood. Accordingly, this review summarizes the latest updates and recommendations about the management of HG and co-administration of tPA in a clinical setting while focusing more on the various experimental models studying: 1. the effect of HG on stroke outcomes; 2. the potential mechanisms involved in worsening the neurovasular injury; 3. the different therapeutic strategies employed to ameliorate the injury, and finally; 4. the interaction between HG and tPA. Developing therapeutic strategies to reduce the hemorrhage risk with tPA in hyperglycemic setting is of great clinical importance. This can best be achieved by conducting robust preclinical studies evaluating the interaction between tPA and other therapeutics in order to develop potential therapeutic strategies with high translational impact. PMID:24619488

  2. Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management

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    Kruyt, Nyika D.; Biessels, Geert Jan; DeVries, J. Hans; Roos, Yvo B.

    2010-01-01

    Patients with acute ischemic stroke frequently test positive for hyperglycemia, which is associated with a poor clinical outcome. This association between poor glycemic control and an unfavorable prognosis is particularly evident in patients with persistent hyperglycemia, patients without a known

  3. Acute Hyperglycemia Associated with Anti-Cancer Medication

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    Yul Hwangbo

    2017-03-01

    Full Text Available Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1 antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis. Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anti-cancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life.

  4. Markers of tissue-specific insulin resistance predict the worsening of hyperglycemia, incident type 2 diabetes and cardiovascular disease.

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    Fízel'ová, Mária; FízeI'ová, Mária; Cederberg, Henna; Stančáková, Alena; Jauhiainen, Raimo; Vangipurapu, Jagadish; Kuusisto, Johanna; Laakso, Markku

    2014-01-01

    We investigated the ability of surrogate markers of tissue-specific insulin resistance (IR, Matsuda IR, Adipocyte IR, Liver IR) to predict deterioration of hyperglycemia, incident type 2 diabetes and cardiovascular events in the Metabolic Syndrome in Men (METSIM) Study. The METSIM Study includes 10,197 Finnish men, aged 45-73 years, and examined in 2005-2010. A total of 558 of 8,749 non-diabetic participants at baseline were diagnosed with new-onset diabetes and 239 with a new CVD event during a 5.9-year follow-up of this cohort (2010-2013). Compared to fasting plasma insulin level, Matsuda IR (IR in skeletal muscle) and Adipocyte IR were significantly better predictors of 2-hour plasma glucose and glucose area under the curve after adjustment for confounding factors. Liver IR was the strongest predictor of both incident type 2 diabetes (hazard ratio = 1.83, 95% confidence interval: 1.68-1.98) and cardiovascular events (hazard ratio = 1.31, 95% confidence interval: 1.15-1.48). Hazard ratios for fasting insulin were 1.37 (95% confidence interval: 1.32-1.42) and 1.11 (95% confidence interval: 1.00-1.24), respectively. Tissue-specific markers of IR, Matsuda IR and Adipocyte IR, were superior to fasting plasma insulin level in predicting worsening of hyperglycemia, and Liver IR was superior to fasting insulin level in predicting incident type 2 diabetes and cardiovascular events.

  5. Hyperglycemia

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    Hyperglycemia means high blood sugar or glucose. Glucose comes from the foods you eat. Insulin is a ... glucose into your cells to give them energy. Hyperglycemia happens when your body doesn't make enough ...

  6. Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis

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    Kennedy, James I.C.; Askelund, Kathryn J.; Premkumar, Rakesh; Phillips, Anthony R.J.; Murphy, Rinki; Windsor, John A.; Petrov, Maxim S.

    2016-01-01

    Abstract Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity. Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders. A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021). Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID:26871770

  7. Transient Hyperglycemia in Hispanic Children With Acute Lymphoblastic Leukemia

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    Baillargeon, Jacques; Langevin, Anne-Marie; Mullins, Judith; Ferry, Robert J.; DeAngulo, Guillermo; Thomas, Paul J.; Estrada, Jaime; Pitney, Aaron; Pollock, Brad H.

    2011-01-01

    Background Transient hyperglycemia occurs commonly during the treatment for childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to examine the incidence of and risk factors for transient hyperglycemia during induction chemotherapy in Hispanic pediatric patients diagnosed with B-Precursor ALL. Procedure The study cohort consisted of 155 Hispanic pediatric patients diagnosed with ALL and treated at one of two South Texas pediatric oncology centers between 1993 and 2002. Hyperglycemia was defined as ≥2 glucose determinations of ≥200 mg/dl during the first 28 days of induction chemotherapy. Results Overall, 11.0% of the study cohort developed transient hyperglycemia during induction chemotherapy. Age and body mass index (BMI) were both positively associated with the risk of hyperglycemia. Females exhibited a substantially higher risk of hyperglycemia than males, but this association did not reach statistical significance after adjusting for other covariates. Among patients who developed hyperglycemia, 100% of those who required insulin were in the 13–18-year age group and reported a family history of diabetes. Hyperglycemic patients classified as obese (BMI ≥ 95 centile) were more than twice as likely to have required insulin therapy compared to overweight patients (BMI 85–<95 centile) and three times as likely to have required insulin compared to normal weight (BMI <85 centile) patients. Conclusions The incidence of chemotherapy-induced transient hyperglycemia in the present study cohort is comparable to that reported in previous pediatric ALL patients. This finding is interesting in view of the elevated prevalence of obesity and the underlying dietary behaviors in this Hispanic study cohort. PMID:15700246

  8. Effect of acute hyperglycemia on clotting time and relative plasma ...

    African Journals Online (AJOL)

    Menstruating females seem to bleed more when they ingest sugar or sugar containing substances. This study was carried out to determine the effect of acute hyperglycemia on clotting time and relative plasma viscosity during menstruation. Forty menstruating females from the St. Philomena School of Midwifery, Benin, ...

  9. Acute hyperglycemia and contrast-induced nephropathy in primary percutaneous coronary intervention.

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    Marenzi, Giancarlo; De Metrio, Monica; Rubino, Mara; Lauri, Gianfranco; Cavallero, Annalisa; Assanelli, Emilio; Grazi, Marco; Moltrasio, Marco; Marana, Ivana; Campodonico, Jeness; Discacciati, Andrea; Veglia, Fabrizio; Bartorelli, Antonio L

    2010-12-01

    Acute hyperglycemia and contrast-induced nephropathy (CIN) are frequently observed in ST-elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), and both are associated with an increased mortality rate. We investigated the possible association between acute hyperglycemia and CIN in patients undergoing primary PCI. We prospectively enrolled 780 STEMI patients undergoing primary PCI. For each patient, plasma glucose levels were assessed at hospital admission. Acute hyperglycemia was defined as glucose levels>198 mg/dL (11 mmol/L). Contrast-induced nephropathy was defined as an increase in serum creatinine>25% from baseline in the first 72 hours. Overall, 148 (19%) patients had acute hyperglycemia; and 113 (14.5%) patients developed CIN. Patients with acute hyperglycemia had a 2-fold higher incidence of CIN than those without acute hyperglycemia (27% vs 12%, P<.001). In-hospital mortality was higher in patients with acute hyperglycemia than in those without acute hyperglycemia (12% vs 3%, P<.001). Mortality rate was also higher in patients developing CIN than in those without this renal complication (27% vs 0.9%, P<.001). Patients with acute hyperglycemia that developed CIN had the highest mortality rate (38%). Acute hyperglycemia was an independent predictor of CIN and in-hospital mortality. In STEMI patients undergoing primary PCI, acute hyperglycemia is associated with an increased risk for CIN and with increased in-hospital mortality. Copyright © 2010 Mosby, Inc. All rights reserved.

  10. Chronic hyperglycemia is related to poor functional outcome after acute ischemic stroke

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    Luitse, Merel Ja; Velthuis, Birgitta K; Kappelle, L Jaap; van der Graaf, Yolanda; Biessels, Geert Jan

    2017-01-01

    BACKGROUND: Acute hyperglycemia is associated with poor functional outcome after ischemic stroke, but the association between chronic antecedent hyperglycemia and outcome is unclear. AIM: We assessed the association between chronic hyperglycemia, measured by hemoglobin A1c, and functional outcome in

  11. Myocardial infarction, acute ischemic stroke, and hyperglycemia triggered by acute chlorine gas inhalation.

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    Kose, Ataman; Kose, Beril; Açikalin, Ayça; Gunay, Nurullah; Yildirim, Cuma

    2009-10-01

    Chlorine is one of the most common substances involved in toxic inhalation. Until now, several accidental exposures have been reported. The damage to the respiratory tract in the immediate phase after exposure to chlorine is well defined. Death occurs particularly due to pulmonary edema with respiratory failure and circulatory collapse. On the other hand, no association with myocardial infarction, acute stroke, severe hyperglycemia, and acute chlorine inhalation has been reported in literature. In the present study, an elderly (74-year-old) and diabetic case with myocardial infarction, acute stroke, hyperglycemia, and respiratory failure associated with acute chlorine intoxication after a diagnosis of acute chlorine poisoning and treatment in the emergency department is reported and the literature is revisited. Physicians should know that in elderly patients with a systemic disease who apply with chlorine gas inhalation, more serious complications along with damage in respiratory tract might be observed.

  12. Alcohol during pregnancy worsens acute respiratory infections in children.

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    Libster, Romina; Ferolla, Fausto M; Hijano, Diego R; Acosta, Patricio L; Erviti, Anabella; Polack, Fernando P

    2015-11-01

    This study explored whether alcohol consumption during pregnancy increased the risk of life-threatening respiratory infections in children. We prospectively evaluated children under the age of two years admitted to hospitals in Buenos Aires, Argentina, with severe acute respiratory infections during the winters of 2011 and 2012. Information on maternal alcohol consumption during the third trimester of pregnancy was collected using standardised questionnaires and categorised as never, low if it was once a week and high if it was equal or more than once a week. Of the 3423 children hospitalised with acute respiratory infection, 2089 (63.7%) had respiratory syncytial virus (RSV). Alcohol consumption during the last trimester was reported by 398 mothers (12.4%) and categorised as low (n = 210, 6.5%) or high (n = 188, 5.9%). A greater effect on life-threatening respiratory infection, defined as oxygen saturation of or up to 87%, was observed with higher alcohol intake due to all viruses and specifically RSV in the logistic regression analyses. Alcohol consumption was strongly associated with life-threatening disease, particularly in boys whose adjusted odds ratio rose from 3.67 to 13.52 when their mothers drank alcohol. Alcohol consumption during pregnancy was associated with life-threatening respiratory infections in boys. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  13. A hemorrhagic transformation model of mechanical stroke therapy with acute hyperglycemia in mice.

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    Couret, David; Bourane, Steeve; Catan, Aurélie; Nativel, Brice; Planesse, Cynthia; Dorsemans, Anne-Claire; Ait-Arsa, Imade; Cournot, Maxime; Rondeau, Philippe; Patche, Jessica; Tran-Dinh, Alexy; Lambert, Gilles; Diotel, Nicolas; Meilhac, Olivier

    2017-12-26

    Clinical benefit for mechanical thrombectomy (MT) in stroke was recently demonstrated in multiple large prospective studies. Acute hyperglycemia (HG) is an important risk factor of poor outcome in stroke patients, including those that underwent MT. The aim of this therapy is to achieve a complete reperfusion in a short time, given that reperfusion damage is dependent on the duration of ischemia. Here, we investigated the effects of acute HG in a mouse model of ischemic stroke induced by middle cerebral artery occlusion (MCAO). Hyperglycemic (intraperitoneal [ip] injection of glucose) and control (ip saline injection) 10-week male C57BL6 mice were subjected to MCAO (30, 90, and 180 min) followed by reperfusion obtained by withdrawal of the monofilament. Infarct volume, hemorrhagic transformation (HT), neutrophil infiltration, and neurological scores were assessed at 24 hr by performing vital staining, ELISA immunofluorescence, and behavioral test, respectively. Glucose injection led to transient HG (blood glucose = 250-390 mg/dL) that significantly increased infarct volume, HT, and worsened neurological outcome. In addition, we report that HG promoted blood-brain barrier disruption as shown by hemoglobin accumulation in the brain parenchyma and tended to increase neutrophil extravasation within the infarcted area. Acute HG increased neurovascular damage for all MCAO durations tested. HTs were observed as early as 90 min after ischemia under hyperglycemic conditions. This model mimics MT ischemia/reperfusion and allows the exploration of brain injury in hyperglycemic conditions. © 2017 Wiley Periodicals, Inc.

  14. Outcome in acute heart failure: prognostic value of acute kidney injury and worsening renal function.

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    Berra, Gregory; Garin, Nicolas; Stirnemann, Jérôme; Jannot, Anne-Sophie; Martin, Pierre-Yves; Perrier, Arnaud; Carballo, Sebastian

    2015-05-01

    The prognostic value of worsening renal function (WRF) in acute heart failure is debated. Moreover, it is not clear if the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in this context is detrimental. In a retrospective cohort study of 646 patients hospitalized for acute heart failure, the risk of death or readmission associated with acute kidney injury (AKI) present at admission, WRF during the 1st 7 days, and up-titration of ACEI/ARB were analyzed in a Cox proportional hazards model. AKI, WRF, hemoglobin concentration, ACEI/ARB up-titration, and use of loop diuretics before admission were significantly associated with the primary outcome in univariate analysis. In a multivariate model, the association remained significant for AKI (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13-1.47; P = .0002), WRF (HR 1.24, 95% CI 1.06-1.45; P = .0059), and ACEI/ARB up-titration (HR 0.79, 95% CI 0.64-0.97; P = .026). There was no excess mortality in patients with ACEI/ARB up-titration despite WRF. Both AKI and WRF are strongly associated with poor outcome in patients hospitalized for acute heart failure. ACEI/ARB up-titration seems to be protective. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance

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    Hameed Laftah Wanoose

    2011-03-01

    Full Text Available AbstractObjectives: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days.Methods: The study included 287 consecutive patients in the Al- Faiha Hospital in Basrah (Southern Iraq during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L and those equal to or more than that. Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L regardless of past history of diabetes.Results: Sixty one point seven percent (177 of patients were admitted with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of ≥140 mg/dl (7.8 mmol/L. There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95�0CI=1.0282-4.4307; p=0.0419 was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and

  16. [Recommendations for the management of emergencies in patients with diabetes, acute metabolic complications of diabetes, and steroid-related hyperglycemia].

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    Álvarez-Rodríguez, Esther; Agud Fernández, María; Villa Álvarez, María Cristina; Caurel Sastre, Zaida; Gallego Mínguez, Isabel; Carballo Cardona, César; Juan Arribas, Artur; Piñero Panadero, Raquel; Rubio Casas, Olga; Sáenz Abad, Daniel; Cuervo Pinto, Rafael

    2016-01-01

    Persons with diabetes make up a large percentage of patients attended in the emergency department. Most will be discharged, but patients who remain under observation in wards managed by the emergency department or who wait are waiting to be admitted to a conventional ward must receive appropriate, protocol-guided treatment for their diabetes. Situations of hyper- or hypoglycemia must be avoided because both worsen prognosis. Emergency physicians must correctly and efficiently prevent, diagnose, and manage acute metabolic complications of diabetes such as simple hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state. They must also be ready to prescribe and properly administer intravenous insulin to critically ill patients. Hyperglycemia induced by treatment with steroids deserves special mention. If this complication develops, the hyperglycemia is intense, influenced by increased insulin resistance and gluconeogenesis in the liver. Thus, it usually appears after meals and is dependent on steroid dose, duration of treatment, and individual predisposition. The recommendations in this paper elaborated by consensus of the Spanish Society of Emergency Medicine (SEMES) experts, are the first to be written specifically for use in emergency departments in Spain. They give a detailed, in-depth overview of emergencies related to diabetes and diabetic complications.

  17. Acute coronary syndrome and acute kidney injury: role of inflammation in worsening renal function.

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    Ortega-Hernández, Jorge; Springall, Rashidi; Sánchez-Muñoz, Fausto; Arana-Martinez, Julio-C; González-Pacheco, Héctor; Bojalil, Rafael

    2017-07-26

    Acute Kidney Injury (AKI), a common complication of acute coronary syndromes (ACS), is associated with higher mortality and longer hospital stays. The role of cytokines and other mediators is unknown in AKI induced by an ACS (ACS-AKI), leading to several unanswered questions. The worsening of renal function is usually seen as a dichotomous phenomenon instead of a dynamic change, so evaluating changes of the renal function in time may provide valuable information in the ACS-AKI setting. The aim of this study was to explore inflammatory factors associated to de novo kidney injury induced by de novo cardiac injury secondary to ACS. One hundred four consecutive patients with ACS were initially included on the time of admission to the Coronary Unit of the Instituto Nacional de Cardiología in Mexico City, from February to May 2016, before any invasive procedure, imaging study, diuretic or anti-platelet therapy. White blood count, hemoglobin, NT-ProBNP, troponin I, C-reactive protein, albumin, glucose, Na + , K + , blood urea nitrogen (BUN), total cholesterol, HDL, LDL, triglycerides, creatinine (Cr), endothelin-1 (ET-1), leukotriene-B4, matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinases-1, resolvin-D1 (RvD1), lipoxin-A4 (LXA4), interleukin-1β, -6, -8, and -10 were measured. We finally enrolled 78 patients, and subsequently we identified 15 patients with ACS-AKI. Correlations were obtained by a Spearman rank test. Low-rank regression, splines regressions, and also protein-protein/chemical interactions and pathways analyses networks were performed. Positive correlations of ΔCr were found with BUN, admission Cr, GRACE score, IL-1β, IL-6, NT-ProBNP and age, and negative correlations with systolic blood pressure, mean-BP, diastolic-BP and LxA4. In the regression analyses IL-10 and RvD1 had positive non-linear associations with ΔCr. ET-1 had also a positive association. Significant non-linear associations were seen with NT-proBNP, admission Cr, BUN

  18. Adverse prognostic influence of diabetes mellitus and hyperglycemia on the clinical course of brain infarct: a review of its causes with special reference to the pathogenesis of hyperglycemia in the acute phase of stroke

    Directory of Open Access Journals (Sweden)

    Charles André

    1992-06-01

    Full Text Available In non-diabetic patients, the appearance of hyperglycemia in the acute phase of stroke is related to the extension of cellular injury, and hence to the physiologic stress response. In animal models of ischemic insult, the deleterious effects of hyperglycemia depend heavily on the production of lactic acid «via» activation of the glycolitic anaerobic pathway. The abnormal production of lactic acid and consequent tissular acidosis appear mainly in the early post-reperfusion period, or in states of marked but partial reduction of blood flow. A direct reduction of cerebral blood flow and, perhaps, the production of a hyperosmolar state may contribute to worsening of the ischemic injury. In diabetic patients, previous hemoreologic and microcirculatory changes, and a greater susceptibility to infections may additionally reduce the chances of complete recovery after stroke.

  19. Worsening renal function definition is insufficient for evaluating acute renal failure in acute heart failure.

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    Shirakabe, Akihiro; Hata, Noritake; Kobayashi, Nobuaki; Okazaki, Hirotake; Matsushita, Masato; Shibata, Yusaku; Nishigoori, Suguru; Uchiyama, Saori; Asai, Kuniya; Shimizu, Wataru

    2018-02-01

    Whether or not the definition of a worsening renal function (WRF) is adequate for the evaluation of acute renal failure in patients with acute heart failure is unclear. One thousand and eighty-three patients with acute heart failure were analysed. A WRF, indicated by a change in serum creatinine ≥0.3 mg/mL during the first 5 days, occurred in 360 patients while no-WRF, indicated by a change Acute kidney injury (AKI) upon admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value and placed into groups based on the degree of AKI: no-AKI (n = 751), Class R (risk; n = 193), Class I (injury; n = 41), or Class F (failure; n = 98). The patients were assigned to another set of four groups: no-WRF/no-AKI (n = 512), no-WRF/AKI (n = 211), WRF/no-AKI (n = 239), and WRF/AKI (n = 121). A multivariate logistic regression model found that no-WRF/AKI and WRF/AKI were independently associated with 365 day mortality (hazard ratio: 1.916; 95% confidence interval: 1.234-2.974 and hazard ratio: 3.622; 95% confidence interval: 2.332-5.624). Kaplan-Meier survival curves showed that the rate of any-cause death during 1 year was significantly poorer in the no-WRF/AKI and WRF/AKI groups than in the WRF/no-AKI and no-WRF/no-AKI groups and in Class I and Class F than in Class R and the no-AKI group. The presence of AKI on admission, especially Class I and Class F status, is associated with a poor prognosis despite the lack of a WRF within the first 5 days. The prognostic ability of AKI on admission may be superior to WRF within the first 5 days. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  20. Transient and persistent worsening renal function during hospitalization for acute heart failure.

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    Krishnamoorthy, Arun; Greiner, Melissa A; Sharma, Puza P; DeVore, Adam D; Johnson, Katherine Waltman; Fonarow, Gregg C; Curtis, Lesley H; Hernandez, Adrian F

    2014-12-01

    Transient and persistent worsening renal function (WRF) may be associated with different risks during hospitalization for acute heart failure. We compared outcomes of patients hospitalized for acute heart failure with transient, persistent, or no WRF. We identified patients 65 years or older hospitalized with acute heart failure from a clinical registry linked to Medicare claims data. We defined WRF as an increase in serum creatinine of ≥ 0.3 mg/dL after admission. We further classified patients with WRF by the difference between admission and last recorded serum creatinine levels into transient WRF (acute heart failure were associated with higher adjusted risks for 90-day all-cause postadmission mortality. Patients with persistent WRF had worse outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. MicroRNAs relate to early worsening of renal function in patients with acute heart failure.

    Science.gov (United States)

    Bruno, Noemi; ter Maaten, Jozine M; Ovchinnikova, Ekaterina S; Vegter, Eline L; Valente, Mattia A E; van der Meer, Peter; de Boer, Rudolf A; van der Harst, Pim; Schmitter, Daniela; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; Pinto, Yigal M; van Veldhuisen, Dirk J; Hillege, Hans L; Berezikov, Eugene; Voors, Adriaan A

    2016-01-15

    Deregulation of microRNAs (miRNAs) may be involved in the pathogenesis of heart failure (HF) and renal disease. Our aim is to describe miRNA levels related to early worsening renal function in acute HF patients. We studied the association between 12 circulating miRNAs and Worsening Renal Function (WRF; defined as an increase in the serum creatinine level of 0.3mg per deciliter or more from admission to day 3), absolute change in creatinine and Neutrophil Gelatinase Associated Lipocalin (NGAL) from admission to day 3 in 98 patients hospitalized for acute HF. At baseline, circulating levels of all miRNAs were lower in patients with WRF, with statistically significant decreased levels of miR-199a-3p, miR-423-3p, and miR-let-7i-5p (p-valueacute HF were consistently lower in patients who developed worsening of renal function. MiR-199a-3p was the best predictor of WRF in these patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Patients With Fibrotic Interstitial Lung Disease Hospitalized for Acute Respiratory Worsening: A Large Cohort Analysis.

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    Moua, Teng; Westerly, Blair D; Dulohery, Megan M; Daniels, Craig E; Ryu, Jay H; Lim, Kaiser G

    2016-05-01

    Acute respiratory worsening (ARW) requiring hospitalization in patients with fibrotic interstitial lung disease (f-ILD) is common. Little is known about the frequency and implications of ARW in IPF and non-IPF ILD patients hospitalized for acute exacerbation (AE) vs known causes of ARW. All consecutive patients with f-ILD hospitalized with ARW at our institution from 2000 to 2014 were reviewed. ARW was defined as any worsening of respiratory symptoms with new or worsened hypoxemia or hypercapnia within 30 days of admission. Suspected AE was defined using modified 2007 American Thoracic Society/European Respiratory Society criteria. Known causes of ARW were reviewed and collated along with in-hospital and all-cause mortality postdischarge. A total of 220 patients (100 with IPF and 120 non-IPF) composed 311 admissions for ARW. Suspected AE (SAE) comprised 52% of ARW admissions, followed by infection (20%), and subacute progression of disease (15%). In-hospital mortality was similar in patients with IPF vs patients without (55 vs 45%, P = .18), but worse in suspected AE admission types (OR, 3.1 [1.9-5.14]). One-year survival after last ARW admission for the whole cohort was 22%, despite only 27% of patients presenting with baseline oxygen requirement at admission and a mean admission Charlson Comorbidity Index score of 5.4 (expected 1-year survival, 89%). Survival after discharge was similar between SAE and secondary ARW admission types in both IPF and non-IPF patients. Among patients with f-ILD, hospitalization for ARW appears associated with significant in-hospital and postdischarge mortality regardless of underlying fibrotic lung disease or non-AE cause of acute respiratory decline. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  3. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

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    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  4. The Influence of Hyperglycemia at Admission on In-hospital Arrhythmia Patients with Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Ahmad Fariz M.Z Zein

    2015-12-01

    were no association between type of ACS, diabetes mellitus (DM, obesity, and hypertension, with the in-hospital arrhythmias. In multivariate analysis, the adjusted OR of HA was 2.85 (95% CI 1.35-6.02, and DM was the confounding variable. Conclusion: the incidence of in-hospital arrhythmias in patients with ACS was 21.55% (95% CI 16.26-26.84. Hyperglycemia at admission may increase the risk of in-hospital arrhythmia in patients with ACS. Key words: hyperglycemia at admission; in-hospital arrhythmia; acute coronary syndrome

  5. IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease

    Science.gov (United States)

    Baek, Jea-Hyun; Zeng, Rui; Weinmann-Menke, Julia; Valerius, M. Todd; Wada, Yukihiro; Ajay, Amrendra K.; Colonna, Marco; Kelley, Vicki R.

    2015-01-01

    Macrophages (Mø) are integral in ischemia/reperfusion injury–incited (I/R-incited) acute kidney injury (AKI) that leads to fibrosis and chronic kidney disease (CKD). IL-34 and CSF-1 share a receptor (c-FMS), and both cytokines mediate Mø survival and proliferation but also have distinct features. CSF-1 is central to kidney repair and destruction. We tested the hypothesis that IL-34–dependent, Mø-mediated mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. In renal I/R, the time-related magnitude of Mø-mediated AKI and subsequent CKD were markedly reduced in IL-34–deficient mice compared with controls. IL-34, c-FMS, and a second IL-34 receptor, protein-tyrosine phosphatase ζ (PTP-ζ) were upregulated in the kidney after I/R. IL-34 was generated by tubular epithelial cells (TECs) and promoted Mø-mediated TEC destruction during AKI that worsened subsequent CKD via 2 distinct mechanisms: enhanced intrarenal Mø proliferation and elevated BM myeloid cell proliferation, which increases circulating monocytes that are drawn into the kidney by chemokines. CSF-1 expression in TECs did not compensate for IL-34 deficiency. In patients, kidney transplants subject to I/R expressed IL-34, c-FMS, and PTP−ζ in TECs during AKI that increased with advancing injury. Moreover, IL-34 expression increased, along with more enduring ischemia in donor kidneys. In conclusion, IL-34-dependent, Mø-mediated, CSF-1 nonredundant mechanisms promote persistent ischemia-incited AKI that worsens subsequent CKD. PMID:26121749

  6. Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction.

    Science.gov (United States)

    Wang, Jiali; Liu, Baoshan; Han, Hui; Yuan, Qiuhuan; Xue, Mengyang; Xu, Feng; Chen, Yuguo

    2015-02-23

    Although hyperglycemia is common in patients with acute myocardial infarction (MI), the underlying mechanisms are largely unknown. Insulin signaling plays a key role in the regulation of glucose homeostasis. In this study, we test the hypothesis that rapid alteration of insulin signaling pathways could be a potential contributor to acute hyperglycemia after MI. Male rats were used to produce MI by ligation of the left anterior descending coronary artery. Plasma glucose and insulin levels were significantly higher in MI rats than those in controls. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. However, insulin-stimulated signaling was not altered significantly in skeletal muscle after MI. The relative mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase were slightly higher in the liver tissue of MI rats than those in controls. Rosiglitazone (ROSI) markedly restored hepatic insulin signaling, inhibited gluconeogenesis and reduced plasma glucose levels in MI rats. Insulin resistance develops rapidly in liver but not skeletal muscle after MI, which contributes to acute hyperglycemia. Therapy aimed at potentiating hepatic insulin signaling may be beneficial for MI-induced hyperglycemia.

  7. Metabolism of biogenic amines in acute cerebral ischemia: Influence of systemic hyperglycemia

    Directory of Open Access Journals (Sweden)

    Milovanović Aleksandar

    2012-01-01

    Full Text Available Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brain circulation in experimental or clinical conditions, neurotransmitter metabolism, primarily of biogenic amines, is disturbed. Many researches with various experimental models of complete ischemia reported a decrease in the content of norepinephrine, dopamine and serotonin in the CNS tissue. It was proven that hyperglycemia can drastically increase cerebral injury followed by short-term cerebral ischemia. Considering the fact that biogenic amines (dopamine, norepinephrine and serotonin influence the size of neurologic damage, as well as the fact that in hyperglycemic conditions infarct size (from the morphological aspect is larger relative to normoglycemic status, the intention was to evaluate the role of biogenic amines in occurrence of damage in conditions of hyperglycemia, i.e. in the case of brain apoplexia in diabetics. Analysis of biogenic amines metabolism in states of acute hyperglycemia, as well as analysis of the effects of reversible and irreversible brain ischemia on metabolism of serotonin, dopamine and norepinephrine, showed that acute hyperglycemia slows down serotonin, dopamine and norepinephrine metabolism in the cerebral cortex and n. caudatus. Brain ischemia in normoglycemic animals by itself has no influence on biogenic amines metabolism, but the effect of ischemia becomes apparent during reperfusion. In recirculation, which corresponds to the occurrences in penumbra, release of biogenic amines is uncontrolled and increased. Brain ischemia in acute hyperglycemic animals

  8. Prognostic impact of in-hospital hyperglycemia in hospitalized patients with acute heart failure: Results of the IN-HF (Italian Network on Heart Failure) Outcome registry.

    Science.gov (United States)

    Targher, Giovanni; Dauriz, Marco; Tavazzi, Luigi; Temporelli, Pier Luigi; Lucci, Donata; Urso, Renato; Lecchi, Gabriella; Bellanti, Giancarlo; Merlo, Marco; Rossi, Andrea; Maggioni, Aldo P

    2016-01-15

    Although diabetes mellitus is frequently associated with heart failure (HF), the association between elevated admission glucose levels and adverse outcomes has not been well established in hospitalized patients with acute HF. We prospectively evaluated in-hospital mortality, post-discharge 1-year mortality and 1-year re-hospitalization rates in the Italian Network on Heart Failure (IN-HF) Outcome registry cohort of 1776 patients hospitalized with acute HF and stratified by their admission glucose levels (i.e., known diabetes, newly diagnosed hyperglycemia, no diabetes). Compared with those without diabetes (n = 586), patients with either known diabetes (n = 749) (unadjusted-odds ratio [OR] 1.64, 95%CI 0.99–2.70) or newly diagnosed hyperglycemia (n = 441) (unadjusted-OR 2.34, 95%CI 1.39–3.94) had higher in-hospital mortality, but comparable post-discharge 1-year mortality rates. After adjustment for age, sex, systolic blood pressure, estimated glomerular filtration rate, left ventricular ejection fraction, HF etiology and HF worsening/de novo presentation, the results remained unchanged in patients with known diabetes (adjusted-OR 1.86, 95%CI 1.01–3.42), while achieved borderline significance in those with newly diagnosed hyperglycemia (adjusted-OR 1.81, 95%CI 0.95–3.45). One-year re-hospitalization rates were lower in patients with newly diagnosed hyperglycemia (adjusted-hazard ratio 0.74, 95%CI 0.56–0.96) than in other groups. Elevated admission blood glucose levels are associated with poorer in-hospital survival outcomes in patients with acute HF, especially in those with previously known diabetes. This finding further highlights the importance of tight glycemic control during hospital stay and address the need of dedicated intervention studies to identify customized clinical protocols to improve in-hospital survival of these high-risk patients.

  9. Risk Factors for Worsening of Acute Pancreatitis in Patients Admitted with Mild Acute Pancreatitis.

    Science.gov (United States)

    Jin, Zhouxiang; Xu, Lubai; Wang, Xiangyu; Yang, Dinghua

    2017-02-26

    BACKGROUND The aim of the present study was to investigate risk factors for developing more severe pancreatitis, including moderately severe (MSAP) and severe acute pancreatitis (SAP), in patients admitted with mild acute pancreatitis (MAP). MATERIAL AND METHODS Patients admitted with MAP to our hospital from March 2013 to May 2016 were included and prospectively evaluated. Possible risk factors for developing MSAP or SAP were age, blood glucose level on admission, etiology, sex, Ranson score, amylase level, Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores, C-reactive protein (CRP) level, serum calcium level, visceral fat area (VFA), body mass index (BMI), whether this was the first episode of AP, and method of administration of octreotide. The effects of variables for developing MSAP or SAP were evaluated using univariate and multivariate logistic regression models. Mortality, hospital duration, and rate of ICU transfer of patients were compared between patients who developed MSAP or SAP and patients who did not. RESULTS A total of 602 patients admitted with MAP were recruited into this study (256 men and 346 women). Seventy-four patients (12.3%) developed MSAP or SAP. According to univariate logistic regression analyses, the results indicated that there were 5 significant differences between patients who developed MSAP or SAP and those who did not: VFA (>100 cm²) (p=0.003), BMI (≥25 kg/m²) (p=0.001), Ranson score(p=0.004), APACHE-II (≥5) (p=0.001), and blood glucose level on admission (>11.1 mmol/L) (p=0.040). Further multivariate logistic regression analyses revealed that BMI (≥25 kg/m²) (p=0.005), APACHE-II (≥5) (p=0.001), and blood glucose level on admission (>11.1 mmol/L) (p=0.004) were independent risk factors for developing MSAP or SAP in patients admitted with MAP. Moreover, patients who developed MSAP or SAP had a mortality rate of 5.4%. CONCLUSIONS Significant risk factors for developing MSAP or SAP in patients admitted

  10. Hyperglycemia in nondiabetic patients during the acute phase of stroke

    OpenAIRE

    Godoy, Daniel Agustin; Soler,Caridad; Videtta,Walter; Castillo Fuenzalida,Luis; Paranhos,Jorge; Costilla, Marcelo; Piñero, Gustavo; Jibaja,Manuel; Melo,Leonardo Jardim Vaz de

    2012-01-01

    OBJECTIVE: To determine patterns of hyperglycemic (HG) control in acute stroke. METHODS: Anonymous survey through Internet questionnaire. Participants included Latin-American physicians specialized in neurocritical care. RESULTS: The response rate was 74%. HG definition varied widely. Fifty per cent considered it when values were >140 mg/dL (7.8 mmol/L). Intravenous (IV) regular insulin was the drug of choice for HG correction. One fifth of the respondents expressed adherence to a protocol. I...

  11. The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial protocol: a randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke.

    Science.gov (United States)

    Bruno, Askiel; Durkalski, Valerie L; Hall, Christiana E; Juneja, Rattan; Barsan, William G; Janis, Scott; Meurer, William J; Fansler, Amy; Johnston, Karen C

    2014-02-01

    Patients with acute ischemic stroke and hyperglycemia have worse outcomes than those without hyperglycemia. Intensive glucose control during acute stroke is feasible and can be accomplished safely but has not been fully assessed for efficacy. The Stroke Hyperglycemia Insulin Network Effort trial aims to determine the safety and efficacy of standard vs. intensive glucose control with insulin in hyperglycemic acute ischemic stroke patients. This is a randomized, blinded, multicenter, phase III trial of approximately 1400 hyperglycemic patients who receive either standard sliding scale subcutaneous insulin (blood glucose range 80-179 mg/dL, 4·44-9·93 mmol/L) or continuous intravenous insulin (target blood glucose 80-130 mg/dL, 4·44-7·21 mmol/L) for up to 72 h, starting within 12 h of stroke symptom onset. The acute treatment phase is single blind (for the patients), but the final outcome assessment is double blind. The study is powered to detect a 7% absolute difference in favorable outcome at 90 days. The primary outcome is a baseline severity adjusted 90-day modified Rankin Scale score, defined as 0, 0-1, or 0-2, if the baseline National Institutes of Health Stroke Scale score is 3-7, 8-14, or 15-22, respectively. The primary safety outcome is the rate of severe hypoglycemia (hyperglycemia. It will determine the potential benefits and risks of intensive glucose control during acute stroke. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

  12. Beta-blockers use and risk of hyperglycemia in acute stroke patients.

    Science.gov (United States)

    Dziedzic, Tomasz; Pera, Joanna; Zur-Wyrozumska, Kamila; Klimkowicz-Mrowiec, Aleksandra; Szczudlik, Andrzej; Slowik, Agnieszka

    2012-07-01

    Beta-adrenergic blockade prevents or diminishes stress-induced hyperglycemia in different experimental models. The aim of the study was to determine if the use of beta-blockers before stroke reduces the risk of acute hyperglycemia in stroke patients. We analyzed the data of 603 consecutive patients with acute ischemic stroke and without pre-stroke diagnosis of diabetes mellitus admitted to stroke unit within 24 h after symptoms onset. Plasma glucose level on admission (6.0 ± 1.4 vs 6.6 ± 1.9 mmol/L, P = 0.01) and fasting glucose on day 1 (5.2 ± 1.1 vs 5.7 ± 1.1 mmol/L, P = 0.02) were significantly lower in patients treated with beta-blockers before stroke than in those who did not receive such a treatment. On multivariate logistic analysis beta-blockers use before stroke was associated with reduced risk of glucose level on admission ≥7.8 mmol/L (OR: 0.22, 95%CI: 0.07-0.74) and fasting glucose on day 1 ≥ 7.0 mmol/L (OR: 0.21, 95%CI: 0.05-0.91). The risk of fasting hyperglycemia defined as glucose ≥6.1 mmol/L did not differ between groups. Beta-blockage before stroke onset may result in lower plasma glucose on admission and prevent early hyperglycemia in patients without pre-stroke diagnosis of diabetes mellitus. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Fuzzy linguistic prediction model for sinoatrial node field potential analysis in acute hyperglycemia environment.

    Science.gov (United States)

    Feng, Yu; Cao, Hui; Wang, Yanxia; Zhang, Yanbin

    2015-01-01

    The objective of this study is to build a fuzzy linguistic prediction model (FLPM) for analyzing the actuation duration of acute hyperglycemia to sinoatrial node field potential. The field potential was recorded using microelectrode arrays (MEA). The experimental data were analyzed using partial least squares (PLS), support vector machine (SVM), back propagation neural network (BPNN) and the proposed method. The experimental results showed that the fuzzy linguistic prediction model could be adopted for predicting the actuation duration of high glucose to the sinoatrial node field potential. Compared with the other aforementioned models, the proposed model had higher prediction accuracy.

  14. Age-dependent differences in diabetes and acute hyperglycemia between men and women with ST-elevation myocardial infarction: a cohort study

    NARCIS (Netherlands)

    Otten, A.M.; Ottervanger, J.P.; Timmer, J.R.; Hof, A.W. van 't; Dambrink, J.H.; Gosselink, A.M.; Hoorntje, J.C.A.; Suryapranata, H.; Maas, A.H.E.M.

    2013-01-01

    BACKGROUND: Both acute hyperglycemia as diabetes results in an impaired prognosis in ST-elevation myocardial infarction (STEMI) patients. It is unknown whether there is a different prevalence of diabetes and acute hyperglycemia in men and women within age-groups. METHODS: Between 2004 and 2010, 4640

  15. Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

    Science.gov (United States)

    Gillies, Nicola; Pendharkar, Sayali A; Asrani, Varsha M; Mathew, Juby; Windsor, John A; Petrov, Maxim S

    2016-01-01

    Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. Interleukin-6 appears to be implicated in the development of chronic

  16. Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans

    DEFF Research Database (Denmark)

    Vollmer, Kirsten; Gardiwal, Husai; Menge, Bjoern A

    2009-01-01

    INTRODUCTION: Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes. It is unclear whether this is a primary defect or a consequence of the hyperglycemia in type 2 diabetes. We examined whether acute...... hyperglycemia reduces the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1, and if so, whether this can be attributed to changes in gastric emptying. PATIENTS AND METHODS: Fifteen nondiabetic individuals participated in a euglycemic clamp and a hyperglycemic clamp experiment, carried...... the hyperglycemic clamp experiments and 83 +/- 3 mg/dl during the euglycemia (P hyperglycemia, but meal ingestion led to a decline in glucose requirements in both experiments (P

  17. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

    Science.gov (United States)

    Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

    2016-12-01

    Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

  18. Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability.

    Science.gov (United States)

    Studer, Valeria; Rocchi, Camilla; Motta, Caterina; Lauretti, Benedetta; Perugini, Jacopo; Brambilla, Laura; Pareja-Gutierrez, Lorena; Camera, Giorgia; Barbieri, Francesca Romana; Marfia, Girolama A; Centonze, Diego; Rossi, Silvia

    2017-01-01

    Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis. The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis. Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed. Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse. Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

  19. Prognostic Impact of BNP Variations in Patients Admitted for Acute Decompensated Heart Failure with In-Hospital Worsening Renal Function.

    Science.gov (United States)

    Stolfo, D; Stenner, E; Merlo, M; Porto, A G; Moras, C; Barbati, G; Aleksova, A; Buiatti, A; Sinagra, G

    2017-03-01

    The significance of worsening renal function (WRF) in patients admitted for acute decompensated heart failure (ADHF) is still controversial. We hypothesised that changes in brain natriuretic peptide (BNP) might identify patients with optimal diuretic responsiveness resulting in transient WRF, not negatively affecting the prognosis. Our aim was to verify if in-hospital trends of BNP might be helpful in the stratification of patients with WRF after treatment for ADHF. 122 consecutive patients admitted for ADHF were enrolled. Brain natriuretic peptide and eGFR were evaluated at admission and discharge. A 20% relative decrease in eGFR defined WRF, whereas a BNP reduction ≥40% was considered significant. The primary combined endpoint was death/urgent heart transplantation and re-hospitalisation for ADHF. Worsening renal function occurred in 23% of patients without differences in outcome between patients with and without WRF (43% vs. 45%, p=0.597). A significant reduction in BNP levels over the hospitalisation occurred in 59% of the overall population and in 71% of patients with WRF. At a median follow-up of 13.0 (IQR 6-36) months, WRF patients with ≥40% BNP reduction had a lower rate of death/urgent heart transplantation/re-hospitalisation compared to WRF patients without BNP reduction (30% and 75%, respectively; p=0.007). Favourable BNP trend was the strongest variable in predicting the outcome in WRF patients (HR 0.222, 95% CI 0.066-0.753, p=0.016). Worsening renal function does not affect the prognosis of ADHF and, when associated with a significant BNP reduction, identifies patients with adequate decongestion at discharge and favourable outcome. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  20. Correlation between Stress Hyperglycemia and Short-Term Prognosis in non Diabetic Patients with Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Rafighdoust Amirhossein

    2009-03-01

    Full Text Available Background: Abnormal hyperglycemia is a common finding in early phase of acute myocardial infarction that is named as stress hyperglycemia. In this study we have evaluated primary blood sugar of non-diabetic patients with acute myocardial infarction at the time of admission to compare the early complications between patients with high or normal blood sugar. We aimed to find any relation between primary blood sugar and post MI complication rate. Materials and Methods: One hundred non-diabetic patients with acute myocardial infarction who were referred to heart emergency ward of Imam Reza Hospital (Mashhad, Iran were included in this study. According to primary blood glucose level, 50 patients with blood glucose > 126 mg/dl were compared with 50 patients with normal blood glucose level. All patients were evaluated during hospitalization and daily clinical examinations laboratory tests, and routine non-invasive assessments were done. The results were analyzed by SPSS software and the level of signification difference was described as p<0.05.Results: Sinus tachycardia, atrial fibrillation, bundle branch block, ventricular extrasystole, prolonged PR-interval and heart failure according to Klip classification and also according to echocardiographic index (EF<50 were statistically significant and more common in hyperglycemic patients (P<0.05. Thromboembolic and mechanical complications (papillary muscle dysfunction, pericarditis, phlebitis and angina were also more common in hyperglycemic group although the differences were not significant statistically. Conclusion: It seems that high rate of early complications in non-diabetic patients with acute myocardial infarction is directly related to primary hyperglycemia (stress hyperglycemia.

  1. Worsening heart failure during hospitalization for acute heart failure: Insights from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF).

    Science.gov (United States)

    Kelly, Jacob P; Mentz, Robert J; Hasselblad, Vic; Ezekowitz, Justin A; Armstrong, Paul W; Zannad, Faiez; Felker, G Michael; Califf, Robert M; O'Connor, Christopher M; Hernandez, Adrian F

    2015-08-01

    Despite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF. We assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1 symptom or sign of new, persistent, or WHF requiring additional intravenous inotropic/vasodilator or mechanical therapy during index hospitalization. We assessed the relationship between WHF and 30-day mortality, 30-day mortality or HF hospitalization, and 180-day mortality. We also assessed whether there was a differential association between early (days 1-3) vs late (day ≥4) WHF and outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients with WHF were more often male and had a history of atrial fibrillation or diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85-18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25-8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values HF during index hospitalization was associated with worse 30- and 180-day outcomes. Worsening HF may represent an important patient-centered outcome in acute HF and a focus of future treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure.

    Science.gov (United States)

    Damman, Kevin; Valente, Mattia A E; van Veldhuisen, Dirk J; Cleland, John G F; O'Connor, Christopher M; Metra, Marco; Ponikowski, Piotr; Cotter, Gad; Davison, Beth; Givertz, Michael M; Bloomfield, Daniel M; Hillege, Hans L; Voors, Adriaan A

    2017-07-08

    The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A₁Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF ( p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.

  3. Relationship of hyperglycemia and prognosis in elderly acute myocardial infarction patients with high risk: a clinical study

    Directory of Open Access Journals (Sweden)

    Yuan GAO

    2013-07-01

    Full Text Available Objective To assess the influence of post-admission random hyperglycemia of elderly patients suffering from acute myocardial infarction (STEMI with elevation of ST segment on cardiac function, coronary perfusion, and the prognosis of one year later. Methods A total of 137 STEMI patients aged over 75 years were enrolled in present study, including 69 cases of random blood glucose ≥11mmol/L (hyperglycemia group and 68 cases of random blood glucose<11mmol/L (control group. All the subjects underwent percutaneous coronary intervention (PCI. The cardiac function before and after operation, postoperative coronary blood flow, serum brain natriuretic peptide (BNP and hypersensitive C reactive protein (hs-CRP values of all the patients were retrospectively analyzed. Patients were followed up for major adverse cardiac events (MACE within 12 months after operation. Results After operation, the left ventricle ejection fraction (LVEF was significantly lower in hyperglycemia group than that in control group (42.64%±5.29% vs 54.13%±4.31%, P=0.031, the BNP and hs-CRP levels were significantly higher in hyperglycemia group than that in control group (619.53±145.77ng/L vs 489.46±159.63ng/L, P=0.035; 26.71±11.28mg/L vs 17.89±9.03mg/ L, P=0.023. The proportion of target coronary blood flow TIMI≤2 was relatively higher, and the incidence of MACE in 12 months of follow-up was also higher in hyperglycemia group compared with that in control group (13.94% vs 2.94%, P=0.030; 19.35% vs 10.29%, P=0.031. Cox proportional hazards regression model showed that age (HR=1.03, 95% CI 1.001-1.043, P=0.009, symptom to door time (HR=1.74, 95% CI 1.005-2.102, P=0.039, KILLIP ≥2 (HR=2.02, 95% CI 1.004-2.871, P=0.010, SYNTAX score (HR=2.88, 95% CI 1.105-2.906, P=0.008, hyperglycemia (HR=2.09, 95% CI 1.011-2.439, P=0.014 were the independent predictors of 12 months MACE. Conclusion Elderly high risk STEMI patients with admission hyperglycemia have worse cardiac

  4. Persistent hyperglycemia is an independent predictor of outcome in acute myocardial infarction

    NARCIS (Netherlands)

    van der Horst, Iwan C. C.; Nijsten, Maarten W. N.; Vogelzang, Mathijs; Zijlstra, Felix

    2007-01-01

    Background: Elevated blood glucose values are a prognostic factor in myocardial infarction (MI) patients. The unfavourable relation between hyperglycemia and outcome is known for admission glucose and fasting glucose after admission. These predictors are single measurements and thus not indicative

  5. Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics.

    Science.gov (United States)

    Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E

    2013-06-01

    To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

  6. Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Paula Bernardo de Carvalho

    2016-11-01

    Full Text Available Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C, the pamidronate group (P, the doxorubicin group (D and the doxorubicin/pamidronate group (DP. The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP. After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP. Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.

  7. The prognostic impact of worsening renal function in Japanese patients undergoing percutaneous coronary intervention with acute coronary syndrome.

    Science.gov (United States)

    Murata, Nobuhiro; Kaneko, Hidehiro; Yajima, Junji; Oikawa, Yuji; Oshima, Toru; Tanaka, Shingo; Kano, Hiroto; Matsuno, Shunsuke; Suzuki, Shinya; Kato, Yuko; Otsuka, Takayuki; Uejima, Tokuhisa; Nagashima, Kazuyuki; Kirigaya, Hajime; Sagara, Koichi; Sawada, Hitoshi; Aizawa, Tadanori; Yamashita, Takeshi

    2015-10-01

    The prognostic impact of worsening renal function (WRF) in acute coronary syndrome (ACS) patients is not fully understood in Japanese clinical practice, and clinical implication of persistent versus transient WRF in ACS patients is also unclear. With a single hospital-based cohort in the Shinken database 2004-2012 (n=19,994), we followed 604 ACS patients who underwent percutaneous coronary intervention (PCI). WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/dl above admission value and maintained until discharge, whereas transient WRF was defined as that WRF resolved at hospital discharge. WRF occurred in 78 patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients (7%). WRF patients were older and had a higher prevalence of chronic kidney disease, history of myocardial infarction (MI), and ST elevation MI. WRF was associated with elevated inflammatory markers and reduced left ventricular (LV) ejection fraction in acute, chronic phase. Incidence of all-cause death and major adverse cardiac events (MACE: all-cause death, MI, and target lesion revascularization) was significantly higher in patients with WRF. Moreover, in the WRF group, incidences of all-cause death and MACE were higher in patients with persistent WRF than those with transient WRF. A multivariate analysis showed that as well as older age, female gender, and intubation, WRF was an independent determinant of the all-cause death in ACS patients who underwent PCI. In conclusion, WRF might have a prognostic impact among Japanese ACS patients who underwent PCI in association with enhanced inflammatory response and LV remodeling. Persistent WRF might portend increased events, while transient WRF might have association with favorable outcomes compared with persistent WRF. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier

  8. Glucose phosphorylation rate in rat parietal cortex during normoglycemia, hypoglycemia, acute hyperglycemia, and in diabetes-prone rats

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    Broendsted, H.E.; Gjedde, A. (Department of General Physiology and Biophysics, Panum Institute, University of Copenhagen (Denmark))

    1990-01-01

    Cerebral metabolic rate for glucose (CMRglc) was studied in rats using (6-{sup 14}C)glucose. After intravenous injection the radioactivity of the parietal cortex was corrected for loss of labeled CO{sub 2} and divided by the integral of the arterial plasma glucose concentration, determined during tracer circulation. Treatment with insulin, resulting in plasma glucose concentrations less than 2.6 mmol/l, reduced CMRglc to 64% of the values found in control animals. CMRglc did not change in animals with acute hyper-glycemia produced by intraperiotoneal injection of a glucose solution or in diabetes-prone rats with or withour insulin treatment. (author).

  9. Sliding-Scale versus Basal-Bolus Insulin in the Management of Severe or Acute Hyperglycemia in Type 2 Diabetes Patients: A Retrospective Study

    Science.gov (United States)

    Zaman Huri, Hasniza; Permalu, Vishaaliny; Vethakkan, Shireene Ratna

    2014-01-01

    Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8±2.3 versus 11.6±3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3±1.9 versus 12.8±2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified. PMID:25181406

  10. Sliding-scale versus basal-bolus insulin in the management of severe or acute hyperglycemia in type 2 diabetes patients: a retrospective study.

    Science.gov (United States)

    Zaman Huri, Hasniza; Permalu, Vishaaliny; Vethakkan, Shireene Ratna

    2014-01-01

    Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8 ± 2.3 versus 11.6 ± 3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3 ± 1.9 versus 12.8 ± 2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.

  11. Red flags for persistent or worsening anxiety and depression after an acute cardiac event: a 6-month longitudinal study in regional and rural Australia.

    Science.gov (United States)

    Murphy, Barbara; Ludeman, Deborah; Elliott, Peter; Judd, Fiona; Humphreys, John; Edington, John; Jackson, Anthony; Worcester, Marian

    2014-09-01

    While early symptoms of anxiety and depression resolve for many patients soon after an acute cardiac event, the persistence or worsening of symptoms indicates increased mortality risk. It is therefore important to identify the predictors, or red flags, of persistent or worsening anxiety and depression symptoms. Most previous research has focussed on metropolitan patients, hence the need for studies of regional and rural dwellers. In this study, 160 cardiac patients consecutively admitted to two hospitals in regional Victoria, Australia, were interviewed in hospital and 2 and 6 months after discharge. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Growth mixture modelling was used to identify the trajectories of anxiety and depression over the 6 months after the acute event, and post-hoc tests identified predictors of persistent or worsening symptoms. For both anxiety and depression, three common symptom trajectories were identified. Inhospital anxiety symptoms tended to persist over time, whereas inhospital depression symptoms resolved for some patients and worsened for others. A mental health history, younger age, smoking, financial stress, poor self-rated health, and social isolation were red flags for persistent anxiety and worsening depression. Additionally, diabetes, and other comorbidities were red flags for persistent anxiety. The results highlight several potential red flags for increased risk of persistent anxiety or worsening depressive symptoms after a cardiac event, including demographic, psychosocial, and behavioural indicators. These red flags could assist with identification of at-risk patients on admission to or discharge from hospital, thereby enabling targeting of interventions. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Worsening Renal Function in Acute Heart Failure Patients Undergoing Aggressive Diuresis is Not Associated with Tubular Injury.

    Science.gov (United States)

    Ahmad, Tariq; Jackson, Keyanna; Rao, Veena S; Tang, W H Wilson; Brisco-Bacik, Meredith A; Chen, Horng H; Felker, G Michael; Hernandez, Adrian F; O'Connor, Christopher M; Sabbisetti, Venkata S; Bonventre, Joseph V; Wilson, F Perry; Coca, Steven G; Testani, Jeffrey M

    2018-01-19

    Background -Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure (AHF) treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers-NAG, NGAL, and KIM-1- are now available that can quantify the degree of renal tubularinjury. The ROSE-AHF trial provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF, as the ROSE-AHF protocol dictated high dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods -Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed ( N =283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated using cystatin C. Results -Consistent with protocol driven aggressive dosing of loop diuretics, participants received a median 560 mg of IV furosemide equivalents (IQR 300-815 mg) which induced a urine output of 8425 mL (IQR 6341-10528 ml) over the 72-hour intervention period. Levels of NAG and KIM-1 did not change with aggressive diuresis ( P >0.59, both), whereas levels of NGAL decreased slightly [-8.7 ng/mg (-169, 35 ng/mg), P renal tubular injury: NGAL ( P =0.21), NAG ( P =0.46), or KIM-1 ( P =0.22). Increases in NGAL, NAG, and KIM-1 were paradoxically associated with improved survival (adjusted HR: 0.80 per 10 percentile increase, 95% CI: 0.69-0.91; P =0.001). Conclusions -Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of AHF patients. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

  13. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Hideki Yoshida

    Full Text Available Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4% developed in induction phase, which was lower incidence than those (10-15% in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥ 10 years was a sole independent risk factor for L-asparaginase-related hyperglycemia (P<0.01, especially in maintenance phase. Contrary to the previous reports, obesity was not associated with L-asparaginase-related hyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients.

  14. Hyperglycemia - infants

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007228.htm Hyperglycemia - infants To use the sharing features on this page, please enable JavaScript. Hyperglycemia is abnormally high blood sugar. The medical term ...

  15. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Yoshida, Hideki; Imamura, Toshihiko; Saito, Akiko M.; Takahashi, Yoshihiro; Suenobu, So-ichi; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Kawasaki, Hirohide; Endo, Mikiya; Hori, Hiroki; Suzuki, Nobuhiro; Kosaka, Yoshiyuki; Kato, Koji; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi; Sato, Atsushi; Horibe, Keizo

    2015-01-01

    Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10–15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (Phyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients. PMID:26317422

  16. Inhaled aerosolized insulin ameliorates hyperglycemia-induced inflammatory responses in the lungs in an experimental model of acute lung injury

    Science.gov (United States)

    2013-01-01

    Introduction Previous studies have shown that patients with diabetes mellitus appear to have a lower prevalence of acute lung injury. We assumed that insulin prescribed to patients with diabetes has an anti-inflammatory property and pulmonary administration of insulin might exert beneficial effects much more than intravenous administration. Methods Twenty-eight mechanically ventilated rabbits underwent lung injury by saline lavage, and then the animals were allocated into a normoglycemia group (NG), a hyperglycemia group (HG), an HG treated with intravenous insulin (HG-VI) group or an HG treated with aerosolized insulin (HG-AI) group with continuous infusion of different fluid solutions and treatments: normal saline, 50% glucose, 50% glucose with intravenous insulin, or 50% glucose with inhaled aerosolized insulin, respectively. After four hours of treatment, the lungs and heart were excised en bloc, and then high-mobility group B1 concentration in bronchoalveolar lavage fluid, interleukin-8 and toll-like receptor 4 mRNA expression in bronchoalveolar lavage fluid cells, and lung myeloperoxidase activity were measured. Results Treatment with both aerosolized insulin and intravenous insulin attenuated toll-like receptor 4 mRNA expressions in the bronchoalveolar lavage fluid cells. Interleukin-8 and toll-like receptor 4 mRNA expression was significantly lower in the HG-AI group than in the HG-IV group. The lung myeloperoxidase activity in the normal healthy group showed significantly lower levels compared to the NG group but not different compared to those of the HG, HG-VI and HG-AI groups. Conclusions The results suggest that insulin attenuates inflammatory responses in the lungs augmented by hyperglycemia in acute lung injury and the insulin's efficacy may be better when administered by aerosol. PMID:23622115

  17. Plasma neutrophil gelatinase-associated lipocalin as a marker for the prediction of worsening renal function in children hospitalized for acute heart failure.

    Science.gov (United States)

    Elsharawy, Sahar; Raslan, Lila; Morsy, Saed; Hassan, Basheir; Khalifa, Naglaa

    2016-01-01

    Acute heart failure (AHF) is frequently associated with worsening renal function in adult patients. Neutrophil gelatinase-associated lipocalin (NGAL) serves as an early marker for acute renal tubular injury. To assess the role of plasma NGAL in predicting worsening renal function (WRF) in children with AHF, we studied 30 children hospitalized for AHF; children with history of chronic renal disease or on nephrotoxic drugs were excluded. Twenty age- and sex-matched healthy children were included in the study as a control group. Echocardiographic examination was performed on admission. Blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR) and plasma NGAL levels were measured on admission and 72 h later. Seventeen (56.6%) patients developed WRF within the three-day follow-up period. At presentation, plasma NGAL level was significantly elevated in children who developed WRF. Admission plasma NGAL level correlated with renal parameters (BUN, creatinine and eGFR) as well as with left ventricular systolic parameters (ejection fraction and fractional shortening). For prediction of WRF, admission plasma, NGAL level>27.5 μg/L had sensitivity and specificity of 90% and 68%, respectively. The area under the receiver-operator curve was higher for NGAL (0.869) than for BUN (0.569) or eGFR (0.684). We conclude that admission plasma NGAL level can predict WRF in children hospitalized for AHF.

  18. Phosphorylated neurofilament subunit NF-H becomes elevated in the cerebrospinal fluid of patients with acutely worsening symptoms of compression myelopathy.

    Science.gov (United States)

    Takahashi, Hiroshi; Aoki, Yasuchika; Nakajima, Arata; Sonobe, Masato; Terajima, Fumiaki; Saito, Masahiko; Taniguchi, Shinji; Yamada, Manabu; Watanabe, Fusako; Furuya, Takeo; Koda, Masao; Yamazaki, Masashi; Takahashi, Kazuhisa; Nakagawa, Koichi

    2014-12-01

    It is known that the severity of compression myelopathy sometimes worsens rapidly and results in poor functional recovery because of limited axonal regeneration. Levels of phosphorylated neurofilament subunit NF-H (pNF-H), which indicate axonal degeneration, are elevated in other neurological disorders. To our knowledge, there has been no examination of pNF-H levels in compression myelopathy. Therefore, we conducted a pilot cross-sectional study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) of patients with worsening symptoms of cervical compression myelopathy. From January 2011 to March 2013, 51 samples of CSF were collected from patients at the time of myelography before spinal surgery. The indications for surgery were acutely worsening compression myelopathy (AM) in eight, chronic compression myelopathy (CM) in six, and lumbar canal stenosis (LCS) in 37 patients. The pNF-H levels were measured using a standard enzyme-linked immunosorbent assay. The mean ± standard deviation pNF-H value was 2127.1 ± 556.8 pg/ml in AM patients, 175.8 ± 67.38 pg/ml in CM patients and 518.7 ± 665.7 pg/ml in LCS patients. A significant increase in pNF-H levels was detected in the CSF of patients with AM compared with those with either CM or LCS. The clinical outcome of surgical treatment for patients with cervical myelopathy was satisfactory in both AM and CM patients. Despite the limitations of small sample size and lack of healthy CSF control data due to ethical considerations, our results suggest that pNF-H in CSF can act as a biomarker that reflects the severity of AM. Copyright © 2014. Published by Elsevier Ltd.

  19. Relationship of Endothelial Cell-Specific Molecule 1 Level in Stress Hyperglycemia Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pilot Study.

    Science.gov (United States)

    Qiu, Chongrong; Sui, Jian; Zhang, Qian; Wei, Peng; Wang, Peng; Fu, Qiang

    2016-10-01

    Endothelial cell-specific molecule 1 ([ESM-1], endocan) is a new biomarker of endothelial dysfunction, which may be involved in the pathogenesis of atherosclerosis and stress hyperglycemia in patients with acute ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated serum ESM-1 levels in patients with stress hyperglycemia having STEMI; 105 patients with STEMI and 33 individuals as a control group were included in the study. The patients were followed up for 3 months and major adverse cardiac events (MACEs) were recorded. Serum ESM-1 level was significantly higher in patients with stress hyperglycemia patients having STEMI (P levels correlated positively with glucose levels (r = .21, P levels >1.01 ng/mL (odds ratio 3.01, 95% confidence interval 1.05-8.64, P stress hyperglycemia having STEMI, admission glucose levels are associated with ESM-1 levels, and ESM-1 is an independent predictor of MACEs. An ESM-1 level >1.01 ng/mL is likely to predict a greater risk of MACEs. © The Author(s) 2015.

  20. Acute Hyperglycemia Abolishes Ischemic Preconditioning by Inhibiting Akt Phosphorylation: Normalizing Blood Glucose before Ischemia Restores Ischemic Preconditioning

    Science.gov (United States)

    Yang, Zequan; Liu, Yuan; Hennessy, Sara; Kron, Irving L.; French, Brent A.

    2013-01-01

    This study examined the hypothesis that acute hyperglycemia (HG) blocks ischemic preconditioning (IPC) by inhibiting Akt phosphorylation. Brief HG of approximately 400 mg/dL was induced in C57BL/6 mice via intraperitoneal injection of 20% dextrose (2 g/kg). All mice underwent 40 min LAD occlusion and 60 min reperfusion. The IPC protocol was 2 cycles of 5 min ischemia and 5 min reperfusion prior to index ischemia. Results. In control mice, infarct size (IF) was 51.7 ± 2.0 (% risk region). Preconditioning reduced IF by 50% to 25.8 ± 3.2 (P insulin 5 min before IPC recovered the cardioprotective effect. Administration of CCPA before index ischemia mimicked IPC effect. The cardioprotective effect of CCPA, not its chronotropic effect, completely disappeared in HG mice. Phosphorylation of cardiac tissue Akt before index ischemia was enhanced by IPC or CCPA but was significantly inhibited by HG in both groups. Normalization of glucose with insulin reversed the inhibition of Akt phosphorylation by HG. Conclusion. HG abolishes the cardioprotective effect of preconditioning by inhibiting Akt phosphorylation. Normalization of blood glucose with insulin suffices to recover the cardioprotective effect of preconditioning. PMID:24371503

  1. Hyperglycemia and Clinical Outcome in Aneurysmal Subarachnoid Hemorrhage A Meta-Analysis

    NARCIS (Netherlands)

    Kruyt, Nyika D.; Biessels, Geert Jan; de Haan, Rob J.; Vermeulen, Marinus; Rinkel, Gabriel J. E.; Coert, Bert; Roos, Yvo B. W. E. M.

    2009-01-01

    Background and Purpose-Hyperglycemia may worsen outcome after aneurysmal subarachnoid hemorrhage. We performed a systematic review to investigate the relation between admission hyperglycemia and outcome after aneurysmal subarachnoid hemorrhage. Methods-We included cohort studies or clinical trials

  2. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans

    Science.gov (United States)

    Perkins, Jennifer M.; Joy, Nino G.; Tate, Donna B.

    2015-01-01

    We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m2) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers. PMID:26015434

  3. The previous use of digoxin does not worsen early outcome of acute coronary syndromes: an analysis of the ARIAM Registry.

    Science.gov (United States)

    Garcia-Rubira, Juan Carlos; Calvo-Taracido, Manuel; Francisco-Aparicio, Francisca; Almendro-Delia, Manuel; Recio-Mayoral, Alejandro; Reina Toral, Antonio; Aramburu-Bodas, Oscar; Gallego García de Vinuesa, Pastora; Cruz Fernández, José Maria; Alcántara, Angel Garcia; Hidalgo-Urbano, Rafael

    2014-10-01

    The aim of the study was to determine the influence of the previous use of digoxin on the hospital mortality and complications of patients admitted because of acute coronary syndrome (ACS). We analyzed the data of patients included in the ARIAM-Andalucia Registry, which involves 49 hospitals in Andalucia, Spain, from 2007 to 2012. Patients on digoxin treatment prior to their admission because of ACS constituted the digoxin group (DG), and were compared with the group of patients not on digoxin. Logistic regression and propensity score matching were used to analyze the differences. We included 20,331 patients, of whom 244 (1.2%) were on digoxin. DG patients were older (73.1 vs 63.7 years old), more often women, and had more diabetes, hypertension, previous myocardial infarction, heart failure, stroke, atrial fibrillation, peripheral vascular disease, obstructive pulmonary disease or kidney disease. On univariate analysis, DG patients had significantly higher hospital mortality (13.5 vs 5.3% P digoxin was not associated with an increase in dysrhythmic complications nor was an independent predictor of mortality during hospitalization.

  4. Postprandial hyperglycemia.

    Science.gov (United States)

    Richards, Robert J

    2003-01-01

    Much attention has been paid to fasting glucose levels in both the diagnosis and management of diabetes mellitus. This test is well ingrained in clinical practice and well accepted by our patients. However, does a fasting glucose level give the clinician a complete picture? Is postprandial hyperglycemia associated with adverse events? This article will explore postprandial glucose levels and compare them to fasting glucose levels. The importance of postprandial and post-challenge (2 hours after a standard oral glucose tolerance test) glucose levels will be discussed. Drugs which address postprandial hyperglycemia will be reviewed briefly.

  5. Admission plasma neutrophil gelatinase associated lipocalin (NGAL) predicts worsening renal function during hospitalization and post discharge outcome in patients with acute heart failure.

    Science.gov (United States)

    Palazzuoli, Alberto; Ruocco, Gaetano; Beltrami, Matteo; Franci, Beatrice; Pellegrini, Marco; Lucani, Barbara; Nuti, Ranuccio; Ronco, Claudio

    2014-09-01

    Abstract Background: The role of neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF), however less data are available in patients admitted for acute HF. We evaluated the role of NGAL in predicting in-hospital worsening renal function (WRF) and post-discharge follow-up during six months period in patients with acute HF. All patients were submitted to creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and B-type natriuretic peptide (BNP) measurement during hospitalization and before discharge. Patients with chronic kidney dysfunction (CKD) demonstrated higher NGAL respect to subject with preserved renal function (241 ± 218 and 130 ± 80 ng/ml; P = 0.0001). In subgroup that developed WRF during hospitalization, NGAL levels were significantly increased respect to patients without WRF (272 ± 205 versus 136 ± 127 ng/ml; P = 0.0001). A cut off of 134 ng/ml has been related to WRF with good sensibility and specificity (92% and 71% AUC 0.83; P = 0.001). Multivariable Cox regression analysis showed that cut-off of 134 ng/ml was the only marker related to death (HR: 1.75; 95% CI: 1.24-2.45; P 130 ng/ml was associated with adverse events during a six-month period. Admission NGAL measurement appears a sensible tool for in-hospital WRF prediction as well as an early marker for adverse outcome during post discharge vulnerable phase.

  6. A systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure.

    Science.gov (United States)

    Fonseca, Cândida; Maggioni, Aldo Pietro; Marques, Filipa; Araújo, Inês; Brás, Daniel; Langdon, Ronald B; Lombardi, Carlo; Bettencourt, Paulo

    2018-01-01

    In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Association of persistent and transient worsening renal function with mortality risk, readmissions risk, length of stay, and costs in patients hospitalized with acute heart failure

    Directory of Open Access Journals (Sweden)

    Palmer JB

    2015-06-01

    Full Text Available Jacqueline B Palmer,1 Howard S Friedman,2 Katherine Waltman Johnson,1 Prakash Navaratnam,2 Stephen S Gottlieb3 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2DataMed Solutions, LLC, New York, NY, USA; 3Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Background: Data comparing effects of transient worsening renal function (WRFt and persistent WRF (WRFp on outcomes in patients hospitalized with acute heart failure (AHF are lacking. We determined the characteristics of hospitalized AHF patients who experienced no worsening renal function (non-WRF, WRFt, or WRFp, and the relationship between cohorts and AHF-related outcomes. Methods and results: A patient’s first AHF hospitalization (index was identified in the Cerner Health Facts® database (January 2008-March 2011. Patients had WRF if serum creatinine (SCr was ≥0.3 mg/dL and increased ≥25% from baseline, and they were designated as WRFp if present at discharge or WRFt if not present at discharge. A total of 55,436 patients were selected (non-WRF =77%, WRFp =10%, WRFt =13%. WRFp had greater comorbidity burden than WRFt. At index hospitalization, WRFp patients had the highest mortality, whereas WRFt patients had the longest length of stay (LOS and highest costs. These trends were observed at 30, 180, and 365 days postdischarge and confirmed by multivariable analyses. WRF patients had more AHF-related readmissions than non-WRF patients. In sensitivity analyses of the patient subset with live index hospitalization discharges, postdischarge LOS and costs were highest in WRFt patients, whereas mortality associated with a HF hospitalization was significantly higher for WRF patients vs non-WRF patients, with no difference between WRFp and WRFt. Conclusion: In patients hospitalized for AHF, WRFp was associated with the highest mortality, whereas WRFt was associated with the highest LOS and costs. WRF patients had higher readmissions than non

  8. Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

    Science.gov (United States)

    Garg, Pankaj; Broadbent, David A; Swoboda, Peter P; Foley, James R J; Fent, Graham J; Musa, Tarique A; Ripley, David P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Haaf, Philip; Kidambi, Ananth; Crandon, Saul; Chew, Pei G; van der Geest, R J; Greenwood, John P; Plein, Sven

    2017-09-25

    Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05). Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.

  9. The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis.

    Science.gov (United States)

    Yoneyama, Satoshi; Terashima, Hideo; Yamaguchi, Ryushiro; Tadano, Sosuke; Ohkohchi, Nobuhiro

    2013-11-01

    The aim of the study was to investigate both the inflammation-boosting effect and the metabolic stress induced by acute hyperglycemia secondary to overfeeding with excessive glucose infusion and the effects of insulin therapy on those events in a rat model of sepsis. Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham operation. Preestablished continuous intravenous glucose infusion was initiated immediately after surgery. First, rats with CLP-inducing sepsis were divided into three groups on the basis of the target blood glucose (BG) levels: high glucose (HG) group (overfed, >300 mg/dL), moderate glucose group (moderate hyperglycemia, 200-300 mg/dL), and no glucose group (100-150 mg/dL). The sham group received the same glucose infusion as that of the HG group. BG and plasma interleukin (IL) 6 levels were monitored over time. All rats were sacrificed 9 h after surgery to evaluate lung histology and measure hepatic total glutathione and malondialdehyde contents. Based on the results, the high glucose and insulin (HI) group was added to septic groups as a model of insulin therapy, in which insulin with the same HG dose as that in the HG group was administered to maintain moderate hyperglycemia. BG level in all groups remained in the preestablished target range throughout the experiment. Plasma IL-6 level in all septic groups increased in a time-dependent manner, whereas that in the sham group with moderate hyperglycemia hardly increased. Nine hours after CLP, plasma IL-6 level in the HG group rose to 7407.5 ± 1987.3 pg/mL, which was three times higher than that in the other septic groups. There was no significant difference among moderate glucose, no glucose, and HI groups, in which BG level remained constant at hyperglycemia in critical illness might excessively boost the existing systemic inflammatory response in a threshold-based manner. Insulin therapy under overfeeding could strongly inhibit such a boosting effect and oxidative stress in

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

    Science.gov (United States)

    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 (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 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. Copyright © 2015 the American Physiological Society.

  11. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? You can often lower your blood ... record for use in an emergency. How Can I Prevent Hyperglycemia? Your best bet is to practice ...

  12. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... will help you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? You can often lower ... full medical record for use in an emergency. How Can I Prevent Hyperglycemia? Your best bet is ...

  13. Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient Ischemic Attack: The CHANCE Study (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events).

    Science.gov (United States)

    Pan, Yuesong; Cai, Xueli; Jing, Jing; Meng, Xia; Li, Hao; Wang, Yongjun; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wei, Tiemin; Wang, Yilong

    2017-11-01

    We aimed to determine the association between stress hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or transient ischemic attack. A subgroup of 3026 consecutive patients from 73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was calculated by fasting plasma glucose divided by GA and categorized into 4 even groups according to the quartiles. The primary outcome was a new stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio and risk of stroke by multivariable Cox regression models adjusted for potential covariates. Among 3026 patients included, a total of 299 (9.9%) new stroke occurred at 3 months. Compared with patients with the lowest quartile, patients with the highest quartile of glucose/GA ratio was associated with an increased risk of stroke at 3 months after adjusted for potential covariates (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06-2.01). Similar results were observed after further adjusted for fasting plasma glucose. We also observed that higher level of glucose/GA ratio was associated with an increased risk of stroke with a threshold of 0.29 using a Cox regression model with restricted cubic spline. Stress hyperglycemia, measured by glucose/GA ratio, was associated with an increased risk of stroke in patients with a minor ischemic stroke or transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2017 American Heart Association, Inc.

  14. Hyperglycemia: a prothrombotic factor?

    National Research Council Canada - National Science Library

    LEMKES, B. A; HERMANIDES, J; DEVRIES, J. H; HOLLEMAN, F; MEIJERS, J. C. M; HOEKSTRA, J. B. L

    2010-01-01

    .... Hyperglycemia plays an important role in the development of these hemostatic abnormalities, as is illustrated by the association with glycemic control and the improvement upon treatment of hyperglycemia...

  15. Mortality Reduction for Fever, Hyperglycemia, and Swallowing Nurse-Initiated Stroke Intervention: QASC Trial (Quality in Acute Stroke Care) Follow-Up.

    Science.gov (United States)

    Middleton, Sandy; Coughlan, Kelly; Mnatzaganian, George; Low Choy, Nancy; Dale, Simeon; Jammali-Blasi, Asmara; Levi, Chris; Grimshaw, Jeremy M; Ward, Jeanette; Cadilhac, Dominique A; McElduff, Patrick; Hiller, Janet E; D'Este, Catherine

    2017-05-01

    Implementation of nurse-initiated protocols to manage fever, hyperglycemia, and swallowing dysfunction decreased death and disability 90 days poststroke in the QASC trial (Quality in Acute Stroke Care) conducted in 19 Australian acute stroke units (2005-2010). We now examine long-term all-cause mortality. Mortality was ascertained using Australia's National Death Index. Cox proportional hazards regression compared time to death adjusting for correlation within stroke units using the cluster sandwich (Huber-White estimator) method. Primary analyses included treatment group only unadjusted for covariates. Secondary analysis adjusted for age, sex, marital status, education, and stroke severity using multiple imputation for missing covariates. One thousand and seventy-six participants (intervention n=600; control n=476) were followed for a median of 4.1 years (minimum 0.3 to maximum 70 months), of whom 264 (24.5%) had died. Baseline demographic and clinical characteristics were generally well balanced by group. The QASC intervention group had improved long-term survival (>20%), but this was only statistically significant in adjusted analyses (unadjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.58-1.07; P =0.13; adjusted HR, 0.77; 95% CI, 0.59-0.99; P =0.045). Older age (75-84 years; HR, 4.9; 95% CI, 2.8-8.7; P stroke severity (HR, 1.5; 95% CI, 1.3-1.9; P stroke) was listed either as the primary or secondary cause of death in 80% (211/264) of all deaths. Our results demonstrate the potential long-term and sustained benefit of nurse-initiated multidisciplinary protocols for management of fever, hyperglycemia, and swallowing dysfunction. These protocols should be a routine part of acute stroke care. URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000563369. © 2017 American Heart Association, Inc.

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term ... body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If ...

  17. Protective effects of flavanol-rich dark chocolate on endothelial function and wave reflection during acute hyperglycemia.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Ruggieri, Fabrizio; Blumberg, Jeffrey B; Stornello, Michele; Ferri, Claudio

    2012-09-01

    Nitric oxide plays a pivotal role in regulating vascular tone. Different studies show endothelial function is impaired during hyperglycemia. Dark chocolate increases flow-mediated dilation in healthy and hypertensive subjects with and without glucose intolerance; however, the effect of pretreatment with dark chocolate on endothelial function and other vascular responses to hyperglycemia has not been examined. Therefore, we aimed to investigate the effects of flavanol-rich dark chocolate administration on (1) flow-mediated dilation and wave reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males, 28.2±2.7 years) randomly received either 100 g/d dark chocolate or flavanol-free white chocolate for 3 days. After 7 days washout period, volunteers were switched to the other treatment. Flow-mediated dilation, stiffness index, reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso-PGF(2α) were evaluated after each treatment phase and OGTT. Compared with white chocolate, dark chocolate ingestion improved flow-mediated dilation (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2α) (Pflavanol-rich dark chocolate. These results suggest cocoa flavanols may contribute to vascular health by reducing the postprandial impairment of arterial function associated with the pathogenesis of atherosclerosis.

  18. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... drives that can carry a person's full medical record for use in an emergency. How Can I Prevent Hyperglycemia? Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ...

  19. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... such as family conflicts or school or dating problems. You may have experienced the dawn phenomenon (a ... high blood glucose early will help you avoid problems associated with hyperglycemia. How Do I Treat Hyperglycemia? ...

  20. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... your blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. ... to detect hyperglycemia so you can treat it early — before it gets worse. If you're new ...

  1. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... t use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If you have ... Research Leaders We Support Your Doctor Student Resources Patient Access to Research Research Resources Practice Resources Ways ...

  2. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High ... called ketones are produced. Your body cannot tolerate large amounts of ketones and will try to get ...

  3. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Matching Gift Fundraising Events Donate Stocks Give by Phone 1-800-DIABETES (800-342-2383) Give by ... t use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If you have ...

  4. Hyperglycemia in Diabetes

    Science.gov (United States)

    ... hyperglycemia because hormones produced to combat illness or stress can also cause your blood sugar to rise. Even people who don't have diabetes may develop hyperglycemia during severe illness. But people ...

  5. Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction

    NARCIS (Netherlands)

    Kant, GD; Dullaart, RPF; Smit, AJ

    Uncomplicated Type I (insulin-dependent) diabetes mellitus is characterized by generalized vasodilatation. Its possible correlates, increased microvascular permeability and endothelial dysfunction, have been associated with long-term complications. The objective was to study the effects of acute

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Diabetes Complications Hypoglycemia Hyperglycemia Skin Complications Eye Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications Hypoglycemia Hyperglycemia Skin Complications Eye Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis ...

  8. Effect of an optimized treatment with insulin on platelet reactivity after discharge in patients with an acute coronary syndrome and hyperglycemia.

    Science.gov (United States)

    Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

    2014-01-01

    Intensive glucose control with insulin in patients with an acute coronary syndrome reduces platelet reactivity during hospitalization, compared to conventional control. However, the effect of strict, long-term glucose control on platelet reactivity in these patients remains uncertain. This is a prospective, randomized trial evaluating the effects of optimized glucose control (target glucose, 80-120mg/dL) with insulin, compared with conventional control (target glucose, <180 mg/dL), on platelet reactivity after hospital discharge in patients with an acute coronary syndrome and hyperglycemia. The primary endpoint was assessment of platelet aggregation after stimulation with adenosine diphosphate 20 μM at 12-month follow-up. One hundred four patients were randomized to optimized management (n=53) or conventional management (n=51). There were no differences between groups in baseline characteristics or platelet function. After 12 months of follow-up, blood glucose levels were significantly lower in the optimized treatment group (104 vs 119 mg/dL; P<.001). However, platelet aggregation following adenosine diphosphate 20 μM stimulation showed no differences between the groups (54.2% [14.3%] vs 55.1% [18.3%] respectively; P=.81). There were no significant differences for other platelet function tests. Long-term optimized glucose control with insulin in patients with an acute coronary syndrome did not result in a reduction in platelet reactivity compared to conventional control. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  9. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If you have type 1, you may ... treating high blood glucose early will help you avoid problems associated with hyperglycemia. How Do I Treat ...

  10. Impact of Acute Hyperglycemia on Myocardial Infarct Size, Area at Risk, and Salvage in Patients With STEMI and the Association With Exenatide Treatment

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Vejlstrup, Niels; Kelbæk, Henning

    2014-01-01

    Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage....... In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction...... between exenatide and hyperglycemia. A total of 210 STEMI patients were randomized to receive intravenous exenatide or placebo before percutaneous coronary intervention. Hyperglycemia was associated with larger area at risk and infarct size compared with patients with normoglycemia, but the salvage index...

  11. Suppression of hypoxia-inducible factor-1alpha and its downstream genes reduces acute hyperglycemia-enhanced hemorrhagic transformation in a rat model of cerebral ischemia.

    Science.gov (United States)

    Chen, Chunhua; Ostrowski, Robert P; Zhou, Changman; Tang, Jiping; Zhang, John H

    2010-07-01

    We evaluated a role of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream genes in acute hyperglycemia-induced hemorrhagic transformation in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 280-300 g (n = 105) were divided into sham, 90 min middle cerebral artery occlusion (MCAO), MCAO plus HIF-1alpha inhibitors, 2-methoxyestradiol (2ME2) or 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), groups. Rats received an injection of 50% dextrose (6 ml/kg intraperitoneally) at 15 min before MCAO. HIF-1alpha inhibitors were administered at the onset of reperfusion. The animals were examined for neurological deficits and sacrificed at 6, 12, 24, and 72 hr following MCAO. The cerebral tissues were collected for histology, zymography, and Western blot analysis. The expression of HIF-1alpha was increased in ischemic brain tissues after MCAO and reduced by HIF-1alpha inhibitors. In addition, 2ME2 reduced the expression of vascular endothelial growth factor (VEGF) and the elevation of active matrix metalloproteinase-2 and -9 (MMP-2/MMP-9) in the ipsilateral hemisphere. Both 2ME2 and YC-1 reduced infarct volume and ameliorated neurological deficits. However, only 2ME2 attenuated hemorrhagic transformation in the ischemic territory. In conclusion, the inhibition of HIF-1alpha and its downstream genes attenuates hemorrhagic conversion of cerebral infarction and ameliorates neurological deficits after focal cerebral ischemia.

  12. Venous thrombosis is associated with hyperglycemia at diagnosis: A case-control study

    NARCIS (Netherlands)

    Cohn, D.M.; Hermanides, J.; De Vries, J.H.; Kamphuisen, P.W.; Huijgen, R.; Meijers, J.C.M.; Hoekstra, J.B.L.; Buller, H.R.

    2009-01-01

    Background: Evidence is mounting that both acute and chronic hyperglycemia activates the coagulation system and thereby potentially contributes to the development of thrombosis. Patients with (undiagnosed) diabetes mellitus, impaired glucose tolerance or stressinduced hyperglycemia may be at greater

  13. The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes mediation by superoxide production, resolution with intensive insulin administration

    National Research Council Canada - National Science Library

    Worthley, Matthew I; Holmes, Andrew S; Willoughby, Scott R; Kucia, Angela M; Heresztyn, Tamila; Stewart, Simon; Chirkov, Yuliy Y; Zeitz, Christopher J; Horowitz, John D

    2007-01-01

    ...) and the short-term effects of aggressive glycemic control on these factors. Hyperglycemia is an independent risk factor for mortality in both diabetic patients and nondiabetic patients with ACS. The mechanism...

  14. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Hypoglycemia Hyperglycemia Skin Complications Eye Complications Neuropathy Foot Complications DKA (Ketoacidosis) & ... Tips for Caregivers Health Insurance Health Insurance ...

  15. pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

    Science.gov (United States)

    Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

    2017-10-01

    Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

  16. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: ... up ' + ' '); $('.survey-form').show(); }, success: function (data) { $('#survey-errors').remove(); $('.survey-form .form-group .survey-alert-wrap'). ...

  17. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... insulin or when the body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If you have type 1, you may not have given yourself enough insulin. If you have type 2, your body may ...

  18. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical ...

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    Full Text Available ... I Prevent Hyperglycemia? Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... Student Resources Patient Access to Research Research Resources Practice Resources Ways to ... Support Newsroom Press Releases For Professionals En ...

  20. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Hyperglycemia? Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can treat it early — before it gets worse. If you're new to type 2 diabetes, join our free Living With Type 2 Diabetes ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If you have type 1, you may not have given yourself enough insulin. If you have type 2, your body may have enough insulin, but it is not ...

  2. In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo vs. worsening) and ejection fraction. Results from IN-HF Outcome Registry.

    Science.gov (United States)

    Senni, Michele; Gavazzi, Antonello; Oliva, Fabrizio; Mortara, Andrea; Urso, Renato; Pozzoli, Massimo; Metra, Marco; Lucci, Donata; Gonzini, Lucio; Cirrincione, Vincenzo; Montagna, Laura; Di Lenarda, Andrea; Maggioni, Aldo P; Tavazzi, Luigi

    2014-05-01

    To investigate the outcomes of hospitalized patients with both de-novo and worsening heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF) (LVEF ≥ 50%), compared to those with reduced LVEF (HFrEF). We studied 1669 patients (22.6% HFpEF) hospitalized for acute HF in the prospective multi-center nationwide Italian Network on Heart Failure (IN-HF) Outcome Registry. In all patients LVEF was assessed during hospitalization. De-novo HF presentations constituted 49.6% of HFpEF and 43.1% of HFrEF hospitalizations. All-cause mortality during hospitalization was lower in HFpEF than HFrEF (2.9% vs 6.5%, p=0.01), but this mortality difference was not significant at 1 year (19.6% vs 24.4%, p=0.06), even after adjusting for clinical covariates. Similarly, there were no differences in 1-year mortality between HFpEF and HFrEF when compared by cause of death (cardiovascular vs non-cardiovascular) or mode of presentation (worsening HF vs de novo). Rehospitalization rates (all-cause, non-cardiovascular, cardiovascular, HF-related) at 90 days and 1 year were also similar. Mode of presentation influenced rehospitalizations in HFpEF, where those presenting with worsening HFpEF had higher all-cause (36.8% vs 21.6%, p=0.001), cardiovascular (28.1% vs 14.9%, p=0.002), and HF-related (21.1% vs 7.7%, p=0.0003) rehospitalization rates at 1 year compared to those with de novo presentations. Outcomes at 1 year following hospitalization for HFpEF are as poor as that of HFrEF. A prior history of HF decompensation or hospitalization identifies patients with HFpEF at particularly high risk of recurrent events. These findings may have implications for clinical practice, quality and process improvements and trial design. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Prevalência e influência da hiperglicemia de estresse no prognóstico em uma coorte de pacientes com síndrome coronariana aguda Influence on prognosis and prevalence of stress hyperglycemia in a cohort of patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Renata de Faria Modenesi

    2012-12-01

    Full Text Available OBJETIVO: Demonstrar a prevalência da hiperglicemia de estresse em coorte de pacientes com síndrome coronariana aguda e a correlação com óbito, insuficiência cardíaca e/ou disfunção ventricular esquerda sistólica, na fase intra-hospitalar. MÉTODOS: Estudo de coorte prospectiva inicial constituída por pacientes internados com síndrome coronariana aguda, com ou sem supradesnivelamento do segmento ST. Foram comparados os grupos para demonstrar a correlação entre hiperglicemia de estresse e eventos cardiovasculares. Na comparação entre os grupos com e sem hiperglicemia de estresse, foram usados o teste do qui-quadrado ou exato de Fisher, e o teste t de student. As variáveis com valor de pOBJECTIVE: To demonstrate the prevalence of stress hyperglycemia in a cohort of patients with acute coronary syndrome and to determine the correlation of stress hyperglycemia with death, heart failure and/or left ventricular systolic dysfunction during the intrahospital phase. METHODS: A prospective initial cohort study of hospitalized patients with acute coronary syndrome with or without ST segment elevation. The groups were compared to demonstrate the correlation between stress hyperglycemia and cardiovascular events. The chi-square test or Fisher's exact test and student's t-test were used to compare the groups with and without stress hyperglycemia. The variables with p<0.20 in the univariate analysis were submitted to logistic regression. RESULTS: In total, 363 patients with an average age of 12.45 ± 62.06 were studied. There was a predominance of males (64.2%. In total, 96 patients (26.4% presented with stress hyperglycemia. There were no differences between the groups with or without stress hyperglycemia. The area under the ROC curve was 0.67 for the relationship between stress hyperglycemia and the composite outcome heart failure, left ventricular systolic dysfunction or death at the end of the hospital admission. The ROC curve proved that

  4. Hyperglycemia (High Blood Glucose)

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  14. Hyperglycemia (High Blood Glucose)

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  18. Hyperglycemia (High Blood Glucose)

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  20. Hyperglycemia (High Blood Glucose)

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  1. Hyperglycemia (High Blood Glucose)

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  9. Hyperglycemia (High Blood Glucose)

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  10. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Association Alert Day® Become a Member Advocacy Home Take Action Advocacy Priorities State Priorities Federal Priorities Advocacy ... insulin or possibly the timing of when you take it. What if it Goes Untreated? Hyperglycemia can ...

  11. Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

    DEFF Research Database (Denmark)

    Major-Pedersen, A; Ihlemann, N; Hermann, T S

    2008-01-01

    -resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when......-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0....... We found no relationship between postprandial hyperglycemia and post-OGL FMD....

  12. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... June 7, 2013 Last Edited: September 16, 2014 Articles from Diabetes Forecast® magazine: bg-and-a1c-hyperglycemia, ... We Are Research Leaders We Support Your Doctor Student Resources Patient Access to Research Research Resources Practice ...

  13. Hyperglycemia (High Blood Glucose)

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    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can treat it early — before it gets worse. If you're new to type 2 diabetes, join our free Living With Type 2 Diabetes program to get help and support during your first ...

  14. Hyperglycemia (High Blood Glucose)

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  15. Hyperglycemia (High Blood Glucose)

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  16. Hyperglycemia (High Blood Glucose)

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  17. Hyperglycemia (High Blood Glucose)

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  18. Hyperglycemia (High Blood Glucose)

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  19. Hyperglycemia (High Blood Glucose)

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  20. Hyperglycemia (High Blood Glucose)

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  1. Hyperglycemia (High Blood Glucose)

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  2. Hyperglycemia (High Blood Glucose)

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  3. Hyperglycemia (High Blood Glucose)

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  4. Prefrontal blood flow and oxygenation measured by NIRS during long-term memory tasks are impaired by acute hyperglycemia (Conference Presentation)

    Science.gov (United States)

    Harris, R. Luke; Bell, Lindsay; Reimer, Andrea; Pettersen, Jacqueline A.; Siakaluk, Paul; Duffels, Brian

    2017-02-01

    Our goal was to use 2-channel frequency domain near-infrared spectroscopy (NIRS) to investigate the hemodynamic and metabolic mechanisms underlying hyperglycemia-associated long-term memory impairment. We hypothesized that prefrontal cortex (PFC) oxygen saturation (%Sat) and perfusion (tHb, i.e. total hemoglobin) would decrease due to hyperglycemia during learning, and then increase during recall. During learning, participants' blood glucose was manipulated with beverages containing either 47.4 mg saccharine control (CON, n = 10), or 50 g dextrose + 23.7 mg saccharine (GLC, n = 10). In the Symbol-Digit Modalities Test (SMDT) participants matched nine symbols to corresponding digits (1-9 inclusive), completing 105 learning and 15 testing trials on day 1 and 15 testing trials on day 2. From learning to recall, CON SMDT performance was unchanged, but GLC SMDT performance was decreased 11% (P = 0.0173). There were significant interactions (2-way ANOVA) between the CON-GLC treatment effects and the learning-recall effects for both PFC perfusion and oxygen saturation. Specifically, comparing learning to recall, CON exhibited no tHb differences but for GLC there was a large tHb decrease during learning with a partial recovery toward CON values during recall (P = 0.0012); and, comparing learning to recall, CON exhibited a large %Sat decrease but GLC exhibited a large %Sat increase (P = 0.021). We speculate that, during learning, after overnight fasting (CON) the PFC demands more hemodynamic and metabolic resources and "works" harder, but with readily available sugar (GLC) the PFC exhibits decreased "effort."

  5. Depression May Worsen Health for Cancer Caregivers

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166958.html Depression May Worsen Health for Cancer Caregivers Identifying signs ... 29, 2017 THURSDAY, June 29, 2017 (HealthDay News) -- Depression is known to be linked to worsening physical ...

  6. [Hypertension after gestational hyperglycemia].

    Science.gov (United States)

    Gonçalves, Luciana C; Silva, Márcia R Gabaldi; Peraçoli, José Carlos; de Silveira, Liciana Vaz A; Padovani, Carlos Roberto; de Pimenta, Walkyria P

    2005-04-01

    To compare hypertension frequency in women, 3 to 12 years after the index-pregnancy, when they were classified into 4 groups: NGT: normal glucose tolerance; GHG: gestational hyperglycemia; GDM: gestacional diabetes mellitus; GDM plus GHG. From 3,113 pregnant women, 535 were participants and selected by a process that was randomized and proportional to the group number. NGT women were different from the others in most of the clinical parameters. All women had their blood pressure evaluated. Statistical analyses were performed by Goodman's and chi-square tests. Hypertension frequency was higher in GDM plus GHG women than in NGT women (40.9 vs. 23.6%; Pdiabetes.

  7. Hyperglycemia has a stronger relation trauma patients than in other critically with outcome in ill patients

    NARCIS (Netherlands)

    Vogelzang, M; Nijboer, JMM; van der Horst, ICC; Zijlstra, F; ten Duis, HJ; Nijsten, MWN

    Background. Acute hyperglycemia is associated with adverse outcome in critically ill patients. Glucose control with insulin improves outcome in surgical intensive care unit (SICU) patients, but the effect in trauma patients is unknown. We investigated hyperglycemia and outcome in SICU patients with

  8. Admission hyperglycemia and outcome after intravenous thrombolysis : is there a difference among the stroke-subtypes?

    NARCIS (Netherlands)

    Miedema, Irene; Luijckx, Gert-Jan; Brouns, Raf; De Keyser, Jacques; Uyttenboogaart, Maarten

    2016-01-01

    Background: The prognostic influence of hyperglycemia in acute stroke has been well established. While in cortical stroke there is a strong association between hyperglycemia and poor outcome, this relation is less clear in lacunar stroke. It has been suggested that this discrepancy is present among

  9. Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis, oxidative stress and pro-inflammatory cytokine expression in vivo

    National Research Council Canada - National Science Library

    Wu, Na; Shen, Haitao; Liu, Henan; Wang, Yanjun; Bai, Yu; Han, Ping

    2016-01-01

    .... In the present study, the influence of acute fluctuant hyperglycemia and persistent hyperglycemia on vascular endothelial cell apoptosis, function, oxidative stress and inflammation was examined in vivo...

  10. [Complications associated with hyperglycemia in liver transplant patients].

    Science.gov (United States)

    Builes Montaño, Carlos Esteban; Montoya, Julián Felipe; Londoño, Carolina Aguilar; Palacios Bayona, Karen Lorena; Restrepo Gutiérrez, Juan Carlos; Restrepo, Johnayro Gutiérrez; Arango Toro, Clara María; Jaimes Barragan, Fabián Alberto

    2014-01-01

    Hyperglycemia is a frequent phenomenon in hospitalized patients that is associated with negative outcomes. It is common in liver transplant patients as a result of stress and is related to immunosuppressant drugs. Although studies are few, a history of diabetes and the presentation of hyperglycemia during liver transplantation have been associated with a higher risk for rejection. To analyze whether hyperglycemia during the first 48hours after liver transplantation was associated with a higher risk for infection, rejection, or longer hospital stay. A retrospective cohort study was conducted on patients above the age of 15years that received a liver transplant. Hyperglycemia was defined as a value above 140mg/dl and it was measured in three different manners (as an isolated value, as a mean value, and as a weighted value over time). The relation of hyperglycemia to a risk for acute rejection, infection, or longer hospital stay was evaluated. Some form of hyperglycemia was present in 94% of the patients during the first 48 post-transplantation hours, regardless of its definition. There was no increased risk for rejection (OR: 1.49; 95%CI: 0.55-4.05), infection (OR: 0.62; 95%CI: 0.16-2.25), or longer hospital stay between the patients that presented with hyperglycemia and those that did not. Hyperglycemia during the first 48hours after transplantation appeared to be an expected phenomenon in the majority of patients and was not associated with a greater risk for rejection or infection and it had no impact on the duration of hospital stay. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  11. What Is the Difference Between Hyperglycemia and Hypoglycemia?

    Science.gov (United States)

    ... Hyperglycemia and Hypoglycemia? What Is the Difference Between Hyperglycemia and Hypoglycemia? Leer este artículo en español By ... What Is Hyperglycemia? What Is Hypoglycemia? What Is Hyperglycemia? In relation to diabetes , hyperglycemia refers to chronically ...

  12. Fatal Metformin Overdose Presenting with Progressive Hyperglycemia

    Directory of Open Access Journals (Sweden)

    Suchard, Jeffrey R

    2008-08-01

    Full Text Available A 29-year-old man with no history of diabetes ingested over 60 grams of metformin in a suicide attempt. He presented to the emergency department with acute renal insufficiency, severe lactic acidosis, and rapidly-progressive hyperglycemia. The patient’s peak serum glucose level of 707 mg/dL is the highest yet reported in a case of metformin toxicity. Treatment included sodium bicarbonate infusion and hemodialysis, but the patient suffered several cardiac arrests with pulseless electrical activity and ultimately expired 25 hours after the ingestion.

  13. Admission hyperglycemia an independent predictor of outcome in ...

    African Journals Online (AJOL)

    Background: Stroke is one of the important causes of long-term disabilityrelated deaths worldwide. Incidence and prevalence of stroke have been steadily increasing in India. Increasing interest has been focused on the role of admission hyperglycemia in the evolution of acute ischemic stroke. Very few studies were ...

  14. Admission Hyperglycemia an Independent Predictor of Outcome in ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... Background: Stroke is one of the important causes of long-term disability- related deaths worldwide. Incidence and prevalence of stroke have been steadily increasing in India. Increasing interest has been focused on the role of admission hyperglycemia in the evolution of acute ischemic stroke. Very few ...

  15. Hyperglycemia and Perioperative Glucose Management

    Science.gov (United States)

    Duncan, Andra E.

    2013-01-01

    Hyperglycemia is associated with increased mortality and morbidity in critically ill patients. Surgical patients commonly develop hyperglycemia related to the hypermetabolic stress response, which increases glucose production and causes insulin resistance. Although hyperglycemia is associated with worse outcomes, the treatment of hyperglycemia with insulin infusions has not provided consistent benefits. Despite early results, which suggested decreased mortality and other advantages of “tight” glucose control, later investigations found no benefit or increased mortality when hyperglycemia was aggressively treated with insulin. Because of these conflicting data, the optimal glucose concentration to improve outcomes in critically ill patients is unknown. There is agreement, however, that hypoglycemia is an undesirable complication of intensive insulin therapy and should be avoided. In addition, the risk of increased glucose variability should be recognized, because of the associated increased risk for worse outcomes. Patients with diabetes mellitus experience chronic hyperglycemia and often require more intensive perioperative glucose management. When diabetic patients are evaluated before surgery, appropriate management of oral hypoglycemic agents is necessary as several of these agents warrant special consideration. Current recommendations for perioperative glucose management from national societies are varied, but, most suggest that tight glucose control may not be beneficial, while mild hyperglycemia appears to be well-tolerated. PMID:22762467

  16. Glucosamine: Can It Worsen Gout Symptoms?

    Science.gov (United States)

    ... symptoms? My husband takes glucosamine supplements to treat gout. But I'm wondering if glucosamine, which contains shellfish, may actually worsen gout symptoms? Answers from April Chang-Miller, M.D. ...

  17. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    Science.gov (United States)

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role of hyperglycemia in CAD associated with type 2 diabetes is less clear. Understanding the mechanisms whereby type 2 diabetes exacerbates CAD offers hope for new therapeutic strategies to prevent and treat atherosclerotic vascular disease. PMID:22055501

  18. Nigerian Honey Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Rats.

    Science.gov (United States)

    Erejuwa, Omotayo O; Nwobodo, Ndubuisi N; Akpan, Joseph L; Okorie, Ugochi A; Ezeonu, Chinonyelum T; Ezeokpo, Basil C; Nwadike, Kenneth I; Erhiano, Erhirhie; Abdul Wahab, Mohd S; Sulaiman, Siti A

    2016-02-24

    Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary to reduce cardiovascular events. Honey reduces hyperglycemia and dyslipidemia. The reproducibility of these beneficial effects and their generalization to honey samples of other geographical parts of the world remain controversial. Currently, data are limited and findings are inconclusive especially with evidence showing honey increased glycosylated hemoglobin in diabetic patients. It was hypothesized that this deteriorating effect might be due to administered high doses. This study investigated if Nigerian honey could ameliorate hyperglycemia and hyperlipidemia. It also evaluated if high doses of honey could worsen glucose and lipid abnormalities. Honey (1.0, 2.0 or 3.0 g/kg) was administered to diabetic rats for three weeks. Honey (1.0 or 2.0 g/kg) significantly (p honey (3.0 g/kg) significantly (p honey using Nigerian honey. However, none of the doses deteriorated hyperglycemia and dyslipidemia.

  19. Ketotic hyperglycemia with movement disorder

    Directory of Open Access Journals (Sweden)

    Disha Awasthi

    2012-01-01

    Full Text Available Chorea, hemichorea-hemiballismus and severe partial seizures may be the presenting features of nonketotic hyperglycemia in older adults with type 2 diabetes, but cases in young adults with type 1 diabetes are rare. We hereby report a very rare case of diabetic ketosis with movement disorder in a young patient.

  20. Influence of HbA1c levels on platelet function profiles associated with tight glycemic control in patients presenting with hyperglycemia and an acute coronary syndrome. A subanalysis of the CHIPS Study ("Control de HIperglucemia y Actividad Plaquetaria en Pacientes con Síndrome Coronario Agudo").

    Science.gov (United States)

    Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

    2013-02-01

    Patients with hyperglycemia, an acute coronary syndrome and poor glycemic control have increased platelet reactivity and poor prognosis. However, it is unclear the influence of a tight glycemic control on platelet reactivity in these patients. This is a subanalysis of the CHIPS study. This trial randomized patients with hyperglycemia to undergo an intensive glucose control (target blood glucose 80-120 mg/dL), or conventional glucose control (target blood glucose <180 mg/dL). We analyzed platelet function at discharge on the subgroup of patients with poor glycemic control, defined with admission levels of HbA1c higher than 6.5%. The primary endpoint was maximal platelet aggregation following stimuli with 20 μM ADP. We also measured aggregation following collagen, epinephrine, and thrombin receptor-activated peptide, as well as P2Y12 reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin. A total of 67 patients presented HbA1c ≥ 6.5% (37 intensive, 30 conventional), while 42 had HbA1c < 6.5% (20 intensive, 22 conventional). There were no differences in baseline characteristics between groups. At discharge, patients with HbA1c ≥6.5% had significantly reduced MPA with intensive glucose control compared with conventional control (46.1 ± 22.3 vs. 60.4 ± 20.0%; p = 0.004). Similar findings were shown with other measures of platelet function. However, glucose control strategy did not affect platelet function parameters in patients with HbA1c < 6.5%. Intensive glucose control in patients presenting with an acute coronary syndrome and hyperglycemia results in a reduction of platelet reactivity only in the presence of elevated HbA1c levels.

  1. An epigenomic signature of postprandial hyperglycemia in peripheral blood leukocytes.

    Science.gov (United States)

    Shim, Sung-Mi; Cho, Yoon-Kyung; Hong, Eun-Jung; Han, Bok-Ghee; Jeon, Jae-Pil

    2016-03-01

    Postprandial hyperglycemia is known to be one of the earliest signs of abnormal glucose homeostasis associated with type 2 diabetes. This study aimed to assess clinical significance of a 1-h postprandial glucose level for the development of diabetes, and identify epigenetic biomarkers of postprandial hyperglycemia. We analyzed clinical data from the oral glucose tolerance tests for healthy subjects (n=4502). The ratio (Glu60/Glu0) of 1-h glucose levels to fasting glucose levels was significantly associated with an insulin sensitive index (QUICKI, quantitative insulin sensitivity check index) (β=0.055, P=1.25E-04) as well as a risk of future pre-diabetic and diabetic conversion. Next, DNA methylation profile analyses of 24 matched pairs of the high and low Glu60/Glu0 ratio subjects showed that specific DNA methylation levels in the promoter region of an olfactory receptor gene (olfactory receptor gene family10 member A4, OR10A4) were associated with the Glu60/Glu0 ratios (β=0.337, P=0.03). Moreover, acute oral glucose challenges decreased the DNA methylation levels of OR10A4 but not the global DNA methylation in peripheral leukocytes of healthy subjects (n=7), indicating that OR10A4 is a specific epigenomic target of postprandial hyperglycemia. This work suggests possible relevance of olfactory receptor genes to an earlier molecular biomarker of peripheral hyperglycemia and diabetic conversion.

  2. Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yunli, E-mail: chrisyu1255@yahoo.com.cn [Department of Pharmaceutics, The Second Affiliated Hospital of Soochow University, Suzhou 215004 (China); Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Wang, Xinting, E-mail: wxinting1986@yahoo.com.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Can, E-mail: ltsan@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Yao, Dan, E-mail: erinyao@126.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Shanghai Institute of Materia Medica, Shanghai 201203 (China); Hu, Mengyue, E-mail: juliahmy@126.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia, E-mail: ljbzd@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Hu, Nan, E-mail: hn_324@163.com [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Li, E-mail: liulee@cpu.edu.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China); Liu, Xiaodong, E-mail: xdliu@cpu.edu.cn [Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009 (China)

    2013-02-01

    Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-day gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K{sub ATP} channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. -- Highlights: ► Gatifloxacin induced hyperglycemia both in diabetic rats and normal rats. ► Gatifloxacin enhanced GLP-1 secretion but inhibited insulin secretion in rats. ► Long-term exposure to high GLP-1 inhibited insulin secretion and biosynthesis. ► GLP-1 over-secretion may be

  3. Experimental hyperglycemia induces an increase of monocyte and T-lymphocyte content in adipose tissue of healthy obese women.

    Directory of Open Access Journals (Sweden)

    Michaela Tencerová

    Full Text Available Hyperglycemia represents one of possible mediators for activation of immune system and may contribute to worsening of inflammatory state associated with obesity. The aim of our study was to investigate the effect of a short-term hyperglycemia (HG on the phenotype and relative content of immune cells in circulation and subcutaneous abdominal adipose tissue (SAAT in obese women without metabolic complications.Three hour HG clamp with infusion of octreotide and control investigations with infusion of octreotide or saline were performed in three groups of obese women (Group1: HG, Group 2: Octreotide, Group 3: Saline, n=10 per group. Before and at the end of the interventions, samples of SAAT and blood were obtained. The relative content of immune cells in blood and SAAT was determined by flow cytometry. Gene expression analysis of immunity-related markers in SAAT was performed by quantitative real-time PCR.In blood, no changes in analysed immune cell population were observed in response to HG. In SAAT, HG induced an increase in the content of CD206 negative monocytes/macrophages (p<0.05 and T lymphocytes (both T helper and T cytotoxic lymphocytes, p<0.01. Further, HG promoted an increase of mRNA levels of immune response markers (CCL2, TLR4, TNFα and lymphocyte markers (CD3g, CD4, CD8a, TBX21, GATA3, FoxP3 in SAAT (p<0.05 and 0.01. Under both control infusions, none of these changes were observed.Acute HG significantly increased the content of monocytes and lymphocytes in SAAT of healthy obese women. This result suggests that the short-term HG can modulate an immune status of AT in obese subjects.

  4. Hyperglycemia Increases Muscle Blood Flow and Alters Endothelial Function in Adolescents with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Amanda S. Dye

    2012-01-01

    Full Text Available Alterations of blood flow and endothelial function precede development of complications in type 1 diabetes. The effects of hyperglycemia on vascular function in early type 1 diabetes are poorly understood. To investigate the effect of hyperglycemia on forearm vascular resistance (FVR and endothelial function in adolescents with type 1 diabetes, FVR was measured before and after 5 minutes of upper arm arterial occlusion using venous occlusion plethysmography in (1 fasted state, (2 euglycemic state (~90 mg/dL; using 40 mU/m2/min insulin infusion, and (3 hyperglycemic state (~200 mg/dL in 11 adolescents with type 1 diabetes. Endothelial function was assessed by the change in FVR following occlusion. Seven subjects returned for a repeat study with hyperglycemia replaced by euglycemia. Preocclusion FVR decreased from euglycemia to hyperglycemia (P=0.003. Postocclusion fall in FVR during hyperglycemia was less than during euglycemia (P=0.002. These findings were not reproduced when hyperglycemia was replaced with a second euglycemia. These results demonstrate that acute hyperglycemia causes vasodilation and alters endothelial function in adolescents with type 1 diabetes. In addition they have implications for future studies of endothelial function in type 1 diabetes and provide insight into the etiology of macrovascular and microvascular complications of type 1 diabetes.

  5. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    OpenAIRE

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role o...

  6. [Effect of postprandial hyperglycemia and hyperinsulinemia on vascular responsiveness].

    Science.gov (United States)

    Zamami, Yoshito; Takatori, Shingo; Iwatani, Yukiko; Yamawaki, Kousuke; Miyashita, Satoko; Yabumae, Nana; Takayama, Fusako; Mio, Mitsunobu; Kawasaki, Hiromu

    2008-03-01

    Recent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin gene-related peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation.

  7. Rapsyn congenital myasthenic syndrome worsened by fluoxetine.

    Science.gov (United States)

    Visser, Amy C; Laughlin, Ruple S; Litchy, William J; Benarroch, Eduardo E; Milone, Margherita

    2017-01-01

    Fluoxetine is a selective serotonin reuptake inhibitor and long-lived open channel blocker of the acetylcholine receptor, often used in the treatment of slow-channel congenital myasthenic syndromes (CMS). We report a 42-year-old woman who had a history of episodic limb weakness that worsened after initiation of fluoxetine for treatment of depression. Genetic testing for CMS revealed a homozygous pathogenic mutation in the rapsyn (RAPSN) gene (p.Asn88Lys). Electrodiagnostic testing was performed before and 1 month after discontinuation of fluoxetine. The 2 Hz repetitive nerve stimulation of the fibular and spinal accessory nerves showed a baseline decrement of 36% and 14%, respectively. One month after discontinuing fluoxetine, the spinal accessory nerve decrement was no longer present, and the decrement in the fibular nerve was improved at 17%. This case demonstrates worsening of both clinical and electrophysiologic findings in a patient with CMS secondary to a RAPSN mutation treated with fluoxetine. Muscle Nerve 55: 131-135, 2017. © 2016 Wiley Periodicals, Inc.

  8. Non Ketotic Hyperosmolar Hyperglycemia presenting as Epilepsia ...

    African Journals Online (AJOL)

    We report a patient with epilepsia partialis continua (EPC) associated with non ketotic hyperosmolar hyperglycemia. EPC is an uncommon presentation of nonketotic hyperglycemia. This case was reported in the Medical Intensive Care Unit in Hamad Medical Corporation, Doha, Qatar. Keywords: Epilepsia partialis continua ...

  9. Prediction of hyperglycemia in preterm newborn infants

    Directory of Open Access Journals (Sweden)

    Falcão Mário Cícero

    1999-01-01

    Full Text Available Many conditions are associated with hyperglycemia in preterm neonates because they are very susceptible to changes in carbohydrate homeostasis. The purpose of this study was to evaluate the occurrence of hyperglycemia in preterm infants undergoing glucose infusion during the first week of life, and to enumerate the main variables predictive of hyperglycemia. This prospective study (during 1994 included 40 preterm neonates (gestational age 31 weeks, birth weight (1500 g, glucose infusion rate (6 mg/kg/min and clinical status (stable vs. unstable. Multivariate analysis by logistic regression gave the following mathematical model for predicting the probability of hyperglycemia: 1/exp{-3.1437 + 0.5819(GA + 0.9234(GIR + 1.0978(Clinical status} The main predictive variables in our study, in increasing order of importance, were gestational age, glucose infusion rate and, the clinical status (stable or unstable of the preterm newborn infant. The probability of hyperglycemia ranged from 4.1% to 36.9%.

  10. Hyperglycemia, a Neglected Factor during Cancer Progression

    Science.gov (United States)

    Shen, Xin; Lei, Jianjun; Xu, Qinhong; Yu, Yongtian; Ma, Qingyong

    2014-01-01

    Recent evidence from large cohort studies suggests that there exists a higher cancer incidence in people with type 2 diabetes (DM2). However, to date, the potential reasons for this association remain unclear. Hyperglycemia, the most important feature of diabetes, may be responsible for the excess glucose supply for these glucose-hungry cells, and it contributes to apoptosis resistance, oncogenesis, and tumor cell resistance to chemotherapy. Considering associations between diabetes and malignancies, the effect of hyperglycemia on cancer progression in cancer patients with abnormal blood glucose should not be neglected. In this paper, we describe the role that hyperglycemia plays in cancer progression and treatment and illustrate that hyperglycemia may contribute to a more malignant phenotype of cancer cells and lead to drug resistance. Therefore, controlling hyperglycemia may have important therapeutic implications in cancer patients. PMID:24864247

  11. Weight Loss & Acute Porphyria

    Science.gov (United States)

    ... APF You are here Home Diet and Nutrition Weight loss & acute Porphyria Being overweight is a particular problem ... of carbohydrate and energy in an effort to lose weight can worsen these diseases. Severe acute attacks have ...

  12. Right ventricular outflow tract tachycardia worsened during pregnancy

    African Journals Online (AJOL)

    Right ventricular outflow tract tachycardia worsened during pregnancy. Y Kambiré, L Konaté, GRC Millogo, E Sib, M Amoussou, LVA Nebié, A Niakara. Abstract. We report the case of a 35 years old woman without underlying heart disease who was diagnosed with a right ventricular outflow tract tachycardia worsened during ...

  13. A case of successful treatment of a patient with hyperglycemia of 2700 mg/dL.

    Science.gov (United States)

    Honda, Yasuyuki; Yanagawa, Youichi; Terazumi, Keiko; Nishi, Kouichirou

    2012-01-01

    A 34-year-old man with obesity who was an avid consumer of soft drinks was found in a coma after complaining of a poor physical condition for a few days. On arrival, he had hyperglycemia of 2700 mg/dL, coma, shock, sepsis, aspiration pneumonia, acute renal failure, acute pancreatitis, liver dysfunction, and systemic mycosis. The rapid infusion of a large volume of isotonic saline, insulin, antibiotics, and ulinastatin was performed, and mechanical ventilation was applied. The treatment was complicated by transient hypernatremia resulting from osmostasis, which gradually decreased. He demonstrated transient decerebrate posturing upon stimulation; however, he became conscious within a week of admission, and his associated diseases also improved. After correcting his hyperglycemia, the patient was discharged on foot. We report our case of a patient with hyperglycemia of 2700 mg/dL, which was the highest value reported in the English literature. During the correction of the hyperglycemia, transient hypernatremia occurred to prevent abrupt decrease in osmolality, which thus resulted in cell swelling.

  14. Worsening renal function in heart failure: the need for a consensus definition.

    Science.gov (United States)

    Sheerin, Noella J; Newton, Phillip J; Macdonald, Peter S; Leung, Dominic Y C; Sibbritt, David; Spicer, Stephen Timothy; Johnson, Kay; Krum, Henry; Davidson, Patricia M

    2014-07-01

    Acute decompensated heart failure is a common cause of hospitalisation. This is a period of vulnerability both in altered pathophysiology and also the potential for iatrogenesis due to therapeutic interventions. Renal dysfunction is often associated with heart failure and portends adverse outcomes. Identifying heart failure patients at risk of renal dysfunction is important in preventing progression to chronic kidney disease or worsening renal function, informing adjustment to medication management and potentially preventing adverse events. However, there is no working or consensus definition in international heart failure management guidelines for worsening renal function. In addition, there appears to be no concordance or adaptation of chronic kidney disease guidelines by heart failure guideline development groups for the monitoring of chronic kidney disease in heart failure. Our aim is to encourage the debate for an agreed definition given the prognostic impact of worsening renal function in heart failure. We present the case for the uptake of the Acute Kidney Injury Network criteria for acute kidney injury with some minor alterations. This has the potential to inform study design and meta-analysis thereby building the knowledgebase for guideline development. Definition consensus supports data element, clinical registry and electronic algorithm innovation as instruments for quality improvement and clinical research for better patient outcomes. In addition, we recommend all community managed heart failure patients have their baseline renal function classified and routinely monitored in accordance with established renal guidelines to help identify those at increased risk for worsening renal function or progression to chronic kidney disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Hyperglucagonemia precedes a decline in insulin secretion and causes hyperglycemia in chronically glucose-infused rats

    Science.gov (United States)

    Jamison, Rachel A.; Stark, Romana; Dong, Jianying; Yonemitsu, Shin; Zhang, Dongyan; Shulman, Gerald I.

    2011-01-01

    Islet damage from glucose toxicity is implicated in the pathogenesis of type 2 diabetes, but the sequence of events leading to islet cell dysfunction and hyperglycemia remains unclear. To examine the early stages of islet pathology resulting from increased basal glucose loads, normal awake rats were infused with glucose continuously for 10 days. Plasma glucose and markers of islet and liver function were monitored throughout the infusion. After initial hyperglycemia, rats adapted to the infusion and maintained euglycemia for approximately 4 days. Continued infusion led to worsening hyperglycemia in just 5% of rats after 6 days, but 69% after 8 days and 89% after 10 days, despite unchanged basal and stimulated plasma insulin and C-peptide concentrations. In contrast, plasma glucagon concentrations increased fivefold. Endogenous glucose production (EGP) was appropriately suppressed after 4 days (2.8 ± 0.7 vs. 6.1 ± 0.4 mg·kg−1·min−1 on day 0, P insulin secretion. Such hyperglucagonemia could lead to excessive glucose production overwhelming the capacity of the β-cell to maintain glucose homeostasis. PMID:21862723

  16. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Danielle Desjardins

    Full Text Available In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE. Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb or vascular endothelial growth factor (VEGF, increased histone deacetylase (HDAC activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA, suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro and fluid transport (in vivo. Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina.

  17. Admission Hyperglycemia and Clinical Outcome in Cerebral Venous Thrombosis

    NARCIS (Netherlands)

    Zuurbier, Susanna M.; Hiltunen, Sini; Tatlisumak, Turgut; Peters, Guusje M.; Silvis, Suzanne M.; Haapaniemi, Elena; Kruyt, Nyika D.; Putaala, Jukka; Coutinho, Jonathan M.

    2016-01-01

    Background and Purpose-Admission hyperglycemia is associated with poor clinical outcome in ischemic and hemorrhagic stroke. Admission hyperglycemia has not been investigated in patients with cerebral venous thrombosis. Methods-Consecutive adult patients with cerebral venous thrombosis were included

  18. Hyperglycemia in bacterial meningitis: a prospective cohort study

    NARCIS (Netherlands)

    Schut, E.S.; Westendorp, W.F.; de Gans, J.; Kruyt, N.D.; Spanjaard, L.; Reitsma, J.B.; van de Beek, D.

    2009-01-01

    ABSTRACT: BACKGROUND: Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis. METHODS: We collected data prospectively between

  19. Patients with worsening chronic heart failure who present to a hospital emergency department require hospital care

    Directory of Open Access Journals (Sweden)

    Shafazand Masoud

    2012-03-01

    Full Text Available Abstract Background Chronic heart failure (CHF is a major public health problem characterised by progressive deterioration with disabling symptoms and frequent hospital admissions. To influence hospitalisation rates it is crucial to identify precipitating factors. To characterise patients with CHF who seek an emergency department (ED because of worsening symptoms and signs and to explore the reasons why they are admitted to hospital. Method Patients (n = 2,648 seeking care for dyspnoea were identified at the ED, Sahlgrenska University Hospital/Östra. Out of 2,648 patients, 1,127 had a previous diagnosis of CHF, and of these, 786 were included in the present study with at least one sign and one symptom of worsening CHF. Results Although several of the patients wanted to go home after acute treatment in the ED, only 2% could be sent home. These patients were enrolled in an interventional study, which evaluated the acute care at home compared to the conventional, in hospital care. The remaining patients were admitted to hospital because of serious condition, including pneumonia/respiratory disease, myocardial infarction, pulmonary oedema, anaemia, the need to monitor cardiac rhythm, pathological blood chemistry and difficulties to communicate. Conclusion The vast majority of patients with worsening CHF seeking the ED required hospital care, predominantly because of co-morbidities. Patients with CHF with symptomatic deterioration may be admitted to hospital without additional emergency room investigations.

  20. Molecular mechanisms of hyperglycemia and cardiovascular-related events in critically ill patients: rationale for the clinical benefits of insulin therapy

    OpenAIRE

    Samer Ellahham

    2010-01-01

    Samer EllahhamParagon Cardiovascular Foundation, Falls Church, VA, USAAbstract: Newly recognized hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease (CVD). Hyperglycemia has been linked to increased morbidity and mortality in critically ill patients, especially when it is newly recognized. Increased rates of reinfarction, rehospitalization, major cardiovascular events, and death in CVD patients have also been found. An expanding bo...

  1. Considering hyperglycemia and thrombolysis in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial

    National Research Council Canada - National Science Library

    Southerland, Andrew M; Johnston, Karen C

    2012-01-01

    ...). The Stroke Hyperglycemia Insulin Network Effort (SHINE) study is a phase III single‐blinded, randomized control trial comparing an intensive level of glucose control with standard of care glucose control in hyperglycemic stroke patients...

  2. Effect of acid-sensing ion channel 1a on the process of liver fibrosis under hyperglycemia

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huan, E-mail: wanghuan7@126.com [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032 (China); Wang, Ying-hong; Yang, Feng; Li, Xiao-feng; Tian, Yuan-yao; Ni, Ming-ming; Zuo, Long-quan; Meng, Xiao-Ming [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032 (China); Huang, Yan, E-mail: aydhy@126.com [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei, 230032 (China)

    2015-12-25

    Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetes complication liver fibrosis. - Highlights: • Hyperglycemia is a risk factor for the process of liver fibrosis. • ASIC1a may be a key factor linking between high glucose and liver fibrosis. • Notch1/Hes-1 may involve to the process of liver fibrosis under hyperglycemia.

  3. Hyperglycemia and Inflammation in older individuals.

    NARCIS (Netherlands)

    de Rekeneire, N.; Peila, R.; Ding, J.; Colbert, L.H.; Visser, M.; Shorr, R.I.; Kritchevsky, S.B.; Kuller, L.H.; Strotmeyer, E.M.; Schwartz, A.V.; Vellas, B.; Harris, T.B.

    2006-01-01

    OBJECTIVE - The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT]) and diabetes in older individuals. RESEARCH DESIGN AND METHODS - Baseline data from the Health, Aging and Body Composition study

  4. Effects of physiological hyperglycemia on duodenal motility and flow events, glucose absorption, and incretin secretion in healthy humans

    NARCIS (Netherlands)

    Kuo, Paul; Wishart, Judith M.; Bellon, Max; Smout, André J.; Holloway, Richard H.; Fraser, Robert J. L.; Horowitz, Michael; Jones, Karen L.; Rayner, Christopher K.

    2010-01-01

    CONTEXT: Acute hyperglycemia slows gastric emptying, but its effects on small intestinal motor activity and glucose absorption are unknown. In type 2 diabetes, the postprandial secretion of glucose-dependent insulinotropic polypeptide (GIP) is preserved, but that of glucagon-like peptide-1 (GLP-1)

  5. Both fasting and glucose-stimulated proinsulin levels predict hyperglycemia and incident type 2 diabetes: a population-based study of 9,396 Finnish men.

    Science.gov (United States)

    Vangipurapu, Jagadish; Stančáková, Alena; Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku

    2015-01-01

    Hyperproinsulinemia is an indicator of β-cell dysfunction, and fasting proinsulin levels are elevated in patients with hyperglycemia. It is not known whether proinsulin levels after a glucose load are better predictors of hyperglycemia and type 2 diabetes than fasting proinsulin. Participants were 9,396 Finnish men (mean±SD, age 57.3±7.1 years, BMI 27.0±4.0 kg/m2) of the population-based METabolic Syndrome In Men Study who were non-diabetic at the recruitment, and who participated in a 6-year follow-up study. Proinsulin and insulin levels were measured in the fasting state and 30 and 120 min after an oral glucose load. Area under the curve (AUC) and proinsulin to insulin ratios were calculated. Fasting proinsulin, proinsulin at 30 min and proinsulin AUC during the first 30 min of an oral glucose tolerance test significantly predicted both the worsening of hyperglycemia and type 2 diabetes after adjustment for confounding factors. Further adjustment for insulin sensitivity (Matsuda index) or insulin secretion (Disposition index) weakened these associations. Insulin sensitivity had a major impact on these associations. Our results suggest that proinsulin in the fasting state and after an oral glucose load similarly predict the worsening of hyperglycemia and conversion to type 2 diabetes.

  6. Lung Adenocarcinoma Presenting as Worsening of Chronic Neck Pain—A Cautionary Tale

    Directory of Open Access Journals (Sweden)

    Neeka N Akhavan

    2017-02-01

    Full Text Available Introduction: Neck pain is a common musculoskeletal problem that up to 70% of the world population will experience at some point in their lives. Intramedullary spinal cord metastasis is an exceedingly rare complication of malignancy that affects less than 1% of all patients with cancer. Case report: We report a case of a 61-year-old man who presented to primary care clinic with 1-month history of worsening neck pain with associated neurologic deficits. Despite initial conservative management, the patient continued to have progressive worsening of sensory and motor deficits. Magnetic resonance imaging of the cervical spine showed vasogenic edema of the brain and spinal cord and nodularity at the C4-C5 level. A computed tomography of the chest showed a dense lesion in the left lower lobe of the lung; histopathology of the biopsied specimen was consistent with moderately differentiated lung adenocarcinoma. Conclusions: A high index of suspicion is necessary when chronic neck pain acutely worsens, changes in character, or is accompanied by neurologic deficits. These clinical signs warrant further investigation into a secondary cause of neck pain. Intramedullary spinal cord metastases are rare complications of systemic cancer that commonly present with neck pain and upper extremity paraesthesias; early diagnosis and management are necessary to prevent complications such as spinal cord hemisection syndrome or spinal cord transection.

  7. Management of hyperglycemia in the neurosurgery patient.

    Science.gov (United States)

    Daniel, Rene; Villuri, Satya; Furlong, Kevin

    2017-10-01

    Hyperglycemia is associated with adverse outcomes in patients who are candidates for or underwent neurosurgical procedures. Specific concerns and settings that relate to these patients are preoperative glycemic control, intraoperative control, management in the neurological intensive care unit (NICU), and postoperative control. In each of these settings, physicians have to ensure appropriate glycemic control to prevent or minimize adverse events. The glycemic control is usually managed by a neurohospitalist in co-management with the neurosurgery team pre- and post-operatively, and by the neurocritical care team in the setting of NICU. In this review article, we outline current standards of care for neurosurgery patients with diabetes mellitus and/or and hyperglycemia and discuss results of most recent clinical trials. We highlight specific concerns with regards to glycemic controls in these patients including enteral tube feeding and parenteral nutrition, the issues of the transition to the outpatient care, and management of steroid-induced hyperglycemia. We also note lack of evidence in some important areas, and the need for more research addressing these gaps. Where possible, we provide suggestions how to manage these patients when there is no underlying guideline.

  8. Management of Hyperglycemia During Enteral and Parenteral Nutrition Therapy

    Science.gov (United States)

    Umpierrez, Guillermo E.

    2013-01-01

    Hyperglycemia is a frequent complication of enteral and parenteral nutrition in hospitalized patients. Extensive evidence from observational studies indicates that the development of hyperglycemia during parenteral and enteral nutrition is associated with an increased risk of death and infectious complications. There are no specific guidelines recommending glycemic targets and effective strategies for the management of hyperglycemia during specialized nutritional support. Managing hyperglycemia in these patients should include optimization of carbohydrate content and administration of intravenous or subcutaneous insulin therapy. The administration of continuous insulin infusion and insulin addition to nutrition bag are efficient approaches to control hyperglycemia during parenteral nutrition. Subcutaneous administration of long-acting insulin with scheduled or corrective doses of short-acting insulin is superior to the sliding scale insulin strategy in patients receiving enteral feedings. Randomized controlled studies are needed to evaluate safe and effective therapeutic strategies for the management of hyperglycemia in patients receiving nutritional support. PMID:23065369

  9. Type 2 diabetes: postprandial hyperglycemia and increased cardiovascular risk

    OpenAIRE

    Ajikumar V Aryangat; John E Gerich

    2010-01-01

    Ajikumar V Aryangat, John E GerichUniversity of Rochester, Rochester, New York, USAAbstract: Hyperglycemia is a major risk factor for both the microvascular and macrovascular complications in  patients with type 2 diabetes. This review summarizes the cardiovascular results of large outcomes trials in diabetes and presents new evidence on the role of hyperglycemia, with particular emphasis on postprandial hyperglycemia, in adverse cardiovascular outcomes in patients with type 2 diabet...

  10. Predicting worsening asthma control following the common cold

    NARCIS (Netherlands)

    Walter, M. J.; Castro, M.; Kunselman, S. J.; Chinchilli, V. M.; Reno, M.; Ramkumar, T. P.; Avila, P. C.; Boushey, H. A.; Ameredes, B. T.; Bleecker, E. R.; Calhoun, W. J.; Cherniack, R. M.; Craig, T. J.; Denlinger, L. C.; Israel, E.; Fahy, J. V.; Jarjour, N. N.; Kraft, M.; Lazarus, S. C.; Lemanske, R. F.; Martin, R. J.; Peters, S. P.; Ramsdell, J. W.; Sorkness, C. A.; Sutherland, E. R.; Szefler, S. J.; Wasserman, S. I.; Wechsler, M. E.

    2008-01-01

    The asthmatic response to the common cold is highly variable, and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multicentric cohort study of 413 adult subjects with asthma, the mini-Asthma Control Questionnaire

  11. Odors as triggering and worsening factors for migraine in men

    Directory of Open Access Journals (Sweden)

    A M Lima

    2011-01-01

    Full Text Available OBJECTIVE: To assess the role of odors in triggering or worsening migraine in men. METHOD: Ninety-eight male migraineurs from the general population were assessed individually through questionnaires. Environmental factors relating to their migraine were reported, with special focus on the role of odors. RESULTS: Odors were the second most frequent triggering factor for migraine attacks (48%, behind stressful situations (59%. Likewise, odors were the second most frequent worsening factor (73%, just behind excessive light (74%. Thirty-three individuals (33.4% stated that odors were both triggering and worsening factors for their migraine attacks. Perfume, cigarette smoke and cleaning products were the most frequent migraine-related odors reported by these male migraineurs. CONCLUSION: This was the first study to assess the role of odors in migraine exclusively in men. There was a high degree of odor-related migraine among these men, thus suggesting that patient education could alert such individuals to gender-related factors, since different triggering and worsening factors have been reported by males and females.

  12. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

    Science.gov (United States)

    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

    2009-01-01

    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  13. Gynura procumbens Extract Alleviates Postprandial Hyperglycemia in Diabetic Mice

    National Research Council Canada - National Science Library

    Sung-In Choi; Mi Hwa Park; Ji-Sook Han

    2016-01-01

    This study was designed to investigate the inhibitory effect of Gynura procumbens extract against carbohydrate digesting enzymes and its ability to ameliorate postprandial hyperglycemia in streptozotocin (STZ...

  14. Clinical Inertia during Postoperative Management of Diabetes Mellitus: Relationship between Hyperglycemia and Insulin Therapy Intensification

    Science.gov (United States)

    Coan, Kathryn E.; Schlinkert, Andrew B.; Beck, Brandon R.; Haakinson, Danielle J.; Castro, Janna C.; Apsey, Heidi A.; Schlinkert,, Richard T.; Cook, Curtiss B.

    2013-01-01

    Objective Our objective was to assess the application of insulin regimens in surgical postoperative patients with diabetes. Methods A chart review was conducted of patients with diabetes who were hospitalized postoperatively between January 1 and April 30, 2011. Analysis was restricted to patients hospitalized for ≥3 days and excluded cases with an endocrinology consult. Insulin regimens were categorized as “basal plus short acting,” “short acting only,” or “none,” and the pattern of use was evaluated by hyperglycemia severity according to tertiles of both mean glucose and the number of glucose measurements >180 mg/dl. Results Among cases selected for analysis (n = 119), examination of changes in insulin use based on tertiles of mean glucose showed that use of basal plus short-acting insulin increased from 10% in the lowest tertile (mean glucose, 120 mg/dl) to 18% in the highest tertile (mean glucose, 198 mg/dl; p insulin only, with 12% receiving no insulin. Intensification of insulin to a basal plus short-acting regimen was also seen when changes were evaluated by the number of measurements >180 mg/dl (p insulin or received no insulin, respectively. Conclusions Use of basal plus short-acting insulin therapy increased with worsening hyperglycemia, but many cases did not have therapy intensified to the recommended insulin regimen—evidence of clinical inertia. Strategies should be devised to overcome inpatient clinical inertia in the treatment of postoperative patients with diabetes. PMID:23911169

  15. Acute Movement Disorder as a Presenting Feature of Hyperglycemia

    African Journals Online (AJOL)

    The female patients had blood sugar levels of 8.1mmol/L, 8.9mm 13.5 mmol/L, and 16.3 mmol/L, respectively. The males had blood sugar levels of 11.5 and 14 mmol/L, respectively. Four (4) of the patients recovered completely from involuntary movements following good glycaemic control and use of haloperidol or ...

  16. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

    Directory of Open Access Journals (Sweden)

    D. Lévigne

    2013-01-01

    Full Text Available Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.. In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia.

  17. Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats.

    Science.gov (United States)

    Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M; Garlick, Rhonda B; Rioux, Jacqueline S; Murphy, Angela L; Roe, Gates B; White, Carl W; Veress, Livia A

    2018-01-01

    Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD 58-67 ) in a whole-body exposure chamber, and given oxygen (0.8 Fi O 2 ) or air (0.21 Fi O 2 ) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

  18. [Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

    Science.gov (United States)

    Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

    2014-03-01

    Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  19. Temporary worsening of kidney function following aortic reconstructive surgery.

    Science.gov (United States)

    Ghaheri, Hafez; Kazemzadeh, Gholam Hossein; Beigi, Ali Akbar

    2008-07-01

    Little is known about the incidence of temporary kidney dysfunction following major vascular surgeries. We aimed to assess the frequency of temporary decreased kidney function following aortic surgeries. In a retrospective study, we assessed 108 hospital records of the patients who had undergone elective open abdominal surgery of aortic aneurysm. Preoperative and postoperative (days 1, 2, and 3) data on estimated glomerular filtration rate (GFR) were collected and evaluated in relation to the patients' clinical characteristics and outcomes. A decline greater than 10% in GFR on day 1 or 2, and then, an increase of GFR to a level of maximum 10% below the baseline value on the third postoperative day was considered as temporary worsening of kidney function. Postoperative alterations of GFR not greater than 10% in relation to the baseline were considered as improved or unchanged kidney function. Two patients with persistent decrease in GFR were excluded. Temporary worsening of kidney function was seen in 25 patients (23.6%). Short-term mortality rate was 44.0% in this group of patients, while it was 17.3% in those without decreased GFR (P = .006). According to the regression analysis, the only predictor of mortality was temporary worsening of kidney function, with a hazard ratio of 4.03 (95% confidence interval, 1.44 to 11.31; P = .008). Nearly 1 out of 4 aortic surgeries results in kidney dysfunction. Albeit temporary in most cases, it seems to be associated with a higher short-term mortality rate.

  20. Hemichorea-hemiballismus associated with hyperglycemia: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Young Jin; Jeong, Hae Woong [Dept.of Radiology, Busan Paik Hospital, Inje University, Busan (Korea, Republic of)

    2017-04-15

    Hemichorea-hemiballism (HCHB) associated with nonketotic hyperglycemia is the most common cause of unilateral chorea in patients with type 2 diabetes mellitus. T1-weighted MRI characteristically demonstrates hyperintensity in the contralateral corpus striatum. Here we describe a case of HCHB associated with nonketotic hyperglycemia and unusual brain involvement. A 51-year-old man presented with involuntary limb movements for several months. He had a history of diabetes mellitus and poorly controlled hyperglycemia. MRI demonstrated characteristic striatal hyperintensity, with involvement of the temporal lobe and midbrain. The patient's hyperglycemia was controlled with medication. However, his involuntary movements were reduced in terms of severity, but not eliminated, by the time of discharge. HCHB associated with hyperglycemia usually resolves rapidly after correction of blood glucose levels; thus, early recognition and glycemic control are needed to prevent an irreversible outcome.

  1. The prevalence of new onset diabetes mellitus after renal transplantation in patients with immediate posttransplant hyperglycemia in a tertiary care centre

    Directory of Open Access Journals (Sweden)

    Saba Samad Memon

    2017-01-01

    Full Text Available Objectives: This study aimed to determine the prevalence of immediate posttransplant hyperglycemia and new onset diabetes after renal transplantation (NODAT. It also aims at answering whether posttransplant hyperglycemia per se is a risk factor for future development of NODAT. Methods: A retrospective study was conducted among patients undergoing kidney transplantation under a single surgical unit in a tertiary care hospital in the past 5 years. All known patients with diabetes were excluded from the study. Immediate postoperative hyperglycemia was defined as random blood sugar (RBS ≥200 mg/dl or requirement of insulin. NODAT was defined as fasting plasma glucose ≥126 mg/dl or RBS ≥200 mg/dl or if the patient is receiving therapy for glycemic control at 6 weeks or 3 months posttransplantation. Results: The study population included 191 patients. The overall prevalence of posttransplant hyperglycemia and NODAT was 31.4% and 26.7%, respectively. NODAT developed in 28 patients (46.7% of those who had posttransplant hyperglycemia. Thus, posttransplant hyperglycemia was associated with a fourfold increased risk of NODAT (P = 0.000. Posttransplant hyperglycemia was associated with increased infections (P = 0.04 and prolonged hospital stay (P = 0.0001. Increased age was a significant risk factor for NODAT (P = 0.000, whereas gender, acute rejection episodes, cadaveric transplant, hepatitis C virus status, human leukocyte antigen mismatch, and high calcineurin levels were not significantly associated with the future development of NODAT. Conclusion: The significant risk of NODAT posed by posttransplant hyperglycemia makes it prudent to follow up these patients more diligently in a resource-limited setting wherein routine monitoring in all patients is cumbersome.

  2. Exercise training attenuates cerebral ischemic hyperglycemia by improving hepatic insulin signaling and β-cell survival.

    Science.gov (United States)

    Park, Sunmin; Kim, Da Sol; Kang, Sunna

    2013-08-06

    Preventing hyperglycemia after acute stroke attenuates complications of cerebral ischemia and reduces the risk of mortality. We investigated whether regular exercise prevents neuronal cell death and post-stroke hyperglycemia in gerbils after cerebral ischemia. Cerebral ischemia was induced by carotid artery occlusion for 8min. The gerbils that underwent ischemic or sham operations were randomly subdivided into exercise (ran on inclined treadmill at 20m/min for 30min 5days per week for 1week prior to surgery) or non-exercise groups. Gerbils were fed a 40% fat diet and after 28days, glucose metabolism, serum cytokine levels and cognitive function was measured. Artery occlusion resulted in a 64% reduction in hippocampal CA1 neurons in comparison to the sham gerbils, and caused decreased neuronal mass and impaired cognitive function. Exercise partially prevented neuronal death and improved ischemia-induced glucose intolerance. Ischemia decreased hepatic insulin signaling and exacerbated insulin resistance whereas exercise prevented the disturbance. Insulin secretion was lower in ischemic gerbils than sham gerbils, due to lowered pancreatic β-cell mass caused by increased β-cell apoptosis and decreased β-cell proliferation, which were also prevented by exercise. Increase of apoptosis was associated with elevated caspase-3 activity, consistent with increased serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. Hippocampal neuronal cell death induces hyperglycemia due to attenuated hepatic insulin signaling and decreased β-cell mass by increased β-cell apoptosis through increased TNF-α and IL-1β levels. Exercise partially prevents this phenomenon suggesting that exercise training may provide neuroprotective benefits from cerebral ischemic hyperglycemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Melatonin rescues cardiac thioredoxin system during ischemia-reperfusion injury in acute hyperglycemic state by restoring Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner.

    Science.gov (United States)

    Yu, Liming; Fan, Chongxi; Li, Zhi; Zhang, Jian; Xue, Xiaodong; Xu, Yinli; Zhao, Guolong; Yang, Yang; Wang, Huishan

    2017-01-01

    Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague Dawley rats were subjected to MI/R surgery and high-glucose (HG, 500 g/L) infusion (4 mL/kg/h) to induce temporary hyperglycemia. Rats were treated with or without melatonin (10 mg/kg/d) during the operation. Furthermore, HG (33 mmol/L)-incubated H9c2 cardiomyoblasts were treated in the presence or absence of luzindole (a competitive melatonin receptor antagonist), DAPT (a γ-secretase inhibitor), LY294002 (a PI3-kinase/Akt inhibitor), or thioredoxin-interacting protein (Txnip) adenoviral vectors. We found that acute hyperglycemia aggravated MI/R injury by suppressing Notch1/Hes1/Akt signaling and intracellular Trx activity. Melatonin treatment effectively ameliorated MI/R injury by reducing infarct size, myocardial apoptosis, and oxidative stress. Moreover, melatonin also markedly enhanced Notch1/Hes1/Akt signaling and rescued intracellular Trx system by upregulating Notch1, N1ICD, Hes1, and p-Akt expressions, increasing Trx activity, and downregulating Txnip expression. However, these effects were blunted by luzindole, DAPT, or LY294002. Additionally, Txnip overexpression not only decreased Trx activity, but also attenuated the cytoprotective effect of melatonin. We conclude that impaired Notch1 signaling aggravates MI/R injury in acute hyperglycemic state. Melatonin rescues Trx system by reducing Txnip expression via Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. Its role as a prophylactic/therapeutic drug deserves further clinical study. © 2016 John Wiley & Sons A/S. Published by John Wiley

  4. Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: an in vivo test of the fuel mediated teratogenesis hypothesis.

    Science.gov (United States)

    Baack, Michelle L; Wang, Chunlin; Hu, Shanming; Segar, Jeffrey L; Norris, Andrew W

    2014-07-01

    Embryonic exposure to excess circulating fuels is proposed to underlie diabetic embryopathy. To isolate the effects of hyperglycemia from the many systemic anomalies of diabetes, we infused 4 mg/min glucose into the left uterine artery of non-diabetic pregnant rats on gestation days (GD) 7-9. Right-sided embryos and dams exhibited no glucose elevation. Embryos were assessed on GD13, comparing the left versus right uterine horns. Hyperglycemic exposure increased rates of embryopathy, resorptions, and worsened embryopathy severity. By contrast, saline infusion did not affect any of these parameters. To assess for possible embryopathy susceptibility bias between uterine horns, separate dams were given retinoic acid (25mg/kg, a mildly embryopathic dose) systemically on GD7.5. The resultant embryopathy rates were equivalent between uterine horns. We conclude that hyperglycemia, even in the absence of systemic maternal diabetes, is sufficient to produce in vivo embryopathy during organogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Impact of hyperglycemia on neuropathological alterations during critical illness.

    Science.gov (United States)

    Sonneville, Romain; den Hertog, Heleen M; Güiza, Fabian; Gunst, Jan; Derese, Inge; Wouters, Pieter J; Brouland, Jean-Philippe; Polito, Andrea; Gray, Françoise; Chrétien, Fabrice; Charlier, Philippe; Annane, Djillali; Sharshar, Tarek; Van den Berghe, Greet; Vanhorebeek, Ilse

    2012-06-01

    Although preventing excessive hyperglycemia during critical illness may provide clinical neuroprotection, it remains debated whether normoglycemia is without risk for the brain. To address this question, we compared the neuropathological alterations in microglia, astrocytes, and neurons, with uncontrolled hyperglycemia, moderately controlled hyperglycemia, and normoglycemia during human critical illness. We further investigated the time course in an animal model. We analyzed brain specimens from patients who died in the intensive care unit and from critically ill rabbits randomized to hyper- or normoglycemia. PATIENTS/OTHER PARTICIPANTS: We compared 10 critically ill patients randomized to normoglycemia (104 ±9 mg/dl) or moderate hyperglycemia (173 ±32 mg/dl), and five patients with uncontrolled hyperglycemia (254 ±83 mg/dl) with 16 controls (out of hospital sudden deaths). Critically ill rabbits were randomized to hyperglycemia (315 ±32 mg/dl) or normoglycemia (85 ±13 mg/dl) and studied after 3 and 7 d. Insulin was infused to control blood glucose. Patients with uncontrolled hyperglycemia showed 3.7-6-fold increased microglial activation, 54-95% reduced number and activation of astrocytes, more than 9-fold increased neuronal and glial apoptosis, and a 1.5-2-fold increase in damaged neurons in hippocampus and frontal cortex (all P ≤ 0.05). Most of these abnormalities were attenuated with moderate hyperglycemia and virtually absent with normoglycemia. Frontal cortex of hyperglycemic rabbits that had been critically ill for 3 d only revealed microglial activation, followed after 7 d by astrocyte and neuronal abnormalities similar to those observed in patients, all prevented by normoglycemia. Preventing hyperglycemia with insulin during critical illness reduced neuropathological abnormalities, with microglial activation being the earliest preventable event. Whether these pathological findings associate with neurological outcome remains unknown.

  6. Examining the effects of hyperglycemia on pancreatic endocrine function in humans

    DEFF Research Database (Denmark)

    Solomon, Thomas P J; Knudsen, Sine H; Karstoft, Kristian

    2012-01-01

    Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease.......Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease....

  7. Maternal hyperglycemia and the 100-g oral glucose tolerance test

    Directory of Open Access Journals (Sweden)

    Tae-Chul Park

    2015-04-01

    Conclusions: These data demonstrate that the detection and management of mild hyperglycemia below the current diagnostic criteria of GDM as well as GDM diagnosed using the 100-g OGTT are necessary for improving pregnancy outcomes.

  8. Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

    National Research Council Canada - National Science Library

    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...

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

    National Research Council Canada - National Science Library

    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...

  10. Hyperglycemia stimulates coagulation, whereas hyperinsulinemia impairs fibrinolysis in healthy humans

    NARCIS (Netherlands)

    Stegenga, Michiel E.; van der Crabben, Saskia N.; Levi, Marcel; de Vos, Alex F.; Tanck, Michael W.; Sauerwein, Hans P.; van der Poll, Tom

    2006-01-01

    Type 2 diabetes and insulin resistance syndromes are associated with an increased risk for cardiovascular and thrombotic complications. A disturbed balance between coagulation and fibrinolysis has been implicated in the pathogenesis hereof. To determine the selective effects of hyperglycemia and

  11. The prevalence and significance of hyperglycemia in hospitalized cats.

    Science.gov (United States)

    Ray, Casey C; Callahan-Clark, Julie; Beckel, Nicole F; Walters, Patricia C

    2009-08-01

    To report the prevalence of hyperglycemia in cats admitted to a veterinary hospital and to determine if hyperglycemic cats had increased morbidity and mortality when compared with normoglycemic cats. DESIGN - Retrospective clinical study. Community-based referral hospital. Nondiabetic cats admitted to the hospital. None. The medical records of nondiabetic cats admitted to the hospital over a 1-year period were reviewed. There were 182 cats that met the criteria for inclusion in the study. Information obtained included signalment, length of hospitalization, initial and highest blood glucose measurement, diagnosis, treatment, and final disposition. Sixty-three percent of cats (116/182) were hyperglycemic at the time of presentation. Total incidence of hyperglycemia at any point during hospitalization was 64% (118/182). No association was found between hyperglycemia either initially or at any point during the hospitalization and mortality. However, a significant association was documented between the presence of hyperglycemia and increased length of hospitalization (LOH) (P=0.04). The duration of LOH was also significantly associated with the degree of hyperglycemia (P=0.01). A number of different disease processes were represented in the study population. However, the number of cats in each disease category was small and no association could be found between any of them and blood glucose affecting mortality and morbidity. The prevalence of hyperglycemia in feline patients admitted to a primary referral hospital was 64%. Cats with hyperglycemia had a longer LOH when compared with normoglycemic cats; however, presence of hyperglycemia did not impact mortality in this population of cats. © Veterinary Emergency and Critical Care Society 2009.

  12. Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude.

    Science.gov (United States)

    Miele, Catherine H; Schwartz, Alan R; Gilman, Robert H; Pham, Luu; Wise, Robert A; Davila-Roman, Victor G; Jun, Jonathan C; Polotsky, Vsevolod Y; Miranda, J Jaime; Leon-Velarde, Fabiola; Checkley, William

    2016-06-01

    Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93-100, 2016.-Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated with cardiovascular complications, it is unclear how worsening hypoxemia of any degree affects cardiometabolic risk factors in high-altitude populations. We studied the relationship between daytime resting oxyhemoglobin saturation and cardiometabolic risk factors in adult participants living in Puno, Peru (3825 m above sea level). We used multivariable logistic regression models to study the relationship between having a lower oxyhemoglobin saturation and markers of cardiometabolic risk. Nine hundred and fifty-four participants (mean age 55 years, 52% male) had information available on pulse oximetry and markers of cardiometabolic risk. Average oxyhemoglobin saturation was 90% (interquartile range 88%-92%) and 43 (4.5%) had excessive erythrocytosis. Older age, decreased height-adjusted lung function, and higher body mass index (BMI) were associated with having an oxyhemoglobin saturation ≤85%. When adjusting for age, sex, socioeconomic status, having excessive erythrocytosis, and site, we found that each 5% decrease in oxyhemoglobin saturation was associated with a higher adjusted odds of metabolic syndrome (OR = 1.35, 95% CI: 1.07-1.72, p 2 mass units (OR = 1.29, 95% CI: 1.00-1.67, p < 0.05), hemoglobin A1c ≥6.5% (OR = 1.66, 95% CI: 1.09-2.51, p < 0.04), and high sensitivity C-reactive protein (hs-CRP) ≥3 mg/L (OR = 1.46, 95% CI: 1.09-1.96, p < 0.01). In high-altitude populations in Puno, Peru, a higher BMI and lower pulmonary function were

  13. Modest hyperglycemia prevents interstitial dispersion of insulin in skeletal muscle.

    Science.gov (United States)

    Kolka, Cathryn M; Castro, Ana Valeria B; Kirkman, Erlinda L; Bergman, Richard N

    2015-02-01

    Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake, but this is blocked in insulin resistance. As glucotoxicity is associated with endothelial dysfunction, the observed hyperglycemia in diet-induced obese dogs may inhibit insulin access to muscle cells, and exacerbate insulin resistance. Here we asked whether interstitial insulin diffusion is reduced in modest hyperglycemia, similar to that induced by a high fat diet. During normoglycemic (100 mg/dl) and moderately hyperglycemic (120 mg/dl) clamps in anesthetized canines, sequential doses of insulin were injected into the vastus medialis of one hindlimb; the contra-lateral limb served as a control. Plasma samples were collected and analyzed for insulin content. Lymph vessels of the hind leg were also catheterized, and lymph samples were analyzed as an indicator of interstitial insulin concentration. Insulin injection increased lymph insulin in normoglycemic animals, but not in hyperglycemic animals. Muscle glucose uptake was elevated in response to hyperglycemia, however the insulin-mediated glucose uptake in normoglycemic controls was not observed in hyperglycemia. Modest hyperglycemia prevented intra-muscularly injected insulin from diffusing through the interstitial space reduced insulin-mediated glucose uptake. Hyperglycemia prevents the appearance of injected insulin in the interstitial space, thus reducing insulin action on skeletal muscle cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

    Science.gov (United States)

    Chang, Jia-Feng; Yeh, Jih-Chen; Chiu, Ya-Lin; Liou, Jian-Chiun; Hsiung, Jing-Ru; Tung, Tao-Hsin

    2017-01-01

    No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Dental findings and identification of undiagnosed hyperglycemia.

    Science.gov (United States)

    Lalla, E; Cheng, B; Kunzel, C; Burkett, S; Lamster, I B

    2013-10-01

    A change in the American Diabetes Association guidelines added hemoglobin A1c (HbA1c) to the assays for diabetes diagnosis, but evidence suggests that glucose vs. HbA1c criteria may identify different segments of the affected population. We previously demonstrated that oral findings offer an opportunity for the detection of undiagnosed abnormal fasting plasma glucose (FPG) among dental patients who present with diabetes risk factors. In this new cross-sectional study, we sought to extend these observations. The first goal, using data from 591 new participants, was to assess our previously identified hyperglycemia detection models when HbA1c is used for case definition. The second goal, using data from our total cohort of 1,097 participants, was to evaluate the models' performance regardless of whether an FPG or an HbA1c is used for diagnosis. The presence of ≥ 26% teeth with deep pockets or ≥ 4 missing teeth correctly identified 72% of pre-diabetes or diabetes cases in the HbA1c sample and 75% in the total population. The addition of a point-of-care HbA1c ≥ 5.7% increased correct identification to 87% and 90%, respectively. These results demonstrate the validity of our prediction models regardless of the test used for diabetes or pre-diabetes diagnosis in the clinical setting and underscore the contribution dentists can make.

  16. Chronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia.

    Science.gov (United States)

    Goshadrou, Fatemeh; Kazerouni, Faranak; Mehranfard, Nasrin; Sadeghi, Bahman

    2015-12-01

    Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor. The majority of the previous studies have shown that the short-term ghrelin treatment induces hyperglycemia and hypoinsulinemia in healthy humans and rodents. However, the results obtained from long-term treatment with ghrelin are not clear enough. In this study, we assessed acute (1 day) and chronic (21 days) effects of intraperitoneally administered ghrelin (at different doses of 1, 10 and 20 μg/kg) during a 12-h fasting period in rats using glucose oxidase method and direct sandwich ELISA (the Enzyme-Linked Immunosorbent Assay) and then compared the effects of exogenous ghrelin on blood glucose and insulin levels on day 21 with those on day 1. The results showed that acute ghrelin administration markedly increased fasting plasma glucose at doses of 1 and 10 μg/kg as well as insulin levels at 1 μg/kg in comparison to control values. Ghrelin (at 1 μg/kg) altered plasma glucose but not insulin levels on the 21st day compared to control values. In addition, the comparison of the influence of ghrelin administration on plasma glucose and insulin levels on day 21 with those on the first day revealed that the chronic administration of ghrelin notably decreased plasma glucose and insulin levels relative to the acute ghrelin treatment. These findings indicate that hyperglycemia and hyperinsulinemia caused by the exogenous ghrelin during acute treatment are temporary and prolonged treatment with ghrelin regulates plasma glucose and restores insulin to normal levels, suggesting a possible role for ghrelin in improving insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury.

    Science.gov (United States)

    García-Arroyo, Fernando E; Cristóbal, Magdalena; Arellano-Buendía, Abraham S; Osorio, Horacio; Tapia, Edilia; Soto, Virgilia; Madero, Magdalena; Lanaspa, Miguel A; Roncal-Jiménez, Carlos; Bankir, Lise; Johnson, Richard J; Sánchez-Lozada, Laura-Gabriela

    2016-07-01

    Recurrent dehydration, such as commonly occurs with manual labor in tropical environments, has been recently shown to result in chronic kidney injury, likely through the effects of hyperosmolarity to activate both vasopressin and aldose reductase-fructokinase pathways. The observation that the latter pathway can be directly engaged by simple sugars (glucose and fructose) leads to the hypothesis that soft drinks (which contain these sugars) might worsen rather than benefit dehydration associated kidney disease. Recurrent dehydration was induced in rats by exposure to heat (36°C) for 1 h/24 h followed by access for 2 h to plain water (W), a 11% fructose-glucose solution (FG, same composition as typical soft drinks), or water sweetened with noncaloric stevia (ST). After 4 wk plasma and urine samples were collected, and kidneys were examined for oxidative stress, inflammation, and injury. Recurrent heat-induced dehydration with ad libitum water repletion resulted in plasma and urinary hyperosmolarity with stimulation of the vasopressin (copeptin) levels and resulted in mild tubular injury and renal oxidative stress. Rehydration with 11% FG solution, despite larger total fluid intake, resulted in greater dehydration (higher osmolarity and copeptin levels) and worse renal injury, with activation of aldose reductase and fructokinase, whereas rehydration with stevia water had opposite effects. In animals that are dehydrated, rehydration acutely with soft drinks worsens dehydration and exacerbates dehydration associated renal damage. These studies emphasize the danger of drinking soft drink-like beverages as an attempt to rehydrate following dehydration. Copyright © 2016 the American Physiological Society.

  18. [Hyperglycemia assessment in the post-anesthesia care unit].

    Science.gov (United States)

    Pereira, Vinicius Rodovalho; Azuma, Rodrigo Akio; Gatto, Bruno Emanuel Oliva; Silva Junior, João Manoel; Carmona, Maria Jose Carvalho; Malbouisson, Luiz Marcelo Sá

    Hyperglycemia in surgical patients may cause serious problems. Analyzing this complication in this scenario contributes to improve the management of these patients. The aim of this study was to evaluate the prevalence of hyperglycemia in the post-anesthetic care unit (PACU) in non-diabetic patients undergoing elective surgery and analyze the possible risk factors associated with this complication. We evaluated non-diabetic patients undergoing elective surgeries and admitted in the PACU. Data were collected from medical records through precoded questionnaire. Hyperglycemia was considered when blood glucose was>120mg.dL-1. Patients with hyperglycemia were compared to normoglycemic ones to assess factors associated with the problem. We excluded patients with endocrine-metabolic disorders, diabetes, children under 18 years, body mass index (BMI) below 18 or above 35, pregnancy, postpartum or breastfeeding, history of drug use, and emergency surgeries. We evaluated 837 patients. The mean age was 47.8±16.1 years. The prevalence of hyperglycemia in the postoperative period was 26.4%. In multivariate analysis, age (OR=1.031, 95% CI 1.017-1.045); BMI (OR=1.052, 95% CI 1.005-1.101); duration of surgery (OR=1.011, 95% CI 1.008-1.014), history of hypertension (OR=1.620, 95% CI 1.053-2.493), and intraoperative use of corticosteroids (OR=5.465, 95% CI 3.421-8.731) were independent risk factors for postoperative hyperglycemia. The prevalence of hyperglycemia was high in the PACU, and factors such as age, BMI, corticosteroids, blood pressure, and duration of surgery are strongly related to this complication. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  19. Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

    NARCIS (Netherlands)

    Laskewitz, Anke J.; van Dijk, Theo H.; Grefhorst, Aldo; van Lierop, Marie-Jose; Schreurs, Marijke; Bloks, Vincent W.; Reijngoud, Dirk-Jan; Dokter, Wim H.; Kuipers, Folkert; Groen, Albert K.

    2012-01-01

    Synthetic glucocorticoids such as prednisolone have potent antiinflammatory actions. Unfortunately, these drugs induce severe adverse effects in patients, many of which resemble features of the metabolic syndrome, such as insulin resistance. In this study, we investigated whether adverse effects of

  20. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

    Science.gov (United States)

    Jokura, Hiroko; Watanabe, Isamu; Umeda, Mika; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Derek M Erion

    Full Text Available Hyperglycemia resulting from type 2 diabetes mellitus (T2DM is the main cause of diabetic complications such as retinopathy and neuropathy. A reduction in hyperglycemia has been shown to prevent these associated complications supporting the importance of glucose control. Glucokinase converts glucose to glucose-6-phosphate and determines glucose flux into the β-cells and hepatocytes. Since activation of glucokinase in β-cells is associated with increased risk of hypoglycemia, we hypothesized that selectively activating hepatic glucokinase would reduce fasting and postprandial glucose with minimal risk of hypoglycemia. Previous studies have shown that hepatic glucokinase overexpression is able to restore glucose homeostasis in diabetic models; however, these overexpression experiments have also revealed that excessive increases in hepatic glucokinase activity may also cause hepatosteatosis. Herein we sought to evaluate whether liver specific pharmacological activation of hepatic glucokinase is an effective strategy to reduce hyperglycemia without causing adverse hepatic lipids changes. To test this hypothesis, we evaluated a hepatoselective glucokinase activator, PF-04991532, in Goto-Kakizaki rats. In these studies, PF-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. During a hyperglycemic clamp in Goto-Kakizaki rats, the glucose infusion rate was increased approximately 5-fold with PF-04991532. This increase in glucose infusion can be partially attributed to the 60% reduction in endogenous glucose production. While PF-04991532 induced dose-dependent increases in plasma triglyceride concentrations it had no effect on hepatic triglyceride concentrations in Goto-Kakizaki rats. Interestingly, PF-04991532 decreased intracellular AMP concentrations and increased hepatic futile cycling. These data suggest that

  2. Blood glucose in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj

    2009-01-01

    Blood glucose is often elevated in acute stroke, and higher admission glucose levels are associated with larger lesions, greater mortality and poorer functional outcome. In patients treated with thrombolysis, hyperglycemia is associated with an increased risk of hemorrhagic transformation...... to the risk of inducing potentially harmful hypoglycemia has been raised. Still, basic and observational research is overwhelmingly in support of a causal relationship between blood glucose and stroke outcome and further research on glucose-lowering therapy in acute stroke is highly warranted....

  3. [Anesthetic management of severe or worsening postpartum hemorrhage].

    Science.gov (United States)

    Aya, A G; Ducloy-Bouthors, A-S; Rugeri, L; Gris, J-C

    2014-12-01

    Risk factors of maternal morbidity and mortality during postpartum hemorrhage (PPH) include non-optimal anesthetic management. As the anesthetic management of the initial phase is addressed elsewhere, the current chapter is dedicated to the management of severe PPH. A literature search was performed using PubMed and Medline databases, and the Cochrane Library, for articles published from 2003 up to and including 2013. Several keywords related to anesthetic and critical care practice, and obstetrical management were used, in various combinations. Guidelines from several societies and organisations were also read. When PPH worsens, one should ask for additional team personnel (professional consensus). Patients should be monitored for heart rate, blood pressure, skin and mucosal pallor, bleeding at skin puncture sites, diuresis and the volume of genital bleeding (grade B). Because of the possible rapid worsening of coagulapathy, patients should undergo regular evaluation of coagulation status (professional consensus). Prevention and management of hypothermia should be considered (professional consensus), by warming intravenous fluids and blood products, and by active body warming (grade C). Antibiotics should be given, if not already administered at the initial phase (professional consensus). Vascular fluids must be given (grade B), the choice being left at the physician discretion. Blood products transfusion should be decided based on the clinical severity of PPH (professional consensus). Priority is given to red blood cells (RBC) transfusion, with the aim to maintain Hb concentration>8g/dL. The first round of products could include 3 units of RBC (professional consensus), and the following round 3 units of RBC, and 3 units of fresh frozen plasma (FFP). The FFP:RBC ratio should be kept between 1:2 and 1:1 (professional consensus). Depending on the etiology of PPH, the early administration of FFP is left at the discretion of the physician (professional consensus

  4. Hyperglycemia in critical patients: Determinants of insulin dose choice

    Directory of Open Access Journals (Sweden)

    Aline Klitzke Paliosa

    Full Text Available Summary Objective: To identify factors that can determine the choice of intermittent subcutaneous regular insulin dose in critically ill patients with hyperglycemia. Method: Cross-sectional study in a general adult ICU with 26 beds, data collected between September and October 2014. The variables analyzed were: sex, age, previous diagnosis of diabetes mellitus, use of corticosteroids, use of lactulose, sepsis, fasting, enteral nutrition, use of dextrose 5% in water, NPH insulin prescription and blood glucose level. Patients with one or more episodes of hyperglycemia (blood glucose greater than 180 mg/dL were included as a convenience sample, not consecutively. Those with continuous insulin prescription were excluded from analysis. Results: We included 64 records of hyperglycemia observed in 22 patients who had at least one episode of hyperglycemia. The median administered subcutaneous regular human insulin was 6 IU and among the factors evaluated only blood glucose levels were associated with the choice of insulin dose administered. Conclusion: Clinical characteristics such as diet, medications and diagnosis of diabetes mellitus are clearly ignored in the decision-making regarding insulin dose to be administered for glucose control in critically ill patients with hyperglycemia.

  5. Hyperglycemia in critical patients: Determinants of insulin dose choice.

    Science.gov (United States)

    Paliosa, Aline Klitzke; Teixeira, Cassiano; Rosa, Regis Goulart; Blatt, Carine Raquel

    2017-05-01

    To identify factors that can determine the choice of intermittent subcutaneous regular insulin dose in critically ill patients with hyperglycemia. Cross-sectional study in a general adult ICU with 26 beds, data collected between September and October 2014. The variables analyzed were: sex, age, previous diagnosis of diabetes mellitus, use of corticosteroids, use of lactulose, sepsis, fasting, enteral nutrition, use of dextrose 5% in water, NPH insulin prescription and blood glucose level. Patients with one or more episodes of hyperglycemia (blood glucose greater than 180 mg/dL) were included as a convenience sample, not consecutively. Those with continuous insulin prescription were excluded from analysis. We included 64 records of hyperglycemia observed in 22 patients who had at least one episode of hyperglycemia. The median administered subcutaneous regular human insulin was 6 IU and among the factors evaluated only blood glucose levels were associated with the choice of insulin dose administered. Clinical characteristics such as diet, medications and diagnosis of diabetes mellitus are clearly ignored in the decision-making regarding insulin dose to be administered for glucose control in critically ill patients with hyperglycemia.

  6. Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

    Directory of Open Access Journals (Sweden)

    Fangming Xiu

    2014-01-01

    Full Text Available 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.

  7. Objectively-measured sleep duration and hyperglycemia in pregnancy

    Science.gov (United States)

    Herring, Sharon J.; Nelson, Deborah B.; Pien, Grace W.; Homko, Carol; Goetzl, Laura M.; Davey, Adam; Foster, Gary D.

    2013-01-01

    Objective Our primary purpose was to assess the impact of objectively-measured nighttime sleep duration on gestational glucose tolerance. We additionally examined associations of objectively-measured daytime sleep duration and nap frequency on maternal glycemic control. Methods 63 urban, low-income, pregnant women wore wrist actigraphs for an average of 6 full days in mid-pregnancy prior to screening for hyperglycemia using the 1-hour oral glucose tolerance test (OGTT). Correlations of nighttime and daytime sleep durations with 1-hour OGTT values were analyzed. Multivariable logistic regression was used to evaluate independent associations between sleep parameters and hyperglycemia, defined as 1-hour OGTT values ≥ 130 mg/dL. Results Mean nighttime sleep duration was 6.9 ± 0.9 hours which was inversely correlated with 1-hour OGTT values (r = −0.28, p = 0.03). Shorter nighttime sleep was associated with hyperglycemia, even after controlling for age and body mass index (adjusted OR: 0.2; 95% CI: 0.1, 0.8). There were no associations of daytime sleep duration and nap frequency with 1-hour OGTT values or hyperglycemia. Conclusions Using objective measures of maternal sleep time, we found that women with shorter nighttime sleep durations had an increased risk of gestational hyperglycemia. Larger prospective studies are needed to confirm our negative daytime sleep findings. PMID:24239498

  8. Objectively measured sleep duration and hyperglycemia in pregnancy.

    Science.gov (United States)

    Herring, Sharon J; Nelson, Deborah B; Pien, Grace W; Homko, Carol; Goetzl, Laura M; Davey, Adam; Foster, Gary D

    2014-01-01

    Our primary purpose was to assess the impact of objectively measured nighttime sleep duration on gestational glucose tolerance. We additionally examined associations of objectively measured daytime sleep duration and nap frequency on maternal glycemic control. Sixty-three urban, low-income, pregnant women wore wrist actigraphs for an average of 6 full days in mid-pregnancy prior to screening for hyperglycemia using the 1-h oral glucose tolerance test (OGTT). Correlations of nighttime and daytime sleep durations with 1-h OGTT values were analyzed. Multivariable logistic regression was used to evaluate independent associations between sleep parameters and hyperglycemia, defined as 1-h OGTT values ≥130 mg/dL. Mean nighttime sleep duration was 6.9±0.9 h which was inversely correlated with 1-h OGTT values (r=-0.28, P=.03). Shorter nighttime sleep was associated with hyperglycemia, even after controlling for age and body mass index (adjusted odds ratio [OR], 0.2 [95% confidence interval {CI}, 0.1-0.8]). There were no associations of daytime sleep duration and nap frequency with 1-h OGTT values or hyperglycemia. Using objective measures of maternal sleep time, we found that women with shorter nighttime sleep durations had an increased risk for gestational hyperglycemia. Larger prospective studies are needed to confirm our negative daytime sleep findings. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Subjective worsening of memory predicts dementia after three years

    Directory of Open Access Journals (Sweden)

    Anne Brækhus

    2009-10-01

    Full Text Available  ABSTRACTStudy Objective:  Design:  Setting:  Paricipants:  Measurements:  Results:  Conclusions:  Key words:  aged, 75 years and over; subjective memory impairment; prospective study; dementiaElderly persons expressing a worsening of memory function are at increased risk ofdeveloping dementia.When adjusting for potential confounding by depressive symptoms, two of the GMSquestions scored at baseline, 'Is it more difficult to remember things than it used to be?' and 'Do youwrite reminders to yourself more often now than before?', were significant predictors of dementiawithin three years, OR = 3.3, 95% CI = 1.2–8.6 and OR = 2.8, 95% CI = 1.0–7.6, respectively.Dementia (DSM-III and DSM-III-R criteria.285 non-demented persons aged 75 years and above at start of study, 77.5% women.Persons living at home.Prospective study of a random sample of older people with follow-ups after three, six, nineand twelve years.To assess whether complaining of memory impairment, as measured by the subjectivepart of the Geriatric Mental State examination (GMS, the Canberra community version, predictslater development of dementia.

  10. Oleanolic acid: a novel cardioprotective agent that blunts hyperglycemia-induced contractile dysfunction.

    Directory of Open Access Journals (Sweden)

    Rudo F Mapanga

    Full Text Available Diabetes constitutes a major health challenge. Since cardiovascular complications are common in diabetic patients this will further increase the overall burden of disease. Furthermore, stress-induced hyperglycemia in non-diabetic patients with acute myocardial infarction is associated with higher in-hospital mortality. Previous studies implicate oxidative stress, excessive flux through the hexosamine biosynthetic pathway (HBP and a dysfunctional ubiquitin-proteasome system (UPS as potential mediators of this process. Since oleanolic acid (OA; a clove extract possesses antioxidant properties, we hypothesized that it attenuates acute and chronic hyperglycemia-mediated pathophysiologic molecular events (oxidative stress, apoptosis, HBP, UPS and thereby improves contractile function in response to ischemia-reperfusion. We employed several experimental systems: 1 H9c2 cardiac myoblasts were exposed to 33 mM glucose for 48 hr vs. controls (5 mM glucose; and subsequently treated with two OA doses (20 and 50 µM for 6 and 24 hr, respectively; 2 Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mM glucose vs. controls (11 mM glucose for 60 min, followed by 20 min global ischemia and 60 min reperfusion ± OA treatment; 3 In vivo coronary ligations were performed on streptozotocin treated rats ± OA administration during reperfusion; and 4 Effects of long-term OA treatment (2 weeks on heart function was assessed in streptozotocin-treated rats. Our data demonstrate that OA treatment blunted high glucose-induced oxidative stress and apoptosis in heart cells. OA therapy also resulted in cardioprotection, i.e. for ex vivo and in vivo rat hearts exposed to ischemia-reperfusion under hyperglycemic conditions. In parallel, we found decreased oxidative stress, apoptosis, HBP flux and proteasomal activity following ischemia-reperfusion. Long-term OA treatment also improved heart function in streptozotocin-diabetic rats. These

  11. Ethanol-induced hypothermia and hyperglycemia in genetically obese mice

    Energy Technology Data Exchange (ETDEWEB)

    Haller, E.W.; Wittmers, L.E. Jr.

    1989-01-01

    Blood glucose and rectal temperatures were monitored in two strains of genetically obese mice (C57 BL/6J ob/ob) prior to and following intragastric ethanol administration in an attempt to relate the hypothermic response to ethanol to extracellular glucose concentration. In contrast to expectation, ethanol administration was typically associated with a hyperglycemia and a hypothermic response. In the ob/ob genotype, the hypothermic response was associated with pronounced hyperglycemia which was more emphatic in older animals. The data support the conclusion that ethanol-induced hypothermia is independent of blood glucose levels. In light of the known sensitivity of ob/ob mice to insulin, it is suggested further that the observed hypothermic response was not a function of the animals' ability to transport glucose into peripheral cells. The observed hyperglycemia of the obese animals was most likely stress-related

  12. Dark adaptation during transient hyperglycemia in type 2 diabetes

    DEFF Research Database (Denmark)

    Holfort, Stig Kraglund; Jackson, Gregory R; Larsen, Michael

    2010-01-01

    It was the purpose of the present study to examine dark adaptation in subjects with type 2 diabetes during transient hyperglycemia. Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to undergo an oral glucose tolerance test (OGTT) or to remain fasting. Dark...... glycemia increased in the 12 OGTT subjects, from 8.6±2.1 at baseline to 21.1±3.6 mM after 80 min. In the OGTT group, four out of seven subjects with delayed dark adaptation at baseline reached normal values during hyperglycemia. All examined aspects of rod adaptation were accelerated by hyperglycemia (time...... to rod-cone break -26%; time to rod intercept -16%, rod sensitivity recovery slope (log units/min) +35%), whereas no measurable change in cone adaptation was seen. The results are consistent with rod adaptation being limited by glycemia and with rod adaptation being delayed in subjects with diabetes...

  13. Intrathoracic impedance vs daily weight monitoring for predicting worsening heart failure events: results of the Fluid Accumulation Status Trial (FAST).

    Science.gov (United States)

    Abraham, William T; Compton, Steven; Haas, Garrie; Foreman, Blair; Canby, Robert C; Fishel, Robert; McRae, Scott; Toledo, Gloria B; Sarkar, Shantanu; Hettrick, Douglas A

    2011-01-01

    The relative sensitivity and unexplained detection rate of changes in intrathoracic impedance has not been compared with standard heart failure (HF) monitoring using daily weight changes. The Fluid Accumulation Status Trial (FAST) prospectively followed 156 HF patients with implanted cardioverter-defibrillator or cardiac resynchronization therapy defibrillator devices modified to record daily changes in intrathoracic impedance in a blinded fashion for 537±312 days. Daily impedance changes were used to calculate a fluid index that could be compared with a prespecified threshold. True positives were defined as adjudicated episodes of worsening HF occurring within 30 days of a fluid index above threshold or an acute weight gain. Unexplained detections were defined as threshold crossings or acute weight gains not associated with worsening HF. Impedance measurements were performed on >99% of follow-up days, compared with only 76% of days for weight measurements. Sixty-five HF events occurred during follow-up (0.32/patient-year). Forty HF events were detected by impedance but not weight, whereas 5 were detected by weight but not impedance. Sensitivity was greater (76% vs 23%; P<.0001) and unexplained detection rate was lower (1.9 vs 4.3/patient-year; P<.0001) for intrathoracic impedance monitoring at the threshold of 60Ω days compared with acute weight increases of 3 lbs in 1 day or 5 lbs in 3 days and also over a wide range of fluid index and weight thresholds. The sensitivity and unexplained detection rate of intrathoracic impedance monitoring was superior to that seen for acute weight changes. Intrathoracic impedance monitoring represents a useful adjunctive clinical tool for managing HF in patients with implanted devices. © 2011 Wiley Periodicals, Inc.

  14. Serum Calcium Increase Correlates With Worsening of Lipid Profile

    Science.gov (United States)

    Gallo, Luigia; Faniello, Maria C.; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S.; Irace, Concetta

    2016-01-01

    Abstract Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk. Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods. We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women. Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk. PMID:26937904

  15. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study

    NARCIS (Netherlands)

    Gast, K.B.; Smit, J.W.A.; Heijer, M. den; Middeldorp, S.; Rippe, R.C.; Cessie, S. le; Koning, E.J. de; Jukema, J.W.; Rabelink, T.J.; Roos, A. de; Rosendaal, F.R.; Mutsert, R. de; Assendelft, P.

    2013-01-01

    OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to

  16. AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits

    Directory of Open Access Journals (Sweden)

    Yi Huang

    2017-09-01

    Full Text Available Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO2, while fewer have been used to in an attempt to reduce oxygen demand (VO2. The cellular energy sensor 5′ adenosine monophosphate-activated protein kinase (AMPK has the potential to modulate both whole-body DO2 and VO2. Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits.Methods: Chronically treated animals received AICAR (40 mg/kg/day, IV for 10 days prior to hemorrhage, while rabbits in the acute study were infused with AICAR (7.5 mg/kg bolus, 2 mg/kg/min infusion or vehicle (0.3 ml/kg saline bolus, 0.03 ml/kg/min infusion IV for 2 h prior to severe hemorrhage. Both acutely and chronically treated animals were sedated (ketamine/xylazine cocktail the morning of the terminal experiment and surgically prepared for hemorrhage, including the implantation of arterial and venous catheters (for blood removal/sampling and drug/vehicle administration and thoracotomy for implantation of transit-time flow transducers (for cardiac output determination.Results: AICAR given acutely lowered arterial blood glucose and increased blood lactate levels before hemorrhage, and abolished the well-documented hemorrhage-induced hyperglycemia seen in vehicle treated animals. Animals given AICAR chronically had blunted hemorrhage-induced hyperglycemia without prior baseline changes. Chronically treated AICAR animals showed significantly lower lactate levels during hemorrhage. Rabbits receiving AICAR both acutely and chronically experienced similar falls in mean arterial pressure, cardiac output and hence DO2 to their vehicle counterparts throughout the hemorrhage period. However, rabbits treated either acutely or chronically with AICAR accumulated

  17. AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits.

    Science.gov (United States)

    Huang, Yi; Ratz, Paul H; Miner, Amy S; Locke, Victoria A; Chen, Grace; Chen, Yang; Barbee, Robert W

    2017-01-01

    Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO2), while fewer have been used to in an attempt to reduce oxygen demand (VO2). The cellular energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK) has the potential to modulate both whole-body DO2 and VO2. Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside) given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits. Methods: Chronically treated animals received AICAR (40 mg/kg/day, IV) for 10 days prior to hemorrhage, while rabbits in the acute study were infused with AICAR (7.5 mg/kg bolus, 2 mg/kg/min infusion) or vehicle (0.3 ml/kg saline bolus, 0.03 ml/kg/min infusion) IV for 2 h prior to severe hemorrhage. Both acutely and chronically treated animals were sedated (ketamine/xylazine cocktail) the morning of the terminal experiment and surgically prepared for hemorrhage, including the implantation of arterial and venous catheters (for blood removal/sampling and drug/vehicle administration) and thoracotomy for implantation of transit-time flow transducers (for cardiac output determination). Results: AICAR given acutely lowered arterial blood glucose and increased blood lactate levels before hemorrhage, and abolished the well-documented hemorrhage-induced hyperglycemia seen in vehicle treated animals. Animals given AICAR chronically had blunted hemorrhage-induced hyperglycemia without prior baseline changes. Chronically treated AICAR animals showed significantly lower lactate levels during hemorrhage. Rabbits receiving AICAR both acutely and chronically experienced similar falls in mean arterial pressure, cardiac output and hence DO2 to their vehicle counterparts throughout the hemorrhage period. However, rabbits treated either acutely or chronically with AICAR accumulated lower oxygen

  18. Managing Hyperglycemia (High Blood Sugar) in the Hospital: a Patient's Guide

    Science.gov (United States)

    Managing Hyperglycemia (High Blood Sugar) in the Hospital A Patient’s Guide Hyperglycemia is the medical term for blood glucose (sugar) ... org/guidelines/index.cfm). www.hormone.org Managing Hyperglycemia (High Blood Sugar) in the Hospital Patient Guide ...

  19. Effect of short-term hyperglycemia on adipose tissue fluxes of selected cytokines in vivo during multiple phases of diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Siklova, Michaela; Simonsen, Lene; Polak, Jan

    2015-01-01

    released in response to short-term hyperglycemia and whether this secretion capacity could be influenced by weight loss. DESIGN, PATIENTS, AND INTERVENTIONS: Output of cytokines and proteins of acute phase from scAT in response to a 3-hours hyperglycemic clamp was evaluated in nine obese women in vivo...... was assessed. RESULTS: Hyperglycemia increased the output of cytokines IL-6, MCP-1, and IL-1Ra from scAT. This effect had a tendency to be reduced after weight loss. The output of other proinflammatory substances from scAT into circulation was not detected. The diet-induced weight loss was associated...... using Fick's principle. Moreover, the output of cytokines was analyzed during a multiphase dietary intervention consisting of 1 month on a very low-calorie diet and subsequent 5-month weight-stabilization phase. MAIN OUTCOME MEASURE(S): The levels of cytokines and proteins of acute phase [IL-6, IL-8, IL...

  20. PEEP in non invasive ventilatory treatment of worsened BPCO

    Directory of Open Access Journals (Sweden)

    Federico Lari

    2009-08-01

    Full Text Available Acute respiratory failure due to exacerbation of chronic pulmonary disease is usually treated with bilevel pressure non invasive ventilation. An high inspiratory pressure is used to improve tidal volume, a lower expiratory pressure is used to neutralize end expiratory positive pressure of patient (PEEPi caused by flow limitation and airway trapping. When ventilators for bilevel pressure ventilation are not available, is useful to administer to patient an external low (5cmH2O positive pressure with simple CPAP systems (Continuous Positive Airway Pressure, such as Venturi like flow generator largely available and well known everywhere.

  1. Effects of Hyperglycemia on Vascular Smooth Muscle Ca2+ Signaling

    Science.gov (United States)

    El-Najjar, Nahed; Kulkarni, Rashmi P.; Nader, Nancy; Hodeify, Rawad

    2017-01-01

    Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca2+ signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model. We find that prolonged exposure of A7r5 cells to hyperglycemia (weeks) is associated with changes to Ca2+ signaling, including most prominently an inhibition of the passive ER Ca2+ leak and the sarcoplasmic reticulum Ca2+-ATPase (SERCA). To translate these findings to the in vivo condition, we used primary VSM cells from normal and diabetic subjects and find that only the inhibition of the ER Ca2+ leaks replicates in cells from diabetic donors. These results show that prolonged hyperglycemia in isolation alters the Ca2+ signaling machinery in VSM cells. However, these alterations are not readily translatable to the whole organism situation where alterations to the Ca2+ signaling machinery are different. PMID:28713824

  2. Remission of active diabetic hepatitis after correction of hyperglycemia

    NARCIS (Netherlands)

    Tak, P. P.; ten Kate, F. J.

    1993-01-01

    A 60-year-old obese woman with type II diabetes mellitus and hepatomegaly exhibited progression of steatosis to hepatitis and cirrhosis. The patient was treated with large amounts of insulin combined with sulfonylurea, resulting in correction of the hyperglycemia. In the subsequent 9 months, weight

  3. Hypertension, Hyperglycemia, and Hyperlipemia among Adolescents with Intellectual Disabilities

    Science.gov (United States)

    Lin, Pei-Ying; Lin, Lan-Ping; Lin, Jin-Ding

    2010-01-01

    The present paper aims to assess the hypertension, hyperglycemia and hyperlipidemia prevalence of adolescents with intellectual disabilities, and to recognize the health disparities between the study participants and the general population. This study conducted a cross-sectional medical chart analysis of 856 students who participated in school…

  4. High-Intensity Interval Training for Improving Postprandial Hyperglycemia

    Science.gov (United States)

    Little, Jonathan P.; Francois, Monique E.

    2014-01-01

    High-intensity interval training (HIIT) has garnered attention in recent years as a time-efficient exercise option for improving cardiovascular and metabolic health. New research demonstrates that HIIT may be particularly effective for improving postprandial hyperglycemia in individuals with, or at risk for, type 2 diabetes (T2D). These findings…

  5. Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

    Science.gov (United States)

    Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

    2014-01-01

    Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

  6. Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

    LENUS (Irish Health Repository)

    O'Donnell, David H

    2010-07-01

    Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

  7. Thyrotropin-releasing hormone (TRH) reverses hyperglycemia in rat.

    Science.gov (United States)

    Luo, LuGuang; Luo, John Z Q; Jackson, Ivor M D

    2008-09-12

    Hyperglycemia in thyrotropin-releasing hormone (TRH) null mice indicates that TRH is involved in the regulation of glucose homeostasis. Further, TRH levels in the pancreas peak during the stages of late embryonic and early neonatal beta cell development. These observations are consistent in linking TRH to islet cell proliferation and differentiation. In this study, we examined the effect of TRH administration in damaged pancreatic rat (streptozotocin, STZ) to determine whether TRH could improve damaged pancreatic beta cells function. We hypothesize that TRH is able to reverse STZ-induced hyperglycemia by increasing pancreatic islet insulin content, preventing apoptosis, and potentially induce islet regeneration. It was found that following intra-peritoneal (ip) injection, TRH (10 microg/kg body weight (bwt)) reverses STZ (65 mg/kg bwt)-induced hyperglycemia (TRH given 3 days after STZ injection). Increased circulating insulin levels and insulin content in extracted pancreas suggests that TRH reversed STZ-induced hyperglycemia through improving pancreatic islet beta cell function. Further studies show a significantly lower level of apoptosis in islets treated with TRH as well as the presence of proliferation marker nestin and Brdu, suggesting that the TRH has the potential to prevent apoptosis and stimulate islet proliferation.

  8. Hyperglycemia associated dissociative fugue (organic dissociative disorder in an elderly

    Directory of Open Access Journals (Sweden)

    Dushad Ram

    2015-01-01

    Full Text Available Inadequate glycemic control in patients with diabetes is known to be associated with psychiatric disorders such as depression, anxiety disorder, and cognitive impairment. However, dissociative syndrome has not been reported so far. Here we are reporting a case of repeated dissociative fugue associated with hyperglycemia, in an elderly with type II diabetes. Possible neurobiological mechanism has been discussed.

  9. The effects of benfotiamine in attenuating hyperglycemia-induced ...

    African Journals Online (AJOL)

    In particular, we emphasize the role of hyperglycemia-induced oxidative stress in the activation of non-oxidative glucose pathways (NOGPs), that may contribute to cardiac pathology. For the second part, we evaluate the utility of benfotiamine (a vitamin B1 derivative) in treating diabetes-related cardiac pathology. The focus ...

  10. Chronic fatigue in type 1 diabetes: highly prevalent but not explained by hyperglycemia or glucose variability.

    Science.gov (United States)

    Goedendorp, Martine M; Tack, Cees J; Steggink, Elles; Bloot, Lotte; Bazelmans, Ellen; Knoop, Hans

    2014-01-01

    OBJECTIVE Fatigue is a classical symptom of hyperglycemia, but the relationship between chronic fatigue and diabetes has not been systematically studied. We investigated prevalence, impact, and potential determinants of chronic fatigue in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Out of 324 randomly selected T1DM outpatients, 214 participated in this cross-sectional observational study. Participants were compared with age- and sex-matched population-based controls. Chronic fatigue, functional impairments, current health status, comorbidity, diabetes-related factors, and fatigue-related cognitions and behaviors were assessed with questionnaires, and HbA1c values and comorbidity were assessed with medical records. Sixty-six patients underwent continuous glucose monitoring combined with an electronic fatigue diary for 5 days. Acute fatigue and four glucose parameters were determined: mean, variability, and relative time spent in hypoglycemia and hyperglycemia. RESULTS T1DM patients were significantly more often chronically fatigued (40%; 95% CI 34-47%) compared with matched controls (7%; 95% CI 3-10%; P Chronically fatigued patients had significantly more functional impairments. Fatigue was the most troublesome symptom. Age, depression, pain, sleeping problems, low self-efficacy concerning fatigue, and physical inactivity were significantly associated with chronic fatigue. Chronically fatigued patients spent slightly less time in hypoglycemia (proportion 0.07 ± 0.06 vs. 0.12 ± 0.10; P = 0.025). Glucose parameters were not related to acute fatigue. CONCLUSIONS Chronic fatigue is highly prevalent and clinically relevant in T1DM. Its significant relationship with cognitive behavioral variables and weak association with blood glucose levels suggests that behavioral interventions could be helpful in managing chronic fatigue in T1DM.

  11. Hospitalization for Recently Diagnosed Versus Worsening Chronic Heart Failure: From the ASCEND-HF Trial.

    Science.gov (United States)

    Greene, Stephen J; Hernandez, Adrian F; Dunning, Allison; Ambrosy, Andrew P; Armstrong, Paul W; Butler, Javed; Cerbin, Lukasz P; Coles, Adrian; Ezekowitz, Justin A; Metra, Marco; Starling, Randall C; Teerlink, John R; Voors, Adriaan A; O'Connor, Christopher M; Mentz, Robert J

    2017-06-27

    age, race, prior ischemic heart disease, or ejection fraction (all interactions, p ≥ 0.23). In this acute HF trial, patient profile differed according to duration of the HF diagnosis. A diagnosis of HF for ≤1 month before hospitalization was independently associated with greater early dyspnea relief and improved post-discharge survival compared to patients with chronic HF diagnoses. The distinction between de novo or recently diagnosed HF and worsening chronic HF should be considered in the design of future acute HF trials. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. Oral contraceptives worsen endotoxin-induced liver injury in rats.

    Science.gov (United States)

    Konno, Akira; Enomoto, Nobuyuki; Takei, Yoshiyuki; Hirose, Miyoko; Ikejima, Kenichi; Sato, Nobuhiro

    2002-08-01

    Oral contraceptives are widely used; however, these drugs occasionally cause liver injury. Recently, it was reported that estriol worsens alcoholic liver injury by the mechanism involving activation of Kupffer cells as a result of gut-derived endotoxin. However, the relationship between oral contraceptives and endotoxin-induced liver injury has not been elucidated. Here we show that oral contraceptives sensitize Kupffer cells via a mechanism dependent on increased gut permeability to endotoxin. Female Wistar rats (200-250 g) were given intraperitoneally a combination of estradiol (35 ng/kg of 17 alpha-Ethynylestradiol) and progesterone (2 microg/kg of Norethindrone), each dose being similar to that contained in oral contraceptives (EP treatment). After 24 hr, a sublethal dose of lipopolysaccharide (LPS; 5 mg/kg) was injected via the tail vein. In some experiments, antibiotics (150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin) were administered orally for 4 days before EP treatment. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated and cultured in RPMI 1640 + 10% fetal bovine serum for 24 hr. After addition of LPS (100 ng/ml) to the culture medium, intracellular calcium concentration ([Ca2+](i) ) was measured with fura-2. Liver histology in rats given EP treatment intraperitoneally followed by an injection of LPS (5 mg/kg) 24 hr later revealed pronounced liver damage with massive necrosis. Whereas mean values of alanine aminotransferase (ALT) in the control, nontreated rats were 30 +/- 6 IU/liter, ALT increased to 75 +/- 21 IU/liter 24 hr after LPS injection. This increase was aggravated 6-fold (483 +/- 118 IU/liter; p< 0.05) by EP treatment. The EP treatment-induced increase in ALT was completely blocked by antibiotics (82 +/- 26 IU/liter; p< 0.05). Gut permeability was increased approximately 10-fold with EP treatment. This increase in gut permeability was not altered by

  13. [Apparent worsening of psoriasis lesions revealing methotrexate overdosage].

    Science.gov (United States)

    Haber, R; Baroudjian, B; Battistella, M; Bagot, M; Petit, A

    2017-09-13

    Methotrexate (MTX) is an antimetabolite drug used in the treatment of cancers and autoimmune diseases and frequently in dermatology for cutaneous and/or arthritic psoriasis. Toxicities due to MTX overdosage are mainly cutaneous, hepatic and hematologic. Herein, we report a case of MTX overdosage presenting as an erosive and an inflammatory flare of preexisting psoriatic plaques and with new palmar lesions. A 51-year-old male with a 6-year history of plaque psoriasis resistant to topical corticosteroids was started for the first time on MTX 20mg weekly. One week later, he presented with fever, general weakness and mucocutaneous ulcerations. Physical examination revealed inflammatory, erythematous and partially erosive annular plaques strictly confined to preexisting psoriatic lesions, along with keratotic psoriatic palmar plaques. Further questioning indicated that the patient was taking MTX 20mg daily. Investigations revealed neutropenia (1040/mm3) and skin histology showed prominent dystrophic keratinocytes and confirmed the diagnosis of methotrexate toxicity. Clinical and biological improvements were observed after cessation of MTX and treatment with folinic acid, IV hydration and urine alkalization. Skin lesions due to acute MTX toxicity are rare, but they herald later-onset pancytopenia. Identification of these cutaneous lesions might enable earlier treatment initiation. The predilection of MTX toxicity for preexisting lesions or the de novo appearance of palmoplantar pustules should not lead to the erroneous diagnosis of psoriasis flare. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Normobaric oxygen worsens outcome after a moderate traumatic brain injury.

    Science.gov (United States)

    Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

    2015-07-01

    Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n = 8) or normal air (n = 8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI.

  15. Are quantitative functional measures more sensitive to worsening MS than traditional measures?

    Science.gov (United States)

    Schwid, S R; Goodman, A D; Apatoff, B R; Coyle, P K; Jacobs, L D; Krupp, L B; Miller, A E; Wende, K E; Brownscheidle, C M; New York State Multiple Sclero

    2000-12-26

    The authors used data collected prospectively during a multicenter trial in 133 patients with secondary progressive MS to assess the relative sensitivity of quantitative functional tests and traditional measures, including the Expanded Disability Status Scale (EDSS) and Ambulation Index. Quantitative functional measures worsened in 69% of patients during an average of 6 months of observation, whereas the Clinical Global Impression of Change worsened in 33% and the EDSS worsened in 25% of patients. These changes should be interpreted in the context of the test-retest reliability for each measure.

  16. Autophagy in muscle of glucose-infusion hyperglycemia rats and streptozotocin-induced hyperglycemia rats via selective activation of m-TOR or FoxO3.

    Directory of Open Access Journals (Sweden)

    Pengfei Lv

    Full Text Available Autophagy is a conserved process in eukaryotes required for metabolism and is involved in diverse diseases. To investigate autophagy in skeletal muscle under hyperglycemia status, we established two hyperglycemia-rat models that differ in their circulating insulin levels, by glucose infusion and singe high-dose streptozotocin injection. We then detected expression of autophagy related genes with real-time PCR and western blot. We found that under hyperglycemia status induced by glucose-infusion, autophagy was inhibited in rat skeletal muscle, whereas under streptozotocin-induced hyperglycemia status autophagy was enhanced. Meanwhile, hyperglycemic gastrocnemius muscle was more prone to autophagy than soleus muscle. Furthermore, inhibition of autophagy in skeletal muscle in glucose-infusion hyperglycemia rats was mediated by the m-TOR pathway while m-TOR and FoxO3 both contributed to enhancement of autophagy in gastrocnemius muscle in streptozotocin-induced hyperglycemia rats. These data shows that insulin plays a relatively more important role than hyperglycemia in regulating autophagy in hyperglycemia rat muscle through selectively activating the m-TOR or FoxO3 pathway in a fiber-selective manner.

  17. Risk factors for perioperative hyperglycemia in primary hip and knee replacements

    Science.gov (United States)

    Jämsen, Esa; Nevalainen, Pasi I; Eskelinen, Antti; Kalliovalkama, Jarkko; Moilanen, Teemu

    2015-01-01

    Background and purpose Background and purpose — Perioperative hyperglycemia has been associated with adverse outcomes in several fields of surgery. In this observational study, we identified factors associated with an increased risk of hyperglycemia following hip and knee replacement. Patients and methods Patients and methods — We prospectively monitored changes in glucose following primary hip and knee replacements in 191 patients with osteoarthritis. Possible associations of patient characteristics and operation-related factors with hyperglycemia (defined as glucose > 7.8 mmol/L in 2 consecutive measurements) and severe hyperglycemia (glucose > 10 mmol/L) were analyzed using binary logistic regression with adjustment for age, sex, operated joint, and anesthesiological risk score. Results Results — 76 patients (40%) developed hyperglycemia, and 48 of them (25% of the whole cohort) had severe hyperglycemia. Glycemic responses were similar following hip replacement and knee replacement. Previously diagnosed diabetes was associated with an increased risk of hyperglycemia and severe hyperglycemia, compared to patients with normal glucose metabolism, whereas newly diagnosed diabetes and milder glucose metabolism disorders had no effect. In patients without previously diagnosed diabetes, increased values of preoperative glycosylated hemoglobin (HbA1c) and fasting glucose on the day of operation were associated with hyperglycemia. Higher anesthesiological risk score—but none of the operation-related factors analyzed—was associated with an increased risk of hyperglycemia. Interpretation Interpretation — Perioperative hyperglycemia is common in primary hip and knee replacements. Previously diagnosed diabetes is the strongest risk factor for hyperglycemia. In patients with no history of diabetes, preoperative HbA1c and fasting glucose on the day of operation can be used to stratify the risk of hyperglycemia. PMID:25409255

  18. Insulin Therapy for the Management of Hyperglycemia in Hospitalized Patients

    Science.gov (United States)

    McDonnell, Marie E.; Umpierrez, Guillermo E.

    2013-01-01

    It has long been established that hyperglycemia with or without a prior diagnosis of diabetes increases both mortality and disease-specific morbidity in hospitalized patients1–4 and that goal-directed insulin therapy can improve outcomes.5–9 During the past decade, since the widespread institutional adoption of intensified insulin protocols after the publication of a landmark trial,5,10 the pendulum in the inpatient diabetes literature has swung away from achieving intensive glucose control and toward more moderate and individualized glycemic targets.11,12 This change in clinical practice is the result of several factors, including challenges faced by hospitals to coordinate glycemic control across all levels of care,13,14 publication of negative prospective trials,15,16 revised recommendations from professional organizations,17,18 and increasing evidence on the deleterious effect of hypoglycemia.19–22 This article reviews the pathophysiology of hyperglycemia during illness, the mechanisms for increased complications and mortality due to hyperglycemia and hypoglycemia, beneficial mechanistic effects of insulin therapy and provides updated recommendations for the inpatient management of diabetes in the critical care setting and in the general medicine and surgical settings.23,24 PMID:22575413

  19. MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Maskomani Silambarasan

    2016-04-01

    Full Text Available Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose and at various time intervals (6, 12, 24 and 48 h. miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

  20. Effectiveness of donepezil in reducing clinical worsening in patients with mild-to-moderate alzheimer's disease

    DEFF Research Database (Denmark)

    Wilkinson, David; Schindler, Rachel; Schwam, Elias

    2009-01-01

    BACKGROUND: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer's disease (AD). METHODS: Data from 906 patients (388 receiving placebo; 518 receiving...

  1. Is It True That Certain Foods Worsen Anxiety and Others Have a Calming Effect?

    Science.gov (United States)

    ... with anxiety: Can diet make a difference? Is it true that certain foods worsen anxiety and others ... But as alcohol is processed by your body, it can make you edgy. Alcohol can also interfere ...

  2. Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Ivanildo I. da S. Júnior

    2017-01-01

    Full Text Available Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w. were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats.

  3. DIETARY HYPERGLYCEMIA, GLYCEMIC INDEX AND METABOLIC RETINAL DISEASES

    Science.gov (United States)

    Chiu, Chung-Jung; Taylor, Allen

    2014-01-01

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0~2 h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4~6 h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that

  4. Prolonged TASER use on exhausted humans does not worsen markers of acidosis.

    Science.gov (United States)

    Ho, Jeffrey D; Dawes, Donald M; Bultman, Laura L; Moscati, Ronald M; Janchar, Timothy A; Miner, James R

    2009-05-01

    There are safety concerns about TASER conducted electrical weapon (CEW) use on humans, and there have been media reports of adverse human outcomes after CEW exposure. Conducted electrical weapons are often used on physically exhausted subjects. A single CEW application of a CEW is generally accepted to be 5 seconds of exposure. Some exposures in reality involve more than 5 seconds. We sought to determine if a prolonged (15 seconds) CEW exposure on exhausted humans caused acidosis, hyperkalemia, serum lactate change, or troponin change. This was a prospective study of generally healthy human volunteers. Medical histories and baseline serum values were obtained, and several of the volunteers did have acute or chronic medical problems. Subjects underwent an exercise protocol until subjective exhaustion. Exhaustion was defined by the volunteer no longer being able to perform the exercise at a given pace. Blood was drawn immediately (defined as within 20 seconds) after exercise and was immediately followed by a 15-second CEW exposure. Blood was drawn immediately after exposure and again at 16 to 24 hours after exposure. Blood was analyzed for pH, pco(2), potassium, lactate, and troponin. Data were compared using Wilcoxon signed rank tests. There were 38 subjects enrolled with an average age of 39 years. The following health conditions were reported among the volunteers: hypertension (2), gastritis/reflux (2), active respiratory tract infections (3), asthma (2), chronic muscular pain conditions (4), pituitary adenoma (1) and glaucoma (1). Sixteen volunteers reported use of prescription medication at the time of their participation. The median initial pH of 7.38 (interquartile range [IQR], 7.35-7.40) decreased to 7.23 (IQR, 7.19-7.31) immediately after exercise. Immediately after exposure, median pH was 7.22 (IQR, 7.18-7.25). It was 7.39 (IQR, 7.37-7.43) at 24 hours. The pCO2 increased from 46.3 (IQR, 43.0-54.5) to 57.4 (IQR, 49.9-67.7) immediately after exercise

  5. The Relationship and Potential Mechanistic Pathways Between Sleep Disturbances and Maternal Hyperglycemia

    Science.gov (United States)

    Izci-Balserak, Bilgay; Pien, Grace W.

    2014-01-01

    This paper reviews recent work investigating the influence of sleep disturbances on maternal hyperglycemia, particularly gestational diabetes mellitus (GDM). The incidence and prevalence of hyperglycemia are increasing worldwide, which is cause for concern because GDM and even mild hyperglycemia are associated with adverse pregnancy outcomes. A better understanding of sleep-related risk factors for maternal hyperglycemia is an important health matter. Evidence demonstrates associations between sleep disturbances, especially sleep-disordered breathing, and hyperglycemia, but causal effects and the underlying mechanisms linking these conditions have not been fully elucidated. Subjective sleep assessments show associations between sleep disturbances and maternal hyperglycemia. There are, however, few studies using objective measures to support these findings. Large prospective studies are required to examine causal relationships between sleep disturbances and maternal hyperglycemia. There is also a need for smaller mechanistic studies to understand the pathophysiology. Furthermore, interventional studies are required to address whether improvement of sleep parameters can prevent/decrease the risk of developing maternal hyperglycemia. Taken together, the data suggests that sleep disturbances during pregnancy are important to identify and manage in order to minimize maternal hyperglycemia and GDM, and improve maternal and fetal well-being. PMID:24398662

  6. Renal dysfunction in African patients with acute heart failure

    NARCIS (Netherlands)

    Sani, Mahmoud U.; Davison, Beth A.; Cotter, Gad; Sliwa, Karen; Edwards, Christopher; Liu, Licette; Damasceno, Albertino; Mayosi, Bongani M.; Ogah, Okechukwu S.; Mondo, Charles; Dzudie, Anastase; Ojji, Dike B.; Voors, Adrian A.

    Aims In Western countries with typically elderly ischaemic acute heart failure patients, predictors and clinical outcome of renal dysfunction and worsening renal function are well described. However, the prevalence, predictors and clinical outcome of renal dysfunction in younger, mainly hypertensive

  7. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia

    Science.gov (United States)

    Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C.; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J.; Schwartz, Alan R.; Shirahata, Machiko

    2014-01-01

    Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.–9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. PMID:25103977

  8. Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia.

    Science.gov (United States)

    Shin, Mi-Kyung; Yao, Qiaoling; Jun, Jonathan C; Bevans-Fonti, Shannon; Yoo, Doo-Young; Han, Woobum; Mesarwi, Omar; Richardson, Ria; Fu, Ya-Yuan; Pasricha, Pankaj J; Schwartz, Alan R; Shirahata, Machiko; Polotsky, Vsevolod Y

    2014-10-01

    Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH. Male C57BL/6J mice underwent carotid sinus nerve dissection (CSND) or sham surgery and then were exposed to IH or intermittent air (IA) for 4 or 6 wk. Hypoxia was administered by decreasing a fraction of inspired oxygen from 20.9% to 6.5% once per minute, during the 12-h light phase (9 a.m.-9 p.m.). As expected, denervated mice exhibited blunted hypoxic ventilatory responses. In sham-operated mice, IH increased fasting blood glucose, baseline hepatic glucose output (HGO), and expression of a rate-liming hepatic enzyme of gluconeogenesis phosphoenolpyruvate carboxykinase (PEPCK), whereas the whole body glucose flux during hyperinsulinemic euglycemic clamp was not changed. IH did not affect glucose tolerance after adjustment for fasting hyperglycemia in the intraperitoneal glucose tolerance test. CSND prevented IH-induced fasting hyperglycemia and increases in baseline HGO and liver PEPCK expression. CSND trended to augment the insulin-stimulated glucose flux and enhanced liver Akt phosphorylation at both hypoxic and normoxic conditions. IH increased serum epinephrine levels and liver sympathetic innervation, and both increases were abolished by CSND. We conclude that chronic IH induces fasting hyperglycemia increasing baseline HGO via the CSN sympathetic output from carotid body chemoreceptors, but does not significantly impair whole body insulin sensitivity. Copyright © 2014 the American Physiological Society.

  9. Effect of hyperglycemia on mortality rates in critically ill children

    Directory of Open Access Journals (Sweden)

    Seongkuk Kim

    2010-03-01

    Full Text Available Purpose : To verify the effect of hyperglycemia on mortality rates in critically ill children and to identify the blood glucose level that influences prognosis. Methods : From July 2006 to June 2008, a total of 206 patients who were admitted to the pediatric intensive care unit (PICU at Asan Medical Center and who survived for more than 7 days were retrospectively reviewed. We analyzed the maximum glucose value within 7 days in PICU, PRISM-III score and SOFA score within 24 hours, and mortality. We did not perform an adjustment analysis of drugs affecting glucose level. Results : The maximum glucose level within 7 days in PICU was higher in the nonsurvival group than in the survival group. Using 4 cutoff values (125, 150, 175, and 200 mg/dL, the mortality of patients with hyperglycemia was found to be 13.0 %, 14.4%, 19.8%, and 21.1%, respectively, and the cutoff values of 175 and 200 mg/dL revealed significant differences in mortalities between the hyperglycemic and normoglycemic groups. The PRISM-III score was not significantly different between the hyperglycemic and normoglycemic groups under a glucose cutoff value of 175 mg/dL, but the SOFA score was higher in the hyperglycemic group. Under a glucose cutoff value of 200 mg/dL, the PRISM-III score was higher in the hyperglycemic group, and the SOFA score did not differ between the 2 groups. Conclusion : Hyperglycemia with a maximal glucose value ?#241;75 mg/dL during the first 7 days after PICU admission was associated with increased mortality in critically ill children.

  10. Chronic hyperglycemia affects bone metabolism in adult zebrafish scale model.

    Science.gov (United States)

    Carnovali, Marta; Luzi, Livio; Banfi, Giuseppe; Mariotti, Massimo

    2016-12-01

    Type II diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia that induce other pathologies including diabetic retinopathy and bone disease. The mechanisms implicated in bone alterations induced by type II diabetes mellitus have been debated for years and are not yet clear because there are other factors involved that hide bone mineral density alterations. Despite this, it is well known that chronic hyperglycemia affects bone health causing fragility, mechanical strength reduction and increased propensity of fractures because of impaired bone matrix microstructure and aberrant bone cells function. Adult Danio rerio (zebrafish) represents a powerful model to study glucose and bone metabolism. Then, the aim of this study was to evaluate bone effects of chronic hyperglycemia in a new type II diabetes mellitus zebrafish model created by glucose administration in the water. Fish blood glucose levels have been monitored in time course experiments and basal glycemia was found increased. After 1 month treatment, the morphology of the retinal blood vessels showed abnormalities resembling to the human diabetic retinopathy. The adult bone metabolism has been evaluated in fish using the scales as read-out system. The scales of glucose-treated fish didn't depose new mineralized matrix and shown bone resorption lacunae associated with an intense osteoclast activity. In addition, hyperglycemic fish scales have shown a significant decrease of alkaline phosphatase activity and increase of tartrate-resistant acid phosphatase activity, in association with alterations in other bone-specific markers. These data indicates an imbalance in bone metabolism, which leads to the osteoporotic-like phenotype visualized through scale mineral matrix staining. The zebrafish model of hyperglycemic damage can contribute to elucidate in vivo the molecular mechanisms of metabolic changes, which influence the bone tissues regulation in human diabetic patients.

  11. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    Science.gov (United States)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

  12. Chorea in the Both Lower Limbs Associated with Nonketotic Hyperglycemia

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    Young-Hee Sung

    2009-10-01

    Full Text Available Hemichorea-hemiballism (HC-HB is a complication of non-ketotic hyperglycemia (NKH; in NKH patients, the frequency of occurrence of HC-HB is greater than that of bilateral chorea. We report the case of a hyperglycemic patient who showed chorea in both the lower limbs. Magnetic resonance imaging (MRI of the brain revealed high signal intensity on T1-weighted images of the bilateral dorsolateral putamen. The abnormal involuntary movements disappeared after oral administration of haloperidol. Our case report that chorea associated with NKH is correlated with the topography of the basal ganglia.

  13. Worsening respiratory function in mechanically ventilated intensive care patients: feasibility and value of xenon-enhanced dual energy CT.

    Science.gov (United States)

    Hoegl, Sandra; Meinel, Felix G; Thieme, Sven F; Johnson, Thorsten R C; Eickelberg, Oliver; Zwissler, Bernhard; Nikolaou, Konstantin

    2013-03-01

    To evaluate the feasibility and incremental diagnostic value of xenon-enhanced dual-energy CT in mechanically ventilated intensive care patients with worsening respiratory function. The study was performed in 13 mechanically ventilated patients with severe pulmonary conditions (acute respiratory distress syndrome (ARDS), n=5; status post lung transplantation, n=5; other, n=3) and declining respiratory function. CT scans were performed using a dual-source CT scanner at an expiratory xenon concentration of 30%. Both ventilation images (Xe-DECT) and standard CT images were reconstructed from a single CT scan. Findings were recorded for Xe-DECT and standard CT images separately. Ventilation defects on xenon images were matched to morphological findings on standard CT images and incremental diagnostic information of xenon ventilation images was recorded if present. Mean xenon consumption was 2.95 l per patient. No adverse events occurred under xenon inhalation. In the visual CT analysis, the Xe-DECT ventilation defects matched with pathologic changes in lung parenchyma seen in the standard CT images in all patients. Xe-DECT provided additional diagnostic findings in 4/13 patients. These included preserved ventilation despite early pneumonia (n=1), more confident discrimination between a large bulla and pneumothorax (n=1), detection of an airway-to-pneumothorax fistula (n=1) and exclusion of a suspected airway-to-mediastinum fistula (n=1). In all 4 patients, the additional findings had a substantial impact on patients' management. Xenon-enhanced DECT is safely feasible and can add relevant diagnostic information in mechanically ventilated intensive care patients with worsening respiratory function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Bilateral cataract formation via acute spontaneous fracture of the lens following treatment of hyperglycemic hyperosmolar syndrome

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    Yevgeniy V. Sychev

    2017-09-01

    Conclusions and importance: Acute transient cataracts that develop during correction of hyperglycemic hyperosmolar syndrome are thought to result from osmotic lens swelling. In this case report, internal fracture of the lens was produced by mechanical forces generated in the process of lens swelling occurring as a consequence of initial hyperglycemia and its subsequent correction. This case represents a rare ocular complication of hyperglycemia correction, and provides new evidence that mechanical forces can be part of diabetic cataractogenesis.

  15. Use of glycated albumin to distinguish occult diabetes mellitus from stress-induced hyperglycemia in Chinese orthopedic trauma patients.

    Science.gov (United States)

    Pan, Jiemin; Zou, Jian; Bao, Yuqian; Zhang, Lei; Han, Junfeng; Tang, Junling; Ma, Xiaojing; Li, Qing; Jia, Weiping

    2012-05-01

    Some nondiabetic trauma patients with hyperglycemia have been found to have occult diabetes mellitus (ODM). We studied whether glycated albumin (GA) was an effective tool for detecting ODM in orthopedic trauma patients with elevated glucose levels. A cross-sectional, sequential case series study of adult patients presenting to the Orthopedic Trauma Center between September 2009 and March 2010 with new limb fractures was performed. Hemoglobin A1c (HbA1c) and GA levels were measured in hyperglycemic patients with no prior diabetes mellitus. A receiver operating characteristic curve was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA in identifying occult diabetes in hospitalized patients with acute hyperglycemia. A total of 2,058 trauma patients were screened and 399 patients (19.4%) with no known diabetes mellitus were noted to be hyperglycemic. Of these 399 patients, 38.3% (n = 153) had ODM according to the HbA1c diagnosis cutoff point. GA level was strongly correlated with HbA1c using Pearson's correlation analysis (r = 0.887, p Chinese orthopedic trauma subjects. II, diagnostic study.

  16. Association of increased morbidity with the occurrence of hyperglycemia in the immediate postoperative period after elective pediatric neurosurgery.

    Science.gov (United States)

    Filho, Nazel Oliveira; Alves, Rodrigo L; Fernandes, Adriano T; Castro, Fernanda S P; Melo, José Roberto Tude; Módolo, Norma S P

    2016-05-01

    OBJECTIVE The acute elevation of blood glucose in perioperative pediatric patients subjected to cardiac surgery and in victims of head trauma is associated with higher rates of postoperative complications. Data on the occurrence of hyperglycemia and its association with unfavorable outcomes among patients who have undergone elective neurosurgery are scarce in the literature. This study aimed to determine whether the occurrence of hyperglycemia during the perioperative period of elective neurosurgery for the resection of tumors of the CNS in children is associated with increased morbidity. METHODS This retrospective cohort analysis included 105 children up to 12 years of age who underwent elective neurosurgery for resection of supratentorial and infratentorial CNS tumors between January 2005 and December 2010 at the São Rafael Hospital, a tertiary care medical center in Salvador, Brazil. Demographic data and intraoperative and postoperative information were collected from the medical records. Differences in blood glucose levels during the perioperative period were evaluated with nonparametric tests. RESULTS The patients who developed postoperative complications exhibited higher blood glucose levels on admission to the intensive care unit (ICU) (162.0 ± 35.8 mg/dl vs 146.3 ± 43.3 mg/dl; p = 0.016) and peak blood glucose levels on postoperative Day 1 (171.9 ± 30.2 mg/dl vs 156.1 ± 43.2 mg/dl; p = 0.008). Multivariate analysis showed that peak blood glucose levels on postoperative Day 1 were independently associated with a higher odds ratio for postoperative complication (OR 1.05). The occurrence of hyperglycemia (>150 mg/dl) upon admission to the ICU was associated with longer ICU (p = 0.003) and hospital (p = 0.001) stays. CONCLUSIONS The occurrence of hyperglycemia during the postoperative period after elective pediatric neurosurgery for the resection of CNS tumors was associated with longer hospital and ICU stays. Postoperative complications were associated

  17. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis

    DEFF Research Database (Denmark)

    Martinez-Lapiscina, Elena H; Arnow, Sam; Wilson, James A

    2016-01-01

    of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. METHODS: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis......, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale...... (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5-5 years). Patients with a p...

  18. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

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    Liang-Jun Yan

    2014-01-01

    Full Text Available Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH, respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

  19. [Large trade clusters as areas of intensified occurrences of states of rapid health worsening in Poland].

    Science.gov (United States)

    Stępień, Michał; Zuzańska-Żyśko, Elżbieta

    2017-01-01

    In the modern world, people gather more increasingly in large clusters such as shopping centres, markets, cinema centres, operas, ferries, liners, recreation areas and resorts. Such clusters predispose to intensified occurrences of states of rapid health worsening and health hazard. The main aim is to indicate that in trade space, especially in municipal markets, states of rapid health worsening and health hazard appear, as well as to characterize the individual incidents and types of medical interventions. The empirical material originates from the sheets of records of first-aid concerning life-saving actions, the nurse work register, as well as the security agency reports. Records of first-aid of events taking place during one selected weekend day, for 6 hours of highest population density, underwent a retrospective analysis. The analysis of the material was carried out in terms of reasons of interventions, in states of rapid health worsening and health hazard, as well as the frequency of calls of medical first-aid service. During 2011, there were approximately 100 such states in the municipal markets which underwent the study. In shopping centres there were 95% of such states. In each of the three analysed areas, the internal factors responsible for rapid health worsening constitute over 60%. Among interventions caused by a disease, states related to circulatory system and nervous system occurred most frequently. Big municipal market themselves are potential areas of an increased occurrence of states of rapid health worsening and health hazard. They can be compared to religious ceremonies described in the subject bibliography. Large trade spaces, especially municipal markets in city centres, generate a high risk of occurrences of states of rapid health worsening and health hazard, in comparison to shopping malls. The risk increases with the age of customers. The incidences related to sicknesses are the majority of interventions in trade areas.

  20. Hyperglycemia suppresses the sympatho-adrenal response to hypoxia, but not to handling stress

    NARCIS (Netherlands)

    Benthem, L; Taborsky, G.J.

    1998-01-01

    We hypothesized that the ability of prior hyperglycemia to suppress the sympatho-adrenal response would depend on the type of stress. To test this hypothesis, hyperglycemia was induced in chronically catheterized rats, before submitting them to either hypoxia (7.5% O-2) or handling stress. Central

  1. Relationship between Inpatient Hyperglycemia and Insulin Treatment after Kidney Transplantation and Future New Onset Diabetes Mellitus

    Science.gov (United States)

    Knowler, William C.; Devarapalli, Yugandhara; Weil, E. Jennifer; Heilman, Raymond L.; Dueck, Amylou; Mulligan, David C.; Reddy, Kunam S.; Moss, Adyr A.; Mekeel, Kristin L.; Mazur, Marek J.; Hamawi, Khaled; Castro, Janna C.; Cook, Curtiss B.

    2010-01-01

    Background and objectives: Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. Design, setting, participants, & measurements: A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose ≥ 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C ≥ 6.5%, fasting venous serum glucose ≥ 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. Results: The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). Conclusion: Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT. PMID:20558559

  2. The Role of Hyperglycemia in Burned Patients: Evidence-Based Studies

    Science.gov (United States)

    Mecott, Gabriel A.; Al-Mousawi, Ahmed M.; Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

    2013-01-01

    Severely burned patients typically experience a systemic response expressed as increased metabolism, inflammation, alteration of cardiac and immune function, and associated hyperglycemia. Hyperglycemia has been associated with an increased risk of morbidity and mortality in critically ill patients. Until recently and for many years, hyperglycemia has been expectantly managed and considered a normal and desired response of an organism to stress. However, findings reported from recent studies now suggest beneficial effects of intensive insulin treatment for critically-ill patients. The literature on the management of hyperglycemia in severely burned patients is sparse, with most of the available studies involving only small numbers of burned patients. The purpose of this article is to describe the pathophysiology of hyperglycemia following severe burns and review the available literature on the outcome of intensive insulin treatment and other anti-hyperglycemic modalities in burned patients in an evidence-based-medicine approach. PMID:19503020

  3. Management of diabetes mellitus: could simultaneous targeting of hyperglycemia and oxidative stress be a better panacea?

    Science.gov (United States)

    Erejuwa, Omotayo O

    2012-01-01

    The primary aim of the current management of diabetes mellitus is to achieve and/or maintain a glycated hemoglobin level of ≤6.5%. However, recent evidence indicates that intensive treatment of hyperglycemia is characterized by increased weight gain, severe hypoglycemia and higher mortality. Besides, evidence suggests that it is difficult to achieve and/or maintain optimal glycemic control in many diabetic patients; and that the benefits of intensively-treated hyperglycemia are restricted to microvascular complications only. In view of these adverse effects and limitations of intensive treatment of hyperglycemia in preventing diabetic complications, which is linked to oxidative stress, this commentary proposes a hypothesis that "simultaneous targeting of hyperglycemia and oxidative stress" could be more effective than "intensive treatment of hyperglycemia" in the management of diabetes mellitus.

  4. Frequency and management of diabetes and hyperglycemia at emergency departments: the GLUCE-URG Study.

    Science.gov (United States)

    Álvarez-Rodríguez, Esther; Laguna Morales, Inmaculada; Rosende Tuya, Alicia; Tapia Santamaría, Raquel; Martín Martínez, Alfonso; López Riquelme, Pascual; Merinero Palomares, Raúl; Portero Sánchez, Isabel

    2017-02-01

    Hyperglycemia is a common finding at hospital emergency rooms in diabetic patients, but few data are available on its frequency, management, and subsequent impact based on the assessment made at Emergency rooms. To ascertain the frequency of diabetes mellitus and hyperglycemia in patients admitted from Emergency rooms. Second, to describe management of hyperglycemia at Emergency rooms, and to analyze its potential impact on the course and management of patients during admission. All patients admitted from the Emergency room for three consecutive weeks were enrolled. Hyperglycemia was defined as two blood glucose measurements ≥ 180mg/dl in the first 48hours after admission. 36.6% of patients admitted from the Emergency room were diabetic, and 58% of these had early, sustained hyperglycemia. On the other hand, 27% of patients admitted from the Emergency room had hyperglycemia (78.3% of diabetic patients and 21.7% with no known diabetes). Diabetic patients with hyperglycemia had higher blood glucose levels than non-diabetic patients (p<.01). Average hospital stay was 8±6.4 days, with no differences between the groups. Hyperglycemia is rarely reported as a diagnosis in the emergency rooms discharge report. In standard hospitalization, this diagnosis appears more commonly in patients with known diabetes (OR 2.5 p<.001). Prevalence of diabetic patients admitted from emergency rooms is very high. In addition, although hyperglycemia is very common in patients admitted from emergency rooms, there is a trend to underestimate its significance. Based on our results, we think that implementation of measures to give greater visibility to diagnosis of hyperglycemia could help improve application of established protocols. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Admission Glucose Levels and the Risk of Acute Kidney Injury in Nondiabetic ST Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention.

    Science.gov (United States)

    Shacham, Yacov; Gal-Oz, Amir; Leshem-Rubinow, Eran; Arbel, Yaron; Keren, Gad; Roth, Arie; Steinvil, Arie

    2015-06-01

    Hyperglycemia upon admission is associated with an increased risk for acute kidney injury (AKI) in ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). However, the relation of this association to the absence of diabetes mellitus (DM) is less studied. We evaluated the effect of acute hyperglycemia levels on the risk of AKI among STEMI patients without DM who were all treated with primary PCI. We retrospectively studied 1,065 nondiabetic STEMI patients undergoing primary PCI. Patients were stratified according to admission glucose levels into normal (200 mg/dl) hyperglycemia groups. Medical records were reviewed for the occurrence of AKI. The mean age was 61 ± 13 years and 81% were males. Hyperglycemia upon hospital admission was present in 402 of 1,065 patients (38%). Patients with severe admission hyperglycemia had a significantly higher rate of AKI compared to patients with no or mild hyperglycemia (20 vs. 7 and 8%, respectively; p = 0.001) and had a significantly greater serum creatinine change throughout hospitalization (0.17 vs. 0.09 and 0.07 mg/dl, respectively; p = 0.04). In multivariate logistic regression, severe hyperglycemia emerged as an independent predictor of AKI (OR = 2.46, 95% CI 1.16-5.28; p = 0.018). Severe admission hyperglycemia is an independent risk factor for the development of AKI among nondiabetic STEMI patients undergoing primary PCI.

  6. Acute rhinosinusitis in adults.

    Science.gov (United States)

    Aring, Ann M; Chan, Miriam M

    2011-05-01

    Rhinosinusitis is one of the most common conditions for which patients seek medical care. Subtypes of rhinosinusitis include acute, subacute, recurrent acute, and chronic. Acute rhinosinusitis is further specified as bacterial or viral. Most cases of acute rhinosinusitis are caused by viral infections associated with the common cold. Symptomatic treatment with analgesics, decongestants, and saline nasal irrigation is appropriate in patients who present with nonsevere symptoms (e.g., mild pain, temperature less than 101°F [38.3°C]). Narrow-spectrum antibiotics, such as amoxicillin or trimethoprim/sulfamethoxazole, are recommended in patients with symptoms or signs of acute rhinosinusitis that do not improve after seven days, or that worsen at any time. Limited evidence supports the use of intranasal corticosteroids in patients with acute rhinosinusitis. Radiographic imaging is not recommended in the evaluation of uncomplicated acute rhinosinusitis. Computed tomography of the sinuses should not be used for routine evaluation, although it may be used to define anatomic abnormalities and evaluate patients with suspected complications of acute bacterial rhinosinusitis. Rare complications of acute bacterial rhinosinusitis include orbital, intracranial, and bony involvement. If symptoms persist or progress after maximal medical therapy, and if computed tomography shows evidence of sinus disease, referral to an otolaryngologist is warranted.

  7. Central nervous system Tuberculosis in a man from Cambodia with worsening headaches.

    Science.gov (United States)

    Krauth, Daniel S; Stone-Garza, Kristi K; Amaro, Deirdre E; Reed, Sharon L; Katsivas, Theodoros F

    2017-10-01

    Central nervous system (CNS) tuberculosis should be considered in patients from endemic nations with worsening neurological symptoms. If imaging reveals possible CNS tuberculomas, potentially life-threatening lesions should be excised and analyzed. When disease is less severe, other tissues possibly infected should be biopsied first for diagnosis to avoid neurosurgery.

  8. Psychosis or Obsessions? Clozapine Associated with Worsening Obsessive-Compulsive Symptoms

    Directory of Open Access Journals (Sweden)

    Jonathan G. Leung

    2016-01-01

    Full Text Available One underrecognized adverse event of clozapine is the emergence or worsening of obsessive-compulsive symptoms (OCS. OCS, particularly violent thoughts, can be inaccurately described as psychosis and result in a misdiagnosis. We report a case of a 42-year-old man, initially diagnosed with schizoaffective, who was placed on clozapine for the management of “violent delusions.” However, clozapine led to a worsening of these violent thoughts resulting in suicidal ideation and hospitalization. After exploration of the intrusive thoughts and noting these to be egodystonic, clearly disturbing, and time consuming, an alternative diagnosis of obsessive-compulsive disorder (OCD was made. Clozapine was inevitably discontinued resulting in a significant reduction of the intrusive thoughts without emergence of psychosis or adverse events. While an overlapping phenomenology between OCD and psychotic disorders has been described, clozapine and other antiserotonergic antipsychotics have been implicated with the emergence or worsening of OCS. Unique to our case is that the patient’s obsessions had been treated as psychosis leading to the inadequate treatment of his primary illness, OCD. This case highlights the potential for OCD to masquerade as a psychotic disorder and reminds clinicians that clozapine may worsen OCS.

  9. Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Spoelstra, JA; Stolk, RP; Cohen, D; Klungel, OH; Erkens, JA; Leufkens, HGM; Grobbee, DE

    (B)ackground: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. Method: In

  10. Race, sex, and risk factors in radiographic worsening of knee osteoarthritis.

    Science.gov (United States)

    Vina, Ernest R; Ran, Di; Ashbeck, Erin L; Ratzlaff, Charles; Kwoh, C Kent

    2017-08-31

    Characterize radiographic worsening in knee osteoarthritis (KOA) by race and sex over 4 years and evaluate the role of established risk factors in observed race/sex differences. Whites (WHs) (694 males and 929 females) and African-Americans (AAs) (92 males and 167 females) at risk for radiographic KOA were eligible. Cox shared frailty models were used to estimate race and sex group differences in radiographic worsening, defined by Kellgren-Lawrence (K-L) and OARSI joint space narrowing (JSN). Mixed effect models for repeated measures were used to estimate race- and sex-specific mean medial and lateral fixed joint space width (fJSW) over 4 years of follow-up, as well as annual loss of fJSW. Risk of OARSI medial JSN grade worsening was higher among AA males than WH females [HR = 2.28, (95% CI: 1.14-4.57)], though adjustment for KOA risk factors attenuated the association. Compared to WH females, WH males had lower risk of K-L grade worsening [adjusted HR = 0.75 (95% CI: 0.58-0.96)]. Mean baseline medial fJSW (mm) was 6.49 in WH and AA males, 5.42 in WH females, and 5.41 in AA females. Annual change in mean medial fJSW was greater in AA males (-0.19mm/year) than in other subgroups (-0.09 WH males, -0.07 WH females, -0.10 AA females, p space loss. Controlling for established risk factors attenuated associations between race/sex and disease worsening, suggesting that risk factors such as obesity, history of knee injury, and bony finger joint enlargements largely explain race/sex variations in rates of KOA development and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Hyperglycemia-induced diaphragm weakness is mediated by oxidative stress

    Science.gov (United States)

    2014-01-01

    Introduction A major consequence of ICU-acquired weakness (ICUAW) is diaphragm weakness, which prolongs the duration of mechanical ventilation. Hyperglycemia (HG) is a risk factor for ICUAW. However, the mechanisms underlying HG-induced respiratory muscle weakness are not known. Excessive reactive oxygen species (ROS) injure multiple tissues during HG, but only one study suggests that excessive ROS generation may be linked to HG-induced diaphragm weakness. We hypothesized that HG-induced diaphragm dysfunction is mediated by excessive superoxide generation and that administration of a specific superoxide scavenger, polyethylene glycol superoxide dismutase (PEG-SOD), would ameliorate these effects. Methods HG was induced in rats using streptozotocin (60 mg/kg intravenously) and the following groups assessed at two weeks: controls, HG, HG + PEG-SOD (2,000U/kg/d intraperitoneally for seven days), and HG + denatured (dn)PEG-SOD (2000U/kg/d intraperitoneally for seven days). PEG-SOD and dnPEG-SOD were administered on day 8, we measured diaphragm specific force generation in muscle strips, force-pCa relationships in single permeabilized fibers, contractile protein content and indices of oxidative stress. Results HG reduced diaphragm specific force generation, altered single fiber force-pCa relationships, depleted troponin T, and increased oxidative stress. PEG-SOD prevented HG-induced reductions in diaphragm specific force generation (for example 80 Hz force was 26.4 ± 0.9, 15.4 ± 0.9, 24.0 ± 1.5 and 14.9 ± 0.9 N/cm2 for control, HG, HG + PEG-SOD, and HG + dnPEG-SOD groups, respectively, P hyperglycemia-induced diaphragm dysfunction. This new mechanistic information could explain how HG alters diaphragm function during critical illness. PMID:24886999

  12. Atypical presentation of central pontine myelinolysis in hyperglycemia

    Directory of Open Access Journals (Sweden)

    Swapna Talluri

    2017-09-01

    Full Text Available Central pontine myelinolysis (CPM usually occurs with rapid correction of severe chronic hyponatremia. Despite the pronounced fluctuations in serum osmolality, CPM is rarely seen in diabetics. This is a case report of CPM associated with hyperglycemia. A 45-year-old non-smoking and non-alcoholic African American male with past medical history of type 2 diabetes, hypertension, stage V chronic kidney disease and hypothyroidism presented with a two-week history of intermittent episodes of gait imbalance, slurred speech and inappropriate laughter. Physical examination including complete neurological assessment and fundoscopic examination were unremarkable. Laboratory evaluation was significant for serum sodium: 140 mmol/L, potassium: 3.9 mmol/L, serum glucose: 178 mg/dL and serum osmolality: 317 mosmol/kg. His ambulatory blood sugars fluctuated between 100 and 600 mg/dL in the six weeks prior to presentation, without any significant or rapid changes in his corrected serum sodium or other electrolyte levels. MRI brain demonstrated a symmetric lesion in the central pons with increased signal intensity on T2- and diffusion-weighted images. After neurological consultation and MRI confirmation, the patient was diagnosed with CPM secondary to hyperosmolar hyperglycemia. Eight-week follow-up with neurology was notable for near-complete resolution of symptoms. This case report highlights the importance of adequate blood glucose control in diabetics. Physicians should be aware of complications like CPM, which can present atypically in diabetics and is only diagnosed in the presence of a high index of clinical suspicion.

  13. Automated quantification reveals hyperglycemia inhibits endothelial angiogenic function.

    Directory of Open Access Journals (Sweden)

    Anthony R Prisco

    Full Text Available Diabetes Mellitus (DM has reached epidemic levels globally. A contributing factor to the development of DM is high blood glucose (hyperglycemia. One complication associated with DM is a decreased angiogenesis. The Matrigel tube formation assay (TFA is the most widely utilized in vitro assay designed to assess angiogenic factors and conditions. In spite of the widespread use of Matrigel TFAs, quantification is labor-intensive and subjective, often limiting experiential design and interpretation of results. This study describes the development and validation of an open source software tool for high throughput, morphometric analysis of TFA images and the validation of an in vitro hyperglycemic model of DM.Endothelial cells mimic angiogenesis when placed onto a Matrigel coated surface by forming tube-like structures. The goal of this study was to develop an open-source software algorithm requiring minimal user input (Pipeline v1.3 to automatically quantify tubular metrics from TFA images. Using Pipeline, the ability of endothelial cells to form tubes was assessed after culture in normal or high glucose for 1 or 2 weeks. A significant decrease in the total tube length and number of branch points was found when comparing groups treated with high glucose for 2 weeks versus normal glucose or 1 week of high glucose.Using Pipeline, it was determined that hyperglycemia inhibits formation of endothelial tubes in vitro. Analysis using Pipeline was more accurate and significantly faster than manual analysis. The Pipeline algorithm was shown to have additional applications, such as detection of retinal vasculature.

  14. Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term.

    Science.gov (United States)

    Frasch, Martin G; Keen, Ashley E; Gagnon, Robert; Ross, Michael G; Richardson, Bryan S

    2011-01-01

    Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping fetal arterial blood pressure during each FHR deceleration (pfetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring.

  15. Non-diabetic hyperglycemia exacerbates disease severity in Mycobacterium tuberculosis infected guinea pigs.

    Directory of Open Access Journals (Sweden)

    Brendan K Podell

    Full Text Available Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since the increased risk of active TB in diabetics has been linked to the severity and duration of hyperglycemia, we investigated what effect diet-induced hyperglycemia had on the severity of Mycobacterium tuberculosis (Mtb infection in non-diabetic guinea pigs. Post-prandial hyperglycemia was induced in guinea pigs on normal chow by feeding a 40% sucrose solution daily or water as a carrier control. Sucrose feeding was initiated on the day of aerosol exposure to the H37Rv strain of Mtb and continued for 30 or 60 days of infection. Despite more severe hyperglycemia in sucrose-fed animals on day 30, there was no significant difference in lung bacterial or lesion burden until day 60. However the higher spleen and lymph node bacterial and lesion burden at day 30 indicated earlier and more severe extrapulmonary TB in sucrose-fed animals. In both sucrose- and water-fed animals, serum free fatty acids, important mediators of insulin resistance, were increased by day 30 and remained elevated until day 60 of infection. Hyperglycemia mediated by Mtb infection resulted in accumulation of advanced glycation end products (AGEs in lung granulomas, which was exacerbated by sucrose feeding. However, tissue and serum AGEs were elevated in both sucrose and water-fed guinea pigs by day 60. These data indicate that Mtb infection alone induces insulin resistance and chronic hyperglycemia, which is exacerbated by sucrose feeding. Moreover, Mtb infection alone resulted in the accumulation tissue and serum AGEs, which are also central to the pathogenesis of diabetes and diabetic complications. The exacerbation of insulin resistance and hyperglycemia by Mtb infection alone may explain why TB is more severe in diabetics with poorly controlled hyperglycemia compared to non-diabetics and patients with properly controlled

  16. Scotopic electrophysiology of the retina during transient hyperglycemia in type 2 diabetes

    DEFF Research Database (Denmark)

    Holfort, Stig Kraglund; Klemp, Kristian; Kofoed, Peter Kristian

    2010-01-01

    PURPOSE: To examine dark-adapted retinal function in subjects with type 2 diabetes during transient hyperglycemia. METHODS: Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to an oral glucose tolerance test (OGTT) or a fasting regimen. One study eye...... by hyperglycemia. The scotopic ffERG amplitudes rose and fell in phase with the glycemia. Implicit times did not change with the rise and fall in glycemia. CONCLUSIONS: The change in scotopic signaling amplitude in the outer and middle layers of retina in subjects with diabetes was proportional to the change...... in capillary glucose. Cone amplitude was not influenced by hyperglycemia in this study....

  17. Opioid-Induced Hyperalgesia - Worsening Pain in Opioid-Dependent Patients

    Science.gov (United States)

    2013-02-01

    presented to the emergency department (ED) with severe pain in his left leg and perineum. The patient had a history of bilateral above- the-knee amputations...and had progressively worsened over the last 3 days since his primary care manager discontinued his hydromorphone, reduced his fentanyl patch from 100...other symptoms. His medical history was significant for posttraumatic stress disorder, anxiety, chronic pain, phantom limb pain, insomnia, and depression

  18. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation.

    Science.gov (United States)

    Peters, Eva M J; Liezmann, Christiane; Spatz, Katharina; Daniltchenko, Maria; Joachim, Ricarda; Gimenez-Rivera, Andrey; Hendrix, Sven; Botchkarev, Vladimir A; Brandner, Johanna M; Klapp, Burghard F

    2011-03-01

    Neuroimmune dysregulation characterizes atopic disease, but its nature and clinical impact remain ill-defined. Induced by stress, the neurotrophin nerve growth factor (NGF) may worsen cutaneous inflammation. We therefore studied the role of NGF in the cutaneous stress response in a mouse model for atopic dermatitis-like allergic dermatitis (AlD). Combining several methods, we found that stress increased cutaneous but not serum or hypothalamic NGF in telogen mice. Microarray analysis showed increased mRNAs of inflammatory and growth factors associated with NGF in the skin. In stress-worsened AlD, NGF-neutralizing antibodies markedly reduced epidermal thickening together with NGF, neurotrophin receptor (tyrosine kinase A and p75 neurotrophin receptor), and transforming growth factor-β expression by keratinocytes but did not alter transepidermal water loss. Moreover, NGF expression by mast cells was reduced; this corresponded to reduced cutaneous tumor necrosis factor-α (TNF-α) mRNA levels but not to changes in mast cell degranulation or in the T helper type 1 (Th1)/Th2 cytokine balance. Also, eosinophils expressed TNF receptor type 2, and we observed reduced eosinophil infiltration after treatment with NGF-neutralizing antibodies. We thus conclude that NGF acts as a local stress mediator in perceived stress and allergy and that increased NGF message contributes to worsening of cutaneous inflammation mainly by enhancing epidermal hyperplasia, pro-allergic cytokine induction, and allergy-characteristic cellular infiltration.

  19. Correlation between Asian dust storms and worsening asthma in Western Japan.

    Science.gov (United States)

    Watanabe, Masanari; Yamasaki, Akira; Burioka, Naoto; Kurai, Jun; Yoneda, Kazuhiko; Yoshida, Atsushi; Igishi, Tadashi; Fukuoka, Yasushi; Nakamoto, Masaki; Takeuchi, Hiromi; Suyama, Hisashi; Tatsukawa, Toshiyuki; Chikumi, Hiroki; Matsumoto, Shingo; Sako, Takanori; Hasegawa, Yasuyuki; Okazaki, Ryota; Horasaki, Kazunori; Shimizu, Eiji

    2011-09-01

    Severe wind storms during spring in East Asia, called Asian dust storms (ADS), have been assessed in the past for their effect on health in Asian countries. Our objective was to study the ADS association with asthma symptoms in adult patients in Japan. We designed a telephone survey to assess ADS influence on upper and lower respiratory, ocular and cutaneous symptoms in 98 patients with adult asthma from April to May 2007. Peak expiratory flow (PEF) was also measured from February to May. Worsening lower respiratory symptoms were noted by 22 of 98 patients during ADS in April, when Japanese cedar pollen levels also increased. During ADS in May, however, Japanese cedar and cypress pollen levels were not elevated, 11 patients had worsening of lower respiratory symptoms. None required emergency treatment for the exacerbation. Lower respiratory symptoms worsening most were cough and sputum; this was more common in patients with allergic rhinitis or atopy than in those without (P dust dispersion period, defined as the ADS day plus the next 6 days, versus 92.0 ± 5.3% during the 7-day period before a dust storm. We found that ADS aggravated lower respiratory symptoms in adult patients with asthma, but this influence was mild.

  20. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  1. Hyperglycemia in pediatric head trauma patients: a cross-sectional study Hiperglicemia em pacientes pediátricos com traumatismo craniencefálico: estudo de corte transversal

    Directory of Open Access Journals (Sweden)

    José Roberto Tude Melo

    2009-09-01

    Full Text Available OBJECTIVE: To verify the prevalence of acute hyperglycemia in children with head trauma stratified by the Glasgow coma scale (GCS. METHOD: A prospective cross-sectional study carried out with information from medical records of pediatric patients presenting with head injury in the emergency room of a referral emergency hospital during a one year period. We considered the cut-off value of 150 mg/dL to define hyperglycemia. RESULTS: A total of 340 children were included and 60 (17.6% had admission hyperglycemia. Hyperglycemia was present in 9% of mild head trauma cases; 30.4% of those with moderate head trauma and 49% of severe head trauma. We observed that among children with higher blood glucose levels, 85% had abnormal findings on cranial computed tomography scans. CONCLUSION: Hyperglycemia was more prevalent in patients with severe head trauma (GCS OBJETIVO: Verificar a prevalência de hiperglicemia aguda em crianças vítimas de trauma craniencefálico, de acordo com a escala de coma de Glasgow (GCS. MÉTODO: Estudo prospectivo, de corte transversal realizado por meio do acompanhamento de prontuários médicos de pacientes na faixa etária pediátrica admitidos na unidade de urgência de um hospital de referência vítimas de traumatismo craniencefálico, durante um ano. Consideramos o valor de corte em 150 mg/dL para definição de hiperglicemia. RESULTADOS: 340 crianças foram incluídas no estudo e 60 (17,6% apresentaram hiperglicemia na admissão. Hiperglicemia esteve presente em 9% dos casos de trauma craniano leve, 30,4% daqueles com trauma craniano moderado e em 49% dos pacientes com trauma craniano grave. Verificamos que, entre as crianças com níveis elevados de glicemia, 85% apresentavam alterações radiológicas verificadas na tomografia computadorizada do crânio. CONCLUSÃO: A hiperglicemia foi mais prevalente em pacientes com traumatismo craniano grave (GCS <8, assim como naqueles com alterações identificadas na tomografia

  2. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis.

    Science.gov (United States)

    Au, Sunny C L; Tang, Shu-Min; Rong, Shi-Song; Chen, Li-Jia; Yam, Jason C S

    2015-03-13

    As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to "hyperglycaemia" and "ROP". Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, Phyperglycemia (Standardized mean difference [SMD] = 1.21, Phyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association.

  3. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis

    Science.gov (United States)

    Au, Sunny C. L.; Tang, Shu-Min; Rong, Shi-Song; Chen, Li-Jia; Yam, Jason C. S.

    2015-01-01

    As the role of hyperglycemia in the development of retinopathy of prematurity (ROP) has not been well established, a meta-analysis of the association between hyperglycemia and ROP was conducted. Studies were identified through literature search in MEDLINE and EMBASE up to June 20, 2014 with keywords related to “hyperglycaemia” and “ROP”. Nine eligible studies involving 1939 neonates with 509 cases of ROP were included. Unadjusted analyses showed that hyperglycemia was significantly associated with ROP (Odds ratio [OR] = 4.16, Phyperglycemia (Standardized mean difference [SMD] = 1.21, Phyperglycemia with ROP (adjusted OR 1.08, P = 0.03); and no significant association on mean glucose level with ROP (adjusted OR = 1.08, P = 0.15). Hence, hyperglycemia cannot be definitely considered as a risk factor for ROP, and further studies should adjust for potential confounding factors to clarify this association. PMID:25766465

  4. Hyperglycemia and Oxidative Stress Strengthen the Association Between Myeloperoxidase and Blood Pressure

    NARCIS (Netherlands)

    van der Zwan, L.P.; Scheffer, P.G.; Dekker, J.M.; Stehouwer, C.D.A.; Heine, R.J.; Teerlink, T.

    2010-01-01

    Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure.

  5. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Alireza Boloori

    Full Text Available Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM. Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT.To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications.We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1 immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid, (2 demographic and medical-related risk factors, and (3 inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1 a time-dependent model to analyze the recurrent cases of hyperglycemia and (2 a time-independent model to analyze the first incidence of hyperglycemia.Age (P = 0.018, HDL cholesterol (P = 0.010, and the average trough level of tacrolimus (P<0.0001 are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001, non-White race (P = 0.002, BMI (P = 0.002, HDL cholesterol (P = 0.003, uric acid (P = 0.012, and using steroid (P = 0.007 are the significant risk factors for the recurrent cases of hyperglycemia.This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.

  6. A Structural Model that Explains the Effects of Hyperglycemia on Collagenolysis

    OpenAIRE

    Stultz, Collin M.; Edelman, Elazer R.

    2003-01-01

    Prior investigations into the effects hyperglycemia on collagen degradation have yielded conflicting results. We present a new formalism for understanding the biochemistry of collagenolysis and the effects of hyperglycemia on collagen degradation. The analysis is based on an understanding of environments that affect the conformational stability of collagen. We suggest that collagen can exist in two distinct conformational states—a native state and a vulnerable state. Vulnerable collagen corre...

  7. Risk factors for worsened quality of life in patients on mechanical ventilation. A prospective multicenter study.

    Science.gov (United States)

    Busico, M; Intile, D; Sívori, M; Irastorza, N; Alvarez, A L; Quintana, J; Vazquez, L; Plotnikow, G; Villarejo, F; Desmery, P

    2016-10-01

    To identify risk factors for worsened quality of life (QoL) and activities of daily living (ADL) at 3 and 12 months after discharge from the Intensive Care Unit (ICU) in patients on mechanical ventilation (MV). A prospective, multicentric observational study was made. Three ICUs in Argentina. The study included a total of 84 out of 129 mainly clinical patients admitted between 2011-2012 and requiring over 24hours of MV. No interventions were carried out. Quality of life was assessed with the EQ-5D (version for Argentina), and ADL with the Barthel index. The EQ-5D and Barthel scores were assessed upon admission to the ICU (baseline) and after three months and one year of follow-up. Comorbidities, delirium, ICU acquired weakness (ICUAW), and medication received were daily assessed during ICU stay. The baseline QoL of the global sample showed a median index of [0.831 (IQR25-75% 0.527-0.931)], versus [0.513 (IQR0.245-0.838)] after three months and [0.850 (IQR0.573-1.00)] after one year. Significant differences were observed compared with QoL in the Argentinean general population [mean 0.880 (CI 0.872-0.888), p<0.001; p<0.001; p0.002]. Individual analysis showed that 67% of the patients had worsened their QoL at three months, while 33% had recovered their QoL. In the multivariate analysis, the variables found to be independent predictors of worsened QoL were a hospital stay ≥21 days [OR 12.57 (2.75-57.47)], age ≥50 years [OR 5.61 (1.27-24.83)], previous poor QoL [OR 0.11 (0.02-0.54)] and persistent ICUAW [OR 8.32 (1.22-56.74)]. Similar results were found for the worsening of ADL. Quality of life is altered after critical illness, and its recovery is gradual over time. Age, length of hospital stay, previous QoL and persistent ICUAW seem to be risk factors for worsened QoL. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  8. Hyperglycemia Interacts with Ischemia in a Synergistic Way on Wound Repair and Myofibroblast Differentiation.

    Science.gov (United States)

    Tobalem, Mickaël; Lévigne, Dominik; Modarressi, Ali; Atashi, Fatemeh; Villard, Frederic; Hinz, Boris; Pittet-Cuénod, Brigitte

    2015-07-01

    Hyperglycemia is known to adversely affect the outcome of ischemic insults, but its interaction with ischemia has not been investigated in wound repair yet. In this study, we develop a new animal model allowing to investigate the interaction between hyperglycemia and ischemia during the wound repair process. We focus on myofibroblast differentiation, a key element of wound repair. Ischemia was inflicted in Wistar rats by resection of the femoral to popliteal arteries on the left side, whereas arteries were dissected without resection on the right side. Full-thickness skin wounds (1 cm(2)) were created on both feet. Hyperglycemia was induced by injection of streptozotocin. Normoglycemic animals served as control (n = 23/group). Blood flow, wound closure, and myofibroblast expression were measured. Wound closure was significantly delayed in ischemic compared with nonischemic wounds in all rats. This delay was almost 5-fold exacerbated in hyperglycemic rats compared with normoglycemic rats, while hyperglycemia alone showed only a slight effect on wound repair. Delayed wound repair was associated with impaired wound contraction and myofibroblast differentiation. Our model allows to specifically quantify the effect of hyperglycemia and ischemia alone or in combination on wound repair. We show that hyperglycemia amplifies the inhibitory effect of ischemia on wound repair and myofibroblast expression. Our data reveal for the first time the synergic aspect of this interaction and therefore stress the importance of a strict glycemic control in the management of ischemic wounds.

  9. Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely-low-birth-weight Infants

    Science.gov (United States)

    Lee, Jan Hau; Hornik, Christoph P.; Testoni, Daniela; Laughon, Matthew M.; Cotten, C. Michael; Maldonado, Ramiro S.; Belcastro, Marc R.; Clark, Reese H.; Smith, P. Brian

    2015-01-01

    Objective To determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely-low-birth-weight (ELBW) infants. Study design In this retrospective database study, we included all ELBW infants who were ≤32 weeks gestational age (GA). We excluded infants without any ophthalmology evaluation and who died before 28 days of life. A multivariable model was constructed to determine the association between hyperglycemia, insulin use, and severe ROP. We defined hyperglycemia as blood glucose (BG) >180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG >150 mg/dL and >200 mg/dL was performed. Results 24,548 infants were included; 2547(10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR]=0.88 [95% CI: 0.66–1.17]). Hyperglycemia and insulin use were not associated with severe ROP (OR=1.43 [0.91–2.23]). BG >150 mg/dL and insulin use were associated with severe ROP (OR=1.34 [1.02–1.76]). Conclusions Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP. PMID:26485249

  10. Mild hyperglycemia triggered islet function recovery in streptozotocin-induced insulin-deficient diabetic rats.

    Science.gov (United States)

    Cheng, Yu; Shen, Jing; Ren, Weizheng; Hao, Haojie; Xie, Zongyan; Liu, Jiejie; Mu, Yiming; Han, Weidong

    2017-01-01

    Moderate elevation of glucose level has been shown to effectively promote β-cell replication in various models in vitro and in normal rodents. Here, we aimed to test the effect of moderately elevated glucose on β-cell mass expansion and islet function recovery in diabetic animal models. A single high dose of streptozotocin was given to induce insulin-deficient diabetes in adult male Sprague-Dawley rats. Then, 48 h after streptozotocin injection, newly diabetic rats were randomly divided into three groups: (i) no treatment to maintain hyperglycemia; (ii) daily exogenous long-acting human insulin analog injection that maintained mild hyperglycemia (15 mmol/L insulin analog injection to restore normoglycemia (blood glucose hyperglycemia. Mild hyperglycemia markedly promoted β-cell proliferation, leading to robust β-cell regeneration. Importantly, rats that maintained mild hyperglycemia showed nearly normal glucose-stimulated insulin secretion, glucose disposal and random blood glucose levels, suggesting almost full restoration of the islet function. Normalization of blood glucose levels profoundly blunted β-cell replication, regeneration and islet function recovery observed in mild hyperglycemia. Our research provides a feasible approach to stimulate in situ β-cell regeneration in diabetic rats, offering new perspectives for diabetes therapy. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  11. Acidosis and coma in adult diabetic maintenance dialysis patients with extreme hyperglycemia.

    Science.gov (United States)

    Popli, Subhash; Sun, Yijuan; Tang, Hon-Lok; Kjellstrand, Carl M; Tzamaloukas, Antonios H; Ing, Todd S

    2013-12-01

    Extreme hyperglycemia (serum glucose ≥ 800 mg/dL or 44.4 mmol/L) is infrequently associated with impaired consciousness in patients on maintenance dialysis. The purpose of this study was to determine features of extreme hyperglycemia that bring about coma in dialysis patients who do not have any of the potential conditions, other than hyperglycemia, that can affect the sensorium. We analyzed 24 episodes of extreme dialysis-associated hyperglycemia in men who did not have neurological disease or sepsis. We compared serum parameters related to hyperglycemia between a group of 12 patients (8 on peritoneal dialysis, 4 on hemodialysis) who were alert and oriented (group A) and another group of 12 patients (5 on peritoneal dialysis, 7 on hemodialysis) who displayed varying degrees of impairment of sensorium, ranging from drowsiness to coma (group B). Group B had, in the serum, lower total carbon dioxide (TCO2, 8 ± 4 vs. 20 ± 3 mmol/L, P patients). Stepwise multiple linear regression identified serum TCO2 and AG as the only predictors of impaired sensorium (r (2) = 0.74. P patients on dialysis with extreme hyperglycemia and no neurological or infectious disease. This association suggests that the presence or absence of DKA is usually the primary etiologic factor in the development of impaired sensorium in these patients.

  12. Acute pancreatitis complicating acute hepatitis A virus infection.

    Science.gov (United States)

    El-Sayed, Rokaya; El-Karaksy, Hanaa

    2012-12-01

    Acute pancreatitis complicating acute hepatitis A is very rare especially in children. We report here an 11 year old female patient with picture of acute hepatitis proved to be caused by hepatitis A. One week later patient's condition worsened, she was jaundiced, with persistent vomiting and looked acutely ill and uncomfortable with severe steady abdominal pain mainly in the epigastrium and upper quadrants. Acute pancreatitis was suspected and proved by a clinical picture associated with elevated serum amylase and serum lipase and by MRCP. The patient was managed conservatively with gradual clinical and laboratory improvement, and she was discharged after one week in a good clinical condition. Copyright © 2012 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

  13. Fetal hyperglycemia changes human preadipocyte function in adult life

    DEFF Research Database (Denmark)

    Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

    2017-01-01

    Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... hyperglycemic groups, O-GDM and O-T1DM, and, as a control group, offspring from the background population (O-BP). Subcutaneous fat biopsies were obtained and preadipocyte cell cultures were established from adult male O-GDM (n = 18, age 30.1 ± 2.5 years), O-T1DM (n = 18, age 31.6 ± 2.2 years), and O-BP (n = 16......; age, 31.5 ± 2.7 years) and cultured in vitro. Main Outcome Measures: First, we studied in vivo adipocyte histology. Second, we studied in vitro preadipocyte leptin secretion, gene expression, and LEP DNA methylation. This was studied in combination with in vitro preadipocyte lipogenesis, lipolysis...

  14. Management of hyperglycemia in type 2 diabetes: evidence and uncertainty

    Science.gov (United States)

    2013-01-01

    The panoply of treatment algorithms, periodically released to improve guidance, is one mean to face therapeutic uncertainty in pharmacological management of hyperglycemia in type 2 diabetes, especially after metformin failure. Failure of recent guidelines to give advice on the use of specific antidiabetic drugs in patients with co-morbidity may generate further uncertainty, given the frequent association of type 2 diabetes with common comorbidity, including, although not limited to obesity, cardiovascular disease, impaired renal function, and frailty. The Italian Association of Diabetologists (Associazione Medici Diabetologi, AMD) recognized the need to develop personalized treatment plans for people with type 2 diabetes, taking into account the patients' individual profile (phenotype), with the objective of the safest possible glycemic control. As not every subject with type 2 diabetes benefits from intensive glycemic control, flexible regimens of treatment with diabetes drugs (including insulin) are needed for reaching individualized glycemic goals. Whether personalized diabetology will improve the quality healthcare practice of diabetes management is unknown, but specific research has been launched. PMID:23721170

  15. Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Rabøl, Rasmus; Højberg, Patricia M V; Almdal, Thomas

    2009-01-01

    AIM: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2......DM. PATIENTS AND METHODS: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration...... and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls. RESULTS: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P

  16. Effects of diabetes mellitus vs. in vitro hyperglycemia on select immune cell functions.

    Science.gov (United States)

    Daoud, A K; Tayyar, M A; Fouda, I M; Harfeil, N Abu

    2009-03-01

    Diabetes mellitus (DM), one of the commonest metabolic disorders, can impair the function of cells involved in cellular and/or humoral immunity. This study sought to define potential effects upon cell-mediated immune cells due to an acute hyperglycemic state (in vitro) for comparison against those that might be attributable to a diabetic phenotype itself. Peripheral blood mononuclear cells (PBMC) were isolated from ten diabetic patients (5 with Type I disease and 5 with Type II) and 10 healthy controls. The cells were then challenged with 1 of 3 different mitogens (concanavalin A, phytohemagglutinin, pokeweed mitogen) in the presence of differing glucose concentrations (0, 100, 200, 400, or 800 mg/dl), and proliferative responses assessed. Neutrophils (PMNC) from the blood samples, exposed to the same experimental conditions, were analyzed for respiratory burst activity using nitroblue tetrazolium. The results indicated that there was significant inhibition of the proliferative responses to mitogens among the stimulated PBMC and in respiratory burst activity among the PMNC obtained from the diabetic patients. However, these effects were not affected by either the added presence of increasing amounts of exogenous glucose, the type of diabetes the patients had, the length of time the patient had had the disease, or whether or not the patients had been receiving insulin treatments. In contrast, the PBMC from healthy individuals appeared to display dose-trend decreases in responsiveness to mitogens; interestingly, similar effects on their PMNC were not evident. It was thus concluded that in situ ongoing repeated hyperglycemic states caused changes in cells of the immune system that could have been caused by repeated "continuous" exposures to excess sugar. Further studies are needed to more clearly identify hyperglycemia (sugar)-sensitive targets on/in these cells that could contribute to the appearance of the diabetic immunodeficiency in these types of patients.

  17. Hyperglycemia is a predictor of prognosis in traumatic brain injury: Tertiary intensive care unit study

    Directory of Open Access Journals (Sweden)

    Berna Terzioglu

    2015-01-01

    Full Text Available Background: Hyperglycemia is frequently encountered in critically ill patients and has been shown to contribute to both morbidity and mortality. We aimed to study the predictive role of blood glucose level in clinical outcomes of mechanically ventilated patients with traumatic brain injury during intensive care unit (ICU stay and to explore its relationship with Glasgow coma scale (GCS and acute physiology and chronic health examination (APACHE II scores that are used in the evaluation of ICU patients as predictor. Materials and Methods: A total of 185 patients with craniocerebral trauma who were hospitalized in the ICU were included in the study. Comparisons of mean glucose values (MGVs and APACHE II scores between survivors and nonsurvivors were made with Student′s t-test and chi-square test. Survival analysis was performed with log rank (Mantel-Cox test and Cox regression was used for mortality risk factors analysis. Results: MGVs at the initial, last, and all measurements were significantly higher for nonsurvivors than for survivors. Hazard rate at any given time point for patients with mean glucose value (MGV between 150 and 179 was found to be 3.691 times that of patients with MGV values between 110 and 149. The hazard rate at any given time point for patients with MGV values ≥180 was found to be 6.571 times that of patients with MGV values between 110 and 149. Conclusion: High glucose level is an independent risk factor for mortality in mechanically ventilated ICU patients with traumatic brain injury.

  18. Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits.

    Science.gov (United States)

    Bonthius, Daniel J; Winters, Zachary; Karacay, Bahri; Bousquet, Samantha Larimer; Bonthius, Daniel J

    2015-01-01

    The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS-/- mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS-/- mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS-/- mice and their wild type controls received alcohol (0.0, 2.2, or 4.4mg/g) daily over postnatal days 4-9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS-/- and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS-/- mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS-/- mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS-/- mice, but not in wild type. Thus, homozygous

  19. Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies.

    Science.gov (United States)

    Felson, David T; Niu, Jingbo; Clancy, Margaret; Aliabadi, Piran; Sack, Burton; Guermazi, Ali; Hunter, David J; Amin, Shreyasee; Rogers, Gail; Booth, Sarah L

    2007-01-01

    To confirm reports that 25-hydroxyvitamin D (25[OH]D) deficiency is associated with an increased risk of joint space narrowing or cartilage loss in osteoarthritis (OA). We measured 25(OH)D levels in subjects from 2 longitudinal cohort studies, the Framingham Osteoarthritis Study and the Boston Osteoarthritis of the Knee Study (BOKS). In the first, weight-bearing anteroposterior (AP) and lateral knee radiographs were obtained on subjects in 1993-1994 and again in 2002-2005 (mean interval 9 years); blood was drawn for measurement of vitamin D status in 1996-2000. In the second, subjects with symptomatic knee OA participating in a natural history study had fluoroscopically positioned semiflexed posteroanterior (PA) and lateral radiography of both knees and magnetic resonance imaging (MRI) of the more symptomatic knee performed at baseline and at 15 and 30 months. Blood was drawn at all visits, and the baseline specimen was used when available. In both studies, we defined radiographic worsening based on joint space loss in the tibiofemoral joint on either AP/PA or lateral weight-bearing views, using a semiquantitative scale (worsening defined as increase by > or =1 on a 0-3 scale). In the BOKS, we evaluated cartilage loss semiquantitatively, using the Whole-Organ Magnetic Resonance Imaging Score. In both studies, 25(OH)D levels were measured by radioimmunoassay. Analyses focused on whether vitamin D levels, defined in tertiles or as deficient (25[OH]D vitamin D deficiency were narrow, suggesting that results were not based on insufficient power. In fact, the risk of worsening was slightly, but not significantly, lower in persons with low levels of vitamin D than in persons with higher levels. In the BOKS, vitamin D levels were unrelated to cartilage loss seen on MRI. The findings indicate that vitamin D status is unrelated to the risk of joint space or cartilage loss in knee OA.

  20. Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term.

    Directory of Open Access Journals (Sweden)

    Martin G Frasch

    Full Text Available Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG.Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping <7.00, spectral edge frequency (SEF increased to 23 ± 2 Hz from 3 ± 1 Hz during each FHR deceleration (p<0.001 and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001.The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG during human labour may be a useful adjunct to FHR monitoring.

  1. Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

    Directory of Open Access Journals (Sweden)

    Montserrat Diaz-Abad

    2013-12-01

    Full Text Available X-linked spinobulbar muscular atrophy (Kennedy’s disease affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

  2. Genetic absence of nNOS worsens fetal alcohol effects in mice. I: behavioral deficits.

    Science.gov (United States)

    Karacay, Bahri; Bonthius, Nancy E; Plume, Jeffrey; Bonthius, Daniel J

    2015-02-01

    Alcohol abuse during pregnancy often induces neuropsychological problems in the offspring, including learning disorders, attention deficits, and behavior problems, all of which are prominent components of fetal alcohol spectrum disorders (FASD). However, not all children who were exposed to alcohol in utero are equally affected by it. While some children have major deficits, others are spared. This unequal vulnerability is likely due largely to differences in fetal genetics. Some fetuses appear to have certain genotypes that make them much more prone to FASD. However, to date, no gene has been identified that worsens alcohol-induced brain dysfunction. Nitric oxide (NO) is a gaseous molecule that can protect developing neurons against alcohol-induced death. In the brain, NO is produced by neuronal nitric oxide synthase (nNOS). In this study, we examined whether homozygous mutation of the nNOS gene in mice worsens the behavioral deficits of developmental alcohol exposure. Wild-type and nNOS(-/-) mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests, including open field activity, the Morris water maze, and paired pulse inhibition. For the wild-type mice, alcohol impaired performance only in the water maze. In contrast, for the nNOS(-/-) mice, alcohol impaired performance on all 3 tasks. Furthermore, the nNOS(-/-) mice were substantially more impaired than wild-type mice in their performance on all 3 of the behavioral tests and at both the low (2.2) and high (4.4) doses of alcohol. Targeted disruption of the nNOS gene worsens the behavioral impact of developmental alcohol exposure and allows alcohol-induced learning problems to emerge that are not seen in wild type. This is the first demonstration that a specific genotype can interact with alcohol to worsen functional brain deficits in an animal model of FASD. Copyright © 2015 by the Research Society on Alcoholism.

  3. A 63-Year-Old Woman With Neurofibromatosis Type 1 and Pulmonary Hypertension With Worsening Hypoxemia.

    Science.gov (United States)

    Chaddha, Udit; Puscas, Ioan; Prosper, Ashley; Ganesh, Sivagini; Yaghmour, Bassam

    2017-10-01

    A 63-year-old woman with a history of neurofibromatosis type-1 (NF-1) and pulmonary arterial hypertension (PAH) thought to be secondary to the NF-1 presented with a few weeks of worsening dyspnea on exertion. She took no medications other than sildenafil for her pulmonary hypertension (PH). She denied tobacco, alcohol, and illicit or anorectic drug use. She had previously worked as a waitress. Her mother and her brother had NF-1 but no PH or lung disease. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Hyperglycemia in pregnancy: prevalence, impact, and management challenges

    Directory of Open Access Journals (Sweden)

    Farrar D

    2016-09-01

    Full Text Available Diane Farrar Bradford Institute for Health Research, Maternal and Child Health, Bradford, UK Abstract: Gestational diabetes mellitus (GDM is one of the most common medical conditions in pregnancy, and the prevalence is growing with increasing rates of women of advanced age becoming pregnant and the increasing prevalence of maternal obesity and inactivity. GDM is associated with an increased risk of maternal and infant short- and long-term ill-health. There is a positive linear association between increasing maternal glucose at oral glucose tolerance testing and risk of important perinatal outcomes, including cesarean section, large for gestational age, and infant adiposity. A “step-up” approach, where diet and lifestyle information is provided followed by pharmacological interventions as required to control and reduce hyperglycemia, is effective at reducing the risk of macrosomia, but treatment of GDM will increase demand on health services. There is limited evidence to suggest which identification strategy is best or what thresholds should be used to diagnose GDM or what the effects of different diagnostic strategies have on short- or long-term maternal and offspring outcomes. Trials of interventions in pregnancy aimed at preventing GDM have not demonstrated a benefit; therefore, trials are needed to evaluate interventions aimed at optimizing the health of all women of childbearing age, outside of pregnancy. A consistent, evidence-based, sustained approach to supporting women to live healthily, including the achievement of a normal body mass index before and after pregnancy, is urgently needed. Keywords: gestational diabetes, adverse perinatal outcomes, screening, glucose threshold criteria

  5. Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats.

    Science.gov (United States)

    Fiordaliso, Fabio; Bianchi, Roberto; Staszewsky, Lidia; Cuccovillo, Ivan; Doni, Mirko; Laragione, Teresa; Salio, Monica; Savino, Costanza; Melucci, Silvia; Santangelo, Francesco; Scanziani, Eugenio; Masson, Serge; Ghezzi, Pietro; Latini, Roberto

    2004-11-01

    Diabetes and oxidative stress concur to cardiac myocyte death in various experimental settings. We assessed whether N-acetyl-L-cysteine (NAC), an antioxidant and glutathione precursor, has a protective role in a rat model of streptozotocin (STZ)-induced diabetes and in isolated myocytes exposed to high glucose (HG). Diabetic rats were treated with NAC (0.5 g/kg per day) or vehicle for 3 months. At sacrifice left ventricle (LV) myocyte number and size, collagen deposition and reactive oxygen species (ROS) were measured by quantitative histological methods. Diabetes reduced LV myocyte number by 29% and increased myocyte volume by 20% compared to non-diabetic controls. NAC protected from myocyte loss (+25% vs. untreated diabetics, P < 0.05) and reduced reactive hypertrophy (-16% vs. untreated diabetics, P < 0.05). Perivascular fibrosis was high in diabetic rats (+88% vs. control, P < 0.001) but prevented by NAC. ROS production and fraction of ROS-positive cardiomyocyte nuclei were drastically raised in diabetic rats (2.4- and 5.1-fold vs. control, P < 0.001) and normalized by NAC. In separate experiments, isolated adult rat ventricular myocytes were incubated in a medium containing high concentrations of glucose (HG, 25 mM) +/- 0.01 mM NAC; myocyte survival (Trypan blue exclusion and apoptosis by TUNEL) and glutathione content were evaluated. The number of dead and apoptotic myocytes increased five and 6.7-fold in HG and glutathione decreased by 48% (P < 0.05). NAC normalized cell death and apoptosis and prevented glutathione loss. NAC effectively protects from hyperglycemia-induced myocyte cell death and compensatory hypertrophy through direct scavenging of ROS and replenishment of the intracellular glutathione content.

  6. An Infant With Non-Ketotic Hyperglycemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Danaei

    2016-02-01

    Full Text Available Introduction Glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH represents a disorder characterized by elevated concentrations of glycine in all body tissues, especially in plasma and cerebrospinal fluids (CSF. NKH is caused by deficiency in the glycine cleavage system (GCS. Most glycine encephalopathy cases occur during the neonatal period. The current report presents a case of NKH neonatal intractable seizures. Evaluating a sick neonate who presents with hypotonia, encephalopathy, and seizures is a diagnostic challenge; a high index of suspicion for timely diagnosis and treatment could prevent severe complications. Case Presentation The patient was a four-day-old baby girl in Iran admitted to the hospital due to hypotonia, lethargy and seizures. On the third day after discharge, the baby gradually lost the ability to suck milk and got sleepy and finally suffered from organ jump and seizures. Sepsis and antibiotics phenytoin tests were conducted and in metabolic testing, high level of glycine in blood and urine was reported and the patient was treated with sodium benzoate dextromethorphan and L-carnitine, after the start of the treatment, seizures and neurologic symptoms and alertness of the baby improved. The patient was discharged by continuing treatment after two weeks with seizure control, improved sucking reflexes and grasp. Conclusions Since most of the symptoms of metabolic diseases in newborns are same as the signs of sepsis or other common diseases of this period, and also early diagnosis and treatment of these illnesses, especially in diseases such as hyperglycemia, can be influential in neural function of babies, it calls for serious attention and clinical vision of the doctors to stop mortality caused by such diseases by early consideration of serious complications.

  7. Irreversible Hemichorea–Hemiballism in a Case of Nonketotic Hyperglycemia Presenting as the Initial Manifestation of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Ujjawal Roy

    2011-08-01

    Full Text Available Background: Hemichorea–hemiballism (HCHB is a hyperkinetic movement disorder with features of both chorea and ballism occurring on the same side. Case report: We present a case of HCHB due to nonketotic hyperglycemia (NKH that was the initial presentation of diabetes and was irreversible clinically even after 6 months of optimal blood sugar control. Discussion: Although HCHB due to hyperglycemia is a potentially reversible condition in the majority of patients, prolonged uncontrolled hyperglycemia may cause ischemic insult and persistent symptoms. Hyperglycemia should always be kept in the list of differentials while dealing with patients who are newly diagnosed with HCHB.

  8. Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function?

    Science.gov (United States)

    Avanzini, Giuliano; Depaulis, Antoine; Tassinari, Alberto; de Curtis, Marco

    2013-11-01

    Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions: The possibility of seizure-dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs. Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug-refractory epilepsies. The mechanisms for SE-related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission. The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause-effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process. The results of EE studies challenge the idea of a common seizure-dependent mechanism for epilepsy progression/intellectual deterioration. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  9. The postpartum period of pregnancy worsens brain injury and functional outcome after cerebellar hemorrhage in rats.

    Science.gov (United States)

    Lekic, Tim; Ostrowski, Robert P; Suzuki, Hidenori; Manaenko, Anatol; Rolland, William; Fathali, Nancy; Tang, Jiping; Zhang, John H

    2011-01-01

    Intracerebral hemorrhage (ICH) is one of the most common causes of maternal deaths related to the postpartum period. This is a devastating form of stroke for which there is no available treatment. Although premenopausal females tend to have better outcomes after most forms of brain injury, the effects of pregnancy and child birth lead to wide maternal physiological changes that may predispose the mother to an increased risk for stroke and greater initial injury. Three different doses of collagenase were used to generate models of mild, moderate and severe cerebellar hemorrhage in postpartum female and male control rats. Brain water, blood-brain barrier rupture, hematoma size and neurological evaluations were performed 24 h later. Postpartum female rats had worsened brain water, blood-brain barrier rupture, hematoma size and neurological evaluations compared to their male counterparts. The postpartum state reverses the cytoprotective effects commonly associated with the hormonal neuroprotection of (premenopausal) female gender, and leads to greater initial injury and worsened neurological function after cerebellar hemorrhage. This experimental model can be used for the study of future treatment strategies after postpartum brain hemorrhage, to gain a better understanding of the mechanistic basis for stroke in this important patient subpopulation.

  10. Worsening of coronary spasm during the perioperative period: A case report

    Science.gov (United States)

    Teragawa, Hiroki; Nishioka, Kenji; Fujii, Yuichi; Idei, Naomi; Hata, Takaki; Kurushima, Shuji; Shokawa, Tomoki; Kihara, Yasuki

    2014-01-01

    We present the case of a 65-year-old male with vasospastic angina (VSA) whose condition worsened during the perioperative period. He had been diagnosed with VSA 10 years prior. He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years. At this juncture, he underwent surgery for relapsed maxillary sublingual carcinoma. He had taken two vasodilators one day prior to surgery. Intravenous infusion of nitroglycerin (NTG) was initiated immediately before the surgery and continued the following day. Instead of stopping NTG, a dermal isosorbide dinitrate tape was applied on post-operative day 1. Two days later, a complete atrioventricular block with pulseless electrical activity appeared. After cardiopulmonary resuscitation, emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries. Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm. During the perioperative period, several factors can trigger coronary vasospasm, including the discontinuation of vasodilators. Thus, surgeons, anesthetists, and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA. PMID:25068030

  11. Cruel to Be Kind: Factors Underlying Altruistic Efforts to Worsen Another Person's Mood.

    Science.gov (United States)

    López-Pérez, Belén; Howells, Laura; Gummerum, Michaela

    2017-07-01

    When aiming to improve another person's long-term well-being, people may choose to induce a negative emotion in that person in the short term. We labeled this form of agent-target interpersonal emotion regulation altruistic affect worsening and hypothesized that it may happen when three conditions are met: (a) The agent experiences empathic concern for the target of the affect-worsening process, (b) the negative emotion to be induced helps the target achieve a goal (e.g., anger for confrontation or fear for avoidance), and (c) there is no benefit for the agent. This hypothesis was tested by manipulating perspective-taking instructions and the goal to be achieved while participants ( N = 140) played a computer-based video game. Participants following other-oriented perspective-taking instructions, compared with those following objective perspective-taking instructions, decided to induce more anger in a supposed fellow participant who was working to achieve a confrontation goal and to induce more fear in a supposed fellow participant who was working to achieve an avoidance goal.

  12. Does mandatory postgraduate clinical training worsen geographic distribution of dentists in Japan?

    Science.gov (United States)

    Hirata, SoIchiro; Okawa, Yoshikazu; Sugito, Hiroki; Mataki, Shiro; Sakayori, Takaharu; Maki, Yoshinobu; Ishii, Takuo

    2013-01-01

    Postgraduate clinical training for dentists has been mandatory in Japan since 2006. Hirata et al. reported that the geographic distribution of postgraduate dental trainees by prefecture in 2006 was worse than that of practicing dentists. This suggests that the postgraduate clinical training system could intensify the problem of distribution of dentists. In this study, therefore, we reviewed the geographic distribution of postgraduate dental trainees and practicing dentists between 2006 and 2010 in detail by city, ward, town and village by using the Lorenz curve and Gini coefficient. The results showed that while there was no significant worsening of geographic distribution of postgraduate dental trainees, the distribution of practicing dentists continued to deteriorate. A number of reasons may explain these findings: the clinical training system is based on a one-year employment contract, and dentists subsequently relocate as driven by the market; and geographic distribution among cities, towns and villages has worsened as a result of the merger of municipalities. The geographic distribution of practicing dentists is expected to deteriorate further if the number of dentists takes a downward turn in the future. Therefore, it is necessary to continuously review the distribution of postgraduate dental trainees.

  13. Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide

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    Wei Li

    2016-01-01

    Full Text Available Diabetes mellitus (DM and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ- treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT, an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT- related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide.

  14. Neonatal hyperglycemia inhibits angiogenesis and induces inflammation and neuronal degeneration in the retina.

    Directory of Open Access Journals (Sweden)

    Elsa Kermorvant-Duchemin

    Full Text Available Recent evidence suggests that transient hyperglycemia in extremely low birth weight infants is strongly associated with the occurrence of retinopathy of prematurity (ROP. We propose a new model of Neonatal Hyperglycemia-induced Retinopathy (NHIR that mimics many aspects of retinopathy of prematurity. Hyperglycemia was induced in newborn rat pups by injection of streptozocine (STZ at post natal day one (P1. At various time points, animals were assessed for vascular abnormalities, neuronal cell death and accumulation and activation of microglial cells. We here report that streptozotocin induced a rapid and sustained increase of glycemia from P2/3 to P6 without affecting rat pups gain weight or necessitating insulin treatment. Retinal vascular area was significantly reduced in P6 hyperglycemic animals compared to control animals. Hyperglycemia was associated with (i CCL2 chemokine induction at P6, (ii a significant recruitment of inflammatory macrophages and an increase in total number of Iba+ macrophages/microglia cells in the inner nuclear layer (INL, and (iii excessive apoptosis in the INL. NHIR thereby reproduces several aspects of ischemic retinopathies, including ROP and diabetic retinopathies, and might be a useful model to decipher hyperglycemia-induced cellular and molecular mechanisms in the small rodent.

  15. Admission Hyperglycemia an Independent Predictor of Outcome in ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... conducted in south India; hence, we intended to do this study. Methods: A total of 198 patients with acute ischemic stroke were included in a hospital-based longitudinal study to identify the independent factors (demographic, clinical, and biochemical parameters) associated with poor outcome (functional ...

  16. Acute heart failure: acute cardiorenal syndrome and role of aggressive decongestion.

    Science.gov (United States)

    Hanna, Elias B; Hanna Deschamps, Eliana

    2014-12-01

    Congestion and acute renal dysfunction are at the center of acute heart failure (HF) syndromes. Acute cardiorenal syndrome, which refers to worsening of renal function in a patient with acute HF syndrome, is partly related to venous congestion and high renal afterload. Aggressive decongestion improves renal and myocardial flow and ventricular loading conditions, potentially resulting in reduced HF progression, rehospitalization, and mortality. High-dose diuretic therapy remains the mainstay therapy. Ultrafiltration and inotropic therapy are useful in the subgroup of patients with a low-output state and diuretic resistance. © 2014 Wiley Periodicals, Inc.

  17. Familial mild hyperglycemia associated with a novel ABCC8-V84I mutation within three generations

    DEFF Research Database (Denmark)

    Gonsorcikova, Lucie; Vaxillaire, Martine; Pruhova, Stepanka

    2011-01-01

    We present a unique case of a 19-year-old man with a positive family history of persistent mild hyperglycemia and a novel V84I mutation in ABCC8. The proband was initially detected to have fasting hyperglycemia (ranging 6.1-6.4 mmol/L) at the age of 12 years. Increased fasting blood glucose...... of the young genes (MODY1-4 and 6), we identified a novel ABCC8 V84I mutation, which segregated with autosomal dominant transmission of mild hyperglycemia within three generations. This mutation that is located in a conserved area of transmembrane domain TMD0 seems to be a rare cause of clinical phenotype...

  18. Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells.

    Science.gov (United States)

    Ortega-Camarillo, C; Guzmán-Grenfell, A M; García-Macedo, R; Rosales-Torres, A M; Avalos-Rodríguez, A; Durán-Reyes, G; Medina-Navarro, R; Cruz, M; Díaz-Flores, M; Kumate, J

    2006-01-01

    The mechanisms related to hyperglycemia-induced pancreatic beta-cell apoptosis are poorly defined. Rat insulin-producing cells (RINm5F) cultured in high glucose concentrations (30 mM) showed increased apoptosis and protein p53 translocation to mitochondria. In addition, hyperglycemia induced both the disruption of mitochondrial membrane potential (Delta psi (m)), and an increase in reactive oxygen species (ROS), as shown by fluorescence changes of JC-1 and dichlorodihydrofluorescein-diacetate (DCDHF-DA), respectively. The increased intracellular ROS by high glucose exposure was blunted by mitochondrial-function and NADPH-oxidase inhibitors. We postulate that the concomitant mobilization of p53 protein to the mitochondria and the subsequent changes on the Delta psi (m), lead to an important pancreatic beta-cell apoptosis mechanism induced by oxidative stress caused by hyperglycemia.

  19. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients

    Science.gov (United States)

    Boloori, Alireza; Saghafian, Soroush; Chakkera, Harini A.; Cook, Curtiss B.

    2015-01-01

    Background Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT). Objective To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications). Methods We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia. Results Age (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (Phyperglycemia, while age (Phyperglycemia. Discussion This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature. PMID:26551468

  20. Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants.

    Science.gov (United States)

    Lee, Jan Hau; Hornik, Christoph P; Testoni, Daniela; Laughon, Matthew M; Cotten, C Michael; Maldonado, Ramiro S; Belcastro, Marc R; Clark, Reese H; Smith, P Brian

    2016-03-01

    This study aims to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. In this retrospective database study, we included all ELBW infants who were ≤ 32 weeks gestational age (GA). We excluded infants without any ophthalmology evaluation and infants who died before 28 days of life. A multivariable model was constructed to determine the association between hyperglycemia, insulin use, and severe ROP. We defined hyperglycemia as blood glucose (BG) > 180 mg/dL. Covariates were GA, small for GA status, discharge year, sex, Apgar score at 5 minutes, mechanical ventilation, oxygen use, bacteremia, and postnatal steroid exposure. We defined severe ROP as ROP requiring bevacizumab, cryotherapy, laser therapy, or vitrectomy. Sensitivity analysis using BG > 150 mg/dL and > 200 mg/dL was performed. A total of 24,548 infants were included; 2,547 (10%) had severe ROP. Hyperglycemia alone was not associated with severe ROP (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.66-1.17). Hyperglycemia and insulin use were not associated with severe ROP (OR, 1.43; 95% CI, 0.91-2.23). BG > 150 mg/dL and insulin use were associated with severe ROP (OR, 1.34; 95% CI, 1.02-1.76). Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, we did observe a possible trend between the use of insulin and severe ROP. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice

    Science.gov (United States)

    Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; MacDougall, Mary; Abboud-Werner, Sherry

    2012-01-01

    Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita −/− mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita −/− and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita −/− mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita −/− teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia

  2. Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia.

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    Junhui Li

    Full Text Available BACKGROUND: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion. METHODOLOGY/PRINCIPAL FINDINGS: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5, Myelin P0 protein (MPP, NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2 were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively. The integrated optical density (IOD of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019, while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively. The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000. CONCLUSIONS/SIGNIFICANCE: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

  3. β3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia.

    Science.gov (United States)

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Gentile, Carmine; Fry, Natasha A; Hamilton, Elisha J; Hawkins, Clare L; Figtree, Gemma A

    2016-02-19

    Perturbed balance between NO and O2 (•-). (ie, NO/redox imbalance) is central in the pathobiology of diabetes-induced vascular dysfunction. We examined whether stimulation of β3 adrenergic receptors (β3 ARs), coupled to endothelial nitric oxide synthase (eNOS) activation, would re-establish NO/redox balance, relieve oxidative inhibition of the membrane proteins eNOS and Na(+)-K(+) (NK) pump, and improve vascular function in a new animal model of hyperglycemia. We established hyperglycemia in male White New Zealand rabbits by infusion of S961, a competitive high-affinity peptide inhibitor of the insulin receptor. Hyperglycemia impaired endothelium-dependent vasorelaxation by "uncoupling" of eNOS via glutathionylation (eNOS-GSS) that was dependent on NADPH oxidase activity. Accordingly, NO levels were lower while O2 (•-) levels were higher in hyperglycemic rabbits. Infusion of the β3 AR agonist CL316243 (CL) decreased eNOS-GSS, reduced O2 (•-), restored NO levels, and improved endothelium-dependent relaxation. CL decreased hyperglycemia-induced NADPH oxidase activation as suggested by co-immunoprecipitation experiments, and it increased eNOS co-immunoprecipitation with glutaredoxin-1, which may reflect promotion of eNOS de-glutathionylation by CL. Moreover, CL reversed hyperglycemia-induced glutathionylation of the β1 NK pump subunit that causes NK pump inhibition, and improved K(+)-induced vasorelaxation that reflects enhancement in NK pump activity. Lastly, eNOS-GSS was higher in vessels of diabetic patients and was reduced by CL, suggesting potential significance of the experimental findings in human diabetes. β3 AR activation restored NO/redox balance and improved endothelial function in hyperglycemia. β3 AR agonists may confer protection against diabetes-induced vascular dysfunction. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Worsening disparities in HPV vaccine utilization among 19-26 year old women.

    Science.gov (United States)

    Dempsey, Amanda; Cohn, Lisa; Dalton, Vanessa; Ruffin, Mack

    2011-01-10

    We evaluated the characteristics associated with uptake of HPV vaccine by 19-26 year old women seen in primary care university-based clinics. Of the 11,545 women analyzed only 18% had initiated the 3-dose vaccine series. Series completion among the sample overall was only 10% in the 30 month study period. Decreased series initiation was associated with older age, public insurance, white race and non-family medicine specialty. Decreased series completion was associated with public insurance and African American race. Utilization disparities by race and insurance worsened over time suggesting that the highest risk populations of women were not getting vaccinated. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Weather conditions may worsen symptoms in rheumatoid arthritis patients: the possible effect of temperature.

    Science.gov (United States)

    Abasolo, Lydia; Tobías, Aurelio; Leon, Leticia; Carmona, Loreto; Fernandez-Rueda, Jose Luis; Rodriguez, Ana Belen; Fernandez-Gutierrez, Benjamin; Jover, Juan Angel

    2013-01-01

    Patients with rheumatoid arthritis (RA) complain that weather conditions aggravate their symptoms. We investigated the short-term effects of weather conditions on worsening of RA and determined possible seasonal fluctuations. We conducted a case-crossover study in Madrid, Spain. Daily cases of RA flares were collected from the emergency room of a tertiary level hospital between 2004 and 2007. 245 RA patients who visited the emergency room 306 times due to RA related complaints as the main diagnostic reason were included in the study. Patients from 50 to 65 years old were 16% more likely to present a flare with lower mean temperatures. Our results support the belief that weather influences rheumatic pain in middle aged patients. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  6. Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit : a randomized pilot study

    NARCIS (Netherlands)

    Sulter, Geert; Elting, Jan Willem; Langedijk, Marc; Maurits, Natasha M; De Keyser, Jacques

    2003-01-01

    BACKGROUND AND PURPOSE: Pathophysiological considerations and observational studies indicate that elevated body temperature, hypoxia, hypotension, and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome. METHODS: Both units were organized with the

  7. Does Mood Disorder Questionnaire identify sub-threshold bipolarity? Evidence studying worsening of quality of life.

    Science.gov (United States)

    Carta, Mauro Giovanni; Norcini-Pala, Andrea; Moro, Maria Francesca; Balestrieri, Matteo; Caraci, Filippo; Dell'Osso, Liliana; Sciascio, Guido Di; Faravelli, Carlo; Hardoy, Maria Carolina; Aguglia, Eugenio; Roncone, Rita; Nardi, Antonio Egidio; Drago, Filippo

    2015-09-01

    It is debated whether the Mood Disorder Questionnaire (MDQ) can generate false positives by screening other disorders as bipolar, or identify sub-threshold bipolarity. The aim is to verify if Quality of Life (QoL) impairment in MQD positives in the community is due to MDQ positivity itself, or to psychiatric diagnosis associated with MDQ positivity (supporting the former hypothesis). Community survey. Sample randomized after stratification of the adult population in the records of seven Italian regions. MDQ; Short Form Health Survey (SF-12); semi-structured clinical interview carried out by clinicians. Positives at MDQ show worsening QoL with an attributable burden of 2.8 ± 1.8 lower than in MDD (5.6 ± 3.6, p < 0.001) or Eating Disorders (4.4 ± 6.6, p < 0.03) and similar to Panic Disorder (2.9 ± 0.9, p = 0.44). The burden is lower in the middle-aged (25-59 years) than in the young (18-24) (4.65 ± 4.5 vs 2.58 ± 2.0, p=0.007) or in the elderly (≥60) (4.12 ± 3.2; p = 0.024). In the elderly the burden is independent from comorbid psychiatric disorders. This is a preliminary study based on one survey not designed to test this specific hypothesis, thus its results have a heuristic value only. The worsening of QoL due to positivity at MDQ is largely independent from comorbid conditions, supporting the hypothesis that MDQ positivity identifies a specific area of suffering that is "subthreshold" to the psychiatric diagnosis, and relevant for public health. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice

    Directory of Open Access Journals (Sweden)

    Jones Jessica E

    2008-07-01

    Full Text Available Abstract Background Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection. Methods BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain, and analyzed 3 and 10 days later (d3, d10. These time points are the peak and resolution (respectively of influenza infection. Results Inflammatory cell influx into the bronchoalveolar lavage (BALF, inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice. Conclusion Smoke induced inflammation does not protect against influenza infection. In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens

  9. Late Controlled Type 2 Diabetes Mellitus with Severe Acute Systemic Infection

    Directory of Open Access Journals (Sweden)

    Cristea Sorina Alina

    2017-05-01

    Full Text Available Background: The last International Diabetes Federation statement showed that in 2015, there were 415 million people diagnosed with diabetes and the expectation for 2040 is around 642 million people all over the world. Diabetes Mellitus is a disease associated with major negative consequences due to its acute and chronic complications with chronic hyperglycemia playing a major role.

  10. Diabetic Hyperglycemia: Link to Impaired Glucose Transport in Pancreatic β Cells

    Science.gov (United States)

    Unger, Roger H.

    1991-03-01

    Glucose uptake into pancreatic β cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia. In both autoimmune and nonautoimmune diabetes, this glucose transport is reduced as a consequence of down-regulation of the normal β-cell transporter. In autoimmune diabetes, circulating immunoglobulins can further impair this glucose transport by inhibiting functionally intact transporters. Insights into mechanisms of the unresponsiveness of β cells to hyperglycemia may improve the management and prevention of diabetes.

  11. Clinical and epidemiological study of stress hyperglycemia among medical intensive care unit patients in Central India

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    Jitendra Sharma

    2017-01-01

    Full Text Available Background: Stress hyperglycemia is common in patients presenting at the emergency medical ward and is associated with poor prognosis and increased risk of mortality. Aims and Objective: To study and determine the prevalence and factors associated with stress hyperglycemia. Materials and Methods: A cross-sectional observational study was performed on 536 nondiabetic patients presented to the Intensive Care Unit (ICU at Gandhi Medical College and allied Hamidia Hospital, Bhopal, between March 31, 2015, and May 28, 2015. A detailed history including demographic profile, presence of chronic disease, history of hospitalization and ICU admission, surgical status, and major reason for ICU admission (i.e., predominant diagnostic category was collected. Hematological and other parameters based on profile of study population were also analyzed. Results: Out of 536 patients, 109 (20.33% had stress hyperglycemia. Out of 109 patients with stress hyperglycemia, 87 (16.23% patients had glycated hemoglobin (HbA1c <5.7% and 22 (4.10% patients had HbA1c between 5.7% and 6.4%. Mean age of the study population was 40.27 ± 1.44 years, with male dominance. Mean random blood glucose level was 181.46 ± 3.80 mg/dl. Frequency of stress hyperglycemia was 24.13% in stroke, 19.54% in multiple organ dysfunction syndrome (MODS, 17.24% in chronic kidney disease (CKD, 12.64% in central nervous system (CNS infection, 8.05% in chronic liver disease (CLD, and 8.05% in seizure patients. Association between stroke and stress hyperglycemia was significant (P = 0.036. Association between hospital stay more than 7 days and stress hyperglycemia was significant in stroke patients (P = 0.0029, CKD patients (P = 0.0036, CLD (P = 0.0099, and MODS patients (P = 0.0328. Conclusions: The factors associated with stress hyperglycemia were stroke, MODS, CKD, CNS infection, CLD, seizure patients, with prolonged hospital stay and expected proportion.

  12. The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study.

    Science.gov (United States)

    Glass, N A; Torner, J C; Frey Law, L A; Wang, K; Yang, T; Nevitt, M C; Felson, D T; Lewis, C E; Segal, N A

    2013-09-01

    To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  13. Hyperglycemia induces abnormalities of gastric myoelectrical activity in patients with type I diabetes mellitus

    NARCIS (Netherlands)

    Jebbink, R. J.; Samsom, M.; Bruijs, P. P.; Bravenboer, B.; Akkermans, L. M.; vanBerge-Henegouwen, G. P.; Smout, A. J.

    1994-01-01

    BACKGROUND/AIMS: Blood glucose concentration has been shown to be an important factor in gastric motility. However, the effect of hyperglycemia on gastric myoelectrical activity has not yet been studied in patients with diabetes. METHODS: Surface electrogastrography was performed in eight patients

  14. Increased intrinsic mitochondrial respiratory capacity in skeletal muscle from rats with streptozotocin-induced hyperglycemia

    DEFF Research Database (Denmark)

    Larsen, Steen; Scheede-Bergdahl, Celena; Whitesell, Thomas

    2015-01-01

    the groups when evaluating the more physiol. complex I and II linked OXPHOS capacity. These findings indicate that chronic hyperglycemia results in an elevated intrinsic mitochondrial respiratory capacity in both soleus and, at varying degree, plantaris muscle, findings that are consistent with human T1DM...

  15. Dietary hyperglycemia, glycemic index and age-related metabolic retinal diseases

    Science.gov (United States)

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during ...

  16. Parental history of diabetes modifies the association between abdominal adiposity and hyperglycemia

    NARCIS (Netherlands)

    van Dam, R M; Boer, J M; Feskens, E.J.; Seidell, J C

    OBJECTIVE: To examine whether the association between abdominal obesity and hyperglycemia differs according to the presence of a parental history of diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 3,068 men and women, aged 20-65 years, without known diabetes who were

  17. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

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    Cynthia Villarreal-Garza

    2012-01-01

    Full Text Available Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC. Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS. A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels.

  18. Effect of Hyperglycemia on Gene Expression during Early Organogenesis in Mice

    NARCIS (Netherlands)

    Zhao, J.; Hakvoort, T.B.M.; Willemsen, A.M.; Jongejan, A.; Sokolovic, M.; Bradley, E.J.; de Boer, V.C.J.; Baas, F.; van Kampen, A.H.C.; Lamers, W.H.

    2016-01-01

    BACKGROUND: Cardiovascular and neural malformations are common sequels of diabetic pregnancies, but the underlying molecular mechanisms remain unknown. We hypothesized that maternal hyperglycemia would affect the embryos most shortly after the glucose-sensitive time window at embryonic day (ED) 7.5

  19. Hyperglycemia prevents the suppressive effect of hyperinsulinemia on plasma adiponectin levels in healthy humans

    NARCIS (Netherlands)

    Blümer, Regje M. E.; van der Crabben, Saskia N.; Stegenga, Michiel E.; Tanck, Michael W.; Ackermans, Mariette T.; Endert, Erik; van der Poll, Tom; Sauerwein, Hans P.

    2008-01-01

    Adiponectin is a fat-derived hormone with insulin-sensitizing properties. In patients with type 2 diabetes plasma adiponectin levels are decreased. Since these patients are characterized by high plasma insulin and glucose concentrations, hyperinsulinemia and hyperglycemia could be responsible for

  20. Hyperglycemia in rodent models of type 2 diabetes requires insulin-resistant alpha cells.

    Science.gov (United States)

    Lee, Young; Berglund, Eric D; Yu, Xinxin; Wang, May-Yun; Evans, Matthew R; Scherer, Philipp E; Holland, William L; Charron, Maureen J; Roth, Michael G; Unger, Roger H

    2014-09-09

    To determine the role of glucagon action in diet-induced and genetic type 2 diabetes (T2D), we studied high-fat-diet-induced obese (DIO) and leptin receptor-defective (LepR(-/-)) rodents with and without glucagon receptors (GcgRs). DIO and LepR(-/-),GcgR(+/+) mice both developed hyperinsulinemia, increased liver sterol response element binding protein 1c, and obesity. DIO GcgR(+/+) mice developed mild T2D, whereas LepR(-/-),GcgR(+/+) mice developed severe T2D. High-fat-fed (HFF) glucagon receptor-null mice did not develop hyperinsulinemia, increased liver sterol response element binding protein 1c mRNA, or obesity. Insulin treatment of HFF GcgR(-/-) to simulate HFF-induced hyperinsulinemia caused obesity and mild T2D. LepR(-/-),GcgR(-/-) did not develop hyperinsulinemia or hyperglycemia. Adenoviral delivery of GcgR to GcgR(-/-),LepR(-/-) mice caused the severe hyperinsulinemia and hyperglycemia of LepR(-/-) mice to appear. Spontaneous disappearance of the GcgR transgene abolished the hyperinsulinemia and hyperglycemia. In conclusion, T2D hyperglycemia requires unsuppressible hyperglucagonemia from insulin-resistant α cells and is prevented by glucagon suppression or blockade.

  1. Low-grade inflammation in young adults exposed to intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Clausen, Tine Dalsgaard; Mathiesen, Elisabeth R

    2012-01-01

    AIM: To investigate associations between fetal exposure to intrauterine hyperglycemia and plasma concentrations of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in adult offspring. METHOD: We studied 597 offspring, aged 18-27years, from four different groups concerning exp...

  2. Levels of the inflammation marker YKL-40 in young adults exposed to intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Dejgaard, Thomas F; Clausen, Tine D

    2016-01-01

    Plasma levels of the inflammatory marker YKL-40 were investigated in 597 adult offspring born to women with and without diabetes during pregnancy. No association between fetal exposure to maternal hyperglycemia and levels of YKL-40 was found. However, female sex and increasing BMI in the offsprin...

  3. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

    Directory of Open Access Journals (Sweden)

    Ashkan Javid

    Full Text Available Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

  4. FASTING VERSUS POSTPRANDIAL HYPERGLYCEMIA AS A TREATMENT TARGET TO LOWER ELEVATED HEMOGLOBIN A1C.

    Science.gov (United States)

    Shaefer, Charles; Reid, Timothy; Vlajnic, Aleksandra; Zhou, Rong; DiGenio, Andres

    2015-12-01

    Postprandial hyperglycemia (PPHG) may need addressing when glycemic control cannot be maintained in patients with type 2 diabetes mellitus. We investigated whether glycated hemoglobin A1c (A1c) levels ≥7.0% can indicate postprandial defects warranting prandial therapy after optimized basal insulin therapy. From 6 clinical trials of insulin glargine treatment, data were pooled from 496 patients with A1c ≥7.0% after 24 weeks. Patient characteristics and clinical outcomes were summarized according to fasting plasma glucose (FPG) target achievement (postprandial blood glucose (PPBG) levels, and PPBG increments (ΔPPBG). Basal and postprandial contributions to hyperglycemia were determined. After 24 weeks of insulin glargine titration, A1c change from baseline was greater in patients with FPG blood glucose postprandial contributions to hyperglycemia increased (>60% regardless of PPBG). Patients with high FPG had lower, but substantial, relative postprandial contributions versus patients achieving FPG target. A similar pattern was observed according to whether patients had a ΔPPBG ≥50 mg/dL after any meal. After optimized basal insulin therapy, elevated A1c is the most effective indicator of residual PPHG, regardless of existent FPG or PPBG. When confronted with an uncontrolled A1c after reasonable titration of basal insulin, clinicians should be aware of probable postprandial contributions to hyperglycemia and consider prandial therapy.

  5. Effect of Hyperglycemia on the Excretory Ducts of the Submandibular Gland (Histologic Study

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    Hanna Ersteniuk

    2016-11-01

    Conclusions. Morphological changes in different subdivisions of the intralobular duct are of dystrophic nature and can be histologically detected since the 28th day of the experiment; they depend on the duration of hyperglycemia and are accompanied by a dynamic decrease in epithelial cell height.

  6. Bromocriptine-Induced Hyperglycemia in Nonobese Diabetic Mice: Kinetics and Mechanisms of Action

    Science.gov (United States)

    Durant, Sylvie; Coulaud, Josiane; Homo-Delarche, Francoise

    2007-01-01

    The effects of bromocriptine (10 mg/kg), known to inhibit prolactin secretion and lower autoimmune processes, were studied on glucose homeostasis in non-fasted non-obese diabetic mice, a spontaneous model of type 1 diabetes. Hyperglycemia was observed 120 and 240 min after i.p. but not s.c. injection. Bromocriptine administration i.p. led to rapid and marked hyperglycemia characterized by sexual dimorphism with males having higher glycemia than females. Bromocriptine induced a rapid but transient decrease in insulinemia in males only and biphasic increases in glucagon levels and a sustained stimulatory effect on circulating corticosterone in both sexes. Bromocriptine-induced hyperglycemia involved D2-dopaminergic receptors, as demonstrated by the inhibitory effect of the D2-dopamine antagonist, metoclopramide (10 mg/kg). Simultaneous injection of bromocriptine and metoclopramide also blocked the rise in blood corticosterone. In conclusion, by inducing hyperglycemia, i.p. bromocriptine administration to prediabetic autoimmune mice may counteract its beneficial anti-immunostimulatory effects. PMID:18084676

  7. Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review

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    Anna Fournier

    2017-05-01

    Full Text Available Incidence of progressive multifocal leukoencephalopathy (PML in HIV-infected patients has declined in the combined antiretroviral therapy (cART era although a growing number of acquired immunodeficiency syndrome (AIDS-related PML-immune reconstitution inflammatory syndromes (PML-IRIS have been published during the same period. Therapeutic management of PML-IRIS is not consensual and mainly relies on corticosteroids. Our main aim was, in addition to provide a thoughtful analysis of published PML-IRIS cases, to assess the benefit of corticosteroids in the management of PML-IRIS, focusing on confirmed cases. We performed a literature review of the 46 confirmed cases of PML-IRIS cases occurring in HIV-infected patients from 1998 to September 2016 (21 unmasking and 25 paradoxical PML-IRIS. AIDS-related PML-IRIS patients were mostly men (sex ratio 4/1 with a median age of 40.5 years (range 12–66. Median CD4 T cell count before cART and at PML-IRIS onset was 45/μl (0–301 and 101/μl (20–610, respectively. After cART initiation, PML-IRIS occurred within a median timescale of 38 days (18–120. Clinical signs were motor deficits (69%, speech disorders (36%, cognitive disorders (33%, cerebellar ataxia (28%, and visual disturbances (23%. Brain MRI revealed hyperintense areas on T2-weighted sequences and FLAIR images (76% and suggestive contrast enhancement (87%. PCR for John Cunningham virus (JCV in cerebrospinal fluid (CSF was positive in only 84% of cases; however, when performed, brain biopsy confirmed diagnosis of PML in 90% of cases and demonstrated histological signs of IRIS in 95% of cases. Clinical worsening related to PML-IRIS and leading to death was observed in 28% of cases. Corticosteroids were prescribed in 63% of cases and maraviroc in one case. Statistical analysis failed to demonstrate significant benefit from steroid treatment, despite spectacular improvement in certain cases. Diagnosis of PML-IRIS should be considered in HIV

  8. Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review.

    Science.gov (United States)

    Fournier, Anna; Martin-Blondel, Guillaume; Lechapt-Zalcman, Emmanuèle; Dina, Julia; Kazemi, Apolline; Verdon, Renaud; Mortier, Emmanuel; de La Blanchardière, Arnaud

    2017-01-01

    Incidence of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients has declined in the combined antiretroviral therapy (cART) era although a growing number of acquired immunodeficiency syndrome (AIDS)-related PML-immune reconstitution inflammatory syndromes (PML-IRIS) have been published during the same period. Therapeutic management of PML-IRIS is not consensual and mainly relies on corticosteroids. Our main aim was, in addition to provide a thoughtful analysis of published PML-IRIS cases, to assess the benefit of corticosteroids in the management of PML-IRIS, focusing on confirmed cases. We performed a literature review of the 46 confirmed cases of PML-IRIS cases occurring in HIV-infected patients from 1998 to September 2016 (21 unmasking and 25 paradoxical PML-IRIS). AIDS-related PML-IRIS patients were mostly men (sex ratio 4/1) with a median age of 40.5 years (range 12-66). Median CD4 T cell count before cART and at PML-IRIS onset was 45/μl (0-301) and 101/μl (20-610), respectively. After cART initiation, PML-IRIS occurred within a median timescale of 38 days (18-120). Clinical signs were motor deficits (69%), speech disorders (36%), cognitive disorders (33%), cerebellar ataxia (28%), and visual disturbances (23%). Brain MRI revealed hyperintense areas on T2-weighted sequences and FLAIR images (76%) and suggestive contrast enhancement (87%). PCR for John Cunningham virus (JCV) in cerebrospinal fluid (CSF) was positive in only 84% of cases; however, when performed, brain biopsy confirmed diagnosis of PML in 90% of cases and demonstrated histological signs of IRIS in 95% of cases. Clinical worsening related to PML-IRIS and leading to death was observed in 28% of cases. Corticosteroids were prescribed in 63% of cases and maraviroc in one case. Statistical analysis failed to demonstrate significant benefit from steroid treatment, despite spectacular improvement in certain cases. Diagnosis of PML-IRIS should be considered in HIV

  9. Transient Hyperglycemia in Patients With Tuberculosis in Tanzania: Implications for Diabetes Screening Algorithms.

    Science.gov (United States)

    Boillat-Blanco, Noémie; Ramaiya, Kaushik L; Mganga, Maliwasa; Minja, Lilian T; Bovet, Pascal; Schindler, Christian; Von Eckardstein, Arnold; Gagneux, Sebastien; Daubenberger, Claudia; Reither, Klaus; Probst-Hensch, Nicole

    2016-04-01

    Diabetes mellitus (DM) increases tuberculosis risk while tuberculosis, as an infectious disease, leads to hyperglycemia. We compared hyperglycemia screening strategies in controls and patients with tuberculosis in Dar es Salaam, Tanzania. Consecutive adults with tuberculosis and sex- and age-matched volunteers were included in a case-control study between July 2012 and June 2014. All underwent DM screening tests (fasting capillary glucose [FCG] level, 2-hour CG [2-hCG] level, and glycated hemoglobin A1c [HbA1c] level) at enrollment, and cases were tested again after receipt of tuberculosis treatment. Association of tuberculosis and its outcome with hyperglycemia was assessed using logistic regression analysis adjusted for sex, age, body mass index, human immunodeficiency virus infection status, and socioeconomic status. Patients with tuberculosis and newly diagnosed DM were not treated for hyperglycemia. At enrollment, DM prevalence was significantly higher among patients with tuberculosis (n = 539; FCG level > 7 mmol/L, 4.5% of patients, 2-hCG level > 11 mmol/L, 6.8%; and HbA1c level > 6.5%, 9.3%), compared with controls (n = 496; 1.2%, 3.1%, and 2.2%, respectively). The association between hyperglycemia and tuberculosis disappeared after tuberculosis treatment (adjusted odds ratio [aOR] for the FCG level: 9.6 [95% confidence interval {CI}, 3.7-24.7] at enrollment vs 2.4 [95% CI, .7-8.7] at follow-up; aOR for the 2-hCG level: 6.6 [95% CI, 4.0-11.1] vs 1.6 [95% CI, .8-2.9]; and aOR for the HbA1c level, 4.2 [95% CI, 2.9-6.0] vs 1.4 [95% CI, .9-2.0]). Hyperglycemia, based on the FCG level, at enrollment was associated with tuberculosis treatment failure or death (aOR, 3.3; 95% CI, 1.2-9.3). Transient hyperglycemia is frequent during tuberculosis, and DM needs confirmation after tuberculosis treatment. Performance of DM screening at tuberculosis diagnosis gives the opportunity to detect patients at risk of adverse outcome. © The Author 2015. Published by Oxford

  10. Admission hyperglycemia causes infarct volume expansion in patients with ICA or MCA occlusion: association of collateral grade on conventional angiography.

    Science.gov (United States)

    Shimoyama, T; Shibazaki, K; Kimura, K; Uemura, J; Shiromoto, T; Watanabe, M; Inoue, T; Iguchi, Y; Mochio, S

    2013-01-01

    Hyperglycemia (HG) is associated with infarct volume expansion in acute ischaemic stroke patients. However, collateral circulation can sustain the ischaemic penumbra and limit the growth of infarct volume. The aim of this study was to determine whether the association between HG and infarct volume expansion is dependent on collateral circulation. We performed a retrospective analysis of 93 acute ischaemic stroke patients with internal carotid artery or middle cerebral artery occlusion within 24 h of onset were retrospectively studied. HG was diagnosed in patients with an admitting blood glucose value ≥140 mg/dl. Angiographic collateral grade 0-1 was designated as poor collateral circulation and grade 2-4 as good collateral circulation. Infarct volume was measured at admission and at again within 7 days using diffusion-weighted magnetic resonance images. Among 34 patients with poor collateral grade, the change in infarct volume was significantly greater in the HG group than in the non-HG group (106.0 ml vs. 22.7 ml, P = 0.002). Among the 59 patients with good collateral circulation, the change in infarct volume was greater in the HG group than in the non-HG group (53.3 ml vs. 10.9 ml, P = 0.047). Multiple regression analysis indicated that admission HG (P = 0.004), baseline National Institutes of Health Stroke Scale score (P = 0.018), and poor collateral circulation (P = 0.040) were independently associated with infarct volume expansion. Infarct volume expansion was greater in individuals with HG on admission regardless of collateral circulation status. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  11. Loperamide-induced Cardiac Depression Is Enhanced by Hyperglycemia: Evidence Relevant to Loperamide Abuse.

    Science.gov (United States)

    Lo, Shih-Hsiang; Niu, Ho-Shan; Cheng, Yung-Ze; Niu, Chiang-Shan; Cheng, Juei-Tang; Ku, Po-Ming

    2017-01-01

    Cardiac dysryhthmias and death are reported after loperamide abuse. The mechanism of death is not clear and cardiac depression may play a role in this mechanism. Loperamide is widely used as an agonist of the μ-opioid receptor (MOR) in clinical practice. In skeletal muscle, an increase in MOR in response to hyperglycemia is largely attributable to higher expression of the transducer and activator of transcription 3 (STAT3), which binds to the promoter of the MOR genes. Therefore, we investigated the changes in cardiac MOR caused by hyperglycemia both in vivo and in vitro. Streptozotocin-induced type 1-like diabetic rats (STZ rats) were used to estimate cardiac performance and changes in cardiac MOR under the influence of loperamide. STAT3 was measured in cultured cardiomyocytes under high glucose (HG) to mimic the in vivo changes. Loperamide-induced reduction of cardiac performance was more marked in STZ rats than in normal rats. The increased MOR in the hearts of STZ rats was reversed by the reduction of hyperglycemia. Higher MOR expression paralleled the increase in STAT3 in cardiomyocytes under HG and was reversed by siRNA of STAT3. Stattic at a dose sufficient to inhibit STAT3 reduced MOR both in vivo and in vitro. Cardiac depression induced by loperamide is enhanced by hyperglycemia due to higher MOR expression, which is associated with higher expression of STAT3 in the heart. These results suggest that loperamide abuse is particularly dangerous for individuals with hyperglycemia. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  12. Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes.

    Science.gov (United States)

    Robinson, Katherine A; Hegyi, Krisztina; Hannun, Yusuf A; Buse, Maria G; Sethi, Jaswinder K

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used "specific" inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not -β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway.

  13. Go-6976 Reverses Hyperglycemia-Induced Insulin Resistance Independently of cPKC Inhibition in Adipocytes

    Science.gov (United States)

    Robinson, Katherine A.; Hegyi, Krisztina; Hannun, Yusuf A.; Buse, Maria G.; Sethi, Jaswinder K.

    2014-01-01

    Chronic hyperglycemia induces insulin resistance by mechanisms that are incompletely understood. One model of hyperglycemia-induced insulin resistance involves chronic preincubation of adipocytes in the presence of high glucose and low insulin concentrations. We have previously shown that the mTOR complex 1 (mTORC1) plays a partial role in the development of insulin resistance in this model. Here, we demonstrate that treatment with Go-6976, a widely used “specific” inhibitor of cPKCs, alleviates hyperglycemia-induced insulin resistance. However, the effects of mTOR inhibitor, rapamycin and Go-6976 were not additive and only rapamycin restored impaired insulin-stimulated AKT activation. Although, PKCα, (but not –β) was abundantly expressed in these adipocytes, our studies indicate cPKCs do not play a major role in causing insulin-resistance in this model. There was no evidence of changes in the expression or phosphorylation of PKCα, and PKCα knock-down did not prevent the reduction of insulin-stimulated glucose transport. This was also consistent with lack of IRS-1 phosphorylation on Ser-24 in hyperglycemia-induced insulin-resistant adipocytes. Treatment with Go-6976 did inhibit a component of the mTORC1 pathway, as evidenced by decreased phosphorylation of S6 ribosomal protein. Raptor knock-down enhanced the effect of insulin on glucose transport in insulin resistant adipocytes. Go-6976 had the same effect in control cells, but was ineffective in cells with Raptor knock-down. Taken together these findings suggest that Go-6976 exerts its effect in alleviating hyperglycemia-induced insulin-resistance independently of cPKC inhibition and may target components of the mTORC1 signaling pathway. PMID:25330241

  14. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

    Science.gov (United States)

    Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

    2017-01-01

    During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

  15. From the Cover: Prolonged Exposure to Volatile Anesthetic Isoflurane Worsens the Outcome of Polymicrobial Abdominal Sepsis.

    Science.gov (United States)

    Koutsogiannaki, Sophia; Schaefers, Matthew M; Okuno, Toshiaki; Ohba, Mai; Yokomizo, Takehiko; Priebe, Gregory P; DiNardo, James A; Sulpicio, Soriano G; Yuki, Koichi

    2017-04-01

    Sepsis continues to result in high morbidity and mortality. General anesthesia is often administered to septic patients, but the impacts of general anesthesia on host defense are not well understood. General anesthesia can be given by volatile and intravenous anesthetics. Our previous in vitro study showed that volatile anesthetic isoflurane directly inhibits leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), critical adhesion molecules on leukocytes. Thus, the role of isoflurane exposure on in vivo LFA-1 and Mac-1 function was examined using polymicrobial abdominal sepsis model in mice. As a comparison, intravenous anesthetic propofol was given to a group of mice. Wild type, LFA-1, Mac-1, and adhesion molecule-1 knockout mice were used. Following the induction of polymicrobial abdominal sepsis by cecal ligation and puncture, groups of mice were exposed to isoflurane for either 2 or 6 h, or to propofol for 6 h, and their outcomes were examined. Bacterial loads in tissues and blood, neutrophil recruitment to the peritoneal cavity and phagocytosis were studied. Six hours of isoflurane exposure worsened the outcome of abdominal sepsis (P sepsis and was associated with impaired neutrophil recruitment and bacterial phagocytosis via reduced LFA-1 and Mac-1 function. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Only adding stationary storage to vaccine supply chains may create and worsen transport bottlenecks.

    Science.gov (United States)

    Haidari, Leila A; Connor, Diana L; Wateska, Angela R; Brown, Shawn T; Mueller, Leslie E; Norman, Bryan A; Schmitz, Michelle M; Paul, Proma; Rajgopal, Jayant; Welling, Joel S; Leonard, Jim; Claypool, Erin G; Weng, Yu-Ting; Chen, Sheng-I; Lee, Bruce Y

    2013-01-01

    Although vaccine supply chains in many countries require additional stationary storage and transport capacity to meet current and future needs, international donors tend to donate stationary storage devices far more often than transport equipment. To investigate the impact of only adding stationary storage equipment on the capacity requirements of transport devices and vehicles, we used HERMES (Highly Extensible Resource for Modeling Supply Chains) to construct a discrete event simulation model of the Niger vaccine supply chain. We measured the transport capacity requirement for each mode of transport used in the Niger vaccine cold chain, both before and after adding cold rooms and refrigerators to relieve all stationary storage constraints in the system. With the addition of necessary stationary storage, the average transport capacity requirement increased from 88% to 144% for cold trucks, from 101% to 197% for pickup trucks, and from 366% to 420% for vaccine carriers. Therefore, adding stationary storage alone may worsen or create new transport bottlenecks as more vaccines flow through the system, preventing many vaccines from reaching their target populations. Dynamic modeling can reveal such relationships between stationary storage capacity and transport constraints.

  17. Bully/Victim Profiles' Differential Risk for Worsening Peer Acceptance: The Role of Friendship.

    Science.gov (United States)

    Kochel, Karen P; Ladd, Gary W; Bagwell, Catherine L; Yabko, Brandon A

    2015-01-01

    Study aims were to: (1) evaluate the association between bully/victim profiles, derived via latent profile analysis (LPA), and changes in peer acceptance from the fall to spring of 7 th grade, and (2) investigate the likelihood of friendlessness, and the protective function of mutual friendship, among identified profiles. Participants were 2,587 7 th graders; peer nomination and rating-scale data were collected in the fall and spring. Four profiles, including bullies, victims, bully-victims, and uninvolved adolescents, were identified at each time point. Findings showed that for victims, more so than for bullies and uninvolved profiles, acceptance scores worsened over time. Results further revealed that bully-victim and victim profiles included a greater proportion of friendless youth relative to the bully profile, which, in turn, contained a greater proportion of friendless adolescents than the uninvolved profile. Findings also provided evidence for the buffering role of friendship among all bully/victim profiles and among bully-victims especially.

  18. Bully/Victim Profiles’ Differential Risk for Worsening Peer Acceptance: The Role of Friendship

    Science.gov (United States)

    Kochel, Karen P.; Ladd, Gary W.; Bagwell, Catherine L.; Yabko, Brandon A.

    2015-01-01

    Study aims were to: (1) evaluate the association between bully/victim profiles, derived via latent profile analysis (LPA), and changes in peer acceptance from the fall to spring of 7th grade, and (2) investigate the likelihood of friendlessness, and the protective function of mutual friendship, among identified profiles. Participants were 2,587 7th graders; peer nomination and rating-scale data were collected in the fall and spring. Four profiles, including bullies, victims, bully-victims, and uninvolved adolescents, were identified at each time point. Findings showed that for victims, more so than for bullies and uninvolved profiles, acceptance scores worsened over time. Results further revealed that bully-victim and victim profiles included a greater proportion of friendless youth relative to the bully profile, which, in turn, contained a greater proportion of friendless adolescents than the uninvolved profile. Findings also provided evidence for the buffering role of friendship among all bully/victim profiles and among bully-victims especially. PMID:26309346

  19. Combination of diabetes and cataract worsens the oxidative stress and micronutrient status in Indians.

    Science.gov (United States)

    Agte, Vaishali V; Tarwadi, Kirtan Vilas

    2008-01-01

    We examined the synergism of cataract and diabetes in micronutrient and antioxidant statuses versus diabetes mellitus and cataract alone. Indian patients with type 2 diabetes mellitus (D; n = 76), those without diabetes and with cataract (NDC; n = 100), those with diabetes and cataract (DC; n = 53), and age- and sex-matched healthy controls (n = 90) 50-70 y were investigated. Plasma oxidative stress as thiobarbituric acid-reactive substances (TBARS) and the status of 11 micronutrients were studied as lens TBARS, opacity, and ratio of soluble to total proteins in patients with cataract with or without diabetes. Lipid profile, fasting glucose, and postprandial glucose were measured for all subjects. A subnormal status of ascorbic acid, beta-carotene, thiamine, and ceruloplasmin was elicited for all four study groups. Plasma TBARS and fasting glucose were significantly higher in the DC group than in the NDC (P selenium. The DC group was found to be significantly different from the other groups with respect to beta-coefficients of a logistic regression equation for plasma levels of selenium, zinc, iron, thiamine, triacylglycerols, total cholesterol, ceruloplasmin, vitamin A, and superoxide dismutase. The combination of diabetes and cataract coupled with gender bias and influence of socioeconomic factors seem to be associated with worsening of micronutrient status, oxidative stress, and lens opacity.

  20. Worsening Cervical Epidural Hematoma After Tissue Plasminogen Activator Administration for Stroke Like Symptoms.

    Science.gov (United States)

    Morimoto, Tadatsugu; Yoshihara, Tomohito; Yakushiji, Yusuke; Eriguchi, Makoto; Hara, Hideo; Sonohata, Motoki; Mawatari, Masaaki

    2016-04-01

    Case report. To report an extremely rare case of stroke-mimicking, cervical spontaneous epidural hematoma (SEH) treated with tissue plasminogen activator (tPA) for hemiparesis followed by emergency cervical decompression. Although hemiparesis caused by cervical SEH is a relatively uncommon symptom compared with tetraparesis, such cases were often misdiagnosed as cerebral infarction and worsened by antithrombic therapy. A case report and literature review are presented. A 71-year-old male presented with sudden neck pain followed by left-sided hemiparesis, and was believed to have had a stroke. He was administered tPA as intracranial computed tomography showed no signs of hemorrhage. However, his neurological condition continued to decline, and MRI of the cervical spine revealed a large spontaneous epidural hematoma. He subsequently underwent evacuation of the epidural hematoma and C3-6 laminoplasty, and his clinical status improved after the surgery. To our knowledge, only three cases of cervical SEH with hemiparesis erroneously treated with tPA resulting in neurological decline because of the enlargement of an existing hematoma, including the current case, have been reported in the English literature. It is important for physicians, especially those who administer tPA treatment, to include cervical SEH in the differential diagnosis of stroke in patients presenting with sudden back pain followed by the onset of neurological deficits including hemiparesis. 5.

  1. Late gadolinium enhancement cardiovascular magnetic resonance predicts clinical worsening in patients with pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Freed Benjamin H

    2012-02-01

    Full Text Available Abstract Background Late gadolinium enhancement (LGE occurs at the right ventricular (RV insertion point (RVIP in patients with pulmonary hypertension (PH and has been shown to correlate with cardiovascular magnetic resonance (CMR derived RV indices. However, the prognostic role of RVIP-LGE and other CMR-derived parameters of RV function are not well established. Our aim was to evaluate the predictive value of contrast-enhanced CMR in patients with PH. Methods RV size, ejection fraction (RVEF, and the presence of RVIP-LGE were determined in 58 patients with PH referred for CMR. All patients underwent right heart catheterization, exercise testing, and N-terminal pro-brain natriuretic peptide (NT-proBNP evaluation; results of which were included in the final analysis if performed within 4 months of the CMR study. Patients were followed for the primary endpoint of time to clinical worsening (death, decompensated right ventricular heart failure, initiation of prostacyclin, or lung transplantation. Results Overall, 40/58 (69% of patients had RVIP-LGE. Patients with RVIP- LGE had larger right ventricular volume index, lower RVEF, and higher mean pulmonary artery pressure (mPAP, all p Conclusions The presence of RVIP-LGE in patients with PH is a marker for more advanced disease and poor prognosis. In addition, this study reveals for the first time that CMR-derived RVEF is an independent non-invasive imaging predictor of adverse outcomes in this patient population.

  2. Significant worsening sperm parameters are associated to testicular hypotrophy in patients with a high grade varicocele.

    Science.gov (United States)

    Guzel, O; Aslan, Y; Balci, M; Tuncel, A; Unal, B; Atan, A

    2015-01-01

    To investigate the relationship between testicular volume and semen parameter sin patients with unilateral high grade left varicocele. One hundred eighty seven patients who had left high grade varicocele aged 19-to-25 years were included in this study. All patients underwent a standard evaluation, including medical history and physical examination. The percentage testicular volume difference between the right and left testicles was calculated. The patients were divided into the following three groups; Group 1 (n=72) testicular volume difference 20% Group 3 (n=41). The mean age and BMI of the patients were 21.5 years and 23.1kg/m(2), respectively (P=.596, P=.943). The semen parameters and testicular volumes of the three groups were compared. The total motile sperm count, percentage of motile sperm, percentage of normal morphology sperm were found to be lower in Group 3 (P=.011, P=.012, P=.029 respectively). The mean testicular volumes for the left and the right testis were found to be 15.2cm(3) and 17.7cm(3) (P<.001), respectively. No significant difference was found in the right testicular volumes between groups (17.4, 17.7 and 18.1cm(3), P=.573). A high grade left testicular varicocele is associated with ipsilateral testicular hypotrophy and parallel to worsened sperm parameters. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Arginase 1 activity worsens lung-protective immunity against Streptococcus pneumoniae infection.

    Science.gov (United States)

    Knippenberg, Sarah; Brumshagen, Christina; Aschenbrenner, Franziska; Welte, Tobias; Maus, Ulrich A

    2015-06-01

    Type 2 helper cell (Th2) dominated chronic lung diseases such as asthma are characterized by an increased risk for bacterial lung infections. However, the underlying mechanisms are poorly defined. Arginase 1 (Arg1) has been suggested to play an important role in the pathophysiology of asthma, and is rapidly induced in lung macrophages by Th2 cytokines, thereby limiting macrophage-derived antimicrobial nitric oxide (NO) production. Here we examined the effect of Th2 cytokine induced upregulation or lung myeloid cell specific conditional knockdown of Arg1 on lung resistance against Streptococcus pneumoniae (Spn) in mice. Lung macrophages responded with a profound induction of Arg1 mRNA and protein to treatment with IL-13 both in vitro and in vivo. IL-13-induced Arg1 activity in the lungs of mice led to significantly attenuated lung-protective immunity against Spn, while conditional Arg1 knockdown had no effect on lung-protective immunity against Spn. Collectively, the data show that Th2 cytokine induced increased Arg1 activity worsens lung-protective immunity against Spn, and interventions to block Th2 cytokine induced lung Arg1 activity may thus be a novel immunomodulatory strategy to lower the risk of bacterial infections in asthmatic patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening.

    Directory of Open Access Journals (Sweden)

    Marilyne Levy

    Full Text Available BACKGROUND: Pulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH. Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level. METHODS/RESULTS: CECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30 or PAH secondary to congenital heart disease (PAH-CHD, n = 30: before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA and/or phosphodiesterase 5 inhibitors (PDE5 significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration. CONCLUSION: CECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.

  5. Pre-Hospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsen Hypocoagulation and Hyperfibrinolysis

    Science.gov (United States)

    2015-07-01

    after severe injury with hemorrhagic shock. J Trauma Acute Care Surg 72(6):1714Y1718, 2012. 6. Marx G, Schuerholz T: Fluid-induced coagulopathy: does the...bleeding. J Trauma 61(6):1350Y1358, 2006. 44. Engels PT, Rezende-Neto JB, Al Mahroos M, Scarpelini S, Rizoli SB, Tien HC: The natural history of trauma

  6. Extreme Insulin Resistance in a Patient with Diabetes Ketoacidosis and Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Yin H. Oo

    2013-01-01

    Full Text Available Hyperglycemia is common in hospitalized patients and associated with adverse clinical outcomes. In hospitalized patients, multiple factors contribute to hyperglycemia, such as underlying medical conditions, pathophysiological stress, and medications. The development of transient insulin resistance is a known cause of hyperglycemia in both diabetic and nondiabetic patients. Though physicians are familiar with common diseases that are known to be associated with insulin resistance, the majority of us rarely come across a case of extreme insulin resistance. Here, we report a case of prolonged course of extreme insulin resistance in a patient admitted with diabetic ketoacidosis (DKA and acute myocardial infarction (MI. The main purpose of this paper is to review the literature to identify the underlying mechanisms of extreme insulin resistance in a patient with DKA and MI. We will also briefly discuss the different clinical conditions that are associated with insulin resistance and a general approach to a patient with severe insulin resistance.

  7. Partial meniscectomy is associated with increased risk of incident radiographic osteoarthritis and worsening cartilage damage in the following year

    Energy Technology Data Exchange (ETDEWEB)

    Roemer, Frank W. [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Kwoh, C.K. [University of Arizona Arthritis Center and University of Arizona College of Medicine, Tucson, AZ (United States); Hannon, Michael J.; Grago, Jason [University of Pittsburgh School of Medicine, Division of Rheumatology and Clinical Immunology, Pittsburgh, PA (United States); Hunter, David J. [University of Sydney, Department of Rheumatology, Royal North Shore Hospital and Kolling Institute, St Leonards (Australia); Eckstein, Felix [Paracelsus Medical University, Institute of Anatomy, Salzburg (Austria); Boudreau, Robert M. [University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, Pittsburgh, PA (United States); Englund, Martin [Lund University, Clinical Epidemiology Unit, Orthopaedics, Department of Clinical Sciences Lund, Lund (Sweden); Guermazi, Ali [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States)

    2017-01-15

    To assess whether partial meniscectomy is associated with increased risk of radiographic osteoarthritis (ROA) and worsening cartilage damage in the following year. We studied 355 knees from the Osteoarthritis Initiative that developed ROA (Kellgren-Lawrence grade ≥ 2), which were matched with control knees. The MR images were assessed using the semi-quantitative MOAKS system. Conditional logistic regression was applied to estimate risk of incident ROA. Logistic regression was used to assess the risk of worsening cartilage damage in knees with partial meniscectomy that developed ROA. In the group with incident ROA, 4.4 % underwent partial meniscectomy during the year prior to the case-defining visit, compared with none of the knees that did not develop ROA. All (n = 31) knees that had partial meniscectomy and 58.9 % (n = 165) of the knees with prevalent meniscal damage developed ROA (OR = 2.51, 95 % CI [1.73, 3.64]). In knees that developed ROA, partial meniscectomy was associated with an increased risk of worsening cartilage damage (OR = 4.51, 95 % CI [1.53, 13.33]). The probability of having had partial meniscectomy was higher in knees that developed ROA. When looking only at knees that developed ROA, partial meniscectomy was associated with greater risk of worsening cartilage damage. (orig.)

  8. Radiological lumbar stenosis severity predicts worsening sagittal malalignment on full-body standing stereoradiographs.

    Science.gov (United States)

    Buckland, Aaron J; Ramchandran, Subaraman; Day, Louis; Bess, Shay; Protopsaltis, Themistocles; Passias, Peter G; Diebo, Bassel G; Lafage, Renaud; Lafage, Virginie; Sure, Akhila; Errico, Thomas J

    2017-05-17

    Patients with degenerative lumbar stenosis (DLS) adopt a forward flexed posture in an attempt to decompress neural elements. The relationship between sagittal alignment and severity of lumbar stenosis has not previously been studied. We hypothesized that patients with increasing radiological severity of lumbar stenosis will exhibit worsening sagittal alignment. This is a cross-sectional study. Our sample consists of patients who have DLS. Standing pelvic, regional, lower extremity and global sagittal alignment, and health-related quality of life (HRQoL) were the outcome measures. Patients with DLS were identified from a retrospective clinical database with corresponding full-body stereoradiographs. Exclusion criteria included coronal malalignment, prior spine surgery, spondylolisthesis>Grade 1, non-degenerative spinal pathology, or skeletal immaturity. Central stenosis severity was graded on axial T2-weighted magnetic resonance imaging (MRI) from L1-S1. Foraminal stenosis and supine lordosis was graded on sagittal T1-weighted images. Standing pelvic, regional, lower extremity, and global sagittal alignment were measured using validated software. The HRQoL measures were also analyzed in relation to severity of stenosis. A total of 125 patients were identified with DLS on appropriate imaging. As central stenosis grade increased, patients displayed significantly increasing standing T1 pelvic angle, pelvic tilt, sagittal vertical axis, and pelvic incidence-lumbar lordosis (pHRQoLs in central or foraminal stenosis. Severity of central lumbar stenosis as graded on MRI correlates with severity of sagittal malalignment. These findings support theories of sagittal malalignment as a compensatory mechanism for central lumbar stenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Regional cortical thinning predicts worsening apathy and hallucinations across the Alzheimer disease spectrum.

    Science.gov (United States)

    Donovan, Nancy J; Wadsworth, Lauren P; Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A

    2014-11-01

    To examine regions of cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers associated with apathy and hallucinations in a continuum of individuals including clinically normal elderly, mild cognitive impairment, and mild AD dementia. Cross-sectional and longitudinal studies. Fifty-seven research sites across North America. Eight-hundred twelve community-dwelling volunteers; 413 participants in the CSF sub-study. Structural magnetic resonance imaging data and CSF concentrations of amyloid-β 1-42, total tau, and phosphorylated tau derived from the Alzheimer Disease Neuroimaging Initiative database were analyzed. Apathy and hallucinations were measured at baseline and over 3 years using the Neuropsychiatric Inventory-Questionnaire. General linear models and mixed effects models were used to evaluate the relationships among baseline cortical thickness in seven regions, and baseline CSF biomarkers, apathy, and hallucinations at baseline and longitudinally. Covariates included diagnosis, sex, age, apolipoprotein E genotype, premorbid intelligence, memory performance, processing speed, antidepressant use, and AD duration. Reduced baseline inferior temporal cortical thickness was predictive of increasing apathy over time, and reduced supramarginal cortical thickness was predictive of increasing hallucinations over time. There was no association with cortical thickness at baseline. CSF biomarkers were not related to severity of apathy or hallucinations in cross-sectional or longitudinal analyses. These results suggest that greater baseline temporal and parietal atrophy is associated with worsening apathy and hallucinations in a large AD spectrum cohort, while adjusting for multiple disease-related variables. Localized cortical neurodegeneration may contribute to the pathophysiology of apathy and hallucinations and their adverse consequences in AD. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All

  10. Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice.

    Science.gov (United States)

    Trevino, Michelle B; Mazur-Hart, David; Machida, Yui; King, Timothy; Nadler, Joseph; Galkina, Elena V; Poddar, Arjun; Dutta, Sucharita; Imai, Yumi

    2015-10-01

    Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-α was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity.

  11. Association between matrix metalloproteinase‐9 and worsening heart failure events in patients with chronic heart failure

    Science.gov (United States)

    Morishita, Tetsuji; Mitsuke, Yasuhiko; Amaya, Naoki; Kaseno, Kenichi; Ishida, Kentaro; Fukuoka, Yoshitomo; Ikeda, Hiroyuki; Tama, Naoki; Yamazaki, Taketoshi; Lee, Jong‐Dae; Tada, Hiroshi

    2017-01-01

    Abstract Aims Matrix metalloproteinase (MMP) is up‐regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF. Methods and results Plasma levels of MMP‐9, TIMP‐1, and brain natriuretic peptide (BNP) were measured in 173 patients with chronic HF. Combined endpoints of worsening HF events were assessed during follow‐up (median 109 months). MMP‐9 and TIMP‐1 levels and the MMP‐9/TIMP‐1 ratio increased with increasing severity of the New York Heart Association class (P for trend = 0.003, 0.011, and 0.005, respectively). Patients with HF events (n = 35) had significantly higher MMP‐9 than those without HF events (P = 0.004). Kaplan–Meier analysis demonstrated a higher probability of HF events with high MMP‐9 values (>23.2 ng/mL; P = 0.005). A multivariate Cox proportional hazard model showed that high MMP‐9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03–13.46; P = 0.043). In patients with lower BNP levels (≤210 pg/mL), the adjusted hazard ratio for HF events was 3.63 (95% CI, 1.20–11.02; P = 0.023) among patients with high MMP‐9 values compared with patients with low BNP and low MMP‐9 values. Conclusions MMP‐9 and TIMP‐1 levels correlate with the severity of chronic HF. MMP‐9 is a strong predictor of HF events, suggesting that a disparity between MMP‐9 and TIMP‐1 levels and increased MMP‐9 levels may help predict HF events. PMID:28772055

  12. Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients.

    Science.gov (United States)

    Lorenz, Georg; Steubl, Dominik; Kemmner, Stephan; Pasch, Andreas; Koch-Sembdner, Wilhelm; Pham, Dang; Haller, Bernhard; Bachmann, Quirin; Mayer, Christopher C; Wassertheurer, Siegfried; Angermann, Susanne; Lech, Maciej; Moog, Philipp; Bauer, Axel; Heemann, Uwe; Schmaderer, Christoph

    2017-10-17

    A novel in-vitro test (T 50 -test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T 50 with all-cause and cardiovascular mortality has not been investigated. We assessed T 50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11-37] months. Serum T 50 exhibited a significant decline between baseline and 24 months (246 ± 64 to 190 ± 68 minutes; p < 0.001). With serum Δ-phosphate showing the strongest independent association with declining T 50 (r = -0.39; p < 0.001) in multivariable linear regression. The rate of decline of T 50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T 50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions.

  13. Regional cortical thinning and cerebrospinal biomarkers predict worsening daily functioning across the Alzheimer disease spectrum

    Science.gov (United States)

    Marshall, Gad A.; Lorius, Natacha; Locascio, Joseph J.; Hyman, Bradley T.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2014-01-01

    Background Impairment in instrumental activities of daily living (IADL) heralds the transition from mild cognitive impairment (MCI) to dementia and is a major source of burden for both the patient and caregiver. Objective To investigate the relationship between IADL and regional cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers cross-sectionally and longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia subjects. Methods Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia subjects participating in the Alzheimer's Disease Neuroimaging Initiative underwent baseline magnetic resonance imaging, baseline lumbar puncture, and clinical assessments, including the Functional Activities Questionnaire used to measure IADL, every 6 to 12 months up to 3 years. General linear regression and mixed effects models were employed. Results IADL impairment was associated with the interactions between lower inferior temporal cortical thickness and diagnosis (p<0.0001), greater lateral occipital cortical thickness and diagnosis (p<0.0001), and greater amyloid-beta 1-42 (Aβ1-42) and diagnosis (p=0.0002) at baseline (driven by AD dementia). Lower baseline supramarginal (p=0.02) and inferior temporal (p=0.05) cortical thickness, lower Aβ1-42 (p<0.0001), and greater total tau (t-tau) (p=0.02) were associated with greater rate of IADL impairment over time. Conclusions Temporal atrophy is associated with IADL impairment in mild AD dementia at baseline, while baseline parietal and temporal atrophy, lower CSF Aβ1-42, and greater t-tau predict worsening IADL impairment over time across the AD spectrum. These results emphasize the importance of assessing IADL at the stage of MCI and even at the transition from CN to MCI. PMID:24685624

  14. Trans-oral endoscopic partial adenoidectomy does not worsen the speech after cleft palate repair.

    Science.gov (United States)

    Abdel-Aziz, Mosaad; Khalifa, Badawy; Shawky, Ahmed; Rashed, Mohammed; Naguib, Nader; Abdel-Hameed, Asmaa

    2016-01-01

    Adenoid hypertrophy may play a role in velopharyngeal closure especially in patients with palatal abnormality; adenoidectomy may lead to velopharyngeal insufficiency and hyper nasal speech. Patients with cleft palate even after repair should not undergo adenoidectomy unless absolutely needed, and in such situations, conservative or partial adenoidectomy is performed to avoid the occurrence of velopharyngeal insufficiency. Trans-oral endoscopic adenoidectomy enables the surgeon to inspect the velopharyngeal valve during the procedure. The aim of this study was to assess the effect of transoral endoscopic partial adenoidectomy on the speech of children with repaired cleft palate. Twenty children with repaired cleft palate underwent transoral endoscopic partial adenoidectomy to relieve their airway obstruction. The procedure was completely visualized with the use of a 70° 4mm nasal endoscope; the upper part of the adenoid was removed using adenoid curette and St. Claire Thompson forceps, while the lower part was retained to maintain the velopharyngeal competence. Preoperative and postoperative evaluation of speech was performed, subjectively by auditory perceptual assessment, and objectively by nasometric assessment. Speech was not adversely affected after surgery. The difference between preoperative and postoperative auditory perceptual assessment and nasalance scores for nasal and oral sentences was insignificant (p=0.231, 0.442, 0.118 respectively). Transoral endoscopic partial adenoidectomy is a safe method; it does not worsen the speech of repaired cleft palate patients. It enables the surgeon to strictly inspect the velopharyngeal valve during the procedure with better determination of the adenoidal part that may contribute in velopharyngeal closure. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  15. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott

    2015-04-01

    Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

  16. Does squatting worsen lower limb ischemia in patients with peripheral arterial disease?

    Science.gov (United States)

    Raghavendra, Gargeshwari Krishnamurthy Guru

    2012-08-01

    Peripheral arterial disease (PAD) is an important cause of morbidity and mortality in the world affecting up to 20% in people over 70 years of age. The prevalence is increasing in India due to combined effects of increased life expectancy, increased tobacco smoking and increased prevalence of diabetes mellitus. The aim of the study was to examine the hypothesis whether squatting posture reduces blood flow to lower limbs resulting in worsening of symptoms of lower limb ischemia in patients with PAD. 10 patients with arterial disorders due to thromboangiitis obliterans (TAO), atherosclerosis and diabetic macro vascular disease were selected for patients and were compared with 10 healthy volunteers as controls. Clinical examination and duplex scan of posterior tibial artery (PTA) and dorsalis pedis artery (DPA) performed in standing and squatting position in a clinical environment. They were asked about symptoms of numbness, ischemic pain and the results were noted. Results were tabulated and analysed using Microsoft Excel®. Members in the control group complained of numbness of both the limbs after a period of 30 min on an average. In the patients group, members while squatting complained of numbness in the involved limb within 5 min. They complained of ischemic pain in the involved limb within 10 min and developed numbness in the opposite limb in within 15 min. Posterior tibial artery and dorsalis pedis artery pulsations disappeared for the entire duration of squatting in both groups as confirmed by duplex scanning. It may be recommended that patients with established peripheral vascular disease should avoid squatting position, even if it is for a very short period of time. It is desirable to advice such patients to use appropriate structures as supports which will allow them to work without squatting. This may also necessitate a change in occupation.

  17. Worsening Cognitive Impairment and Neurodegenerative Pathology Progressively Increase Risk for Delirium

    Science.gov (United States)

    Davis, Daniel H.J.; Skelly, Donal T.; Murray, Carol; Hennessy, Edel; Bowen, Jordan; Norton, Samuel; Brayne, Carol; Rahkonen, Terhi; Sulkava, Raimo; Sanderson, David J.; Rawlins, J. Nicholas; Bannerman, David M.; MacLullich, Alasdair M.J.; Cunningham, Colm

    2015-01-01

    Background Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. Methods Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. Results In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. Conclusion A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology. PMID:25239680

  18. Post-operative morbidity, but not mortality, is worsened by operative delay in septic diverticulitis.

    Science.gov (United States)

    Mozer, Anthony B; Spaniolas, Konstantinos; Sippey, Megan E; Celio, Adam; Manwaring, Mark L; Kasten, Kevin R

    2017-02-01

    Optimal timing of surgery for acute diverticulitis remains unclear. A non-operative approach followed by elective surgery 6-week post-resolution is favored. However, a subset of patients fail on the non-operative management during index admission. Here, we examine patients requiring emergent operation to evaluate the effect of surgical delay on patient outcomes. Patients undergoing emergent operative intervention for acute diverticulitis were queried using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2012. Primary endpoints of 30-day overall morbidity and mortality were evaluated via univariate and multivariate analysis. Of the 2,119 patients identified for study inclusion, 57.2 % (n = 1212) underwent emergent operative intervention within 24 h, 26.3 % (n = 558) between days 1-3, 12.9 % (n = 273) between days 3-7, and 3.6 % (n = 76) greater than 7 days from admission. End colostomy was performed in 77.4 % (n = 1,640) of cases. Unadjusted age and presence of major comorbidities increased with operative delay. Further, unadjusted 30-day overall morbidity, mortality, septic complications, and post-operative length of stay increased significantly with operative delay. On multivariate analysis, operative delay was not associated with increased 30-day mortality but was associated with increased 30-day overall morbidity. Hartmann's procedure has remained the standard operation in emergent surgical management of acute diverticulitis. Delay in definitive surgical therapy greater than 24 h from admission is associated with higher rates of morbidity and protracted post-operative length of stay, but there is no increase in 30-day mortality. Prospective study is necessary to further answer the question of surgical timing in acute diverticulitis.

  19. Sensor-augmented insulin pump therapy to treat hyperglycemia at the coronary care unit: a randomized clinical pilot trial

    NARCIS (Netherlands)

    Hermanides, Jeroen; Engström, Annemarie E.; Wentholt, Iris M. E.; Sjauw, Krischan D.; Hoekstra, Joost B. L.; Henriques, Jose P. S.; DeVries, J. Hans

    2010-01-01

    BACKGROUND: The relationship between admission hyperglycemia and adverse outcome in myocardial infarction has been shown consistently. However, achieving and maintaining normoglycemia in ST elevated myocardial infarction (STEMI) patients has proven difficult. This study aimed to investigate the

  20. Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients

    DEFF Research Database (Denmark)

    Kjersem, H; Hilsted, J; Madsbad, S

    1988-01-01

    Polymorphonuclear leucocyte (PMN) ingestion of particles coated with lipopolysaccharide (LPS) from Escherichia coli was compared to other PMN functions in seven patients with insulin dependent diabetes mellitus (IDDM) during short-term controlled metabolic changes from normo- to hyperglycemia...... without ketoacidosis. Factors known to interfere with PMN functions were excluded. PMN ingestion of particles coated with both LPS and bovine serum albumin became reduced from normo- to hyperglycemia. PMN motility was impaired in IDDM, but did not seem to be affected by short-term changes in metabolic...... control. PMN metabolism did not change from normo-to hyperglycemia. Particle-uptake by diabetic PMN is impaired after short term hyperglycemia in the range normally occurring in diabetics in every-day life....

  1. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits.

    Science.gov (United States)

    Aghajanyan, Anush; Movsisyan, Zaruhi; Trchounian, Armen

    2017-01-01

    Diabetes mellitus (DM) is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia).

  2. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

    Science.gov (United States)

    Aghajanyan, Anush; Movsisyan, Zaruhi

    2017-01-01

    Diabetes mellitus (DM) is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia). PMID:28758125

  3. Artificial Pancreas for Control of BG and Insulin Levels in Hospitalized Patients with Diabetes and Stress Hyperglycemia

    National Research Council Canada - National Science Library

    Joseph, Jeffrey I

    2007-01-01

    ... with Diabetes and Stress Hyperglycemia , (Principal Investigator: Jeffrey Joseph, DO; Award Number: W81XWH-04-1-0004). The original tasks set forth in the statement of work for this research project are given in Table 1...

  4. C-peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation

    National Research Council Canada - National Science Library

    Bhatt, Mahendra Prasad; Lim, Young-Cheol; Hwang, JongYun; Na, SungHun; Kim, Young-Myeong; Ha, Kwon-Soo

    2013-01-01

    .... We investigated the protective mechanism of C-peptide against hyperglycemia-induced apoptosis using human umbilical vein endothelial cells and streptozotocin diabetic mice. High glucose (33 mmol/L...

  5. Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

    Directory of Open Access Journals (Sweden)

    Anush Aghajanyan

    2017-01-01

    Full Text Available Diabetes mellitus (DM is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia.

  6. Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking.

    Science.gov (United States)

    Otero-Losada, Matilde E; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Müller, Angélica; Ottaviano, Graciela; Moriondo, Marisa; Cutrin, Juan C; Milei, José

    2013-04-01

    Atherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption' effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations. ApoE-/- mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized ( W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W16, C16, L16). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant. TREATMENT increased drinking volumes (vs W8: 4 fold C8, p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (-54%, p<0.05 vs W8). I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (-15%, p<0.05 vs W8) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7 fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). TREATMENT caused plaque area increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and 68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16: 71% C16, p<0.01 and 46% L16, p<0.04). Age also caused plaque area increase

  7. A psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R cognitive distress, fatigue, hyperglycemia, and hypoglycemia subscales in patients with type 1 and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    April N Naegeli

    2010-03-01

    Full Text Available April N Naegeli1, Timothy E Stump2, Risa P Hayes11Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Consultant, Indianapolis, IN, USAObjective: To explore the use of Diabetes Symptom Checklist-Revised (DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia subscales as measures of acute diabetesassociated symptoms in patients with both type 1 and 2 diabetes.Research design and methods: Our study was conducted in context of two international, multicenter, randomized clinical trials for inhaled insulin. Confirmatory factor analyses and assessments of reliability and construct validity were performed.Results: Study participants were 371 patients with type 2 (56% male; mean age, 57 years and 481 with type 1 diabetes (57% male, mean age, 40 years. In both populations a four-factor model was the best fit. Cronbach’s α ≥ 0.79 and intraclass correlation coefficient ≥0.63; subscales correlated (P ≤ 0.05 with measures of well-being and satisfaction (0.12 ≤ r ≤ 0.71. In patients with type 1 diabetes, three subscales correlated (P < 0.05 with A1C.Conclusions: The psychometric properties of the DSC-R Cognitive Distress, Fatigue, Hyperglycemia, and Hypoglycemia suggest they may be utilized in clinical trials as reliable and valid measures of acute symptoms of diabetes.Keywords: Diabetes Symptom Checklist-Revised, DSC-R, type 1 diabetes, type 2 diabetes, psychometric validation

  8. Artificial hyperglycemia as a factor potentiating selectively an anti-tumoral radiation effect

    Energy Technology Data Exchange (ETDEWEB)

    Loginov, V.M. (Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Nejrokhirurgii)

    1983-07-01

    An important peculiarity of tumoral cells is their ability for intensive glycolysis. Potential biochemical mechanisms of this phenomenon are considered in the review. A tumoral process is closely connected with the changes in glucose metabolism in an organism. Therefore artificial hyperglycemia (AH) can be an instrument for intervention into tumoral cell energetics. Many experimental data show an increase of glucose consumption at AH. Long-term AH causes a reduction of tumor pH. Various view points on AH antitumoral effect mechanism are considered. Data on changes in a sound organism in case of long-term AH are given. It has been found that AH does not cause irreversible changes on the part of organs and systems of the organism. Experimental data on a possibility of using short-term hyperglycemia as a factor selectively potentiating antitumoral radiation effect are considered.

  9. Effects of Infantile Repeated Hyperglycemia on Behavioral Alterations in Adult Rats

    Directory of Open Access Journals (Sweden)

    Malihe Moghadami

    2012-09-01

    Full Text Available Anxiety symptoms have been reported to be present in many patients with diabetes mellitus. However, little is known about the effects of hyperglycemia in critical periods of the central nervous system development. We assessed locomotive, exploratory, and anxiety behaviors in adult rats that remained from infantile repeated hyperglycemia by the open field and elevated plus maze tests. Our findings showed significant hypo activity, reduced locomotive/exploratory activities, increased fear related behaviors, and anxiety state between hyperglycemic and control adult males and the same differences were observed among females. In addition, no significant behavioral alterations between male and female animals were observed. This study determined that repeated increments in daily blood sugar levels in newborns may affect neuronal functions and provide behavioral abnormalities in adults.

  10. Modulation of miR29a improves impaired post-ischemic angiogenesis in hyperglycemia.

    Science.gov (United States)

    Chen, Lingdan; Okeke, Emmanuel; Ayalew, Dawit; Wang, Danny; Shahid, Lyeba; Dokun, Ayotunde O

    2017-08-01

    Individuals with diabetes mellitus suffer from impaired angiogenesis and this contributes to poorer peripheral arterial disease outcomes. In experimental peripheral arterial disease, angiogenesis and perfusion recovery are impaired in mice with diabetes. We recently showed that a disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) is upregulated in ischemic endothelial cells and plays a key role in post-ischemic angiogenesis and perfusion recovery following experimental peripheral arterial disease. Here we investigated the role of miR29a in the regulation of endothelial cell ADAM12 expression in ischemia and how hyperglycemia negatively affects this regulation. We also explored whether modulating miR29a can improve impaired post-ischemic angiogenesis associated with hyperglycemia. Additionally, we tested whether miR29a modulation could improve post ischemic angiogenesis in the setting of impaired vascular endothelial growth factor signaling. We forced miR29a expression in ischemic endothelial cells and assessed ADAM12 expression. We also evaluated whether hyperglycemia in vivo and in vitro impair ischemia-induced ADAM12 upregulation and miR29a downregulation. Lastly, we determined whether modulating endothelial cell miR29a expression in ischemia and hyperglycemia could improve impaired endothelial cell functions. We found under ischemic conditions where ADAM12 is upregulated in endothelial cells, miR29a is downregulated. Forced expression of miR29a in ischemic endothelial cell prevented ADAM12 upregulation . In ischemic hind limbs of mice with type 1 diabetes and in endothelial cells exposed to simulated ischemia plus hyperglycemia, ADAM12 upregulation and miR29a downregulation were blunted while angiogenesis was impaired. Knocking down miR29a with an miR29a inhibitor was sufficient to improve ADAM12 upregulation and angiogenesis in simulated ischemia plus hyperglycemia. It was also sufficient to improve perfusion recovery in type 1 diabetes

  11. The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats

    DEFF Research Database (Denmark)

    Kruse, Carla R; Singh, Mansher; Sørensen, Jens A

    2016-01-01

    BACKGROUND: Multiple previous studies have established that high systemic blood glucose concentration impairs skin wound healing. However, the effects of local hyperglycemia on wound healing are not well defined. Comprehensive animal studies and in vitro studies using both fibroblasts and keratin......BACKGROUND: Multiple previous studies have established that high systemic blood glucose concentration impairs skin wound healing. However, the effects of local hyperglycemia on wound healing are not well defined. Comprehensive animal studies and in vitro studies using both fibroblasts...

  12. Effect of single oral dose of proanthocyanidin on postprandial hyperglycemia in healthy rats: A comparative study with sitagliptin

    OpenAIRE

    Sulaiman, Amal Ajaweed

    2014-01-01

    Background: Many of flavonoid rich natural products found to have a significant influence on postprandial hyperglycemia, a major risk factor for diabetic complications. Enhancement of insulinotropic gut hormones by inhibition of dipeptidyl peptidase-IV (DPP-IV) are among the newest strategies for treatments of Type 2 diabetes which thought to be the underlying action through which flavonoid can reduce postprandial hyperglycemia. Aim: This study aim was designed to investigate the potential ro...

  13. Current Understanding of Metformin Effect on the Control of Hyperglycemia in Diabetes

    OpenAIRE

    An, Hongying; He, Ling

    2016-01-01

    Metformin is a first line oral anti-diabetic agent that has been used clinically to treat patients with type 2 diabetes for over 60 years. Due to its efficacy in therapy and affordable price, metformin is taken by over 150 million people each year. Metformin improves hyperglycemia mainly through the suppression of hepatic gluconeogenesis along with the improvement of insulin signaling. However, its mechanism of action remains partially understood and controversial, especially in regards to th...

  14. The clinical management of hyperglycemia in pregnancy complicated by maturity-onset diabetes of the young.

    Science.gov (United States)

    Bacon, Siobhan; Schmid, Jasmin; McCarthy, Ailbhe; Edwards, Jackie; Fleming, Aileen; Kinsley, Brendan; Firth, Richard; Byrne, Bridgette; Gavin, Claire; Byrne, Maria M

    2015-08-01

    Women with maturity-onset diabetes of the young (MODY) are often first identified and diagnosed with diabetes during pregnancy. Genetics and hyperglycemia play an important role in determining fetal size in MODY pregnancies. The principal objective of the current study is to determine the outcomes and clinical management of hyperglycemia in pregnancies complicated by glucokinase gene (GCK) and hepatocyte nuclear factor (HNF)-1α MODY mutations. A retrospective chart review of 37 women with a GCK/HNF-1α mutation was conducted. Data on variables such as birthweight, mode of delivery, and the treatment of hyperglycemia were available on 89 pregnancies. The birthweight in unaffected GCK offspring was significantly higher than in the affected GCK offspring (4.8 [4.1-5.2] kg vs 3.2 [3.1-3.7] kg; P = .01). Seven-point home blood glucose monitoring over a 7-day period in each trimester demonstrated higher fasting and postprandial glycemic excursions in the first trimester of GCK pregnancies when compared to HNF-1α pregnancies (fasting 104 [90-115] mg/dL vs 84 [77-88] mg/dL; P = .01 and postprandial 154 [135-196] mg/dL vs 111 [100-131] mg/dL; P = .04) despite insulin treatment. There was a higher percentage of miscarriages in the GCK group when compared to the HNF-1α MODY group (33.3% vs 14%; P = .07), which was similar to the background population. Insulin initiated at an early gestation appeared to lower the incidence of macrosomia in GCK unaffected offspring. Hyperglycemia in HNF-1α pregnancies is easily managed with current insulin protocols; in contrast, glycemic excursions are difficult to manage in GCK pregnancies. There was an increased percentage of miscarriages in GCK pregnancies highlighting the importance of a diagnosis of GCK-MODY in women prior to conception and the necessity for preconception care. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.

    OpenAIRE

    Rossetti, L; Smith, D; Shulman, G I; Papachristou, D; DeFronzo, R A

    1987-01-01

    Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with phlorizin to normalize glucose tolerance; group IV, phlorizi...

  16. Insulin resistance and inflammation are a cause of hyperglycemia after pediatric cardiopulmonary bypass surgery.

    Science.gov (United States)

    Floh, Alejandro A; Manlhiot, Cedric; Redington, Andrew N; McCrindle, Brian W; Clarizia, Nadia A; Caldarone, Christopher A; Schwartz, Steven M

    2015-09-01

    Hyperglycemia is common after pediatric cardiopulmonary bypass (CPB) surgery and is attributed to a state of insulin resistance. We examined the role of CPB-induced inflammation on postoperative plasma glucose, insulin, and the glucose-to-insulin ratio, which was used as a marker of insulin resistance; a decrease in the ratio reflects increased resistance. We conducted an ancillary study on a previously published randomized trial of children undergoing CPB surgery. Serial blood glucose, insulin, and cytokines were drawn after CPB and at selected intervals for up to 48 hours after surgery. The primary outcome was plasma insulin levels and glucose-to-insulin ratio. Glucose delivery and feeding status were monitored for potential modifying effects. The 299 children studied were predominantly male (55%) with a median age of 2.7 (interquartile range [IQR]: 0.5-6.5) years, and weight of 12.6 (IQR: 6.4-10.8) kg. Operations had a median Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery complexity score of 1 (IQR: 1-2) and CPB time of 82 (IQR: 58-122) minutes. Hyperglycemia occurred in 85% of subjects; odds of hyperglycemia peaked at 6 hours after CPB. Plasma glucose was associated with increased insulin and a lower glucose-to-insulin ratio. Increased interleukin (IL)-6 concentrations were associated with increased glucose (estimate [EST]: 0.55 (±0.13) mmol/L; P insulin (EST: 1.14 (±0.12) μmol/L; P insulin ratio (EST: 0.21 (±0.03) mmol/μmol; P Hyperglycemia after pediatric CPB surgery is associated with hyperinsulinemia, which may reflect insulin resistance in some patients. Inflammation induced by CPB may play a causative role in insulin resistance. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  17. Stress Hyperglycemia in Pediatric Critical Illness: The Intensive Care Unit Adds to the Stress!

    OpenAIRE

    Srinivasan, Vijay

    2012-01-01

    Stress hyperglycemia (SH) commonly occurs during critical illness in children. The historical view that SH is beneficial has been questioned in light of evidence that demonstrates the association of SH with worse outcomes. In addition to intrinsic changes in glucose metabolism and development of insulin resistance, specific intensive care unit (ICU) practices may influence the development of SH during critical illness. Mechanical ventilation, vasoactive infusions, renal replacement therapies,...

  18. Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

    Science.gov (United States)

    Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

    2017-01-01

    A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m2) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns

    OpenAIRE

    Allard, C.; Desgagné, V; Patenaude, J; Lacroix, M; Guillemette, L; Battista, MC; Doyon, M; Ménard, J; Ardilouze, JL; P Perron; Bouchard, L.; Hivert, MF

    2015-01-01

    Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether ...

  20. SILIBININ DIHEMISUCCINATE DAMPENS POSTPRANDIAL HYPERGLYCEMIA IN NORMAL RATS CHALLENGED WITH CARBOHYDRATES LOAD: COMPARATIVE STUDY WITH ACARBOSE

    OpenAIRE

    Bushra Hassan Marouf

    2012-01-01

    Postprandial hyperglycemia is a major risk factor for diabetic complications leading to disabilities and mortality in diabetics. Silibinin (SDH), a flavonoid, has been tried in traditional medicine for treating many disorders including diabetes. The present study was designed to evaluate the potential of SDH to damp postprandial blood glucose level after maltose and glucose loading in normal rats. Normal, non-diabetic male Albino Wistar rats were treated with 100mg/kg SDH orally to evaluate t...

  1. Localized fetomaternal hyperglycemia: spatial and kinetic definition by positron emission tomography.

    Directory of Open Access Journals (Sweden)

    Jianrong Yao

    2010-08-01

    Full Text Available Complex but common maternal diseases such as diabetes and obesity contribute to adverse fetal outcomes. Understanding of the mechanisms involved is hampered by difficulty in isolating individual elements of complex maternal states in vivo. We approached this problem in the context of maternal diabetes and sought an approach to expose the developing fetus in vivo to isolated hyperglycemia in the pregnant rat.We hypothesized that glucose infused into the arterial supply of one uterine horn would more highly expose fetuses in the ipsilateral versus contralateral uterine horn. To test this, the glucose tracer [18F]fluorodeoxyglucose (FDG was infused via the left uterine artery. Regional glucose uptake into maternal tissues and fetuses was quantified using positron emission tomography (PET. Upon infusion, FDG accumulation began in the left-sided placentae, subsequently spreading to the fetuses. Over two hours after completion of the infusion, FDG accumulation was significantly greater in left compared to right uterine horn fetuses, favoring the left by 1.9+/-0.1 and 2.8+/-0.3 fold under fasted and hyperinsulinemic conditions (p<10(-11 n=32-35 and p<10(-12 n=27-45 respectively. By contrast, centrally administered [3H]-2-deoxyglucose accumulated equally between the fetuses of the two uterine horns. Induction of significant hyperglycemia (10(3 mg/dL localized to the left uterine artery was sustained for at least 48 hours while maternal euglycemia was maintained.This approach exposes selected fetuses to localized hyperglycemia in vivo, minimizing exposure of the mother and thus secondary effects. Additionally, a set of less exposed internal control fetuses are maintained for comparison, allowing direct study of the in vivo fetal effects of isolated hyperglycemia. Broadly, this approach can be extended to study a variety of maternal-sided perturbations suspected to directly affect fetal health.

  2. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Firth, R.G.; Bell, P.M.; Marsh, H.M.; Hansen, I.; Rizza, R.A.

    1986-05-01

    Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using (2-/sup 3/H) or (3-/sup 3/H) glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM.

  3. Inhibition of ERK1/2 worsens intestinal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Kechen Ban

    Full Text Available BACKGROUND: The role of extracellular signal-regulated protein kinase (ERK in intestinal ischemia/reperfusion (I/R injury has not been well investigated. The aim of the current study was to examine the effect of inhibition of the ERK pathway in an in vitro and in vivo model of intestinal I/R injury. METHODS: ERK1/2 activity was inhibited using the specific inhibitor, U0126, in intestinal epithelial cells under hypoxia/reoxygenation conditions and in mice subjected to 1 hour of intestinal ischemia followed by 6 hours reperfusion. In vitro, cell proliferation was assessed by MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay, apoptosis by DNA fragmentation, and migration using an in vitro model of intestinal wound healing. Cells were also transfected with a p70S6K plasmid and the effects of overexpression similarly analyzed. In vivo, the effects of U0126 on intestinal cell proliferation and apoptosis, intestinal permeability, lung and intestinal neutrophil infiltration and injury, and plasma cytokine levels were measured. Survival was also assessed after U0126. Activity of p70S6 kinase (p70S6K was measured by Western blot. RESULTS: In vitro, inhibition of ERK1/2 by U0126 significantly decreased cell proliferation and migration but enhanced cell apoptosis. Overexpression of p70S6K promoted cell proliferation and decreased cell apoptosis. In vivo, U0126 significantly increased cell apoptosis and decreased cell proliferation in the intestine, increased intestinal permeability, intestinal and lung neutrophil infiltration, and injury, as well as systemic pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β. Mortality was also significantly increased by U0126. Inhibition of ERK1/2 by U0126 also abolished activity of p70S6K both in vitro and in vivo models. CONCLUSION: Pharmacologic inhibition of ERK1/2 by U0126 worsens intestinal IR injury. The detrimental effects are mediated, at least in part, by inhibition of p70S6K, the major

  4. Cerebroplacental Ratio in Reduced Fetal Movements: Evidence for Worsening Fetal Hypoxemia.

    Science.gov (United States)

    Binder, Julia; Monaghan, Caitriona; Thilaganathan, Baskaran; Morales-Roselló, José; Khalil, Asma

    2017-08-07

    To investigate the fetal cerebroplacental ratio (CPR) in women presenting with reduced fetal movements (RFM). This is a retrospective cohort study conducted over a 7-year period at a Fetal Medicine Unit at a tertiary referral centre. 4500 singleton pregnancies presenting with RFM after 36 weeks' gestation and 1527 control pregnancies at a similar gestation without RFM were analysed. Fetal biometry and Doppler parameters were recorded and converted into centiles and multiples of the median (MoM). The CPR was defined as the ratio between the middle cerebral artery (MCA) pulsatility index (PI) and the umbilical artery (UA) PI. Maternal and pregnancy characteristics were obtained from hospital records. The MCA PI MoM (median 0.95; IQR 0.84-1.09 vs 0.97; 0.86-1.11, pMoM (median 0.97; IQR 0.83-1.15 vs 0.99; 0.85-1.16, p=0.018) were significantly lower in pregnancies with RFM when compared to controls. Women presenting with multiple episodes of RFM, defined as ≥ 2 episodes, demonstrated significantly lower CPR PI MoM (median 0.90; IQR 0.81-1.12 vs 0.96; 0.84-1.08, p=0.021) compared to single episodes. Logistic regression analysis demonstrated a significant association between maternal age (OR 0.96, 95%CI 0.93-0.99), non-Caucasian ethnicity (OR 0.72; 95% CI 0.53- 0.97), estimated fetal weight (EFW) (OR 1.01; CI 1.00-1.02), CPR PI MoM (OR 0.24; 95% CI 0.12-0.47) and the risk of recurrent RFM. Pregnancies complicated by multiple episodes of RFM show significantly lower CPR PI MoM and MCA PI MoM when compared to single episodes and controls. This is likely to represent evidence of worsening fetal hypoxemia in women presenting with recurrent RFM. This article is protected by copyright. All rights reserved.

  5. A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo

    Directory of Open Access Journals (Sweden)

    Shi-Jie Zhang

    2016-02-01

    Full Text Available Gestational diabetes mellitus (GDM is one of the leading causes of fetal malformations. However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. In this study, a high concentration of glucose (0.2 mmol per egg was injected into the air sac of chick embryos on embryo development day (EDD 1 to develop a hyperglycemia model. Results showed that 47.3% of embryonic eye malformation happened on EDD 5. In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. A reduction in Pax6 gene expression induced eye malformation in chick embryos. However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation.

  6. Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats

    Directory of Open Access Journals (Sweden)

    Nor Adlin Yusoff

    2015-08-01

    Full Text Available Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL. Further in vivo confirmatory tests showed AE (500 mg/kg to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg, sucrose (4 g/kg and starch (3 g/kg loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.

  7. Obesity and Hyperglycemia in Korean Men with Klinefelter Syndrome: The Korean Endocrine Society Registry

    Directory of Open Access Journals (Sweden)

    Seung Jin Han

    2016-12-01

    Full Text Available BackgroundThe aim of this study was to investigate the prevalence of obesity in Korean men with Klinefelter syndrome (KS and the associated risk factors for obesity and hyperglycemia.MethodsData were collected retrospectively from medical records from 11 university hospitals in Korea between 1994 and 2014. Subjects aged ≥18 years with newly diagnosed KS were enrolled. The following parameters were recorded at baseline before treatment: chief complaint, height, weight, fasting glucose level, lipid panel, blood pressure, testosterone, luteinizing hormone, follicle-stimulating hormone, karyotyping patterns, and history of hypertension, diabetes, and dyslipidemia.ResultsData were analyzed from 376 of 544 initially enrolled patients. The rate of the 47 XXY chromosomal pattern was 94.1%. The prevalence of obesity (body mass index ≥25 kg/m2 in Korean men with KS was 42.6%. The testosterone level was an independent risk factor for obesity and hyperglycemia.ConclusionObesity is common in Korean men with KS. Hypogonadism in patients with KS was associated with obesity and hyperglycemia.

  8. [Correlation between hyperglycemia levels and periodontitis in 545 officeholders in Nantong city].

    Science.gov (United States)

    Mei, You-min; Zhou, Yan

    2015-08-01

    To identify the relationship between hyperglycemia levels and periodontitis by investigating the levels of hyperglycemia and periodontal conditions of officeholders in Nantong city. From January 2013 to January 2014, 545 officeholders were randomly selected in Nantong City who underwent physical examination and divided into 2 groups: young of middle-aged adults(≤60 years) and old adults (>60 years). The data was analyzed with Chi-square test and multi-factors logistic regression by using SPSS 16.0 software package. There was a significant correlation between blood glucose levels and periodontitis. Multi-factor Logistic regression analysis showed that in the whole population, smoking, age, blood glucose levels were significantly correlated with the degree of periodontitis (PSmoking and low level of education were associated with periodontitis in young and middle-aged adults. In old people, blood glucose level more than 7.0 mmol/L and smoking were the risk factors for periodontitis. Hyperglycemia level is risk factor for periodontitis, which has an effect mainly on old adults.

  9. Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.

    Science.gov (United States)

    Burke, Susan J; Batdorf, Heidi M; Eder, Adrianna E; Karlstad, Michael D; Burk, David H; Noland, Robert C; Floyd, Z Elizabeth; Collier, J Jason

    2017-03-01

    Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+ cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Glucose transporters: cellular links to hyperglycemia in insulin resistance and diabetes.

    Science.gov (United States)

    Stringer, Danielle M; Zahradka, Peter; Taylor, Carla G

    2015-03-01

    Abnormal expression and/or function of mammalian hexose transporters contribute to the hallmark hyperglycemia of diabetes. Due to different roles in glucose handling, various organ systems possess specific transporters that may be affected during the diabetic state. Diabetes has been associated with higher rates of intestinal glucose transport, paralleled by increased expression of both active and facilitative transporters and a shift in the location of transporters within the enterocyte, events that occur independent of intestinal hyperplasia and hyperglycemia. Peripheral tissues also exhibit deregulated glucose transport in the diabetic state, most notably defective translocation of transporters to the plasma membrane and reduced capacity to clear glucose from the bloodstream. Expression of renal active and facilitative glucose transporters increases as a result of diabetes, leading to elevated rates of glucose reabsorption. However, this may be a natural response designed to combat elevated blood glucose concentrations and not necessarily a direct effect of insulin deficiency. Functional foods and nutraceuticals, by modulation of glucose transporter activity, represent a potential dietary tool to aid in the management of hyperglycemia and diabetes. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Acute Bronchitis

    Science.gov (United States)

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  12. Dynapenic abdominal obesity as predictor of mortality and disability worsening in older adults: A 10-year prospective study.

    Science.gov (United States)

    Rossi, Andrea P; Fantin, Francesco; Caliari, Cesare; Zoico, Elena; Mazzali, Gloria; Zanardo, Marina; Bertassello, Paolo; Zanandrea, Valeria; Micciolo, Rocco; Zamboni, Mauro

    2016-02-01

    There are relatively few prospective studies evaluating the combined effect of abdominal obesity and low muscle strength on worsening disability and on mortality. The study aimed at evaluating prospectively the prognostic value of dynapenic abdominal obesity definition on disability worsening in a 5.5-year follow-up and mortality in a 10-year follow-up. In 93 men and 169 women aged between 66 and 78 years, leg isometric strength, waist circumference (WC), BMI, glycemia, HOMA, lipid profile, vitamin D3, albumin, fibrinogen, physical activity level, income, smoking status and comorbidities were evaluated at the baseline. Reported disabilities were measured at baseline, 1-y, 2-y, 3-y and 5.5-y follow-up and mortality rate was evaluated during a 10-y follow-up. The study population was categorized in dynapenic abdominal obese (D/AO), nondynapenic abdominal obese (ND/AO), dynapenic nonabdominal obese (D/NAO), nondynapenic nonabdominal obese (ND/NAO) according to muscle strength/WC tertiles. D/NAO subjects presented a disability worsening risk of 1.69 times (95%CI:1.11-2.57), ND/AO subjects showed a 2-fold increase in risk (95%CI:1.34-2.98), while being D/AO more than trebled the risk, even after considering confounding variables (HR:3.39,95%CI:1.91-6.02). Mortality risk after adjustment for other confounding variables was 1.57 (95%CI:1.16-2.13) for ND/AO and 2.46 (95%CI:1.34-4.52) for D/AO. Dynapenic abdominal obese subjects are at higher risk of worsening disability and mortality than subjects with dynapenia or central fat distribution only. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. A diagnostic study in patients with sciatica establishing the importance of localization of worsening of pain during coughing, sneezing and straining to assess nerve root compression on MRI.

    Science.gov (United States)

    Verwoerd, Annemieke J H; Mens, Jan; El Barzouhi, Abdelilah; Peul, Wilco C; Koes, Bart W; Verhagen, Arianne P

    2016-05-01

    To test whether the localization of worsening of pain during coughing, sneezing and straining matters in the assessment of lumbosacral nerve root compression or disc herniation on MRI. Recently the diagnostic accuracy of history items to assess disc herniation or nerve root compression on magnetic resonance imaging (MRI) was investigated. A total of 395 adult patients with severe sciatica of 6-12 weeks duration were included in this study. The question regarding the influence of coughing, sneezing and straining on the intensity of pain could be answered on a 4 point scale: no worsening of pain, worsening of back pain, worsening of leg pain, worsening of back and leg pain. Diagnostic odds ratio's (DORs) were calculated for the various dichotomization options. The DOR changed into significant values when the answer option was more narrowed to worsening of leg pain. The highest DOR was observed for the answer option 'worsening of leg pain' with a DOR of 2.28 (95 % CI 1.28-4.04) for the presence of nerve root compression and a DOR of 2.50 (95 % CI 1.27-4.90) for the presence of a herniated disc on MRI. Worsening of leg pain during coughing, sneezing or straining has a significant diagnostic value for the presence of nerve root compression and disc herniation on MRI in patients with sciatica. This study also highlights the importance of the formulation of answer options in history taking.

  14. Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction

    DEFF Research Database (Denmark)

    Gheorghiade, Mihai; Greene, Stephen J; Butler, Javed

    2015-01-01

    IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem. OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, ...

  15. Worsening of malnutrition-inflammation score is associated with high ratio of extracellular to total body water in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Narihito Tatsumoto

    2012-06-01

    Full Text Available The Malnutrition-Inflammation Score (MIS has been reported to be associated with mortality in hemodialysis (HD patients. Bioelectrical impedance analysis is useful for assessing the body fluid components. The purpose of this study is to evaluate the association between change in MIS and fluid components in HD patients. A total of 76 patients who were receiving a 5-hour HD, 3 times weekly, were enrolled in this study. MIS was performed every 6 months. Using IN BODY 720, body fluid components were estimated once a year, including intracellular water (ICW, extracellular water (ECW, total body water (TBW, total body fat, body fat percentage and ECW/TBW ratio. In univariate analysis, worsening of MIS was correlated positively with age and ECW/TBW ratio. In multivariate analysis, worsening of MIS was significantly associated with higher ECW/TBW ratio. Higher ECW/TBW ratio remained significantly correlated with worsening of MIS in non-obese HD patients, but not in obese patients. In conclusion, non-obese HD patients who has higher ECW/TBW ratio should be considered to be a risk group for malnutrition.

  16. Ludwig's Angina: A Nightmare Worsened by Adverse Drug Reaction to Antibiotics.

    Science.gov (United States)

    Hisham, Mohamed; Sivakumar, Mundilipalayam N; Senthil Kumar, R S; Nandakumar, P

    2017-03-01

    A 52-year-old obese gentleman presented to the hospital with complaints of fever and shortness of breath for 10 days. He was admitted in the ward and treated for acute exacerbation of asthma. He was shifted to the Intensive Care Unit (ICU) for persistent fever, neck swelling, airway obstruction and desaturation. Ludwig's angina was suspected and computed tomography of neck confirmed it. A difficult airway was anticipated and preceded with surgical tracheostomy. The patient had hypersensitivity reactions to piperacillin/tazobactam; hence, he was treated with clindamycin and metronidazole. The patient improved and was discharged after five days of ICU stay and 12 days of hospitalization. This case summarizes the rare incidence of Ludwig's angina with antibiotic adverse reactions. If angioneurotic edema is coincidental with features of Ludwig's angina, it becomes more challenging. Early identification, securing the airway, and antibiotic administration are the keystone to better survival.

  17. Diffuse glioblastoma resembling acute hemorrhagic leukoencephalitis.

    Science.gov (United States)

    Schettino, Carla; Caranci, Ferdinando; Lus, Giacomo; Signoriello, Elisabetta; Eoli, Marica; Anghileri, Elena; Pollo, Bianca; Melone, Mariarosa A B; Di Iorio, Giuseppe; Finocchiaro, Gaetano; Ugga, Lorenzo; Tedeschi, Enrico

    2017-10-01

    We report the case of a young man with sudden onset of diplopia after an upper respiratory tract infection. Based on the first radiological findings acute hemorrhagic leukoencephalitis, a variant of acute disseminated encephalomyelitis, was suspected and treatment with high dose intravenous dexamethasone was started but it was stopped for intolerance. The patient clinically worsened, developing gait instability, ataxia and ophthalmoplegia; brain MRI performed 20 days later showed severe progression of the disease with subependymal dissemination. After brain biopsy of the right temporal lesion the histological diagnosis was glioblastoma. These findings suggest that MRI features of acute hemorrhagic leukoencephalitis may dissimulate the diagnosis of diffuse glioma/glioblastoma. This case underscores the importance of considering diffuse glioma in the differential diagnosis of atypical signs and symptoms of acute hemorrhagic leukoencephalitis and underlines the relevant role of integrating neuroradiologic findings with neuropathology.

  18. Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: results of the cystic fibrosis related diabetes therapy trial

    National Research Council Canada - National Science Library

    Moran, Antoinette; Pekow, Penelope; Grover, Patricia; Zorn, Martha; Slovis, Bonnie; Pilewski, Joseph; Tullis, Elizabeth; Liou, Theodore G; Allen, Holley

    2009-01-01

    Cystic fibrosis-related diabetes (CFRD) without fasting hyperglycemia (CFRD FH-) is not associated with microvascular or macrovascular complications, leading to controversy about the need for treatment...

  19. Hyperglycemia Induces a Dynamic Cooperativity of Histone Methylase and Demethylase Enzymes Associated With Gene-Activating Epigenetic Marks That Coexist on the Lysine Tail

    National Research Council Canada - National Science Library

    Daniella Brasacchio; Jun Okabe; Christos Tikellis; Aneta Balcerczyk; Prince George; Emma K. Baker; Anna C. Calkin; Michael Brownlee; Mark E. Cooper; Assam El-Osta

    2009-01-01

    Hyperglycemia Induces a Dynamic Cooperativity of Histone Methylase and Demethylase Enzymes Associated With Gene-Activating Epigenetic Marks That Coexist on the Lysine Tail Daniella Brasacchio 1 , Jun...

  20. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Kjeld Schmiegelow

    2017-04-01

    Full Text Available During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both, bone toxicities (including osteonecrosis, thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia, high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

  1. What drives progressive motor deficits in patients with acute pontine infarction?

    Directory of Open Access Journals (Sweden)

    Jue-bao Li

    2015-01-01

    Full Text Available Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deficits, and ensuing that damage to the corticospinal tracts may be responsible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.

  2. Dietary iron supplements may affect stress adaptation and aggravate stress hyperglycemia in a rat model of psychological stress.

    Science.gov (United States)

    Feng, Yan; Qi, Rui; Xu, Manni; Shen, Zhilei; Li, Min

    2012-06-01

    Iron supplementation is believed to decrease the risk of iron-deficiency anemia or low birth weight. In modern society, a majority of people are in a continual state of stress. Stress-induced hyperglycemia, known as transient hyperglycemia, may be a risk factor causing diabetes. To understand the role of iron in people under stress, it is necessary to evaluate the effect of iron supplementation on glucose or stress hyperglycemia. The effect of a diet containing non-heme iron (80 or 320 mg/kg) on Sprague-Dawley rats and those under psychological stress was evaluated. Compared with control rats, a high-iron diet (320 mg/kg) increased blood glucose transiently in normal rats but induced hyperglycemia persistently in stressed rats throughout the experiment. Iron supplements further aggravated iron deposition and oxidative stress injury to the liver induced by the stress exposure. Glucose-related stress hormones were also affected by iron supplementation in stressed rats. Oxidative stress may be one of the main reasons for insulin resistance. Moreover, changes in stress hormones indicate that high-iron supplements may affect stress adaptation. Both are primary reasons for the hyperglycemia induced by iron supplementation in stressed rats. Gaining an insight into the mechanisms and correlations of these changes may be beneficial to human health and is important for the prevention of pathologic glycemia-related diseases. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. Are There Benefits for Gestational Diabetes Mellitus in Treating Lower Levels of Hyperglycemia Than Standard Recommendations?

    Science.gov (United States)

    Nguyen, Thi Hoang Lan; Yang, Ji Wei; Mahone, Michèle; Godbout, Ariane

    2016-12-01

    The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosis of gestational diabetes mellitus (GDM) are generating discussion regarding their universal adoption. Our centre is currently using stricter GDM diagnostic criteria than those proposed by the IADPSG. Evaluation of complication rates and their predictors in our cohort may provide insight for the care of this high-risk population. Therefore, we determined complication rates and identified antepartum maternal predictors of adverse outcomes in our cohort with mild GDM. A retrospective cohort study was performed between 2005 and 2011. It included women with and without GDM, which was diagnosed if fasting plasma glucose levels were 5.0 or above or 2-hour post 75 gram oral glucose tolerance test (OGTT) were 7.8 mmol/L or higher. A total of 3712 women, with and without diabetes, were included. Rates of macrosomia and pre-eclampsia were significantly higher in the group with GDM but were lower than the rates usually reported. Macrosomia, the need for insulin therapy or caesarean section and postpartum glucose intolerance predictors included prepregnancy body mass index, excessive gestational weight gain and OGTT screening results, although no specific threshold was found. This study provides insight into GDM-related complications rates and the benefits of intervention in a large cohort of women with levels of hyperglycemia lower than those currently recommended for diagnosis of GDM. These findings suggest a continuous association between adverse outcomes and maternal hyperglycemia and highlight the important role of maternal risk factors other than glycemic results in the development of pregnancy-related complications. Milder forms of hyperglycemia that would not be identified by IADPSG guidelines may benefit from treatment. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  4. Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia in mice.

    Science.gov (United States)

    Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

    2015-12-01

    Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the last decade, affecting about 2 to 5% pregnant women. Even among women who have gestational hyperglycemia may also be positively related to adverse outcomes as GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with diabetes and insulin resistance and its expression was reported to be negatively regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a role in a gestational hyperglycemia mouse model. Mice were divided into non-pregnant and pregnant groups, and each comprised three subgroups: control, high-fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of triglycerides, total cholesterol, glucose, and insulin, as well as conducted thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides, total cholesterol, glucose, and insulin levels in the serum. Additionally, thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship correlation between Hsp70 and BAT functions. Hsp70 level is associated with hyperglycemia during pregnancy. Our results support the role of Hsp70 in facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3 pathway.

  5. Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation.

    Science.gov (United States)

    Xi, Gang; Wai, Christine; White, Morris F; Clemmons, David R

    2017-02-03

    Diabetes is a major risk factor for the development of atherosclerosis, but the mechanism by which hyperglycemia accelerates lesion development is not well defined. Insulin and insulin-like growth factor I (IGF-I) signal through the scaffold protein insulin receptor substrate 1 (IRS-1). In diabetes, IRS-1 is down-regulated, and cells become resistant to insulin. Under these conditions, the IGF-I receptor signals through an alternate scaffold protein, SHPS-1, resulting in pathophysiologic stimulation of vascular smooth muscle cell (VSMC) migration and proliferation. These studies were undertaken to determine whether IRS-1 is functioning constitutively to maintain VSMCs in their differentiated state and, thereby, inhibit aberrant signaling. Here we show that deletion of IRS-1 expression in VSMCs in non-diabetic mice results in dedifferentiation, SHPS-1 activation, and aberrant signaling and that these changes parallel those that occur in response to hyperglycemia. The mice showed enhanced sensitivity to IGF-I stimulation of VSMC proliferation and a hyperproliferative response to vascular injury. KLF4, a transcription factor that induces VSMC dedifferentiation, was up-regulated in IRS-1-/- mice, and the differentiation inducer myocardin was undetectable. Importantly, these changes were replicated in wild-type mice during hyperglycemia. These findings illuminate a new function of IRS-1: that of maintaining cells in their normal, differentiated state. Because IRS-1 is down-regulated in states of insulin resistance that occur in response to metabolic stresses such as obesity and cytokine stimulation, the findings provide a mechanism for understanding how patients with metabolic stress and/or diabetes are predisposed to developing vascular complications. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Prioletta, Annamaria; Zuo, Pengou; Folli, Franco

    2013-01-01

    Diabetes mellitus is associated to an increased risk of cardiovascular diseases. Hyperglycemia is an important factor in cardiovascular damage, working through different mechanisms such as activation of protein kinase C, polyol and hexosamine pathways, advanced glycation end products production. All of these pathways, in association to hyperglycemia-induced mitochondrial dysfunction and endoplasmic reticulum stress, promote reactive oxygen species (ROS) accumulation that, in turn, promote cellular damage and contribute to the diabetic complications development and progression. ROS can directly damage lipids, proteins or DNA and modulate intracellular signaling pathways, such as mitogen activated protein kinases and redox sensitive transcription factors causing changes in protein expression and, therefore, irreversible oxidative modifications. Hyperglycemia-induced oxidative stress induces endothelial dysfunction that plays a central role in the pathogenesis of micro- and macro-vascular diseases. It may also increase pro-inflammatory and pro-coagulant factors expression, induce apoptosis and impair nitric oxide release. Oxidative stress induces several phenotypic alterations also in vascular smooth-muscle cell (VSMC). ROS is one of the factors that can promote both VSMC proliferation/migration in atherosclerotic lesions and VSMC apoptosis, which is potentially involved in atherosclerotic plaque instability and rupture. Currently, there are contrasting clinical evidences on the benefits of antioxidant therapies in the prevention/treatment of diabetic cardiovascular complications. Appropriate glycemic control, in which both hypoglycemic and hyperglycemic episodes are reduced, in association to the treatment of dyslipidemia, hypertension, kidney dysfunction and obesity, conditions which are also associated to ROS overproduction, can counteract oxidative stress and, therefore, both microvascular and macrovascular complications of diabetes mellitus.

  7. Hyperglycemia promotes K-Ras-induced lung tumorigenesis through BASCs amplification.

    Directory of Open Access Journals (Sweden)

    Carla Micucci

    Full Text Available Oncogenic K-Ras represents the most common molecular change in human lung adenocarcinomas, the major histologic subtype of non-small cell lung cancer (NSCLC. The presence of K-Ras mutation is associated with a poor prognosis, but no effective treatment strategies are available for K-Ras -mutant NSCLC. Epidemiological studies report higher lung cancer mortality rates in patients with type 2 diabetes. Here, we use a mouse model of K-Ras-mediated lung cancer on a background of chronic hyperglycemia to determine whether elevated circulating glycemic levels could influence oncogenic K-Ras-mediated tumor development. Inducible oncogenic K-Ras mouse model was treated with subtoxic doses of streptozotocin (STZ to induce chronic hyperglycemia. We observed increased tumor mass and higher grade of malignancy in STZ treated diabetic mice analyzed at 4, 12 and 24 weeks, suggesting that oncogenic K-Ras increased lung tumorigenesis in hyperglycemic condition. This promoting effect is achieved by expansion of tumor-initiating lung bronchio-alveolar stem cells (BASCs in bronchio-alveolar duct junction, indicating a role of hyperglycemia in the activity of K-Ras-transformed putative lung stem cells. Notably, after oncogene K-Ras activation, BASCs show upregulation of the glucose transporter (Glut1/Slc2a1, considered as an important player of the active control of tumor cell metabolism by oncogenic K-Ras. Our novel findings suggest that anti-hyperglycemic drugs, such as metformin, may act as therapeutic agent to restrict lung neoplasia promotion and progression.

  8. Efficacy of a hyperglycemia treatment program in a Vascular Surgery Department supervised by Endocrinology.

    Science.gov (United States)

    Caimari, Francisca; González, Cintia; Ramos, Analía; Chico, Ana; Cubero, José M; Pérez, Antonio

    2016-01-01

    The aim of this study was to evaluate the strategy and efficacy of a hyperglycemia treatment program supervised by Endocrinology. All patients with type 2 diabetes hospitalized at the vascular surgery department over a 12 month period were retrospectively reviewed. Clinical characteristics and hyperglycemia treatment during hospitalization, at discharge and 2-6 month after discharge were collected. Glycemic control was assessed using capillary blood glucose profiles and HbA1c at admission and 2-6 months post-discharge. A total of 140 hospitalizations of 123 patients were included. The protocol to choose the insulin regimen was applied in 96.4% of patients (22.8% correction dose, 23.6% basal-correction dose and 50% basal-bolus-correction dose [BBC]). Patients with BBC had higher HbA1c (7.7±1.5% vs. 6.7 ±0.8%; P<.001) and mean glycemia on the first day of hospitalization (184.4±59.2 vs. 140.5±31.4mg/dl; P<.001). Mean blood glucose was reduced to 162.1±41.8mg/dl in the middle and 160.8±43.3mg/dl in the last 24h of hospitalization in patients with BBC (P=.007), but did not change in the remaining patients. In 22.1% patients with treatment changes performed at discharge, HbA1c decreased from 8.2±1.6 to 6.8±1.6% at 2-6 months post-discharge (P=.019). The hyperglycemia treatment protocol applied by an endocrinologist in the hospital, allows the identification of the appropriate therapy and the improvement of the glycemic control during hospitalization and discharge, supporting its efficacy in clinical practice. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Physical exercise reduces pyruvate carboxylase (PCB) and contributes to hyperglycemia reduction in obese mice.

    Science.gov (United States)

    Muñoz, Vitor Rosetto; Gaspar, Rafael Calais; Crisol, Barbara Moreira; Formigari, Guilherme Pedron; Sant'Ana, Marcella Ramos; Botezelli, José Diego; Gaspar, Rodrigo Stellzer; da Silva, Adelino S R; Cintra, Dennys Esper; de Moura, Leandro Pereira; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2017-07-14

    The present study evaluated the effects of exercise training on pyruvate carboxylase protein (PCB) levels in hepatic tissue and glucose homeostasis control in obese mice. Swiss mice were distributed into three groups: control mice (CTL), fed a standard rodent chow; diet-induced obesity (DIO), fed an obesity-inducing diet; and a third group, which also received an obesity-inducing diet, but was subjected to an exercise training protocol (DIO + EXE). Protocol training was carried out for 1 h/d, 5 d/wk, for 8 weeks, performed at an intensity of 60% of exhaustion velocity. An insulin tolerance test (ITT) was performed in the last experimental week. Twenty-four hours after the last physical exercise session, the animals were euthanized and the liver was harvested for molecular analysis. Firstly, DIO mice showed increased epididymal fat and serum glucose and these results were accompanied by increased PCB and decreased p-Akt in hepatic tissue. On the other hand, physical exercise was able to increase the performance of the mice and attenuate PCB levels and hyperglycemia in DIO + EXE mice. The above findings show that physical exercise seems to be able to regulate hyperglycemia in obese mice, suggesting the participation of PCB, which was enhanced in the obese condition and attenuated after a treadmill running protocol. This is the first study to be aimed at the role of exercise training in hepatic PCB levels, which may be a novel mechanism that can collaborate to reduce the development of hyperglycemia and type 2 diabetes in DIO mice.

  10. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study.

    Science.gov (United States)

    Gast, Karin B; Smit, Johannes W A; den Heijer, Martin; Middeldorp, Saskia; Rippe, Ralph C A; le Cessie, Saskia; de Koning, Eelco J P; Jukema, J W; Rabelink, Ton J; de Roos, Albert; Rosendaal, Frits R; de Mutsert, Renée

    2013-08-01

    The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to subclinical atherosclerosis. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, a cohort of persons of 45-65 years, BMI, waist circumference (WC), fasting glucose (FPG), HbA1c and insulin concentrations were measured and the revised HOMA-IR was calculated. The carotid Intima-Media Thickness (cIMT) was measured by ultrasound. We performed linear regression analyses between standardized values of FPG, HbA1c, HOMA-IR, BMI, WC with cIMT, and subsequently included age, sex, ethnicity, education and smoking, HOMA-IR, HbA1c and FPG, BMI and WC in the models. After exclusion of participants with glucose lowering therapy (n = 356) or missing data (n = 252), this analysis included 6065 participants, 43% men, and mean (SD) cIMT of 616 (92) μm. Differences in cIMT (95% CI) per SD were: FPG: 16 (10,21); HbA1c: 12 (7,16); HOMA-IR: 11 (6,16) μm. These associations attenuated after adjustments, and attenuated most strongly after adjustment for WC. Differences in cIMT (95% CI) per SD in the full model were: FPG: 4 (0,7); HbA1c: 2 (-1,5); HOMA-IR: 0 (-3,3); BMI 16 (13,19); WC: 18 (14,21) μm. In middle-aged individuals, we observed similar contributions of insulin resistance and hyperglycemia to subclinical atherosclerosis. These contributions were largely explained by abdominal adiposity, emphasizing the importance of weight management. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Specific MAPK inhibitors prevent hyperglycemia-induced renal diseases in type 1 diabetic mouse model.

    Science.gov (United States)

    Hong, Zhe; Hong, Zongyuan; Wu, Denglong; Nie, Hezhongrong

    2016-08-01

    Mitogen-activated protein kinase (MAPK) and renin-angiotensin system (RAS) play critical roles in the process of renal diseases, but their interaction has not been comprehensively discussed. In the present studies, we investigated the renoprotective effects of MPAK inhibitors on renal diseases in type 1 diabetic mouse model, and clarify the crosstalk among MAPK signaling. Type 1 diabetic mouse model was established in male C57BL/6 J mice, and treated with or without 10 mg/kg MAPK blockers, including ERK inhibitor PD98059, p38 inhibitor SB203850, and JNK inhibitor SP600125 for four weeks. Hyperglycemia induced renal injuries, but treating them with MAPK inhibitors significantly decreased glomerular volume and glycogen in renal tissues. Although slightly changed body weight and fasting blood glucose levels, MAPK inhibitors attenuated blood urea nitrogen, urea protein, and microalbuminuria. Administration also reduced the diabetes-induced RAS activation, including angiotensin II converting enzyme (c) and Ang II, which contributed to its renal protective effects in the diabetic mice. In addition, the anti-RAS of MAPK inhibitor treatment markedly reduced gene expression of tumor necrosis factor-α, interleukin-6, and inducible nitric oxide synthase, fibrotic accumulation, and transforming growth factor-β1 levels in renal tissues. Furthermore, chemical inhibitors and genetic siRNA results identified the crosstalk among the three MAPK signaling, and proved JNK signaling played a critical role in MAPK-mediated ACE pathway in hyperglycemia state. Collectively, these results support the therapeutic effects of MAPK-specific inhibitors, especially JNK inactivation, on hyperglycemia-induced renal damages.

  12. Robust brain hyperglycemia during general anesthesia: relationships with metabolic brain inhibition and vasodilation

    Directory of Open Access Journals (Sweden)

    R. Aaron eBola

    2016-02-01

    Full Text Available Glucose is the main energetic substrate for the metabolic activity of brain cells and its proper delivery into the extracellular space is essential for maintaining normal neural functions. Under physiological conditions, glucose continuously enters the extracellular space from arterial blood via gradient-dependent facilitated diffusion governed by the GLUT-1 transporters. Due to this gradient-dependent mechanism, glucose levels rise in the brain after consumption of glucose-containing foods and drinks. Glucose entry is also accelerated due to local neuronal activation and neuro-vascular coupling, resulting in transient hyperglycemia to prevent any metabolic deficit. Here, we explored another mechanism that is activated during general anesthesia and results in significant brain hyperglycemia. By using enzyme-based glucose biosensors we demonstrate that glucose levels in the nucleus accumbens (NAc strongly increase after iv injection of Equthesin, a mixture of chloral hydrate and sodium pentobarbital that is often used for general anesthesia in rats. By combining electrochemical recordings with brain, muscle, and skin temperature monitoring, we show that the gradual increase in brain glucose occurring during the development of general anesthesia tightly correlate with decreases in brain-muscle temperature differentials, suggesting that this rise in glucose is related to metabolic inhibition. While the decreased consumption of glucose by brain cells could contribute to the development of hyperglycemia, an exceptionally strong positive correlation (r=0.99 between glucose rise and increases in skin-muscle temperature differentials was also found, suggesting the strong vasodilation of cerebral vessels as the primary mechanism for accelerated entry of glucose into brain tissue. Our present data could explain drastic differences in basal glucose levels found in awake and anesthetized animal preparations. They also suggest that glucose entry into brain

  13. Hyperglycemia effect on coronary disease in patients with metabolic syndrome evaluated by intracoronary ultrasonography.

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    Beatriz Dal Santo Francisco Bonamichi

    Full Text Available Metabolic syndrome (MS is characterized by dyslipidemia, central obesity, hypertension and hyperglycemia. However, type 2 diabetes mellitus (T2DM may or may not be present in metabolic syndrome. MS and T2DM are considered important cardiovascular risk factors, but the role of hyperglycemia in coronary disease is still contested in the literature. Therefore, we decided to evaluate the effect of hyperglycemia on the severity of coronary disease in MS patients, with or without T2DM, submitted to coronary angiography (CA and intravascular ultrasonography (IVUS.This is a cross sectional, observational study with 100 MS patients (50% with T2DM, 60% male. All of the patients had been referred for CA procedures. The obstruction was considered severe when stenosis was greater than 70% and moderate if it was between 50-69%. Patients detected with a moderate obstruction by CA were indicated to IVUS. A minimal luminal area of less than 4mm2 detected by IVUS was also considered severe. IDF criteria were used to define Metabolic Syndrome and T2DM diagnosis was defined according to the American Diabetes Association criteria. Student's t-test and Pearson Chi-square were used for statistical analysis, considering p < 0.05 statistically significant.The majority of T2DM patients presented severe arterial lesions (74% vs 22%, p<0.001. Using CA procedure, 12% of T2DM had moderate obstructions, compared to 38% of the non-diabetic group (p< 0.05. 8% of patients with moderate lesions by CA were diagnosed with a luminal area less than 4mm2 using IVUS. This luminal area was significantly smaller in the T2DM group than in the control group (3.8mm2 ± 2.42. vs 4.6mm2 ± 2.58, p = 0.03.Patients with MS and T2DM submitted to angiography and IVUS, had more severe coronary lesions compared to MS patients without diabetes. This finding suggests that beyond insulin resistance that is present in MS, hyperglycemia may also play a role in the development of atherosclerotic disease

  14. Diabetes subdiagnosticado e necrose miocárdica: preditores de hiperglicemia no infarto do miocárdio Unrecognized diabetes and myocardial necrosis: predictors of hyperglycemia in myocardial infarction

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    Renata Teixeira Ladeira

    2013-05-01

    Full Text Available FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina, fatores do metabolismo glicídico [hemoglobina glicada (HbA1c, insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina, glicerídeos (triglicérides, VLDL e ácido graxo, fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1, inflamação (proteína C reativa ultrassensível e necrose miocárdica (CK-MB e troponina. Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p BACKGROUND: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine; glucose metabolism factors [glycated hemoglobin (HbA1c; insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin; glycerides (triglycerides, VLDL and fatty acids; coagulation factors (factor VII, fibrinogen, plasminogen

  15. TBI risk stratification at presentation: a prospective study of the incidence and timing of radiographic worsening in the Parkland Protocol.

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    Phelan, Herb A; Eastman, Alexander L; Madden, Christopher J; Aldy, Kim; Berne, John D; Norwood, Scott H; Scott, William W; Bernstein, Ira H; Pruitt, Jeffrey; Butler, Gordon; Rogers, Lowery; Minei, Joseph P

    2012-08-01

    We have created a theoretical algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI) known as the Parkland Protocol, which stratifies patients into low-, medium-, and high-risk categories for spontaneous progression of hemorrhage. This prospective study characterizes the incidence and timing of radiographic progression of the TBI patterns in these categories. Inclusion criterion was presentation with intracranial blood between February 2010 and March 2011; exclusion was receipt of only one computed tomographic scan of the head during the inpatient stay or preinjury warfarin. At admission, all patients were preliminarily categorized per the Parkland Protocol as follows: low risk (LR), patients meeting the modified Berne-Norwood criteria; moderate risk (MR), injuries larger than the modified Berne-Norwood criteria without requiring a neurosurgical procedure; high risk (HR), any patient with a craniotomy/monitor. A total of 245 patients with intracranial hemorrhage were enrolled during the 13-month study period. Of patients preliminarily classified as LR at admission (n = 136), progression was seen in 25.0%. Spontaneous worsening was seen in 7.4% of LR patients at 24 hours after injury, and no LR patients progressed at 72 hours after injury. In patients initially classified as MR at admission (n = 42), progression was seen in 42.9%, with 91.5% of patients demonstrating stable computed tomographic head scans at 72 hours after injury. In patients initially classified as HR (n = 67), 64.2% demonstrated spontaneous progression of their TBI patterns, with 10.5% continuing to progress at 72 hours after injury. Most repeat scans were performed as routinely scheduled studies (81-91%). Increases in the incidence of spontaneous worsening were seen as severities of injury progressed from the Parkland Protocol's LR to MR to HR arms. The time frames for these spontaneous worsenings seem to be such that the protocol's theoretical recommendations for

  16. Worsening anatomic outcomes following aflibercept for neovascular age-related macular degeneration in eyes previously well controlled with ranibizumab

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    Nudleman E

    2016-06-01

    Full Text Available Eric Nudleman,1 Jeremy D Wolfe,2,3 Maria A Woodward,4 Yoshihiro Yonekawa,2,3 George A Williams,2,3 Tarek S Hassan2,3 1Department of Ophthalmology, Shiley Eye Center, University of California, San Diego, La Jolla, CA, 2Beaumont Eye Institute, Oakland University William Beaumont School of Medicine, 3Associated Retinal Consultants, Royal Oak, 4Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI, USA Purpose: Antivascular endothelial growth factor injection is the mainstay of treating neovascular age-related macular degeneration (AMD. Previous studies have shown that switching treatment from ranibizumab to aflibercept led to an improvement in eyes with recalcitrant activity. Herein, we identify a unique subset of patients whose eyes with neovascular AMD were previously well controlled with ranibizumab injections were then worsened after being switched to aflibercept. Methods: This is a retrospective interventional case series. Eyes with neovascular AMD, previously well controlled with monthly injections of ranibizumab, which then developed worsening of subretinal fluid after being switched to aflibercept were included. Results: A total of 17 eyes were included. All eyes developed increased subretinal fluid when switched from ranibizumab to aflibercept. Fourteen patients were switched back to ranibizumab after a single injection of aflibercept and had subsequent rapid resolution of subretinal fluid. Three patients continued with monthly aflibercept injections for two subsequent months and demonstrated the persistence of the increased subretinal fluid until they were switched back to treatment with ranibizumab at which time the fluid resolved. No eye had persistent decline in visual acuity. Conclusion: Switching from intravitreal ranibizumab to aflibercept in eyes with well-controlled neovascular AMD may result in worsening in a subset of patients and resolves when therapy is switched back to ranibizumab. Keywords: anti

  17. Cerebral venous thrombosis due to cryptogenic organising pneumopathy with antiphospholipid syndrome worsened by heparin-induced thrombocytopenia.

    Science.gov (United States)

    Hsieh, J; Kuzmanovic, I; Vargas, M I; Momjian-Mayor, I

    2013-07-09

    Cerebral venous thrombosis (CVT) has usually been ascribed to prothrombotic conditions, oral contraceptives, pregnancy, malignancy, infection, head injury or mechanical precipitants. The case reported here illustrates two rare causes of CVT observed in the same patient: the presence of antiphospholipid antibodies associated with an asymptomatic cryptogenic organising pneumopathy (COP) which were considered the origin of the venous cerebral thrombosis and heparin-induced thrombocytopenia (HIT) which was responsible for the worsening of the thrombosis observed a few days after the introduction of treatment. Moreover, we provide here additional positive experience in the treatment of both, CVT and HIT, by fondaparinux with bridging to warfarin given their successful evolution under this anticoagulant option.

  18. Financial crisis 2007-2009. How real estate bubble and transparency and accountability issues generated and worsen the crisis

    OpenAIRE

    Bilal Aziz

    2012-01-01

    This paper seeks to explain some main factors behind the Financial Crisis 2007–2009 with a special focus on the Real Estate Bubble and Transparency and Accountability Issues in US Financial System and how these two factors generated and worsen the crisis. Financial Crisis 2007–2009, which starts from the United States sub–prime mortgage market and spread to US financial sector and later on spread to the rest of world, is said to be an even bigger crisis than the Great Depression of 1929. This...

  19. Allergic contact cheilitis from a lipstick misdiagnosed as herpes labialis: Subsequent worsening due to Zovirax contact allergy.

    Science.gov (United States)

    Ozkaya, Esen; Topkarci, Zeynep; Ozarmağan, Güzin

    2007-08-01

    A 29-year-old Turkish woman with allergic contact cheilitis from a lipstick was misdiagnosed as herpes labialis and subsequently worsened with the application of Zovirax cream. Patch tests were positive to Zovirax cream, propylene glycol, the patient's favourite lipstick and propyl gallate. No reaction was seen with Zovirax ophthalmic ointment and Zovirax tablet. The propylene glycol component of the Zovirax cream and the propyl gallate component of the lipstick were regarded as the responsible contact sensitizers. The differential diagnosis was challenging due to concomitant contact sensitization with these agents.

  20. Insulin therapy normalizes reduced myocardial β-adrenoceptors at both the onset and after sustained hyperglycemia in diabetic rats.

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    Haley, James M; Thackeray, James T; Kolajova, Maria; Thorn, Stephanie L; DaSilva, Jean N

    2015-07-01

    Reduced cardiac β-adrenoceptors (β-AR) and cardiovascular (CV) dysfunction occur in diabetes mellitus (DM) and can be normalized by insulin. It is unclear how the duration of untreated hyperglycemia prior to intervention impacts insulin's effects. This study assesses insulin's effect on reduced myocardial β-AR and CV function, comparing insulin therapy at the onset of hyperglycemia and after a sustained period of hyperglycemia in streptozotocin (STZ) rats. Ex vivo biodistribution experiments with [(3)H]CGP12177 were performed in high-fat fed STZ rats after 8 weeks of hyperglycemia evaluating cardiac β-AR expression. Western blotting of β-AR subtypes was completed in parallel. Serial echocardiography at 0, 6, and 8 weeks post-STZ investigated CV function. Sub-groups of hyperglycemic rats were treated with insulin early, at 1 week post-STZ (InsE) for 7 weeks, or late at 6 weeks post-STZ (InsL) for 2 weeks to observe how the duration of hyperglycemia prior to insulin impacts its effects. Reduced myocardial [(3)H]CGP12177 binding occurred 8 weeks post-STZ in hyperglycemics, but was normal in both insulin treatments. Western blotting supported reduced β1-AR in hyperglycemics, but not in either treatment. InsE and InsL treatments improved prolonged mitral valve deceleration (MVD) observed in hyperglycemic animals, but hyperglycemic and InsL still displayed reduced heart rates (HR). This work supports that glycemic control with insulin normalizes cardiac β-AR effectively regardless of prior hyperglycemia but HR may not recover as readily, indirectly supporting the utility of [(11)C]CGP12177 positron emission tomography (PET) in assessing cardiac β-AR and their modulation with glycemic therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A STUDY TO ESTABLISH ASSOCIAT ION OF HYPERGLYCEMIA AND INPATIENT MORTALITY IN PATIENTS WITH UNDIAGNOSED DIABETES MELLITUS

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    Mohd

    2015-06-01

    Full Text Available The aim of this study was to establish the prevalence, survival, and outcome of patients presented with in - hospital hyperglycemia in which there is prior history of diabetes and without a history of diabetes. We reviewed the medical records of 2000 consecu tive adult patients admitted to MNR Medical College, a teaching hospital in Telangana; from Jan 2014 to Nov 2014 and 1886 patients were studied 144 were excluded as glycemic records were not available. New hyperglycemia was defined as fasting glucose level of 126 mg/dl on admission or in - hospital or random blood glucose of more than 200 mg/dl or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 11.96% had no history of diabetes before the admission. It was observed that there was higher in - hospital mortality rate (16.21% in newly diagnosed hyperglycemia when compared to known diabetic patients (3.31% and subjects with normoglycemia (1.56%; both P < 0.01. In addition, new hyperglycemic patients had a prolonged hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Ou r results indicate that in - hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significan tly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.

  2. Extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in mice.

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    Wang, Jian-Yun; Zhu, Chuang; Qian, Tian-Wei; Guo, Hao; Wang, Dong-Dong; Zhang, Fan; Yin, Xiaoxing

    2015-01-01

    Oxidative stress has a central role in the progression of diabetes mellitus (DM), which can directly result in the injury of islet β cells and consequent hyperglycemia. The aim of the present study was to evaluate the possible protective effects of black bean peel extract (BBPE), pomegranate peel extract (PPE) and a combination of the two (PPE + BBPE) on streptozotocin-induced DM mice. Oxidative stress was assessed by the levels of total antioxidative capability and glutathione in the serum. Fasting blood glucose and insulin levels, as well as the pancreas weight index and the histological changes in the pancreas, were also determined. The results showed that, after fours weeks of treatment with PPE, BBPE or PPE + BBPE, DM mice showed, to different degrees, a decrease in blood glucose, increases in insulin secretion and the pancreas weight index, and an increase in antioxidative activity. These changes were particularly evident in the DM mice subjected to the combined intervention strategy of PPE + BBPE. The histological findings indicated that the injury to the pancreatic islets in DM mice was also ameliorated following treatment. In conclusion, PPE and BBPE, particularly the combination of the two, have the ability to ameliorate hyperglycemia by inhibiting oxidative stress-induced pancreatic damage; this finding may be useful in the prevention and treatment of DM.

  3. Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice.

    Science.gov (United States)

    Park, Sang Hyun; Ko, Sung Kwon; Choi, Jin Gyu; Chung, Sung Hyun

    2006-03-01

    Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of Salicornia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

  4. Chronic Hyperglycemia Modulates Rat Osteoporotic Cortical Bone Microarchitecture into Less Fragile Structures

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    Cristina de Mello-Sampayo

    2017-01-01

    Full Text Available There is controversy concerning the diabetes impact on bone quality, notorious in type 2 diabetic postmenopausal women. One pointed cause might be uncontrolled glycemia. In this study, the effect of chronic hyperglycemia in bone turnover, morphology, and biomechanics was evaluated in female Wistar rats in the presence/absence of estrogens (ovariectomy. Animals (n=28 were divided into sham, ovariectomized (OVX, hyperglycemic (streptozotocin 40 mg/kg, single-dose i.p.-STZ, and hyperglycemic-ovariectomized (STZ + OVX animals. Blood biomarkers were estimated 60 days postovariectomy. Body weight, vertebral microarchitecture (L4-histomorphometry, femur biomechanical properties (bending tests, tibia ultrastructure (scanning electron microscopy, and femur and urinary calcium (atomic absorption were also evaluated. The increased PINP/CTX ratio of hyperglycemic animals and the similar ratio between STZ + OVX and healthy animals contrasting with the lower ratio of OVX (in line with its histomorphometric data suggest a tendency for improved bone formation in hyperglycemic-ovariectomized animals. The increased tibia medullar canal, which contrasts with the unaffected cortical thickness of both hyperglycemic groups while that of OVX decreased, was associated to the increased stiffness and strength of STZ + OVX bones compared to those of OVX, in line with the observed ultrastructure. Concluding, chronic hyperglycemia in ovariectomized female rats causes bone morphological changes that translate positively in the ultrastructure and mechanical properties of cortical bones.

  5. Deletion of the Men1 Gene Prevents Streptozotocin-Induced Hyperglycemia in Mice

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    Yuqing Yang

    2010-01-01

    Full Text Available Diabetes ultimately results from an inadequate number of functional beta cells in the islets of Langerhans. Enhancing proliferation of functional endogenous beta cells to treat diabetes remains underexplored. Here, we report that excision of the Men1 gene, whose loss-of-function mutation leads to inherited multiple endocrine neoplasia type 1 (MEN1, rendered resistant to streptozotocin-induced hyperglycemia in a tamoxifen-inducible and temporally controlled Men1 excision mouse model as well as in a tissue-specific Men1 excision mouse model. Men1 excision prevented mice from streptozotocin-induced hyperglycemia mainly through increasing the number of functional beta cells. BrdU incorporation by beta cells, islet size, and circulating insulin levels were significantly increased in Men1-excised mice. Membrane localization of glucose transporter 2 was largely preserved in Men1-excised beta cells, but not in Men1-expressing beta cells. Our findings suggest that repression of menin, a protein encoded by the Men1 gene, might be a valuable means to maintain or increase the number of functional endogenous beta cells to prevent or ameliorate diabetes.

  6. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

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    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  7. Alleviating Effects of Baechu Kimchi Added Ecklonia cava on Postprandial Hyperglycemia in Diabetic Mice.

    Science.gov (United States)

    Lee, Hyun-Ah; Song, Yeong-Ok; Jang, Mi-Soon; Han, Ji-Sook

    2013-09-01

    In this study, we investigated the inhibitory effects of Baechu kimchi added Ecklonia cava on the activities of α-glucosidase and α-amylase and its alleviating effect on the postprandial hyperglycemia in STZ-induced diabetic mice. Baechu kimchi added Ecklonia cava (BKE, 15%) was fermented at 5°C for 28 days. Optimum ripened BKE was used in this study as it showed the strongest inhibitory activities on α-glucosidase and α-amylase by fermentation time among the BKEs in our previous study. The BKE was extracted with 80% methanol and the extract solution was concentrated, and then used in this study. The BKE extract showed higher inhibitory activities than Baechu kimchi extract against α-glucosidase and α-amylase. The IC50 values of the BKE extract against α-glucosidase and α-amylase were 0.58 and 0.35 mg/mL, respectively; BKE exhibited a lower α-glucosidase inhibitory activity but a higher α-amylase inhibitory activity than those of acarbose. The BKE extract alleviated postprandial hyperglycemia caused by starch loading in normal and streptozotocin-induced diabetic mice. Furthermore, the BKE extract significantly lowered the incremental area under the curve in both normal and diabetic mice (P<0.05). These results indicated that the BKE extract may delay carbohydrate digestion and thus glucose absorption.

  8. Effects of Hyperglycemia and Effects of Ketosis on Cerebral Perfusion, Cerebral Water Distribution, and Cerebral Metabolism

    Science.gov (United States)

    Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O’Donnell, Martha

    2012-01-01

    Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury. PMID:22498698

  9. Insulin requirements in non-critically ill hospitalized patients with diabetes and steroid-induced hyperglycemia.

    Science.gov (United States)

    Spanakis, Elias K; Shah, Nina; Malhotra, Keya; Kemmerer, Terri; Yeh, Hsin-Chieh; Golden, Sherita Hill

    2014-04-01

    Steroid-induced hyperglycemia is common in hospitalized patients with diabetes mellitus. Guidelines for glucose management in this setting are lacking. We conducted a retrospective chart review of non-critically ill patients with diabetes receiving steroids, hospitalized from January 2009 to October 2012. Fifty-eight patients were identified from 247 consults. Multivariable linear regression was used to assess median daily insulin requirements of normoglycemic patients compared with hyperglycemic patients. Of the 58 total patients included in our study, 20 achieved normoglycemia during admission (patient-day weighted mean blood glucose [PDWMBG] level = 154 ± 16 mg/dL) and 38 remained hyperglycemic (PDWMBG level = 243 ± 39 mg/dL; P insulin (median interquartile range [IQR])(23.6 [17.9, 31.2] vs 20.1 [16.5, 24.4]; P = 0.35); higher units of nutritional insulin (45.5 [34.2, 60.4] vs 20.1 [16.4, 24.5]; P insulin (5.8 [4.1, 8.1] vs 13.0 [10.2, 16.5]; P insulin (total daily dose [TDD]: 7.4% vs 23.4%; P insulin (TDD: 58.1% vs 36.2%; P hyperglycemia receiving steroids require a higher percentage of TDD insulin therapy as nutritional insulin to achieve normoglycemia.

  10. Umbilical cord oxidative stress in infants of diabetic mothers and its relation to maternal hyperglycemia.

    Science.gov (United States)

    Sarikabadayi, Yusuf Unal; Aydemir, Ozge; Aydemir, Cumhur; Uras, Nurdan; Oguz, Serife Suna; Erdeve, Omer; Dilmen, Ugur

    2011-01-01

    There is growing body of evidence that oxidative stress plays an important role in the pathogenesis of diabetes mellitus (DM) and in development of maternal and fetal complications of diabetic pregnancies. The aim of the present study was to investigate total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in infants of diabetic mothers (IDM) and to reveal the influence of maternal hyperglycemia on these parameters. A prospective controlled study was conducted between March 2010 and November 2010. Umbilical cord blood was taken from IDM and controls for TAC and TOS measurement, and OSI was calculated. IDM were divided into two groups, either of mothers treated with insulin during pregnancy or of those treated with a carbohydrate-restricted diet. Thirty-six IDM and 14 infants born to non-diabetic mothers were enrolled. Infants of insulin-treated mothers (group 1) and infants of mothers managed with a carbohydrate-restricted diet (group 2) had significantly higher TOS (p IDM, and a significant relation exists between the degree of maternal hyperglycemia in pregnancy and oxidative stress in the newborn at birth.

  11. Hyperglycemia at the Time of Acquiring Central Catheter-Associated Bloodstream Infections Is Associated With Mortality in Critically Ill Children.

    Science.gov (United States)

    Marsillio, Lauren E; Ginsburg, Sarah L; Rosenbaum, Cecilia H; Coffin, Susan E; Naim, Maryam Y; Priestley, Margaret A; Srinivasan, Vijay

    2015-09-01

    Hyperglycemia is common and may be a risk factor for nosocomial infections, including central catheter-associated bloodstream infections in critically ill children. It is unknown whether hyperglycemia at the time of acquiring central catheter-associated bloodstream infections in pediatric critical illness is associated with worse outcomes. We hypothesized that hyperglycemia (blood glucose concentration > 126 mg/dL [> 7 mmol/L]) at the time of acquiring central catheter-associated bloodstream infections (from 4 d prior to the day of first positive blood culture, i.e., central catheter-associated bloodstream infections) in critically ill children is common and associated with ICU mortality. Retrospective observational cohort study. Fifty-five-bed PICU and 26-bed cardiac ICU at an academic freestanding children's hospital. One hundred sixteen consecutively admitted critically ill children from January 1, 2008, to June 30, 2012, who were 0-21 years with central catheter-associated bloodstream infections were included. We excluded children with diabetes mellitus, metabolic disorders, and those with a "do not attempt resuscitation" order. None. The study cohort had an overall ICU mortality of 23%, with 48% of subjects developing hyperglycemia at the time of acquiring central catheter-associated bloodstream infections. Compared with survivors, nonsurvivors experienced more hyperglycemia both at the time of acquiring central catheter-associated bloodstream infections and subsequently. Median blood glucose at the time of acquiring central catheter-associated bloodstream infections was higher in nonsurvivors compared with survivors (139.5 mg/dL [7.7 mmol/L] vs 111 mg/dL [6.2 mmol/L]; p 7 mmol/L) during the 7 days following central catheter-associated bloodstream infections (in comparison to 45% of survivors; p = 0.03). After controlling for severity of illness and interventions, hyperglycemia at the time of acquiring central catheter-associated bloodstream infections

  12. Urinary dysfunction with detrusor hyperactivity in women with Parkinson's disease cannot be blamed as a factor of worsening motor performance

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    Raimundo Nonato Campos-Sousa

    2013-09-01

    Full Text Available Introduction Detrusor hyperactivity is the leading cause of urinary dysfunction in Parkinson's disease (PD. There are few studies correlating PD clinical aspects with this autonomic feature. Methods A cohort of 63 women with PD were prospectively examined for assessment of clinical aspects and disease severity using unified Parkinson's disease rating scale and Hoehn-Yahr scale, respectively. The urologic function was evaluated by the urodynamic study. Two groups were categorized at this time - groups with and without detrusor hyperactivity. After seven years, the same parameters were re-evaluated. Results Progression of the disease on mental scores was found in the group with detrusor hyperactivity. On follow-up, clinical symptoms and severity did not show significant worsening between the groups. Conclusion Detrusor hyperactivity is a frequent urodynamic finding in PD, and even though it is associated with dopaminergic dysfunction, it cannot be blamed as a factor of worsening motor performance, but is probably associated with poor cognitive and mental prognosis.

  13. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose?

    Science.gov (United States)

    Lagard, Camille; Chevillard, Lucie; Malissin, Isabelle; Risède, Patricia; Callebert, Jacques; Labat, Laurence; Launay, Jean-Marie; Laplanche, Jean-Louis; Mégarbane, Bruno

    2016-11-01

    Poisoning with opioid analgesics including tramadol represents a challenge. Tramadol may induce respiratory depression, seizures and serotonin syndrome, possibly worsened when in combination to benzodiazepines. Our objectives were to investigate tramadol-related neurotoxicity, consequences of diazepam/tramadol combination, and mechanisms of drug-drug interactions in rats. Median lethal-doses were determined using Dixon-Bruce's up-and-down method. Sedation, seizures, electroencephalography and plethysmography parameters were studied. Concentrations of tramadol and its metabolites were measured using liquid-chromatography-high-resolution-mass-spectrometry. Plasma, platelet and brain monoamines were measured using liquid-chromatography coupled to fluorimetry. Median lethal-doses of tramadol and diazepam/tramadol combination did not significantly differ, although time-to-death was longer with combination (P=0.04). Tramadol induced dose-dependent sedation (Pdiazepam/tramadol combination abolished seizures but significantly enhanced sedation (Pdiazepam/tramadol combination. Interestingly neither pretreatment with cyproheptadine (a serotonin-receptor antagonist) nor a benserazide/5-hydroxytryptophane combination (enhancing brain serotonin) reduced tramadol-induced seizures. Our study shows that diazepam/tramadol combination does not worsen tramadol-induced fatality risk but alters its toxicity pattern with enhanced respiratory depression but abolished seizures. Drug-drug interaction is mainly pharmacodynamic but increased plasma M1 and M5 metabolites may also contribute to enhancing respiratory depression. Tramadol-induced seizures are independent of brain serotonin. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Does varenicline worsen psychiatric symptoms in patients with schizophrenia or schizoaffective disorder? A review of published studies.

    Science.gov (United States)

    Cerimele, Joseph M; Durango, Alejandra

    2012-08-01

    To review published cases and prospective studies describing the use of varenicline in patients with schizophrenia and schizoaffective disorder. PubMed, PsychINFO, and the Cochrane Database were searched in July 2011 using the key words schizophrenia, schizoaffective disorder, psychosis, positive symptoms, negative symptoms, aggression, hostility, suicidal ideation AND varenicline to identify reports published between January 2006 and July 2011 in English. Five case reports, 1 case series, 1 retrospective study, 10 prospective studies (17 publications), and 1 meeting abstract describing the use of varenicline in patients with schizophrenia or schizoaffective disorder were identified. Review articles and articles describing findings other than the use of varenicline in patients with schizophrenia or schizoaffective disorder were excluded. Thirteen reports were included in the final analysis. Information on each study's patient population, age, diagnosis, medication treatment, tobacco use history, adverse effects, and outcome was collected from the published reports. Of the 260 patients with schizophrenia or schizoaffective disorder who received varenicline in these published reports, 13 patients (5%) experienced the onset or worsening of any psychiatric symptom, although 3 of the 13 patients experienced a very brief negative effect after 1 dose. No patients experienced suicidal ideation or suicidal behaviors. Published reports suggest that, in most stable, closely monitored patients with schizophrenia or schizoaffective disorder, varenicline treatment is not associated with worsening of psychiatric symptoms. Current, prospective studies are assessing effectiveness and further assessing safety in this population. © Copyright 2012 Physicians Postgraduate Press, Inc.

  15. Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.

    Science.gov (United States)

    Núñez, Julio; Miñana, Gema; Santas, Enrique; Bertomeu-González, Vicente

    2015-05-01

    Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney. Worsening renal function that occurs in patients with acute heart failure has been classified as cardiorenal syndrome type 1. In this setting, worsening renal function is a common finding and is due to complex, multifactorial, and not fully understood processes involving hemodynamic (renal arterial hypoperfusion and renal venous congestion) and nonhemodynamic factors. Traditionally, worsening renal function has been associated with worse outcomes, but recent findings have revealed mixed and heterogeneous results, perhaps suggesting that the same phenotype represents a diversity of pathophysiological and clinical situations. Interpreting the magnitude and chronology of renal changes together with baseline renal function, fluid overload status, and clinical response to therapy might help clinicians to unravel the clinical meaning of renal function changes that occur during an episode of heart failure decompensation. In this article, we critically review the contemporary evidence on the pathophysiology and clinical aspects of worsening renal function in acute heart failure. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Activities of Daily Living (ADL) Trajectories Surrounding Acute Hospitalization of Long-stay Nursing Home Residents

    Science.gov (United States)

    Kruse, Robin L.; Petroski, Gregory F.; Mehr, David R.; Banaszak-Holl, Jane; Intrator, Orna

    2013-01-01

    OBJECTIVES To explore patterns of change in nursing home residents’ activities of daily living (ADLs), particularly surrounding acute hospital stays. DESIGN Longitudinal study using Medicare and Minimum Data Set (MDS) assessments SETTING National sample of long-stay nursing home residents PARTICIPANTS We identified 40,128 residents who were hospitalized for the seven most common inpatient diagnoses. Each hospital admission was at least 90 days after any prior hospitalization and had at least two preceding MDS assessments. MEASUREMENTS We represented residents’ ADL function with the MDS ADL-Long form score, a simple sum of seven self-care variables coded from 0 (independent) to 4 (totally dependent). Scores ranged from 0 to 28; higher scores indicated greater impairment. We jointly estimated a linear mixed model describing ADL trajectories with mortality and hospital readmission. RESULTS Before hospitalization, the most common trajectory represented stability (53.7%), with 27.5% of residents worsening and 18.8% improving. ADL function after hospital discharge was most often characterized by stability (43.1%) or worsening (39.2%). Mortality (20.3%) was higher for those with worsening pre-hospital ADL function (28.9%) compared to those with stable (19.1%) or improving (11.3%) trajectories. Hospital diagnosis was associated with both the amount of ADL worsening and the rate of subsequent ADL change. Most residents with the best initial function continued to worsen after hospital discharge. Cognitive impairment was associated with poorer ADL function and accelerated worsening of ADLs. CONCLUSION For many long-stay nursing home residents acute hospitalization is accompanied by substantial and sustained ADL worsening. Thus, acute hospitalization presents an opportunity to revisit care goals; our results can help inform decision-making. PMID:24219192

  17. Bronchitis - acute

    Science.gov (United States)

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflamed tissue in the main ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  18. Acute cholecystitis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000264.htm Acute cholecystitis To use the sharing features on this page, please enable JavaScript. Acute cholecystitis is sudden swelling and irritation of the gallbladder. ...

  19. Treatment of hyperglycaemia in patients with acute stroke.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  20. Genetic absence of nNOS worsens fetal alcohol effects in mice. II: microencephaly and neuronal losses.

    Science.gov (United States)

    Karacay, Bahri; Mahoney, Jo; Plume, Jeffrey; Bonthius, Daniel J

    2015-02-01

    Prenatal alcohol exposure can kill developing neurons, leading to microencephaly and mental retardation. However, not all fetuses are equally vulnerable to alcohol's neurotoxic effects. While some fetuses are severely affected and are ultimately diagnosed with fetal alcohol syndrome (FAS), others have no evidence of neuropathology and are behaviorally normal. These widely different outcomes among alcohol-exposed fetuses are likely due, in part, to genetic differences. Some fetuses possess genotypes that make them much more vulnerable than others to alcohol's teratogenic effects. However, to date, only 1 gene has been identified whose mutation can worsen alcohol-induced behavioral deficits in an animal model of FAS. That gene is neuronal nitric oxide synthase (nNOS). The purpose of this study was to determine whether mutation of nNOS can likewise worsen alcohol-induced microencephaly and lead to permanent neuronal deficits. Wild-type and nNOS(-/-) mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests; the results of which are reported in the companion paper. The brains were then weighed, and stereological cell counts were performed on the cerebral cortex and hippocampal formation, which are the brain regions that mediate the aforementioned behavioral tasks. Alcohol caused dose-dependent microencephaly, but only in the nNOS(-/-) mice and not in wild-type mice. Alcohol-induced neuronal losses were more severe in the nNOS(-/-) mice than in the wild-type mice in all of the brain regions examined, including the cerebral cortex, hippocampal CA3 subregion, hippocampal CA1 subregion, and dentate gyrus. Targeted mutation of the nNOS gene increases the vulnerability of the developing brain to alcohol-induced growth restriction and neuronal losses. This increased neuropathology is associated with worsened behavioral dysfunction. The results demonstrate the critical importance

  1. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes

    Science.gov (United States)

    Mathews, Clayton E.; Xue, Song; Posgai, Amanda; Lightfoot, Yaima L.; Li, Xia; Lin, Andrea; Wasserfall, Clive; Haller, Michael J.; Schatz, Desmond

    2015-01-01

    Most natural history models for type 1 diabetes (T1D) propose that overt hyperglycemia results after a progressive loss of insulin-secreting β-cell mass and/or function. To experimentally address this concept, we prospectively determined morning blood glucose measurements every other day in multiple cohorts (total n = 660) of female NOD/ShiLtJ mice starting at 8 weeks of age until diabetes onset or 26 weeks of age. Consistent with this notion, a majority of mice that developed diabetes (354 of 489 [72%]) displayed a progressive increase in blood glucose with transient excursions >200 mg/dL, followed by acute and persistent hyperglycemia at diabetes onset. However, 135 of the 489 (28%) diabetic animals demonstrated normal glucose values followed by acute (i.e., sudden) hyperglycemia. Interestingly, diabetes onset occurred earlier in mice with acute versus progressive disease onset (15.37 ± 0.3207 vs. 17.44 ± 0.2073 weeks of age, P < 0.0001). Moreover, the pattern of onset (i.e., progressive vs. acute) dramatically influenced the ability to achieve reversal of T1D by immunotherapeutic intervention, with increased effectiveness observed in situations of a progressive deterioration in euglycemia. These studies highlight a novel natural history aspect in this animal model, one that may provide important guidance for the selection of subjects participating in human trials seeking disease reversal. PMID:26216853

  2. Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species production in macrophages.

    Directory of Open Access Journals (Sweden)

    Carlos Zgheib

    Full Text Available Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized by insulin resistance and resulting hyperglycemia, which is associated with impaired wound healing. The clinical complications associated with hyperglycemia are attributed, in part, to the increased production of reactive oxygen species (ROS. Recent studies revealed that long non-coding RNAs (lncRNAs play important regulatory roles in many biological processes. Specifically, lncRNA Lethe has been described as exhibiting an anti-inflammatory effect by binding to the p65 subunit of NFκB and blocking its binding to DNA and the subsequent activation of downstream genes. We therefore hypothesize that dysregulation of Lethe's expression plays a role in hyperglycemia-induced ROS production. To test our hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM or high glucose (25 mM for 24h. High glucose conditions significantly induced ROS production and NOX2 gene expression in RAW cells, while significantly decreasing Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the increased ROS production induced by high glucose conditions, while also attenuating the upregulation of NOX2 expression. Similar results was found also in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage (BMM. Furthermore, overexpression of Lethe in RAW cells treated with high glucose significantly reduced the translocation of p65-NFkB to the nucleus, which resulted in decreased NOX2 expression and ROS production. Interestingly, these findings are consistent with the decreased Lethe gene expression and increased NOX2 gene expression observed in a mouse model of diabetic wound healing. These findings provide the first evidence that lncRNA Lethe is involved in the regulation of ROS production in macrophages through modulation of NOX2 gene expression via NFκB signaling. Moreover, this is the first report to describe a role of lncRNAs, in particular

  3. Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species production in macrophages.

    Science.gov (United States)

    Zgheib, Carlos; Hodges, Maggie M; Hu, Junyi; Liechty, Kenneth W; Xu, Junwang

    2017-01-01

    Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized by insulin resistance and resulting hyperglycemia, which is associated with impaired wound healing. The clinical complications associated with hyperglycemia are attributed, in part, to the increased production of reactive oxygen species (ROS). Recent studies revealed that long non-coding RNAs (lncRNAs) play important regulatory roles in many biological processes. Specifically, lncRNA Lethe has been described as exhibiting an anti-inflammatory effect by binding to the p65 subunit of NFκB and blocking its binding to DNA and the subsequent activation of downstream genes. We therefore hypothesize that dysregulation of Lethe's expression plays a role in hyperglycemia-induced ROS production. To test our hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM) or high glucose (25 mM) for 24h. High glucose conditions significantly induced ROS production and NOX2 gene expression in RAW cells, while significantly decreasing Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the increased ROS production induced by high glucose conditions, while also attenuating the upregulation of NOX2 expression. Similar results was found also in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage (BMM). Furthermore, overexpression of Lethe in RAW cells treated with high glucose significantly reduced the translocation of p65-NFkB to the nucleus, which resulted in decreased NOX2 expression and ROS production. Interestingly, these findings are consistent with the decreased Lethe gene expression and increased NOX2 gene expression observed in a mouse model of diabetic wound healing. These findings provide the first evidence that lncRNA Lethe is involved in the regulation of ROS production in macrophages through modulation of NOX2 gene expression via NFκB signaling. Moreover, this is the first report to describe a role of lncRNAs, in particular Lethe, in

  4. Acute Pancreatitis Complicated with Diabetic Ketoacidosis in a Young Adult without Hypertriglyceridemia: A Case Report.

    Science.gov (United States)

    Kim, Jung Hyun; Oh, Myung Jin

    2016-11-25

    Systemic complications related to acute pancreatitis include acute respiratory distress syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation, hypocalcemia, hyperglycemia, and insulin dependent diabetes or diabetic ketoacidosis. In practice, the development of diabetic ketoacidosis induced by acute pancreatitis is rare and generally associated with hypertriglyceridemia. However, herein we report a case of a 34-year-old female without hypertriglyceridemia, who was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis. The patient was admitted with complaints of febrile sensation, back pain, and abdominal pain around the epigastric area. Levels of serum amylase and lipase were elevated to 663 U/L and 3,232 U/L. Contrast-enhanced abdominal CT showed pancreatic swelling, peri-pancreatic fat infiltration and fluid collection. The patient was initially diagnosed with simple acute pancreatitis. Though the symptoms were rapidly relieved after initiation of treatment, severe hyperglycemia (575 mg/dL), severe metabolic acidosis (pH 6.9), and ketonuria developed at four days after hospitalization. However, serum triglyceride levels remained within the normal range (134 mg/dL). Finally, the patient was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis unrelated to hypertriglyceridemia. She recovered through insulin and fluid therapy, and receives insulin therapy at the outpatient clinic.

  5. Chronic Pulsatile Hyperglycemia Reduces Insulin Secretion and Increases Accumulation of Reactive Oxygen Species in Fetal Sheep Islets

    Science.gov (United States)

    Green, Alice S.; Chen, Xiaochuan; Macko, Antoni R.; Anderson, Miranda J.; Kelly, Amy C.; Hart, Nathaniel J.; Lynch, Ronald M.; Limesand, Sean W.

    2012-01-01

    Children from diabetic pregnancies have a greater incidence of Type 2 diabetes. Our objective was to determine if exposure to mild-moderate hyperglycemia, modeling managed diabetic pregnancies, affects fetal β-cell function. In sheep fetuses β-cell responsiveness was examined after two weeks of sustained hyperglycemia with 3 pulses/day, mimicking postprandial excursions, and compared to saline-infused controls (n=10). Two pulsatile hyperglycemia treatments were studied: mild (mPHG, n=5) with +15% sustained and +55% pulse; and moderate (PHG, n=10) with +20% sustained and +100% pulse. Fetal glucose-stimulated insulin secretion and glucose potentiated arginine insulin secretion were lower (Pinsulin) but not mPHG fetuses (1.21±0.08 and 4.25±0.56 ng/ml) compared to controls (1.58±0.25 and 4.51±0.56 ng/ml). Islet insulin content was 35% lower in PHG and 35% higher in mPHG versus controls (PInsulin secretion and maximally stimulated insulin release were also reduced (Pinsulin content. Isolated PHG islets also had 63% greater (Pinsulin resistance. Our findings show that PHG induced dysregulation of islet ROS handling and decreased islet insulin content, but these outcomes are independent. The β-cell outcomes were dependent on the severity of hyperglycemia because mPHG fetuses had no distinguishable impairments in ROS handling or insulin secretion but greater insulin content. PMID:22182602

  6. Effect of hyperalimentation and insulin-treated hyperglycemia on tyrosine levels in very preterm infants receiving parenteral nutrition.

    Science.gov (United States)

    Mayes, Kelly; Tan, Maw; Morgan, Colin

    2014-01-01

    Hyperalimentation describes the increase in glucose, amino acids (AAs), and lipid intake designed to overcome postnatal growth failure in preterm infants. Preterm infants are dependent on phenylalanine metabolism to maintain tyrosine levels because of tyrosine concentration limits in parenteral nutrition (PN). We hypothesized that hyperalimentation would increase individual AA levels when compared with the control group but avoid high phenylalanine/tyrosine levels. To compare the plasma AA profiles on days 8-10 of life in preterm infants receiving a hyperalimentation vs a control regimen. Infants hyperglycemia, insulin use, urea, and AA profile. Plasma profiles of 23 individual AA levels were measured on days 8-10 using ion exchange chromatography. One hundred forty-two infants were randomized with 118 AA profiles obtained on days 8-10. There were no differences in birth weight or gestation between groups. There was an increase (P insulin-treated hyperglycemia. No difference between the groups was apparent in tyrosine levels when substratified for insulin-treated hyperglycemia. All insulin vs no insulin comparisons showed lower tyrosine levels with insulin treatment (P insulin-treated hyperglycemia.

  7. Pathophysiological aspects of hyperglycemia in children with meningococcal sepsis and septic shock: A prospective, observational cohort study

    NARCIS (Netherlands)

    J.J. Verhoeven (Jennifer)

    2011-01-01

    textabstractIntroduction: The objective of this study was to investigate the occurrence of hyperglycemia and insulin response in critically ill children with meningococcal disease in the intensive care unit of an academic children's hospital.Methods: Seventy-eight children with meningococcal disease

  8. Hyperglycemia in children with meningococcal sepsis and septic shock: The relation between plasma levels of insulin and inflammatory mediators

    NARCIS (Netherlands)

    D.A. van Waardenburg (Dick); T.C. Jansen (Tim); G. Vos (Gijs); W.A. Buurman (Wim)

    2006-01-01

    textabstractContext: Hyperglycemia and insulin resistance are common findings in critically ill adult patients and are associated with increased morbidity and mortality. Objectives: The objective of this study was to investigate the hyperglycemic response to critical illness in children. Design: The

  9. Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia

    Science.gov (United States)

    Meek, Thomas H.; Dorfman, Mauricio D.; Matsen, Miles E.; Fischer, Jonathan D.; Cubelo, Alexis; Kumar, Monica R.; Taborsky, Gerald J.

    2015-01-01

    Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. As expected, plasma glucagon levels were elevated in STZ-DM rats, and although liraglutide treatment lowered glucagon levels to those of nondiabetic controls, it failed to attenuate diabetic hyperglycemia, elevated rates of glucose appearance (Ra), or increased hepatic gluconeogenic gene expression. In contrast, it markedly reduced levels of both plasma ketone bodies and hepatic expression of the rate-limiting enzyme involved in ketone body production. To independently confirm this finding, in a separate study, treatment of STZ-DM rats with a glucagon-neutralizing antibody was sufficient to potently lower plasma ketone bodies but failed to normalize elevated levels of either blood glucose or Ra. These data suggest that in rats with uDM, hyperglucagonemia is required for ketosis but not for increased HGP or hyperglycemia. PMID:25633417

  10. Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

    Science.gov (United States)

    Adipose tissue macrophages play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet-induced obesity has been shown to lead to adipose tissue macrophages accumulation in rodents;however, the impact of hyperglycemia on adipose tissue macrophages dynamics in high-fat diet-fed ...

  11. Acute Peripheral but Not Central Administration of Olanzapine Induces Hyperglycemia Associated with Hepatic and Extra-Hepatic Insulin Resistance

    NARCIS (Netherlands)

    Girault, Elodie M.; Alkemade, Anneke; Foppen, Ewout; Ackermans, Mariëtte T.; Fliers, Eric; Kalsbeek, Andries

    2012-01-01

    Atypical antipsychotic drugs such as Olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying the metabolic side-effects of these centrally acting drugs are still unknown to a large extent. We compared the effects of peripheral

  12. Delayed diagnosis and worsening of pain following orthopedic surgery in patients with complex regional pain syndrome (CRPS).

    Science.gov (United States)

    Lunden, Lars K; Kleggetveit, Inge P; Jørum, Ellen

    2016-04-01

    Complex regional pain syndrome (CRPS) is a serious and disabling chronic pain condition, usually occurring in a limb. There are two main types, CRPS 1 with no definite nerve lesion and CRPS 2 with an identified nerve lesion. CRPS 1 and 2 may occur following an injury (frequently following fractures), surgery or without known cause. An early diagnosis and start of adequate treatment is considered desirable for patients with CRPS. From the clinical experience of the principal investigator, it became apparent that CRPS often remained undiagnosed and that the clinical conditions of many patients seemed to be worsened following orthopedic surgery subsequent to the initial eliciting event. The aim of the present retrospective study of 55 patients, all diagnosed with either CRPS 1 or 2, was to evaluate the time from injury until diagnosis of CRPS and the effect on pain of orthopedic surgical intervention subsequent to the original injury/surgery. Clinical symptoms with an emphasis on pain were assessed by going through the patients' records and by information given during the investigation at Oslo University Hospital, where the patients also were examined clinically and with EMG/neurography. Alteration in pain was evaluated in 27 patients who underwent orthopedic surgery subsequent to the eliciting injury. Of a total of 55 patients, 28 women and 27 men (mean age 38.7 (SD 12.3), 38 patients were diagnosed with CRPS type 1, and 17 with CRPS type 2. Mean time before diagnosis was confirmed was 3.9 years (SD1.42, range 6 months-10 years). The eliciting injuries for both CRPS type 1 and type 2 were fractures, squeeze injuries, blunt injuries, stretch accidents and surgery. A total of 27 patients (14 men and 13 women) were operated from one to 12 times at a later stage (from 6 months to several years) following the initial injury or any primary operation because of fracture. A total of 22 patients reported a worsening of pain following secondary surgical events, while four

  13. Financial crisis 2007-2009. How real estate bubble and transparency and accountability issues generated and worsen the crisis

    Directory of Open Access Journals (Sweden)

    Bilal Aziz

    2012-07-01

    Full Text Available This paper seeks to explain some main factors behind the Financial Crisis 2007–2009 with a special focus on the Real Estate Bubble and Transparency and Accountability Issues in US Financial System and how these two factors generated and worsen the crisis. Financial Crisis 2007–2009, which starts from the United States sub–prime mortgage market and spread to US financial sector and later on spread to the rest of world, is said to be an even bigger crisis than the Great Depression of 1929. This crisis is unique in this way and we haven’t seen such a bigger impact world wide from any other crisis. This paper would empirically prove the main causes which are right in the heart of the crisis and least discussed

  14. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.

    Science.gov (United States)

    Jing, Yu-Hong; Song, Yan-Feng; Yao, Ya-Ming; Yin, Jie; Wang, De-Gui; Gao, Li-Ping

    2014-10-01

    Hyperglycemia is an essential risk factor for mothers and fetuses in gestational diabetes. Clinical observation has indicated that the offspring of mothers with diabetes shows impaired somatosensory function and IQ. However, only a few studies have explored the effects of hyperglycemia on fetal brain development. Neurodevelopment is susceptible to environmental conditions. Thus, this study aims to investigate the effects of maternal hyperglycemia on fetal brain development and to evaluate insulin and insulin-like growth factor-I (IGF-I) signals in fetal brain under hyperglycemia or controlled hyperglycemia. At day 1 of pregnancy, gestational rats were intraperitoneally injected with streptozocin (60 mg/kg). Some of the hyperglycemic gestational rats were injected with insulin (20 IU, two times a day) to control hyperglycemia; the others were injected with saline of equal volume. The gestational rats were sacrificed at days 14, 16, and 18 of embryo development. The dendritic spines of subplate cortex neurons in the fetal brain were detected by Golgi-Cox staining. The mRNA levels of insulin receptors (IRs) and IGF-IR in the fetal brain were measured using qRT-PCR. The protein levels of synaptophysin, IR, and IGF-IR in the fetal brain were detected by western blot. No significant difference in fetal brain formation was observed between the maternal hyperglycemic group and insulin-treated group. By contrast, obvious retardation of dendritic development in the fetus was observed in the maternal hyperglycemic group. Similarly, synaptophysin expression was lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. The mRNA and protein expression levels of IRs in the fetal brain were higher in the hyperglycemic group than in the insulin-treated group. By contrast, the levels of IGF-IR in the brain were lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. These results suggested that

  15. Latent Growth-Curve Analysis Reveals That Worsening Parkinson’s Disease Quality of Life Is Driven by Depression

    Science.gov (United States)

    Jones, Jacob D.; Marsiske, Michael; Okun, Michael S.; Bowers, Dawn

    2016-01-01

    Objective Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a wide variety of symptoms. The current study examined the influence of apathy, depression and motor symptoms on quality of life (QoL) in PD patients. Information was drawn from an 18-month period. Method Participants (N = 397) were assessed for apathy (Apathy Scale; Starkstein et al., 1992), depression (Beck Depression Inventory-II; Beck, Steer, Ball & Ranieri, 1996), motor severity (Unified Parkinson’s Disease Rating Scale, Part III; UPDRS; Fahn, Elton & Committee, 1987), and QoL (Parkinson’s Disease Questionnaire-39; Jenkinson, Fitzpatrick, Peto, Greenhall, & Hyman,1997) at 3 time points: an initial clinical evaluation (baseline), a 6-month follow-up, and an 18-month follow-up. Latent growth-curve models were used to determine the influence of apathy, depression, and motor symptoms on QoL trajectories. Results Greater difficulties with QoL at baseline showed the strongest relationship to more severe depression symptoms, followed by more severe motor symptoms, younger age, and less education (all p values < .001). Worsening of QoL over the 18-month period was only predicted by a worsening of depression (p = .003). The relationship between QoL and depression symptoms remained significant in a subsample of nondepressed PD patients. Conclusion Overall, findings from the current study suggest that self-reported QoL among PD patients is primarily related to depression. Future efforts to improving clinical care of PD patients may benefit by focusing on improving psychosocial adjustment or treatments targeting depression. PMID:25365564

  16. Latent growth-curve analysis reveals that worsening Parkinson's disease quality of life is driven by depression.

    Science.gov (United States)

    Jones, Jacob D; Marsiske, Michael; Okun, Michael S; Bowers, Dawn

    2015-07-01

    Parkinson's disease (PD) is a neurodegenerative disorder resulting in a wide variety of symptoms. The current study examined the influence of apathy, depression and motor symptoms on quality of life (QoL) in PD patients. Information was drawn from an 18-month period. Participants (N = 397) were assessed for apathy (Apathy Scale; Starkstein et al., 1992), depression (Beck Depression Inventory-II; Beck, Steer, Ball & Ranieri, 1996), motor severity (Unified Parkinson's Disease Rating Scale, Part III; UPDRS; Fahn, Elton & Committee, 1987), and QoL (Parkinson's Disease Questionnaire-39; Jenkinson, Fitzpatrick, Peto, Greenhall, & Hyman,1997) at 3 time points: an initial clinical evaluation (baseline), a 6-month follow-up, and an 18-month follow-up. Latent growth-curve models were used to determine the influence of apathy, depression, and motor symptoms on QoL trajectories. Greater difficulties with QoL at baseline showed the strongest relationship to more severe depression symptoms, followed by more severe motor symptoms, younger age, and less education (all p values < .001). Worsening of QoL over the 18-month period was only predicted by a worsening of depression (p = .003). The relationship between QoL and depression symptoms remained significant in a subsample of nondepressed PD patients. Overall, findings from the current study suggest that self-reported QoL among PD patients is primarily related to depression. Future efforts to improving clinical care of PD patients may benefit by focusing on improving psychosocial adjustment or treatments targeting depression. (c) 2015 APA, all rights reserved).

  17. A Chinese Herbal Medicine, Tokishakuyakusan, Reduces the Worsening of Impairments and Independence after Stroke: A 1-Year Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Hirozo Goto

    2011-01-01

    Full Text Available In post-stroke patients, the recurrence of stroke and progression of impairments lead to a bedridden state and dementia. As for their treatments, only anti-hypertension and anti-coagulation therapies to prevent the recurrence of stroke are available. In Asia, post-stroke patients with impairments are often treated with herbal medicine. The present study evaluated the effectiveness of tokishakuyakusan (TS in improving the impairment and independence in post-stroke patients. Thirty-one post-stroke patients (mean age = 81.4 years were recruited and enrolled. Participants were randomly assigned to the TS group (n = 16 or non-treatment (control group (n = 15 and treated for 12 months. Impairments were assessed using the Stroke Impairment Assessment Set (SIAS. Independence was evaluated using the functional independence measure (FIM. For each outcome measure, mean change was calculated every 3 months. The results were that impairments according to SIAS did not significantly change in the TS group. In contrast, SIAS significantly worsened in the control group. There was a significant difference between the two groups. In each term of SIAS, affected lower extremity scores, abdominal muscle strength, function of visuospatial perception, and so forth. in the TS group were better than those in the control group. Independence according to FIM did not change significantly in the TS group. In contrast, FIM significantly worsened in the control group. There was also a significant difference between the two groups. In conclusion, TS was considered to suppress the impairments of lower limbs and to exert a favorable effect on cerebral function for post-stroke patients.

  18. Moderate hyperglycaemia is associated with favourable outcome in acute lacunar stroke

    NARCIS (Netherlands)

    Uyttenboogaart, Maarten; Koch, Marcus W; Stewart, Roy E; Vroomen, Patrick C; Luijckx, Gert-Jan; De Keyser, Jacques

    Hyperglycaemia in acute ischaemic stroke is traditionally associated with a worsened outcome. However, it is unclear whether the impact of hyperglycaemia on stroke outcome is similar in lacunar and non-lacunar infarctions. The relation between serum glucose measured within 6 h after stroke onset and

  19. Current understanding of metformin effect on the control of hyperglycemia in diabetes.

    Science.gov (United States)

    An, Hongying; He, Ling

    2016-03-01

    Metformin is a first-line oral anti-diabetic agent that has been used clinically to treat patients with type 2 diabetes for over 60 years. Due to its efficacy in therapy and affordable price, metformin is taken by more than 150 million people each year. Metformin improves hyperglycemia mainly through the suppression of hepatic gluconeogenesis along with the improvement of insulin signaling. However, its mechanism of action remains partially understood and controversial, especially in regard to the role of AMPK in metformin's action and the mechanism of AMPK activation. In this review, we discuss recent advances in the understanding of metformin's suppression of hepatic glucose production and the mechanism related to the improvement of insulin signaling. © 2016 Society for Endocrinology.

  20. Hyperglycemia and insulin resistance and the risk of BPH/LUTS: an update of recent literature.

    Science.gov (United States)

    Breyer, Benjamin N; Sarma, Aruna V

    2014-12-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are highly prevalent in older men and represent a substantial challenge to public health. Increasing epidemiologic evidence suggests that diabetes and associated hyperglycemia and insulin resistance significantly increase the risks of BPH and LUTS. Plausible pathophysiologic mechanisms to explain these associations include increased sympathetic tone, stimulation of prostate growth by insulin and related trophic factors, alterations in sex steroid hormone expression, and induction of systemic inflammation and oxidative stress. This article presents a comprehensive update of the current understanding of clinical and epidemiologic research on diabetes and BPH/LUTS, describes hypothesized pathophysiologic mechanisms linking these conditions, and recommends future directions for research.