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Sample records for acute hyperglycemia worsens

  1. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats.

    PubMed

    Huang, Jingyang; Liu, Baoyi; Yang, Chenghui; Chen, Haili; Eunice, Dzivor; Yuan, Zhongrui

    2013-10-16

    Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

  2. Stereotypies as a manifestation of acute hyperglycemia without ketosis.

    PubMed

    Baizabal-Carvallo, José Fidel; Ondo, William G

    2012-04-15

    Acute hyperglycemia without ketosis is recognized to induce movement disorders characterized by hemichorea, hemiballismus, or hemidystonia. A video-case of hyperkinetic movement disorder resembling stereotypies in the context of uncompensated hyperglycemia without ketosis is presented, expanding the clinical phenotype of this disorder.

  3. Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model

    PubMed Central

    Guo, Chuang; Zhang, Shuai; Li, Jia-Yi; Ding, Chen; Yang, Zhao-Hui; Chai, Rui; Wang, Xu; Wang, Zhan-You

    2016-01-01

    Compelling evidence has indicated that dysregulated glucose metabolism links Alzheimer’s disease (AD) and diabetes mellitus (DM) via glucose metabolic products. Nevertheless, because of the lack of appropriate animal models, whether chronic hyperglycemia worsens AD pathologies in vivo remains to be confirmed. Here, we crossed diabetic mice (Pdx1+/− mice) with Alzheimer mice (APP/PS1 transgenic mice) to generate Pdx1+/−/APP/PS1. We identified robust increases in tau phosphorylation, the loss of the synaptic spine protein, amyloid-β (Aβ) deposition and plaque formation associated with increased microglial and astrocyte activation proliferation, which lead to exacerbated memory and cognition deficits. More importantly, we also observed increased glucose intolerance accompanied by Pdx1 reduction, the formation of advanced glycation end-products (AGEs), and the activation of the receptor for AGEs (RAGE) signaling pathways during AD progression; these changes are thought to contribute to the processing of Aβ precursor proteins and result in increased Aβ generation and decreased Aβ degradation. Protein glycation, increased oxidative stress and inflammation via hyperglycemia are the primary mechanisms involved in the pathophysiology of AD. These results indicate the pathological relationship between these diseases and provide novel insights suggesting that glycemic control may be beneficial for decreasing the incidence of AD in diabetic patients and delaying AD progression. PMID:27406855

  4. Acute Hyperglycemia Associated with Anti-Cancer Medication

    PubMed Central

    Hwangbo, Yul

    2017-01-01

    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. PMID:28345313

  5. The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization.

    PubMed

    Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

    2016-01-01

    Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke.

  6. Hyperglycemia in acute heart failure: an opportunity to intervene?

    PubMed

    Lazzeri, Chiara; Valente, Serafina; Gensini, Gian Franco

    2014-09-01

    In patients with acute heart failure (AHF) syndromes, little data are so far available on the relation between glucose values and insulin resistance and mortality, both in the short and long term. The present review is aimed at summarizing available evidence on the prognostic role of hyperglycemia in acute heart failure syndromes. Despite the fact that glucose values are widely measured, inexpensive, and easy to interpret, hyperglycemia in AHF patients still appears to be (or at least to have been) a neglected factor. Scarce information is available on incidence of admission hyperglycemia (especially in nondiabetic AHF patients) and data on in-hospital and discharge glucose values are lacking. Overall, the scarcity of data and the unanswered questions conjure up the need for trials investigating the clinical and prognostic role of glucose abnormalities (hyperglycemia and acute insulin resistance) on admission and during hospital stay in AHF patients. Preliminary evidence suggests that hyperglycemia is an important prognostic factor in AHF; however, whether targeting hyperglycemia via an aggressive versus permissive glycemic management strategy influences AHF outcomes remains unknown.

  7. Hyperglycemia

    MedlinePlus

    Hyperglycemia means high blood sugar or glucose. Glucose comes from the foods you eat. Insulin is a hormone that moves glucose into your ... taking medicines correctly. Other problems that can raise blood sugar include infections, certain medicines, hormone imbalances, or ...

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

    PubMed

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

    2017-02-01

    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 patients with acute ischemic stroke. Methods We included 812 patients with acute ischemic stroke (mean age 66 ± 14 years; 61.5% male). Patients were categorized per hemoglobin A1c level: no (<39 mmol/mol), moderate (39-42 mmol/mol), or severe chronic hyperglycemia (>42 mmol/mol). Poor functional outcome was defined as modified Rankin Scale score > 2 after 3 months. The relation between chronic hyperglycemia and functional outcome was assessed with a Poisson regression analysis and expressed as risk ratios with 95% confidence intervals with no chronic hyperglycemia as the reference. Results Moderate chronic hyperglycemia was present in 234 (28.8%) patients and severe chronic hyperglycemia in 183 (22.5%) patients. Acute hyperglycemia on admission was present in 338 (41.6%) patients. Severe chronic hyperglycemia was associated with poor outcome (risk ratios 1.40; 95% confidence interval 1.09-1.79). After adjustment for age, sex, stroke severity, vascular risk factors, and acute hyperglycemia on admission the risk ratios was 1.35 (95% confidence interval 1.04-1.76). Moderate chronic hyperglycemia was not associated with poor outcome (risk ratios 1.12; 95% confidence interval 0.87-1.44). Conclusion Severe chronic hyperglycemia is associated with poor functional outcome in patients with acute ischemic stroke. This association is independent of hyperglycemia in the acute stage of stroke and of an unfavorable vascular risk factor profile.

  9. Acute Clinical Worsening after Steroid Administration in Cervical Myelitis May Reveal a Subdural Arteriovenous Fistula

    PubMed Central

    Rain, Silvia; Udding, Jan; Broere, Daniel

    2016-01-01

    Subdural arteriovenous fistula (SDAVF) is a rare condition characterized by clinical manifestations ranging from mild bilateral sensory deficits to quadriplegia. The diagnosis is often delayed due to unspecific neurological symptoms, initially diagnosed as polyneuropathy or myelopathy. The diagnosis can be delayed for as long as 1–15 years. The following report describes a cervical SDAVF case initially misdiagnosed as myelitis transversa and treated with intravenous steroids. A 56-year-old male presented with sensory deficits and mild leg and right arm weakness. Cervical MRI showed a central medullary hyperintense lesion with contrast enhancement. After metabolic, infectious, and malignant causes were excluded, myelitis transversa was presumed and the patient was treated intravenously with methylprednisolone. Shortly after that, he developed quadriplegia. Cervical MRI imaging showed engorged cervical perimedullary vessels, which were not visible on the initial MRI. The diagnosis was revised and a SDAVF identified. Prompt surgical treatment led to a complete recovery. The effect of intravenous steroids in SDAVF is controversial. Acute clinical worsening after steroid administration is previously reported in several publications; however, due to the paucity of clinical studies on SDAVF, this effect remains mostly overlooked or unknown. The findings in this patient support the causative relation between SDAVF clinical worsening and steroid administration. We propose that acute clinical worsening under steroids in patients initially diagnosed with myelitis should raise suspicion of an SDAVF. PMID:27920716

  10. Intravenous tPA Therapy Does Not Worsen Acute Intracerebral Hemorrhage in Mice

    PubMed Central

    Foerch, Christian; Rosidi, Nathanael L.; Schlunk, Frieder; Lauer, Arne; Cianchetti, Flor A.; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Steinmetz, Helmuth; Schaffer, Chris B.; Lo, Eng H.

    2013-01-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy. PMID:23408937

  11. Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice.

    PubMed

    Foerch, Christian; Rosidi, Nathanael L; Schlunk, Frieder; Lauer, Arne; Cianchetti, Flor A; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Steinmetz, Helmuth; Schaffer, Chris B; Lo, Eng H

    2013-01-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.

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

    PubMed

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

    2015-08-03

    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.

  13. Effects of acute hyperglycemia on myocardial glycolytic activity in humans.

    PubMed Central

    Wisneski, J A; Stanley, W C; Neese, R A; Gertz, E W

    1990-01-01

    The effects of hyperglycemia on myocardial glucose metabolism were investigated in seven healthy male subjects (age 24 +/- 4 yr). [6-14C]Glucose and [U-13C]lactate were infused as tracers. Circulating glucose was elevated to two hyperglycemic levels using a clamp technique for 1 h at each level. The mean arterial glucose concentration was 4.95 +/- 0.29 (control), 8.33 +/- 0.31 and 10.84 +/- 0.60 mumols/ml, respectively. Glucose extraction increased significantly from control (0.15 +/- 0.13 mumols/ml) during each level of the glucose clamp (0.28 +/- 0.12, P less than 0.02, and 0.54 +/- 0.14 mumols/ml, P less than 0.005, respectively). Myocardial production of 14CO2 showed that during control 9 +/- 10% of exogenous glucose was oxidized immediately upon extraction. Despite a significant increase in the amount of exogenous glucose oxidized with level II hyperglycemia, it represented only 32 +/- 10% of the glucose extracted. [13C]Lactate analysis showed that the myocardium was releasing lactate; during control 40 +/- 30% of this lactate was derived from exogenous glucose and during hyperglycemia this value increased to 97 +/- 37% (P less than 0.005). Thus, these data show that during short-term hyperglycemia, myocardial glucose extraction is enhanced. However, despite increases in exogenous glucose oxidation and the contribution of exogenous glucose to lactate release, the majority of the extracted glucose (i.e., 57%) is probably stored as glycogen. PMID:2185277

  14. Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models.

    PubMed

    Saha, Joy K; Xia, Jinqi; Grondin, Janet M; Engle, Steven K; Jakubowski, Joseph A

    2005-11-01

    The effects of anesthetic agents, commonly used in animal models, on blood glucose levels in fed and fasted rats were investigated. In fed Sprague-Dawley rats, ketamine (100 mg/kg)/xylazine (10 mg/kg) (KX) produced acute hyperglycemia (blood glucose 178.4 +/- 8.0 mg/dl) within 20 min. The baseline blood glucose levels (104.8 +/- 5.7 mg/dl) reached maximum levels (291.7 +/- 23.8 mg/dl) at 120 min. Ketamine alone did not elevate glucose levels in fed rats. Isoflurane also produced acute hyperglycemia similar to KX. Administration of pentobarbital sodium did not produce hyperglycemia in fed rats. In contrast, none of these anesthetic agents produced hyperglycemia in fasted rats. The acute hyperglycemic effect of KX in fed rats was associated with decreased plasma levels of insulin, adrenocorticotropic hormone (ACTH), and corticosterone and increased levels of glucagon and growth hormone (GH). The acute hyperglycemic response to KX was dose-dependently inhibited by the specific alpha2-adrenergic receptor antagonist yohimbine (1-4 mg/kg). KX-induced changes of glucoregulatory hormone levels such as insulin, GH, ACTH, and corticosterone were significantly altered by yohimbine, whereas the glucagon levels remained unaffected. In conclusion, the present study indicates that both KX and isoflurane produce acute hyperglycemia in fed rats. The effect of KX is mediated by modulation of the glucoregulatory hormones through stimulation of alpha2-adrenergic receptors. Pentobarbital sodium did not produce hyperglycemia in either fed or fasted rats. Based on these findings, it is suggested that caution needs to be taken when selecting anesthetic agents, and fed or fasted state of animals in studies of diabetic disease or other models where glucose and/or glucoregulatory hormone levels may influence outcome and thus interpretation. However, fed animals are of value when exploring the hyperglycemic response to anesthetic agents.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

    PubMed

    Breidthardt, Tobias; Socrates, Thenral; Noveanu, Markus; Klima, Theresia; Heinisch, Corinna; Reichlin, Tobias; Potocki, Mihael; Nowak, Albina; Tschung, Christopher; Arenja, Nisha; Bingisser, Roland; Mueller, Christian

    2011-03-01

    We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.

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

    PubMed Central

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

    2017-01-01

    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/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 with MAP

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

    PubMed

    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

  19. Influence on prognosis and prevalence of stress hyperglycemia in a cohort of patients with acute coronary syndrome

    PubMed Central

    Modenesi, Renata de Faria; Pena, Felipe Montes; de Faria, Carlos Augusto Cardoso; Carvalho, Ricardo Viana; de Souza, Nelson Robson Mendes; Soares, Jamil da Silva; Mesquita, Evandro Tinoco

    2012-01-01

    Objective 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 stress hyperglycemia was the predictor of the composite outcome (death, heart failure and/or ventricular dysfunction). The multivariate analysis did not indicate age, stress hyperglycemia or admission heart rate as risk factors. Conclusion Stress hyperglycemia was common in the studied sample. In the univariate analysis, the presence of stress hyperglycemia was associated with such events as death, heart failure and/or intrahospital ventricular dysfunction in patients with acute coronary syndrome. PMID:23917932

  20. Association of statin use and stress-induced hyperglycemia in patients with acute ST-elevation myocardial infarction

    PubMed Central

    Yan, Chen; Qin, Ma; Juan, Yang S; Tao, Li Y; dong, Gao M; Zechun, Zeng; Chun, Yang X; Liang, Cong H; Yin, Liu

    2016-01-01

    Background Only a few information is available on the risk of stress hyperglycemia following acute myocardial infarction after statin use. We investigate the association of stress-induced hyperglycemia following statin use in patients with acute myocardial infarction. Methods An observational analysis of 476 consecutive patients who suffered acute myocardial infarction was carried out. All selected patients were divided into diabetes mellitus and non-diabetes based on the presence or absence of diabetes. The cardiac incidence of in-hospital and stress-induced hyperglycemia was recorded. Results Among patients with stress hyperglycemia in non-diabetes mellitus subgroups, the average fasting plasma glucose values in statin users were higher than in non-statin users (P < 0.05). But in diabetes mellitus subgroups, the average fasting plasma glucose did not have a significant difference between statin users and non-statin users (P > 0.05). In non-diabetes mellitus patients, the incidence of stress hyperglycemia with statin therapy was significantly higher than with non-statin therapy (P = 0.003). But in diabetes mellitus patients group, there is no significant difference in incidence of stress hyperglycemia between patients with statin therapy and patients without statin therapy (P = 0.902).The incidence of heart failure and in-hospital mortality of acute myocardial infarction in patients with stress-induced hyperglycemia was significantly higher than in non-hyperglycemia patients (P < 0.05). Conclusion Statins are related to higher stress hyperglycemia and cardiac incidences after acute myocardial infarction. PMID:27158481

  1. Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium.

    PubMed

    Weng, Yi-Ming; Chang, Meng-Wei; Weng, Chia-Sui

    2008-11-01

    Pituitary apoplexy indicates pituitary adenoma hemorrhage, which could result in acute pituitary insufficiency and mortality. The typical symptoms are headache, visual disturbance, nausea, vomiting, altered mental status, and panhypopituitarism. However, cortisol-induced hyperglycemia and acute delirium could be an initial presentation of a pituitary adenoma hemorrhage with stormy release of the adrenocorticotrophic hormone. A 28-year-old woman presented with severe vomiting, irritable state, and delusion. She had medical history of irregular menstrual cycles and marked body weight gain after her second childbirth 8 years ago. She was diagnosed of diabetic ketoacidosis 2 days before this visiting at local medical department. On physical examination, Cushing appearance without definite neurological deficit was disclosed. Further blood tests revealed high blood sugar, cortisol, and adrenocorticotrophic hormone levels without evidence of diabetic ketoacidosis. The brain computed tomography and magnetic resonance imaging showed pituitary macroadenoma and pituitary hemorrhage. Cushing disease with pituitary apoplexy was then diagnosed. Conservative management with delayed neurosurgery was applied. The patient became clear with normalized cortisol and blood sugar levels soon after. Follow-up computed tomography scan of the brain revealed no progression of tumor bleeding or mass effect. To our knowledge, pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium has never been reported before. This case reminds us of pituitary apoplexy and its rare manifestations.

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

    PubMed

    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.

  3. Impact of acute and chronic hyperglycemia on in-hospital outcomes of patients with acute myocardial infarction.

    PubMed

    Fujino, Masashi; Ishihara, Masaharu; Honda, Satoshi; Kawakami, Shoji; Yamane, Takafumi; Nagai, Toshiyuki; Nakao, Kazuhiro; Kanaya, Tomoaki; Kumasaka, Leon; Asaumi, Yasuhide; Arakawa, Tetsuo; Tahara, Yoshio; Nakanishi, Michio; Noguchi, Teruo; Kusano, Kengo; Anzai, Toshihisa; Goto, Yoichi; Yasuda, Satoshi; Ogawa, Hisao

    2014-12-15

    This study was undertaken to assess the impact of acute hyperglycemia (acute-HG) and chronic hyperglycemia (chronic-HG) on short-term outcomes in patients with acute myocardial infarction (AMI). This study consisted of 696 patients with AMI. Acute-HG was defined as admission plasma glucose ≥200 mg/dl and chronic-HG as hemoglobin A1c ≥6.5%. Acute-HG was associated with higher peak serum creatine kinase (4,094 ± 4,594 vs 2,526 ± 2,227 IU/L, p <0.001) and in-hospital mortality (9.8% vs 1.6%, p <0.001). On the contrary, there was no significant difference in peak creatine kinase (2,803 ± 2,661 vs 2,940 ± 3,181 IU/L, p = 0.59) and mortality (3.3 vs 3.7%, p = 0.79) between patients with chronic-HG and those without. Multivariate analysis showed that admission plasma glucose was an independent predictor of in-hospital mortality (odds ratio 1.15, 95% confidence interval 1.05 to 1.27, p <0.001), but hemoglobin A1c was not. When only patients with acute-HG were analyzed, chronic-HG was associated with a significantly smaller infarct size (3,221 ± 3,001 vs 5,904 ± 6,473 IU/L, p <0.001) and lower in-hospital mortality (5.5 vs 18.9%, p = 0.01). In conclusion, these results suggested that acute-HG, but not chronic-HG, was associated with adverse short-term outcomes after AMI. Paradoxically, in patients with acute-HG, chronic-HG might abate the adverse effects of acute-HG.

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

    PubMed

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

    2010-02-01

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

  5. Urine Albumin Excretion as a Marker of Acute Glycemic Changes in Isolated Postprandial Hyperglycemia

    PubMed Central

    Shilpasree, Alagilawada S; Patil, Vidya S; Patil, Vijayetha P; Ingleshwar, Deepti G

    2017-01-01

    Introduction: Postprandial hyperglycemia is a major risk factor for the development of cardiovascular diseases (CVDs), and Most of the times it occurs in patients with normal glycemic control diagnosed by fasting blood glucose (FBG) and glycated hemoglobin levels. Urine albumin excretion (UAE) is an independent predictor of CVD risk. Aim: To estimate UAE in isolated postprandial hyperglycemia (IPPHG) patients and to assess the relationship of UAE with FBG and postprandial blood glucose (PPBG) levels. Settings and Design: A cross-sectional study was carried out in 318 patients with Type II diabetes in the age group 30–60 years for 6 months. Materials and Methods: Patients were divided into five groups based on their FBG and PPBG values. UAE and lipid profile were measured in all the groups. Statistical Analysis: UAE and lipid profile in different groups were compared using ANOVA. Regression analysis was used to predict the variation of UAE with FBG, PPBG, and total cholesterol (TC). Results: Patients with IPPHG had significantly higher albumin excretion compared to normoglycemia (NG) group [P < 0.0001]. In impaired glucose tolerance and isolated fasting hyperglycemia groups, it did not differ significantly from NG group [P = 0.206 and P = 0.173]. Lipid profile did not show any significant difference between the groups. On regression analysis, PPBG but not FBG or TC correlated positively with UAE. Conclusion: UAE is easy, less expensive, and Widely available method done on spot urine samples which predicts the acute glycemic changes and increased risk of developing CVDs in patients with IPPHG. PMID:28042215

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

    PubMed

    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.

  7. [IC triage in patients with an acutely worsening condition; challenges, considerations and decisions].

    PubMed

    Savelkoul, C; Klijnsma, A F; Balk, E; Janse, A; Tjan, D H T

    2016-01-01

    Acute intensive care (IC) triage involves a challenging decision-making process. Physicians are required to make life or death decisions about an unfamiliar patient within a short time frame. An 84-year-old female was admitted to the stroke unit following an extensive cerebral infarction. The intensive care unit (ICU) physician was consulted because of a suspected severe abdominal sepsis even though ICU treatment had never previously been discussed. A 77-year-old female with a previous history of myocardial infarction and severe COPD developed acute respiratory failure on the ward, and was admitted to the ICU for support by a mechanical ventilator. The family felt this was an inappropriate course of treatment, considering her former poor quality of life. When physicians are confronted with sudden deterioration of the patient's clinical condition without advanced care planning a limited-time IC treatment trial is often initiated, possibly leading to inappropriate ICU admissions. ICU treatment options should preferably be discussed beforehand; preliminary background information regarding the patient's wishes is essential for adequate decision-making.

  8. Influence of acute hyperglycemia on otoacoustic emissions and the medial olivocochlear reflexa)

    PubMed Central

    Jacobs, Peter G.; Konrad-Martin, Dawn; Mcmillan, Garnett P.; McDermott, Daniel; Fausti, Stephen A.; Kagen, David; Wan, Eric A.

    2012-01-01

    Stimulus-frequency (SF) otoacoustic emission (OAE) amplitude and the amplitude of medial olivocochlear (MOC) inhibition of SF OAEs for ipsilateral, contralateral and bilateral MOC reflex elicitors were recorded in six subjects with type 2 diabetes during a glucose tolerance test (GTT). Five of the six subjects were tested twice for a total of 11 trials and three subjects were tested in a control experiment. During the GTT experiment, the subjects’ blood glucose was elevated from a euglycemic level below 150 mg/dL to a hyperglycemic level above 160 mg/dL following the consumption of a bolus of 80 g of sugar. A subset of three subjects were tested in a control experiment during which SF OAE and MOC reflex measurements were made while blood sugar levels remained constant within the euglycemic region. Mean SF OAE amplitudes were elevated following glucose consumption. A statistically significant increase in MOC inhibition amplitude was observed during elevated sugar levels for the 11 GTT trials. Maximum inhibition occurred about an hour after glucose consumption when blood glucose levels peaked. Results indicate that acute hyperglycemia influences efferent control of the cochlea in people with type 2 diabetes. PMID:22352503

  9. Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?

    PubMed Central

    Wernly, Bernhard; Lichtenauer, Michael; Franz, Marcus; Kabisch, Bjoern; Muessig, Johanna; Masyuk, Maryna; Kelm, Malte; Hoppe, Uta C.; Jung, Christian

    2016-01-01

    Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient

  10. Renal impairment and worsening of renal function in acute heart failure: can new therapies help? The potential role of serelaxin.

    PubMed

    Schmieder, Roland E; Mitrovic, Veselin; Hengstenberg, Christian

    2015-08-01

    Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.

  11. Association of Hyperglycemia with In-Hospital Mortality and Morbidity in Libyan Patients with Diabetes and Acute Coronary Syndromes

    PubMed Central

    Benamer, Sufyan; Eljazwi, Imhemed; Mohamed, Rima; Masoud, Heba; Tuwati, Mussa; Elbarsha, Abdulwahab M.

    2015-01-01

    Objective Hyperglycemia on admission and during hospital stay is a well-established predictor of short-term and long-term mortality in patients with acute myocardial infarction. Our study investigated the impact of blood glucose levels on admission and in-hospital hyperglycemia on the morbidity and mortality of Libyan patients admitted with acute coronary syndromes (acute myocardial infarction and unstable angina). Methods In this retrospective study, the records of patients admitted with acute coronary syndrome to The 7th Of October Hospital, Benghazi, Libya, between January 2011 and December 2011 were reviewed. The level of blood glucose on admission, and the average blood glucose during the hospital stay were recorded to determine their effects on in-hospital complications (e.g. cardiogenic shock, acute heart failure, arrhythmias, and/or heart block) and mortality. Results During the study period, 121 patients with diabetes were admitted with acute coronary syndrome. The mortality rate in patients with diabetes and acute coronary syndrome was 12.4%. Patients with a mean glucose level greater than 200mg/dL had a higher in-hospital mortality and a higher rate of complications than those with a mean glucose level ≤200mg/dL (27.5% vs. 2.6%, p<0.001 and 19.7% vs. 45.5%, p=0.004, respectively). There was no difference in in-hospital mortality between patients with a glucose level at admission ≤140mg/dL and those admitted with a glucose level >140mg/dL (6.9% vs. 14.3%; p=0.295), but the rate of complications was higher in the latter group (13.8% vs. 34.1%; p=0.036). Patients with admission glucose levels >140mg/dL also had a higher rate of complications at presentation (26.4% vs. 6.9%; p=0.027). Conclusion In patients with diabetes and acute coronary syndrome, hyperglycemia during hospitalization predicted a worse outcome in terms of the rates of in-hospital complications and in-hospital mortality. Hyperglycemia at the time of admission was also associated with

  12. Hyperglycemia in acute aluminum phosphide poisoning as a potential prognostic factor.

    PubMed

    Mehrpour, O; Alfred, S; Shadnia, S; Keyler, D E; Soltaninejad, K; Chalaki, N; Sedaghat, M

    2008-07-01

    Aluminum phosphide (AlP) is a solid fumigant widely used in Iran as a grain preservative. When reacted with water or acids, AIP produces phosphine gas, a mitochondrial poison that interferes with oxidative phosphorylation and protein synthesis. Poisoning by AIP is one of the most important causes of fatal chemical toxicity in Iran. There are few studies in the medical literature addressing prognostic factors associated with AlP poisoning. In this prospective study conducted across a 14-month period commencing on 21st March 2006, we enrolled all patients admitted to the ICU of Loghman-Hakim Hospital Poison Center (Tehran, Iran) with AIP poisoning, no history of diabetes mellitus diagnosed before hospitalization, and normal body mass index. We recorded patient-specific demographic information, blood glucose level on presentation (before treatment), arterial blood gas (ABG) analysis, time elapsed between ingestion and presentation, ingested dose, duration of intensive care admission, and outcome data related to each presentation. We enrolled the group of patients who survived the intoxication as a control group and compared their blood glucose levels with those who died because of AlP poisoning. Data were analyzed by Statistical Product and Service Solutions (SPSS) software (Version 12; Chicago, Ilinois, USA) using logistic regression, Pearson correlation coefficient and Student's t-test. P values of 0.05 or less were considered as the statistical significant levels. Forty-five patients (21 women and 24 men) with acute AlP poisoning were included in the study. The mean age was 27.3 +/- 11.5 years (range: 14-62 years). Thirteen patients survived (29%) and 32 expired (71%). AlP poisoning followed deliberate ingestion in all patients. The time elapsed between ingestion and arrival at the hospital was 3.2 +/- 0.4 h. There was no significant difference between survived and non-survived groups according to age, gender, and time to treatment. However, the difference between

  13. Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats.

    PubMed

    Sato, K; Fujita, S; Iemitsu, M

    2014-09-01

    Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.

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

    PubMed

    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 (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.

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

    PubMed

    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.

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

    PubMed

    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) (P<0.05). After white chocolate ingestion, flow-mediated dilation was reduced after OGTT from 7.88±0.68 to 6.07±0.76 (P=0.027), 6.74±0.51 (P=0.046) at 1 and 2 h after the glucose load, respectively. Similarly, after white chocolate but not after dark chocolate, wave reflections, blood pressure, and endothelin-1 and 8-iso-PGF(2α) increased after OGTT. OGTT causes acute, transient impairment of endothelial function and oxidative stress, which is attenuated by flavanol-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.

  17. Miglitol improves postprandial endothelial dysfunction in patients with acute coronary syndrome and new-onset postprandial hyperglycemia

    PubMed Central

    2013-01-01

    Background Hyperglycemia, a risk factor for development of cardiovascular disease, causes endothelial dysfunction. Alpha-glucosidase inhibitors (α-GIs) improve postprandial hyperglycemia (PPHG) and may have favorable effects on associated cardiovascular disease. Effects of α-GIs in patients with acute coronary syndrome (ACS) and PPHG remain unclear; thus, we assessed the effect of α-GI miglitol on endothelial function in such patients by digital reactive hyperemia peripheral arterial tonometry (RH-PAT). Methods Fifty-four patients with ACS who underwent primary percutaneous coronary intervention were enrolled in the study: 36 with new-onset PPHG and 18 with normal glucose tolerance. Eighteen PPHG patients were given 50 mg of miglitol with each meal for 1 week. Endothelial function was assessed on the basis of the RH-PAT index (RHI) before and after the 1-week miglitol treatment. The other 18 PPHG patients and the 18 NGT patients were not given any anti-diabetic agent for 1 week, and endothelial function was assessed. Results Postprandial RHI decreased significantly in patients with PPHG. Miglitol improved PPHG significantly; postprandial RHI also improved (p = 0.007). Significant inverse correlation was found between the postprandial change in RHI and postprandial fasting-to-60-minutes surge in glucose (r = -0.382, p = 0.009). Moreover, the improvement in endothelial function correlated with the reduced postprandial glucose surge achieved with miglitol (r = -0.462, p = 0.001). Conclusions Postprandial changes in glucose are related to endothelial dysfunction in ACS. Miglitol-based improvement in PPHG appears to improve endothelial function. The effect of miglitol on glucose-dependent endothelial function might improve outcomes of ACS. PMID:23777506

  18. Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model.

    PubMed

    Chen, C H; Manaenko, A; Zhan, Y; Liu, W W; Ostrowki, R P; Tang, J; Zhang, J H

    2010-08-11

    Hyperglycemia is one of the major factors for hemorrhagic transformation after ischemic stroke. In this study, we tested the effect of hydrogen gas on hemorrhagic transformation in a rat focal cerebral ischemia model. Sprague-Dawley rats (n=72) were divided into the following groups: sham; sham treated with hydrogen gas (H(2)); Middle Cerebral Artery Occlusion (MCAO); and MCAO treated with H(2) (MCAO+H(2)). All rats received an injection of 50% dextrose (6 ml/kg i.p.) and underwent MCAO 15 min later. Following a 90 min ischemic period, hydrogen was inhaled for 2 h during reperfusion. We measured the level of blood glucose at 0 h, 0.5 h, 4 h, and 6 h after dextrose injection. Infarct and hemorrhagic volumes, neurologic score, oxidative stress (evaluated by measuring the level of 8 Hydroxyguanosine (8OHG), 4-Hydroxy-2-Nonenal (HNE) and nitrotyrosine), and matrix metalloproteinase (MMP)-2/MMP-9 activity were measured at 24 h after ischemia. We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. This effect of hydrogen was accompanied by a reduction of the expression of 8OHG, HNE, and nitrotyrosine and the activity of MMP-9. Furthermore, a reduction of the blood glucose level from 500+/-32.51 to 366+/-68.22 mg/dl at 4 h after dextrose injection was observed in hydrogen treated animals. However, the treatment had no significant effect on the expression of ZO-1, occludin, collagen IV or aquaporin4 (AQP4). In conclusion, hydrogen gas reduced brain infarction, hemorrhagic transformation, and improved neurological function in rats. The potential mechanisms of decreased oxidative stress and glucose levels after hydrogen treatment warrant further investigation.

  19. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

    PubMed Central

    Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

    2016-01-01

    Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

  20. Hyperglycemia - infants

    MedlinePlus

    High blood sugar - infants; High blood glucose level - infants ... have a low insulin level that results in high blood sugar. ... hyperglycemia often have no symptoms. Sometimes, babies with high blood sugar will produce large amounts of urine ...

  1. Effects of intra-aortic balloon pump versus centrifugal pump on myocardial energetics and systemic circulation in a porcine model of rapidly worsening acute heart failure.

    PubMed

    Ntalianis, Argyrios S; Drakos, Stavros G; Charitos, Christos; Dolou, Paraskevi; Pierrakos, Charalampos N; Terrovitis, John V; Papaioannou, Theodoros; Charitos, Efstratios; Nanas, John N

    2008-01-01

    The present experimental study compared the effectiveness of counterpulsation provided by the intra-aortic balloon pump (IABP) versus that of a nonpulsatile, radial-flow centrifugal pump (CFP) in rapidly worsening acute heart failure (HF). Eighteen pigs were included in the study. After the induction of acute moderate HF, circulatory support was randomly provided with either the IABP or CFP. No significant change in cardiac output (CO) and mean aortic pressure (MAP) was observed with either pump. The IABP caused a significantly greater decrease than the CFP in 1) double product (13.138 +/- 2.476 mm Hg/min vs. 14.217 +/- 2.673 mm Hg/min, p = 0.023), 2) left ventricular systolic pressure (LVSP, 100 +/- 8 mm Hg vs. 106 +/- 10 mm Hg, p = 0.046), and 3) end-diastolic aortic pressure (EDAP, 70 +/- 6 mm Hg vs. 86 +/- 6 mm Hg, p = 0.000). The effects of both pumps on total tension time index and LAD flow were similar. After the induction of severe HF, the IABP had its main effects on afterload and decreased LVSP from 88 +/- 6 mm Hg to 78 +/- 9 mm Hg, (p = 0.008), and EDAP from 57 +/- 9 mm Hg to 49 +/- 14 mm Hg, (p = 0.044), whereas the CFP exerted its effects mainly on preload, lowering LV end-diastolic pressure from 19 +/- 5 mm Hg to 11 +/- 4 mm Hg, (p = 0.002). CO and MAP were similarly increased by both assist systems. The IABP (by lowering afterload) and CFP (by lowering preload) both offered significant mechanical support in acute HF. However, afterload reduction offered principally by the IABP seems preferable for the recovery of the acutely failing heart.

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

    PubMed

    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 < 0.001), and more cardiogenic shock, but less ventricular fibrillation, and no differences in atrioventricular block, stroke or reinfarction. After the multivariate analysis, DG had no significant influence on hospital prognosis [odds ratio (OR) 1.21, 95% confidence interval 0.79-1.86]. The analysis of a propensity-matched cohort of 464 patients (232 DG and 232 NoDG) did not find differences in hospital mortality (13.4 vs 13.4%) nor other complications. In our cohort of ACS patients, the previous treatment with digoxin was not associated with an increase in dysrhythmic complications nor was an independent predictor of mortality during hospitalization.

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

    PubMed Central

    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 < 0.01-0.0001), and endothelial function was decreased (P < 0.0005) during euinsulinemia-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

  4. [A case of acute ethanol intoxication with remarkable hyperglycemia by "ume-shu", a Japanese apricot liquor made with a large amount of sugar].

    PubMed

    Sugano, Takayuki; Kojima, Naoki; Kaneko, Susumu; Ishida, Junro; Terada, Taizo; Inagawa, Hiroshi; Okada, Yasusei

    2002-07-01

    A 19-year-old woman ingested 2.2 L of "umeshu", a Japanese apricot liquor made with a large amount of sugar. She was unconscious and in shock. The estimated blood ethanol concentration was 607 mg/dl, and the blood glucose level was 576 mg/dl. Because her respiration and circulation was highly suppressed, blood purification was indicated. Continuous hemodiafiltration (CHDF) was performed instead of hemodialysis because her hemodynamics was unstable. After CHDF was instituted, her blood glucose level reduced to normal range, and her consciousness became alert. CHDF was effective in eliminating ethanol and stabilizing her hemodynamics within an early stage. Though acute ethanol intoxication is known to inhibit glucogenesis, leading to hypoglycemia, marked hyperglycemia was seen in this case. Ingestion of a large amount of glucose-rich liquor and being in shock seemed to be the causes of hyperglycemia.

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

    PubMed

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

    2015-12-15

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

  6. Molecular cloning of glucose transporter 1 in grouper Epinephelus coioides and effects of an acute hyperglycemia stress on its expression and glucose tolerance.

    PubMed

    Liu, Hongyu; Dong, Xiaohui; Chi, Shuyan; Yang, Qihui; Zhang, Shuang; Chen, Liqiao; Tan, Beiping

    2017-02-01

    The glucose transporter family proteins play pivotal roles in glucose metabolism. In this study, we successfully cloned the orange spotted grouper (Epinephelus coioides) glucose transporter 1 (EcGlut1) gene (GenBank accession: JQ623903). The full-length EcGlut1 cDNA was 2126 bp with a 1476 bp ORF, a 437bp5'-UTR and 223bp3'-UTR. EcGlut1 is predicted to encode a 491 amino acid protein with a MW of 53.9 kDa, a pI of 8.66 and a Pfam domain. Bioinformatics analysis revealed that EcGlut1 was evolutionally conserved between fishes with 80-89 % amino acid identities. EcGlut1 was expressed predominantly in heart and liver and at lower levels in muscle, intestine, stomach and brain. We also investigated the effect of acute hyperglycemia stress on EcGlut1 expression. In glucose tolerance test, changes in EcGlut1 mRNA expression in response to glucose injection and glucose metabolism-related indictors were assessed at the same time. Glucose injection significantly suppressed EcGlut1 mRNA expression in liver at 12 h and in brain at 24 h postinjection (P < 0.05). EcGlut1 mRNA levels in heart were increased at 6 h (P < 0.05). Plasma glucose level increased significantly and reached its maximum at 3 h postinjection (P < 0.05). The spatiotemporal expression of EcGlut1 and glucose metabolism suggested that orange spotted grouper might rely on fat anabolism to reduce acute hyperglycemia stress and the delayed transcription of EcGlut1 gene might be one reason for glucose intolerance in E. coioides.

  7. Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages

    PubMed Central

    Carnuta, Mihaela G.; Sanda, Gabriela M.; Stancu, Camelia S.; Popescu, Andreea C.; Popescu, Mihaela R.; Vlad, Adelina; Dimulescu, Doina R.; Simionescu, Maya; Sima, Anca V.

    2016-01-01

    We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration. PMID:27519051

  8. Hyperglycemia in Diabetes

    MedlinePlus

    ... include: Cardiovascular disease Nerve damage (neuropathy) Kidney damage (diabetic nephropathy) or kidney failure Damage to the blood vessels ... supplement if you have high blood sugar. Emergency treatment for severe hyperglycemia If you have signs and ...

  9. Worsening of Lymphopenia during Apremilast Treatment

    PubMed Central

    Kolios, Antonios G.A.; French, Lars E.; Navarini, Alexander A.

    2016-01-01

    Apremilast is an oral phosphodiesterase IV inhibitor recently registered for the treatment of psoriasis and psoriatic arthritis in Switzerland and other countries. Even though it offers only moderate efficacy compared to biologics, many patients prefer drugs given by the oral route. Apremilast is frequently used in private practice, as it showed no relevant safety signals in clinical trials and often, laboratory tests are omitted completely. Here we report a patient who developed acute lymphopenia and worsening of psoriasis during apremilast treatment, which resolved with discontinuation of apremilast. We suggest that at least in prospective registries, that regular monitoring of laboratory surrogate markers should be performed on a long-term basis to detect rare but potentially important safety signals. PMID:27920684

  10. Chromium supplementation improved post-stroke brain infarction and hyperglycemia.

    PubMed

    Chen, Wen-Ying; Mao, Frank Chiahung; Liu, Chia-Hsin; Kuan, Yu-Hsiang; Lai, Nai-Wei; Wu, Chih-Cheng; Chen, Chun-Jung

    2016-04-01

    Hyperglycemia is common after acute stroke and is associated with a worse outcome of stroke. Thus, a better understanding of stress hyperglycemia is helpful to the prevention and therapeutic treatment of stroke. Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications. In this study, we investigated whether post-stroke hyperglycemia involved chromium dynamic mobilization in a rat model of permanent focal cerebral ischemia and whether dietary supplement of chromium improved post-stroke injury and alterations. Stroke rats developed brain infarction, hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance. Post-stroke hyperglycemia was accompanied by elevated secretion of counter-regulatory hormones including glucagon, corticosterone, and norepinephrine, decreased insulin signaling in skeletal muscles, and increased hepatic gluconeogenesis. Correlation studies revealed that counter-regulatory hormone secretion showed a positive correlation with chromium loss and blood glucose increased together with chromium loss. Daily chromium supplementation increased tissue chromium levels, attenuated brain infarction, improved hyperglycemia, and decreased plasma levels of glucagon and corticosterone in stroke rats. Our findings suggest that stroke rats show disturbance of tissue chromium homeostasis with a net loss through urinary excretion and chromium mobilization and loss might be an alternative mechanism responsible for post-stroke hyperglycemia.

  11. Hyperglycemia, tumorigenesis, and chronic inflammation.

    PubMed

    Chang, Shu-Chun; Yang, Wei-Chung Vivian

    2016-12-01

    Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells. Therefore, uncontrolled proinflammatory responses could conceivably create a chronic inflammatory state, promoting a tumor-favorable microenvironment and potentially triggering immune overactivation and cancer growth. To further understand how hyperglycemia contributes to immune overactivation, the tumor microenvironment and the development of chronic inflammation-associated tumors may provide insights into tumor biology and immunology. This paper provides a brief introduction to hyperglycemia-associated diseases, followed by a comprehensive overview of the current findings of regulatory molecular mechanisms of glycosylation on proteoglycans in the extracellular matrix under hyperglycemic conditions. Then, the authors discuss the role of hyperglycemia in tumorigenesis (particularly in prostate, liver, colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia to chronic inflammation. The authors end with a brief discussion on the future perspectives of hyperglycemia/tumorigenesis and potential applications of alternative/effective therapeutic strategies for hyperglycemia-associated cancers.

  12. Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes

    PubMed Central

    Nystoriak, Matthew A.; Nieves-Cintrón, Madeline; Patriarchi, Tommaso; Buonarati, Olivia R.; Prada, Maria Paz; Morotti, Stefano; Grandi, Eleonora; Fernandes, Julia Dos Santos; Forbush, Katherine; Hofmann, Franz; Sasse, Kent C.; Scott, John D.; Ward, Sean M.; Hell, Johannes W.; Navedo, Manuel F.

    2017-01-01

    Hypercontractility of arterial myocytes and enhanced vascular tone during diabetes are, in part, attributed to the effects of increased glucose (hyperglycemia) on L-type CaV1.2 channels. In murine arterial myocytes, kinase-dependent mechanisms mediate the increase in CaV1.2 activity in response to increased extracellular glucose. We identified a subpopulation of the CaV1.2 channel pore-forming subunit (α1C) within nanometer proximity of protein kinase A (PKA) at the sarcolemma of murine and human arterial myocytes. This arrangement depended upon scaffolding of PKA by an A-kinase anchoring protein 150 (AKAP150) in mice. Glucose-mediated increases in CaV1.2 channel activity were associated with PKA activity, leading to α1C phosphorylation at Ser1928. Compared to arteries from low-fat diet (LFD)–fed mice and nondiabetic patients, arteries from high-fat diet (HFD)–fed mice and from diabetic patients had increased Ser1928 phosphorylation and CaV1.2 activity. Arterial myocytes and arteries from mice lacking AKAP150 or expressing mutant AKAP150 unable to bind PKA did not exhibit increased Ser1928 phosphorylation and CaV1.2 current density in response to increased glucose or to HFD. Consistent with a functional role for Ser1928 phosphorylation, arterial myocytes and arteries from knockin mice expressing a CaV1.2 with Ser1928 mutated to alanine (S1928A) lacked glucose-mediated increases in CaV1.2 activity and vasoconstriction. Furthermore, the HFD-induced increases in CaV1.2 current density and myogenic tone were prevented in S1928A knockin mice. These findings reveal an essential role for α1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes. PMID:28119464

  13. Glucose metabolism and hyperglycemia.

    PubMed

    Giugliano, Dario; Ceriello, Antonio; Esposito, Katherine

    2008-01-01

    Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA1c), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that HbA1c should be <7%. The measurement of the HbA1c concentration is considered the gold standard for assessing long-term glycemia; however, it does not reveal any information on the extent or frequency of blood glucose excursions, but provides an overall mean value only. Postprandial hyperglycemia occurs frequently in patients with diabetes receiving active treatment and can occur even when metabolic control is apparently good. Interventional studies indicate that reducing postmeal glucose excursions is as important as controlling fasting plasma glucose in persons with diabetes and impaired glucose tolerance. Evidence exists for a causal relation between postmeal glucose increases and microvascular and macrovascular outcomes; therefore, it is not surprising that treatment with different compounds that have specific effects on postprandial glucose regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappaB activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA1c, fasting glucose, and postmeal glucose peak.

  14. Glucosamine: Can It Worsen Gout Symptoms?

    MedlinePlus

    ... Gout 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. ...

  15. 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").

    PubMed

    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.

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

    SciTech Connect

    Yu, Yunli; Wang, Xinting; Liu, Can; Yao, Dan; Hu, Mengyue; Li, Jia; Hu, Nan; Liu, Li; Liu, Xiaodong

    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

  17. Glycerol and Fatty Acids in Serum Predict the Development of Hyperglycemia and Type 2 Diabetes in Finnish Men

    PubMed Central

    Mahendran, Yuvaraj; Cederberg, Henna; Vangipurapu, Jagadish; Kangas, Antti J.; Soininen, Pasi; Kuusisto, Johanna; Uusitupa, Matti; Ala-Korpela, Mika; Laakso, Markku

    2013-01-01

    OBJECTIVE We investigated the association of fasting serum glycerol and fatty acids (FAs) as predictors for worsening of hyperglycemia and incident type 2 diabetes. RESEARCH DESIGN AND METHODS Cross-sectional and longitudinal analyses of the population-based METabolic Syndrome in Men (METSIM) Study included 9,398 Finnish men (mean age 57 ± 7 years). At baseline, levels of serum glycerol, free FAs (FFAs), and serum FA profile, relative to total FAs, were measured with proton nuclear magnetic resonance spectroscopy. RESULTS At baseline, levels of glycerol, FFAs, monounsaturated FAs, saturated FAs, and monounsaturated n-7 and -9 FAs, relative to total FAs, were increased in categories of fasting and 2-h hyperglycemia, whereas the levels of n-3 and n-6 FAs, relative to total FAs, decreased (N = 9,398). Among 4,335 men with 4.5-year follow-up data available, 276 developed type 2 diabetes. Elevated levels of glycerol, FFAs, monounsaturated FAs, and saturated and monounsaturated n-7 and -9 FAs, relative to total FAs, predicted worsening of hyperglycemia and development of incident type 2 diabetes after adjustment for confounding factors. n-6 FAs, mainly linoleic acid (LA), relative to total FAs, were associated with reduced risk for the worsening of hyperglycemia and conversion to type 2 diabetes. CONCLUSIONS Our large population-based study shows that fasting serum levels of glycerol, FFAs, monounsaturated FAs, saturated FAs, and n-7 and -9 FAs are biomarkers for an increased risk of development of hyperglycemia and type 2 diabetes, whereas high levels of serum n-6 FAs, reflecting dietary intake of LA, were associated with reduced risk for hyperglycemia and type 2 diabetes. PMID:24026559

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

    PubMed

    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.

  19. Hyperglycemia secondary to consumption of cocaine and atypical antipsychotic drugs.

    PubMed

    Argente Villaplana, Carlos R; Civera Andrés, Miguel; Real Collado, José T; Martínez-Hervás, Sergio; Ascaso Gimilio, Juan F; Carmena Rodríguez, Rafael

    2008-10-01

    Drugs such as cocaine and atypical antipsychotic agents, such as olanzapine, are sometimes related to hyperglycemia. Whereas cocaine raises plasma glucose through catecholamine release, atypical antipsychotic agents mainly increase appetite and induce weight gain and the development of metabolic syndrome. Moreover, the latter group of drugs also act independently from weight gain or adiposity, due to inhibition of beta pancreatic cells and reduction of peripheral insulin action. We present the case of a 29-year-old non-diabetic woman with severe acute hyperglycemia in the context of a suicide attempt through intake of olanzapine and cocaine. After discontinuation of olanzapine and cocaine consumption, glycemia was immediately normalized without subsequent diagnosis of diabetes.

  20. Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis.

    PubMed

    Huo, Mingyu; Huang, Yuhong; Qu, Dan; Zhang, Hongsong; Wong, Wing Tak; Chawla, Ajay; Huang, Yu; Tian, Xiao Yu

    2017-03-01

    BMAL1, the nonredundant transcription factor in the core molecular clock, has been implicated in cardiometabolic diseases in mice and humans. BMAL1 controls the cyclic trafficking of Ly6c(hi) monocytes to sites of acute inflammation. Myeloid deficiency of Bmal1 also worsens chronic inflammation in diet-induced obesity. We studied whether myeloid Bmal1 deletion promotes atherosclerosis by enhancing monocyte recruitment to atherosclerotic lesions. By generating Bmal1(FloxP/FloxP);LysM(Cre) mice on the Apoe(-/-) background, we showed that Bmal1 deletion in myeloid cells increased the size of atherosclerotic lesions. Bmal1 deficiency in monocytes and macrophages resulted in an increased total number of lesional macrophages in general and Ly6c(hi) infiltrating monocyte-macrophages in particular, accompanied by skewed M2 to M1 macrophage phenotype. Ly6c(hi) and/or Ly6c(lo) monocyte subsets in blood, spleen, and bone marrow were not altered. Cell tracking and adoptive transfer of Ly6c(hi) monocytes showed Bmal1 deficiency induced more trafficking of Ly6c(hi) monocytes to atherosclerotic lesions, preferential differentiation of Ly6c(hi) monocytes into M1 macrophages, and increased macrophage content and lesion size in the carotid arteries. We demonstrated that Bmal1 deficiency in macrophages promotes atherosclerosis by enhancing recruitment of Ly6c(hi) monocytes to atherosclerotic lesions.-Huo, M., Huang, Y., Qu, D., Zhang, H., Wong, W. T., Chawla, A., Huang, Y., Tian, X. Y. Myeloid Bmal1 deletion increases monocyte recruitment and worsens atherosclerosis.

  1. Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways.

    PubMed

    Mapanga, Rudo F; Essop, M Faadiel

    2016-01-15

    The incidence of cardiovascular complications associated with hyperglycemia is a growing global health problem. This review discusses the link between hyperglycemia and cardiovascular diseases onset, focusing on the role of recently emerging downstream mediators, namely, oxidative stress and glucose metabolic pathway perturbations. The role of hyperglycemia-mediated activation of nonoxidative glucose pathways (NOGPs) [i.e., the polyol pathway, hexosamine biosynthetic pathway, advanced glycation end products (AGEs), and protein kinase C] in this process is extensively reviewed. The proposal is made that there is a unique interplay between NOGPs and a downstream convergence of detrimental effects that especially affect cardiac endothelial cells, thereby contributing to contractile dysfunction. In this process the AGE pathway emerges as a crucial mediator of hyperglycemia-mediated detrimental effects. In addition, a vicious metabolic cycle is established whereby hyperglycemia-induced NOGPs further fuel their own activation by generating even more oxidative stress, thereby exacerbating damaging effects on cardiac function. Thus NOGP inhibition, and particularly that of the AGE pathway, emerges as a novel therapeutic intervention for the treatment of cardiovascular complications such as acute myocardial infarction in the presence hyperglycemia.

  2. Stress Induced Hyperglycemia and the Subsequent Risk of Type 2 Diabetes in Survivors of Critical Illness

    PubMed Central

    Plummer, Mark P.; Finnis, Mark E.; Phillips, Liza K.; Kar, Palash; Bihari, Shailesh; Biradar, Vishwanath; Moodie, Stewart; Horowitz, Michael; Shaw, Jonathan E.; Deane, Adam M.

    2016-01-01

    Objective Stress induced hyperglycemia occurs in critically ill patients who have normal glucose tolerance following resolution of their acute illness. The objective was to evaluate the association between stress induced hyperglycemia and incident diabetes in survivors of critical illness. Design Retrospective cohort study. Setting All adult patients surviving admission to a public hospital intensive care unit (ICU) in South Australia between 2004 and 2011. Patients Stress induced hyperglycemia was defined as a blood glucose ≥ 11.1 mmol/L (200 mg/dL) within 24 hours of ICU admission. Prevalent diabetes was identified through ICD-10 coding or prior registration with the Australian National Diabetes Service Scheme (NDSS). Incident diabetes was identified as NDSS registration beyond 30 days after hospital discharge until July 2015. The predicted risk of developing diabetes was described as sub-hazard ratios using competing risk regression. Survival was assessed using Cox proportional hazards regression. Main Results Stress induced hyperglycemia was identified in 2,883 (17%) of 17,074 patients without diabetes. The incidence of type 2 diabetes following critical illness was 4.8% (821 of 17,074). The risk of diabetes in patients with stress induced hyperglycemia was approximately double that of those without (HR 1.91 (95% CI 1.62, 2.26), p<0.001) and was sustained regardless of age or severity of illness. Conclusions Stress induced hyperglycemia identifies patients at subsequent risk of incident diabetes. PMID:27824898

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

    PubMed

    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 < 0.05) increased high density lipoprotein (HDL) cholesterol while it significantly (p < 0.05) reduced hyperglycemia, triglycerides (TGs), very low density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, coronary risk index (CRI) and cardiovascular risk index (CVRI). In contrast, honey (3.0 g/kg) significantly (p < 0.05) reduced TGs and VLDL cholesterol. This study confirms the reproducibility of glucose lowering and hypolipidemic effects of honey using Nigerian honey. However, none of the doses deteriorated hyperglycemia and dyslipidemia.

  4. Transient Worsening of Photosensitivity due to Cholelithiasis in a Variegate Porphyria Patient

    PubMed Central

    Susa, Shinji; Sato-Monma, Fumiko; Ishii, Kouta; Hada, Yurika; Takase, Kaoru; Tada, Kyoko; Wada, Kiriko; Kameda, Wataru; Watanabe, Kentaro; Oizumi, Toshihide; Suzuki, Tamio; Daimon, Makoto; Kato, Takeo

    2016-01-01

    Variegate porphyria (VP) is an autosomal dominant disease caused by mutations of the protoporphyrinogen oxidase (PPOX) gene. This porphyria has unique characteristics which can induce acute neurovisceral attacks and cutaneous lesions that may occur separately or together. We herin report a 58-years-old VP patient complicated with cholelithiasis. A sequencing analysis indicated a novel c.40G>C mutation (p.G14R) in the PPOX gene. His cutaneous photosensitivity had been worsening for 3 years before the emergence of cholecystitis and it then gradually improved after cholecystectomy and ursodeoxycholic acid treatment with a slight decline in the porphyrin levels in his blood, urine and stool. In VP patients, a worsening of photosensitivity can thus be induced due to complications associated with some other disease, thereby affecting their porphyrin-heme biosynthesis. PMID:27746433

  5. Hyperglycemia enhances excessive superoxide anion radical generation, oxidative stress, early inflammation, and endothelial injury in forebrain ischemia/reperfusion rats.

    PubMed

    Tsuruta, Ryosuke; Fujita, Motoki; Ono, Takeru; Koda, Yoichi; Koga, Yasutaka; Yamamoto, Takahiro; Nanba, Masahiro; Shitara, Masaki; Kasaoka, Shunji; Maruyama, Ikuro; Yuasa, Makoto; Maekawa, Tsuyoshi

    2010-01-14

    The aim of this study was to confirm the effect of acute hyperglycemia on the superoxide anion radical (O(2)(-)) generation, using a novel electrochemical O(2)(-) sensor in forebrain ischemia/reperfusion rats. Fourteen male Wistar rats were allocated to a normoglycemia group (n= 7) and a hyperglycemia group (n=7). Hyperglycemia was induced by intravenous infusion of glucose solution. Forebrain ischemia was induced by bilateral common carotid arteries occlusion with hemorrhagic hypotension for 10 min and then was reperfused. The generated O(2)(-) was measured as the current produced, which was integrated as a quantified partial value of electricity (Q), in the jugular vein using the O(2)(-) sensor. The reacted O(2)(-) current and the Q began to increase gradually during the forebrain ischemia in both groups. These values increased remarkably just after reperfusion in the normoglycemia group and were further increased significantly in the hyperglycemia group after the reperfusion. Concentrations of malondialdehyde (MDA) and high-mobility group box 1 (HMGB1) in the brain and plasma, and soluble intercellular adhesion molecule-1 (ICAM-1) in the plasma in the hyperglycemia group were significantly higher than those in the normoglycemia group. Brain and plasma MDA, HMGB1, and ICAM-1 were correlated with a sum of Q during ischemia and after reperfusion. In conclusion, acute transient hyperglycemia enhanced the O(2)(-) generation in blood and exacerbated oxidative stress, early inflammation, and endothelial injury after the forebrain ischemia/reperfusion in the rats.

  6. Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1 diabetes

    PubMed Central

    Novak, B. J.; Blake, D. R.; Meinardi, S.; Rowland, F. S.; Pontello, A.; Cooper, D. M.; Galassetti, P. R.

    2007-01-01

    Recent technical advances allow detection of several hundred volatile organic compounds (VOCs) in human exhaled air, many of which reflect unidentified endogenous pathways. Our group has previously estimated plasma glucose levels in healthy adults during a standard oral glucose tolerance test via exhaled VOC analysis. As a result of the metabolic characteristics of hyperglycemia in the diabetic (low insulin and increased free fatty acids and ketones), we hypothesized that different exhaled VOC profiles may be present in children with type 1 diabetes mellitus (T1DM) during spontaneous hyperglycemia. Exhaled methyl nitrate strongly correlated specifically with the acute, spontaneous hyperglycemia of T1DM children. Eighteen experiments were conducted among 10 T1DM children. Plasma glucose and exhaled gases were monitored during either constant euglycemia (n = 5) or initial hyperglycemia with gradual correction (n = 13); all subjects received i.v. insulin and glucose as needed. Gas analysis was performed on 1.9-liter breath samples via gas chromatography using electron capture, flame ionization, and mass selective detection. Among the ≈100 measured exhaled gases, the kinetic profile of exhaled methyl nitrate, commonly present in room air in the range of 5–10 parts per trillion, was most strongly statistically correlated with that of plasma glucose (P = 0.003–0.001). Indeed, the kinetic profiles of the two variables paralleled each other in 16 of 18 experiments, including repeat subjects who at different times displayed either euglycemia or hyperglycemia. PMID:17895380

  7. Hospital-Related Delirium May Help Worsen Dementia

    MedlinePlus

    ... medlineplus.gov/news/fullstory_163123.html Hospital-Related Delirium May Help Worsen Dementia But disorienting condition can ... WEDNESDAY, Jan. 18, 2017 (HealthDay News) -- Hospitalization-related delirium may speed mental decline in patients with dementia, ...

  8. Hyperglycemia impairs atherosclerosis regression in mice.

    PubMed

    Gaudreault, Nathalie; Kumar, Nikit; Olivas, Victor R; Eberlé, Delphine; Stephens, Kyle; Raffai, Robert L

    2013-12-01

    Diabetic patients are known to be more susceptible to atherosclerosis and its associated cardiovascular complications. However, the effects of hyperglycemia on atherosclerosis regression remain unclear. We hypothesized that hyperglycemia impairs atherosclerosis regression by modulating the biological function of lesional macrophages. HypoE (Apoe(h/h)Mx1-Cre) mice express low levels of apolipoprotein E (apoE) and develop atherosclerosis when fed a high-fat diet. Atherosclerosis regression occurs in these mice upon plasma lipid lowering induced by a change in diet and the restoration of apoE expression. We examined the morphological characteristics of regressed lesions and assessed the biological function of lesional macrophages isolated with laser-capture microdissection in euglycemic and hyperglycemic HypoE mice. Hyperglycemia induced by streptozotocin treatment impaired lesion size reduction (36% versus 14%) and lipid loss (38% versus 26%) after the reversal of hyperlipidemia. However, decreases in lesional macrophage content and remodeling in both groups of mice were similar. Gene expression analysis revealed that hyperglycemia impaired cholesterol transport by modulating ATP-binding cassette A1, ATP-binding cassette G1, scavenger receptor class B family member (CD36), scavenger receptor class B1, and wound healing pathways in lesional macrophages during atherosclerosis regression. Hyperglycemia impairs both reduction in size and loss of lipids from atherosclerotic lesions upon plasma lipid lowering without significantly affecting the remodeling of the vascular wall.

  9. Chorea-Ballismus Associated with Hyperglycemia

    PubMed Central

    KOCASOY ORHAN, Elif; ATMACA, M. Mert; ATMACA, Melek; HANAĞASI, Haşmet A.

    2013-01-01

    Chorea-ballismus which is a rare complication of nonketotic hyperglycemia may be the first symptom of type 2 diabetes mellitus. In this paper, we present two patients, who had involuntary movements and were diagnosed as having ballismus-chorea associated with nonketotic hyperglycemia. While one of the patients was not diagnosed with diabetes mellitus, the other one did not administer insulin therapy for a long time which was prescribed. The patients were investigated by cranial imaging and biochemical tests. The symptoms improved in one of them within hours, however, it took days to improve for the other one. This clinical situation, which is thought to be caused by hyperglycemia, cerebral ischemia and failure of gamma-aminobutyric acid (GABA) and which probably improves with regulation of blood glucose levels, should be kept in mind by emergency physicians, because it can be the first presentation of type 2 diabetes mellitus.

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

    PubMed Central

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

    2016-01-01

    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. PMID:27617745

  11. Predictors of disability worsening in clinically isolated syndrome

    PubMed Central

    Jokubaitis, Vilija G; Spelman, Tim; Kalincik, Tomas; Izquierdo, Guillermo; Grand'Maison, François; Duquette, Pierre; Girard, Marc; Lugaresi, Alessandra; Grammond, Pierre; Hupperts, Raymond; Cabrera-Gomez, José; Oreja-Guevara, Celia; Boz, Cavit; Giuliani, Giorgio; Fernández-Bolaños, Ricardo; Iuliano, Gerardo; Lechner-Scott, Jeannette; Verheul, Freek; van Pesch, Vincent; Petkovska-Boskova, Tatjana; Fiol, Marcela; Moore, Fraser; Cristiano, Edgardo; Alroughani, Raed; Bergamaschi, Roberto; Barnett, Michael; Slee, Mark; Vella, Norbert; Herbert, Joseph; Shaw, Cameron; Saladino, Maria Laura; Amato, Maria Pia; Liew, Danny; Paolicelli, Damiano; Butzkueven, Helmut; Trojano, Maria

    2015-01-01

    Objective To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression. Results About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening. Interpretation This study provides class IV evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors. PMID:26000321

  12. Administration of Anti-Reg I and Anti-PAPII Antibodies Worsens Pancreatitis

    PubMed Central

    Viterbo, Domenico; Callender, Gordon E; DiMaio, Theresa; Mueller, Cathy M; Smith-Norowitz, Tamar; Zenilman, Michael E; Bluth, Martin H

    2009-01-01

    Context The regeneration protein family (Reg), which includes Reg I and PAPII, is expressed in pancreas acinar cells, and increases in acute pancreatitis. We have demonstrated that Reg gene knockdown worsens severity of acute pancreatitis in the rat and hypothesize that the proteins offer a protective effect in this disease. Objective We investigated the ability of anti-Reg and anti-PAP antibody to neutralize pancreatic Reg protein and affect pancreatitis severity. Intervention Pancreatitis was induced in rats by retrograde ductal injection of 4% sodium taurocholate. Animals Eighty-four rats: 48 with induced pancreatitis, 30 sham operated, and 6 normal animals. Setting Intraductal anti-Reg I and/or anti-PAPII antibody was administered at induced pancreatitis and sham operated subgroups of 6 rats each. Main outcome measure Serum and pancreata were harvested 24 and/or 48 hours later and assessed for pancreatitis severity by pancreatic wet weight, serum C-reactive protein (CRP), amylase, PAPII levels, and histopathology. Results Animals induced with pancreatitis with administration of anti-Reg/PAP antibodies had significantly higher wet weights compared with taurocholate and histopathological analysis revealed that anti-Reg/PAP treated animals had worse tissue inflammation and necrosis compared with controls. Serum CRP, amylase, and Reg levels did not significantly differ between experimental and sham control groups. Conclusions Administration of anti-Reg/PAP antibody worsened taurocholate-induced organ specific pancreatitis. These data suggest that the Reg family of proteins is protective in acute pancreatitis. PMID:19129610

  13. Non-Cholesterol Sterol Levels Predict Hyperglycemia and Conversion to Type 2 Diabetes in Finnish Men

    PubMed Central

    Cederberg, Henna; Gylling, Helena; Miettinen, Tatu A.; Paananen, Jussi; Vangipurapu, Jagadish; Pihlajamäki, Jussi; Kuulasmaa, Teemu; Stančáková, Alena; Smith, Ulf; Kuusisto, Johanna; Laakso, Markku

    2013-01-01

    We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes. PMID:23840693

  14. [A Case of Renal Cell Carcinoma with High Everolimus Blood Concentrations and Hyperglycemia Due to Everolimus-Induced Hepatic Dysfunction].

    PubMed

    Takasaki, Shinya; Kikuchi, Masafumi; Kawasaki, Yoshihide; Ito, Akihiro; Arai, Yoichi; Yamaguchi, Hiroaki; Mano, Nariyasu

    2017-01-01

    We report the case of a patient who had renal cell carcinoma with high everolimus blood concentrations and hyperglycemia due to everolimus-induced hepatic dysfunction. A 74-year-old man who underwent right nephrectomy for renal cell carcinoma was administered everolimus for multiple lung metastases. Everolimus caused grade 3 hepatic dysfunction and hyperglycemia; hence, high blood levels of everolimus were observed. Although the patient was re-administrated everolimus after recovering from hepatic dysfunction, hepatic function test values worsened again. Everolimus was discontinued before its blood concentration increased, and the patient was switched to axitinib treatment. Therefore, the measurement of everolimus blood level is considered useful for the management of adverse events in renal cell carcinoma.

  15. Recognizing the Symptoms of Worsening Heart Valve Disease

    MedlinePlus

    ... Aortic Aneurysm More Recognizing the Symptoms of Worsening Heart Valve Disease Updated:Sep 29,2016 Would you recognize the ... Options • Recovery and Healthy Living Goals • Personal Stories Heart Valve Disease Symptoms Dr. Robert Bonow describes the symptoms that ...

  16. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

    ERIC Educational Resources Information Center

    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…

  17. Hyperglycemia and Diabetes Mellitus Following Organ Transplantation.

    PubMed

    Galindo, Rodolfo J; Wallia, Amisha

    2016-02-01

    Hyperglycemia is common following organ transplantation, regardless of the pre-transplant diabetes status. Transient post-transplant hyperglycemia and/or new-onset diabetes after transplantation (NODAT) are common and are associated with increased morbidity and mortality. NODAT and type 2 diabetes share similar characteristics, but the pathophysiology may differ. Immunosuppressive agents and steroids play a key role in the development of NODAT. Glycemic control is challenging in this population due to fluctuating renal/end-organ function, immunosuppressive dosing, nutritional status, and drug-drug interactions. A proactive and multidisciplinary approach is essential, along with flexible protocols to adjust to patient status, type of organ transplanted, and corticosteroid regimens. Insulin is the preferred agent for hospitalized patients and during the early post-transplant period; optimal glycemic control (BG < 180 mg/dl with minimal hypoglycemia [<70 mg/dl]) is desired.

  18. Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine.

    PubMed

    Nagata, Masashi; Nakajima, Mayumi; Ishiwata, Yasuyoshi; Takahashi, Yutaka; Takahashi, Hiromitsu; Negishi, Kenichi; Yasuhara, Masato

    2016-01-01

    Acute administration of olanzapine rapidly elevates blood glucose levels. However, the mechanism underlying the rapid development of hyperglycemia with the administration of olanzapine remains unclear. The aim of the present study was to clarify the mechanism underlying olanzapine-induced acute hyperglycemia. Male Wistar rats received an intravenous infusion of saline (control) or olanzapine 2.5, 5, or 10 mg/kg. Blood samples were obtained periodically after olanzapine infusion to determine serum concentrations of glucose, olanzapine, and several endogenous substances. In a separate experiment, rats received an intravenous injection of propranolol (2 mg/kg) 30 min before infusion of olanzapine (10 mg/kg). The intravenous infusion of olanzapine induced dose-dependent increases in the serum concentrations of glucose, epinephrine, and insulin. Pretreatment with propranolol suppressed olanzapine-induced elevations in the serum concentration of glucose, but did not affect the serum concentration of olanzapine or olanzapine-induced increase in the serum concentration of epinephrine. Although the serum concentration of corticosterone increased after administration of olanzapine, no significant differences were observed among the olanzapine dose groups. Furthermore, administration of olanzapine did not affect the serum concentration of glucagon or histamine. We developed a pharmacokinetic-pharmacodynamic model assuming that the olanzapine-induced secretion of epinephrine leads to elevated serum glucose concentrations. This model appeared to satisfactorily characterize olanzapine-induced hyperglycemia. In conclusion, a single intravenous dose of olanzapine dose-dependently increased the serum concentration of glucose in rats, and epinephrine plays a role in olanzapine-induced acute hyperglycemia.

  19. Image-size differences worsen stereopsis independent of eye position

    PubMed Central

    Vlaskamp, Björn N. S.; Filippini, Heather R.; Banks, Martin S.

    2010-01-01

    With the eyes in forward gaze, stereo performance worsens when one eye’s image is larger than the other’s. Near, eccentric objects naturally create retinal images of different sizes. Does this mean that stereopsis exhibits deficits for such stimuli? Or does the visual system compensate for the predictable image-size differences? To answer this, we measured discrimination of a disparity-defined shape for different relative image sizes. We did so for different gaze directions, some compatible with the image-size difference and some not. Magnifications of 10–15% caused a clear worsening of stereo performance. The worsening was determined only by relative image size and not by eye position. This shows that no neural compensation for image-size differences accompanies eye-position changes, at least prior to disparity estimation. We also found that a local cross-correlation model for disparity estimation performs like humans in the same task, suggesting that the decrease in stereo performance due to image-size differences is a byproduct of the disparity-estimation method. Finally, we looked for compensation in an observer who has constantly different image sizes due to differing eye lengths. She performed best when the presented images were roughly the same size, indicating that she has compensated for the persistent image-size difference. PMID:19271927

  20. Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Marchi, E; Torella, R

    1989-12-01

    The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

  1. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  2. Hyperglycemia and diabetes have different impacts on outcome of ischemic and hemorrhagic stroke

    PubMed Central

    Snarska, Katarzyna K.; Bachórzewska-Gajewska, Hanna; Kapica-Topczewska, Katarzyna; Drozdowski, Wiesław; Chorąży, Monika; Kułakowska, Alina

    2016-01-01

    Introduction Stroke is the second leading cause of long-term disability and death worldwide. Diabetes and hyperglycemia may impact the outcome of stroke. We examined the impact of hyperglycemia and diabetes on in-hospital death among ischemic and hemorrhagic stroke patients. Material and methods Data from 766 consecutive patients with ischemic (83.15%) and hemorrhagic stroke were analyzed. Patients were classified into four groups: ischemic and diabetic; ischemic and non-diabetic; hemorrhagic and diabetic; and hemorrhagic and non-diabetic. Serum glucose was measured on admission at the emergency department together with biochemical and clinical parameters. Results Mean admission glucose in ischemic stroke patients with diabetes was higher than in non-diabetic ones (p < 0.001) and in hemorrhagic stroke patients with diabetes than in those without diabetes (p < 0.05). Mean admission glucose in all patients who died was significantly higher than in patients who survived. In multivariate analysis, the risk factors for outcome in patients with ischemic stroke and without diabetes were age, admission glucose level and estimated glomerular filtration rate (eGFR), while in diabetics they were female gender, admission glucose level, and eGFR; in patients with hemorrhagic stroke and without diabetes they were age and admission glucose levels. The cut-off value in predicting death in patients with ischemic stroke and without diabetes was above 113.5 mg/dl, while in diabetics it was above 210.5 mg/dl. Conclusions Hyperglycemia on admission is associated with worsened clinical outcome and increased risk of in-hospital death in ischemic and hemorrhagic stroke patients. Diabetes increased the risk of in-hospital death in hemorrhagic stroke patients, but not in ischemic ones. PMID:28144261

  3. Hyperglycemia triggers HIPK2 protein degradation

    PubMed Central

    Granato, Marisa; Cuomo, Laura; Pistritto, Giuseppa; Cirone, Mara; D'Orazi, Gabriella

    2017-01-01

    Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2. We focused on the effect of high glucose (HG) on HIPK2 protein stability and the underlying mechanisms. We found that HG reduced HIPK2 protein levels, therefore impairing HIPK2-induced p53 apoptotic activity. HG-triggered HIPK2 protein downregulation was rescued by both proteasome inhibitor MG132 and by protein phosphatase inhibitors Calyculin A (CL-A) and Okadaic Acid (OA). Looking for the phosphatase involved, we found that protein phosphatase 2A (PP2A) induced HIPK2 degradation, as evidenced by directly activating PP2A with FTY720 or by silencing PP2A with siRNA in HG condition. The effect of PP2A on HIPK2 protein degradation could be in part due to hypoxia-inducible factor-1 (HIF-1) activity which has been previously shown to induce HIPK2 proteasomal degradation through several ubiquitin ligases. Validation analysed performed with HIF-1α dominant negative or with silencing of Siah2 ubiquitin ligase clearly showed rescue of HG-induced HIPK2 degradation. These findings demonstrate how hyperglycemia, through a complex protein cascade, induced HIPK2 downregulation and consequently impaired p53 apoptotic activity, revealing a novel link between diabetes/obesity and tumor resistance to therapies. PMID:27901482

  4. [Management of hyperglycemia in hospitalized patients].

    PubMed

    Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María Pilar; Madrigal-Santillán, Eduardo Osiris; Morales-González, José Antonio; Vera-Lastra, Olga Lidia

    2015-01-01

    Diabetes is a global health problem and Mexico rank sixth in prevalence of this entity. In our country, is the leading cause of death and is a major cause of hospital care being responsible for about 1 in 5 discharges. In the hospital setting, it has been observed that hyperglycemia, both diabetic and non-diabetic patients, is associated with an increased risk of complications, disability and death, and that adequate control in the blood glucose level produces a reduction in these complications. With these bases, several associations have recommended the treatment of hospital hyperglycemia through insulin administration, with the therapeutic goal of maintaining a fasting blood glucose level between 100-140 mg/dL and glucose at any time of day less than 180 mg/dL. The insulin application method most recommended consisting in a basal-bolus regimen which has shown efficacy with a low risk of hypoglycemia. The usual practice of the application of insulin through a correction scheme should be abandoned because it is inefficient and involves risks.

  5. Armanni-Ebstein Lesions in Terminal Hyperglycemia.

    PubMed

    Zhou, Chong; Yool, Andrea J; Byard, Roger W

    2016-12-16

    Armanni-Ebstein lesions (AEL) occur in deaths related to uncontrolled diabetes mellitus. To investigate the relationship between AEL and terminal hyperglycemia, we retrospectively reviewed 71 cases with vitreous glucose levels ≥11.1 mmol/L; 27 (38%) cases had AEL (vitreous glucose 14.0-77.3 mmol/L); and 44 cases (62%) did not (vitreous glucose 11.1-91.9 mmol/L). There was no significant difference (p = 0.271) in vitreous glucose levels between the cases with AEL (mean 39.2, SD 16.7 mmol/L) and those without (mean 34.2, SD 19.8 mmol/L). Similarly, there was no difference in the degree of dehydration, renal failure, or osmolality. However, there was a significantly higher level of β-hydroxybutyrate among the cases with AEL compared to those without (p = 0.007), suggesting that ketoacidosis may facilitate the development of AEL. Given the possible synergistic role of β-hydroxybutyrate, the correlation between AEL and terminal hyperglycemia in animal studies may not be applicable to humans. AEL may also possibly occur with sublethal elevations in glucose.

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

    PubMed

    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.

  7. Effect of Admission Hyperglycemia on 6-Month Functional Outcome in Patients with Spontaneous Cerebellar Hemorrhage

    PubMed Central

    Tao, Chuanyuan; Hu, Xin; Wang, Jiajing; You, Chao

    2017-01-01

    Background Cerebellar hemorrhage (CH) has a quite different treatment strategy and prognostic factors compared with supratentorial intracerebral hemorrhage (ICH). The prognostic role of hyperglycemia has been discussed mainly in cases of supratentorial hemorrhage; it remains to be elucidated following CH. We aimed to determine the association of hyperglycemia on admission with 6-month functional outcome in CH patients. Material/Methods We retrospectively analyzed 77 patients with acute CH between September 2010 and April 2015 in West China Hospital. Blood glucose level was measured when the patients were admitted. Primary outcome was 6-month functional outcome, which could comprehensively reflect the patient’s recovery of physical and social ability after stroke and was assessed by the modified Rankin scale (mRS). Association of hyperglycemia with functional outcome was identified in logistic regression models. Results There were 50 (64.9%) patients with poor functional outcomes. Patients with poor outcome were much older (P<0.001) and had a significantly higher glucose level on admission (P<0.001), a lower Glasgow Coma Scale score (P<0.001), a larger hematoma (P=0.003), and a higher incidence of intraventricular extension (P=0.002), brainstem compression (P=0.013), and hydrocephalus (P=0.023). Multivariate analysis showed that hyperglycemia (OR 1.50, 95% CI 1.07–2.08, P=0.017 when glucose level was analyzed as a continuous variable; OR 7.46, 95% CI 1.41–39.51, P=0.018 when glucose level was dichotomized by the critical threshold of 6.78 mmol/L) emerged as an independent predictor for adverse functional outcome at 6 months. Conclusions To the best of our knowledge, this is the first study focusing on the relationship between hyperglycemia and long-term functional outcome after CH. The study combined with previous pertinent reports definitely indicates the poor effect of hyperglycemia on both supra- and infratentorial ICH independent of hemorrhage site

  8. Effect of Admission Hyperglycemia on 6-Month Functional Outcome in Patients with Spontaneous Cerebellar Hemorrhage.

    PubMed

    Tao, Chuanyuan; Hu, Xin; Wang, Jiajing; You, Chao

    2017-03-08

    BACKGROUND Cerebellar hemorrhage (CH) has a quite different treatment strategy and prognostic factors compared with supratentorial intracerebral hemorrhage (ICH). The prognostic role of hyperglycemia has been discussed mainly in cases of supratentorial hemorrhage; it remains to be elucidated following CH. We aimed to determine the association of hyperglycemia on admission with 6-month functional outcome in CH patients. MATERIAL AND METHODS We retrospectively analyzed 77 patients with acute CH between September 2010 and April 2015 in West China Hospital. Blood glucose level was measured when the patients were admitted. Primary outcome was 6-month functional outcome, which could comprehensively reflect the patient's recovery of physical and social ability after stroke and was assessed by the modified Rankin scale (mRS). Association of hyperglycemia with functional outcome was identified in logistic regression models. RESULTS There were 50 (64.9%) patients with poor functional outcomes. Patients with poor outcome were much older (P<0.001) and had a significantly higher glucose level on admission (P<0.001), a lower Glasgow Coma Scale score (P<0.001), a larger hematoma (P=0.003), and a higher incidence of intraventricular extension (P=0.002), brainstem compression (P=0.013), and hydrocephalus (P=0.023). Multivariate analysis showed that hyperglycemia (OR 1.50, 95% CI 1.07-2.08, P=0.017 when glucose level was analyzed as a continuous variable; OR 7.46, 95% CI 1.41-39.51, P=0.018 when glucose level was dichotomized by the critical threshold of 6.78 mmol/L) emerged as an independent predictor for adverse functional outcome at 6 months. CONCLUSIONS To the best of our knowledge, this is the first study focusing on the relationship between hyperglycemia and long-term functional outcome after CH. The study combined with previous pertinent reports definitely indicates the poor effect of hyperglycemia on both supra- and infratentorial ICH independent of hemorrhage site

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

    PubMed

    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.

  10. Hyperglycemia Induces Embryopathy, Even in the Absence of Systemic Maternal Diabetes: An In Vivo Test of the Fuel Mediated Teratogenesis Hypothesis

    PubMed Central

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

    2014-01-01

    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 (25 mg/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. PMID:24721120

  11. Hyperglycemia accelerates apparent diffusion coefficient-defined lesion growth after focal cerebral ischemia in rats with and without features of metabolic syndrome.

    PubMed

    Tarr, David; Graham, Delyth; Roy, Lisa A; Holmes, William M; McCabe, Christopher; Mhairi Macrae, I; Muir, Keith W; Dewar, Deborah

    2013-10-01

    Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.

  12. Stress Hyperglycemia During Surgery and Anesthesia: Pathogenesis and Clinical Implications.

    PubMed

    Palermo, Nadine E; Gianchandani, Roma Y; McDonnell, Marie E; Alexanian, Sara M

    2016-03-01

    Numerous studies have demonstrated an association between hyperglycemia in the perioperative period and adverse clinical outcomes. Many patients who experience hyperglycemia while hospitalized do not have a known history of diabetes and experience a transient phenomenon often described as "stress hyperglycemia" (SH). We discuss the epidemiology and pathogenesis of SH as well as evidence to date regarding predisposing factors and outcomes. Further research is needed to identify the long-term sequelae of SH as well as perioperative measures that may modulate glucose elevations and optimal treatment strategies.

  13. Thyroid function and stress hormones in children with stress hyperglycemia.

    PubMed

    Bordbar, Mohammad Reza; Taj-Aldini, Reza; Karamizadeh, Zohre; Haghpanah, Sezaneh; Karimi, Mehran; Omrani, Gholam Hossein

    2012-12-01

    The purpose of the study is to determine the prevalence of stress hyperglycemia and to investigate how thyroid and stress hormones alter during stress hyperglycemia in children admitted to pediatric emergency wards. A prospective cross-sectional study was conducted in children, less than 19 years old, who were admitted to pediatric emergency wards of Nemazee and Dastgheib Hospitals, Shiraz, Southern Iran. Those patients taking steroids, beta-agonists or intravenously administered glucose before venipuncture, and patients with diabetes mellitus (DM) or thyroid diseases were excluded. Children with blood glucose ≥ 150 mg/dL during admission were regarded as cases. The controls were age- and- sex- matched, euglycemic children. Stress hormones including cortisol, insulin, growth hormone, and prolactin were measured, and thyroid function was tested with a radioimmunoassay (RIA) method in all cases and controls. The results showed that among 1,054 screened children, 39 cases (3.7 %) had stress hyperglycemia and 89 controls were included in the study. The occurrence of hyperglycemia was independent of sex, but it occurred mostly in children under 6 years old. Hyperglycemia occurred more frequently in patients with a positive family history of DM (odds ratio = 3.2, 95 % CI = 1.3-7.9, and P = 0.009). There were no significant differences between cases and controls regarding any hormones except higher cortisol, and lower total T3 and T4 in cases compared with controls. Neither of cases developed diabetes in the 24-month follow-up period. These findings led us to the conclusion that stress hyperglycemia is occasionally seen in critically ill patients. Among the stress hormones measured, only cortisol increased during hyperglycemia. It seems that hyperglycemia is not an important risk factor for future diabetes.

  14. Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia.

    PubMed

    Amaral, Fernanda G; Turati, Ariane O; Barone, Mark; Scialfa, Julieta H; do Carmo Buonfiglio, Daniella; Peres, Rafael; Peliciari-Garcia, Rodrigo A; Afeche, Solange C; Lima, Larissa; Scavone, Cristoforo; Bordin, Silvana; Reiter, Russel J; Menna-Barreto, Luiz; Cipolla-Neto, José

    2014-08-01

    Melatonin is a neurohormone that works as a nighttime signal for circadian integrity and health maintenance. It is crucial for energy metabolism regulation, and the diabetes effects on its synthesis are unresolved. Using diverse techniques that included pineal microdialysis and ultrahigh-performance liquid chromatography, the present data show a clear acute and sustained melatonin synthesis reduction in diabetic rats as a result of pineal metabolism impairment that is unrelated to cell death. Hyperglycemia is the main cause of several diabetic complications, and its consequences in terms of melatonin production were assessed. Here, we show that local high glucose (HG) concentration is acutely detrimental to pineal melatonin synthesis in rats both in vivo and in vitro. The clinically depressive action of high blood glucose concentration in melatonin levels was also observed in type 1 diabetes patients who presented a negative correlation between hyperglycemia and 6-sulfatoxymelatonin excretion. Additionally, high-mean-glycemia type 1 diabetes patients presented lower 6-sulfatoxymelatonin levels when compared to control subjects. Although further studies are needed to fully clarify the mechanisms, the present results provide evidence that high circulating glucose levels interfere with pineal melatonin production. Given the essential role played by melatonin as a powerful antioxidant and in the control of energy homeostasis, sleep and biological rhythms and knowing that optimal glycemic control is usually an issue for patients with diabetes, melatonin supplementation may be considered as an additional tool to the current treatment.

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

    PubMed Central

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

    2002-01-01

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

  16. Serum Calcium Increase Correlates With Worsening of Lipid Profile

    PubMed Central

    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

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

    PubMed

    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.

  18. Loss of matrix metalloproteinase-8 is associated with worsened recovery after ischemic kidney injury.

    PubMed

    Basu, Rajit K; Donaworth, Emily; Siroky, Brian; Devarajan, Prasad; Wong, Hector R

    2015-04-01

    Acute kidney injury (AKI) leads to chronic kidney disease. The mechanisms involved with recovery from AKI are poorly understood and molecular mediators responsible for healing and restoration of kidney function are understudied. We previously discovered differential expression of matrix metalloproteinase-8 (MMP-8) mRNA and protein in patients with severe sepsis associated AKI versus sepsis without AKI. Here, we demonstrate the involvement of MMP-8 in purely ischemic AKI. Mice subjected to 30 min of bilateral renal ischemia developed increased plasma creatinine and MMP-8 expression within 24 h versus sham controls. After an initial surge and subsequent return toward baseline, both kidney MMP-8 expression and activity exhibited a late increase (Days 5-7 post-ischemia reperfusion) in mice subjected to AKI. Neutrophil infiltration of the kidney was significantly higher after AKI in wild-type mice than in MMP-8 null mice, starting at 4 days. Additionally, MMP-8 null mice subjected to AKI demonstrated a persistent histopathologic and functional injury and worsened health (greater overall weight loss) versus wild-type cohorts after seven days. Taken together, our findings suggest that MMP-8 is involved with restoration of baseline kidney health after ischemic kidney injury and that a potential mechanism involves the interaction of MMP-8 and neutrophil recruitment to the site of injury.

  19. Hyperglycemia in Critically Ill Patients: Management and Prognosis

    PubMed Central

    Godinjak, Amina; Iglica, Amer; Burekovic, Azra; Jusufovic, Selma; Ajanovic, Anes; Tancica, Ira; Kukuljac, Adis

    2015-01-01

    Introduction: Hyperglycemia is a common complication of critical illness. Patients in intensive care unit with stress hyperglycemia have significantly higher mortality (31%) compared to patients with previously confirmed diabetes (10%) or normoglycemia (11.3%). Stress hyperglycemia is associated with increased risk of critical illness polyneuropathy (CIP) and prolonged mechanical ventilation. Intensive monitoring and insulin therapy according to the protocol are an important part of the treatment of critically ill patients. Objective: To evaluate the incidence of stress hyperglycemia, complications and outcome in critically ill patients in our Medical intensive care unit. Materials and methods: This study included 100 patients hospitalized in Medical intensive care unit during the period January 2014–March 2015 which were divided into three groups: Diabetes mellitus, stress-hyperglycemia and normoglycemia. During the retrospective-prospective observational clinical investigation the following data was obtained: age, gender, SAPS, admission diagnosis, average daily blood glucose, highest blood glucose level, glycemic variability, vasopressor and corticosteroid therapy, days on mechanical ventilation, total days of hospitalization in Medical intensive care unit, and outcome. Results: Patients with DM treated with a continuous insulin infusion did not have significantly more complications than patients with normoglycemia, unlike patients with stress hyperglycemia, which had more severe prognosis. There was a significant difference between the maximum level of blood glucose in recovered and patients with adverse outcome (p = 0.0277). Glycemic variability (difference between max. and min. blood glucose) was the strongest predictor of adverse outcome. The difference in glycemic variability between the stress-hyperglycemia and normoglycemic group was statistically significant (p = 0.0066). There was no statistically significant difference in duration of mechanical

  20. Outcomes and worsening renal function in patients hospitalized with heart failure with preserved ejection fraction.

    PubMed

    Sharma, Kavita; Hill, Terence; Grams, Morgan; Daya, Natalie R; Hays, Allison G; Fine, Derek; Thiemann, David R; Weiss, Robert G; Tedford, Ryan J; Kass, David A; Schulman, Steven P; Russell, Stuart D

    2015-11-15

    Heart failure with preserved ejection fraction (HFpEF) has been described as a disease of elderly subjects with female predominance and hypertension. Our clinical experience suggests patients with HFpEF from an urban population are far more heterogenous, with greater co-morbidities and significant inhospital morbidity. There are limited data on the hospitalization course and outcomes in acute decompensated HFpEF. Hospitalizations for acute heart failure at our institution from July 2011 to June 2012 were identified by International Classification of Diseases, Ninth Revision, codes and physician review for left ventricular ejection fraction ≥50% and were reviewed for patient characteristics and clinical outcomes. Worsening renal function (WRF) was defined as creatinine increase of ≥0.3 mg/dl by 72 hours after admission. Hospital readmission and mortality data were captured from electronic medical records and the Social Security Death Index. Of 434 heart failure admissions, 206 patients (47%) with HFpEF were identified. WRF developed in 40%, the highest reported in HFpEF to date, and was associated with higher blood pressure and lower volume of diuresis. Compared to previous reports, hospitalized patients with HFpEF were younger (mean age 63.2 ± 13.6 years), predominantly black (74%), and had more frequent and severe co-morbidities: hypertension (89%), diabetes (56%), and chronic kidney disease (55%). There were no significant differences in 1- and 12-month outcomes by gender, race, or WRF. In conclusion, we found hospitalized patients with HFpEF from an urban population develop a high rate of WRF are younger than previous cohorts, often black, and have greater co-morbidities than previously described.

  1. Combination approaches to attenuate hemorrhagic transformation after tPA thrombolytic therapy in patients with poststroke hyperglycemia/diabetes.

    PubMed

    Fan, Xiang; Jiang, Yinghua; Yu, Zhanyang; Yuan, Jing; Sun, Xiaochuan; Xiang, Shuanglin; Lo, Eng H; Wang, Xiaoying

    2014-01-01

    To date, tissue type plasminogen activator (tPA)-based thrombolytic stroke therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 5% of stroke patients in the USA. This may be related, in part, to the elevated risk of symptomatic intracranial hemorrhage, and consequently limited therapeutic time window. Clinical investigations demonstrate that poststroke hyperglycemia is one of the most important risk factors that cause intracerebral hemorrhage and worsen neurological outcomes. There is a knowledge gap in understanding the underlying molecular mechanisms, and lack of effective therapeutics targeting the severe complication. This short review summarizes clinical observations and experimental investigations in preclinical stroke models of the field. The data strongly suggest that interactions of multiple pathogenic factors including hyperglycemia-mediated vascular oxidative stress and inflammation, ischemic insult, and tPA neurovascular toxicity in concert contribute to the BBB damage-intracerebral hemorrhagic transformation process. Development of combination approaches targeting the multiple pathological cascades may help to attenuate the hemorrhagic complication.

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

    PubMed

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

    2014-01-01

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

  3. Objectively-measured sleep duration and hyperglycemia in pregnancy

    PubMed Central

    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

  4. NAP reduces murine microvascular endothelial cells proliferation induced by hyperglycemia.

    PubMed

    D'Amico, Agata Grazia; Scuderi, Soraya; Maugeri, Grazia; Cavallaro, Sebastiano; Drago, Filippo; D'Agata, Velia

    2014-11-01

    Hyperglycemia has been identified as a risk factor responsible for micro- and macrovascular complications in diabetes. NAP (Davunetide) is a peptide whose neuroprotective actions are widely demonstrated, although its biological role on endothelial dysfunctions induced by hyperglycemia remains uninvestigated. In the present study we hypothesized that NAP could play a protective role on hyperglycemia-induced endothelial cell proliferation. To this end we investigated the effects of NAP on an in vitro model of murine microvascular endothelial cells grown in high glucose for 7 days. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and cyclin D1 protein expression analysis revealed that NAP treatment significantly reduces viability and proliferation of the cells. Hyperglycemia induced the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase and/or phosphatidylinositol-3 kinase/Akt pathways in a time-dependent manner. NAP treatment reduced the phosphorylation levels of ERK and AKT in cells grown in high glucose. These evidences suggest that NAP might be effective in the regulation of endothelial dysfunction induced by hyperglycemia.

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

    SciTech Connect

    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

  6. Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

    SciTech Connect

    Rolo, Anabela P.; Palmeira, Carlos M. . E-mail: palmeira@ci.uc.pt

    2006-04-15

    Hyperglycemia resulting from uncontrolled glucose regulation is widely recognized as the causal link between diabetes and diabetic complications. Four major molecular mechanisms have been implicated in hyperglycemia-induced tissue damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway flux, increased advanced glycation end product (AGE) formation, and increased polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the causal link between high glucose and the pathways responsible for hyperglycemic damage. In fact, diabetes is typically accompanied by increased production of free radicals and/or impaired antioxidant defense capabilities, indicating a central contribution for reactive oxygen species (ROS) in the onset, progression, and pathological consequences of diabetes. Besides oxidative stress, a growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. Mutations in mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and nuclear-encoded uncoupling proteins (UCPs) in {beta}-cell glucose toxicity. This review focuses on a range of mitochondrial factors important in the pathogenesis of diabetes. We review the published literature regarding the direct effects of hyperglycemia on mitochondrial function and suggest the possibility of regulation of mitochondrial function at a transcriptional level in response to hyperglycemia. The main goal of this review is to include a fresh consideration of pathways involved in hyperglycemia-induced diabetic complications.

  7. CT and MR Unilateral Brain Features Secondary to Nonketotic Hyperglycemia Presenting as Hemichorea-Hemiballism

    PubMed Central

    Suárez-Vega, Víctor Manuel; Sánchez Almaraz, Carlos; Bernardo, Ana Isabel; Rodríguez-Díaz, Ricardo; Díez Barrio, Ana; Martín Gil, Leticia

    2016-01-01

    Hemichorea-hemiballism is an unusual hyperkinetic movement disorder characterized by continuous involuntary movements of an entire limb or both limbs on one side of the body. The acute onset of this disorder occurs with an insult in contralateral basal ganglia. Ischemic events represent the most common cause. Nonketotic hyperglycemia comes in second place. Nonketotic hyperglycemic hemichorea-hemiballism (NHH) is a rare cause of unilateral brain abnormalities on imaging studies confined to basal ganglia (mainly putaminal region as well as caudate nucleus). Subtle hyperdensity in striatal region can be found on CT studies whereas brain MR imaging typically shows T1 hyperintensity and T2 hypointensity in the basal ganglia contralateral to the movements. Diagnosis is based on both glucose levels and neuroimaging findings. Elevated blood glucose and hemoglobin A1c levels occur with poorly controlled diabetes. In this case report, our aim is to present neuroimaging CT and MR unilateral findings in an elderly woman secondary to nonketotic hyperglycemia presenting as hemichorea-hemiballism. PMID:27247821

  8. Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial

    PubMed Central

    El-Mallakh, Rif S.; Vöhringer, Paul A.; Ostacher, Michael M.; Baldassano, Claudia F.; Holtzman, Niki S.; Whitham, Elizabeth A.; Thommi, Sairah B.; Goodwin, Frederick K.; Ghaemi, S. Nassir

    2015-01-01

    Background The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. Methods As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue versus discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. Results In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs NRC was 0.85 ± 0.37 (SE), df=28, p =0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals [9.9%, 46.5%], p = 0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. Conclusions In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, versus antidepressant discontinuation. PMID:26142612

  9. Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion

    SciTech Connect

    Risinger, F.O.; Cunningham, C.L. )

    1992-01-01

    Genetic differences in the hyperglycemic response to acute ethanol exposure and ethanol-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J and DBA/2J mice were injected with ethanol and blood glucose levels determined over 4 h. C57 mice demonstrated greater dose-dependent elevations in blood glucose compared to DBA mice. In a conditioned taste aversion procedure, water deprived mice received ethanol injections immediately after access to a NaCl flavored solution. DBA mice developed aversion to the ethanol-paired flavor at a lower dose than C57 mice. These results provide further support for a possible inverse genetic relationship between sensitivity to ethanol-induced hyperglycemia and sensitivity to conditioned taste aversion.

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

    ERIC Educational Resources Information Center

    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…

  11. Hyperglycemia associated dissociative fugue (organic dissociative disorder) in an elderly.

    PubMed

    Ram, Dushad; Ashoka, H G; Gowdappa, Basavnna

    2015-01-01

    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.

  12. Hemichorea/Hemiballism Associated with Hyperglycemia: Report of 20 Cases

    PubMed Central

    Cosentino, Carlos; Torres, Luis; Nuñez, Yesenia; Suarez, Rafael; Velez, Miriam; Flores, Martha

    2016-01-01

    Background Hemichorea/hemiballism associated with nonketotic hyperglycemia is a well-recognized syndrome, but few case series have been reported in the literature. Case Report We describe 20 patients with hemichorea/hemiballism associated with hyperglycemia (9 males and 11 females) with mean age of 67.8 years. Ten patients had a previous diagnosis of type 2 diabetes mellitus, and one had type 1 diabetes mellitus. Six of them had documentation of poor diabetic control over at least the last 3 months. Nine patients had new-onset hyperglycemia with a diagnosis of diabetes mellitus made after discharge. Seventeen patients had unilateral chorea/ballism, while three had bilateral chorea/ballism. Eighteen cases had striatal hyperdensities on computed tomography (CT) and/or hyperintense signals on magnetic resonance imaging (MRI). The putamen was affected in all cases, and the caudate nucleus was involved in nine. Discussion Hemichorea/hemiballism associated with nonketotic hyperglycemia can be the presenting sign of diabetes mellitus in almost half of cases or can occur after a few months of poor glycemic control in patients with diagnosed diabetes. This case series is one of the largest to date and adds valuable information about clinical and neuroimaging features that are comparable with published data but also emphasize the role of adequate diabetes mellitus control. PMID:27536463

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

    SciTech Connect

    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 {mu}g/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.

  14. High-Intensity Interval Training for Improving Postprandial Hyperglycemia

    ERIC Educational Resources Information Center

    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…

  15. Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

    PubMed Central

    Rakoczy, Elizabeth P.; Rahman, Ireni S. Ali; Binz, Nicolette; Li, Cai-Rui; Vagaja, Nermina N.; de Pinho, Marisa; Lai, Chooi-May

    2010-01-01

    One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors—hyperglycemia and vascular endothelial growth factor—interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/−) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema. PMID:20829433

  16. [NOPHAL Proyect: an integreting vision of hyperglycemia at the hospital].

    PubMed

    Tamez-Pérez, Héctor Eloy; Gómez-de Ossio, María Dolores; Bahena-García, Ana; Rodríguez-Valadez, Florisa; Tamez-Peña, Alejandra Lorena

    2009-01-01

    Patients with hyperglycemia are more likely to be hospitalized, and evidence links it with poor outcomes. Recognizing the importance of glycemic control, we develop a multidisciplinary educational program on inpatient glycemic management, with metabolic goals that are reasonable, achievable and safe.

  17. Diesel exhaust worsens cardiac conduction instability in dobutamine-challenged spontaneously hypertensive rats

    EPA Science Inventory

    This study demonstrated that diesel exhaust worsened arrhythmia and cardiac function during dobutamine (simulated exercise) challenge in normotensive and hypertensive rats. The data presented here are a mathematically-derived indicator of cardiac risk, which can be used for risk ...

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

    DTIC Science & Technology

    2013-02-01

    shown to reduce pain . Amantadine is an NMDA receptor antagonist that may mitigate central sensitization. Adjuvant analgesics may lessen nociceptive ...FEB 2013 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Opioid-induced hyperalgesia--worsening pain in opioid-dependent...Report Opioid-induced hyperalgesia—worsening pain in opioid-dependent patients☆ Abstract Patients with chronic opioid use are commonly treated in the

  19. Neurotrophin Genes and Antidepressant-Worsening Suicidal Ideation: A Prospective Case-Control Study

    PubMed Central

    Ramoz, Nicolas; Shekhtman, Tatyana; Courtet, Philippe; Gorwood, Philip; Kelsoe, John R.

    2016-01-01

    Background: Antidepressant-worsening suicidal ideation is a rare but serious phenomenon. This study aimed to test for association between antidepressant-worsening suicidal ideation and polymorphisms of BDNF/NTRK2 neurotrophin pathway genes, known to be involved in depression and suicide. Methods: This was a case-control study comparing patients with antidepressant-worsening suicidal ideation to patients without. Patients were collected from the GENESE cohort (3771 depressed tianeptine-treated outpatients). Antidepressant-worsening suicidal ideation was defined by an increase of at least 2 points on the Montgomery-Åsberg Depression Rating Scale-item10 during treatment. Controls were matched for age, sex, and baseline Montgomery-Åsberg Depression Rating Scale-item10 score. Thirteen single nucleotide polymorphisms covering 5 BDNF/NTRK2 pathway genes were genotyped. Results: A total 78 cases and 312 controls were included. Two NTRK2 single nucleotide polymorphisms were associated to antidepressant-worsening suicidal ideation: rs1439050 (P=.01) and rs1867283 (P=.04). Association with rs1439050 remained significant after adjustment for potentially confounding factors, including previous suicide attempts (P<.01). Conclusions: This naturalistic prospective study is consistent with previous studies on highlighting the potential role of the neurotrophin pathway, and especially of NTRK2, in antidepressant-worsening suicidal ideation. PMID:27378793

  20. Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice.

    PubMed

    Su, Zhiguang; Li, Yuhua; James, Jessica C; Matsumoto, Alan H; Helm, Gregory A; Lusis, Aldons J; Shi, Weibin

    2006-05-15

    Dyslipidemia and hyperglycemia are integral components of the metabolic perturbations in type 2 diabetes. Apolipoprotein E-deficient (apoE(-/-)) mice develop severe hyperlipidemia and significant hyperglycemia when fed a western diet containing 21% fat (w/w), 0.15% cholesterol and 19.5% casein. Using an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) apoE(-/-) mice, we performed quantitative trait locus (QTL) analysis to identify loci contributing to hyperglycemia and associated traits. Fasting plasma levels of glucose, insulin and serum amyloid-P (SAP) and body weight in 234 female F2 mice were measured after being fed the western diet for 12 weeks. QTL analysis revealed one significant QTL, named Bglu3 [95.8 cM, logarithm of odds ratio (OR)(LOD) 4.1], on chromosome 1 and a suggestive QTL on chromosome 9 (38 cM, LOD 2.3) that influenced plasma glucose levels. Bglu3 coincided with loci on distal chromosomal 1 that had a major influence on plasma SAP levels and body weight. Significant correlations between plasma glucose, SAP and body weight were observed in F2 mice. Thus, these results demonstrate genetic linkages of hyperglycemia and body weight with SAP, a marker of the acute-phase response, in hyperlipidemic apoE(-/-) mice and suggest a probability for the Sap gene to be a positional candidate of Bglu3.

  1. Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway.

    PubMed

    Vasconcelos-Dos-Santos, A; Loponte, H F B R; Mantuano, N R; Oliveira, I A; de Paula, I F; Teixeira, L K; de-Freitas-Junior, J C M; Gondim, K C; Heise, N; Mohana-Borges, R; Morgado-Díaz, J A; Dias, W B; Todeschini, A R

    2017-03-20

    Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes. Biopsies from patients with colon carcinoma show increased levels of GFAT and consequently aberrant glycans' expression suggesting an increase of HBP flow in human colon cancer. All together, our results open the possibility that HBP links hyperglycemia, aberrant glycosylation and tumor malignancy, and suggest this pathway as a potential therapeutic target for colorectal cancer.

  2. Pathway for the management of hyperglycemia in critical care units.

    PubMed

    Herzog, Eyal; Aziz, Emad; Croitor, Sherryl; Frankenberger, Olivier; Gurunathan, Rajan; Albu, Jeanine; Mezitis, Nicholas

    2006-06-01

    Inhospital morbidity and mortality are increased in hyperglycemia. Normalization of blood glucose levels using intensive insulin infusion protocols improves clinical outcomes. Insulin infusion algorithms have been shown to be safe and effective; however, a major obstacle in their implementation is their complexity. We have developed a novel pathway for the management of hyperglycemia, which introduces the "wheel" concept for insulin dosing complemented by "catchup" insulin dosing. The "wheel" serves as a treatment guide. It is made up of 4 concentric circles. The inner circle features blood glucose ranges and the 3 outer circles correspond to increasing rates of insulin infusion. Simple guidelines are provided to facilitate conversion from insulin infusion to a subcutaneous insulin-delivery regimen in preparation for transfer from the critical care unit setting. Our protocols eliminate reliance on the familiar "sliding scale" insulin administration schemes with the introduction of "catchup" insulin dosing to supplement the basic regimen. This pathway is comprehensive yet simple and provides guidelines for treatment of hyperglycemia for all patients screened to a critical care unit or to a stepdown unit.

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

    PubMed Central

    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

  4. DIETARY HYPERGLYCEMIA, GLYCEMIC INDEX AND METABOLIC RETINAL DISEASES

    PubMed Central

    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

  5. Prognostic Significance of Hyperglycemia in Patients with Brain Tumors: a Meta-Analysis.

    PubMed

    Liu, Hongwei; Liu, Zhixiong; Jiang, Bing; Ding, Xiping; Huo, Lei; Wan, Xin; Liu, Jinfang; Xia, Zhenyun

    2016-04-01

    Hyperglycemia has been associated with poor outcomes of patients with various diseases. There were several studies published to assess the association between hyperglycemia and prognosis of patients with brain tumors, but no consistent conclusion was available. We therefore performed a meta-analysis of available studies to evaluate the prognostic role of hyperglycemia in brain tumors. Several common databases were searched for eligible studies on the association between hyperglycemia and survival of patients with brain tumors. Two investigators used a set of predefined inclusion criteria to assess eligible studies independently. The pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the prognostic role of hyperglycemia. Finally, seven studies with a total of 2168 patients with brain tumors were included into the meta-analysis. Meta-analysis of total seven studies showed that hyperglycemia was significantly associated with shorter overall survival of brain tumors (HR = 2.04, 95% CI 1.51-2.76, P < 0.001). Meta-analysis of studies focusing on hyperglycemia showed that hyperglycemia was still significantly associated with shorter overall survival of brain tumors (HR = 1.82, 95% CI 1.29-2.59, P = 0.001). Meta-analysis of three studies on diabetes showed that diabetes was significantly associated with shorter overall survival of brain tumors (HR = 2.09, 95% CI 1.22-3.57, P = 0.007). Meta-regression analysis showed that there was no obvious difference in the roles of between hyperglycemia caused by glucocorticoids and hyperglycemia from diabetes (P = 0.25). Thus, hyperglycemia has an obvious prognostic significance in patients with brain tumors, and hyperglycemia is significantly associated with shorter overall survival of brain tumors.

  6. Minimal Clinically Important Worsening on the Progressive Supranuclear Palsy Rating Scale

    PubMed Central

    Hewer, Sarah; Varley, Sue; Boxer, Adam L.; Paul, Eldho; Williams, David R

    2016-01-01

    Structured Abstract Introduction Despite the widespread use of the PSP rating scale it is not known what change in this scale is meaningful for patients. Methods We analyzed data from a large clinical trial in PSP-Richardson’s syndrome (AL-108-231) to calculate minimal clinically important worsening. This was defined as the difference in mean change of PSP rating scale in subjects rated ‘a little worse’ and those rated ‘unchanged’ on the Clinicians’ Global Impression of Change Scale. A multivariate analysis using logistic regression assessed the relationship between clinical worsening, PSP rating scale, depression and activities of daily living. Results The minimal clinically important worsening on the PSP rating scale was 5.7 points, corresponding to the mean decline over six months in the trial. Changes in activities of daily living and PSP rating scale were significantly associated with clinical worsening. Conclusion Clinically meaningful change is measurable on the PSP rating scale over six months. PMID:27324431

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

    PubMed Central

    2016-01-01

    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. PMID:27313938

  8. Adenosine A₂A-receptor antagonist istradefylline enhances the motor response of L-DOPA without worsening dyskinesia in MPTP-treated common marmosets.

    PubMed

    Uchida, Shin-ichi; Tashiro, Tomomi; Kawai-Uchida, Mika; Mori, Akihisa; Jenner, Peter; Kanda, Tomoyuki

    2014-01-01

    The adenosine A₂A-receptor antagonist istradefylline decreases OFF time in patients with Parkinson's disease who are already treated with optimal doses of dopaminergic medication but can cause an increase in non-troublesome dyskinesia. Preclinical experiments have shown that A₂A antagonists are most effective in potentiating motor function when combined with sub-maximal doses of L-DOPA. However, the effects of combining istradefylline with sub-optimal L-DOPA treatment on established dyskinesia have not been studied. We now examine the effects of acute and repeated administration of istradefylline on dyskinesia in MPTP-treated common marmosets previously primed to exhibit involuntary movements by prior exposure to L-DOPA. In these animals, single dose acute oral administration of istradefylline (10 mg/kg) enhanced and prolonged the anti-parkinsonian effects of a sub-optimal dose of L-DOPA (2.5 mg/kg). The chronic co-administration of istradefylline (10 mg/kg) with L-DOPA (2.5 mg/kg) for 21 days did not worsen the severity of existing dyskinesia. Rather, the severity of dyskinesia tended to be reduced over the 21-day treatment period. These results suggest that istradefylline can be used to potentiate the effects of sub-optimal doses of L-DOPA in the treatment of Parkinson's disease without causing or worsening dyskinesia.

  9. Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis

    SciTech Connect

    Palmeira, Carlos M. Rolo, Anabela P.; Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B.

    2007-12-01

    Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes.

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

    PubMed

    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.

  11. Gynura procumbens Extract Alleviates Postprandial Hyperglycemia in Diabetic Mice

    PubMed Central

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

    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)-induced diabetic mice. G. procumbens extract showed prominent α-glucosidase and α-amylase inhibitory effects. The half-maximal inhibitory concentration (IC50) of G. procumbens extract against α-glucosidase and α-amylase was 0.092±0.018 and 0.084±0.027 mg/mL, respectively, suggesting that the α-amylase inhibition activity of the G. procumbens extract was more effective than that of the positive control, acarbose (IC50=0.164 mg/mL). The increase in postprandial blood glucose levels was more significantly alleviated in the G. procumbens extract group than in the control group of STZ-induced diabetic mice. Moreover, the area under the curve significantly decreased with G. procumbens extract administration in STZ-induced diabetic mice. These results suggest that G. procumbens extract may help alleviate postprandial hyperglycemia by inhibiting carbohydrate digesting enzymes. PMID:27752493

  12. Locating the source of hyperglycemia: Liver versus muscle

    PubMed Central

    YU, Haoyong; ZHOU, Dequan; JIA, Weiping; GUO, ZengKui

    2014-01-01

    Background Glucose homeostasis relies on insulin to suppress hepatic glucose production and to stimulate glucose uptake by peripheral tissues (primarily skeletal muscle) during and after a meal or glucose load. Glucose metabolism impairments in the liver and/or muscle attenuate these insulin actions, causing hyperglycemia. Thus, identifying the loci of the impairments can improve the understanding of hyperglycemia and enable organtargeted interventions. Methods Studies were performed to identify such loci using modified oral glucose tolerance test (OGTT) techniques in individuals with type 2 diabetes (T2D) and overweight/obese individuals. Results Individuals with severe T2D were found to have significantly impaired glucose metabolism in both the liver and muscle. In contrast, impairments in glucose metabolism in individuals with non-severe T2D were predominantly localized in the liver or muscle, but not both. Similarly, milder impairments in overweight or obese individuals were clearly localized in either the liver or muscle, but not both. All these impairments are quantifiable. Conclusion Impairments in glucose metabolism in the liver and muscle can be differentiated and quantified in a clinical setting. PMID:22074132

  13. Fetal cardiac effects of maternal hyperglycemia during pregnancy.

    PubMed

    Corrigan, Niamh; Brazil, Derek P; McAuliffe, Fionnuala

    2009-06-01

    Maternal diabetes mellitus is associated with increased teratogenesis, which can occur in pregestational type 1 and type 2 diabetes. Cardiac defects and with neural tube defects are the most common malformations observed in fetuses of pregestational diabetic mothers. The exact mechanism by which diabetes exerts its teratogenic effects and induces embryonic malformations is unclear. Whereas the sequelae of maternal pregestational diabetes, such as modulating insulin levels, altered fat levels, and increased reactive oxygen species, may play a role in fetal damage during diabetic pregnancy, hyperglycemia is thought to be the primary teratogen, causing particularly adverse effects on cardiovascular development. Fetal cardiac defects are associated with raised maternal glycosylated hemoglobin levels and are up to five times more likely in infants of mothers with pregestational diabetes compared with those without diabetes. The resulting anomalies are varied and include transposition of the great arteries, mitral and pulmonary atresia, double outlet of the right ventricle, tetralogy of Fallot, and fetal cardiomyopathy.A wide variety of rodent models have been used to study diabetic teratogenesis. Both genetic and chemically induced models of type 1 and 2 diabetes have been used to examine the effects of hyperglycemia on fetal development. Factors such as genetic background as well as confounding variables such as obesity appear to influence the severity of fetal abnormalities in mice. In this review, we will summarize recent data on fetal cardiac effects from human pregestational diabetic mothers, as well as the most relevant findings in rodent models of diabetic cardiac teratogenesis.

  14. Effect of cimetidine on pentamidine induced hyperglycemia in rats.

    PubMed

    Arino, Toru; Karakawa, Seiji; Ishiwata, Yasuyoshi; Nagata, Masashi; Yasuhara, Masato

    2012-10-15

    The antiprotozoal agent pentamidine, used for the treatment of Pneumocystis jirovecii pneumonia (PCP), is known to cause abnormalities in blood glucose homeostasis, such as hypoglycemia and hyperglycemia. Pentamidine has been reported to be a substrate of organic cation transporter 1 (OCT1). We investigated the combination effects of cimetidine, an OCT1 inhibitor, on the pharmacokinetics of pentamidine and on pentamidine-induced hyperglycemia. Pentamidine was infused intravenously to rats for 20 min at a dose of 7.5 or 15 mg/kg and serum samples were obtained periodically. The serum concentration of glucose did not change significantly after pentamidine infusion at 7.5mg/kg, while it increased with pentamidine at 15 mg/kg, and the maximal concentration of glucose was 167 ± 36 mg/dl, 30 min after the start of pentamidine infusion. Cimetidine (50mg/kg) enhanced the pentamidine-induced elevation of glucose concentration and the maximal concentration of glucose was 208 ± 33 mg/dl in the pentamidine 15 mg/kg treated group. Cimetidine combination significantly reduced total body clearance of pentamidine and increased pentamidine concentrations in the liver, kidneys, and lungs. A significant correlation was found between changes in serum glucose concentrations and serum concentrations of pentamidine 30 min after the start of pentamidine infusion. These results suggest that the hyperglycemic effect of pentamidine is dependent on the concentration of pentamidine and can be enhanced by cimetidine combination.

  15. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis

    PubMed Central

    Li, Shi-jun; Wang, Tao; Wang, Lin; Pang, Zhan-qi; Ma, Ben; Li, Ya-wen; Yang, Jian; Dong, He

    2016-01-01

    Abstract Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias. A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone. The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia. As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess. PMID:27057898

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

    PubMed Central

    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

  17. Excess α-synuclein worsens disease in mice lacking ubiquitin carboxy-terminal hydrolase L1.

    PubMed

    Shimshek, Derya R; Schweizer, Tatjana; Schmid, Peter; van der Putten, P Herman

    2012-01-01

    Mutations in α-synuclein (αSN) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have been linked to familial Parkinson's disease (PD). Physical and functional interactions between these two proteins have been described. Whether they act additively in vivo to influence disease has remained controversial. αSN is a presynaptic protein and the major constituent of Lewy inclusions, histopathological hallmarks of PD. UCH-L1 regulates ubiquitin stability in the nervous system and its loss results in neurodegeneration in peripheral and central neurons. Here, we used genetics to show that UCH-L1-deficiency together with excess αSN worsen disease. Double mutant mice show earlier-onset motor deficits, a shorter lifespan and forebrain astrogliosis but the additive disease-worsening effects of UCH-L1-deficiency and excess αSN are not accompanied by microgliosis, ubiquitin pathology or changes in pathological αSN protein levels and species.

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

    PubMed

    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. Predicting favorable and unfavorable consequences of perceptual learning: worsening and the peak shift.

    PubMed

    Wisniewski, Matthew G

    2017-04-01

    Discrimination learning can cause improved and worsened ability to perceive differences. This subsequently affects how stimuli are associated with meanings and behaviors. Here, human listeners were trained with frequency-modulated (FM) tonal sweeps (500-1000 Hz) in a paradigm where one FM rate (8.29 octaves per second) required a 'Target' response, while a rate either slower (5.76 octaves per second) or faster (11.94 octaves per second) required a 'Non-Target' response. Training led to a shift in 'Target' responding along the FM rate dimension away from the 'Target' in a direction opposite the trained 'Non-Target'. This peak shift was paralleled by an asymmetry in acuity along the FM rate dimension in an untrained ABX task (a.k.a. match-to-sample). Performance improved relative to pre-training on trials where the 'Target' was contrasted with stimuli nearer the trained 'Non-Target'. Performance worsened on trials containing stimuli displaced along the FM dimension further from the trained 'Non-Target'. A connectionist model of perceptual learning containing non-associative representational modification and associative-based task-specific reweighting was able to simulate behavior. Simulations generated novel testable predictions regarding peak shift and worsening as a result of discrimination learning. Data have theoretical and practical consequences for predicting trends in the generalization of learned behaviors and modifiable perceptual acuities.

  20. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    PubMed

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  1. Spontaneous and transient predinner hyperglycemia in some patients with diabetes

    PubMed Central

    Li, Wei; Du, Si-na; Shi, Min-jia; Sun, Zhan-zhan

    2016-01-01

    Abstract Blood glucose fluctuations have higher risk than absolute blood glucose level in diabetic chronic complications. At present, “dawn phenomenon” is well known by clinicians, but “dusk phenomenon” has not been recognized. This study explored the objective existence of “dusk phenomenon” (spontaneous and transient predinner hyperglycemia) and its clinical significance. The data of 54 patients with diabetes, who received routine insulin pump therapy between December 2010 and October 2012 in our hospital, were retrospectively analyzed. These patients included 4 patients with type 1 diabetes mellitus (DM) (T1DM) and 50 patients with type 2 DM (T2DM). According to the difference between predinner and postlunch blood glucose levels, the 50 patients with T2DM were divided into dusk phenomenon group (4 patients, all the differences ≥0 mmol/L during insulin pump therapy), nondusk phenomenon group (12 patients, all the differences <0 mmol/L during insulin pump therapy), and suspicious group (34 patients, the differences were uncertain during insulin pump therapy). In the 4 patients with T1DM of this study, the differences all were more than 0 mmol/L during insulin pump therapy. The changes in blood glucose levels were observed, and the correlations of blood glucose level with other factors were analyzed in T1DM and T2DM patients, respectively. In T1DM patients, blood glucose level was significantly higher in predinner than in prebreakfast and prelunch (all P < 0.01), and in postdinner 2 hour than in postlunch 2 hour (P = 0.021). The predinner blood level had no significant correlations with the blood glucose level at other time points and insulin dosages (all P > 0.05). In T2DM patients, the predinner blood glucose level was significantly higher in dusk phenomenon group than in suspicious group and nondusk phenomenon group (all P < 0.05). In dusk phenomenon group, the blood glucose level remained rising from predinner to prebed, and

  2. Hemiballism-hemichorea induced by ketotic hyperglycemia: case report with PET study and review of the literature

    PubMed Central

    2014-01-01

    Hemiballism-hemichorea (HB-HC) is commonly used to describe the basal ganglion dysfunction in non-ketotic hyperglycemic elderly patients. Here we report two elderly female patients with acute onset of involuntary movements induced by hyperglycemia with positive urine ketones. We described the computed tomography and magnetic resonance imaging findings in these two patients, which is similar to that of non-ketotic hyperglycemic HB-HC patients. FDG-PET was performed and the glucose metabolism in the corresponding lesion in these two patients was contradictory with each other. We tried to clarify the underlying mechanisms of HB-HC and explain the contradictory neuroradiological findings in FDG-PET as being performed at different clinical stages. PMID:25031834

  3. Persistent impaired glucose metabolism in a zebrafish hyperglycemia model.

    PubMed

    Capiotti, Katiucia Marques; Antonioli, Régis; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

    2014-05-01

    Diabetes mellitus (DM) affects over 10% of the world's population. Hyperglycemia is the main feature for the diagnosis of this disease. The zebrafish (Danio rerio) is an established model organism for the study of various metabolic diseases. In this paper, hyperglycemic zebrafish, when immersed in a 111 mM glucose solution for 14 days, developed increased glycation of proteins from the eyes, decreased mRNA levels of insulin receptors in the muscle, and a reversion of high blood glucose level after treatment with anti-diabetic drugs (glimepiride and metformin) even after 7 days of glucose withdrawal. Additionally, hyperglycemic zebrafish developed an impaired response to exogenous insulin, which was recovered after 7 days of glucose withdrawal. These data suggest that the exposure of adult zebrafish to high glucose concentration is able to induce persistent metabolic changes probably underlined by a hyperinsulinemic state and impaired peripheral glucose metabolism.

  4. CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion.

    PubMed

    Nakamura, Yuji; Kanai, Takanori; Saeki, Keita; Takabe, Miho; Irie, Junichiro; Miyoshi, Jun; Mikami, Yohei; Teratani, Toshiaki; Suzuki, Takahiro; Miyata, Naoteru; Hisamatsu, Tadakazu; Nakamoto, Nobuhiro; Yamagishi, Yoshiyuki; Higuchi, Hajime; Ebinuma, Hirotoshi; Hozawa, Shigenari; Saito, Hidetsugu; Itoh, Hiroshi; Hibi, Toshifumi

    2013-04-15

    Glucagon-like peptide-1 (GLP-1) promotes insulin release; however, the relationship between the GLP-1 signal and chronic pancreatitis is not well understood. Here we focus on chemokine (C-C motif) ligand 2 (CCL2) and its receptor (CCR2) axis, which regulates various immune cells, including macrophages, to clarify the mechanism of GLP-1-mediated insulin secretion in chronic pancreatitis in mice. One and multiple series of repetitive cerulein administrations were used to induce acute and chronic cerulein pancreatitis, respectively. Acute cerulein-administered CCR2-knockout (KO) mice showed suppressed infiltration of CD11b(+)Gr-1(low) macrophages and pancreatic inflammation and significantly upregulated insulin secretion compared with paired wild-type (WT) mice. However, chronic cerulein-administered CCR2-KO mice showed significantly increased infiltration of CD11b(+)/Gr-1(-) and CD11b(+)/Gr-1(high) cells, but not CD11b(+)/Gr-1(low) cells, in pancreas with severe inflammation and significantly decreased insulin secretion compared with their WT counterparts. Furthermore, although serum GLP-1 levels in chronic cerulein-administered WT and CCR2-KO mice were comparably upregulated after cerulein administrations, GLP-1 receptor levels in pancreases of chronic cerulein-administered CCR2-KO mice were significantly lower than in paired WT mice. Nevertheless, a significantly higher hyperglycemia level in chronic cerulein-administered CCR2-KO mice was markedly restored by treatment with a GLP-1 analog to a level comparable to the paired WT mice. Collectively, the CCR2/CCL2 axis-mediated CD11b(+)-cell migration to the pancreas is critically involved in chronic pancreatitis-mediated hyperglycemia through the modulation of GLP-1 receptor expression and insulin secretion.

  5. Intracardiac impedance after cardiac resynchronization therapy is a novel predictor for worsening of heart failure.

    PubMed

    Suzuki, Hitoshi; Nodera, Minoru; Kamioka, Masashi; Kaneshiro, Takashi; Kamiyama, Yoshiyuki; Takeishi, Yasuchika

    2017-02-08

    Intrathoracic impedance measured by cardiac resynchronization therapy (CRT) varies because several factors other than pulmonary congestion may affect this parameter. Therefore, we hypothesized that changes in intracardiac impedance between the right and left ventricular leads would be more accurate to identify worsening heart failure in patients with CRT. The study enrolled 21 patients with CRT defibrillator (15 males, 70 ± 12 years). During the follow-up period (12 ± 7 months), the subjects experienced 37 fluid index threshold (60 ohm-days) crossing events. These events were divided into two groups whether hospitalization due to worsening heart failure was required (group-H, n = 14) or not (group-NH, n = 23). Based on the intracardiac impedance at the beginning of increasing fluid index (BI) and the crossing of 60 ohm-days (CI), the rate of impedance change (BI-CI/BI) was estimated. Then, the time elapsed from BI to CI (T) was evaluated. We calculated the rate of intracardiac impedance change per day (BI-CI/BI × T) in each group. The rate of intrathoracic impedance change per day was also determined using the same method. The median rate of intracardiac impedance change per day was 0.27 (IQR 0.22-0.54) %/day in group-H, and 0 (IQR 0-0.08) %/day in group-NH with a significant difference (P < 0.0001), whereas the rate of intrathoracic impedance change per day was similar between the two groups. By receiver operating characteristic curve for identification of hospitalization due to worsening heart failure, the best cutoff value of the rate of intracardiac impedance change per day was 0.20%/day (sensitivity 92%, specificity 88%, and AUC 0.98). In contrast, the best cutoff value of the rate of intrathoracic impedance change per day was 0.19%/day (sensitivity 86%, specificity 43%, and AUC 0.68). These results suggest that increased rate of change of decreasing intracardiac impedance measured by CRT is a novel useful predictor for

  6. New-Onset Diabetes After Acute and Critical Illness: A Systematic Review.

    PubMed

    Jivanji, Chirag J; Asrani, Varsha M; Windsor, John A; Petrov, Maxim S

    2017-03-13

    Hyperglycemia is commonly observed during acute and critical illness. Recent studies have investigated the risk of developing diabetes after acute and critical illness, but the relationship between degree of in-hospital hyperglycemia and new-onset diabetes has not been investigated. This study examines the evidence for the relationship between in-hospital hyperglycemia and prevalence of new-onset diabetes after acute and critical illness. A literature search was performed of the MEDLINE, EMBASE, and Scopus databases for relevant studies published from January 1, 2000, through August 4, 2016. Patients with no history of diabetes before hospital discharge were included in the systematic review. In-hospital glucose concentration was classified as normoglycemia, mild hyperglycemia, or severe hyperglycemia for the meta-analysis. Twenty-three studies were included in the systematic review, and 18 of these (111,078 patients) met the eligibility criteria for the meta-analysis. The prevalence of new-onset diabetes was significantly related to in-hospital glucose concentration and was 4% (95% CI, 2%-7%), 12% (95% CI, 9%-15%), and 28% (95% CI, 18%-39%) for patients with normoglycemia, mild hyperglycemia, and severe hyperglycemia, respectively. The prevalence of new-onset diabetes was not influenced by disease setting, follow-up duration, or study design. In summary, this study found stepwise growth in the prevalence of new-onset diabetes with increasing in-hospital glucose concentration. Patients with severe hyperglycemia are at the highest risk, with 28% developing diabetes after hospital discharge.

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

    PubMed

    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.

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

    PubMed Central

    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

  9. [Hyperglycemia and cardiovascular risk: lessons from randomized trials].

    PubMed

    Grimaldi, André

    2010-04-20

    Diabetes is a major cardiovascular risk factor However, hyperglycemia is much more closely associated with microangiopathy than with macrovascular complications. Epidemiologic studies have shown a 15% increase of myocardial infarction for 1% increase in HbA1c level. It is accepted but not absolutely demonstrated, that reduction of HbA1c results in an equal reduction of cardiovascular events. An initial good glycemic control has long-term benefical effects on the risk of cardiovascular disease. On the contrary, benefit of an intensive glucose control is not demonstrated in diabetic patients with previous myocardial infarction. Two recent studies (ACCORD and VADT) showed an increase of cardiovascular mortality by severe hypoglycemia. In diabetic patients with previous myocardial infarction, glycemic goal must be modulated by the hypoglycaemic risk. A goal of 7.5% HbA1c seems reasonable for the diabetic patients treated by sulfonylureas or insulin, at risk of hypoglycaemia. HbA1c target < 7% remains the general goal and HbA1c target < 6.5% is appropriated to the patients treated by insulin sensitizing medications without risk of hypoglycaemia.

  10. Brain Hyperglycemia Induced by Heroin: Association with Metabolic Neural Activation.

    PubMed

    Solis, Ernesto; Bola, R Aaron; Fasulo, Bradley J; Kiyatkin, Eugene A

    2017-02-15

    Glucose enters the brain extracellular space from arterial blood, and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (∼150-200 μM or ∼15-25% over resting baseline). When the heroin dose was doubled and tripled, the increase became progressively larger in magnitude and longer in duration. Heroin-induced glucose increases also occurred in other brain structures (medial thalamus, lateral striatum, hippocampus), suggesting that brain hyperglycemia is a whole-brain phenomenon but changes were notably distinct in each structure. While local vasodilation appears to be the possible mechanism underlying the rapid rise in extracellular glucose levels, the driving factor for this vasodilation (central vs peripheral) remains to be clarified. The heroin-induced NAc glucose increases positively correlated with increases in intracerebral heat production determined in separate experiments using multisite temperature recordings (NAc, temporal muscle and skin). However, glucose levels rise very rapidly, preceding much slower increases in brain heat production, a measure of metabolic activation associated with glucose consumption.

  11. Hyperglycemia-Induced Vasculopathy in the Murine Vitelline Vasculature

    PubMed Central

    Pinter, Emese; Mahooti, Sepi; Wang, Yi; Imhof, Beat A.; Madri, Joseph A.

    1999-01-01

    Maternal diabetes mellitus is associated with an increased incidence of congenital abnormalities as well as embryonic and perinatal lethality. In particular, a wide range of cardiovascular abnormalities have been noted in children of diabetic mothers and in the offspring of diabetic animals. The vascular system is the first organ system to develop in the embryo and is critical for normal organogenesis. The organization of mesodermal cells into endothelial and hematopoietic cells and into a complex vascular system is, in part, mediated by a series of specific cell-cell, cell-extracellular matrix, and cell-factor interactions. PECAM-1 expression has been observed during the earliest stages of vasculogenesis, and changes in PECAM-1 tyrosine phosphorylation have been associated with endothelial cell migration, vasculogenesis, and angiogenesis both in vitro and in vivo. In this report we demonstrate that exposure to hyperglycemia during gastrulation causes yolk sac and embryonic vasculopathy in cultured murine conceptuses and in the conceptuses of streptozotocin-induced diabetic pregnant mice. In addition, we correlate the presence of yolk sac and embryonic vasculopathy with the failure of PECAM-1 tyrosine dephosphorylation during the formation of blood islands/vessels from clusters of extra-embryonic and embryonic angioblasts in the murine conceptus using both in vitro and in vivo models. The importance of these findings in the development of vasculopathy in the offspring of diabetic mothers and the potential effects and benefits of glucose regulation during the periods of vasculogenesis/angiogenesis in embryonic development are discussed. PMID:10329590

  12. [Effects of maternal hyperglycemia on fetal growing mechanism].

    PubMed

    Kobayashi, A; Ueda, Y; Morikawa, H; Mochizuki, M

    1991-03-01

    The aim of this study was to clarify the effects of maternal hyperglycemia on fetal growth in rats. In streptozotocin (STZ)-induced diabetic rats, maternal serum glucose levels during pregnancy were controlled by daily injection of NPH insulin or saline from day 3 to 21 of pregnancy. The body weight, hepatic glycogen content and serum concentrations of insulin and Insulin-like Growth Factor-I (IGF-I) in fetuses from these rats were measured on Day 21 of pregnancy. Fetal body weight positively correlated with maternal mean blood glucose (MBG) during pregnancy in the groups of diabetic mothers whose MBG was less than 220 mg/dl, whereas a negative correlation was observed in the groups whose MBG was more than 220 mg/dl. In addition, a similar correlation between hepatic glycogen content, serum concentrations of insulin or IGF-I and maternal MBG was observed. On the other hand, in the culture of fetal rat hepatocytes, glycogen content indicated a dose-related increase according to the increase in glucose concentration in the medium. These results suggest that the growth retardation observed in rats whose maternal mean glucose level is higher than 220 mg/dl is not caused by abnormalities in the metabolic function of the fetal metabolic organ (liver), but it is caused by a decrease in the production and/or secretion of growth-promoting factors (for example insulin and IGF-I) in the fetuses.

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

    PubMed Central

    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 (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. 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

  14. Non Diabetic and Stress Induced Hyperglycemia [SIH] in Orthopaedic Practice What do we know so Far?

    PubMed Central

    Kaur, Randeep; Sud, Ambuj; Ghorpade, Nilesh; Gupta, Manu

    2014-01-01

    Hyperglycemia is also seen amongst non-diabetics and can cause significant morbidity and mortality. SIH has been reported in literature and studied in relation to trauma and critically ill patients. However, literature specific to orthopaedics on this topic is very small. Further, management of hyperglycemia in such patients is still a matter of debate and no universal consensus exists regarding its management. Future studies are needed on this topic to provide appropriate management guidelines and optimal patient outcomes. PMID:25478381

  15. The mechanism underlying the central glucagon-induced hyperglycemia and anorexia in chicks.

    PubMed

    Honda, Kazuhisa; Kamisoyama, Hiroshi; Uemura, Taku; Yanagi, Takashi; Saito, Noboru; Kurose, Yohei; Sugahara, Kunio; Katoh, Kazuo; Hasegawa, Shin

    2012-11-01

    We investigated the mechanism underlying central glucagon-induced hyperglycemia and anorexia in chicks. Male 8-day-old chicks (Gallus gallus) were used in all experiments. Intracerebroventricular administration of glucagon in chicks induced hyperglycemia and anorexia from 30 min after administration. However, the plasma insulin level did not increase until 90 min after glucagon administration, suggesting that glucose-stimulated insulin secretion from pancreatic beta cells may be suppressed by central glucagon. The plasma corticosterone concentration significantly increased from 30 min to 120 min after administration, suggesting that central glucagon activates the hypothalamic pituitary adrenal (HPA) axis in chicks. However, central administration of corticotropin-releasing factor (CRF), which activates the HPA axis in chicken hypothalamus, significantly reduced not only food intake but also plasma glucose concentration, suggesting that CRF and the activation of the HPA axis are related to the glucagon-induced anorexia but not hyperglycemia in chicks. Phentolamine, an α-adrenergic receptor antagonist, significantly attenuated the glucagon-induced hyperglycemia, suggesting that glucagon induced hyperglycemia at least partly via α-adrenergic neural pathway. Co-administration of phentolamine and α-helical CRF, a CRF receptor antagonist, significantly attenuated glucagon-induced hyperglycemia and anorexia. It is therefore likely that central administration of glucagon suppresses food intake at least partly via CRF-induced anorexigenic pathway in chicks.

  16. Nuclear Factor Erythroid 2-Related Factor 2 Deletion Impairs Glucose Tolerance and Exacerbates Hyperglycemia in Type 1 Diabetic MiceS⃞

    PubMed Central

    Aleksunes, Lauren M.; Reisman, Scott A.; Yeager, Ronnie L.; Goedken, Michael J.

    2010-01-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic β-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum β-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels. PMID:20086057

  17. Bacterial Respiratory Tract Infections are Promoted by Systemic Hyperglycemia after Severe Burn Injury in Pediatric Patients

    PubMed Central

    Kraft, Robert; Herndon, David N; Mlcak, Ronald P; Finnerty, Celeste C; Cox, Robert A; Williams, Felicia N; Jeschke, Marc G

    2014-01-01

    Background Burn injuries are associated with hyperglycemia leading to increased incidence of infections with pneumonia being one of the most prominent and adverse complication. Recently, various studies in critically ill patients indicated that increased pulmonary glucose levels with airway/blood glucose threshold over 150 mg/dl lead to an overwhelming growth of bacteria in the broncho-pulmonary system, subsequently resulting in an increased risk of pulmonary infections. The aim of the present study was to determine whether a similar cutoff value exists for severely burned pediatric patients. Methods One-hundred six severely burned pediatric patients were enrolled in the study. Patients were divided in two groups: high (H) defined as daily average glucose levels >75% of LOS >150 mg/dl), and low (L) with daily average glucose levels >75% of the LOS <150 mg/dl). Incidences of pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS) were assessed. Incidence of infections, sepsis, and respiratory parameters were recorded. Blood was analyzed for glucose and insulin levels. Statistical analysis was performed using Student’s t-test and chi-square test. Significance was set at p<0.05. Results Patient groups were similar in demographics and injury characteristics. Pneumonia in patients on the mechanical ventilation (L: 21% H: 32%) and off mechanical ventilation (L: 5% H: 15%), as well as ARDS were significantly higher in the high group (L: 3% H: 19%), p<0.05, while atelectasis was not different. Patients in the high group required significantly longer ventilation compared to low patients (p<0.05). Furthermore, incidence of infection and sepsis were significantly higher in the high group, p<0.05. Conclusion Our results indicate that systemic glucose levels over 150 mg/dl are associated with a higher incidence of pneumonia confirming the previous studies in critically ill patients. PMID:24074819

  18. Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis

    PubMed Central

    Qi, Guo-Yan; Liu, Peng

    2013-01-01

    Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy. PMID:24348721

  19. Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats.

    PubMed

    Soejima, Yoshiteru; Hu, Qin; Krafft, Paul R; Fujii, Mutsumi; Tang, Jiping; Zhang, John H

    2013-09-01

    Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O₂, 2.5 atmosphere absolutes) 1 h daily for 5 days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl₂), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats.

  20. Administration of caffeic acid worsened bone mechanical properties in female rats.

    PubMed

    Zych, Maria; Folwarczna, Joanna; Pytlik, Maria; Sliwiński, Leszek; Gołden, Magdalena A; Burczyk, Jan; Trzeciak, Henryk I

    2010-03-01

    Natural phenolic acids, commonly present in plants that are normally consumed in the diet, have been reported to exert antiresorptive and/or bone formation increasing activity. The aim of the present study was to investigate the effects of ferulic, caffeic, P-coumaric, and chlorogenic acids on the skeletal system of normal, mature female rats. The phenolic acids (10 mg/kg p. o. daily for 4 weeks) were administered to 3-month-old female Wistar Cmd:(WI)WU rats. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, and mechanical properties were examined. Phenolic acids had differential effects on the rat skeletal system. Although none of them affected bone macrometric parameters, mass and mineralization, all of them increased the width of femoral trabeculae. Administration of caffeic acid worsened bone mechanical properties (decreasing ultimate load sustained by the femur in three-point bending test). In conclusion, high intake of caffeic acid may unfavorably affect the skeletal system.

  1. Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification.

    PubMed

    Ferreira, Carlos R; Ziegler, Shira G; Gupta, Ashutosh; Groden, Catherine; Hsu, Kevin S; Gahl, William A

    2016-05-01

    Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification.

  2. Clinical inquiries: Do glucosamine and chondroitin worsen blood sugar control in diabetes?

    PubMed

    Marshall, Peter D; Poddar, Sourav; Tweed, Elizabeth M; Brandes, Lisa

    2006-12-01

    Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance (SOR: A, consistent, good-quality patient-oriented evidence). Some preliminary evidence suggests that glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose intolerance or diabetes (SOR: C, extrapolation from disease-oriented evidence). Long-term effects are unknown; however, no compelling theoretical or incidental data suggest that long-term results should be different (SOR: C, expert opinion). Further studies are required to clarify the effects of glucosamine on patients with poorly controlled diabetes or glucose intolerance.

  3. The right to health in the courts of Brazil: worsening health inequities?

    PubMed

    Ferraz, Octavio Luiz Motta

    2009-01-01

    This article analyzes the recent and growing phenomenon of right-to-health litigation in Brazil from the perspective of health equity. It argues that the prevailing model of litigation is likely worsening the country's already pronounced health inequities. The model is characterized by a prevalence of individualized claims demanding curative medical treatment (most often drugs) and by a high success rate for the litigant. Both elements are largely a consequence of the way Brazilian judges have interpreted the scope of the right to health recognized in Article 6 and Article 196 of the Brazilian constitution, that is, as an entitlement of individuals to the satiSfaction of all their health needs with the most advanced treatment available, irrespective of its costs. Given that resources are always scarce in relation to the health needs of the population as a whole, this interpretation can only be sustained at the expense of universality, that is, so long as only a part of the population is granted this unlimited right at any given time. The individuals and (less often) groups who manage to access the judiciary and realize this right are therefore privileged over the rest of the population. This is potentially detrimental to health equity because the criterion for privileging litigants over the rest of the population is not based on any conception of need or justice but purely on their ability to access the judiciary, something that only a minority of citizens possess. This paper examines studies that are beginning to confirm that a majority of right-to-health litigants come from social groups that are already considerably advantaged in terms of all socioeconomic indicators, including health conditions. It is a plausible assumption that the model of right-to-health litigation currently prevalent in Brazil is likely worsening health inequities.

  4. Development of hyperglycemia and diabetes in captive Polish bank voles.

    PubMed

    Bartelik, Aleksandra; Ciesla, Maciej; Kotlinowski, Jerzy; Bartelik, Stanislaw; Czaplicki, Dominik; Grochot-Przeczek, Anna; Kurowski, Krzysztof; Koteja, Paweł; Dulak, Jozef; Józkowicz, Alicja

    2013-03-01

    Diabetes has been detected in Danish and Swedish bank voles (Myodes glareolus). There are no data, however, concerning the prevalence of diabetes in populations from other geographic regions. We investigated the frequency and physiological effects of glucose metabolism disorders in captive bank voles from Poland. Single measurement of fasting blood glucose concentration performed in the 3-4month old captive-born bank Polish voles without any disease symptoms showed that 8% of individuals (22/284) displayed an impaired fasting glucose (IFG, blood glucose (BG) ≥100mg/dL) and 1% (4/284) showed hyperglycemia (BG ≥126mg/dL) which could suggest diabetes. Next, we analyzed blood glucose in samples taken once a month from an additional cohort of bank voles with (FHD), or without (H), a family history of diabetes. The prevalence of IFG at age six months was 26% (16/62) among bank voles from the H group. In the FHD group the prevalence increased to 49% (43/88), and additional 12% (11/88) became diabetic (DB, BG ≥126mg/dL at two time points). Postnatal stress (three maternal deprivations before weaning) did not affect the risk of developing IFG or DB in H voles, but significantly reduced the frequency of glucose metabolism disorders (IFG and DB combined) in FHD voles. IFG was associated with hyperinsulinemia, but not with other biochemical disturbances. Diabetic animals displayed a progressive malformation and vacuolization of β-cells in the pancreas, without visible leukocytic infiltrations. In summary, our results indicate that Polish captive bank voles can develop diabetes, which shows features of both type 1 and type 2 diabetes in humans. Risk of diabetes is higher in animal with FHD.

  5. Lactoferrin ameliorates corticosterone-related acute stress and hyperglycemia in rats

    PubMed Central

    MAEKAWA, Yuta; SUGIYAMA, Akihiko; TAKEUCHI, Takashi

    2016-01-01

    We aimed to assess the effects of lactoferrin (Lf) on glycemic regulatory responses under restraint stress (RS) in rats. Bovine Lf (bLf, 100 mg/kg) was intraperitoneally administered to rats before oral saline administration or oral glucose tolerance test (OGTT) following 60 min of RS load. In the case of oral saline administration, RS significantly raised plasma glucose, but bLf did not affect the level. Plasma glucose in OGTT showed an overall lower transition in the bLf group, and the levels at 30 and 180 min or the area under the curve (AUC) were significantly decreased. Although bLf suppressed an increase in plasma corticosterone during RS, the levels of plasma insulin, epinephrine and glucagon were not changed by the bLf treatment. PMID:27941304

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

    PubMed Central

    Zhao, Jing; Hakvoort, Theodorus B. M.; Willemsen, A. Marcel; Jongejan, Aldo; Sokolovic, Milka; Bradley, Edward J.; de Boer, Vincent C. J.; Baas, Frank; van Kampen, Antoine H. C.; Lamers, Wouter 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 in mice. Methods Mice were made diabetic with streptozotocin, treated with slow-release insulin implants and mated. Pregnancy aggravated hyperglycemia. Gene expression profiles were determined in ED8.5 and ED9.5 embryos from diabetic and control mice using Serial Analysis of Gene Expression and deep sequencing. Results Maternal hyperglycemia induced differential regulation of 1,024 and 2,148 unique functional genes on ED8.5 and ED9.5, respectively, mostly in downward direction. Pathway analysis showed that ED8.5 embryos suffered mainly from impaired cell proliferation, and ED9.5 embryos from impaired cytoskeletal remodeling and oxidative phosphorylation (all P ≤ E-5). A query of the Mouse Genome Database showed that 20–25% of the differentially expressed genes were caused by cardiovascular and/or neural malformations, if deficient. Despite high glucose levels in embryos with maternal hyperglycemia and a ~150-fold higher rate of ATP production from glycolysis than from oxidative phosphorylation on ED9.5, ATP production from both glycolysis and oxidative phosphorylation was reduced to ~70% of controls, implying a shortage of energy production in hyperglycemic embryos. Conclusion Maternal hyperglycemia suppressed cell proliferation during gastrulation and cytoskeletal remodeling during early organogenesis. 20–25% of the genes that were differentially regulated by hyperglycemia were associated with relevant congenital malformations. Unexpectedly, maternal hyperglycemia also endangered the energy supply of the embryo by suppressing its glycolytic capacity. PMID:27433804

  7. Impact of Hyperglycemia on Outcomes among Patients Receiving Neoadjuvant Chemotherapy for Bulky Early Stage Cervical Cancer

    PubMed Central

    Lu, Huai-wu; Zhang, Bing-zhong; Wang, Li-juan; Lin, Zhong-qiu

    2016-01-01

    Background The impact of hyperglycemia on survival of patients undergoing neoadjuvant chemotherapy (NACT) for bulky early stage cervical cancer (BESCC) has not been explored. Method Records of patients who received NACT and radical hysterectomy in our institution between January 2005 and June 2010 were reviewed. Results In total, 347 patients were included. The median follow-up time was 37 months (range: 4–65). Patients with hyperglycemia (fasting blood glucose ≥ 100 mg/dl) had shorter recurrence-free survival (RFS) (univariate hazard ratio [HR] = 1.95, 95% confidence interval [CI] [1.16, 3.28], P = 0.010) and cancer-specific survival (CSS) (univariate HR = 2.24, 95% CI [1.33, 3.78], P = 0.002) compared with those with euglycemia (fasting blood glucose <100 mg/dl). In multivariate analysis, positive surgical margins, parametrium invasion, node metastasis, hyperglycemia and complete response to NACT independently predicted recurrence and cancer-specific death. To further validate the prognostic value of hyperglycemia, we conducted a subgroup analysis based on patient baseline characteristics and prognostic effect of hyperglycemia remained significant in all subgroups. On multivariable logistic regression analysis, euglycemia before NACT, squamous cell tumor and pre-treatment squamous cell carcinoma antigen levels < 3.5 ng/ml were identified as independent predictors of complete response after NACT. Conclusions FBG ≥100 mg/dl is a negative prognostic predictor for cervical cancer patients receiving NACT for BESCC. Patients with hyperglycemia are less likely to achieve complete response after NACT. Our findings underscore the clinical utility of hyperglycemia screening of for cervical cancer patients. PMID:27851819

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

    PubMed Central

    Roy, Ujjawal; Das, Shyamal Kumar; Mukherjee, Adreesh; Biswas, Debsadhan; Pan, Koushik; Biswas, Atanu; Panwar, Ajay

    2016-01-01

    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. PMID:27679748

  9. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis: A Case Report.

    PubMed

    Li, Shi-Jun; Wang, Tao; Wang, Lin; Pang, Zhan-Qi; Ma, Ben; Li, Ya-Wen; Yang, Jian; Dong, He

    2016-04-01

    Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias.A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone.The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia.As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess.

  10. The glucose intolerance of acute pancreatitis: hormonal response to arginine.

    PubMed

    Solomon, S S; Duckworth, W C; Jallepalli, P; Bobal, M A; Iyer, R

    1980-01-01

    Patients with acute pancreatitis were studied by arginine infusion at 48--72 h. 7--10 days, and 18--21 days after onset of their illness. Plasma glucose, insulin, and glucagon values were determined. Acute pancreatitis was characterized by fasting hyperglycemia and hyperglucagonemia, associated with relative hyoinsulinemia. Arginine stimulation early in the disease (48--72 h) demonstrated hyperglycemia and hyperglucagonemia, which normalized by 18--21 days. Both phases of the normal biphasic insulin response to arginine were decreased during the initial arginine infusion. By 18--21 days, although the first phase was completely normal, the second phase of insulin secretion remained depressed. Acute pancreatitis is associated with damage to both the endocrine and exocrine pancreas. Glucose intolerance seen with this disease appears to be the result of hyperglucagonemia and relative hypoinsulinemia. Although the healing process at 3 wk is associated with return of plasma glucose and glucagon concentrations to normal, the impaired second phase insulin secretion persists.

  11. Hyperglycemia is a predictor of mortality and morbidity in low birth weight newborn.

    PubMed

    Banik, S K; Baki, M A; Sarker, S; Rahat, F; Akhter, S; Nahar, N

    2014-07-01

    Early onset of hyperglycemia is common among low birth weight neonates. Increased risk for death and major morbidities has been observed among hyperglycemic low birth weight infants. This prospective observational study was done to find out hyperglycemia as a predictor of increased morbidity and mortality in the low birth weight sick newborn and was conducted among the hospitalized newborn of Special Care Baby Unit (SCABU), BIRDEM hospital, Dhaka, Bangladesh from July 2009 to December 2009. A total of 198 LBW neonates were included in this study. One third (30.8%) LBW neonates were found hyperglycemic. The mean gestational age was 33.2±3.6 weeks and mean birth weight was 1535.8±780gm in the hyperglycemic neonates. In this study, highest prevalence of hyperglycemia was observed in birth weight <1000gm (38.46%) and in gestational age ≤28 weeks (46.15%). Apnoea, confirmed sepsis and suspected sepsis, confirmed necrotizing enterocollitis (NEC) and neonatal jaundice showed statistically significant association with hyperglycemia than that of non hyperglycemic group. Mortality of neonates in hyperglycemic group was higher (31.15%) than that of non hyperglycemic neonates (10.22%) and the difference in mortality between two groups were found statistically significant (p<0.002). From this study it can be concluded that hyperglycemia in early neonatal period is related to increased morbidity and mortality in low birth weight newborn.

  12. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1

    PubMed Central

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner. PMID:27383386

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

    PubMed Central

    Jiang, Zhengdong

    2016-01-01

    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. PMID:27433288

  14. Genetic activation of mTORC1 signaling worsens neurocognitive outcome after traumatic brain injury.

    PubMed

    Rozas, Natalia S; Redell, John B; Hill, Julia L; McKenna, James; Moore, Anthony N; Gambello, Michael J; Dash, Pramod K

    2015-01-15

    Although the mechanisms that contribute to the development of traumatic brain injury (TBI)-related deficits are not fully understood, it has been proposed that altered energy utilization may be a contributing factor. The tuberous sclerosis complex, a heterodimer composed of hamartin/Tsc-1 and tuberin/Tsc-2, is a critical regulatory node that integrates nutritional and growth signals to govern energy using processes by regulating the activity of mechanistic Target of Rapamycin complex 1 (mTORC1). mTORC1 activation results in enhanced protein synthesis, an energy consuming process. We show that mice that have a heterozygous deletion of Tsc2 exhibit elevated basal mTORC1 activity in the cortex and the hippocampus while still exhibiting normal motor and neurocognitive functions. In addition, a mild closed head injury (mCHI) that did not activate mTORC1 in wild-type mice resulted in a further increase in mTORC1 activity in Tsc2(+/KO) mice above the level of activity observed in uninjured Tsc2(+/KO) mice. This enhanced level of increased mTORC1 activity was associated with worsened cognitive function as assessed using the Morris water maze and context discrimination tasks. These results suggest that there is a threshold of increased mTORC1 activity after a TBI that is detrimental to neurobehavioral performance, and interventions to inhibit excessive mTORC1 activation may be beneficial to neurocognitive outcome.

  15. Excess Visceral Adipose Tissue Worsens the Vascular Endothelial Function in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Kurozumi, Akira; Okada, Yosuke; Arao, Tadashi; Tanaka, Yoshiya

    2016-01-01

    Objective Visceral fat obesity and metabolic syndrome correlate with atherosclerosis in part due to insulin resistance and various other factors. The aim of this study was to determine the relationship between vascular endothelial dysfunction and excess visceral adipose tissue (VAT) in Japanese patients with type 2 diabetes mellitus (T2DM). Methods In 71 T2DM patients, the reactive hyperemia index (RHI) was measured using an Endo-PAT 2000, and VAT and subcutaneous adipose tissue (SAT) were measured via CT. We also measured various metabolic markers, including high-molecular-weight adiponectin (HMW-AN). Results VAT correlated negatively with the natural logarithm of RHI (L_RHI), the primary endpoint (p=0.042, r=-0.242). L_RHI did not correlate with SAT, VAT/SAT, abdominal circumference, homeostasis model assessment for insulin resistance, urinary C-peptide reactivity, HMW-AN, or alanine amino transferase, the secondary endpoints. A linear multivariate analysis via the forced entry method using age, sex, VAT, and smoking history as independent variables and L_RHI as the dependent variable revealed a lack of any determinants of L_RHI. Conclusion Excess VAT worsens the vascular endothelial function, represented by RHI which was analyzed using Endo-PAT, in Japanese patients with T2DM. PMID:27803400

  16. Desiccating Stress-Induced MMP Production and Activity Worsens Wound Healing in Alkali-Burned Corneas

    PubMed Central

    Bian, Fang; Pelegrino, Flavia S. A.; Pflugfelder, Stephen C.; Volpe, Eugene A.; Li, De-Quan; de Paiva, Cintia S.

    2015-01-01

    Purpose To evaluate the effects of dry eye on ocular surface protease activity and sight threatening corneal complications following ocular surface chemical injury. Methods C57BL/6 mice were subjected to unilateral alkali burn (AB) with or without concomitant dry eye for 2 or 5 days. Mice were observed daily for appearance of corneal perforation. Whole corneas were harvested and lysed for RNA extraction. Quantitative real-time PCR was performed to measure expression of inflammation cytokines, matrix metalloproteinases (MMP). Matrix metalloproteinase–9 activity, gelatinase activity, and myeloperoxidase (MPO) activity were evaluated in corneal lysates. Presence of infiltrating neutrophils was evaluated by immunohistochemistry and flow cytometry. Results Eyes subjected to the combined model of AB and dry eye (CM) had 20% sterile corneal perforation rate as soon as 1 day after the initial injury, which increased to 35% by 5 days, delayed wound closure and increased corneal opacity. Increased levels of IL-1β, -6, and MMPs-1, -3, -8, -9, and -13, and chemokine (C-X-C motif) ligand 1 (CSCL1) transcripts were found after 2 days in CM compared with AB corneas. Increased MMP-1, -3, -9, and -13 immunoreactivity and gelatinolytic activity were seen in CM corneas compared with AB. Increased neutrophil infiltration and MPO activity was noted in the CM group compared with AB 2 days post injury. Conclusions Desiccating stress worsens outcome of ocular AB, creating a cytokine and protease storm with greater neutrophil infiltration, increasing the risk of corneal perforation. PMID:26225631

  17. Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy.

    PubMed

    Ahuja, Shradha; Makkar, Priyanka; Gupta, Sorab; Vigoda, Ivette

    2016-05-01

    Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer.

  18. Identifying and managing factors that interfere with or worsen blood pressure control.

    PubMed

    Basile, Jan N; Bloch, Michael J

    2010-03-01

    Hypertension is a major risk factor for ischemic heart disease, stroke, and heart failure. Even moderate blood pressure (BP) elevation can have a significant impact on outcomes. Maintaining BP within recommended levels significantly reduces the risk of cardiovascular morbidity and mortality. Yet, more than one-third of people receiving treatment for hypertension in the United States have uncontrolled BP. When faced with a patient whose BP is no longer controlled, clinicians need to develop a differential diagnosis of potential contributing factors. These factors may include BP measurement issues, poor adherence to antihypertensive medications, therapeutic inertia on the part of clinicians, lifestyle changes, secondary causes of hypertension, or ingestion of substances that interfere with BP control. Patients who demonstrate a deterioration in BP control should be questioned about adherence, recent changes to diet and lifestyle, signs and symptoms of secondary causes of hypertension, and use of any concomitant medications or other substances that may be known to increase BP or interfere with antihypertensive therapy. Common substances that can interfere with BP control include nonsteroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, glucocorticoids, antidepressants, decongestants, alcohol, or other stimulants like cocaine and methamphetamines. Because of the high prevalence of both osteoarthritis and hypertension among elderly people, NSAIDs are a common potential factor in this age group. In the face of worsening BP control, clinicians must actively investigate potential contributing factors and appropriately increase or adjust antihypertensive therapy.

  19. Genetic Activation of mTORC1 Signaling Worsens Neurocognitive Outcome after Traumatic Brain Injury

    PubMed Central

    Rozas, Natalia S.; Redell, John B.; Hill, Julia L.; McKenna, James; Moore, Anthony N.; Gambello, Michael J.

    2015-01-01

    Abstract Although the mechanisms that contribute to the development of traumatic brain injury (TBI)-related deficits are not fully understood, it has been proposed that altered energy utilization may be a contributing factor. The tuberous sclerosis complex, a heterodimer composed of hamartin/Tsc-1 and tuberin/Tsc-2, is a critical regulatory node that integrates nutritional and growth signals to govern energy using processes by regulating the activity of mechanistic Target of Rapamycin complex 1 (mTORC1). mTORC1 activation results in enhanced protein synthesis, an energy consuming process. We show that mice that have a heterozygous deletion of Tsc2 exhibit elevated basal mTORC1 activity in the cortex and the hippocampus while still exhibiting normal motor and neurocognitive functions. In addition, a mild closed head injury (mCHI) that did not activate mTORC1 in wild-type mice resulted in a further increase in mTORC1 activity in Tsc2+/KO mice above the level of activity observed in uninjured Tsc2+/KO mice. This enhanced level of increased mTORC1 activity was associated with worsened cognitive function as assessed using the Morris water maze and context discrimination tasks. These results suggest that there is a threshold of increased mTORC1 activity after a TBI that is detrimental to neurobehavioral performance, and interventions to inhibit excessive mTORC1 activation may be beneficial to neurocognitive outcome. PMID:25025304

  20. Paradoxical Worsening of Tubercular Serpiginous-Like Choroiditis after Initiation of Antitubercular Therapy

    PubMed Central

    Esen, Ebru; Sızmaz, Selçuk; Kunt, Zeynep; Demircan, Nihal

    2016-01-01

    In this study, a case with tubercular choroiditis showing severe macular edema and progression of choroidal lesions following initiation of antitubercular treatment is presented and the management of posterior uveitis associated with tuberculosis is evaluated. A 40-year-old female patient was admitted with decreased vision in her right eye and her fundoscopic examination revealed serpiginous choroiditis. It was learned from her medical history that she had taken antitubercular therapy 9 years ago. Mantoux tuberculin skin test showed an area of induration measuring 15 mm and a positive interferon-gamma release assay was documented. Additionally, sequelae lesions due to previous tubercular infection were remarkable on her chest imaging. By excluding other causes of uveitis, the patient was considered presumed ocular tuberculosis and a full standard course of 4-drug antitubercular therapy was initiated. On the seventh day of the treatment existing choroidal lesions showed progression, new foci of choroiditis appeared and severe macular edema occurred. After adding systemic corticosteroid to the treatment, the macular edema resolved and choroidal lesions began to inactivate. In patients with tubercular choroiditis, continued progression may develop after initiation of antitubercular therapy. This paradoxical worsening is thought to be a hyperacute immunologic reaction occurring against antigen load released after antitubercular therapy. This phenomenon may be suppressed by the addition of systemic corticosteroids to the treatment. PMID:28058156

  1. Esophageal mucosal damage may promote dysmotility and worsen esophageal acid exposure.

    PubMed

    Meneghetti, Adam T; Tedesco, Pietro; Damani, Tanuja; Patti, Marco G

    2005-12-01

    This study determines the relationship among esophageal dysmotility, esophageal acid exposure, and esophageal mucosal injury in patients with gastroesophageal reflux disease (GERD). A total of 827 patients with GERD (confirmed by ambulatory pH monitoring) were divided into three groups based on the degree of mucosal injury: group A, no esophagitis, 493 patients; group B, esophagitis grades I to III, 273 patients; and group C, Barrett's esophagus, 61 patients. As mucosal damage progressed from no esophagitis to Barrett's esophagus, there was a significant decrease in lower esophageal sphincter pressure and amplitude of peristalsis in the distal esophagus, with a subsequent increase in the number of reflux episodes in 24 hours, the number of reflux episodes longer than 5 minutes, and the reflux score. These data suggest that in patients with GERD, worsening of esophageal mucosal injury may determine progressive deterioration of esophageal motor function with impairment of acid clearance and increase of esophageal acid exposure. These findings suggest that Barrett's esophagus is an end-stage form of gastroesophageal reflux, and that if surgical therapy is performed early in the course of the disease, this cascade of events might be blocked.

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

    PubMed

    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.

  3. Protein C deficiency in insulin-dependent diabetes: a hyperglycemia-related phenomenon.

    PubMed

    Ceriello, A; Quatraro, A; Dello Russo, P; Marchi, E; Barbanti, M; Milani, M R; Giugliano, D

    1990-08-13

    In 30 insulin-dependent diabetic patients protein C (PC) antigen and PC activity were significantly lower than those of matched control healthy subjects. An inverse correlation between fasting plasma glucose and both PC concentration and activity was present in diabetics, while a direct correlation between PC concentration and PC activity was observed. Induced hyperglycemia in diabetic and normal subjects was able to decrease both PC antigen levels and PC activity, and heparin reversed in part this effect. In diabetic patients euglycemia obtained by insulin infusion restored to normal the depressed PC levels. Heparin did not alter both the basal PC concentration and activity in healthy controls. These data stress the major role of hyperglycemia in determining PC decrease in diabetics, and suggest that PC reduction is probably associated to hyperglycemia-enhanced thrombin formation.

  4. Nitrones Reverse Hyperglycemia-Induced Endothelial Dysfunction in Bovine Aortic Endothelial Cells

    PubMed Central

    Headley, Colwyn A.; DiSilvestro, David; Hemann, Craig; Bryant, Kelsey E.; Chen, Chun-Aun; Das, Amlan; Ziouzenkova, Ouliana; Durand, Grégory; Villamena, Frederick A.

    2016-01-01

    Hyperglycemia has been implicated in the development of endothelial dysfunction through heightened ROS production. Since nitrones reverse eNOS dysfunction, increase antioxidant enzyme activity, and suppress pro-apoptotic signaling pathway and mitochondrial dysfunction from ROS-induced toxicity, the objective of this study was to determine whether nitrone spin traps DMPO, PBN and PBN-LA were effective at duplicating these effects and improving glucose uptake in an in vitro model of hyperglycemia-induced dysfunction using bovine aortic endothelial cells (BAEC). BAEC were cultured in DMEM medium with low (5.5 mM glucose, LG) or high glucose (50 mM, HG) for 14 days to model in vivo hyperglycemia as experienced in humans with metabolic disease. Improvements in cell viability, intracellular oxidative stress, NO and tetrahydrobiopterin levels, mitochondrial membrane potential, glucose transport, and activity of antioxidant enzymes were measured from single treatment of BAEC cells with nitrones for 24 h after hyperglycemia. Chronic hyperglycemia significantly increased intracellular ROS by 50%, decreased cell viability by 25%, reduced NO bioavailability by 50%, and decreased BH4 levels by 15% thereby decreasing NO production. Intracellular glucose transport and SOD activity were also decreased by 50% and 25% respectively. Nitrone (PBN and DMPO, 50 μM) treatment of BAEC cells grown in hyperglycemic conditions resulted in in the normalization of outcome measures except for SOD and catalase activities. Our findings demonstrate that the nitrones reverse the deleterious effects of hyperglycemia in BAEC cells. We believe that in vivo testing of these nitrone compounds in models of cardiometabolic disease is warranted. PMID:26774452

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

    PubMed Central

    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

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

    PubMed

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

    2012-06-01

    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

  7. Hyperglycemia as an effect of cardiopulmonary bypass: intra-operative glucose management.

    PubMed

    Najmaii, Samira; Redford, Daniel; Larson, Douglas F

    2006-06-01

    Cardiopulmonary bypass (CPB) is associated with surgical stress, hypothermia, hyperoxia, enhancement of neuroendocrine outflow, and administration of glucogenic catecholamines that are associated with glucogonolysis and glucogenesis that result in hyperglycemia. The hyperglycemic state during CPB has been associated with adverse outcomes, such as infection, neurological impairment, cardiac dysfunction, prolonged hospitalization, and higher mortality rates. This report justifies vigilant monitoring of blood glucose levels and a rational protocol for the treatment of hyperglycemia of all open heart surgical patients that may improve post-CPB surgical outcomes.

  8. Hyperglycemia and Endothelial Dysfunction in Atherosclerosis: Lessons from Type 1 Diabetes

    PubMed Central

    Funk, Steven Daniel; Yurdagul, Arif; Orr, A. Wayne

    2012-01-01

    A clear relationship between diabetes and cardiovascular disease has been established for decades. Despite this, the mechanisms by which diabetes contributes to plaque formation remain in question. Some of this confusion derives from studies in type 2 diabetics where multiple components of metabolic syndrome show proatherosclerotic effects independent of underlying diabetes. However, the hyperglycemia that defines the diabetic condition independently affects atherogenesis in cell culture systems, animal models, and human patients. Endothelial cell biology plays a central role in atherosclerotic plaque formation regulating vessel permeability, inflammation, and thrombosis. The current paper highlights the mechanisms by which hyperglycemia affects endothelial cell biology to promote plaque formation. PMID:22489274

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

    PubMed Central

    Sharma, Jitendra; Chittawar, Sachin; Maniram, Ram Singh; Dubey, T. N.; Singh, Ambrish

    2017-01-01

    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. PMID:28217513

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

    NASA Astrophysics Data System (ADS)

    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. Acute Exacerbations of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Collard, Harold R.; Moore, Bethany B.; Flaherty, Kevin R.; Brown, Kevin K.; Kaner, Robert J.; King, Talmadge E.; Lasky, Joseph A.; Loyd, James E.; Noth, Imre; Olman, Mitchell A.; Raghu, Ganesh; Roman, Jesse; Ryu, Jay H.; Zisman, David A.; Hunninghake, Gary W.; Colby, Thomas V.; Egan, Jim J.; Hansell, David M.; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kondoh, Yasuhiro; Lynch, David A.; Müller-Quernheim, Joachim; Myers, Jeffrey L.; Nicholson, Andrew G.; Selman, Moisés; Toews, Galen B.; Wells, Athol U.; Martinez, Fernando J.

    2007-01-01

    The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed. PMID:17585107

  12. Bed Rest Worsens Impairments in Fat and Glucose Metabolism in Older, Overweight Adults

    PubMed Central

    2014-01-01

    Background. The effects of bed rest on the dysregulation of fatty acid and glucose metabolism have not been addressed in the older population. Objective. We examined the effect of 10 days of bed rest on fatty acid kinetics and hepatic and peripheral insulin resistance in aging. Methods. We utilized an octreotide, basal glucagon replacement, multistage insulin infusion, and the concomitant infusion of [6,6 2H2]glucose to derive insulin-mediated suppression of glucose production and insulin-stimulated glucose disposal in nine older, overweight individuals (body mass index 28.1 ± 1.7 kg m−2; 39.9% ± 1.9% fat). During the multistage insulin infusion, we also infused [1-13C]palmitate to examine free fatty acid rate of appearance (R a). Results. Body weight, % body fat, and energy metabolism did not change with bed rest. There was a significant decrease (−2291 ± 316cm3) in visceral fat, and no change in abdominal subcutaneous fat with bed rest. Insulin-mediated suppression of glucose production was modest prior to bed rest and was further reduced (>15% ± 2%) by bed rest. There was also a minor decrease in the insulin-mediated suppression of free fatty acid R a after bed rest and, as a consequence, a small variation in plasma free fatty acid from pre- to post-bed rest in the first stage of the multistage insulin infusion. There was also a significant bed rest–induced decline (>2.0 ± 0.6 mg kg FFM−1 min− 1) in insulin-stimulated glucose disposal. Conclusions. Preexisting impairments in insulin sensitivity are worsened by bed rest and seem linked to alterations in the regulation of free fatty acid in older, overweight individuals. PMID:23902932

  13. Moderate exercise training does not worsen left ventricle remodeling and function in untreated severe hypertensive rats.

    PubMed

    Boissiere, Julien; Eder, Véronique; Machet, Marie-Christine; Courteix, Daniel; Bonnet, Pierre

    2008-02-01

    Exercise training and hypertension induced cardiac hypertrophy but modulate differently left ventricle (LV) function. This study set out to evaluate cardiac adaptations induced by moderate exercise training in normotensive and untreated severe hypertensive rats. Four groups of animals were studied: normotensive (Ctl) and severe hypertensive (HT) Wistar rats were assigned to be sedentary (Sed) or perform a moderate exercise training (Ex) over a 10-wk period. Severe hypertension was induced in rat by a two-kidney, one-clip model. At the end of the training period, hemodynamic parameters and LV morphology and function were assessed using catheterism and conventional pulsed Doppler echocardiography. LV histology was performed to study fibrosis infiltrations. Severe hypertension increased systolic blood pressure to 202 +/- 9 mmHg and induced pathological hypertrophy (LV hypertrophy index was 0.34 +/- 0.02 vs. 0.44 +/- 0.02 in Ctl-Sed and HT-Sed groups, respectively) with LV relaxation alteration (early-to-atrial wave ratio = 2.02 +/- 0.11 vs. 1.63 +/- 0.12). Blood pressure was not altered by exercise training, but arterial stiffness was reduced in trained hypertensive rats (pulse pressure was 75 +/- 7 vs. 62 +/- 3 mmHg in HT-Sed and HT-Ex groups, respectively). Exercise training induced eccentric hypertrophy in both Ex groups by increasing LV cavity without alteration of LV systolic function. However, LV hypertrophy index was significantly decreased in normotensive rats only (0.34 +/- 0.02 vs. 0.30 +/- 0.02 in Ctl-Sed and Ctl-Ex groups, respectively). Moreover, exercise training improved LV passive filling in Ctl-Ex rats but not in Ht-Ex rats. In this study, exercise training did not reduce blood pressure and induced an additional physiological hypertrophy in untreated HT rats, which was slightly blunted when compared with Ctl rats. However, cardiac function was not worsened by exercise training.

  14. Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice

    PubMed Central

    Trevino, Michelle B.; Mazur-Hart, David; Machida, Yui; King, Timothy; Nadler, Joseph; Galkina, Elena V.; Poddar, Arjun; Dutta, Sucharita

    2015-01-01

    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. PMID:26296152

  15. Combined Vitamin C and Vitamin E Deficiency Worsens Early Atherosclerosis in ApoE-Deficient Mice

    PubMed Central

    Babaev, Vladimir R.; Li, Liying; Shah, Sanket; Fazio, Sergio; Linton, MacRae F.; May, James M.

    2010-01-01

    Objective Atherosclerosis is an inflammatory condition associated with oxidative stress, but controversy persists regarding whether antioxidants such as vitamins C and E are preventative. To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis, four combinations of vitamin supplementation (Low C/Low E, Low C/High E, High C/Low E, High C/High E) were studied in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice also unable to synthesize their own vitamin C (gulo−/−). The effect of a more severe depletion of vitamin C alone was evaluated in a second experiment using gulo−/− mice carrying the hemizygous deletion of SVCT2, the vitamin C transporter. Methods and Results After 8 weeks on a high-fat diet (16% lard, 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2-3-fold in males, although only plaque macrophage content was increased in females. A more severe deficiency of vitamin C in gulo−/− mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apoE−/− mice compared to littermates on a diet replete in vitamin C, again most clearly in males. Conclusion Combined vitamin E and C deficiencies are required to worsen early atherosclerosis in an apoE-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete. PMID:20558818

  16. Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

    PubMed

    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.

  17. Chronic widespread pain is associated with worsening frailty in European men

    PubMed Central

    Wade, Katie Fredrika; Lee, David M.; McBeth, John; Ravindrarajah, Rathi; Gielen, Evelien; Pye, Stephen R.; Vanderschueren, Dirk; Pendleton, Neil; Finn, Joseph D.; Bartfai, György; Casanueva, Felipe F.; Forti, Gianni; Giwercman, Aleksander; Huhtaniemi, Ilpo T.; Kula, Krzysztof; Punab, Margus; Wu, Frederick C. W.; O'Neill, Terence W.

    2016-01-01

    Background: we hypothesised that chronic widespread pain (CWP), by acting as a potential stressor, may predispose to the development of, or worsening, frailty. Setting: longitudinal analysis within the European Male Ageing Study (EMAS). Participants: a total of 2,736 community-dwelling men aged 40–79. Methods: subjects completed a pain questionnaire and shaded a manikin, with the presence of CWP defined using the American College of Rheumatology criteria. Physical activity, smoking, alcohol consumption and depression were measured. Repeat assessments took place a median of 4.3 years later. A frailty index (FI) was used, with frail defined as an FI >0.35. The association between CWP at baseline and the new occurrence of frailty was examined using logistic regression; the association between CWP at baseline and change in FI was examined using negative binomial regression. Results: at baseline, 218 (8.3%) men reported CWP. Of the 2,631 men who were defined as non-frail at baseline, 112 (4.3%) were frail at follow-up; their mean FI was 0.12 (SD 0.1) at baseline and 0.15 (SD 0.1) at follow-up, with a mean change of 0.03 (SD 0.08) P ≤ 0.001. Among men who were non-frail at baseline, those with CWP were significantly more likely to develop frailty. After adjustment for age and centre, compared with those with no pain, those with CWP at baseline had a 70% higher FI at follow-up; these associations remained significant after further adjustment for smoking, body mass index, depression, physical activity and FI at baseline. Conclusion: the presence of CWP is associated with an increased risk of frailty in older European men. PMID:26679698

  18. [Improvement of hospital hyperglycemia: creation of a new governance model?].

    PubMed

    Sofrà, Daniela; Berwart, Sylvie Masmont; Egli, Marc; Ruiz, Juan

    2012-06-06

    The report of significant decrease of the inpatient hospital mortality and morbidity with an efficient insulin therapy has demonstrated the need of a good glycaemic control for patients hospitalised in acute care. However, one is faced with numerous difficulties in the hospital management of patients with hyperglycaemia, errors often occur when prescribing insulin, and the management skills are insufficient. Our goal is to change the medical and nursing practices to evolve towards an efficient and safe management of the hospitalised patient. The model we lay out in this article is based upon observation of the therapeutic support of patients with a chronic condition, whilst using a systemic management approach.

  19. [Diabetes mellitus in acute pancreatitis].

    PubMed

    Díaz-Rubio, José Luis; Torre-Delgadillo, Aldo; Robles-Díaz, Guillermo

    2002-01-01

    Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.

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

    PubMed Central

    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

  1. Zinc supplementation alleviates hyperglycemia and associated metabolic abnormalities in streptozotocin-induced diabetic rats.

    PubMed

    Barman, Susmita; Srinivasan, Krishnapura

    2016-12-01

    The cause and effect relationship between diabetes and zinc is complex and unclear. This animal study has examined the potential of zinc supplementation in beneficial modulating hyperglycemia, insulin secretion, and metabolic abnormalities associated with diabetes. The study was conducted in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were subjected to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed significant control on hyperglycemia and hypoinsulinemia. There was a significant reduction in protein glycosylation, glucosuria, and urinary excretion of proteins and urea in diabetic animals maintained on a zinc-supplemented diet. Diabetic rats showed significantly higher plasma albumin and lower plasma urea and creatinine levels upon zinc supplementation. Significant alterations in insulin sensitivity indices HOMA-IR, HOMA-B, and QUICKI were also indicated by zinc supplementation. The pathological abnormalities in pancreatic islets of diabetic animals were significantly alleviated by dietary zinc intervention. This study provides the first evidence that zinc supplementation can partially ameliorate the severity of diabetic hyperglycemia and associated metabolic abnormalities, hypoinsulinemia, insulin resistance, and altered pancreatic morphology. Thus, zinc supplementation may offer a significant potential for clinical application in managing diabetic hyperglycemia and related metabolic complications.

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

    PubMed Central

    Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K.; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael

    2016-01-01

    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. PMID:27340827

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  4. Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking

    PubMed Central

    2013-01-01

    Background 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. Methods 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 (Treatment: 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. Results 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

  5. Does hysteroscopy worsen prognosis in women with type II endometrial carcinoma?

    PubMed Central

    Kong, Wei-Min; Yan, Zhen; Han, Chao; Zhao, Hui; Liu, Ting-Ting; Zhang, Tong-Qing; Song, Dan; Jiao, Si-Meng; Zhou, Chunxiao

    2017-01-01

    Background Prior studies evaluating the impact of hysteroscopy on outcomes in endometrial cancer have predominantly evaluated type I tumors. We sought to evaluate whether hysteroscopy worsens prognosis in type II endometrial cancer. Methods A retrospective cohort analysis of 140 patients from two institutions with type II endometrial cancer was performed. Women who underwent either diagnostic hysteroscopy (HSC) or dilation and curettage (D&C) for cancer diagnosis from June 2001 until June 2010 were included. The clinical and pathologic characteristics, including peritoneal cytology results were reviewed. The primary endpoint was disease-specific survival (DSS). The exposure of interest was hysteroscopy. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Results There was no difference in age, histology, stage, depth of myometrial invasion, adnexal involvement, or nodal metastasis between HSC and D&C patients. Positive cytology was found in 16/54 (30%) patients following HSC and in 10/86 (12%) following D&C (p = 0.008). Fourteen patients with stage I and II disease had positive peritoneal cytology, with 11/40 (27.5%) patients in the HSC group and 3/59 (5%) patients in the D&C group(p = 0.002). Median DSS was clinically different for the HSC and D&C groups, but statistical significance was not reached (53 versus 63.5 months, p = 0.34). For stage I and II patients, 18/99 (18%) were dead of EC, with a median DSS of 60 months for HSC and 71 months for D&C (p = 0.82). Overall 46 (33%) patients developed a recurrence, with 18/54 (33%) in the HSC group compared to 28/86 (32%) in the D&C group (p = 0.92). There was no difference in recurrence location between groups. Conclusions Diagnostic hysteroscopy significantly increased the rate of positive peritoneal cytology at the time of surgical staging in this cohort of patients with type II EC. However, we were unable to detect a difference in prognosis as measured by DSS. PMID

  6. Inhibition of ERK1/2 Worsens Intestinal Ischemia/Reperfusion Injury

    PubMed Central

    Ban, Kechen; Peng, Zhanglong; Kozar, Rosemary A.

    2013-01-01

    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 effector of mammalian

  7. Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function.

    PubMed

    Suzuki, Kunihiro; Olah, Gabor; Modis, Katalin; Coletta, Ciro; Kulp, Gabriella; Gerö, Domokos; Szoleczky, Petra; Chang, Tuanjie; Zhou, Zongmin; Wu, Lingyun; Wang, Rui; Papapetropoulos, Andreas; Szabo, Csaba

    2011-08-16

    The goal of the present studies was to investigate the role of changes in hydrogen sulfide (H(2)S) homeostasis in the pathogenesis of hyperglycemic endothelial dysfunction. Exposure of bEnd3 microvascular endothelial cells to elevated extracellular glucose (in vitro "hyperglycemia") induced the mitochondrial formation of reactive oxygen species (ROS), which resulted in an increased consumption of endogenous and exogenous H(2)S. Replacement of H(2)S or overexpression of the H(2)S-producing enzyme cystathionine-γ-lyase (CSE) attenuated the hyperglycemia-induced enhancement of ROS formation, attenuated nuclear DNA injury, reduced the activation of the nuclear enzyme poly(ADP-ribose) polymerase, and improved cellular viability. In vitro hyperglycemia resulted in a switch from oxidative phosphorylation to glycolysis, an effect that was partially corrected by H(2)S supplementation. Exposure of isolated vascular rings to high glucose in vitro induced an impairment of endothelium-dependent relaxations, which was prevented by CSE overexpression or H(2)S supplementation. siRNA silencing of CSE exacerbated ROS production in hyperglycemic endothelial cells. Vascular rings from CSE(-/-) mice exhibited an accelerated impairment of endothelium-dependent relaxations in response to in vitro hyperglycemia, compared with wild-type controls. Streptozotocin-induced diabetes in rats resulted in a decrease in the circulating level of H(2)S; replacement of H(2)S protected from the development of endothelial dysfunction ex vivo. In conclusion, endogenously produced H(2)S protects against the development of hyperglycemia-induced endothelial dysfunction. We hypothesize that, in hyperglycemic endothelial cells, mitochondrial ROS production and increased H(2)S catabolism form a positive feed-forward cycle. H(2)S replacement protects against these alterations, resulting in reduced ROS formation, improved endothelial metabolic state, and maintenance of normal endothelial function.

  8. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

    PubMed Central

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

  9. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats.

    PubMed

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6-7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.

  10. Reduced glucose clearance as the major determinant of postabsorptive hyperglycemia in diabetic rats.

    PubMed

    Wi, J K; Kim, J K; Youn, J H

    1998-02-01

    The relationships between postabsorptive glucose concentration and hepatic glucose output (HGO) and glucose clearance were studied in rats one day after treatment with various doses of streptozotocin (STZ; 0, 15, 30, 40, 50, or 75 mg/kg; n = 6 per dose; study 1). Glucose fluxes were estimated using a prolonged (6-h) infusion of [3-3H]glucose to ensure complete tracer equilibration at hyperglycemia. Postabsorptive glucose was significantly increased at the high doses of STZ (50 and 75 mg/kg; P < 0.01) and was strongly correlated with glucose clearance across all doses (r = -0.85, P < 0.001) but less strongly with HGO (r = 0.46, P < 0.01). In the group treated with 50 mg/kg STZ, postabsorptive glucose was increased twofold compared with the control (i.e., zero dose) group, with no change in HGO and a 45% decrease in glucose clearance, indicating that the hyperglycemia was due to a decrease in glucose clearance. To understand the cellular mechanisms of decreased glucose clearance in STZ diabetic rats, skeletal muscle glucose clearance and intracellular glucose and glucose 6-phosphate (G-6-P) concentrations were determined in normal and STZ (50 mg/kg) diabetic rats at their postabsorptive glucose levels as well as at matched hyperglycemia (12 mM; study 2). Glucose clearance was significantly decreased in soleus (P < 0.05) muscles of the diabetic rats, and this was associated with significantly decreased intracellular glucose and G-6-P levels at matched hyperglycemia (P < 0.05), suggestive of decreased glucose transport. In conclusion, postabsorptive hyperglycemia in STZ diabetic rats was largely due to decreased glucose clearance, although increased HGO may also have been a contributing factor at the highest STZ dose. The decrease in postabsorptive glucose clearance in STZ diabetic rats appeared to be associated with an impairment of glucose transport in soleus (type I) muscles.

  11. Cardiorenal biomarkers in acute heart failure

    PubMed Central

    Choudhary, Rajiv; Gopal, Dipika; Kipper, Ben A.; De La Parra Landa, Alejandro; Lee, Hermineh Aramin Elizabeth; Shah, Saloni; Maisel, Alan S.

    2012-01-01

    Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient's bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients. PMID:23097660

  12. Determining the Minimally Important Difference in the Clinical Disease Activity Index For Improvement and Worsening in Early Rheumatoid Arthritis

    PubMed Central

    Curtis, JR; Yang, S; Chen, L; Pope, JE; Keystone, EC; Haraoui, B; Boire, G; Thorne, JC; Tin, D; Hitchon, CA; Bingham, CO; Bykerk, VP

    2015-01-01

    Background Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimally clinically important differences (MCID) for some measures, such as the clinical disease activity index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. Methods Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cutpoints were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Specificity, positive predictive value and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, HAQ and DAS28 improvement. Discrimination was examined using area under receiver operator curves (ROC). Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. Results A total of 578 patients (mean (SD) age 54.1 (15.3) years; 75% women, median (IQR) disease duration 5.3 (3.3, 8.0) months) contributed 1169 visit pairs to the improvement analysis. The MCID cutpoints for improvement were 12 (patients starting in high disease activity, CDAI>22), 6 (moderate, CDAI 10–22), and 1 (low disease activity, CDAI <10). Performance characteristics were acceptable using these cutpoints for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. Conclusions These minimally important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice. PMID:25988705

  13. Maintaining end-expiratory transpulmonary pressure prevents worsening of ventilator-induced lung injury caused by chest wall constriction in surfactant-depleted rats

    PubMed Central

    Loring, Stephen H.; Pecchiari, Matteo; Valle, Patrizia Della; Monaco, Ario; Gentile, Guendalina; D'Angelo, Edgardo

    2014-01-01

    Objective To see whether in acute lung injury (ALI) 1) compression of the lungs caused by thoracoabdominal constriction degrades lung function and worsens ventilator-induced lung injury (VILI), and 2) maintaining end-expiratory transpulmonary pressure (Pl) by increasing positive end-expiratory pressure (PEEP) reduces the deleterious effects of chest wall constriction. Design Experimental study in rats. Setting Physiology laboratory. Interventions ALI was induced in 3 groups of 9 rats by saline lavage. Nine animals immediately sacrificed served as control group. Group L had lavage only, group LC had the chest wall constricted with an elastic binder, and group LCP had the same chest constriction but with PEEP raised to maintain end-expiratory Pl. After lavage, all groups were ventilated with the same pattern for 1½ hr. Measurements and Main Results Pl, measured with an esophageal balloon-catheter, lung volume changes, arterial blood gasses and pH were assessed during mechanical ventilation (MV). Lung wet-to-dry ratio (W/D), albumin, TNF-α, IL-1β, IL-6, IL-10, and MIP-2 in serum and bronchoalveolar lavage fluid (BALF), and serum E-selectin and von Willebrand Factor (vWF) were measured at the end of MV. Lavage caused hypoxemia and acidemia, increased lung resistance and elastance, and decreased end-expiratory lung volume. With prolonged MV, lung mechanics, hypoxemia, and W/D were significantly worse in group LC. Pro-inflammatory cytokines except E-selectin were elevated in serum and BALF in all groups, with significantly greater levels of TNF-α, IL-1β, and IL-6 in group LC, which also exhibited significantly worse bronchiolar injury and greater heterogeneity of airspace expansion at a fixed Pl than other groups. Conclusions Chest wall constriction in ALI reduces lung volume, worsens hypoxemia, and increases pulmonary edema, mechanical abnormalities, pro-inflammatory mediator release, and histological signs of VILI. Maintaining end-expiratory Pl at preconstriction

  14. Hyperglycemia-conditioned increase in alpha-2-macroglobulin in healthy normal subjects: a phenomenon correlated with deficient antithrombin III activity.

    PubMed

    Ceriello, A; Quatraro, A; Dello Russo, P; Marchi, E; Barbanti, M; Giugliano, D

    1989-01-01

    Induced hyperglycemia in normal subjects increases alpha 2-macroglobulin (alpha 2M) activity and alpha 2M concentration and reduces antithrombin III (ATIII) activity, while it does not affect ATIII plasma concentration. Hyperglycemia-determined variations in ATIII activity and alpha 2M molecules are correlated in an inverse and parallel fashion. A compensatory role for the increase in alpha 2M in the regulation of the coagulation system may be hypothesized. Moreover, these data provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may influence the levels of some risk factors for the development of complications in diabetes.

  15. Ludwig's Angina: A Nightmare Worsened by Adverse Drug Reaction to Antibiotics

    PubMed Central

    Hisham, Mohamed; Sivakumar, Mundilipalayam N.; Senthil Kumar, R. S.; Nandakumar, P.

    2017-01-01

    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.

  16. Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke

    PubMed Central

    Winek, Katarzyna; Engel, Odilo; Koduah, Priscilla; Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Dames, Claudia; Kershaw, Olivia; Gruber, Achim D.; Curato, Caterina; Oyama, Naoki; Meisel, Christian; Meisel, Andreas

    2016-01-01

    Background and Purpose— Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain–gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke. Methods— We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry. Results— We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups. Conclusions— Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome. PMID:27056982

  17. Radiographic basal ganglia abnormalities secondary to nonketotic hyperglycemia with unusual clinical features

    PubMed Central

    Choi, Ju Young; Park, Joon Min; Kim, Kyung Hwan; Park, Jun Seok; Shin, Dong Wun; Kim, Hoon; Jeon, Woo Chan; Kim, Hyun Jong

    2016-01-01

    A 77-year-old woman was admitted to a local clinic for altered consciousness and presented with a suspected basal ganglion hemorrhage detected on brain computed tomography. The patient was stuporous, but her vital signs were stable. Her initial blood glucose was 607 mg/dL, and a hyperdense lesion was found in the right basal ganglion on brain computed tomography. T1-weighted magnetic resonance imaging revealed high signal intensity in the right basal ganglion. Electroencephalography showed no seizure activity. The patient was treated with a fluid infusion, and serum glucose level was controlled with insulin. The patient gradually recovered consciousness and was alert within 24 hours as serum glucose level normalized. The basal ganglion lesion caused by hyperglycemia was not accompanied by involuntary limb movement. This is the first report of a patient presenting with decreased consciousness and typical neural radiographic changes associated with nonketotic hyperglycemia but without movement abnormalities. PMID:28168232

  18. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review

    PubMed Central

    Tamez-Pérez, Héctor Eloy; Quintanilla-Flores, Dania Lizet; Rodríguez-Gutiérrez, René; González-González, José Gerardo; Tamez-Peña, Alejandra Lorena

    2015-01-01

    Steroids are drugs that have been used extensively in a variety of conditions. Although widely prescribed for their anti-inflammatory and immunosuppressive properties, glucocorticoids have several side effects, being hyperglycemia one of the most common and representative. In the present review, we discuss the main epidemiologic characteristics associated with steroid use, with emphasis on the identification of high risk populations. Additionally we present the pathophysiology of corticosteroid induced hyperglycemia as well as the pharmacokinetics and pharmacodynamics associated with steroid use. We propose a treatment strategy based on previous reports and the understanding of the mechanism of action of both, the different types of glucocorticoids and the treatment options, in both the ambulatory and the hospital setting. Finally, we present some of the recent scientific advances as well as some options for future use of glucocorticoids. PMID:26240704

  19. Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective

    PubMed Central

    Shakya, Sajina; Wang, Yan; Mack, Judith A.; Maytin, Edward V.

    2015-01-01

    Ulcers and chronic wounds are a particularly common problem in diabetics and are associated with hyperglycemia. In this targeted review, we summarize evidence suggesting that defective wound healing in diabetics is causally linked, at least in part, to hyperglycemia-induced changes in the status of hyaluronan (HA) that resides in the pericellular coat (glycocalyx) of endothelial cells of small cutaneous blood vessels. Potential mechanisms through which exposure to high glucose levels causes a loss of the glycocalyx on the endothelium and accelerates the recruitment of leukocytes, creating a proinflammatory environment, are discussed in detail. Hyperglycemia also affects other cells in the immediate perivascular area, including pericytes and smooth muscle cells, through exposure to increased cytokine levels and through glucose elevations in the interstitial fluid. Possible roles of newly recognized, cross-linked forms of HA, and interactions of a major HA receptor (CD44) with cytokine/growth factor receptors during hyperglycemia, are also discussed. PMID:26448756

  20. Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

    PubMed

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo

    2011-06-01

    Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

  1. Effect of thiamine pyrophosphate on retinopathy induced by hyperglycemia in rats: A biochemical and pathological evaluation

    PubMed Central

    Cinici, Emine; Ahiskali, Ibrahim; Cetin, Nihal; Suleyman, Bahadir; Kukula, Osman; Altuner, Durdu; Coban, Abdulkadir; Balta, Hilal; Kuzucu, Mehmet; Suleyman, Halis

    2016-01-01

    Purpose: Information is lacking on the protective effects of thiamine pyrophosphate (TPP) against hyperglycemia-induced retinopathy in rats. This study investigated the biochemical and histopathological aspects of the effect of TPP on hyperglycemia-induced retinopathy induced by alloxan in rats. Materials and Methods: The rats were separated into a diabetic TPP-administered group (DTPG), a diabetes control group (DCG) and a healthy group (HG). While the DTPG was given TPP, the DCG and HG were administered distilled water as a solvent at the same concentrations. This procedure was repeated daily for 3 months. At the end of this period, all of the rats were euthanized under thiopental sodium anesthesia, and biochemical and histopathological analyses of the ocular retinal tissues were performed. The results of the DTPG were compared with those of the DCG and HG. Results: TPP prevented hyperglycemia by increasing the amount of malondialdehyde and decreasing endogen antioxidants, including total glutathione, glutathione reductase, glutathione S-transferase and superoxide dismutase. In addition, the amounts of the DNA oxidation product 8-hydroxyguanine were significantly lower in the retinas of the DTPG compared to the DCG. In the retinas of the DCG, there was a marked increase in vascular structures and congestion, in addition to edema. In contrast, little vascularization and edema were observed in the DTPG, and there was no congestion. The results suggest that TPP significantly reduced the degree of hyperglycemia-induced retinopathy. Conclusions: The results of this study indicate that TPP may be useful for prophylaxis against diabetic retinopathy. PMID:27488151

  2. Effects of hyperglycemia on bone metabolism and bone matrix in goldfish scales.

    PubMed

    Kitamura, Kei-Ichiro; Andoh, Tadashi; Okesaku, Wakana; Tazaki, Yuya; Ogai, Kazuhiro; Sugitani, Kayo; Kobayashi, Isao; Suzuki, Nobuo; Chen, Wenxi; Ikegame, Mika; Hattori, Atsuhiko

    2017-01-01

    Increased risk of fracture associated with type 2 diabetes has been a topic of recent concern. Fracture risk is related to a decrease in bone strength, which can be affected by bone metabolism and the quality of the bone. To investigate the cause of the increased fracture rate in patients with diabetes through analyses of bone metabolism and bone matrix protein properties, we used goldfish scales as a bone model for hyperglycemia. Using the scales of seven alloxan-treated and seven vehicle-treated control goldfish, we assessed bone metabolism by analyzing the activity of marker enzymes and mRNA expression of marker genes, and we measured the change in molecular weight of scale matrix proteins with SDS-PAGE. After only a 2-week exposure to hyperglycemia, the molecular weight of α- and β-fractions of bone matrix collagen proteins changed incrementally in the regenerating scales of hyperglycemic goldfish compared with those of euglycemic goldfish. In addition, the relative ratio of the γ-fraction significantly increased, and a δ-fraction appeared after adding glyceraldehyde-a candidate for the formation of advanced glycation end products in diabetes-to isolated type 1 collagen in vitro. The enzymatic activity and mRNA expression of osteoblast and osteoclast markers were not significantly different between hyperglycemic and euglycemic goldfish scales. These results indicate that hyperglycemia is likely to affect bone quality through glycation of matrix collagen from an early stage of hyperglycemia. Therefore, non-enzymatic glycation of collagen fibers in bone matrix may lead to the deterioration of bone quality from the onset of diabetes.

  3. Concurrent hyperglycemia does not influence the long-term prognosis of unresectable hepatocellular carcinomas

    PubMed Central

    Li, Xiao-Ping; Chen, Zhen; Meng, Zhi-Qiang; Huang, Wen-Xia; Liu, Lu-Ming

    2003-01-01

    AIM: The association has been established between the disorder of carbohydrate metabolism and liver cancer. However, little is known regarding the impact of concurrent hyperglycemia on prognosis of hepatocellular carcinoma (HCC). The present study aimed at solving this problem. METHODS: A total of 225 patients included in this study, were admitted from January 1998 to December 2001 for an unresectable HCC proven by histological and imaging examinations. Most of the patients received interventional treatment, radiation and biotherapy. Response was evaluated by computerized tomography (CT) scan conducted 4-6 weeks following completion of the treatment, and then every 3 months. Survival was calculated from the beginning of treatment using the Kaplan-Meier method. Pretreatment, treatment and follow-up variables with possible prognostic significance were analyzed. A stepwise multivariate analysis was performed using the Cox regression model, and a prognostic index was obtained. RESULTS: No differences were observed in survival parameters between the patients with and without hyperglycemia, median survival times of the patients were being 26 ± 3.46 months and 29.5 ± 2.04 months, respectively, and the 3-year survival rate was 8.36% and 9.62%, respectively. The univariate analysis indicated that there were several survival-associated variables including serum AFP level, clinical stage, Child-Pugh grade, method of treatment, size and number of tumor nodule (s). However, only the clinical stage, Child-Pugh grade and the treatment procedure were proved to be independent prognostic factors in the multivariate analysis. CONCLUSION: This study indicates that hyperglycemia does not influence the long-term prognosis of HCC, and concurrent hyperglycemia should not be considered as an unfavorable prognostic factor during the treatment of patients with HCC. PMID:12918136

  4. [The current aspects of the pharmacological correction of hyperglycemia in patients with non-insulin-dependent diabetes mellitus (type 2)].

    PubMed

    Gorbenko, N I

    1999-01-01

    Data on the mechanisms of developing of hyperglycemia in patients with diabetes mellitus (type 2) are analyzed and reviewed. The current concept of hypoglycemic therapy aimed both at amelioration of hyperglycemia symptoms and reduction of the risk of diabetic micro- and macroangiopathies is considered. The main directions of pharmacological action of hypoglycemic drugs (both in use and in the stage of design) and data of the efficiency and possible incidental action are presented.

  5. Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice.

    PubMed

    Yoshida, Mei; Hayashi, Kaori; Watadani, Risa; Okano, Yoshiyasu; Tanimura, Keiya; Kotoh, Jun; Sasaki, Daiki; Matsumoto, Kozo; Maeda, Akihiko

    2017-02-14

    The study examined whether royal jelly (RJ) can prevent obesity and ameliorate hyperglycemia in type 2 diabetes. This study utilized obese/diabetic KK-Ay mice. RJ (10 mg/kg) was administered by oral gavage. Body weight, plasma glucose and insulin levels were measured. mRNA and protein levels were determined using quantitative reverse transcription polymerase chain reaction and western blotting, respectively. Four weeks of RJ administration improved hyperglycemia and partially suppressed body weight gain, although the latter effect did not reach statistical significance. In addition, RJ administration did not improve insulin resistance. RJ administration suppressed the mRNA expression of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, in the liver. Simultaneously, RJ administration induced adiponectin (AdipoQ) expression in abdominal fat, adiponectin receptor-1 (AdipoR1) expression in the liver and phosphorylated AMP-activated protein kinase (pAMPK) expression, which suppressed G6Pase levels in the livers of KK-Ay mice. pAMPK levels were also increased in skeletal muscle, but glucose transporter-4 (Glut4) translocation was not increased in the RJ supplementation group. The improvement in hyperglycemia due to long-term RJ administration may be because of the suppression of G6Pase expression through the upregulation of AdipoQ and AdipoR1 mRNA and pAMPK protein expressions.

  6. Dolphins as animal models for type 2 diabetes: sustained, post-prandial hyperglycemia and hyperinsulinemia.

    PubMed

    Venn-Watson, Stephanie; Carlin, Kevin; Ridgway, Sam

    2011-01-01

    There is currently no known natural animal model that fully complements type 2 diabetes in humans. Criteria for a true natural animal model include the presence of a fasting hyperglycemia, evidence of insulin resistance, and pathologies matching that reported in humans. To investigate the bottlenose dolphin (Tursiops truncatus) as a comparative model for type 2 diabetes in humans, hourly plasma and urine chemistry changes, including glucose, were analyzed among five healthy, adult dolphins for 24 h following ingestion of 2.5-3.5 kg of mackerel or 2-3 L of 10% dextrose in ionosol. Fasting and 2 h post-prandial insulin levels were also determined among five adult dolphins to assess the presence of hyperinsulinemia. Finally, a case-control study compared insulin and glucagon levels among dolphins with and without iron overload, a condition associated with insulin resistance in humans. Both protein and dextrose meals caused significant increases in plasma glucose during the 0-5 h post-prandial period; dolphins fed dextrose demonstrated a sustained hyperglycemia lasting 5-10 h. Fasting plasma insulin levels among healthy dolphins mimicked those found in humans with some insulin resistance. Dolphins with hemochromatosis had higher post-prandial plasma insulin levels compared to controls. We conclude that bottlenose dolphins can demonstrate metabolic responses consistent with type 2 diabetes, specifically sustained hyperglycemia and hyperinsulinemia. Understanding more about how and why dolphins have a diabetes-like metabolism may provide new research avenues for diabetes in humans.

  7. Obesity and Hyperglycemia in Korean Men with Klinefelter Syndrome: The Korean Endocrine Society Registry

    PubMed Central

    Han, Seung Jin; Kim, Kyung-Soo; Kim, Wonjin; Kim, Jung Hee; Lee, Yong-ho; Nam, Ji Sun; Seo, Ji A; Kim, Bu Kyung; Lee, Jihyun; Chung, Jin Ook; Kim, Min-Hee; Sohn, Tae-Seo; Choi, Han Seok; Hong, Seong Bin

    2016-01-01

    Background The 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. Methods Data 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. Results Data 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. Conclusion Obesity is common in Korean men with KS. Hypogonadism in patients with KS was associated with obesity and hyperglycemia. PMID:28029029

  8. Serum potassium concentration in hyperglycemia of diabetes mellitus with long-term dialysis.

    PubMed

    Tzamaloukas, A H; Avasthi, P S

    1987-05-01

    Severe hyperkalemia (serum potassium level >6 mmol per liter [mEq per liter]), often with electrocardiographic disturbances, was noted at presentation in 30% of 73 hyperglycemic episodes (serum glucose concentration >25 mmol per liter [455 mg per dl]) observed in 15 in-hospital patients with insulin-dependent diabetes mellitus who were receiving long-term hemodialysis or peritoneal dialysis. Serum glucose concentration and total carbon dioxide content correlated significantly with the presenting serum potassium concentration. Treatment with parenteral insulin alone resulted in a decrease of the serum glucose value from 41 +/- 14 (standard deviation) to 11 +/- 5 mmol per liter (P <.001) and of serum potassium level from 5.2 +/- 1.2 to 4.0 +/- 0.6 mmol per liter (P <.001). The changes in serum glucose concentration and in carbon dioxide content and the serum potassium concentration at hyperglycemia were found to be independent correlates of the decrease in potassium concentration during treatment. Insulin alone resulted in correction of hyperkalemia in all instances. Posttreatment hypokalemia was noted in only two instances, each associated with both ketoacidosis and low-normal serum potassium concentration at hyperglycemia. Giving insulin is the only treatment usually needed for the hyperkalemia of hyperglycemia in patients on ongoing dialysis.

  9. Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice

    PubMed Central

    YOSHIDA, Mei; HAYASHI, Kaori; WATADANI, Risa; OKANO, Yoshiyasu; TANIMURA, Keiya; KOTOH, Jun; SASAKI, Daiki; MATSUMOTO, Kozo; MAEDA, Akihiko

    2016-01-01

    The study examined whether royal jelly (RJ) can prevent obesity and ameliorate hyperglycemia in type 2 diabetes. This study utilized obese/diabetic KK-Ay mice. RJ (10 mg/kg) was administered by oral gavage. Body weight, plasma glucose and insulin levels were measured. mRNA and protein levels were determined using quantitative reverse transcription polymerase chain reaction and western blotting, respectively. Four weeks of RJ administration improved hyperglycemia and partially suppressed body weight gain, although the latter effect did not reach statistical significance. In addition, RJ administration did not improve insulin resistance. RJ administration suppressed the mRNA expression of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, in the liver. Simultaneously, RJ administration induced adiponectin (AdipoQ) expression in abdominal fat, adiponectin receptor-1 (AdipoR1) expression in the liver and phosphorylated AMP-activated protein kinase (pAMPK) expression, which suppressed G6Pase levels in the livers of KK-Ay mice. pAMPK levels were also increased in skeletal muscle, but glucose transporter-4 (Glut4) translocation was not increased in the RJ supplementation group. The improvement in hyperglycemia due to long-term RJ administration may be because of the suppression of G6Pase expression through the upregulation of AdipoQ and AdipoR1 mRNA and pAMPK protein expressions. PMID:27890887

  10. Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats †

    PubMed Central

    Yusoff, Nor Adlin; Ahmad, Mariam; Al-Hindi, Bassel; Widyawati, Tri; Yam, Mun Fei; Mahmud, Roziahanim; Abdul Razak, Khairul Niza; Asmawi, Mohd Zaini

    2015-01-01

    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. PMID:26308046

  11. Inhibitory effects of hyssop (Hyssopus officinalis) extracts on intestinal alpha-glucosidase activity and postprandial hyperglycemia.

    PubMed

    Miyazaki, Hiroyuki; Matsuura, Hideyuki; Yanagiya, Chikako; Mizutani, Junya; Tsuji, Masayoshi; Ishihara, Chiaki

    2003-10-01

    It has been known that Hyssopus officinalis (hyssop) is a herb that grows in the wild and is a source of natural antioxidants. We previously reported that a-glucosidase inhibitors, (2S, 3S)1-O-beta-D-6'-O-cinnamoylglucopyranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol and (2S, 3S)1-O-beta-D-glucopranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol, from the dry leaves of hyssop, were isolated. This study examined the alpha-glucosidase inhibitory effects of hyssop extracts on intestinal carbohydrate absorption in rat everted gut sac and carbohydrate-loaded hyperglycemia in mice. In the everted gut sac experiment, 10 mM sucrose- and 5 mM maltose-treated increases in glucose concentration in the serosal compartment were inhibited in the presence of 0.5 and 1.0 mg/ mL hyssop extracts, although a 10 mM glucose-induced increase in serosal glucose was not inhibited by the extracts. Additionally, hyperglycemia in sucrose- and maltose-loaded mice was significantly suppressed at an early stage, within 30 to 60 min by oral pre-administration of 300 and 100 mg/kg hyssop extracts, respectively. These findings suggest that hyssop extracts inhibited the digestion of complex carbohydrates, but not that of absorbable monosaccharide, and might be a useful supplemental food for hyperglycemia.

  12. A synergistic therapeutic scheme for hyperglycemia and nephrotic disorders in diabetes.

    PubMed

    He, Qingyi; Zhang, Xing; Han, Baosan; Xu, Jianzhong; Tang, Kanglai; Fu, Zhiren; Yin, Hao

    2014-01-01

    We previously demonstrated that the utilization of an electrospun scaffold could boost functional outputs of transplanted islets. In this study, we aim to develop a drug-eluting scaffold with a payload of pioglitazone to simultaneously rein in hyperglycemia and recoup lost renal functions in diabetic mice that underwent islet transplantation. The in vivo proliferation of islets was measured by a non-invasive bio-imaging technology whereas the blood insulin, blood glucose and renal proteins were assayed. The local stimulation of transplanted islets by pioglitazone saw an accelerated in vivo proliferation without apoptosis caused by the drug-eluting scaffold. In addition, pioglitazone contributed to an increased secretion of insulin and C-peptide 2, giving rise to an accelerated rein-in of hyperglycemia and enhanced tolerance of sudden oral glucose challenge. Moreover, the accelerated decrease of blood creatinine, urine creatinine and blood urea nitrogen suggested that pioglitazone contributed to the recovery of renal functions compromised by diabetes. Our bioengineering strategy effectively ameliorated hyperglycemia and associated nephrotic disorders, and shed a new light on an engineering approach to combat diabetes.

  13. Foam cells generated by a combination of hyperglycemia and hyperlipemia in rats.

    PubMed

    Sano, Jun-ichi; Shirakura, Shiro; Oda, Shoji; Hara, Takuji; Ishihara, Tokuhiro

    2004-12-01

    Diabetes is a major risk factor for atherosclerosis, as well as hyperlipemia. Investigators have suggested that denatured lipoprotein in hyperglycemia transforms macrophages into foam cells, which correlates with the development or progression of atherosclerosis. In the present study, we examined the generation of foam cells in rats caused by a combination of hyperglycemia and hyperlipemia. Streptozotocin-induced diabetic male Wister rats were fed a high cholesterol diet (HCD) containing 1% cholesterol and 0.5% cholic acid to maintain a hyperglycemic and hyperlipemic state. Animals fed the HCD for 8 weeks or longer showed a high incidence of foam cell accumulation in the renal glomerulus, intima of aortic arch, splenic red pulp and marginal zone, liver sinusoid and intestinal lamina propria. The foam cells exhibited positive staining for antimonocyte/macrophage antibody and lipids in all these tissues. Anti-rat apolipoprotein B (apo B) antibody revealed that positive staining existed only in the cytoplasm of glomerular foam cells. These results suggest that the origin of these foam cells can be attributed to lipid-laden macrophages. The generation of foam cells in the hyperglycemia-hyperlipidemia supervening rat model presented in the present study might be a useful tool for investigations of the pathogenesis of foam cells.

  14. Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer

    PubMed Central

    Litchfield, Lacey M.; Mukherjee, Abir; Eckert, Mark A.; Johnson, Alyssa; Mills, Kathryn A.; Pan, Shawn; Shridhar, Viji; Lengyel, Ernst; Romero, Iris L.

    2015-01-01

    Increasing interest in repurposing the diabetic medication metformin for cancer treatment has raised important questions about the translation of promising preclinical findings to therapeutic efficacy, especially in non-diabetic patients. A significant limitation of the findings to date is the use of supraphysiologic metformin doses and hyperglycemic conditions in vitro. Our goals were to determine the impact of hyperglycemia on metformin response and to address the applicability of metformin as a cancer therapeutic in non-diabetic patients. In normoglycemic conditions, lower concentrations of metformin were required to inhibit cell viability, while metformin treatment in hyperglycemic conditions resulted in increased glucose uptake and glycolytic flux, contributing to cell survival. Mechanistically, maintenance of c-Myc expression under conditions of hyperglycemia or via gene amplification facilitated metabolic escape from the effects of metformin. In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice. These findings indicate that hyperglycemia inhibits the anti-cancer effects of metformin in vitro and in vivo. Furthermore, our results suggest that metformin may elicit stronger responses in normoglycemic vs. hyperglycemic patients, highlighting the need for prospective clinical testing in patients without diabetes. PMID:26172303

  15. Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Stante, A; Dello Russo, P; Torella, R

    1989-01-01

    Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

  16. Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.

    PubMed

    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.

  17. A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo

    PubMed Central

    Zhang, Shi-Jie; Li, Yi-Fang; Tan, Rui-Rong; Tsoi, Bun; Huang, Wen-Shan; Huang, Yi-Hua; Tang, Xiao-Long; Hu, Dan; Yao, Nan; Yang, Xuesong; Kurihara, Hiroshi; Wang, Qi; He, Rong-Rong

    2016-01-01

    ABSTRACT 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. PMID:26744353

  18. Mild Hyperthermia Worsens the Neuropathological Damage Associated with Mild Traumatic Brain Injury in Rats

    PubMed Central

    Sakurai, Atsushi; Atkins, Coleen M.; Alonso, Ofelia F.; Bramlett, Helen M.

    2012-01-01

    Abstract The effects of slight variations in brain temperature on the pathophysiological consequences of acute brain injury have been extensively described in models of moderate and severe traumatic brain injury (TBI). In contrast, limited information is available regarding the potential consequences of temperature elevations on outcome following mild TBI (mTBI) or concussions. One potential confounding variable with mTBI is the presence of elevated body temperature that occurs in the civilian or military populations due to hot environments combined with exercise or other forms of physical exertion. We therefore determined the histopathological effects of pre- and post-traumatic hyperthermia (39°C) on mTBI. Adult male Sprague-Dawley rats were divided into 3 groups: pre/post-traumatic hyperthermia, post-traumatic hyperthermia alone for 2 h, and normothermia (37°C). The pre/post-hyperthermia group was treated with hyperthermia starting 15 min before mild parasagittal fluid-percussion brain injury (1.4–1.6 atm), with the temperature elevation extending for 2 h after trauma. At 72 h after mTBI, the rats were perfusion-fixed for quantitative histopathological evaluation. Contusion areas and volumes were significantly larger in the pre/post-hyperthermia treatment group compared to the post-hyperthermia and normothermic groups. In addition, pre/post-traumatic hyperthermia caused the most severe loss of NeuN-positive cells in the dentate hilus compared to normothermia. These neuropathological results demonstrate that relatively mild elevations in temperature associated with peri-traumatic events may affect the long-term functional consequences of mTBI. Because individuals exhibiting mildly elevated core temperatures may be predisposed to aggravated brain damage after mTBI or concussion, precautions should be introduced to target this important physiological variable. PMID:22026555

  19. Allergic contact cheilitis from a lipstick misdiagnosed as herpes labialis: Subsequent worsening due to Zovirax contact allergy.

    PubMed

    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 sensitivity and first-phase insulin secretion in obese Chinese with hyperglycemia in 30 and/or 60 min during glucose tolerance tests.

    PubMed

    Hong, Jie; Zhang, Yi-Fei; Gu, Wei-qiong; Zhang, Yu-wen; Su, Yu-xia; Chi, Zhen-ni; Wang, Wei-qing; Li, Xiao-ying; Ning, Guang

    2008-01-01

    The purpose of this study was to investigate insulin sensitivity and first-phase insulin secretion in obesity with hyperglycemia in 30 and/or 60 min during oral glucose tolerance (OGTT, glucose > or = 11.1 mmol/l, post-loading hyperglycemia, PLH) in Chinese population. A total of 196 nondiabetic subjects were included in the present study, among them 99 had normal glucose tolerance (NGT, subdivided into 32 lean NGT and 67 obese NGT), 74 had obesity with impaired glucose tolerance (IGT) and 23 had obesity with PLH. A standard 75-g oral glucose tolerance test was performed after fasting and at 30 min, 1, 2 and 3 h. Insulin sensitivity index (S(I)) was assessed by the Bergman's minimal model method with frequently sampled intravenous glucose tolerance test (FSIGTT), insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S(I) was used to determine whether AIRg was adequate to compensate for insulin resistance. S(I) was significantly equally lower in three obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT controls, and reduced to the same extent in IGT and PLH subjects. There was no significant difference among lean NGT, IGT and PLH subjects. DI value was reduced from obese NGT individuals, IGT and PLH subjects had a similar lower level of DI. In conclusion, our present results demonstrated that the pathophysiological basis of obese subjects with PLH were clearly insulin resistance and defective in first-phase insulin secretion as that in IGT subjects in Chinese population.

  1. Dissociation of Hyperglycemia from Altered Vascular Contraction and Relaxation Mechanisms in Caveolin-1 Null Mice

    PubMed Central

    Pojoga, Luminita H.; Yao, Tham M.; Opsasnick, Lauren A.; Garza, Amanda E.; Reslan, Ossama M.; Adler, Gail K.; Williams, Gordon H.

    2014-01-01

    Hyperglycemia and endothelial dysfunction are associated with hypertension, but the specific causality and genetic underpinning are unclear. Caveolin-1 (cav-1) is a plasmalemmal anchoring protein and modulator of vascular function and glucose homeostasis. Cav-1 gene variants are associated with reduced insulin sensitivity in hypertensive individuals, and cav-1−/− mice show endothelial dysfunction, hyperglycemia, and increased blood pressure (BP). On the other hand, insulin-sensitizing therapy with metformin may inadequately control hyperglycemia while affecting the vascular outcome in certain patients with diabetes. To test whether the pressor and vascular changes in cav-1 deficiency states are related to hyperglycemia and to assess the vascular mechanisms of metformin under these conditions, wild-type (WT) and cav-1−/− mice were treated with either placebo or metformin (400 mg/kg daily for 21 days). BP and fasting blood glucose were in cav-1−/− > WT and did not change with metformin. Phenylephrine (Phe)- and KCl-induced aortic contraction was in cav-1−/− < WT; endothelium removal, the nitric-oxide synthase (NOS) blocker l-NAME (Nω-nitro-l-arginine methyl ester), or soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) enhanced Phe contraction, and metformin blunted this effect. Acetylcholine-induced relaxation was in cav-1−/− > WT, abolished by endothelium removal, l-NAME or ODQ, and reduced with metformin. Nitric oxide donor sodium nitroprusside was more potent in inducing relaxation in cav-1−/− than in WT, and metformin reversed this effect. Aortic eNOS, AMPK, and sGC were in cav-1−/− > WT, and metformin decreased total and phosphorylated eNOS and AMPK in cav-1−/−. Thus, metformin inhibits both vascular contraction and NO-cGMP-dependent relaxation but does not affect BP or blood glucose in cav-1−/− mice, suggesting dissociation of hyperglycemia from altered vascular function in cav-1

  2. Loss of TLR2 Worsens Spontaneous Colitis in MDR1A Deficiency through Commensally Induced Pyroptosis

    PubMed Central

    Ey, Birgit; Eyking, Annette; Klepak, Magdalena; Salzman, Nita H.; Göthert, Joachim R.; Rünzi, Michael; Schmid, Kurt W.; Gerken, Guido; Podolsky, Daniel K.

    2013-01-01

    Variants of the multidrug resistance gene (MDR1/ABCB1) have been associated with increased susceptibility to severe ulcerative colitis (UC). In this study, we investigated the role of TLR/IL-1R signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency. Double- or triple-null mice lacking TLR2, MD-2, MyD88, and MDR1A were generated in the FVB/N background. Deletion of TLR2 in MDR1A deficiency resulted in fulminant pancolitis with early expansion of CD11b+ myeloid cells and rapid shift toward TH1-dominant immune responses in the lamina propria. Colitis exacerbation in TLR2/MDR1A double-knockout mice required the unaltered commensal microbiota and the LPS coreceptor MD-2. Blockade of IL-1β activity by treatment with IL-1R antagonist (IL-1Ra; Anakinra) inhibited colitis acceleration in TLR2/MDR1A double deficiency; intestinal CD11b+Ly6C+-derived IL-1β production and inflammation entirely depended on MyD88. TLR2/MDR1A double-knockout CD11b+ myeloid cells expressed MD-2/TLR4 and hyperresponded to nonpathogenic Escherichia coli or LPS with reactive oxygen species production and caspase-1 activation, leading to excessive cell death and release of proinflammatory IL-1β, consistent with pyroptosis. Inhibition of reactive oxygen species–mediated lysosome degradation suppressed LPS hyperresponsiveness. Finally, active UC in patients carrying the TLR2-R753Q and MDR1-C3435T polymorphisms was associated with increased nuclear expression of caspase-1 protein and cell death in areas of acute inflammation, compared with active UC patients without these variants. In conclusion, we show that the combined defect of two UC susceptibility genes, MDR1A and TLR2, sets the stage for spontaneous and uncontrolled colitis progression through MD-2 and IL-1R signaling via MyD88, and we identify commensally induced pyroptosis as a potential innate immune effector in severe UC pathogenesis. PMID:23636052

  3. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  4. Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury

    PubMed Central

    Li, Dongpeng; Ma, Shanshan; Guo, Dewei; Cheng, Tian; Li, Hongwei; Tian, Yi; Li, Jianbin; Guan, Fangxia; Yang, Bo; Wang, Jian

    2016-01-01

    Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague–Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID:26886755

  5. Worsening of attitudes toward epilepsy following less influential media coverage of epilepsy-related car accidents: An infodemiological approach.

    PubMed

    Okumura, Akihisa; Abe, Shinpei; Kurahashi, Hirokazu; Takasu, Michihiko; Ikeno, Mitsuru; Nakazawa, Mika; Igarashi, Ayuko; Shimizu, Toshiaki

    2016-11-01

    To evaluate changes in the attitudes of nonmedical university students toward epilepsy in 2015, the present study compared the results of questionnaire surveys from four different time periods: before media coverage of epilepsy-related car accidents (2008-2010), during a period of abundant media coverage (2011-2012), after media coverage (2013-2014), and after novel media coverage (2015). The nonmedical students that completed the questionnaire were divided into four groups: 2008-2010, 2011-2012, 2013-2014, and 2015. The rates of students that had read or heard about epilepsy decreased significantly in 2015 compared with those in 2013-2014. Attitudes toward epilepsy had also worsened in 2015. The rates of students that would not oppose their children playing with or attending school alongside children with epilepsy and those who thought that people with epilepsy should be hired in the same way as other people had decreased significantly in 2015 compared with those in 2011-2012 and 2013-2014. Analyses of information-seeking behavior on the Internet showed that the increase in Google search volume and Wikipedia page views was much less in 2015 than in 2011 and 2012. These findings suggest that familiarity with epilepsy had worsened even after media coverage of novel epilepsy-related car accidents. This suggests that media coverage in 2015 was less influential than that in 2011 and 2012.

  6. The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions.

    PubMed

    Ambrosy, Andrew P; Butler, Javed; Ahmed, Ali; Vaduganathan, Muthiah; van Veldhuisen, Dirk J; Colucci, Wilson S; Gheorghiade, Mihai

    2014-05-13

    Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output, and reduces pulmonary capillary wedge pressure without causing deleterious increases in heart rate or decreases in blood pressure. Moreover, it is also a neurohormonal modulator at low doses. In the pivotal DIG (Digitalis Investigation Group) trial, digoxin therapy was shown to reduce all-cause and HF-specific hospitalizations but had no effect on survival. With the discovery of neurohormonal blockers capable of reducing mortality in HF with reduced ejection fraction, the results of the DIG trial were viewed as neutral, and the use of digoxin declined precipitously. Although modern drug and device-based therapies have dramatically improved the survival of ambulatory patients with HF, outcomes for patients with worsening chronic HF, defined as deteriorating signs and symptoms on standard therapy often leading to unscheduled clinic or emergency department visits or hospitalization, have largely remained unchanged over the past 2 decades. The available data suggest that a therapeutic trial of digoxin may be appropriate in patients with worsening chronic heart failure who remain symptomatic.

  7. Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

    PubMed

    Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud

    2016-01-01

    Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy.

  8. Acute pancreatitis: The stress factor

    PubMed Central

    Binker, Marcelo G; Cosen-Binker, Laura I

    2014-01-01

    Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. PMID:24914340

  9. Robust Brain Hyperglycemia during General Anesthesia: Relationships with Metabolic Brain Inhibition and Vasodilation

    PubMed Central

    Bola, R. Aaron; Kiyatkin, Eugene A.

    2016-01-01

    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, which 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 tissue could be

  10. Resveratrol rescues hyperglycemia-induced endothelial dysfunction via activation of Akt

    PubMed Central

    Li, Jin-yi; Huang, Wei-qiang; Tu, Rong-hui; Zhong, Guo-qiang; Luo, Bei-bei; He, Yan

    2017-01-01

    Resveratrol (RSV), a phytoalexin, has shown to prevent endothelial dysfunction and reduce diabetic vascular complications and the risk of cardiovascular diseases. The aim of this study was to investigate the signaling mechanisms underlying the protecting effects of RSV against endothelial dysfunction during hyperglycemia in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with RSV, and then exposed to high glucose (HG, 30 mmol/L). Akt-Ser473 phosphorylation, eNOS-Ser1177 phosphorylation, and PTEN protein levels in the cells were detected using Western blot. For in vivo studies, WT and Akt−/− mice were fed a normal diet containing RSV (400 mg·kg−1·d−1) for 2 weeks, then followed by injection of STZ to induce hyperglycemia (300 mg/dL). Endothelial function was evaluated using aortic rings by assessing ACh-induced vasorelaxation. RSV (5–20 μmol/L) dose-dependently increased Akt-Ser473 phosphorylation, accompanied by increased eNOS-Ser1177 phosphorylation in HUVECs; these effects were more prominent under HG stimulation. Transfection with Akt siRNA abolished RSV-enhanced eNOS phosphorylation and NO release. Furthermore, RSV (5–20 μmol/L) dose-dependently decreased the levels of PTEN, which was significantly increased under HG stimulation, and PTEN overexpression abolished RSV-stimulated Akt phosphorylation in HG-treated HUVECs. Moreover, RSV dramatically increased 26S proteasome activity, which induced degradation of PTEN. In in vivo studies, pretreatment with RSV significantly increased Akt and eNOS phosphorylation in aortic tissues and ACh-induced vasorelaxation, and improved diabetes-induced endothelial dysfunction in wild-type mice but not in Akt−/− mice. RSV attenuates endothelial function during hyperglycemia via activating proteasome-dependent degradation of PTEN, which increases Akt phosphorylation, and consequentially upregulation of eNOS-derived NO production. PMID:27941804

  11. Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve.

    PubMed

    Atif, Fahim; Prunty, Megan C; Turan, Nefize; Stein, Donald G; Yousuf, Seema

    2017-03-14

    We investigated the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in brain, spinal cord and sciatic nerve tissue in male rats. Animals were rendered hyperglycemic by a single dose of streptozotocin (STZ). P4 treatment was started after hyperglycemia was confirmed and body weight and blood glucose levels were monitored once/week for 5weeks. Rats underwent behavioral testing at week 5 and were then euthanized for histology. We assessed the expression of markers of angiogenesis (vascular endothelial growth factor (VEGF)), inflammation (interleukin-6 (IL-6)) and tissue injury (CD11b, NG2, COX2 and matrix metalloproteinase-2 (MMP-2)) in the brain, spinal cord and sciatic nerve. We also examined the regenerative effect of P4 on pathological changes in intra-epidermal nerve fibers (IENF) of the footpads. Diabetes/hyperglycemia led to body weight loss over 5weeks and P4 treatment reduced this loss. At week 5, blood-glucose levels were significantly lower in the P4-treated diabetic group compared to vehicle. Compared to sham or P4-treated groups, the diabetic vehicle group showed hyperactivity on the spontaneous locomotor activity test. Western blot data revealed upregulation of VEGF, IL-6, CD11b, NG2, COX2 and MMP-2 levels in the vehicle group and P4 treatment normalized these expression levels. IENF densities were reduced in the vehicle group and normalized after P4 treatment. We conclude that P4 can reduce some of the chronic pathological responses to STZ-induced diabetes.

  12. Low Vitamin D Levels Do Not Predict Hyperglycemia in Elderly Endurance Athletes (but in Controls)

    PubMed Central

    Nistler, Sonja; Batmyagmar, Delgerdalai; Ponocny-Seliger, Elisabeth; Perkmann, Thomas; Scherzer, Thomas M.; Kundi, Michael; Endler, Georg; Ratzinger, Franz; Pilger, Alexander; Wagner, Oswald F.; Winker, Robert

    2016-01-01

    Background and Aim Recent studies revealed a link between hypovitaminosis D3 and the risk for hyperglycemia. Further mechanistic and interventional investigations suggested a common reason for both conditions rather than a causal relationship. Exposure to sunlight is the most relevant source of vitamin D3 (25(OH)D), whereas adipose tissue is able to store relevant amounts of the lipophilic vitamin. Since running/bicycling leads to increased out-door time and alters physiological response mechanisms, it can be hypothesized that the correlation between hypovitaminosis D3 and hyperglycemia might be disturbed in outdoor athletes. Methods 47 elderly marathoners/bicyclists and 47 age/sex matched controls were studied in a longitudinal setting at baseline and after three years. HbA1c as a surrogate for (pre-)diabetic states was quantified via HPLC, 25(OH)D levels were measured by means of chemiluminescent assays. Physical performance was assessed by ergometry. Results When adjusted for seasonal variations, 25(OH)D was significantly higher in athletes than in controls. 25(OH)D levels inversely correlated with triglycerides in both groups, whereas only in controls an association between high BMI or low physical performance with hypovitaminosis D3 had been found. Likewise, the presence of hypovitaminosis D3 at baseline successfully predicted hyperglycemia at the follow up examinations within the control group (AUC = 0.85, 95% CI [0.74, 0.96], p < .001, statistically independent from BMI), but not in athletes. Conclusion Our data suggest that mechanisms of HbA1c elevation might differ between athletes and controls. Thus, intense physical activity must be taken into account as a potential pre-analytic confounder when it is aimed to predict metabolic risk by vitamin D3 levels. PMID:27304888

  13. Hyperglycemia impedes definitive endoderm differentiation of human embryonic stem cells by modulating histone methylation patterns.

    PubMed

    Chen, A C H; Lee, Y L; Fong, S W; Wong, C C Y; Ng, E H Y; Yeung, W S B

    2017-03-10

    Exposure to maternal diabetes during fetal growth is a risk factor for the development of type II diabetes (T2D) in later life. Discovery of the mechanisms involved in this association should provide valuable background for therapeutic treatments. Early embryogenesis involves epigenetic changes including histone modifications. The bivalent histone methylation marks H3K4me3 and H3K27me3 are important for regulating key developmental genes during early fetal pancreas specification. We hypothesized that maternal hyperglycemia disrupted early pancreas development through changes in histone bivalency. A human embryonic stem cell line (VAL3) was used as the cell model for studying the effects of hyperglycemia upon differentiation into definitive endoderm (DE), an early stage of the pancreatic lineage. Hyperglycemic conditions significantly down-regulated the expression levels of DE markers SOX17, FOXA2, CXCR4 and EOMES during differentiation. This was associated with retention of the repressive histone methylation mark H3K27me3 on their promoters under hyperglycemic conditions. The disruption of histone methylation patterns was observed as early as the mesendoderm stage, with Wnt/β-catenin signaling being suppressed during hyperglycemia. Treatment with Wnt/β-catenin signaling activator CHIR-99021 restored the expression levels and chromatin methylation status of DE markers, even in a hyperglycemic environment. The disruption of DE development was also found in mouse embryos at day 7.5 post coitum from diabetic mothers. Furthermore, disruption of DE differentiation in VAL3 cells led to subsequent impairment in pancreatic progenitor formation. Thus, early exposure to hyperglycemic conditions hinders DE development with a possible relationship to the later impairment of pancreas specification.

  14. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.

    PubMed

    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.

  15. Hyperglycemia effect on coronary disease in patients with metabolic syndrome evaluated by intracoronary ultrasonography

    PubMed Central

    Bonamichi, Beatriz Dal Santo Francisco; Parente, Erika Bezerra; Campos, Ana Carolina Noronha; Cury, Adriano Namo; Salles, João Eduardo Nunes

    2017-01-01

    Introduction 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). Materials and methods 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. Results and discussion 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). Conclusion 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

  16. Myocardial function and hemoglobin oxygen affinity during hyperglycemia in the fetal lamb.

    PubMed Central

    Bard, H; Fouron, J C; De Muylder, X; Ducharme, G; Lafond, J S

    1986-01-01

    To determine the effects of maternal hyperglycemia on fetal hemodynamic and cardiac function, a study was carried out on nine chronically catheterized fetal sheep. In six fetuses, glucose was infused intravenously with an initial dose of 5 mg/kg per min. Data were compared with controls. This dose was gradually increased to 16 mg/kg per min by the fifth day. The initial blood glucose was 14.7 +/- 3.0 mg/dl and increased to 54.6 +/- 16.4 mg/dl by the last day of the infusion period (P less than 0.001). The PO2 decreased from a baseline of 20.25 +/- 3.40 to 15.88 +/- 5.24 mmHg (P less than 0.01). Similarly significant decreases were also observed for the blood O2 content and O2 hemoglobin saturation: 8.5 +/- 1.7 to 6.4 +/- 2.2 ml/dl and 62.3 +/- 13.6 to 46.1 +/- 17.6%, respectively, during hyperglycemia (P less than 0.01). The duration of the preejection period (PEP) before the start of the experiment was 45 +/- 4 ms; a final value of 57 +/- 10 ms was obtained (P less than 0.01). However, the electromechanical delay and ejection time (ET) showed no significant variation. The ratio of the PEP/ET increased from 0.31 +/- 0.04 to 0.38 +/- 0.07 (P less than 0.01) during hyperglycemia. The reticulocytes increased from 1.4 +/- 1.8 to 3.1 +/- 2.9% (P less than 0.05) and the 2,3-diphosphoglycerate decreased from 4.4 +/- 1.1 to 2.8 +/- 1.2 mumol/g hemoglobin (P less than 0.005). This study demonstrated that fetal hyperglycemia depresses myocardial function in the fetal lamb. The changes in cardiac function could not be explained by the small drop in O2 saturation. PMID:3722375

  17. Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways.

    PubMed

    Slotkin, Theodore A; Card, Jennifer; Seidler, Frederic J

    2014-01-01

    This study explores how glucocorticoids sensitize the developing brain to the organophosphate pesticide, chlorpyrifos. Pregnant rats received a standard therapeutic dose (0.2mg/kg) of dexamethasone on gestational days 17-19; pups were given subtoxic doses of chlorpyrifos on postnatal days 1-4 (1mg/kg, <10% cholinesterase inhibition). We evaluated serotonin (5HT) synaptic function from postnatal day 30 to day 150, assessing the expression of 5HT receptors and the 5HT transporter, along with 5HT turnover (index of presynaptic impulse activity) in brain regions encompassing all the 5HT projections and cell bodies. These parameters are known targets for neurodevelopmental effects of dexamethasone and chlorpyrifos individually. In males, chlorpyrifos evoked overall elevations in the expression of 5HT synaptic proteins, with a progressive increase from adolescence to adulthood; this effect was attenuated by prenatal dexamethasone treatment. The chlorpyrifos-induced upregulation was preceded by deficits in 5HT turnover, indicating that the receptor upregulation was an adaptive response to deficient presynaptic activity. Turnover deficiencies were magnified by dexamethasone pretreatment, worsening the functional impairment caused by chlorpyrifos. In females, chlorpyrifos-induced receptor changes reflected relative sparing of adverse effects compared to males. Nevertheless, prenatal dexamethasone still worsened the 5HT turnover deficits and reduced 5HT receptor expression in females, demonstrating the same adverse interaction. Glucocorticoids are used in 10% of U.S. pregnancies, and are also elevated in maternal stress; accordingly, our results indicate that this group represents a large subpopulation that may have heightened vulnerability to developmental neurotoxicants such as the organophosphates.

  18. Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.

    PubMed

    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.

  19. Minireview: Glucagon in the Pathogenesis of Hypoglycemia and Hyperglycemia in Diabetes

    PubMed Central

    2012-01-01

    Pancreatic islet α-cell glucagon secretion is critically dependent on pancreatic islet β-cell insulin secretion. Normally, a decrease in the plasma glucose concentration causes a decrease in β-cell insulin secretion that signals an increase in α-cell glucagon secretion during hypoglycemia. In contrast, an increase in the plasma glucose concentration, among other stimuli, causes an increase in β-cell insulin secretion that signals a decrease, or at least no change, in α-cell glucagon secretion after a meal. In absolute endogenous insulin deficiency (i.e. in type 1 diabetes and in advanced type 2 diabetes), however, β-cell failure results in no decrease in β-cell insulin secretion and thus no increase in α-cell glucagon secretion during hypoglycemia and no increase in β-cell insulin secretion and thus an increase in α-cell glucagon secretion after a meal. In type 1 diabetes and advanced type 2 diabetes, the absence of an increment in glucagon secretion, in the setting of an absent decrement in insulin secretion and an attenuated increment in sympathoadrenal activity, in response to falling plasma glucose concentrations plays a key role in the pathogenesis of iatrogenic hypoglycemia. In addition, there is increasing evidence that, in the aggregate, suggests that relative hyperglucagonemia, in the setting of deficient insulin secretion, plays a role in the pathogenesis of hyperglycemia in diabetes. If so, abnormal glucagon secretion is involved in the pathogenesis of both hypoglycemia and hyperglycemia in diabetes. PMID:22166985

  20. Extreme hyperglycemia with ketoacidosis and hyperkalemia in a patient on chronic hemodialysis.

    PubMed

    Gupta, Arvin; Rohrscheib, Mark; Tzamaloukas, Antonios H

    2008-10-01

    A patient on hemodialysis for end-stage renal disease secondary to diabetic nephropathy was admitted in a coma with Kussmaul breathing and hypertension (232/124 mmHg). She had extreme hyperglycemia (1884 mg/dL), acidosis (total CO(2) 4 mmol/L), hyperkalemia (7.2 mmol/L) with electrocardiographic abnormalities, and hypertonicity (330.7 mOsm/kg). Initial treatment with insulin drip resulted in a decrease in serum potassium to 5.3 mmol/L, but no significant change in mental status or other laboratory parameters. Hemodialysis of 1.75 hours resulted in rapid decline in serum glucose and tonicity and rapid improvement of the acidosis, but no change in mental status, which began to improve slowly after the hemodialysis was stopped, but with ongoing treatment with continuous insulin infusion. The rate of decline in tonicity during hemodialysis (14.5 mOsm/kg/h) was high, raising concerns about neurological complications. In this case, extreme hyperglycemia with ketoacidosis, hyperkalemia, and coma developing in a hemodialysis patient responded to insulin infusion. Monitoring of the clinical status and the pertinent laboratory values is required to assess the need for other therapeutic measures including volume and potassium replacement and emergency dialysis. The indications for and risks of emergency dialysis in this setting are not clearly defined.

  1. Obesity and hyperglycemia lead to impaired post-ischemic recovery after permanent ischemia in mice

    PubMed Central

    Tulsulkar, Jatin; Nada, Shadia E.; Slotterbeck, Brandon D.; McInerney, Marcia F.; Shah, Zahoor A.

    2015-01-01

    Objective Obesity-induced diabetes has increased over the years and has become one of the risk factors for stroke. We investigated the influence of diet-induced obesity and hyperglycemia on permanent distal middle cerebral artery occlusion (pMCAO) induced ischemic stroke in mice. Methods Male C57/Bl6 mice were treated with a high fat/ high carbohydrate diet [HFCD/obese and hyperglycemia (O/H)] or a normal diet (control) for 3.5 months, subjected to pMCAO and sacrificed after 7 days. Results Infarct volume analysis showed no differences between the O/H and control group, whereas neurological deficits were significantly higher in the O/H group compared to the control group. Sirtuin (Sirt1) was overexpressed and NADPH oxidase was reduced in the O/H group. O/H mice had significantly lower expression of Wnt and glycogen synthase kinase 3 α and β, a key component in the Wnt signaling pathway. Translocation of apoptosis inducing factor (AIF) to the nucleus was observed in both the O/H and control groups, but O/H mice showed a higher expression of AIF in the nucleus. Conclusions Our data suggest that impaired Wnt signaling and active apoptosis results in reduced post-stroke recovery in obese and hyperglycemic mice. PMID:26694743

  2. Enhydrin Regulates Postprandial Hyperglycemia in Diabetic Rats by Inhibition of α-Glucosidase Activity.

    PubMed

    Serra-Barcellona, C; Habib, N C; Honoré, S M; Sánchez, S S; Genta, S B

    2017-02-04

    During the last few years, numerous attempts were made to identify effective α-glucosidase inhibitors from natural sources in order to develop new alternatives for diabetes management. Smallanthus sonchifolius (yacon) leaves were found to be effective in controlling postprandial hyperglycemia. Enhydrin, a constituent of yacon leaves, was noted for its significant hypoglycemic properties in diabetic rats. These properties were also demonstrated for yacon leaves decoction, which is rich in phenolic compounds such as chlorogenic acid and its derivatives. The purpose of the present study was to evaluate the potential of yacon leaves decoction and the isolated compound enhydrin to inhibit α-glucosidase enzyme, a possible mechanism of the above antihyperglycemic effect. In vitro assays showed that both 10% decoction and enhydrin significantly inhibited the activity of the yeast α-glucosidase enzyme in a dose-dependent manner, IC50 values being 50.40 and 134.17 μg/ml, respectively. In vivo experiments showed a rapid decrease in the hyperglycemic peak after sucrose load (2 g/kg body weight) in normal rats treated with the 10% decoction (140 mg/kg) and enhydrin (0.8 mg/kg). Both treatments caused a significant decrease in blood glucose levels in diabetic rats after sucrose load compared to diabetic control. These results suggest that both products assayed could be effective in the management of postprandial hyperglycemia through inhibition of α-glucosidase in the small intestine.

  3. Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.

    PubMed

    Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O'Donnell, Martha

    2012-07-01

    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.

  4. Polyopes lancifolia Extract, a Potent α-Glucosidase Inhibitor, Alleviates Postprandial Hyperglycemia in Diabetic Mice.

    PubMed

    Min, Seong Won; Han, Ji Sook

    2014-01-01

    This study was designed to investigate the inhibitory effects of Polyopes lancifolia extract (PLE) on α-glucosidase activity, α-amylase activitiy, and postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. The results of this study revealed a marked inhibitory effect of PLE on α-glucosidase and α-amylase activities. The IC50s of PLE against α-glucosidase and α-amylase were 0.20 mg/mL and 0.35 mg/mL, respectively. PLE was a more effective inhibitor of α-glucosidase and α-amylase activities than acarbose, the positive control. The postprandial blood glucose levels of STZ-induced diabetic mice were significantly lower in the PLE treated group than in the control group. Moreover, PLE administration was associated with a decreased area under the curve for the glucose response in diabetic mice. These results indicate that PLE may be a potent inhibitor of α-glucosidase and α-amylase activities and may suppress postprandial hyperglycemia.

  5. Hyperglycemia, hypoglycemia and glycemic variability in the elderly: a fatal triad?

    PubMed

    Monami, Matteo; Aleffi, Sara

    2016-06-22

    Diabetes mellitus is one of the most important causes of cardiovascular morbidity and mortality; the incidence of chronic complications of diabetes appears to be closely related to the degree of hyperglycaemia. However, results of clinical trials showed that intensive treatment of hyperglycaemia prevents microvascular complications, but has little or no effect on the incidence of cardiovascular events. Different hypoglycaemic drugs show different effects on cardiovascular risk. However, those trials have shown a neutral effect on cardiovascular mortality. This paradoxical result could be explained with the frequent use, in the past, of glucose-lowering agents capable of increasing the risk of hypoglicemia, glycemic variability and weight gain. In conclusion, an adequate glycemic control, in particular in elderly patients, should be achieved, whenever possible, using agents not inducing hypogycemia, glucose fluctuations, and weight gain. In fact, hypoglycaemia and glucose variability should be considered as independent cardiovascular risk factors to a similar extent to hyperglycemia. In this article, the author will review literature supporting the hypothesis that hyperglycemia, hypoglycaemia and glycemic variability are a fatal triad capable of increasing morbidity and mortality in patients with diabetes mellitus.

  6. Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy independently of hyperglycemia and oxidative stress.

    PubMed

    Friederich-Persson, Malou; Thörn, Erik; Hansell, Peter; Nangaku, Masaomi; Levin, Max; Palm, Fredrik

    2013-11-01

    Diabetic nephropathy is strongly associated with both increased oxidative stress and kidney tissue hypoxia. The increased oxidative stress causes increased kidney oxygen consumption resulting in kidney tissue hypoxia. To date, it has been difficult to determine the role of kidney hypoxia, per se, for the development of nephropathy. We tested the hypothesis that kidney hypoxia, without confounding factors such as hyperglycemia or elevated oxidative stress, results in nephropathy. To induce kidney hypoxia, dinitrophenol (30 mg per day per kg bodyweight by gavage), a mitochondrial uncoupler that increases oxygen consumption and causes kidney hypoxia, was administered for 30 consecutive days to rats. Thereafter, glomerular filtration rate, renal blood flow, kidney oxygen consumption, kidney oxygen tension, kidney concentrations of glucose and glycogen, markers of oxidative stress, urinary protein excretion, and histological findings were determined and compared with vehicle-treated controls. Dinitrophenol did not affect arterial blood pressure, renal blood flow, glomerular filtration rate, blood glucose, or markers of oxidative stress but increased kidney oxygen consumption, and reduced cortical and medullary concentrations of glucose and glycogen, and resulted in intrarenal tissue hypoxia. Furthermore, dinitrophenol treatment increased urinary protein excretion, kidney vimentin expression, and infiltration of inflammatory cells. In conclusion, increased mitochondrial oxygen consumption results in kidney hypoxia and subsequent nephropathy. Importantly, these results demonstrate that kidney tissue hypoxia, per se, without confounding hyperglycemia or oxidative stress, may be sufficient to initiate the development of nephropathy and therefore demonstrate a new interventional target for treating kidney disease.

  7. Inhibition of hyperglycemia-induced angiogenesis and breast cancer tumor growth by systemic injection of microRNA-467 antagonist.

    PubMed

    Krukovets, Irene; Legerski, Matthew; Sul, Pavel; Stenina-Adognravi, Olga

    2015-09-01

    Abnormal angiogenesis in multiple tissues is a key characteristic of the vascular complications of diabetes. However, angiogenesis may be increased in one tissue but decreased in another in the same patient at the same time point in the disease. The mechanisms of aberrant angiogenesis in diabetes are not understood. There are no selective therapeutic approaches to target increased neovascularization without affecting physiologic angiogenesis and angiogenesis in ischemic tissues. We recently reported a novel miRNA-dependent pathway that up-regulates angiogenesis in response to hyperglycemia in a cell- and tissue-specific manner. The goal of the work described herein was to test whether systemic administration of an antagonist of miR-467 would prevent hyperglycemia-induced local angiogenesis in a tissue-specific manner. We examined the effect of the antagonist on hyperglycemia-induced tumor growth and angiogenesis and on skin wound healing in mouse models of diabetes. Our data demonstrated that the systemic injection of the antagonist prevented hyperglycemia-induced angiogenesis and growth of mouse and human breast cancer tumors, where the miR-467 pathway was active in hyperglycemia. In tissues where the miR-467-dependent mechanism was not activated by hyperglycemia, there was no effect of the antagonist: the systemic injection did not affect skin wound healing or the growth of prostate tumors. The data show that systemic administration of the miR-467 antagonist could be a breakthrough approach in the treatment and prevention of diabetes-associated breast cancer in a tissue-specific manner without affecting physiologic angiogenesis and angiogenesis in ischemic tissues.

  8. Ultrasound pleural effusion sign as a useful marker for identifying heart failure worsening in established heart failure patients during follow-up.

    PubMed

    Kataoka, Hajime

    2012-01-01

    Clinical significance of UltraSound Pleural Effusion (US-PLE) and test characteristics of this sign for identifying worsening heart failure (HF) during follow-up of HF patients are unclear. Clinical records of 83 established HF patients were examined. The diagnosis of worsening HF was classified as "highly certain,"probable,"uncertain," or "no" based on the combination of the changes in symptoms/signs and B-type natriuretic peptide (BNP). Routine test included searching for the US-PLE sign. During a follow-up of 652±456 days, 1826 visits were evaluated. Among the 83 study patients, 78 had at least one of the following: worsening symptom(s), HF-related sign(s), and/or elevated BNP levels (≥3-fold increase) at one or more clinic visits. The US-PLE sign was present at 83 visits of 49 study patients. Its appearance was associated with the presence of HF-related symptom(s)/sign(s) and BNP elevation (odds ratio, 53-177, P<.0001 each). The test characteristics of the US-PLE sign for diagnosis of high possibility of worsening HF status fulfilling the "highly certain" or "probable" criteria were: sensitivity (76.6%), specificity (98.6%), positive predictive value (71.1%), and negative predictive value (99.0%). The US-PLE sign has high diagnostic accuracy for identifying worsening HF, including asymptomatic events, in HF patients during follow-up.

  9. Endovascular management of acute limb ischemia.

    PubMed

    Peeters, P; Verbist, J; Keirse, K; Deloose, K; Bosiers, M

    2010-06-01

    Acute limb ischemia (ALI) refers to a rapid worsening of limb perfusion resulting in rest pain, ischemic ulcers or gangrene. With an estimated incidence of 140 million/year, ALI is serious limb-threatening and life-threatening medical emergency demanding prompt action. Three prospective, randomized clinical trials provide data on trombolytic therapy versus surgical intervention in patients with acute lower extremity ischemia. Although they did not give us the final answer, satisfactory results are reported for percutaneous thrombolysis compared with surgery. Moreover, they suggest an important advantage of thrombolysis in acute bypass graft occlusions. Therefore, we believe thrombolytic therapy should be a part of the vascular surgeon's armamentarium to safely and successfully treat ALI patients.

  10. Pathophysiology of ischaemic acute kidney injury.

    PubMed

    Kanagasundaram, Nigel Suren

    2015-03-01

    Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia - its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of 'organ cross-talk' will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms.

  11. India's Worsening Uranium Shortage

    SciTech Connect

    Curtis, Michael M.

    2007-01-15

    As a result of NSG restrictions, India cannot import the natural uranium required to fuel its Pressurized Heavy Water Reactors (PHWRs); consequently, it is forced to rely on the expediency of domestic uranium production. However, domestic production from mines and byproduct sources has not kept pace with demand from commercial reactors. This shortage has been officially confirmed by the Indian Planning Commission’s Mid-Term Appraisal of the country’s current Five Year Plan. The report stresses that as a result of the uranium shortage, Indian PHWR load factors have been continually decreasing. The Uranium Corporation of India Ltd (UCIL) operates a number of underground mines in the Singhbhum Shear Zone of Jharkhand, and it is all processed at a single mill in Jaduguda. UCIL is attempting to aggrandize operations by establishing new mines and mills in other states, but the requisite permit-gathering and development time will defer production until at least 2009. A significant portion of India’s uranium comes from byproduct sources, but a number of these are derived from accumulated stores that are nearing exhaustion. A current maximum estimate of indigenous uranium production is 430t/yr (230t from mines and 200t from byproduct sources); whereas, the current uranium requirement for Indian PHWRs is 455t/yr (depending on plant capacity factor). This deficit is exacerbated by the additional requirements of the Indian weapons program. Present power generation capacity of Indian nuclear plants is 4350 MWe. The power generation target set by the Indian Department of Atomic Energy (DAE) is 20,000 MWe by the year 2020. It is expected that around half of this total will be provided by PHWRs using indigenously supplied uranium with the bulk of the remainder provided by breeder reactors or pressurized water reactors using imported low-enriched uranium.

  12. Experimentally induced diabetes worsens neuropathology, but not learning and memory, in middle aged 3xTg mice.

    PubMed

    Hayashi-Park, Emi; Ozment, Bria N; Griffith, Chelsea M; Zhang, Haiying; Patrylo, Peter R; Rose, Gregory M

    2017-03-30

    Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The cause of the disease is still unknown, but amyloid plaques and neurofibrillary tangles in the brain are thought to play a role. However, transgenic mouse models expressing these neuropathological features do not show severe or consistent cognitive impairments. There is accumulating evidence that diabetes increases the risk for developing AD. We tested the hypothesis that experimentally induced diabetes would exacerbate cognitive symptoms in a mouse model of AD. Diabetes was induced in 12-month old 3xTg mice using streptozotocin (STZ; 90mg/kg, i.p., on two successive days). Hyperglycemia was verified by sampling blood glucose levels. Three months after injection (at 15 months of age), the mice were behaviorally tested in the Morris water maze and contextual fear conditioning. Subsequently, the hippocampal region was examined using immunohistochemistry (6E10 antibody for amyloid) and immunoblotting (AT8 antibody for phosphorylated tau). No differences were found in learning or memory between the vehicle-treated control and STZ-treated groups. A significant increase in the number of amyloid-positive plaques was observed in the subiculum of STZ-treated mice; very few plaques were seen in other hippocampal regions in either group. No differences in AT8 load were observed. These results reinforce that amyloid plaques, per se, are not sufficient to cause memory impairments. Further, while diabetes can enhance this aspect of brain pathology, the combination of disrupted glucose metabolism and the transgenes is still not sufficient to cause the severe cognitive impairments associated with clinical AD.

  13. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  14. Hyperglycemia Differentially Affects Maternal and Fetal DNA Integrity and DNA Damage Response

    PubMed Central

    Moreli, Jusciele B.; Santos, Janine H.; Lorenzon-Ojea, Aline Rodrigues; Corrêa-Silva, Simone; Fortunato, Rodrigo S.; Rocha, Clarissa Ribeiro; Rudge, Marilza V.; Damasceno, Débora C.; Bevilacqua, Estela; Calderon, Iracema M.

    2016-01-01

    Objective: Investigate the DNA damage and its cellular response in blood samples from both mother and the umbilical cord of pregnancies complicated by hyperglycemia. Methods: A total of 144 subjects were divided into 4 groups: normoglycemia (ND; 46 cases), mild gestational hyperglycemia (MGH; 30 cases), gestational diabetes mellitus (GDM; 45 cases) and type-2 diabetes mellitus (DM2; 23 cases). Peripheral blood mononuclear cell (PBMC) isolation and/or leukocytes from whole maternal and umbilical cord blood were obtained from all groups at delivery. Nuclear and mitochondrial DNA damage were measured by gene-specific quantitative PCR, and the expression of mRNA and proteins involved in the base excision repair (BER) pathway were assessed by real-time qPCR and Western blot, respectively. Apoptosis was measured in vitro experiments by caspase 3/7 activity and ATP levels. Results: GDM and DM2 groups were characterized by an increase in oxidative stress biomarkers, an increase in nuclear and mitochondrial DNA damage, and decreased expression of mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1) involved in BER. The levels of hyperglycemia were associated with the in vitro apoptosis pathway. Blood levels of DNA damage in umbilical cord were similar among the groups. Newborns of diabetic mothers had increased expression of BER mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1, POLβ and FEN1). A diabetes-like environment was unable to induce apoptosis in the umbilical cord blood cells. Conclusions: Our data show relevant asymmetry between maternal and fetal blood cell susceptibility to DNA damage and apoptosis induction. Maternal cells seem to be more predisposed to changes in an adverse glucose environment. This may be due to differential ability in upregulating multiple genes involved in the activation of DNA repair response, especially the BER mechanism. However if this study shows a more effective adaptive response by the fetal organism, it also calls for

  15. Acute kidney injury requiring haemodialysis following ingestion of mephedrone

    PubMed Central

    Rhidian, Rhys; Babu, Adarsh

    2013-01-01

    A 25-year-old man was found to have acute kidney injury (AKI) following ingestion of mephedrone. He presented to this local emergency department with worsening bilateral loin pain. He became oligoanuric, serum creatine peaked at 1214 µmol/l and he required several sessions of haemodialysis before kidney function began to improve. The mechanism of AKI and legal aspects of the use of mephedrone are discussed. PMID:23456157

  16. Exposure to Indoor Particulate Matter Worsens the Symptoms and Acute Exacerbations in Chronic Obstructive Pulmonary Disease Patients of Southwestern Taiwan: A Pilot Study

    PubMed Central

    Chi, Miao-Ching; Guo, Su-Er; Hwang, Su-Lun; Chou, Chiang-Ting; Lin, Chieh-Mo; Lin, Yu-Ching

    2016-01-01

    Ambient particulate matter (PM) can trigger adverse reactions in the respiratory system, but less is known about the effect of indoor PM. In this longitudinal study, we investigated the relationships between indoor PM and clinical parameters in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Indoor air quality (PM2.5 and PM10 levels) was monitored in the patients’ bedroom, kitchen, living room, and front door at baseline and every two months for one year. At each home visit, the patients were asked to complete spirometry and questionnaire testing. Exacerbations were assessed by chart review and questionnaires during home visits. Generalized estimating equation (GEE) analysis (n = 83) showed that the level of wheezing was significantly higher in patients whose living room and kitchen had abnormal (higher than ambient air quality standards in Taiwan) PM2.5 and PM10 levels. Patients who lived in houses with abnormal outdoor PM2.5 levels had higher COPD Assessment Test scores (physical domain), and those who lived in houses with abnormal PM10 levels in the living room and kitchen had higher London Chest Activity of Daily Living scores. Increased PM levels were associated with worse respiratory symptoms and increased risk of exacerbation in patients with moderate to very severe COPD. PMID:28025521

  17. Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass.

    PubMed Central

    Garcia, D L; Anderson, S; Rennke, H G; Brenner, B M

    1988-01-01

    Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, approximately equal to 42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (approximately equal to 30 vol/dl) by feeding a low iron diet or prevented (approximately equal to 50 vol/dl) by administration of recombinant human erythropoietin (r-HuEpo). In functional studies performed 4 weeks after renal ablation, untreated rats exhibited mild anemia with systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Preventing anemia with r-HuEpo worsened systemic and glomerular hypertension, effects largely obviated by induction of more marked anemia with the low iron diet. Untreated rats followed for 6 weeks postablation exhibited progressive proteinuria and sclerosis involving 12% of glomeruli, contrasted with 33% in rats given r-HuEpo. Even after 12 weeks, sclerosis involved only 6% of glomeruli in rats with more severe anemia but progressed to 30% in untreated rats. Thus, anemia limits systemic and glomerular hypertension and glomerular injury, whereas its prevention by r-HuEpo severely accelerates hemodynamically mediated glomerular injury in this model. These results suggest that anemia is a hemodynamically favorable adaptation to chronic renal disease and that its overly vigorous correction may have adverse renal hemodynamic and structural consequences. PMID:3413082

  18. Decreased senescence marker protein-30 could be a factor that contributes to the worsening of glucose tolerance in normal aging.

    PubMed

    Hasegawa, Goji

    2010-01-01

    In our recent paper, we proposed that senescence marker protein-30 (SMP30) could be a novel molecule which was involved in an impairment of β-cell function with aging. SMP30 knockout (KO) mice and wild-type (WT) mice were fed a standard diet (SD) or a high fat diet (HFD) for 8 weeks from 7 weeks of age. In an intraperitoneal glucose tolerance test at 15 weeks of age, blood glucose levels in SD-fed KO mice were significantly increased by 25% at 30 min after glucose administration compared to SD-fed WT mice. Insulin levels in SD-fed KO mice were significantly decreased by 37% at 30 min postglucose compared to SD-fed WT mice. Interestingly, an insulin tolerance test showed a greater glucose lowering effect in SD-fed KO mice. Morphometric analysis revealed no differences in the degree of HFD-induced compensatory increase in β-cell mass and proliferation. Collectively, these data indicate that impairment of the early phase of insulin secretion underlies glucose intolerance in KO mice. Decreased SMP30 may contribute to the worsening of glucose tolerance that occurs in normal aging.

  19. The role played by serine proteases in the development and worsening of vascular complications in type 1 diabetes mellitus.

    PubMed

    Finotti, Paola

    2006-08-01

    Much attention has been given to the role played by serine proteases in the development and worsening of vascular complications in Type 1 diabetes mellitus. A generalized increase in proteolytic activity, either due to a true increase in concentration of specific proteases or defects of their protease inhibitors, represents an early marker of diabetes. However, the precise molecular mechanism whereby an unopposed proteolytic activity leads to overt vascular alterations has not fully been elucidated as yet. The picture is further complicated by the fact that, although sharing the same function, serine proteases constitute a structurally heterogeneous class of molecules. Besides classical proteases, for most part belonging to coagulative and fibrinolytic systems, other unrelated molecules exhibit serine-like protease activity and are capable of triggering both inflammatory and immune reactions. The specific role of these non classical serine proteases in the complex pathogenesis of diabetes and its vascular complications is attracting a new investigative interest, as these molecules may represent additional therapeutic targets. This review will focus on most recent acquisitions on this issue relevant to Type 1 diabetes.

  20. Chronic methamphetamine exposure prior to middle cerebral artery occlusion increases infarct volume and worsens cognitive injury in Male mice.

    PubMed

    Zuloaga, Damian G; Wang, Jianming; Weber, Sydney; Mark, Gregory P; Murphy, Stephanie J; Raber, Jacob

    2016-08-01

    Emerging evidence indicates that methamphetamine (MA) abuse can impact cardiovascular disease. In humans, MA abuse is associated with an increased risk of stroke as well as an earlier age at which the stroke occurs. However, little is known about how chronic daily MA exposure can impact ischemic outcome in either humans or animal models. In the present study, mice were injected with MA (10 mg/kg, i.p.) or saline once daily for 10 consecutive days. Twenty-four hours after the final injection, mice were subjected to transient middle cerebral artery occlusion (tMCAO) for one hour followed by reperfusion. Mice were tested for novel object memory at 96 h post-reperfusion, just prior to removal of brains for quantification of infarct volume using 2,3,5-Triphenyltetrazolium Chloride (TTC) staining. Mice treated with MA prior to tMCAO showed decreased object memory recognition and increased infarct volume compared to saline-treated mice. These findings indicate that chronic MA exposure can worsen both cognitive and morphological outcomes following cerebral ischemia.

  1. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity

    PubMed Central

    Patel, Vaibhav B.; Mori, Jun; McLean, Brent A.; Basu, Ratnadeep; Das, Subhash K.; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M.; Grant, Maria B.; Lopaschuk, Gary D.

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance. PMID:26224885

  2. Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.

    PubMed

    Hourdé, Christophe; Joanne, Pierre; Medja, Fadia; Mougenot, Nathalie; Jacquet, Adeline; Mouisel, Etienne; Pannerec, Alice; Hatem, Stéphane; Butler-Browne, Gillian; Agbulut, Onnik; Ferry, Arnaud

    2013-05-01

    It is well known that inactivity/activity influences skeletal muscle physiological characteristics. However, the effects of inactivity/activity on muscle weakness and increased susceptibility to muscle contraction-induced injury have not been extensively studied in mdx mice, a murine model of Duchenne muscular dystrophy with dystrophin deficiency. In the present study, we demonstrate that inactivity (ie, leg immobilization) worsened the muscle weakness and the susceptibility to contraction-induced injury in mdx mice. Inactivity also mimicked these two dystrophic features in wild-type mice. In contrast, we demonstrate that these parameters can be improved by activity (ie, voluntary wheel running) in mdx mice. Biochemical analyses indicate that the changes induced by inactivity/activity were not related to fiber-type transition but were associated with altered expression of different genes involved in fiber growth (GDF8), structure (Actg1), and calcium homeostasis (Stim1 and Jph1). However, activity reduced left ventricular function (ie, ejection and shortening fractions) in mdx, but not C57, mice. Altogether, our study suggests that muscle weakness and susceptibility to contraction-induced injury in dystrophic muscle could be attributable, at least in part, to inactivity. It also suggests that activity exerts a beneficial effect on dystrophic skeletal muscle but not on the heart.

  3. Intra-Abdominal Complications after Curative Gastrectomies Worsen Prognoses of Patients with Stage II–III Gastric Cancer

    PubMed Central

    A.T.M. Abdul, Kader; Murakami, Yuki; Yoshimoto, Miwa; Onishi, Kazunari; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Fukumoto, Yoji; Takano, Shuichi; Tokuyasu, Naruo; Osaki, Tomohiro; Saito, Hiroaki; Ikeguchi, Masahide

    2016-01-01

    Background Postoperative complications have been shown to worsen prognoses of various cancer types. Methods We retrospectively analyzed 265 patients with stage II-III gastric cancer who underwent curative gastrectomies between 1991 and 2010 at Tottori University Hospital to determine the effect of postoperative intra-abdominal complication (IAC) on prognosis. Results Of the 265 patients, 38 (14.3%) developed postoperative IACs of grade ≥ 2, of whom significantly more patients were male. Patients in the IAC group were significantly older than patients in the non-complication (NC) group. The NC group had significantly better survival than did the IAC group (P < 0.0001). Within the IAC group, 5-year survival rates did not significantly differ between patients with infectious complication subgroup (24.6%) and the non-infectious subgroup (46.2%). Grade of complication was not related to prognosis. Lengths of time before starting adjuvant chemotherapy (AC) after surgery were significantly longer for the IAC group (55.3 ± 34.7 days) than for the NC group: (26.6 ± 11.9 days; P = 0.0023). Prognosis of patients who took AC within 6 weeks after surgery tended to be better than that of patients who took AC > 6 weeks after surgery (P = 0.071). In multivariate analysis, IAC was an independent predictor of prognosis, as were age, invasion depth, and lymph node metastasis. Conclusion Postoperative IACs were related to poorer survival for patients with stage II–III gastric cancer. PMID:27708536

  4. Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  5. Inflammation and Hyperglycemia Mediate Deaf1 Splicing in the Pancreatic Lymph Nodes via Distinct Pathways During Type 1 Diabetes

    PubMed Central

    Fuhlbrigge, Rebecca; Taylor, Cariel; Creusot, Remi J.; Nishikawa-Matsumura, Teppei; Whiting, Chan C.; Schartner, Jill M.; Akter, Rahima; von Herrath, Matthias; Fathman, C. Garrison

    2015-01-01

    Peripheral tolerance is partially controlled by the expression of peripheral tissue antigens (PTAs) in lymph node stromal cells (LNSCs). We previously identified a transcriptional regulator, deformed epidermal autoregulatory factor 1 (Deaf1), that can regulate PTA expression in LNSCs of the pancreatic lymph nodes (PLNs). During the pathogenesis of type 1 diabetes (T1D), Deaf1 is spliced to form the dominant-negative isoform Deaf1-Var1. Here we show that Deaf1-Var1 expression correlates with the severity of disease in NOD mice and is reduced in the PLNs of mice that do not develop hyperglycemia. Inflammation and hyperglycemia independently drive Deaf1 splicing through activation of the splicing factors Srsf10 and Ptbp2, respectively. Inflammation induced by injection of activated splenocytes increased Deaf1-Var1 and Srsf10, but not Ptbp2, in the PLNs of NOD.SCID mice. Hyperglycemia induced by treatment with the insulin receptor agonist S961 increased Deaf1-Var1 and Ptbp2, but not Srsf10, in the PLNs of NOD.B10 and NOD mice. Overexpression of PTBP2 and/or SRSF10 also increased human DEAF1-VAR1 and reduced PTA expression in HEK293T cells. These data suggest that during the progression of T1D, inflammation and hyperglycemia mediate the splicing of DEAF1 and loss of PTA expression in LNSCs by regulating the expression of SRSF10 and PTBP2. PMID:25187368

  6. Transgenerational Glucose Intolerance of Tumor Necrosis Factor with Epigenetic Alteration in Rat Perirenal Adipose Tissue Induced by Intrauterine Hyperglycemia

    PubMed Central

    Su, Rina; Yan, Jie; Yang, Huixia

    2016-01-01

    Changes in DNA methylation may play a role in the genetic mechanism underlying glucose intolerance in the offspring of mothers with diabetes. Here, we established a rat model of moderate intrauterine hyperglycemia induced by streptozotocin to detect glucose and lipid metabolism of first-generation (F1) and second-generation (F2) offspring. Moderate intrauterine hyperglycemia induced high body weight in F1 and F2 offspring of diabetic mothers. F1 offspring had impaired glucose tolerance and abnormal insulin level. Additionally, F1 and F2 offspring that were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets. The tumor necrosis factor (Tnf) gene was upregulated in perirenal adipose tissue from F1 offspring and relatively increased in F2 offspring. Both F1 and F2 offspring showed similar hypomethylation level at the −1952 site of Tnf. We confirmed that DNA methylation occurs in offspring exposed to intrauterine hyperglycemia and that the DNA methylation is intergenerational and inherited. PMID:26881249

  7. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    SciTech Connect

    Piteau, Shalea; Olver, Amy; Kim, Su-Jin; Winter, Kyle; Pospisilik, John Andrew; Lynn, Francis; Manhart, Susanne; Demuth, Hans-Ulrich; Speck, Madeleine; Pederson, Raymond A.; McIntosh, Christopher H.S.

    2007-11-03

    In type 2 diabetes (T2DM) {beta}-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 {+-} 3.8%) than ZF rats (48.8 {+-} 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 {+-} 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.

  8. Cadmium and naphthalene-induced hyperglycemia in the fiddler crab, Uca pugilator: Differential modes of action on the neutroendocrine system

    SciTech Connect

    Reddy, P.S.; Katyayani, R.V.; Fingerman, M.

    1996-03-01

    Hyperglycemia is a typical response of aquatic organisms to heavy metals. In crustaceans, the medulla terminalis X-organ-sinus gland neuroendocrine complex in the eyestalk is the source of the crustacean hyperglycemic hormone (CHH). The role of CHH in pollutant-induced b1ood glucose changes has only recently begun to be studied. Reddy provided evidence that CHH mediates cadmium-induced hyperglycemia in the red swamp crayfish, Procambarus clarkii. In a study of another hormonally-regulated function, color changes, cadmium exposure resulted in pigment in the melanophores of the fiddler crab, Uca pugilator, becoming less dispersed than in unexposed crabs. Earlier studies showed that, like cadmium, both a PCB, Aroclor 1242, and naphthalene induced black pigment aggregation in Uca poor. In general, when crabs are exposed to a pollutant, hydrocarbon or cadmium, they aggregate the pigment in their melanophores, but apparently by different mechanisms. Hydrocarbons appear to inhibit release of black pigment-dispersing hormone (BDPH), whereas cadmium appears to inhibit its synthesis. These apparent different modes of action of cadmium and naphthalene on the color change mechanism led us to compare the impact of these pollutants on the hormonal regulation of blood glucose in Uca pugilator. The present study was performed to determine (1) whether cadmium and naphthalene induce hyperglycemia in Uca pugilator, (2) whether CH has a role, if naphthalene and cadmium do induce hyperglycemia, and (3) the effects, if any, of cadmium and naphthalene on CHH activity in the eyestalk neuroendocrine complex.

  9. Sexual dimorphism of hyperglycemia and glucose tolerance in Wistar fatty rats.

    PubMed

    Kava, R A; West, D B; Lukasik, V A; Greenwood, M R

    1989-02-01

    Obese and lean male and female Wistar fatty rats were fed a high-sucrose (68% of calories) diet from 5 to 22 wk of age. Obese males, but not obese females, developed hyperglycemia in the fed state and were more glucose intolerant during an intragastric glucose tolerance test than obese females. Lean Wistar fatty rats did not become hyperglycemic on the sucrose diet. Obese males also showed a smaller insulin response during the glucose tolerance test than did obese females. The Wistar fatty rat is a sexually dimorphic model of non-insulin-dependent diabetes mellitus in which the male but not the female obese rats become diabetic. The diabetic condition and impaired glucose tolerance in the obese male Wistar fatty rat may be related to impaired pancreatic insulin release and peripheral insulin resistance.

  10. Anorexia nervosa complicated by diabetes mellitus: the case for permissive hyperglycemia.

    PubMed

    Brown, Carrie; Mehler, Philip S

    2014-09-01

    The coexistence of Type 1 Diabetes Mellitus and anorexia nervosa results in an increased incidence of known diabetic complications such as retinopathy and nephropathy, presumably because blood glucose is difficult to control within the throes of comorbid anorexia nervosa. In addition, even when a diabetic patient with anorexia nervosa has committed to resolving his or her eating disorder, glucose control is again difficult and fraught with complexity and peril as will be highlighted in the following case report. Prudence dictates that strict glucose control is not indicated for the relatively short period of time that constitutes the early stage of refeeding in a patient with severe anorexia nervosa. Rather, "permissive hyperglycemia" may be the more optimal course to pursue, as a clinical strategy which is considerate of both the criticality of the refeeding treatment plan and of the long-term nature of the diabetic illness.

  11. Current Understanding of Metformin Effect on the Control of Hyperglycemia in Diabetes

    PubMed Central

    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 the role of AMPK in metformin’s action and the mechanism of AMPK activation. In this review, we will discuss recent advances in the understanding of metformin’s suppression of hepatic glucose production and the mechanism related to the improvement of insulin signaling. PMID:26743209

  12. Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations.

    PubMed

    Ceriello, A; Marchi, E; Palazzni, E; Quatraro, A; Giugliano, D

    1990-01-01

    Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned héparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia.

  13. Hyper-G stress-induced hyperglycemia in rats mediated by glucoregulatory hormones

    NASA Technical Reports Server (NTRS)

    Daligcon, B. C.; Oyama, J.

    1985-01-01

    The present investigation is concerned with possible relations of the hyperglycemic response of rats exposed to hyper-G stress to (1) alterations in blood levels of the glucoregulatory hormones and gluconeogenic substrates, and (2) changes in insulin response on muscle glucose uptake. Male Sprague-Dawley rats weighing 250-300 g were used in the study. The results of the experiments indicate that the initial rapid rise in blood glucose of rats exposed to hyper-G stress is mediated by increases in circulating catecholamines and glucagon, both potent stimulators of hepatic gluconeogenesis. Lactate, derived from epinephrine stimulation of muscle glycogenolysis, appears to be a major precursor for the initial rise in blood glucose. The inhibition of the insulin-stimulated glucose uptake by muscle tissues may be a factor in the observed sustained hyperglycemia.

  14. Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.

    PubMed

    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. Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC

    PubMed Central

    2013-01-01

    Background Endothelial dysfunction precedes pathogenesis of vascular complications in diabetes. In recent years, the mechanisms of endothelial dysfunction were investigated to outline strategies for its treatment. However, the therapies for dysfunctional endothelium resulted in multiple clinical trial failures and remain elusive. There is a need for defining hyperglycemia-induced endothelial dysfunction with both generic and specific dysfunctional changes in endothelial cells (EC) using a systems approach. In this study, we investigated hyperglycemia-induced endothelial dysfunction in HUVEC and HMVEC. We investigated hyperglycemia-induced functional changes (superoxide (O2‾), and hydrogen peroxide (H2O2) production and mitochondrial membrane polarization) and gene expression fingerprints of related enzymes (nitric oxide synthase, NAD(P)H oxidase, and reactive oxygen species (ROS) neutralizing enzymes) in both ECs. Method Gene expression of NOS2, NOS3, NOX4, CYBA, UCP1, CAT, TXNRD1, TXNRD2, GPX1, NOX1, SOD1, SOD2, PRDX1, 18s, and RPLP0 were measured using real-time PCR. O2‾ production was measured with dihydroethidium (DHE) fluorescence measurement. H2O2 production was measured using Amplex Red assay. Mitochondrial membrane polarization was measured using JC-10 based fluorescence measurement. Results We showed that the O2‾ levels increased similarly in both ECs with hyperglycemia. However, these endothelial cells showed significantly different underlying gene expression profile, H2O2 production and mitochondrial membrane polarization. In HUVEC, hyperglycemia increased H2O2 production, and hyperpolarized mitochondrial membrane. ROS neutralizing enzymes SOD2 and CAT gene expression were downregulated. In contrast, there was an upregulation of nitric oxide synthase and NAD(P)H oxidase and a depolarization of mitochondrial membrane in HMVEC. In addition, ROS neutralizing enzymes SOD1, GPX1, TXNRD1 and TXNRD2 gene expression were significantly upregulated in high

  16. Hyperglycemia Reduces Functional Expression of Astrocytic Kir4.1 Channels and Glial Glutamate Uptake

    PubMed Central

    Rivera-Aponte, David E.; Méndez-González, Miguel P.; Rivera-Pagán, Aixa F.; Kucheryavykh, Yuriy V.; Kucheryavykh, Lilia Y.; Skatchkov, Serguei N.; Eaton, Misty J.

    2015-01-01

    Diabetics are at risk for a number of serious health complications including an increased incidence of epilepsy and poorer recovery after ischemic stroke. Astrocytes play a critical role in protecting neurons by maintaining extracellular homeostasis and preventing neurotoxicity through glutamate uptake and potassium buffering. These functions are aided by the presence of potassium channels, such as Kir4.1 inwardly rectifying potassium channels, in the membranes of astrocytic glial cells. The purpose of the present study was to determine if hyperglycemia alters Kir4.1 potassium channel expression and homeostatic functions of astrocytes. We used q-PCR, Western blot, patch-clamp electrophysiology studying voltage and potassium step responses and a colorimetric glutamate clearance assay to assess Kir4.1 channel levels and homeostatic functions of astrocytes grown in normal and high glucose conditions. We found that astrocytes grown in high glucose (25 mM) had an approximately 50% reduction in Kir4.1 mRNA and protein expression as compared with those grown in normal glucose (5 mM). These reductions occurred within 4 to 7 days of exposure to hyperglycemia, whereas reversal occurred between 7 to 14 days after return to normal glucose. The decrease in functional Kir channels in the astrocytic membrane was confirmed using barium to block Kir channels. In the presence of 100 μm barium, the currents recorded from astrocytes in response to voltage steps were reduced by 45%. Furthermore, inward currents induced by stepping extracellular [K+]o from 3 to 10 mM (reflecting potassium uptake) were 50% reduced in astrocytes grown in high glucose. In addition, glutamate clearance by astrocytes grown in high glucose was significantly impaired. Taken together, our results suggest that down-regulation of astrocytic Kir4.1 channels by elevated glucose may contribute to the underlying pathophysiology of diabetes-induced CNS disorders and contribute to the poor prognosis after stroke. PMID

  17. Dysregulation of peripheral endocannabinoid levels in hyperglycemia and obesity: Effect of high fat diets.

    PubMed

    Matias, Isabel; Petrosino, Stefania; Racioppi, Alessandro; Capasso, Raffaele; Izzo, Angelo A; Di Marzo, Vincenzo

    2008-04-16

    Increasing evidence indicates that endocannabinoid (EC) signalling is dysregulated during hyperglycemia and obesity, particularly at the level of anandamide (AEA) and/or 2-arachidonoylglycerol (2-AG) concentrations in tissues involved in the control of energy intake and processing, such as the liver, white adipose tissue and pancreas. Here we review this previous evidence and provide new data on the possible dysregulation of EC levels in organs with endocrine function (adrenal glands and thyroid), involved in energy expenditure (brown adipose tissue and skeletal muscle), or affected by the consequences of metabolic disorders (heart and kidney), obtained from mice fed for 3, 8 and 14 weeks with two different high fat diets (HFDs), with different fatty acid compositions and impact on fasting glucose levels. Statistically significant elevations (in the skeletal muscle, heart and kidney) or reductions (in the thyroid) of the levels of either AEA or 2-AG, or both, were found. Depending on the diet, these changes preceded or accompanied the development of overt obesity and/or hyperglycemia. In the adrenal gland, first a reduction and then an elevation of EC levels were observed. In the brown fat, a very early elevation of both AEA and 2-AG normalized levels was observed with one of the diets, whereas delayed decreases were explained by an increase of the amount of fat tissue weight induced by the HFDs. The potential implications of these and previous findings in the general framework of the proposed roles of the EC system in the control of metabolic, endocrine and cardiovascular and renal functions are discussed.

  18. GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.

    PubMed

    Marucci, Antonella; di Mauro, Lazzaro; Menzaghi, Claudia; Prudente, Sabrina; Mangiacotti, Davide; Fini, Grazia; Lotti, Giuseppe; Trischitta, Vincenzo; Di Paola, Rosa

    2013-01-01

    Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment strategies of type 2 diabetes. Down-regulation of GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired insulin signaling and action in cultured human liver cells. In addition, GALNT2 mRNA levels are down-regulated in liver of spontaneously insulin resistant, diabetic Goto-Kakizaki rats. To investigate the role of GALNT2 in human hyperglycemia, we measured GALNT2 mRNA expression levels in peripheral whole blood cells of 84 non-obese and 46 obese non-diabetic individuals as well as of 98 obese patients with type 2 diabetes. We also measured GALNT2 mRNA expression in human U937 cells cultured under different glucose concentrations. In vivo studies indicated that GALNT2 mRNA levels were significantly reduced from non obese control to obese non diabetic and to obese diabetic individuals (p<0.001). In vitro studies showed that GALNT2 mRNA levels was reduced in U937 cells exposed to high glucose concentrations (i.e. 25 mmol/l glucose) as compared to cells exposed to low glucose concentration (i.e. 5.5 mmol/l glucose +19.5 mmol/l mannitol). In conclusion, our data indicate that GALNT2 is down-regulated in patients with type 2 diabetes and suggest that this association is, at least partly, secondary to hyperglycemia. Further studies are needed to understand whether GALNT2 down-regulation plays a pathogenic role in maintaining and/or aggravating the metabolic abnormalities of diabetic milieu.

  19. Musa sapientum with exercises attenuates hyperglycemia and pancreatic islet cells degeneration in alloxan-diabetic rats

    PubMed Central

    Akinlolu, Adelaja Abdulazeez; Salau, Bamidele A.; Ekor, Martins; Otulana, Jubril

    2015-01-01

    Aim: We tested the hypothesis that administrations of methanolic extracts of Musa sapientum sucker (MEMS) with exercises attenuated hyperglycemia in alloxan-diabetic rats. Materials and Methods: A total of 40 adult male rats were divided into equal eight groups. Normoglycemic Group A was Control. Alloxan (180 mg/kg, i.p.) was administered to rats in Groups B - H to induce diabetes. Group B (diabetic control) received physiological saline. Groups C - H received MEMS (5 mg/kg), MEMS (10 mg/kg), Glibenclamide (5 mg/kg), MEMS (5 mg/kg) + exercises, MEMS (10 mg/kg) + exercises and Exercises only, respectively. Changes in body weight, blood glucose levels (BGL) and pancreatic histology were evaluated during or at the end of experiment. Body weights and BGL of rats were expressed as mean ± standard deviation and analyzed using the statistical software program SPSS 15. Statistical comparisons were done using the Student’s t-test for unpaired samples. Differences between groups were determined as significant at P ≤ 0.05. Results: Significantly (P < 0.05) decreased bodyweight was observed in B and H compared to A and C - G. Treatment with MEMS significantly (P < 0.05) decreased elevated BGL in C and D. Hypoglycemic effect of MEMS appeared enhanced with exercises in F and G. Exercises regimen alone (H) resulted in percentage reduction in BGL lower than those of C - G. Histopathological examinations revealed normal pancreas (A), atrophied islet cells (B), hyperplasia with adequate population of islet cells (C - G), and reduced hyperplasia of islet cells (H). Conclusion: MEMS with exercises attenuated hyperglycemia in alloxan-diabetic rats. PMID:26401408

  20. Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide.

    PubMed

    Kitasato, Lisa; Tojo, Taiki; Hatakeyama, Yuko; Kameda, Ryo; Hashikata, Takehiro; Yamaoka-Tojo, Minako

    2012-06-29

    The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing

  1. Pathogenesis and management of postprandial hyperglycemia: role of incretin-based therapies

    PubMed Central

    Gerich, John

    2013-01-01

    Postprandial plasma glucose concentrations are an important contributor to glycemic control. There is evidence suggesting that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic agents that predominantly reduce postprandial plasma glucose levels. DPP-4 inhibitors are associated with fewer gastrointestinal side effects than GLP-1 receptor agonists and are administered orally, unlike GLP-1 analogs, which are administered as subcutaneous injections. GLP-1 receptor agonists are somewhat more effective than DPP-4 inhibitors in reducing postprandial plasma glucose and are usually associated with significant weight loss. For these reasons, GLP-1 receptor agonists are generally preferred over DPP-4 inhibitors as part of combination treatment regimens in patients with glycated hemoglobin levels above 8.0%. This article reviews the pathogenesis of postprandial hyperglycemia, the mechanisms by which GLP-1 receptor agonists and DPP-4 inhibitors reduce postprandial plasma glucose concentrations, and the results of recent clinical trials (ie, published 2008 to October 2012) that evaluated the effects of these agents on postprandial plasma glucose levels when evaluated as monotherapy compared with placebo or as add-on therapy to metformin, a sulfonylurea, or insulin. Findings from recent clinical studies suggest that both GLP-1 receptor agonists and DPP-4 inhibitors could become valuable treatment options for optimizing glycemic control in patients unable to achieve glycated hemoglobin goals on basal insulin, with the added benefits of weight loss and a low risk of hypoglycemia. PMID:24403842

  2. Relationship between hyperglycemia, hormone disturbances, and clinical evolution in severely hyperglycemic post surgery critically ill children: an observational study

    PubMed Central

    2014-01-01

    Background To study hormonal changes associated with severe hyperglycemia in critically ill children and the relationship with prognosis and length of stay in intensive care. Methods Observational study in twenty-nine critically ill children with severe hyperglycemia defined as 2 blood glucose measurements greater than 180 mg/dL. Severity of illness was assessed using pediatric index of mortality (PIM2), pediatric risk of mortality (PRISM) score, and pediatric logistic organ dysfunction (PELOD) scales. Blood glucose, glycosuria, insulin, C-peptide, cortisol, corticotropin, insulinlike growth factor-1, growth hormone, thyrotropin, thyroxine, and treatment with insulin were recorded. β-cell function and insulin sensitivity and resistance were determined on the basis of the homeostatic model assessment (HOMA), using blood glucose and C-peptide levels. Results The initial blood glucose level was 249 mg/dL and fell gradually to 125 mg/dL at 72 hours. Initial β-cell function (49.2%) and insulin sensitivity (13.2%) were low. At the time of diagnosis of hyperglycemia, 50% of the patients presented insulin resistance and β-cell dysfunction, 46% presented isolated insulin resistance, and 4% isolated β-cell dysfunction. β-cell function improved rapidly but insulin resistance persisted. Initial glycemia did not correlate with any other factor, and there was no relationship between glycemia and mortality. Patients who died had higher cortisol and growth hormone levels at diagnosis. Length of stay was correlated by univariate analysis, but not by multivariate analysis, with C-peptide and glycemic control at 24 hours, insulin resistance, and severity of illness scores. Conclusions Critically ill children with severe hyperglycemia initially present decreased β-cell function and insulin sensitivity. Nonsurvivors had higher cortisol and growth hormone levels and developed hyperglycemia later than survivors. PMID:24628829

  3. Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity

    PubMed Central

    Deshpande, Mandar; Thandavarayan, Rajarajan A.; Xu, Jiang; Yang, Xiao-Ping; Palaniyandi, Suresh S.

    2016-01-01

    Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7–11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm2 Vs 221 ± 10 μm2; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction. PMID:27736868

  4. Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: new insights into the insulin effect.

    PubMed

    Francés, Daniel E; Ronco, María T; Monti, Juan A; Ingaramo, Paola I; Pisani, Gerardo B; Parody, Juan P; Pellegrino, José M; Sanz, Paloma Martín; Carrillo, María C; Carnovale, Cristina E

    2010-05-01

    In this study, we analyzed the contribution of hydroxyl radical in the liver apoptosis mediated by hyperglycemia through the Bax-caspase pathway and the effects of insulin protection against the apoptosis induced by hyperglycemia. Male adult Wistar rats were randomized in three groups: control (C) (sodium citrate buffer, i.p.), streptozotocin (STZ)-induced diabetic (SID) (STZ 60 mg/kg body weight, i.p.), and insulin-treated SID (SID+I; 15 days post STZ injection, SID received insulin s.c., twice a day, 15 days). Rats were autopsied on day 30. In liver tissue, diabetes promoted a significant increase in hydroxyl radical production which correlated with lipid peroxidation (LPO) levels. Besides, hyperglycemia significantly increased mitochondrial BAX protein expression, cytosolic cytochrome c levels, and caspase-3 activity leading to an increase in apoptotic index. Interestingly, the treatment of diabetic rats with desferoxamine or tempol (antioxidants/hydroxyl radical scavengers) significantly attenuated the increase in both hydroxyl radical production and in LPO produced by hyperglycemia, preventing apoptosis by reduction of mitochondrial BAX and cytosolic cytochrome c levels. Insulin treatment showed similar results. The finding that co-administration of antioxidants/hydroxyl radical scavengers together with insulin did not provide any additional benefit compared with those obtained using either inhibitors or insulin alone shows that it is likely that insulin prevents oxidative stress by reducing the effects of hydroxyl radicals. Importantly, insulin significantly increased apoptosis inhibitor protein expression by induction of its mRNA. Taken together, our studies support that, at least in part, the hydroxyl radical acts as a reactive intermediate, which leads to liver apoptosis in a model of STZ-mediated hyperglycemia. A new anti-apoptosis signal for insulin is shown, given by an increase of apoptosis inhibitor protein.

  5. Serum tonicity, extracellular volume and clinical manifestations in symptomatic dialysis-associated hyperglycemia treated only with insulin.

    PubMed

    Tzamaloukas, A H; Rohrscheib, M; Ing, T S; Siamopoulos, K C; Elisaf, M F; Spalding, C T

    2004-09-01

    The absence of osmotic diuresis modifies the effects of hyperglycemia on body fluids in patients with advanced renal failure. To determine the relationship between clinical manifestations and abnormalities in tonicity and extracellular volume in such patients, we analyzed 43 episodes of severe dialysis-associated hyperglycemia (serum glucose exceeding 600 mg/dL) treated only with insulin. The main manifestations were dyspnea in 22 cases (pulmonary edema in 19), nausea and vomiting in 15, coma in 13 and seizures in 3, while 5 patients had no symptoms. Treatment with insulin resulted in a decrease in serum glucose value from 913 +/- 197 mg/dL to 170 +/- 78 mg/dL, an increase in serum sodium level from 125 +/- 5 to 136 +/- 5 mmol/L, and a fall in calculated serum tonicity value from 300 +/- 13 to 282 +/- 11 mmol/kg (all at p < 0.001). The ratio of the change in serum sodium level over change in serum glucose concentration was -1.50 +/- 0.22 mmol/L per 100 mg/dL. The percent increase in extracellular volume secondary to hyperglycemia developing from the prior euglycemic state and calculated from changes in serum sodium and chloride concentrations, was 10.9% +/- 4.6% (1.5% +/- 0.6% per 100 mg/dL increase in serum glucose level). All clinical manifestations dissipated after correction of hyperglycemia in 42 patients. One woman developed during treatment a fatal myocardial infarction. Dialysis patients with severe hyperglycemia may develop symptoms as a result of hypertonicity and extracellular expansion. Insulin alone may be sufficient treatment for these symptoms. The changes in serum tonicity and electrolytes during treatment are consistent with theoretical predictions.

  6. Treatment of hyperglycaemia in patients with acute stroke.

    PubMed

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

    2016-03-01

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

  7. General Medical Considerations for the Wilderness Adventurer: Medical Conditions That May Worsen With or Present Challenges to Coping With Wilderness Exposure.

    PubMed

    Cushing, Tracy A; Roberts, William O; Hackett, Peter; Dexter, William W; Brent, Jeff S; Young, Craig C; Fudge, Jessie R; Hawkins, Seth C; DeLoughery, Thomas G; Thomas, Benjamin J; Tabin, Geoffrey C; Jacoby, Leah E; Asplund, Chad A

    2015-09-01

    Participation in wilderness and adventure sports is on the rise, and as such, practitioners will see more athletes seeking clearance to participate in these events. The purpose of this article is to describe specific medical conditions that may worsen or present challenges to the athlete in a wilderness environment.

  8. General Medical Considerations for the Wilderness Adventurer: Medical Conditions That May Worsen With or Present Challenges to Coping With Wilderness Exposure.

    PubMed

    Cushing, Tracy A; Roberts, William O; Hackett, Peter; Dexter, William W; Brent, Jeff S; Young, Craig C; Fudge, Jessie R; Hawkins, Seth C; DeLoughery, Thomas G; Thomas, Benjamin J; Tabin, Geoffrey C; Jacoby, Leah E; Asplund, Chad A

    2015-12-01

    Participation in wilderness and adventure sports is on the rise, and as such, practitioners will see more athletes seeking clearance to participate in these events. The purpose of this article is to describe specific medical conditions that may worsen or present challenges to the athlete in a wilderness environment.

  9. Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy.

    PubMed

    Zhan, Yang; Shi, Hong; Caligiuri, Stephanie P B; Wu, Yinghong; Declercq, Vanessa; Taylor, Carla G; Zahradka, Peter; Ogborn, Malcolm R; Aukema, Harold M

    2015-02-01

    Dietary conjugated linoleic acid (CLA) reduces indicators of early renal disease progression and the associated elevated cyclooxygenase (COX) levels in young obese rats with obesity-associated nephropathy (OAN). Therefore, renal function and injury and COX and its metabolites were assessed in obese fa/fa Zucker rats with more advanced renal disease. Obese rats at 16 weeks of age were provided with either cis(c)9, trans(t)11 (fa/fa-9,11) or t10,c12 (fa/fa-10,12) CLA for 8 weeks, and compared to lean (lean-CTL) and obese (fa/fa-CTL) rats provided the control diet without CLA. Obese rats displayed significantly reduced renal function and increased renal injury compared to lean rats. In the obese rat groups, glomerular hypertrophy was reduced in both CLA-supplemented groups. While all other measures of renal function or injury were not different in fa/fa-9,11 compared to fa/fa-CTL rats, the fa/fa-10,12 rats had greater renal hypertrophy, glomerular fibrosis, fibrosis, tubular casts and macrophage infiltration compared to the fa/fa-CTL and fa/fa-9,11 groups. The fa/fa-10,12 group also had elevated levels of renal COX1, which was associated with increased levels of two oxylipins produced by this enzyme, 6-keto-prostaglandin F(1α), and thromboxane B₂. Renal linoleic acid and its lipoxygenase products also were lower in obese compared to lean rats, but CLA supplementation had no effect on these or any other lipoxygenase oxylipins. In summary, supplementation with c9,t11 CLA did not improve more advanced OAN and t10,c12 CLA worsened the renal pathology. Altered production of select COX1 derived oxylipins was associated with the detrimental effect of the t10,c12 isomer.

  10. Clinical characteristics related to worsening of motor function assessed by the Unified Parkinson's Disease Rating Scale in the elderly population.

    PubMed

    Liepelt-Scarfone, Inga; Lerche, Stefanie; Behnke, Stefanie; Godau, Jana; Gaenslen, Alexandra; Pausch, Christoph; Fassbender, Klaus; Brockmann, Kathrin; Srulijes, Karin; Huber, Heiko; Wurster, Isabel; Berg, Daniela

    2015-02-01

    There is evidence that nigrostriatal pathology may at least partly underlie mild Parkinsonian signs. We evaluated whether an increase in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) could be predicted by the presence of risk and prodromal markers for neurodegenerative diseases in elderly individuals without those diseases. Therefore, we analyzed the UPDRS-III score and various risk and prodromal markers known to antecede neurodegenerative diseases in a population-based cohort comprising 807 individuals free of neurodegenerative diseases at baseline. After 5 years, eight persons (1.0 %) were diagnosed with Parkinson's Disease (PD). Of those, seven (87.5 %) had motor worsening ≥3 points on the UPDRS-III from baseline to follow-up, one had two points increase. Of the 788 people without PD, 568 (72.1 %) showed no increase in the UPDRS-III scale, 220 (27.9 %) had ≥1 point increase and out of these 104 (13.2 %) had an increase of ≥3 points in the UPDRS-III score after 5 years. We identified an age >60 years (relative risk, RR = 1.7; confidence interval, CI 1.3-2.1) and the occurrence of ≥2 risk factors (RR = 1.5; CI 1.2-1.9) as possible predictors of motor progression. After 5 years, individuals with an increase in the UPDRS-III score had more often a one-sided reduced arm swing (p < 0.001) and identified less odors in the Sniffin' sticks test (p < 0.041) than persons with stable motor performance. Our data support the assumption that progression of Parkinsonian signs assessed by the UPDRS-III parallels the development of prodromal markers for neurodegenerative diseases in the elderly population.

  11. Caregivers had neighbourhood support but perceived it unsatisfactory and worsened: England Community Life Survey, 2012-2014.

    PubMed

    Shiue, Ivy

    2017-03-11

    There has been limited research studying neighbourhood support for caregivers. Therefore, the aim of the present study was to investigate the support from neighbourhoods between both caregivers and non-caregivers in a country-wide and population-based setting. Data were retrieved from England Community Life Survey, 2012-2014, a new annual household survey conducted by face-to-face interview since 2012, with a representative sample size of 5-6000 adult (aged 16 years and over) resident per year in England. Chi-square test and logistic regression modelling were performed to examine the variance in support from and perception toward neighbourhoods between caregivers and non-caregivers. Of 15,320 study participants, 2315 (16.0%) had a caring responsibility. There was not much variance in feeling belonging, comfortably asking neighbours to keep keys, comfortably asking neighbours to mind children, believing neighbours pulling together and trusting people in the neighbourhood between caregivers and non-caregivers. However, caregivers seemed to be more likely to chat to neighbours (OR 0.77, 95% CI 0.69-0.87, P < 0.001) and comfortably ask neighbours to help collect grocery (OR 0.89, 95% CI 0.81-0.98, P = 0.023). In addition, caregivers tended to perceive their neighbourhoods unsatisfactory (OR 1.17, 95% CI 1.05-1.32, P = 0.007) and worsened in the last 2 years (OR 1.36, 95% CI 1.22-1.51, P < 0.001). For future research, a longitudinal neighbourhood monitoring surveillance for all people would be suggested. For practice and policy, environmental health and nursing programs might need to extend education trainings and interventions to cover all neighbourhoods at different time points that can lessen both disease and caregiving burden and therefore optimize health and quality of life.

  12. Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats.

    PubMed

    Yarrow, Joshua F; Toklu, Hale Z; Balaez, Alex; Phillips, Ean G; Otzel, Dana M; Chen, Cong; Wronski, Thomas J; Aguirre, J Ignacio; Sakarya, Yasemin; Tümer, Nihal; Scarpace, Philip J

    2016-04-01

    Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23-34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that "westernized" HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development.

  13. Infrared warming reduced winter wheat yields and some physiological parameters, which were mitigated by irrigation and worsened by delayed sowing.

    PubMed

    Fang, Shibo; Su, Hua; Liu, Wei; Tan, Kaiyan; Ren, Sanxue

    2013-01-01

    Winter wheat has a central role in ensuring the food security and welfare of 1.3 billion people in China. Extensive previous studies have concluded that winter wheat yields would decrease with higher temperatures, owing to warming-induced soil drying or shortening of phenophase. Temperature in China is predicted to increase by 1-5°C by 2100, which may greatly impact plant production and cause other negative effects. We performed a manipulative field experiment, creating diverse growth regimes for wheat by infrared radiation (IR) warming day and night, including IR warming only (DW), IR warming + delayed sowing dates (DS), IR warming + increased irrigation (IW), and a control (CK). The results show that IR warming increased daily average wheat canopy and soil temperatures by 2.0°C and 2.3°C, respectively. DW was associated with an advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on the photosynthetic apparatus of wheat varied with season as well as significant differences were found in the booting stage. DS represented a worsened situation, lowering yield per plant by 16.4%, with a significant decline in aboveground biomass and functional leaf area. Wheat under DS showed double-peak patterns of diurnal gas exchange during booting stages and, consequently, lower photosynthetic capacity with high transpiration for cooling. Significantly lower actual water use efficiency and intrinsic water use efficiency from jointing to anthesis stages were also found under DS. However, IW had no significant difference from CK, irrespective of yield and photosynthesis. Therefore, we concluded that delayed sowing date may not be a good choice for winter wheat, whereas a thoroughly-watered wheat agroecosystem should be promoted in the context of global warming.

  14. Infrared Warming Reduced Winter Wheat Yields and Some Physiological Parameters, Which Were Mitigated by Irrigation and Worsened by Delayed Sowing

    PubMed Central

    Fang, Shibo; Su, Hua; Liu, Wei; Tan, Kaiyan; Ren, Sanxue

    2013-01-01

    Winter wheat has a central role in ensuring the food security and welfare of 1.3 billion people in China. Extensive previous studies have concluded that winter wheat yields would decrease with higher temperatures, owing to warming-induced soil drying or shortening of phenophase. Temperature in China is predicted to increase by 1–5°C by 2100, which may greatly impact plant production and cause other negative effects. We performed a manipulative field experiment, creating diverse growth regimes for wheat by infrared radiation (IR) warming day and night, including IR warming only (DW), IR warming + delayed sowing dates (DS), IR warming + increased irrigation (IW), and a control (CK). The results show that IR warming increased daily average wheat canopy and soil temperatures by 2.0°C and 2.3°C, respectively. DW was associated with an advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on the photosynthetic apparatus of wheat varied with season as well as significant differences were found in the booting stage. DS represented a worsened situation, lowering yield per plant by 16.4%, with a significant decline in aboveground biomass and functional leaf area. Wheat under DS showed double-peak patterns of diurnal gas exchange during booting stages and, consequently, lower photosynthetic capacity with high transpiration for cooling. Significantly lower actual water use efficiency and intrinsic water use efficiency from jointing to anthesis stages were also found under DS. However, IW had no significant difference from CK, irrespective of yield and photosynthesis. Therefore, we concluded that delayed sowing date may not be a good choice for winter wheat, whereas a thoroughly-watered wheat agroecosystem should be promoted in the context of global warming. PMID:23874424

  15. Testicular ischemia following mesh hernia repair and acute prostatitis

    PubMed Central

    Pietro, Pepe; Francesco, Aragona

    2007-01-01

    We present a case of a man admitted to our Hospital for right acute scrotum that six months before had undergone a right hernioplasty with mesh implantation. Clinical history and testicular color Doppler sonography (CDS) patterns suggested an orchiepididymitis following acute prostatitis. After 48h the clinical picture worsened and testicular CDS showed a decreased telediastolic velocity that suggested testicular ischemia. The patient underwent surgical exploration: spermatic cord appeared stretched by an inflammatory tissue in absence of torsion and releasing of spermatic cord was performed. In patients with genitourinary infection who previously underwent inguinal mesh implantation, testicular CDS follow-up is mandatory. PMID:19718342

  16. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes.

    PubMed

    Mathews, Clayton E; Xue, Song; Posgai, Amanda; Lightfoot, Yaima L; Li, Xia; Lin, Andrea; Wasserfall, Clive; Haller, Michael J; Schatz, Desmond; Atkinson, Mark A

    2015-11-01

    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.

  17. Hyperglycemia-induced teratogenesis is mediated by a functional deficiency of arachidonic acid.

    PubMed Central

    Goldman, A S; Baker, L; Piddington, R; Marx, B; Herold, R; Egler, J

    1985-01-01

    Congenital malformations now represent the largest single cause of mortality in the infant of the diabetic mother. The mechanism by which diabetes exerts its teratogenic effects is not known. This study evaluated whether arachidonic acid might be involved, a possibility raised by the role of arachidonic acid in palatal elevation and fusion, processes analogous to neural tube folding and fusion. This hypothesis was tested in two animal models of diabetic embryopathy, the in vivo pregnant diabetic rat and the in vitro hyperglycemic mouse embryo culture. The subcutaneous injection of arachidonic acid (200-400 mg/kg per day) into pregnant diabetic rats during the period of organ differentiation (days 6-12) did not alter the maternal glucose concentration, the maternal weight gain, or the weight of the embryos. However, the incidence of neural tube fusion defects was reduced from 11% to 3.8% (P less than 0.005), the frequency of cleft palate was reduced from 11% to 4% (P less than 0.005), and the incidence of micrognathia was reduced from 7% to 0.8% (P less than 0.001). The addition of arachidonic acid to B10.A mouse embryos in culture also resulted in a reversal of hyperglycemia-induced teratogenesis. The teratogenic effect of D-glucose (8 mg/ml) in the medium resulted in normal neural tube fusion in only 32% of the embryos (P less than 0.006 when compared to controls). Arachidonic acid supplementation (1 or 10 micrograms/ml) produced a rate of neural tube fusion (67%) that was not significantly different from that observed in controls. The evidence presented indicates that arachidonic acid supplementation exerts a significant protective effect against the teratogenic action of hyperglycemia in both in vivo (rat) and in vitro (mouse) animal models. These data therefore suggest that the mechanism mediating the teratogenic effect of an increased glucose concentration involves a functional deficiency of arachidonic acid at a critical stage of organogenesis. Images PMID

  18. Hyperglycemia is Associated with the Incidence of Frailty and Lower Extremity Mobility Limitations in Older Women

    PubMed Central

    Kalyani, Rita Rastogi; Tian, Jing; Xue, Qian-Li; Walston, Jeremy; Cappola, Anne R.; Fried, Linda P.; Brancati, Frederick L.; Blaum, Caroline S.

    2012-01-01

    Objectives To determine the degree to which hyperglycemia predicts the development of frailty and/or lower extremity mobility limitations. Design Secondary data analysis of longitudinal data collected in a prospective cohort study. Setting Baltimore, Maryland Participants We examined 329 women from the Women’s Health and Aging Studies II aged 70–79 years at baseline who had all variables needed for analysis. Methods Hemoglobin A1c [HbA1c] at baseline was the independent variable and categorized as: <5.5%, 5.5 to 5.9%, 6.0–6.4%, 6.5–7.9%, ≥8%. The incidence of frailty and lower extremity mobility limitations (based on self-reported walking difficulty, walking speed, and short performance physical battery [SPPB] score) was determined (follow-up≈9 years). Frailty was assessed using the Cardiovascular Health Study criteria. Covariates included demographics, body mass index, interleukin-6, and clinical history of comorbidities. Statistical analyses included Kaplan-Meier survival curves and Cox regression models adjusting for key covariates. Results In time-to-event analyses, HbA1c category was associated with incidence of walking difficulty (p=0.049) and low physical performance (p=0.001); association with incidence of frailty and low walking speed had a trend towards significance (both p=0.10). In demographics-adjusted regression models, HbA1c≥8% (versus<5.5%) was associated with an approximately three-times increased risk of incident frailty and three-to-five times increased risk of lower extremity mobility limitations (all p<0.05). In fully adjusted models, HbA1c≥8% (versus<5.5%) was associated with incident frailty (hazard ratio[HR]=3.33, 95% confidence interval=1.24–8.93), walking difficulty (HR=3.47,1.26–9.55), low walking speed (HR=2.82,1.19–6.71), and low physical performance (HR=3.60,1.52–8.53). Conclusions Hyperglycemia is associated with the development of frailty and lower extremity mobility limitations in older women; future studies

  19. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

    SciTech Connect

    Mitrakou, A.; Kelley, D.; Veneman, T.; Jenssen, T.; Pangburn, T.; Reilly, J.; Gerich, J. )

    1990-11-01

    To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with (14C)glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2. In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects, but glucose Rd was not significantly different in NIDDM and nondiabetic subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.

  20. Treatment for acute asthma in the Emergency Department: practical aspects.

    PubMed

    Urso, D L

    2010-03-01

    This article describes the management of acute asthma exacerbation in the Emergency Department (ED). An asthma exacerbation can be defined as clinical worsening of disease or an asymptomatic decrease in peak flows. Acute exacerbations of asthma may represent reactions to airway irritants or failures of chronic treatment. Hospitalizations and ED visits account for a large proportion of the health-care cost burden of asthma. The assessment of an asthma exacerbation constitutes a process with two different dimensions: to determine the severity of attack, and to evaluate the response to treatment. The principal goals of managing an asthma acute exacerbation may be summarized as maintenance of adequate arterial oxygen saturation with supplemental oxygen, relief of airflow obstruction with repetitive administration of short acting beta-2 agonists (SABA), and treatment of airway inflammation with systemic corticosteroids (CS) to prevent future relapses. SABA, oxygen, and CS form the basis of management of acute asthma exacerbation but a role is emerging for anthicolinergics.

  1. Diabetes mellitus, hyperglycemia, hemoglobin A1C and the risk of prosthetic joint infections in total hip and knee arthroplasty.

    PubMed

    Maradit Kremers, Hilal; Lewallen, Laura W; Mabry, Tad M; Berry, Daniel J; Berbari, Elie F; Osmon, Douglas R

    2015-03-01

    Diabetes mellitus is an established risk factor for infections but evidence is conflicting to what extent perioperative hyperglycemia, glycemic control and treatment around the time of surgery modify the risk of prosthetic joint infections (PJIs). In a cohort of 20,171 total hip and knee arthroplasty procedures, we observed a significantly higher risk of PJIs among patients with a diagnosis of diabetes mellitus (hazard ratio [HR] 1.55, 95% CI 1.11, 2.16), patients using diabetes medications (HR 1.56, 95% CI 1.08, 2.25) and patients with perioperative hyperglycemia (HR 1.59, 95% CI 1.07, 2.35), but the effects were attenuated after adjusting for body mass index, type of surgery, ASA score and operative time. Although data were limited, there was no association between hemoglobin A1c values and PJIs.

  2. Hyperglycemia Induces Skin Barrier Dysfunctions with Impairment of Epidermal Integrity in Non-Wounded Skin of Type 1 Diabetic Mice

    PubMed Central

    Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakagawa, Takahiko; Nakae, Yuki; Terashima, Tomoya; Kurakane, Takeshi; Kubota, Mamoru; Maegawa, Hiroshi; Udagawa, Jun

    2016-01-01

    Diabetes causes skin complications, including xerosis and foot ulcers. Ulcers complicated by infections exacerbate skin conditions, and in severe cases, limb/toe amputations are required to prevent the development of sepsis. Here, we hypothesize that hyperglycemia induces skin barrier dysfunction with alterations of epidermal integrity. The effects of hyperglycemia on the epidermis were examined in streptozotocin-induced diabetic mice with/without insulin therapy. The results showed that dye leakages were prominent, and transepidermal water loss after tape stripping was exacerbated in diabetic mice. These data indicate that hyperglycemia impaired skin barrier functions. Additionally, the distribution of the protein associated with the tight junction structure, tight junction protein-1 (ZO-1), was characterized by diffuse and significantly wider expression in the diabetic mice compared to that in the control mice. In turn, epidermal cell number was significantly reduced and basal cells were irregularly aligned with ultrastructural alterations in diabetic mice. In contrast, the number of corneocytes, namely, denucleated and terminally differentiated keratinocytes significantly increased, while their sensitivity to mechanical stress was enhanced in the diabetic mice. We found that cell proliferation was significantly decreased, while apoptotic cells were comparable in the skin of diabetic mice, compared to those in the control mice. In the epidermis, Keratin 5 and keratin 14 expressions were reduced, while keratin 10 and loricrin were ectopically induced in diabetic mice. These data suggest that hyperglycemia altered keratinocyte proliferation/differentiation. Finally, these phenotypes observed in diabetic mice were mitigated by insulin treatment. Reduction in basal cell number and perturbation of the proliferation/differentiation process could be the underlying mechanisms for impaired skin barrier functions in diabetic mice. PMID:27846299

  3. Hyperglycemia and advanced glycosylation end products suppress adipocyte apoE expression: implications for adipocyte triglyceride metabolism.

    PubMed

    Espiritu, Doris Joy; Huang, Zhi Hua; Zhao, Yong; Mazzone, Theodore

    2010-10-01

    Endogenous adipocyte apolipoprotein E (apoE) plays an important role in adipocyte lipoprotein metabolism and lipid flux. A potential role for hyperglycemia in regulating adipocyte apoE expression and triglyceride metabolism was examined. Exposure of adipocytes to high glucose or advanced glycosylation end product-BSA significantly suppressed apoE mRNA and protein levels. This suppression was significantly attenuated by antioxidants or inhibitors of the NF-κB transcription pathway. Hyperglycemia in vivo led to adipose tissue oxidant stress and significant reduction in adipose tissue and adipocyte apoE mRNA level. Incubation with antioxidant in organ culture completely reversed this suppression. Hyperglycemia also reduced adipocyte triglyceride synthesis, and this could be completely reversed by adenoviral-mediated increases in apoE. To more specifically evaluate an in vivo role for adipocyte apoE expression on organismal triglyceride distribution in vivo, WT or apoE knockout (EKO) adipose tissue was transplanted in EKO recipient mice. After 12 wk, WT adipocytes transplanted in EKO mice accumulated more triglyceride compared with transplanted EKO adipocytes. In addition, EKO recipients of WT adipose tissue had reduced hepatic triglyceride content compared with EKO recipients transplanted with EKO adipose tissue. Our results demonstrate that hyperglycemia and advanced glycosylation end products suppress the expression of adipocyte apoE in vitro and in vivo and thereby reduce adipocyte triglyceride synthesis. In vivo results using adipose tissue transplantation suggest that reduction of adipocyte apoE, and subsequent reduction of adipocyte triglyceride accumulation, could influence lipid accumulation in nonadipose tissue.

  4. Analysis of the effect of canagliflozin on renal glucose reabsorption and progression of hyperglycemia in zucker diabetic Fatty rats.

    PubMed

    Kuriyama, Chiaki; Xu, Jun Zhi; Lee, Seunghun Paul; Qi, Jenson; Kimata, Hirotaka; Kakimoto, Tetsuhiro; Nakayama, Keiko; Watanabe, Yoshinori; Taniuchi, Nobuhiko; Hikida, Kumiko; Matsushita, Yasuaki; Arakawa, Kenji; Saito, Akira; Ueta, Kiichiro; Shiotani, Masaharu

    2014-11-01

    Sodium-glucose cotransporter 2 (SGLT2) plays a major role in renal glucose reabsorption. To analyze the potential of insulin-independent blood glucose control, the effects of the novel SGLT2 inhibitor canagliflozin on renal glucose reabsorption and the progression of hyperglycemia were analyzed in Zucker diabetic fatty (ZDF) rats. The transporter activity of recombinant human and rat SGLT2 was inhibited by canagliflozin, with 150- to 12,000-fold selectivity over other glucose transporters. Moreover, in vivo treatment with canagliflozin induced glucosuria in mice, rats, and dogs in a dose-dependent manner. It inhibited apparent glucose reabsorption by 55% in normoglycemic rats and by 94% in hyperglycemic rats. The inhibition of glucose reabsorption markedly reduced hyperglycemia in ZDF rats but did not induce hypoglycemia in normoglycemic animals. The change in urinary glucose excretion should not be used as a marker to predict the glycemic effects of this SGLT2 inhibitor. In ZDF rats, plasma glucose and HbA1c levels progressively increased with age, and pancreatic β-cell failure developed at 13 weeks of age. Treatment with canagliflozin for 8 weeks from the prediabetic stage suppressed the progression of hyperglycemia, prevented the decrease in plasma insulin levels, increased pancreatic insulin contents, and minimized the deterioration of islet structure. These results indicate that selective inhibition of SGLT2 with canagliflozin controls the progression of hyperglycemia by inhibiting renal glucose reabsorption in ZDF rats. In addition, the preservation of β-cell function suggests that canagliflozin treatment reduces glucose toxicity via an insulin-independent mechanism.

  5. Hyperglycemia Induces Skin Barrier Dysfunctions with Impairment of Epidermal Integrity in Non-Wounded Skin of Type 1 Diabetic Mice.

    PubMed

    Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakagawa, Takahiko; Nakae, Yuki; Terashima, Tomoya; Kurakane, Takeshi; Kubota, Mamoru; Maegawa, Hiroshi; Udagawa, Jun

    2016-01-01

    Diabetes causes skin complications, including xerosis and foot ulcers. Ulcers complicated by infections exacerbate skin conditions, and in severe cases, limb/toe amputations are required to prevent the development of sepsis. Here, we hypothesize that hyperglycemia induces skin barrier dysfunction with alterations of epidermal integrity. The effects of hyperglycemia on the epidermis were examined in streptozotocin-induced diabetic mice with/without insulin therapy. The results showed that dye leakages were prominent, and transepidermal water loss after tape stripping was exacerbated in diabetic mice. These data indicate that hyperglycemia impaired skin barrier functions. Additionally, the distribution of the protein associated with the tight junction structure, tight junction protein-1 (ZO-1), was characterized by diffuse and significantly wider expression in the diabetic mice compared to that in the control mice. In turn, epidermal cell number was significantly reduced and basal cells were irregularly aligned with ultrastructural alterations in diabetic mice. In contrast, the number of corneocytes, namely, denucleated and terminally differentiated keratinocytes significantly increased, while their sensitivity to mechanical stress was enhanced in the diabetic mice. We found that cell proliferation was significantly decreased, while apoptotic cells were comparable in the skin of diabetic mice, compared to those in the control mice. In the epidermis, Keratin 5 and keratin 14 expressions were reduced, while keratin 10 and loricrin were ectopically induced in diabetic mice. These data suggest that hyperglycemia altered keratinocyte proliferation/differentiation. Finally, these phenotypes observed in diabetic mice were mitigated by insulin treatment. Reduction in basal cell number and perturbation of the proliferation/differentiation process could be the underlying mechanisms for impaired skin barrier functions in diabetic mice.

  6. Therapeutic Potential of Moringa oleifera Leaves in Chronic Hyperglycemia and Dyslipidemia: A Review

    PubMed Central

    Mbikay, Majambu

    2012-01-01

    Moringa oleifera (M. oleifera) is an angiosperm plant, native of the Indian subcontinent, where its various parts have been utilized throughout history as food and medicine. It is now cultivated in all tropical and sub-tropical regions of the world. The nutritional, prophylactic, and therapeutic virtues of this plant are being extolled on the Internet. Dietary consumption of its part is therein promoted as a strategy of personal health preservation and self-medication in various diseases. The enthusiasm for the health benefits of M. oleifera is in dire contrast with the scarcity of strong experimental and clinical evidence supporting them. Fortunately, the chasm is slowly being filled. In this article, I review current scientific data on the corrective potential of M. oleifera leaves in chronic hyperglycemia and dyslipidemia, as symptoms of diabetes and cardiovascular disease (CVD) risk. Reported studies in experimental animals and humans, although limited in number and variable in design, seem concordant in their support for this potential. However, before M. oleifera leaf formulations can be recommended as medication in the prevention or treatment of diabetes and CVD, it is necessary that the scientific basis of their efficacy, the therapeutic modalities of their administration and their possible side effects be more rigorously determined. PMID:22403543

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

    PubMed Central

    Larsen, Steen; Scheede-Bergdahl, Celena; Whitesell, Thomas; Boushel, Robert; Bergdahl, Andreas

    2015-01-01

    Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost or complete insulin deficiency. Widespread tissue dysfunction and deleterious diabetes-complications are associated with long-term elevations of blood glucose. The aim of this study was to investigate the effects of type I diabetes, as induced by streptozotocin, on the mitochondria in skeletal muscles that predominantly consist of either slow or fast twitch fibers. Soleus (primarily slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type) were removed in order to measure mitochondrial protein expression and integrated mitochondrial respiratory function. Mitochondrial capacity for oxidative phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative) soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOS capacity, whereas no difference was detected between the groups when evaluating the more physiological 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 patients. PMID:26197936

  8. Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents

    PubMed Central

    Scarlett, Jarrad M.; Rojas, Jennifer M.; Matsen, Miles E.; Kaiyala, Karl J.; Stefanovski, Darko; Bergman, Richard N.; Nguyen, Hong T.; Dorfman, Mauricio D.; Lantier, Louise; Wasserman, David H.; Mirzadeh, Zaman; Unterman, Terry G.; Morton, Gregory J.; Schwartz, Michael W.

    2016-01-01

    Type 2 diabetes (T2D) is among the most common and costly disorders worldwide1. The goal of current medical management of T2D is to transiently ameliorate hyperglycemia through daily dosing of one or more anti-diabetic drugs. Hypoglycemia and weight are common side effects of therapy, and sustained disease remission is not obtainable with non-surgical approaches. Based on the potent glucose-lowering response elicited by activation of brain fibroblast growth factor (FGF) receptors2–4, we explored the anti-diabetic efficacy of centrally administered FGF1, which, unlike other FGF peptides, activates all FGF receptor subtypes5. We report that a single intracerebroventricular (i.c.v.) injection of FGF1 at a dose one-tenth of that needed for systemic anti-diabetic efficacy induces sustained diabetes remission in both mouse and rat models of T2D. This anti-diabetic effect is not secondary to weight loss, does not increase the risk of hypoglycemia, and involves a novel and incompletely understood mechanism for increasing glucose clearance from the bloodstream. We conclude that the brain has the inherent potential to induce diabetes remission and that brain FGF receptors are potential pharmacological targets for achieving this goal. PMID:27213816

  9. Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes.

    PubMed

    Fu, Zhuo; Gilbert, Elizabeth R; Pfeiffer, Liliane; Zhang, Yanling; Fu, Yu; Liu, Dongmin

    2012-06-01

    While peripheral insulin resistance is common during obesity and aging in mice and people, the progression to type 2 diabetes (T2D) is largely due to loss of β-cell mass and function through apoptosis. We recently reported that genistein, a soy derived isoflavone, can improve glycemic control and β-cell function in insulin-deficient diabetic mice. However, whether it can prevent β-cell loss and diabetes in T2D mice is unknown. Our current study aimed to investigate the effect of dietary supplemented genistein in a nongenetic T2D mouse model. Nongenetic, middle-aged obese diabetic mice were generated by high fat diet and a low dose of streptozotocin injection. The effect of dietary supplementation of genistein on glycemic control and β-cell mass and function was determined. Dietary intake of genistein (250 mg·kg(-1) diet) improved hyperglycemia, glucose tolerance, and blood insulin level in obese diabetic mice, whereas it did not affect body weight gain, food intake, fat deposit, plasma lipid profile, and peripheral insulin sensitivity. Genistein increased the number of insulin-positive β-cell in islets, promoted islet β-cell survival, and preserved islet mass. In conclusion, dietary intake of genistein could prevent T2D via a direct protective action on β-cells without alteration of periphery insulin sensitivity.

  10. Parp Inhibition Prevents Ten-Eleven Translocase Enzyme Activation and Hyperglycemia-Induced DNA Demethylation

    PubMed Central

    Dhliwayo, Nyembezi; Sarras, Michael P.; Luczkowski, Ernest; Mason, Samantha M.

    2014-01-01

    Studies from human cells, rats, and zebrafish have documented that hyperglycemia (HG) induces the demethylation of specific cytosines throughout the genome. We previously documented that a subset of these changes become permanent and may provide, in part, a mechanism for the persistence of complications referred to as the metabolic memory phenomenon. In this report, we present studies aimed at elucidating the molecular machinery that is responsible for the HG-induced DNA demethylation observed. To this end, RNA expression and enzymatic activity assays indicate that the ten-eleven translocation (Tet) family of enzymes are activated by HG. Furthermore, through the detection of intermediates generated via conversion of 5-methyl-cytosine back to the unmethylated form, the data were consistent with the use of the Tet-dependent iterative oxidation pathway. In addition, evidence is provided that the activity of the poly(ADP-ribose) polymerase (Parp) enzyme is required for activation of Tet activity because the use of a Parp inhibitor prevented demethylation of specific loci and the accumulation of Tet-induced intermediates. Remarkably, this inhibition was accompanied by a complete restoration of the tissue regeneration deficit that is also induced by HG. The ultimate goal of this work is to provide potential new avenues for therapeutic discovery. PMID:24722243

  11. Vitamin C intake reduces the cytotoxicity associated with hyperglycemia in prediabetes and type 2 diabetes.

    PubMed

    Franke, Silvia Isabel Rech; Müller, Luiza Louzada; Santos, Maria Carolina; Fishborn, Arcênio; Hermes, Liziane; Molz, Patrícia; Pereira, Camila Schreiner; Wichmann, Francisca Maria Assmann; Horta, Jorge André; Maluf, Sharbel Weidner; Prá, Daniel

    2013-01-01

    Hyperglycemia leads to the formation of free radicals and advanced glycation end-products (AGEs). Antioxidants can reduce the level of protein glycation and DNA damage. In this study, we compared the levels of vitamin C intake, which is among the most abundant antioxidants obtained from diet, with the levels of fasting plasma glucose (FPG), glycated hemoglobin (A1C), DNA damage, and cytotoxicity in prediabetic subjects and type 2 diabetic subjects. Our results indicated that there was no significant correlation between FPG or A1C and DNA damage parameters (micronuclei, nucleoplasmic bridges, and nuclear buds). FPG and A1C correlated with necrosis (r = 0.294; P = 0.013 and r = 0.401; P = 0.001, resp.). Vitamin C intake correlated negatively with necrosis and apoptosis (r = -0.246; P = 0.040, and r = -0.276; P = 0.021, resp.). The lack of a correlation between the FPG and A1C and DNA damage could be explained, at least in part, by the elimination of cells with DNA damage by either necrosis or apoptosis (cytotoxicity). Vitamin C appeared to improve cell survival by reducing cytotoxicity. Therefore, the present results indicate the need for clinical studies to evaluate the effect of low-dose vitamin C supplementation in type 2 diabetes.

  12. Acid Sphingomyelinase Deficiency Prevents Diet-induced Hepatic Triacylglycerol Accumulation and Hyperglycemia in Mice*

    PubMed Central

    Deevska, Gergana M.; Rozenova, Krassimira A.; Giltiay, Natalia V.; Chambers, Melissa A.; White, James; Boyanovsky, Boris B.; Wei, Jia; Daugherty, Alan; Smart, Eric J.; Reid, Michael B.; Merrill, Alfred H.; Nikolova-Karakashian, Mariana

    2009-01-01

    Acid sphingomyelinase plays important roles in ceramide homeostasis, which has been proposed to be linked to insulin resistance. To test this association in vivo, acid sphingomyelinase deletion (asm–/–) was transferred to mice lacking the low density lipoprotein receptor (ldlr–/–), and then offsprings were placed on control or modified (enriched in saturated fat and cholesterol) diets for 10 weeks. The modified diet caused hypercholesterolemia in all genotypes; however, in contrast to asm+/+/ldlr–/–, the acid sphingomyelinase-deficient littermates did not display hepatic triacylglyceride accumulation, although sphingomyelin and other sphingolipids were substantially elevated, and the liver was enlarged. asm–/–/ldlr–/– mice on a modified diet did not accumulate body fat and were protected against diet-induced hyperglycemia and insulin resistance. Experiments with hepatocytes revealed that acid sphingomyelinase regulates the partitioning of the major fatty acid in the modified diet, palmitate, into two competitive and inversely related pools, triacylglycerides and sphingolipids, apparently via modulation of serine palmitoyltransferase, a rate-limiting enzyme in de novo sphingolipid synthesis. These studies provide evidence that acid sphingomyelinase activity plays an essential role in the regulation of glucose metabolism by regulating the hepatic accumulation of triacylglycerides and sphingolipids during consumption of a diet rich in saturated fats. PMID:19074137

  13. Hyperglycemia magnifies bupivacaine-induced cell apoptosis triggered by mitochondria dysfunction and endoplasmic reticulum stress.

    PubMed

    Li, Le; Ye, Xiao-ping; Lu, Ai-zhu; Zhou, Shu-qin; Liu, Hui; Liu, Zhong-jie; Jiang, Shan; Xu, Shi-yuan

    2013-06-01

    Nerve cell injury associated with apoptosis plays an important role in the development of diabetic peripheral neuropathy (DPN). However, it remains unclear whether preexisting or potential neurocyte damage induced by hyperglycemia increases sensitivity to local anesthetics. SH-SY5Y cells were pretreated with a high concentration of glucose in vitro, to imitate DPN prior to administration of bupivacaine or placebo. Cell viability and apoptosis were investigated with a CCK-8 assay and flow cytometry, respectively. In addition, mitochondrial membrane potential, reactive oxygen species (ROS), mitochondrially generated ROS, and activity of mitochondrial complexes I and III were studied to explore the molecular mechanism of bupivacaine-induced mitochondrial injury. Grp78 and caspase-12 expression were measured by qRT-PCR and Western blot, representing endoplasmic reticulum (ER) stress. Cell structure was also assessed via transmission electron microscopy. Incubation with bupivacaine decreased the activity of mitochondrial complexes I and III; increased ROS production at cell and mitochondrial levels, mitochondrial potential depolarization, and Grp78 and caspase-12 expression at both transcription and translation levels; and affected cell structure, which could be enhanced by glucose pretreatment. These findings indicate that mitochondrial dysfunction and ER stress related to ROS are involved in bupivacaine-induced apoptosis and may be enhanced by glucose administration.

  14. Spontaneous hyperglycemia and impaired glucose tolerance in athymic nude BALB/c mice.

    PubMed

    Zeidler, A; Tosco, C; Kumar, D; Slavin, B; Parker, J

    1982-09-01

    Basal plasma glucose, glucose tolerance, and insulin secretion were investigated in young and mature athymic nude BALB/c mice and in age-matched controls. Basal plasma glucose levels in male athymic nude mice were similar to those of controls at 1, 3, and 4 wk of age. At 6, 8, and 12 wk of age, male athymic nudes had significantly higher basal plasma glucose levels when compared with controls (P less than 0.01). Plasma immunoreactive insulin concentrations were similar in athymic nudes and controls at 1 wk of age, but at 3 wk of age and subsequently at 6, 8, and 12 wk athymic nude mice had significantly decreased insulin levels when compared with their age-matched controls (P less than 0.05). We found impaired glucose tolerance in male athymic nude mice at all age groups when compared with both female athymic nudes and control BALB/c mice. The discovery of a spontaneous diabetic syndrome (hyperglycemia, impaired glucose tolerance, and decreased insulin secretion) in a colony of athymic nude mice may provide an excellent model for studying the genetics and interactions between the immune and endocrine systems.

  15. Interleukin-1 promotes hyperglycemia and insulitis in mice normally resistant to streptozotocin-induced diabetes.

    PubMed Central

    Zunino, S. J.; Simons, L. F.; Sambrook, J. F.; Gething, M. J.

    1994-01-01

    By administering physiological doses of interleukin-1 (IL-1) concurrently with multiple low doses of the beta cell toxin streptozotocin (MSZ), we observed an augmentation of diabetes by IL-1 in four different strains of mice. Augmentation of hyperglycemia by IL-1 was most prominent in the two MSZ-resistant mouse strains Balb/cJ and A/J. Furthermore, concurrent treatment with IL-1 and MSZ rendered these MSZ-resistant mice susceptible to the development of significant insulitis when compared to mice treated with MSZ alone. Development of insulitis was dependent upon the dose of IL-1; it was only observed at an IL-1 dose of 250 ng/kg body weight. Analysis of the leukocytic infiltrate in the islets of mice after treatment with 250 ng/kg IL-1 plus MSZ revealed the presence of L3T4+ and Lyt-2+ T lymphocytes. Administration of MSZ alone or IL-1 alone did not produce diabetes in the MSZ-resistant mice, indicating that neither of these agents was toxic to the beta cells by itself. We conclude that IL-1 synergizes with MSZ to augment diabetes in mice that are normally resistant to the diabetogenic effects of MSZ. Images Figure 3 Figure 4 PMID:8080048

  16. Stress Hyperglycemia in Pediatric Critical Illness: The Intensive Care Unit Adds to the Stress!

    PubMed Central

    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, cardiopulmonary bypass and extracorporeal life support, therapeutic hypothermia, prolonged immobility, nutrition support practices, and the use of medications are all known to mediate development of SH in critical illness. Tight glucose control (TGC) to manage SH has emerged as a promising therapy to improve outcomes in critically ill adults, but results have been inconclusive. Large variations in ICU practices across studies likely resulted in inconsistent results. Future studies of TGC need to take into account the impact of commonly used ICU practices and, ideally, standardize protocols in an attempt to improve the accuracy of conclusions from such studies. PMID:22401321

  17. Hyperglycemia- and neuropathy-induced changes in mitochondria within sensory nerves

    PubMed Central

    Hamid, Hussein S; Mervak, Colin M; Münch, Alexandra E; Robell, Nicholas J; Hayes, John M; Porzio, Michael T; Singleton, J Robinson; Smith, A Gordon; Feldman, Eva L; Lentz, Stephen I

    2014-01-01

    Objective This study focused on altered mitochondrial dynamics as a potential mechanism for diabetic peripheral neuropathy (DPN). We employed both an in vitro sensory neuron model and an in situ analysis of human intraepidermal nerve fibers (IENFs) from cutaneous biopsies to measure alterations in the size distribution of mitochondria as a result of hyperglycemia and diabetes, respectively. Methods Neurite- and nerve-specific mitochondrial signals within cultured rodent sensory neurons and human IENFs were measured by employing a three-dimensional visualization and quantification technique. Skin biopsies from distal thigh (DT) and distal leg (DL) were analyzed from three groups of patients; patients with diabetes and no DPN, patients with diabetes and confirmed DPN, and healthy controls. Results This analysis demonstrated an increase in mitochondria distributed within the neurites of cultured sensory neurons exposed to hyperglycemic conditions. Similar changes were observed within IENFs of the DT in DPN patients compared to controls. This change was represented by a significant shift in the size frequency distribution of mitochondria toward larger mitochondria volumes within DT nerves of DPN patients. There was a length-dependent difference in mitochondria within IENFs. Distal leg IENFs from control patients had a significant shift toward larger volumes of mitochondrial signal compared to DT IENFs. Interpretation The results of this study support the hypothesis that altered mitochondrial dynamics may contribute to DPN pathogenesis. Future studies will examine the potential mechanisms that are responsible for mitochondrial changes within IENFs and its effect on DPN pathogenesis. PMID:25493271

  18. Hyperglycemia Induced and Intrinsic Alterations in Type 2 Diabetes-Derived Osteoclast Function

    PubMed Central

    Catalfamo, Dana L.; Britten, Todd M.; Storch, Douglas I.; Calderon, Nadia L.; Sorenson, Heather L.; Wallet, Shannon M.

    2012-01-01

    Periodontal disease-associated alveolar bone loss is a co-morbidity of type-2-diabetes, where the roles of osteoclasts are poorly understood. Objective To evaluate osteoclast differentiation and function in the context of type-2-diabetes. Materials/Methods Bone marrow-derived osteoclasts from db/db mice, a model of type-2-diabetes, as well as human osteoclasts derived from peripheral blood of individuals with type-2-diabetes were evaluated for differentiation, resorption, and soluble mediator expression. Results While db/db mice were hyperglycemic at time of cell harvest, human participants were glycemically controlled. Although db/db cultures resulted in a higher number of larger osteoclasts, individual cell RANKL-mediated bone resorption was similar to that observed in diabetes-free OCs. Osteoclasts derived from individuals with type-2-diabetes differentiated similarly to controls with again no difference in bone resorbing capacity. Murine and human type-2-diabetes cultures both displayed inhibition of LPS-induced deactivation and increased pro-osteoclastogenic mediator expression. Conclusions Hyperglycemia plays a role in aberrant osteoclast differentiation leading to an increased capacity for bone resorption. Osteoclasts derived from murine models of and individuals with type-2-diabetes are unable to be inhibited by LPS, again leading to increased capacity for bone resorption. Here environmental and intrinsic mechanisms associated with the increased alveolar bone loss observed in periodontal patients with type-2-diabetes are described. PMID:24079914

  19. [Advantages and disadvantages of insulin therapy in elderly diabetics with asymptomatic hyperglycemia].

    PubMed

    Straumann, M; Staffelbach, O; Sonnenberg, G E; Keller, U; Berger, W

    1979-12-01

    15 elderly diabetic patients with fasting blood glucose levels above 160 mg/100 ml, without hyperglycemic symptoms and previously treated with oral antidiabetic agents, were put on insulin. The change of treatment regimen was made in the outpatient department. Frequent clinical and laboratory controls were performed and the patients were given full instructions for injection technique and diet. On the insulin regimen a prompt and lasting improvement was observed in the metabolic parameters (blood glucose levels both fasting and after food intake, Hb A1c, serum insulin, glucagon and serum lipid concentrations). The so-called "asymptomatic" patients noticed a marked improvement in their general status and performance. Three months after insulin therapy was started 13 of our 15 patients preferred the insulin treatment to oral agents. However, weight gain and a tendency to hypoglycemia were noticed in less disciplined patients. In addition, considerable time was spent on instruction of the patients. Bearing these factors in mind, insulin therapy in elderly diabetics with so-called "sysmptomatic hyperglycemia" can be regarded as worthwhile.

  20. Pleurotus tuber-regium Polysaccharides Attenuate Hyperglycemia and Oxidative Stress in Experimental Diabetic Rats

    PubMed Central

    Huang, Hui-Yu; Korivi, Mallikarjuna; Chaing, Ying-Ying; Chien, Ting-Yi; Tsai, Ying-Chieh

    2012-01-01

    Pleurotus tuber-regium contains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties of P. tuber-regium polysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P) were extracted from three different strains of P. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly (P < 0.01) lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited (P < 0.01) the lipid peroxidation index (malondialdehyde), and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize that P. tuber-regium polysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats. PMID:22973406

  1. Mode of action of dopamine in inducing hyperglycemia in the fresh water edible crab, Oziothelphusa senex senex.

    PubMed

    Swetha, Ch; Sainath, S B; Reddy, P Sreenivasula

    2014-11-01

    The objective of this study was to investigate the mode of action of dopamine in regulating hemolymph sugar level in the fresh water edible crab, Oziothelphusa senex senex. Injection of dopamine produced hyperglycemia in a dose-dependent manner in intact crabs but not in eyestalkless crabs. Administration of dopamine resulted in a significant decrease in total carbohydrates and glycogen levels with a significant increase in glycogen phosphorylase activity levels in hepatopancreas and muscle of intact crabs, indicating dopamine-induced glycogenolysis resulting in hyperglycemia. Bilateral eyestalk ablation resulted in significant increase in the total carbohydrates and glycogen levels with a significant decrease in the activity levels of phosphorylase in the hepatopancreas and muscle of the crabs. Eyestalk ablation resulted in significant decrease in hemolymph hyperglycemic hormone levels. The levels of hyperglycemic hormone in the hemolymph of dopamine injected crabs were significantly higher than in control crabs. However, no significant changes in the levels of hemolymph hyperglycemic hormone and sugar and tissue carbohydrate and phosphorylase activity were observed in dopamine injected eyestalk ablated crabs when compared with eyestalk ablated crabs. These results support an earlier hypothesis in crustaceans that dopamine acts as a neurotransmitter and induces hyperglycemia by triggering the release of hyperglycemic hormone in the crab, O. senex senex.

  2. Inhibition of diabetic-cataract by vitamin K1 involves modulation of hyperglycemia-induced alterations to lens calcium homeostasis.

    PubMed

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, Ramar

    2014-11-01

    This study investigated the potential of vitamin K1 against streptozotocin-induced diabetic cataract in Wistar rats. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, accumulation of sorbitol and formation of advanced glycation end product (AGE) in eye lens. Hyperglycemia in lens also resulted in superoxide anion and hydroxyl radical generation and less reduced glutathione suggesting oxidative stress in lens. Hyperglycemia also resulted in increase in lens Ca2+ and significant inhibition of lens Ca2+ ATPase activity. These changes were associated with cataract formation in diabetic animals. By contrast treatment of diabetic rats with vitamin K1 (5 mg/kg, sc, twice a week) resulted in animals with partially elevated blood glucose and with transparent lenses having normal levels of sorbitol, AGE, Ca2+ ATPase, Ca2+, and oxidative stress. Vitamin K 1 may function to protect against cataract formation in the STZ induced diabetic rat by affecting the homeostasis of blood glucose and minimizing subsequent oxidative and osmotic stress. Thus, these results show that Vitamin K1 inhibits diabetic-cataract by modulating lens Ca2+ homeostasis and its hypoglycemic effect through its direct action on the pancreas.

  3. Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia

    PubMed Central

    Morimoto, M; Lee, E-Y; Zhang, X; Inaba, Y; Inoue, H; Ogawa, M; Shirasawa, T; Yokosuka, O; Miki, T

    2016-01-01

    Background/Objective: Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial. Methods: We examined the antidiabetic effect of EPA in insulin receptor mutant (InsrP1195L/+) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia. Results: EPA supplementation was found to alleviate hyperglycemia of InsrP1195L/+ mice fed HFD (InsrP1195L/+/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in InsrP1195L/+ mice but not in wild-type mice, suggesting that InsrP1195L/+ mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of InsrP1195L/+ mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia. Conclusions: EPA exerts an antidiabetic effect in InsrP1195L/+/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia. PMID:27348201

  4. Allelic variation on chromosome 5 controls beta-cell mass expansion during hyperglycemia in leptin receptor-deficient diabetes mice.

    PubMed

    Luo, Na; Liu, Shun Mei; Liu, Hong; Li, Qiong; Xu, Qun; Sun, Xi; Davis, Brandi; Li, Jing; Chua, Streamson

    2006-05-01

    Leptin signaling is a critical component of normal insulin sensitivity. Overt hyperglycemia and type 2 diabetes mellitus can be manifested in states of leptin signaling deficiencies by the additional effects of other genetic factors. We have previously described the contrasting insulin sensitivities and glycemic states of two congenic diabetes (db/db) mouse strains. C57BL/6J db/db mice have mild insulin resistance and achieve euglycemia with mild hyperinsulinemia. FVB db/db mice have severe insulin resistance and are hyperglycemic despite escalating hyperinsulinemia with expanded pancreatic beta-cell mass. Analysis of obese progeny from the two reciprocal backcrosses suggests that genetic modifiers for insulin sensitivity are separable from loci that modulate beta-cell mass. A genome scan of the backcross to FVB suggests that one or more modifier genes are present on chromosome 5. This evidence is supported by the phenotypes of multiple incipient congenic strains wherein the hyperglycemia observed in obese FVB mice is reproduced. With similar degrees of hyperglycemia in obese mice of these strains, the haplotype at chromosome 5 is associated with beta-cell mass and circulating insulin concentrations. Finally, we offer arguments that production of multiple incipient congenic lines is an economical alternative to the production of speed congenic strains.

  5. Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice.

    PubMed

    Yamauchi, Rie; Kobayashi, Misato; Matsuda, Yuji; Ojika, Makoto; Shigeoka, Shigeru; Yamamoto, Yuko; Tou, Yoshie; Inoue, Takashi; Katagiri, Takao; Murai, Atsushi; Horio, Fumihiko

    2010-05-12

    Epidemiological surveys have demonstrated that habitual coffee consumption reduces the risk of type 2 diabetes. The aim of this work was to study the antidiabetic effect of coffee and caffeine in spontaneously diabetic KK-A(y) mice. KK-A(y) mice were given regular drinking water (controls) or 2-fold diluted coffee for 5 weeks. Coffee ingestion ameliorated the development of hyperglycemia and improved insulin sensitivity. White adipose tissue mRNA levels of inflammatory cytokines (MCP-1, IL-6, and TNFalpha), adipose tissue MCP-1 concentration, and serum IL-6 concentration in the coffee group were lower than the control group. Moreover, coffee ingestion improved the fatty liver. Caffeine ingestion as drinking water also caused an amelioration of hyperglycemia and an improvement of fatty liver. These results suggest that coffee exerts a suppressive effect on hyperglycemia by improving insulin sensitivity, partly due to reducing inflammatory cytokine expression and improving fatty liver. Moreover, caffeine may be one of the effective antidiabetic compounds in coffee.

  6. mRNA and Protein levels of rat pancreas specific protein disulphide isomerase are downregulated during Hyperglycemia.

    PubMed

    Gupta, Rajani; Bhar, Kaushik; Sen, Nandini; Bhowmick, Debajit; Mukhopadhyay, Satinath; Panda, Koustubh; Siddhanta, Anirban

    2016-02-01

    Diabetes (Type I and Type II) which affects nearly every organ in the body is a multi-factorial non-communicable disorder. Hyperglycemia is the most characteristic feature of this disease. Loss of beta cells is common in both types of diabetes whose detailed cellular and molecular mechanisms are yet to be elucidated. As this disease is complex, identification of specific biomarkers for its early detection, management and devising new therapies is challenging. Based on the fact that functionally defective proteins provide the biochemical basis for many diseases, in this study, we tried to identify differentially expressed proteins during hyperglycemia. For that, hyperglycemia was induced in overnight fasted rats by intra-peritoneal injection of streptozotocin (STZ). The pancreas was isolated from control and treated rats for subsequent analyses. The 2D-gel electrophoresis followed by MALDI-TOF-MS-MS analyses revealed several up- and down-regulated proteins in hyperglycemic rat pancreas including the downregulation of a pancreas specific isoform of protein disulphide isomerase a2 (Pdia2).This observation was validated by western blot. Quantitative PCR experiments showed that the level of Pdia2 mRNA is also proportionally reduced in hyperglycemic pancreas.

  7. Oral administration of green algae, Euglena gracilis, inhibits hyperglycemia in OLETF rats, a model of spontaneous type 2 diabetes.

    PubMed

    Shimada, Ryoko; Fujita, Miho; Yuasa, Masahiro; Sawamura, Hiromi; Watanabe, Toshiaki; Nakashima, Ayaka; Suzuki, Kengo

    2016-11-09

    In the present study, the effects of Euglena and paramylon on hyperglycemia were examined in Otsuka Long-Evans Tokushima fatty (OLETF; type 2 diabetes mellitus model) rats. OLETF rats were fed an AIN-93 M diet containing cellulose, Euglena, or paramylon for 10 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. An oral glucose-tolerance test (OGTT) was performed at 0 and 10 weeks. OLETF control rats were obese because of bulimia and showed abdominal fat accumulation and hyperglycemia. Euglena supplementation improved hyperglycemia and decreased food intake, body weight gain, and abdominal fat. However, there were no changes in the paramylon-supplemented group compared to the OLETF control group. Triglyceride concentrations in the serum and liver were lower in Euglena-supplemented rats than in OLETF control rats. There was a correlation between hepatic triglyceride concentration and the area under the curve (AUC) of OGTT at 10 weeks. This suggests that the improvement in glycemic control in the Euglena-supplemented group may depend on substances other than paramylon present in Euglena.

  8. Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes.

    PubMed

    Zhang, Mingfeng; Lin, Qing; Qi, Tong; Wang, Tiankun; Chen, Ching-Cheng; Riggs, Arthur D; Zeng, Defu

    2016-01-19

    We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9(+) (Sox9(+)) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9(+) ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9(+) ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300-450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9(+) ductal cell differentiation into β cells in adult mice.

  9. One-year treatment of Alzheimer's disease with acetylcholinesterase inhibitors: improvement on ADAS-cog and TMT A, no change or worsening on other tests.

    PubMed

    Borkowska, Alina; Ziolkowska-Kochan, Marzena; Rybakowski, Janusz K

    2005-08-01

    The aim of this study was to assess cognitive functioning measured by selected psychometric and neuropsychological tools in patients with Alzheimer's disease (AD) after 1-year treatment with acetylcholinesterase inhibitors. Seventy-six patients (22 male and 54 female) with a mild to moderate stage of AD, aged 56-86 (mean 68) years, were treated. Forty-seven received donepezil (mean dose 9.3 mg/d) and 29 rivastigmine (mean dose 8.5 mg/d). Cognitive measurements included: the mini mental state examination (MMSE), the Alzheimer disease assessment scale-cognitive (ADAS- cog), the trail making test (TMT) and the Stroop color word interference test. The assessments were made before and after 3, 6 and 12 months of treatment. A significant improvement in ADAS-cog (p < 0.001, 83% of patients improved) and a worsening in MMSE (84% of patients worsened, p < 0.01 after 6 and 12 months) was noted after the 1 year treatment. A majority of patients (57%) improved in the TMT-A (p < 0.001), measuring psychomotor speed and worsened in the TMT-B (p < 0.01, after 12 months), and Stroop B test (p < 0.001), measuring working memory and executive functions, 53% and 61%, respectively. Most patients (83%) did not change their performance in the Stroop A (improvement after 3 months, p < 0.001, worsening after 6 and 12 months p < 0.01) test measuring verbal abilities, after 1 year treatment. The results obtained suggest that the treatment with cholinergic drugs may improve global cognitive functioning (ADAS-cog) and psychomotor speed (TMT A), however, such treatment is unable to prevent the deterioration of working memory and executive functions.

  10. Do changes in subjective sleep and biological rhythms predict worsening in postpartum depressive symptoms? A prospective study across the perinatal period.

    PubMed

    Krawczak, Elizabeth M; Minuzzi, Luciano; Hidalgo, Maria Paz; Frey, Benicio N

    2016-08-01

    Abnormalities of sleep and biological rhythms have been widely implicated in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). However, less is known about the influence of biological rhythm disruptions across the perinatal period on postpartum depression (PPD). The objective of this study was to prospectively evaluate the relationship between subjective changes in both sleep and biological rhythms and worsening of depressive symptoms from pregnancy to the postpartum period in women with and without mood disorders. Eighty-three participants (38 euthymic women with a history of a mood disorder and 45 healthy controls) were studied. Participants completed subjective assessments of sleep (Pittsburgh Sleep Quality Index), biological rhythm disturbances (Biological Rhythms Interview of Assessment in Neuropsychiatry), and depressive symptoms (Edinburgh Postnatal Depression Scale) prospectively at two time points: third trimester of pregnancy and at 6-12 weeks postpartum. Multivariate regression analyses showed that changes in biological rhythms across the perinatal period predicted worsening of depressive symptoms in both groups. Moreover, women with a history of a mood disorder showed higher levels of sleep and biological rhythm disruption during both pregnancy and the postpartum period. These findings suggest that disruptions in biological rhythms during the perinatal period increase the risk for postpartum mood worsening in healthy pregnant as well as in pregnant women with a history of mood disorders.

  11. A teenager presents with fulminant hepatic failure and acute hemolytic anemia.

    PubMed

    Bose, Somnath; Sonny, Abraham; Rahman, Nadeem

    2015-03-01

    A teenager was admitted to an outside hospital ED following an episode of melena. He had been complaining of intermittent abdominal pain, nausea, malaise, and easy fatigability for 2 months, with significant worsening of symptoms 2 weeks prior to this episode. He had no significant medical, surgical, or family history. On presentation at the outside ED, he was found to be profoundly icteric and encephalopathic. Initial laboratories suggested anemia, acute kidney injury, and acute liver failure, leading to a presumptive diagnosis of acute fulminant liver failure necessitating transfer to our institution.

  12. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  13. Fasiglifam/TAK-875, a Selective GPR40 Agonist, Improves Hyperglycemia in Rats Unresponsive to Sulfonylureas and Acts Additively with Sulfonylureas.

    PubMed

    Ito, Ryo; Tsujihata, Yoshiyuki; Suzuki, Masami; Miyawaki, Kazumasa; Matsuda, Kae; Takeuchi, Koji

    2016-04-01

    Sulfonylureas (SUs) are widely used insulin secretagogues, but they have adverse effects including hypoglycemia and secondary failure. Fasiglifam/TAK-875, a selective GPR40 agonist, enhances glucose-stimulated insulin secretion and improves hyperglycemia. In the present study, we compared the in vivo glucose-lowering effects of fasiglifam with SUs. The risk of secondary failure of fasiglifam and the efficacy in rats desensitized to SUs were also evaluated. Moreover, we assessed whether fasiglifam was effective when combined with SUs. In diabetic neonatally streptozotocin-induced rats 1.5 days after birth (N-STZ-1.5), oral administrations of fasiglifam (3-30 mg/kg) dose dependently improved glucose tolerance; the effect was greater than that of glibenclamide at maximal effective doses (glucose AUC: fasiglifam, -37.6%; glibenclamide, -12.3%). Although the glucose-lowering effects of glibenclamide (10 mg/kg/day) were completely diminished in N-STZ-1.5 rats after 4 weeks of treatment, effects were maintained in rats receiving fasiglifam (10 mg/kg/day), even after 15 weeks. Fasiglifam (3-10 mg/kg) was still effective in two models desensitized to SUs: 15-week glibenclamide-treated N-STZ-1.5 rats and aged Zucker diabetic fatty (ZDF) rats. Acute administration of fasiglifam (3 mg/kg) and glimepiride (10 mg/kg) in combination additively decreased glucose AUC (fasiglifam, -25.3%; glimepiride, -20.0%; combination, -43.1%). Although glimepiride (10 mg/kg) decreased plasma glucose below normal in nonfasted control rats, fasiglifam (3 mg/kg) maintained normoglycemia, and no further exaggeration of hypoglycemia was observed with combination treatment. These results indicate that GPR40 agonists could be more effective and durable than SUs. Our results also provide new insights into GPR40 pharmacology and rationale for the use of GPR40 agonists in diabetic patients with SU failure.

  14. Acute primary haemorrhagic omental torsion mimicking perforated appendicitis: an unorthodox surgical paradox.

    PubMed

    Rehman, Abdul

    2014-08-01

    Acute primary haemorrhagic omental torsion is an atypical and deceptive cause of acute abdomen that could closely mimic a myriad of intra-abdominal catastrophes, especially perforated appendicitis. The author reports a 30 years man who had presented with gradually worsening right-sided abdominal pain of 2 days duration. Laboratory work-up and abdominal radiographs were inconclusive. Abdominal sonography detected presence of free fluid in the pelvic cul-de-sac. Based on clinical and sonographic findings, presumptive diagnosis of perforated appendicitis was made and the patient was explored through extended Rockey-Davis incision. About 500 - 700 ml of dark-coloured blood (haemoperitoneum) was present in the peritoneal cavity and the pelvis secondary to acute haemorrhagic omental torsion. The appendix was grossly normal. Omentectomy and prophylactic appendicectomy resulted in uneventful recovery of the patient. Acute primary omental torsion is an uncommon pathology that must be kept in mind during differential diagnosis of acute abdomen, especially acute or perforated appendicitis.

  15. [Acute pancreatitis].

    PubMed

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

    2014-03-01

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

  16. Bronchitis - acute

    MedlinePlus

    ... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...

  17. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...

  18. A Conceptual Model for Episodes of Acute, Unscheduled Care.

    PubMed

    Pines, Jesse M; Lotrecchiano, Gaetano R; Zocchi, Mark S; Lazar, Danielle; Leedekerken, Jacob B; Margolis, Gregg S; Carr, Brendan G

    2016-10-01

    We engaged in a 1-year process to develop a conceptual model representing an episode of acute, unscheduled care. Acute, unscheduled care includes acute illnesses (eg, nausea and vomiting), injuries, or exacerbations of chronic conditions (eg, worsening dyspnea in congestive heart failure) and is delivered in emergency departments, urgent care centers, and physicians' offices, as well as through telemedicine. We began with a literature search to define an acute episode of care and to identify existing conceptual models used in health care. In accordance with this information, we then drafted a preliminary conceptual model and collected stakeholder feedback, using online focus groups and concept mapping. Two technical expert panels reviewed the draft model, examined the stakeholder feedback, and discussed ways the model could be improved. After integrating the experts' comments, we solicited public comment on the model and made final revisions. The final conceptual model includes social and individual determinants of health that influence the incidence of acute illness and injury, factors that affect care-seeking decisions, specific delivery settings where acute care is provided, and outcomes and costs associated with the acute care system. We end with recommendations for how researchers, policymakers, payers, patients, and providers can use the model to identify and prioritize ways to improve acute care delivery.

  19. Cutaneous approach towards clinical and pathophysiological aspects of hyperglycemia by ATR FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Eikje, Natalja Skrebova; Sota, Takayuki; Aizawa, Katsuo

    2007-07-01

    Attempts were made to non-invasively detect glucose-specific spectral signals in the skin by ATR-FTIR spectroscopy. In vivo spectra were collected from the inner wrists of healthy, prediabetes and diabetes subjects in the 750-4000 cm -1 region, with a closer assessment of the glucose-related region between 1000 and 1180 cm -1. Spectra in vivo showed glucose-specific peaks at 1030, 1080, 1118 and 1151 cm -1, as a variety of glucose solutions are found in vitro. Based on the differences of intensities at 1030 and 1118 cm -1 two spectral patterns were seen: I 1118 > I 1030 for a diabetes and I 1030> I 1118 for non-diabetes subjects. The peak at 1030 cm -1 was used to assess glucose concentrations in the skin due to its good correlation with glucose concentrations in vitro. Calculated mean values of the peak at 1030 cm -1 showed evidence of correlation with blood glucose levels when grouped as <= 140, 140-200 and >= 200 mg/dL, though there was no constant correlation between them when compared before/after OGTT or at the fasting/postprandial states. Absorbances at 1030 cm -1 were not only increased in a dose-dependent manner in a diabetes patient, but were also generally higher than in non-diabetes subjects at 30 min OGTT assessment. Also we could monitor absorbances at 1030 cm -1 and determine their changes in the skin tissue at different times of OGTT. We assume that our approach to in vivo measurement and monitoring of glucose concentrations at 1030 cm -1 may be one of the indicators to assess glucose activity level and its changes in the skin tissue, and has further implications in the study of clinical and pathophysiological aspects of hyperglycemia in diabetes and non-diabetes subjects by ATR-FTIR spectroscopy.

  20. All-Cause Mortality for Diabetics or Individuals with Hyperglycemia Applying for Life Insurance.

    PubMed

    Freitas, Stephen A; MacKenzie, Ross; Wylde, David N; Roudebush, Bradley T; Bergstrom, Richard L; Holowaty, J Carl; Hart, Anna; Rigatti, Steven J; Gill, Stacy J

    2016-01-01

    Diabetics and individuals with lab results consistent with a diagnosis of diabetes or hyperglycemia were extracted from data covering US residents who applied for life insurance between January 2007 and January 2014. Information about these applicants was matched to the Social Security Death Master File (SSDMF) and another commercially available death source file to determine vital status. Due to the inconsistencies of reporting within the death files, there were two cohorts of death cases, one including the imputed year of birth (full cohort of deaths), and the second where the date of birth was known (reduced cohort of deaths). The study had approximately 8.5 million person-years of exposure. Actual to expected (A/E) mortality ratios were calculated using the Society of Actuaries 2008 Valuation Basic Table (2008VBT) select table, age last birthday and the 2010 US population as expected mortality rates. With the 2008VBT as an expected basis, the overall A/E mortality ratio was 3.15 for the full cohort of deaths and 2.56 for the reduced cohort of deaths. Using the US population as the expected basis, the overall A/E mortality ratio was 0.98 for the full cohort of deaths and 0.79 for the reduced cohort. Since there was no smoking status information in this study, all expected bases were not smoker distinct. A/E mortality ratios varied by disease treatment category and were considerably higher in individuals using insulin. A/E mortality ratios decreased with increasing age and took on a J-shaped distribution with increasing BMI (Body Mass Index). The lowest mortality ratios were observed for overweight and obese individuals. The A/E mortality ratio based on the 2008VBT decreased with the increase in applicant duration, which was defined as the time since initial life insurance application.

  1. Maternal insulin resistance and transient hyperglycemia impact the metabolic and endocrine phenotypes of offspring

    PubMed Central

    Kahraman, Sevim; Dirice, Ercument; De Jesus, Dario F.; Hu, Jiang

    2014-01-01

    Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, glucagon, and active GLP-1 were higher in control pups from LIRKO mothers. Analyses of the endocrine pancreas revealed significantly reduced β-cell area in control offspring of LIRKO mothers shortly after birth. β-Cell proliferation and total islet number were also lower in control offspring of LIRKO mothers during early postnatal days. Together, these data indicate that maternal hyperinsulinemia and the transient hyperglycemia impair endocrine pancreas development in the control offspring and induce multiple metabolic alterations in early postnatal life. The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development. PMID:25249504

  2. Hyperglycemia-induced GLP-1R downregulation causes RPE cell apoptosis.

    PubMed

    Kim, Dong-Il; Park, Min-Jung; Choi, Joo-Hee; Lim, Seul-Ki; Choi, Hak-Jong; Park, Soo-Hyun

    2015-02-01

    Glucagon-like peptide-1 receptor (GLP-1R) is closely associated with the onset of diabetes and its complications. However, its roles in diabetic retinopathy are unknown. Retinal pigment epithelial (RPE) cells are a crucial component of the outer blood-retina barrier and their death is related to the progression of diabetic retinopathy. Thus, we examined the pathophysiological role of GLP-1R in RPE cell apoptosis. We found that GLP-1R expression was lower in the isolated neuroretina and RPE cells of streptozotocin-treated rats than in vehicle-treated rats. High-glucose treatment also decreased GLP-1R expression in a human RPE cell line (ARPE-19 cells). GLP-1R was silenced in ARPE-19 cells, in order to elucidate the pathophysiological roles of GLP-1R. This increased intracellular reactive oxygen species (ROS) generation and activated p53-mediated Bax promoter and endoplasmic reticulum (ER) stress signaling. We also found that GLP-1R knockdown-mediated p53 expression was regulated by ER stress. Interestingly, antioxidant treatment and peroxiredoxin 1 (Prx1) overexpression attenuated GLP-1R knockdown-induced ER stress signaling and p53 expression. Finally, to confirm that GLP-1R activation has protective effects, ARPE-19 cells were treated with exendin-4, a synthetic GLP-1R agonist. This attenuated high-glucose-induced ROS generation, ER stress signaling, and p53 expression. Collectively, these results indicated that hyperglycemia decreases GLP-1R expression in RPE cells. Such a decrease generates intracellular ROS, which increases ER stress-mediated p53 expression, and subsequently causes apoptosis by increasing Bax promoter activity. Our data suggested that regulation of GLP-1R expression is a promising approach for the treatment of diabetic retinopathy.

  3. Effects of compound K on hyperglycemia and insulin resistance in rats with type 2 diabetes mellitus.

    PubMed

    Jiang, Shuang; Ren, Dayong; Li, Jianrui; Yuan, Guangxin; Li, Hongyu; Xu, Guangyu; Han, Xiao; Du, Peige; An, Liping

    2014-06-01

    Compound K (CK) is a final metabolite of panaxadiol ginsenosides from Panax ginseng. Although anti-diabetic activity of CK has been reported in recent years, the molecular mechanism of CK in the treatment of diabetes mellitus remains unclear. In the present investigation, we established a rat model of type 2 diabetes mellitus (T2DM) with insulin resistance using high-fat diet (HFD) and streptozotocin (STZ), and attempted to verify more details and exact mechanisms in the treatment of T2DM. CK was administered orally at three doses [300, 100 and 30 mg/kg bodyweight (b.w.)] to the diabetic rats. Bodyweight, food-intake, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin sensitivity (ISI), total glycerin (TG), total cholesterol (TC), as well as oral glucose tolerance test (OGTT) were evaluated in normal and diabetic rats. According to our results, CK could improve bodyweight and food-intake of diabetic rats. CK exhibited dose-dependent reduction of FBG, TG and TC of diabetic rats. CK treatment also enhanced FINS and ISI. Meanwhile, the glucose tolerance observed in the present study was improved significantly by CK. It is concluded from the results that CK may have improving effects on hyperglycemia and insulin resistance of diabetic rats. Furthermore, research showed that CK could promote the expression of InsR, IRS1, PI3Kp85, pAkt and Glut4 in skeletal muscle tissue of diabetic rats. These results indicate that the hypoglycemic activity of CK is mediated by improvement of insulin sensitivity, which is closely related to PI3K/Akt signaling pathway.

  4. Endothelial cells respond to hyperglycemia by increasing the LPL transporter GPIHBP1.

    PubMed

    Pei-Ling Chiu, Amy; Wang, Fulong; Lal, Nathaniel; Wang, Ying; Zhang, Dahai; Hussein, Bahira; Wan, Andrea; Vlodavsky, Israel; Rodrigues, Brian

    2014-06-01

    In diabetes, when glucose uptake and oxidation are impaired, the heart is compelled to use fatty acid (FA) almost exclusively for ATP. The vascular content of lipoprotein lipase (LPL), the rate-limiting enzyme that determines circulating triglyceride clearance, is largely responsible for this FA delivery and increases following diabetes. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein [GPIHBP1; a protein expressed abundantly in the heart in endothelial cells (EC)] collects LPL from the interstitial space and transfers it across ECs onto the luminal binding sites of these cells, where the enzyme is functional. We tested whether ECs respond to hyperglycemia by increasing GPIHBP1. Streptozotocin diabetes increased cardiac LPL activity and GPIHBP1 gene and protein expression. The increased LPL and GPIHBP1 were located at the capillary lumen. In vitro, passaging EC caused a loss of GPIHBP1, which could be induced on exposure to increasing concentrations of glucose. The high-glucose-induced GPIHBP1 increased LPL shuttling across EC monolayers. GPIHBP1 expression was linked to the EC content of heparanase. Moreover, active heparanase increased GPIHBP1 gene and protein expression. Both ECs and myocyte heparan sulfate proteoglycan-bound platelet-derived growth factor (PDGF) released by heparanase caused augmentation of GPIHBP1. Overall, our data suggest that this protein "ensemble" (heparanase-PDGF-GPIHBP1) cooperates in the diabetic heart to regulate FA delivery and utilization by the cardiomyocytes. Interrupting this axis may be a novel therapeutic strategy to restore metabolic equilibrium, curb lipotoxicity, and help prevent or delay heart dysfunction that is characteristic of diabetes.

  5. Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia.

    PubMed

    Khalifi, Saeedeh; Rahimipour, Ali; Jeddi, Sajad; Ghanbari, Mahboubeh; Kazerouni, Faranak; Ghasemi, Asghar

    2015-01-30

    Reduction in nitric oxide (NO) production and bioavailability contribute to the pathogenesis of type 2 diabetes. Administration of nitrate has strong NO-like outcomes in both animals and humans. In this study, we examined the effects of dietary nitrate on glucose tolerance and lipid profile in type 2 diabetic rats. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Thirty-two male Wistar rats were divided into 4 groups: controls (C), control+nitrate (CN), diabetes (D), and diabetes+nitrate (DN). For 8 weeks, the CN and DN groups consumed sodium nitrate (100 mg/L in drinking water) while the C and D groups consumed tap water. Serum nitrate+nitrite (NOx), glucose, lipid profile, total antioxidant capacity (TAC), and catalase (CAT) activity were measured before and at the end of the study. Systolic blood pressure (SBP) was measured every 10 days. Intravenous glucose tolerance test (IVGTT) was performed at the end of the study. Serum NOx decreased in diabetic rats and dietary nitrate restored it to normal values. Increases in serum glucose levels was significantly lower in the DN group compared to the D group (24.1% vs. 90.2%; p < 0.05). Nitrate therapy in diabetic rats significantly improved lipid profile, glucose tolerance (AUC: 20264 ± 659 vs. 17923 ± 523; p < 0.05 for D and DN groups respectively) and restored elevated SBP to normal values. Diabetic rats had lower TAC and CAT activity and dietary nitrate restored these to normal status. In conclusion, dietary nitrate prevented increase in SBP and serum glucose, improved glucose tolerance and restored dyslipidemia in an animal model of hyperglycemia.

  6. Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia.

    PubMed

    Francés, Daniel E A; Ingaramo, Paola I; Mayoral, Rafael; Través, Paqui; Casado, Marta; Valverde, Ángela M; Martín-Sanz, Paloma; Carnovale, Cristina E

    2013-03-01

    Increased expression of COX-2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX-2 protects hepatocytes from several pro-apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX-2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain wild type (Wt) and transgenic in COX-2 (hCOX-2 Tg) were separated into Control (vehicle) and SID (streptozotocin induced diabetes, 200 mg/kg body weight, i.p.). Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. This situation was improved in diabetic COX-2 Tg. In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. Pro-apoptotic state in the liver of diabetic animals was improved by over-expression of COX-2. We also analyzed the roles of high glucose-induced apoptosis and hCOX-2 in vitro. Non-transfected and hCOX-2-transfected cells were cultured at 5 and 25 mM of glucose by 72 h. At 25 mM there was an increase in apoptosis in non-transfected cells versus those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX-2-transfected cells was suppressed by addition of DFU (COX-2 selective inhibitor), and mimicked by addition of PGE(2) in non-transfected cells. Taken together, these results demonstrate that hyperglycemia-induced hepatic apoptosis is protected by hCOX-2 expression.

  7. β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.

    PubMed

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A; Hamilton, Elisha J; Figtree, Gemma A; Rasmussen, Helge H

    2015-09-01

    Dysregulated nitric oxide (NO)- and superoxide (O2 (·-))-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na(+)-K(+) pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na(+)-K(+) pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47(phox) to p22(phox) with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na(+)-K(+) pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22(phox) with p47(phox), abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na(+)-K(+) pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na(+)-K(+) pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes.

  8. β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade

    PubMed Central

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A.; Hamilton, Elisha J.; Figtree, Gemma A.

    2015-01-01

    Dysregulated nitric oxide (NO)- and superoxide (O2·−)-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na+-K+ pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na+-K+ pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47phox and membranous p22phox NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47phox to p22phox with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na+-K+ pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22phox with p47phox, abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na+-K+ pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na+-K+ pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes. PMID:26063704

  9. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    PubMed Central

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

  10. Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases

    PubMed Central

    Yamazaki, Hideya; Kotsuma, Tadayuki; Akiyama, Hironori; Takenaka, Tadashi; Masui, Koji; Yoshioka, Yasuo; Uesugi, Yasuo; Shimbo, Taiju; Yoshikawa, Nobuhiko; Yoshioka, Hiroto; Arika, Takumi; Tanaka, Eiichi; Narumi, Yoshifumi

    2017-01-01

    Purpose We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. Material and methods To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case reports Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. Discussion and conclusions To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV. PMID:28344606

  11. UCP2 overexpression worsens mitochondrial dysfunction and accelerates disease progression in a mouse model of amyotrophic lateral sclerosis.

    PubMed

    Peixoto, Pablo M; Kim, Hyun-Jeong; Sider, Brittany; Starkov, Anatoly; Horvath, Tamas L; Manfredi, Giovanni

    2013-11-01

    Mitochondrial dysfunction leading to deficits in energy production, Ca(2+) uptake capacity, and free radical generation has been implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) caused by mutations in Cu,Zn superoxide dismutase (SOD1). Numerous studies link UCP2, a member of the uncoupling protein family, to protection of neurons from mitochondrial dysfunction and oxidative damage in various mouse models of acute stress and neurodegeneration, including Parkinson's disease. Here, we tested the potential neuroprotective effects of UCP2 and its ability to modulate mitochondrial function, in the G93A mutant SOD1 mouse model of familial ALS. Disease phenotype, mitochondrial bioenergetics, and Ca(2+) uptake capacity were investigated in the central nervous system of double transgenic mice, expressing both human mutant G93A SOD1 and human UCP2 (hUCP2). Unexpectedly, hUCP2 expression accelerated the disease course of SOD1 mutant mice. In addition, we did not observe a classical uncoupling effect of hUCP2 in G93A brain mitochondria, although we did detect a decrease in reactive oxygen species (ROS) production from mitochondria challenged with the respiratory chain inhibitors rotenone and antimycin A. We also found that mitochondrial Ca(2+) uptake capacity was decreased in the double transgenic mice, as compared to G93A mice. In summary, our results indicate that the neuroprotective role of UCP2 in neurodegeneration is disease-specific and that, while a mild uncoupling by UCP2 in brain mitochondria may protect against neurodegeneration in some injury paradigms, the mitochondrial damage and the disease caused by mutant SOD1 cannot be ameliorated by UCP2 overexpression.

  12. Diesel Exhaust Worsens Cardiac Conduction Instability in Dobutamine-Challenged Wistar-Kyoto and Spontaneously Hypertensive Rats.

    PubMed

    Hazari, Mehdi S; Lancaster, Jarrett L; Starobin, Joseph M; Farraj, Aimen K; Cascio, Wayne E

    2017-04-01

    Short-term exposure to air pollution, particularly from vehicular sources, increases the risk of acute clinical cardiovascular events. However, cardiotoxicity is not always clearly discernible under ambient conditions; therefore, more subtle measures of cardiac dysfunction are necessary to elucidate the latent effects of exposure. Determine the effect of whole diesel exhaust (DE) exposure on reserve of refractoriness (RoR), an intrinsic electrophysiological measure of the heart's minimum level of refractoriness relative to development of electrical conduction instability, in rats undergoing exercise-like stress. Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters to continuously collect electrocardiogram (ECG) and heart rate were exposed to 150 µg/m(3) of DE and challenged with dobutamine 24 h later to mimic exercise-induced increases of the heart rate. The Chernyak-Starobin-Cohen (CSC) model was then applied to the ECG-derived QT and RR intervals collected during progressive increases in heart rate to calculate RoR for each rat. Filtered air-exposed WKY and SH rats did not have any decrease in RoR, which indicates increased risk of cardiac conduction instability; however, DE caused a significant decrease in both strains. Yet, the decrease in RoR in SH rats was eight times steeper when compared to WKY rats indicating greater cardiac conduction instability in the hypertensive strain. These data indicate that after exposure to DE, risk of cardiac instability increases during increasing stress, particularly in the presence of underlying cardiovascular disease. Furthermore, the CSC model, which was previously shown to reveal cardiac risk in humans, can be applied to rodent toxicology studies.

  13. L-leucine supplementation worsens the adiposity of already obese rats by promoting a hypothalamic pattern of gene expression that favors fat accumulation.

    PubMed

    Zampieri, Thais T; Torres-Leal, Francisco L; Campaña, Amanda B; Lima, Fabio B; Donato, Jose

    2014-04-02

    Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD) for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.

  14. Evaluation Series on Safety and Efficacy of Nutritional Supplements in Newly Diagnosed Hyperglycemia: A Placebo-Controlled, Randomized Study

    PubMed Central

    Thacker, Hemant; Bantwal, Ganapati; Jain, Sunil; Kalra, Sanjay; Kale, Shailaja; Saboo, Banshi; Gupta, Jugal B.; Sivam, Sakthivel

    2016-01-01

    Background: Diabetes is endemic with developing economies contributing to the bulk of this pandemic. Despite the evidence of incremental benefit of glycemic control starting early in life, acceptance of and adherence to modern medications remain suboptimal. Aims: To determine the hemoglobin A1c (HbA1c)-lowering efficacy and safety of nutritional supplement, PreCrea®, in adult Indians with newly diagnosed hyperglycemia. Materials and Methods: Double-blind, randomized study conducted in six diabetes centers in India. A total of 193 treatment-naïve subjects with newly diagnosed hyperglycemia and fasting plasma glucose (FPG) >100 mg/dL were randomized into either PreCrea® 600 mg (n = 90) or matched placebo (n = 89) capsules twice daily, along with lifestyle modification, for 12 weeks. The main outcomes were changes in HbA1c and FPG levels, attainment of the American Diabetes Association (ADA)-defined goals for HbA1c, and clinical and biochemical measures of safety. Results: At 12 weeks, mean HbA1c in PreCrea® group reduced by 0.91% compared with 0.08% increase in the placebo group (P < .001). The reductions in the mean FPG at week 4 (P < .001) and week 12 (P = 0.04) were significant compared to the baseline. ADA goal of HbA1c <7% increased from 15.5% at the baseline to 35.6% at week 12 in PreCrea® subjects. Clinical safety and biochemical safety did not change. Hypoglycemia and weight gain were not observed with PreCrea®. Conclusions: Nearly 1% point reduction in HbA1c at week 12 with PreCrea® is comparable with most first-line glucose-lowering drugs. The safety and tolerability of PreCrea® highlights its potential as a first-line therapy in newly detected hyperglycemia. PMID:27042609

  15. Targeting the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic cardiomyopathy in mice.

    PubMed

    Huynh, Karina; Kiriazis, Helen; Du, Xiao-Jun; Love, Jane E; Gray, Stephen P; Jandeleit-Dahm, Karin A; McMullen, Julie R; Ritchie, Rebecca H

    2013-07-01

    Cardiac oxidative stress is an early event associated with diabetic cardiomyopathy, triggered by hyperglycemia. We tested the hypothesis that targeting left-ventricular (LV) reactive oxygen species (ROS) upregulation subsequent to hyperglycemia attenuates type 1 diabetes-induced LV remodeling and dysfunction, accompanied by attenuated proinflammatory markers and cardiomyocyte apoptosis. Male 6-week-old mice received either streptozotocin (55mg/kg/day for 5 days), to induce type 1 diabetes, or citrate buffer vehicle. After 4 weeks of hyperglycemia, the mice were allocated to coenzyme Q10 supplementation (10mg/kg/day), treatment with the angiotensin-converting-enzyme inhibitor (ACE-I) ramipril (3mg/kg/day), treatment with olive oil vehicle, or no treatment for 8 weeks. Type 1 diabetes upregulated LV NADPH oxidase (Nox2, p22(phox), p47(phox) and superoxide production), LV uncoupling protein UCP3 expression, and both LV and systemic oxidative stress (LV 3-nitrotyrosine and plasma lipid peroxidation). All of these were significantly attenuated by coenzyme Q10. Coenzyme Q10 substantially limited type 1 diabetes-induced impairments in LV diastolic function (E:A ratio and deceleration time by echocardiography, LV end-diastolic pressure, and LV -dP/dt by micromanometry), LV remodeling (cardiomyocyte hypertrophy, cardiac fibrosis, apoptosis), and LV expression of proinflammatory mediators (tumor necrosis factor-α, with a similar trend for interleukin IL-1β). Coenzyme Q10's actions were independent of glycemic control, body mass, and blood pressure. Coenzyme Q10 compared favorably to improvements observed with ramipril. In summary, these data suggest that coenzyme Q10 effectively targets LV ROS upregulation to limit type 1 diabetic cardiomyopathy. Coenzyme Q10 supplementation may thus represent an effective alternative to ACE-Is for the treatment of cardiac complications in type 1 diabetic patients.

  16. Effects of hyperglycemia on lonidamine-induced acidification and de-energization of human melanoma xenografts and sensitization to melphalan

    PubMed Central

    Nath, Kavindra; Nelson, David S.; Heitjan, Daniel F.; Zhou, Rong; Leeper, Dennis B.; Glickson, Jerry D.

    2015-01-01

    We seek to exploit the natural tendency of melanomas and other tumors to convert glucose to lactate as a method for selective intracellular acidification of cancer cells and for potentiating the activity of N-mustard antineoplastic agents. We performed this study to evaluate whether induction of hyperglycemia (26 mM) could enhance the effects of lonidamine (LND, 100 mg/kg; i.p.) on inducing intracellular acidification, bioenergetic decline and potentiation of the activity of melphalan (LPAM) against DB-1 melanoma xenografts in mice. Intracellular pH (pHi), extracellular pH (pHe) and bioenergetics (βNTP/Pi) were reduced by 0.7 units (p<0.001), 0.3 units (p>0.05) and 51.4% (p<0.05), respectively. Therapeutic response to LPAM (7.5 mg/kg; i.v.) + LND (100 mg/kg; i.p.) was reduced by about a factor of 3 under hyperglycemic conditions compared to normoglycemia, producing a growth delay of 7.76 d (tumor doubling time = 5.31 d, cell kill = 64%) compared to LND alone of 1.70 d and LPAM alone of 0.29 d. Under normoglycemic conditions LND plus LPAM produced a growth delay of 17.75 d, corresponding to a cell kill of 90 % at the same doses for each of these agents. The decrease in tumor cell kill under hyperglycemic conditions correlates with an increase in tumor ATP levels resulting from increased glycolytic activity. However, hyperglycemia substantially increases lactic acid production in tumors by a factor of ~6 (p<0.05), but hyperglycemia did not increase the effects of LND on acidification of the tumor most likely because of the strong buffering action of carbon dioxide (the pKa of carbonic acid is 6.4). Therefore, this study demonstrates that addition of glucose during treatment with LND diminishes the activity of this agent. PMID:25702942

  17. Prior Exercise Training Prevent Hyperglycemia in STZ Mice by Increasing Hepatic Glycogen and Mitochondrial Function on Skeletal Muscle.

    PubMed

    de Carvalho, Afonso Kopczynski; da Silva, Sabrina; Serafini, Edenir; de Souza, Daniela Roxo; Farias, Hemelin Resende; de Bem Silveira, Gustavo; Silveira, Paulo Cesar Lock; de Souza, Claudio Teodoro; Portela, Luis Valmor; Muller, Alexandre Pastoris

    2017-04-01

    Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. We investigated the effect of a prior 30 days voluntary exercise protocol on STZ-diabetic CF1 mice. Glycemia, and the liver and skeletal muscle glycogen, mitochondrial function, and redox status were analyzed up to 5 days after STZ injection. Animals were engaged in the following groups: Sedentary vehicle (Sed Veh), Sedentary STZ (Sed STZ), Exercise Vehicle (Ex Veh), and Exercise STZ (Ex STZ). Exercise prevented fasting hyperglycemia in the Ex STZ group. In the liver, there was decreased on glycogen level in Sed STZ group but not in EX STZ group. STZ groups showed decreased mitochondrial oxygen consumption compared to vehicle groups, whereas mitochondrial H2 O2 production was not different between groups. Addition of ADP to the medium did not decrease H2 O2 production in Sed STZ mice. Exercise increased GSH level. Sed STZ group increased nitrite levels compared to other groups. In quadriceps muscle, glycogen level was similar between groups. The Sed STZ group displayed decreased O2 consumption, and exercise prevented this reduction. The H2 O2 production was higher in Ex STZ when compared to other groups. Also, GSH level decreased whereas nitrite levels increased in the Sed STZ compared to other groups. The PGC1 α levels increased in Sed STZ, Ex Veh, and Ex STZ groups. In summary, prior exercise training prevents hyperglycemia in STZ-mice diabetic associated with increased liver glycogen storage, and oxygen consumption by the mitochondria of skeletal muscle implying in increased oxidative/biogenesis capacity, and improved redox status of both tissues. J. Cell. Biochem. 118: 678-685, 2017. © 2016 Wiley Periodicals, Inc.

  18. A Family History of Diabetes Modifies the Association between Elevated Urine Albumin Concentration and Hyperglycemia in Nondiabetic Mexican Adolescents

    PubMed Central

    Jiménez-Corona, Aida; Ávila-Hermosillo, Antonio; Nelson, Robert G.; Ramírez-López, Guadalupe

    2015-01-01

    We examined the frequency of elevated urine albumin concentration (UAC) and its association with metabolic syndrome (MetS) and metabolic markers in 515 nondiabetic Mexican adolescents stratified by family history of diabetes (FHD). UAC was measured in a first morning urine sample and considered elevated when excretion was ≥20 mg/mL. MetS was defined using International Diabetes Federation criteria. Fasting insulin, insulin resistance, and lipids were evaluated. Multivariate logistic regression was performed. Elevated UAC was present in 12.4% and MetS was present in 8.9% of the adolescents. No association was found between elevated UAC and MetS. Among adolescents with FHD, 18.4% were overweight and 20.7% were obese, whereas, among those without a FHD, 15.9% were overweight and 7.5% were obese. Hyperglycemia was higher in those with elevated UAC than in those without (44.4% versus 5.1%, p = 0.003). Hyperglycemia (OR = 9.8, 95% CI 1.6–59.4) and number of MetS components (OR = 4.5, 95% CI 1.5–13.3) were independently associated with elevated UAC. Among female participants, abdominal obesity was associated with elevated UAC (OR = 4.5, 95% CI 1.2–16.9). Conclusion. Elevated UAC was associated neither with MetS nor with any metabolic markers in nondiabetic adolescents. However, FHD modified the association of elevated UAC with hyperglycemia and the number of MetS components. PMID:26347891

  19. A Family History of Diabetes Modifies the Association between Elevated Urine Albumin Concentration and Hyperglycemia in Nondiabetic Mexican Adolescents.

    PubMed

    Jiménez-Corona, Aida; Ávila-Hermosillo, Antonio; Nelson, Robert G; Ramírez-López, Guadalupe

    2015-01-01

    We examined the frequency of elevated urine albumin concentration (UAC) and its association with metabolic syndrome (MetS) and metabolic markers in 515 nondiabetic Mexican adolescents stratified by family history of diabetes (FHD). UAC was measured in a first morning urine sample and considered elevated when excretion was ≥20 mg/mL. MetS was defined using International Diabetes Federation criteria. Fasting insulin, insulin resistance, and lipids were evaluated. Multivariate logistic regression was performed. Elevated UAC was present in 12.4% and MetS was present in 8.9% of the adolescents. No association was found between elevated UAC and MetS. Among adolescents with FHD, 18.4% were overweight and 20.7% were obese, whereas, among those without a FHD, 15.9% were overweight and 7.5% were obese. Hyperglycemia was higher in those with elevated UAC than in those without (44.4% versus 5.1%, p = 0.003). Hyperglycemia (OR = 9.8, 95% CI 1.6-59.4) and number of MetS components (OR = 4.5, 95% CI 1.5-13.3) were independently associated with elevated UAC. Among female participants, abdominal obesity was associated with elevated UAC (OR = 4.5, 95% CI 1.2-16.9). Conclusion. Elevated UAC was associated neither with MetS nor with any metabolic markers in nondiabetic adolescents. However, FHD modified the association of elevated UAC with hyperglycemia and the number of MetS components.

  20. Administration of Lactobacillus casei and Bifidobacterium bifidum Ameliorated Hyperglycemia, Dyslipidemia, and Oxidative Stress in Diabetic Rats

    PubMed Central

    Sharma, Poonam; Bhardwaj, Priyanka; Singh, Rambir

    2016-01-01

    Background: The present work was planned to evaluate the antihyperglycemic, lipid-lowering, and antioxidant effect of Lactobacillus casei and Bifidobacterium bifidum in streptozotocin (STZ)-induced diabetic rats. Methods: Single daily dose of 1 × 107 cfu/ml of L. casei and B. bifidum alone and in combination of both was given to Wistar rats orally by gavaging for 28 days. Glucose tolerance test, fasting blood glucose (FBG), lipid profile, and glycosylated hemoglobin (HbA1c) were measured from blood. Glycogen from thigh muscles and liver and oxidative stress parameters from pancreas were analyzed. Results: Administration of L. casei and B. bifidum alone and in combination of both to diabetic rats decreased serum FBG (60.47%, 55.89%, and 56.49%, respectively), HbA1c (28.11%, 28.61%, and 28.28%), total cholesterol (171.69%, 136.47%, and 173.58%), triglycerides (9.935%, 8.58%, and 7.91%), low-density lipoproteins (53.27%, 53.35%, and 52.91%) and very low-density lipoproteins (10%, 8.58%, and 11.15%, respectively) and increased high-density lipoproteins (13.73%, 15.47%, and 15.47%), and insulin (19.50%, 25.80%, and 29.47%, respectively). The treatment also resulted in increase in muscle (171.69%, 136.47%, and 173.58%) and liver (25.82%, 6.63%, and 4.02%) glycogen level. The antioxidant indexes in pancreas of diabetic rats returned to normal level with reduction in lipid peroxidation (30.89%, 46.46%, and 65.36%) and elevation in reduced glutathione (104.5%, 161.34%, and 179.04%), superoxide dismutase (38.65%, 44.32%, and 53.35%), catalase (13.08%, 27%, and 31.52%), glutathione peroxidase (55.56%, 72.23%, and 97.23%), glutathione reductase (49.27%, 88.40%, and 110.86%), and glutathione-S-transferase (140%, 220%, and 246.6%, respectively) on treatment with L. casei, B. bifidum, and combination treatment. Conclusions: Administration of L. casei and B. bifidum alone and in combination of both ameliorated hyperglycemia, dyslipidemia, and oxidative stress in STZ

  1. Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study).

    PubMed

    Singh, J P; Larson, M G; O'Donnell, C J; Wilson, P F; Tsuji, H; Lloyd-Jones, D M; Levy, D

    2000-08-01

    described in subjects with hyperglycemia.

  2. Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform.

    PubMed

    Yi, Ting; Cheema, Yaser; Tremble, Sarah M; Bell, Stephen P; Chen, Zengyi; Subramanian, Meenakumari; LeWinter, Martin M; VanBuren, Peter; Palmer, Bradley M

    2012-11-02

    It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG) and that exposure of zinc ion (Zn2+) to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR) at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our results suggest that the

  3. Lesser than diabetes hyperglycemia in pregnancy is related to perinatal mortality: a cohort study in Brazil

    PubMed Central

    2011-01-01

    Background Gestational diabetes related morbidity increases along the continuum of the glycemic spectrum. Perinatal mortality, as a complication of gestational diabetes, has been little investigated. In early studies, an association was found, but in more recent ones it has not been confirmed. The Brazilian Study of Gestational Diabetes, a cohort of untreated pregnant women enrolled in the early 1990's, offers a unique opportunity to investigate this question. Thus, our objective is to evaluate whether perinatal mortality increases in a continuum across the maternal glycemic spectrum. Methods We prospectively enrolled and followed 4401 pregnant women attending general prenatal care clinics in six Brazilian state capitals, without history of diabetes outside of pregnancy, through to birth, and their offspring through the early neonatal period. Women answered a structured questionnaire and underwent a standardized 2-hour 75-g oral glucose tolerance test (OGTT). Obstetric care was maintained according to local protocols. We obtained antenatal, delivery and neonatal data from hospital records. Odds ratios (OR) were estimated using logistic regression. Results We ascertained 97 perinatal deaths (67 fetal and 31 early neonatal). Odds of dying increased according to glucose levels, statistically significantly so only for women delivering at gestational age ≥34 weeks (p < 0.05 for glycemia-gestational age interaction). ORs for a 1 standard deviation difference in glucose, when analyzed continuously, were for fasting 1.47 (95% CI 1.12, 1.92); 1-h 1.55 (95% CI 1.15, 2.07); and 2-h 1.53 (95% CI 1.15, 2.02). The adjusted OR for IADPSG criteria gestational diabetes was 2.21 (95% CI 1.15, 4.27); and for WHO criteria gestational diabetes, 3.10 (95% CI 1.39, 6.88). Conclusions In settings of limited detection and treatment of gestational diabetes mellitus, women across a spectrum of lesser than diabetes hyperglycemia, experienced a continuous rise in perinatal death with

  4. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  5. Risk factors for neurological worsening and symptomatic watershed infarction in internal carotid artery aneurysm treated by extracranial-intracranial bypass using radial artery graft.

    PubMed

    Matsukawa, Hidetoshi; Tanikawa, Rokuya; Kamiyama, Hiroyasu; Tsuboi, Toshiyuki; Noda, Kosumo; Ota, Nakao; Miyata, Shiro; Oda, Jumpei; Takeda, Rihee; Tokuda, Sadahisa; Kamada, Kyousuke

    2016-08-01

    OBJECT The revascularization technique, including bypass created using the external carotid artery (ECA), radial artery (RA), and M2 portion of middle cerebral artery (MCA), has remained indispensable for treatment of complex aneurysms. To date, it remains unknown whether diameters of the RA, superficial temporal artery (STA), and C2 portion of the internal carotid artery (ICA) and intraoperative MCA blood pressure have influences on the outcome and the symptomatic watershed infarction (WI). The aim of the present study was to evaluate the factors for the symptomatic WI and neurological worsening in patients treated by ECA-RA-M2 bypass for complex ICA aneurysm with therapeutic ICA occlusion. METHODS The authors measured the sizes of vessels (RA, C2, M2, and STA) and intraoperative MCA blood pressure (initial, after ICA occlusion, and after releasing the RA graft bypass) in 37 patients. Symptomatic WI was defined as presence of the following: postoperative new neurological deficits, WI on postoperative diffusion-weighted imaging, and ipsilateral cerebral blood flow reduction on SPECT. Neurological worsening was defined as the increase in 1 or more modified Rankin Scale scores. First, the authors performed receiver operating characteristic curve analysis for continuous variables and the binary end point of the symptomatic WI. The clinical, radiological, and physiological characteristics of patients with and without the symptomatic WI were compared using the log-rank test. Then, the authors compared the variables between patients with and without neurological worsening at discharge and at the 12-month follow-up examination or last hospital visit. RESULTS Symptomatic WI was observed in 2 (5.4%) patients. The mean MCA pressure after releasing the RA graft (< 55 mm Hg; p = 0.017), mean (MCA pressure after releasing the RA graft)/(initial MCA pressure) (< 0.70 mm Hg; p = 0.032), and mean cross-sectional area ratio ([RA/C2 diameter](2) < 0.40 mm [p < 0.0001] and [STA/C2

  6. Mulberry leaf phenolics ameliorate hyperglycemia-induced oxidative stress and stabilize mitochondrial membrane potential in HepG2 cells.

    PubMed

    Zou, Yu-Xiao; Shen, Wei-Zhi; Liao, Sen-Tai; Liu, Fan; Zheng, Shan-Qing; Blumberg, Jeffrey B; Chen, C-Y Oliver

    2014-12-01

    To investigate the effect of phenolics in mulberry leaves (mulberry leaf phenolics; MLP) on hyperglycemia-induced oxidative stress and mitochondrial membrane potential (ΔΨm) in HepG2 cells; we treated HepG2 with glucose [5.5 (N-Glc) or 50 mmol/L (Hi-Glc)] with or without MLP at 10 or 100 µmol/L gallic acid equivalents and assessed level of reactive oxidant species (ROS), ΔΨm, malondialdehyde (MDA) and nuclear factor-kappaB (NF-κB) activation. Hi-Glc-induced oxidative damage was demonstrated by a series of increase in superoxides (560%, 0.5 h), MDA (400%, 24 h), NF-κB activation (474%, 4 h) and a wild fluctuation of ΔΨm relative to the control cells (p ≤ 0.05). MLP treatments ameliorate Hi-Glc-induced negative effects by a 40% reduction in ROS production, 34-44% reduction in MDA production, over 35% inhibition of NF-κB activation, as well as exert protective effect on HepG2 cells from change in ΔΨm. Our data show that MLP in vitro can protect hepatoctyes from hyperglycemia-induced oxidative damages.

  7. Antihyperglycemic Potential of Grewia asiatica Fruit Extract against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms

    PubMed Central

    Khattab, Hala A. H.; El-Shitany, Nagla A.; Abdallah, Inas Z. A.; Yousef, Fatimah M.; Alkreathy, Huda M.

    2015-01-01

    Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200 mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1β, and tumor necrosis factor- (TNF-) α are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1β and TNF-α. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic β-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect. PMID:26347423

  8. Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose.

    PubMed

    Frantz, Stefan; Calvillo, Laura; Tillmanns, Jochen; Elbing, Inka; Dienesch, Charlotte; Bischoff, Hilmar; Ertl, Georg; Bauersachs, Johann

    2005-04-01

    Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.

  9. Hyperglycemia and Inflammatory Property of Circulating Monocytes are Associated with Inflammatory Property of Carotid Plaques in Patients Undergoing Carotid Endarterectomy

    PubMed Central

    Tanaka, Masashi; Masuda, Shinya; Matsuo, Yoshiyuki; Sasaki, Yousuke; Yamakage, Hajime; Muranaka, Kazuya; Wada, Hiromichi; Hasegawa, Koji; Tsukahara, Tetsuya; Shimatsu, Akira

    2016-01-01

    Aim: This study aims to determine the association between glucose metabolism and proinflammatory/anti-inflammatory properties of circulating monocytes or those of carotid plaques in patients who underwent carotid endarterectomy. Methods: Clinical characteristics and expression levels of proinflammatory/anti-inflammatory markers in circulating monocytes/carotid plaques were examined in 12 patients with diabetes and 12 patients without diabetes. Results: Circulating monocytes from patients with diabetes revealed higher tumor necrosis factor (TNF)-α and lower interleukin (IL)-10 expression levels compared with those from patients without diabetes, which was also observed in carotid plaques from patients with diabetes. Hyperglycemia revealed positive and negative correlations with the ratios of IL-6+ and IL-10+ cells in carotid plaques, respectively. Moreover, we determined a positive correlation between circulating monocytes and carotid plaques with respect to TNF-α and IL-6 expressions. Conclusions: The inflammatory property of circulating monocytes was associated with that of carotid plaques. Hyperglycemia increased inflammatory properties and decreased anti-inflammatory properties of carotid plaques. PMID:27001002

  10. Alleviation of Hyperglycemia Induced Vascular Endothelial Injury by Exenatide Might Be Related to the Reduction of Nitrooxidative Stress

    PubMed Central

    Zhao, Qian; Xu, Chun-ling; Xiong, Hai-yan; Huang, Wen; Zhang, Mei; Wang, Yun; Wang, Si-yu

    2013-01-01

    We will investigate the effects of exenatide on vascular endothelial injury and nitrooxidative stress in hyperglycemia both in vivo and in vitro and explore the role of nitrooxidative stress in endothelium-protective action of exenatide. Healthy male Wistar rats were randomly divided into 4 groups: control, diabetes mellitus (DM) model, low dose of exenatide treatment, and high dose of exenatide treatment. In vitro study showed that, compared with control group, the DM rats exhibited a lowered endothelium-dependent relaxation and damaged structural integrity of thoracic aortas, and there was a significant increase in plasma nitrotyrosine concentration. These parameters were improved after treatment with either low dose or high dose of exenatide for 45 days. In vitro study showed that exendin-4 (the active ingredient of exenatide) attenuated HUVECs injury induced by high glucose, with improving cell viability and attenuating cell apoptosis. Exendin-4 also significantly alleviated the increased malondialdehyde (MDA), nitrotyrosine content, and inducible nitric oxide synthase (iNOS) expression induced by high glucose in HUVECs. In conclusion, this study demonstrates that exenatide treatment can alleviate the vascular endothelial injury, as well as attenuating the nitrooxidative stress in hyperglycemia, implying that the endothelium-protective effect of exenatide might be related to the reduction of nitrooxidative stress. PMID:24371833

  11. Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice.

    PubMed

    Sim, Mi-Ok; Ham, Ju Ri; Lee, Hae-In; Seo, Kwon-Il; Lee, Mi-Kyung

    2014-06-05

    This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid β-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.

  12. Spirulina versicolor improves insulin sensitivity and attenuates hyperglycemia-mediated oxidative stress in fructose-fed rats

    PubMed Central

    Hozayen, Walaa G.; Mahmoud, Ayman M.; Soliman, Hanan A.; Mostafa, Sanura R.

    2016-01-01

    Aim: The current study aimed to investigate the anti-hyperglycemic, anti-hyperlipidemic and insulin sensitizing effects of the cyanobacterium Spirulina versicolor extract in fructose-fed rats. Materials and Methods: Rats were fed 30% fructose solution in drinking water for 4 weeks. Animals exhibited hyperglycemia and hyperinsulinemia were selected for further investigations. Diabetic and control rats were orally supplemented with 50 mg/kg body weight S. versicolor extract for 4 weeks. Results: At the end of 8 weeks, fructose-fed rats showed a significant increase in serum glucose, insulin, cholesterol, triglycerides, cardiovascular risk indices and insulin resistance. Treatment of the fructose-fed rats with S. versicolor extract improved this metabolic profile. Fructose feeding produced a significant increase in serum tumor necrosis factor alpha and a decrease in adiponectin levels. In addition, fructose-fed rats exhibited a significant increase in liver, kidney and heart lipid peroxidation levels, and declined antioxidant defenses. Supplementation of the fructose-fed rats with S. versicolor extract reversed these alterations. Conclusion: S. versicolor attenuates hyperglycemia-mediated oxidative stress and inflammation, and is thus effective in improving insulin sensitivity in fructose-fed rats. PMID:27069726

  13. Green Synthesis of Oxovanadium(IV)/chitosan Nanocomposites and Its Ameliorative Effect on Hyperglycemia, Insulin Resistance, and Oxidative Stress.

    PubMed

    Liu, Yanjun; Jie, Xu; Guo, Yongli; Zhang, Xin; Wang, Jingfeng; Xue, Changhu

    2016-02-01

    In this paper, the preparation, characterization, and ameliorative effect on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, oxidative stress in mice of novel oxovanadium(IV)/chitosan (OV/CS) nanocomposites were investigated. The nanobiocomposite was produced by chemical reduction by chitosan and L-ascorbic acid using microwave heating, under environment-friendly conditions, using aqueous solutions, and notably, by using both mediators as reducing and stabilizing agents. In addition, OV/CS nanocomposites were characterized by transmission electron microscopy, energy dispersive spectroscopy, particle size, and zeta potential measurements. In vivo experiments were designed to examine whether the OV/CS nanocomposites would provide additional benefits on oxidative stress, hyperglycemia, and insulin resistance in mice with type 2 diabetes. The results rendered insulin resistant by treating with OV/CS nanocomposites alleviate insulin resistance and improve oxidative stress. Such nanocomposite seem to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes.

  14. Protective effects of Zygophyllum album extract against deltamethrin-induced hyperglycemia and hepato-pancreatic disorders in rats.

    PubMed

    Feriani, Anouar; Hachani, Rafik; Kaabi, Belhassen; Ncir, Marwa; El Feki, Abdelfattah; Allagui, Mohamed Salah

    2016-06-23

    The current study was designed to investigate the possible mechanism involved in hyperglycemia induced by chronic exposure to deltamethrin (DLM) in rat and to assess whether this damage is amenable to modulation by Zygophyllum album. DLM, a synthetic pyrethroid pesticide, was administrated at a dose of 4 mg/kg body mass, during 60 days. Compared with control, DLM showed a significant increase of blood glucose (p ≤ 0.01) and glycosylated hemoglobin levels (p ≤ 0.01) and a clear decrease (p ≤ 0.01) of insulin and total hemoglobin levels. In addition, hepatic glycogen content and the activity of hexokinase decreased (p ≤ 0.01), whereas the activities of glucose-6-phosphatase and glycogen phosphorylase were significantly increased (p ≤ 0.01). Moreover, pancreatic lipid peroxidation (TBARS level) was higher (p ≤ 0.01) and oxidative stress biomarkers (SOD, CAT, GPx, and GSH) were altered owing to DLM toxicity. However, Z. album, when combined with DLM, significantly ameliorated almost all the hepato-pancreatic disorders induced by DLM alone. Furthermore, Z. album supplement was found to be effective in preserving the normal histological appearance of hepatic and pancreatic tissue. In conclusion, this study suggested that, owing to its antioxidant effects, methanolic extract of Z. album (MEZAL) can potentially prevent the hyperglycemia observed in DLM-treated group.

  15. Lectin from Crataeva tapia Bark Improves Tissue Damages and Plasma Hyperglycemia in Alloxan-Induced Diabetic Mice

    PubMed Central

    da Rocha, Amanda Alves; Araújo, Tiago Ferreira da Silva; da Fonseca, Caíque Silveira Martins; da Mota, Diógenes Luís; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso; Correia, Maria Tereza dos Santos; Lima, Vera Lúcia de Menezes

    2013-01-01

    Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil. Progressive decline in renal and hepatic functions has been described in patients with diabetes mellitus, and mortality rate is increased in patients with chronic liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark lectin (CrataBL) improves hyperglycemia and renal and hepatic damage in diabetic mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at dose of 10 mg/Kg/day and 20 mg/Kg/day for 10 days significantly reduced serum glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine, aspartate aminotransferase, and alanine aminotransferase were also significantly reduced after treatment with both doses of CrataBL. Furthermore, histological analysis of liver, kidney, and pancreas revealed an improvement in the tissue morphology upon treatment with CrataBL. The results suggest that CrataBL has a beneficial hypoglycemic activity and improves the renal and hepatic complications of diabetes. Therefore, this lectin may be a promising agent for the treatment of diabetes, and this might be the basis for its use in the folk medicine as an alternative treatment to manage diabetes-related complications such as hyperglycemia and tissue damage. PMID:24324521

  16. Phagocytosis via Complement or Fc-Gamma Receptors Is Compromised in Monocytes from Type 2 Diabetes Patients with Chronic Hyperglycemia

    PubMed Central

    Restrepo, Blanca I.; Twahirwa, Marcel; Rahbar, Mohammad H.; Schlesinger, Larry S.

    2014-01-01

    Type 2 diabetes patients (DM2) have a higher risk of tuberculosis (TB) that may be attributed to functional defects in their mononuclear phagocytes given the critical role of these cells in Mycobacterium tuberculosis containment. Our previous findings suggest that monocytes from DM2 have reduced association with serum-opsonized M. tuberculosis. To determine if this alteration is due to defects in phagocytosis via complement or Fc-gamma receptors (FcγRs), in this study we evaluated the uptake of sheep red blood cells coated with IgG or complement, respectively, by monocytes from individuals with and without DM2. We found that chronic hyperglycemia was significantly associated with reduced phagocytosis via either receptor by univariable and multivariable analyses. This defect was independent of host serum opsonins and flow cytometry data indicated this was not attributed to reduced expression of these phagocytic receptors on DM2 monocytes. The positive correlation between both pathways (R = 0.64; p = 0.003) indicate that monocytes from individuals with chronic hyperglycemia have a defect in the two predominant phagocytic pathways of these cells. Given that phagocytosis is linked to activation of effector mechanisms for bacterial killing, it is likely that this defect is one factor contributing to the higher susceptibility of DM2 patients to pathogens like M. tuberculosis. PMID:24671137

  17. Dietary obacunone supplementation stimulates muscle hypertrophy, and suppresses hyperglycemia and obesity through the TGR5 and PPARγ pathway

    SciTech Connect

    Horiba, Taro; Katsukawa, Masahiro; Mita, Moeko; Sato, Ryuichiro

    2015-08-07

    Obacunone is a limonoid that is predominantly found in Citrus. Although various biological activities of limonoids have been reported, little is known about the beneficial effects of obacunone on metabolic disorders. In the present study, we examined the effects of dietary obacunone supplementation on obese KKAy mice, to clarify the function of obacunone in metabolic regulation. Mice were pair-fed a normal diet either alone or supplemented with 0.1% w/w obacunone for 28 days. Compared with the control, obacunone-fed mice had lower glycosylated hemoglobin, blood glucose, and white adipose tissue weight, although there was no significant difference in body weight. Obacunone treatment also significantly increased the weight of the gastrocnemius and quadriceps muscles. Reporter gene assays revealed that obacunone stimulated the transcriptional activity of the bile acids-specific G protein-coupled receptor, TGR5, in a dose-dependent manner. In addition, obacunone inhibited adipocyte differentiation in 3T3-L1 cells and antagonized ligand-stimulated peroxisome proliferator-activated receptor γ (PPARγ) transcriptional activity. These results suggest that obacunone stimulates muscle hypertrophy and prevents obesity and hyperglycemia, and that these beneficial effects are likely to be mediated through the activation of TGR5 and inhibition of PPARγ transcriptional activity. - Highlights: • Citrus limonoid obacunone prevents hyperglycemia in obese, diabetic KKAy mice. • Obacunone reduces fat content and stimulates muscle hypertrophy in KKAy mice. • Obacunone stimulates TGR5 transcriptional activities. • Obacunone antagonizes PPARγ and inhibits lipid accumulation in adipocytes.

  18. Serial investigation of continuous glucose monitoring in a very low birth weight infant with transient late-onset hyperglycemia.

    PubMed

    Nakamura, Toshihiko; Hatanaka, Daisuke; Nakamura, Mari; Kusakari, Michiko; Takahashi, Hidehiro; Kamohara, Takashi

    2016-12-16

    Transient late-onset hyperglycemia was detected in a very low birth weight (VLBW) infant (gestational age 28 weeks, birth weight 1,082 g) by routine point-of-care glucose monitoring. The infant had no clinical symptom. Serial continuous glucose monitoring (CGM) was conducted for 3 days at 31, 35, and 39 weeks' post conceptual age. The difference values between the maximum and minimum blood glucose levels during the interval from one enteral feeding to the next enteral feeding were 32.3±14.3 mg/dL, 47.5±22.9 mg/dL, and 27.5±12.9 mg/dL for the 1(st), 2(nd), and 3(rd) CGM, respectively. The serial change in the values was statistically significant (p<0.01).CGM is widely used as a routine clinical practice, which is true even in VLBW infants. Hyperglycemic events detected by only once of CGM in otherwise healthy preterm infants have already been reported on larger numbers of patients. To our knowledge, this is the first report that the change of glucose intolerance in a VLBW infant with transient late-onset hyperglycemia was investigated by serial CGM.

  19. Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: review of published reports.

    PubMed

    Tzamaloukas, Antonios H; Ing, Todd S; Elisaf, Moses S; Raj, Dominic S C; Siamopoulos, Kostas C; Rohrscheib, Mark; Murata, Glen H

    2011-06-01

    The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K(+)) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K(+) during treatment of DH with insulin included the starting serum K(+) level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.

  20. Intraperitoneal administration of CDP-choline and its cholinergic and pyrimidinergic metabolites induce hyperglycemia in rats: involvement of the sympathoadrenal system.

    PubMed

    Ilcol, Y O; Cansev, M; Yilmaz, M S; Hamurtekin, E; Ulus, I H

    2007-01-01

    CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit neuroprotective actions. On the other hand, little is known regarding its peripheral actions. Intraperitoneal administration of CDP-choline (200-600 micromol/kg) induced a dose- and time-dependent hyperglycemia in rats. Hyperglycemic response to CDP-choline was associated with several-fold elevations in serum concentrations of CDP-choline and its metabolites. Intraperitoneal administration of phosphocholine, choline, cytidine, cytidine monophosphate, cytidine diphosphate, cytidine triphosphate, uridine, uridine monophosphate, uridine diphosphate and uridine triphosphate also produced significant hyperglycemia. Pretreatment with atropine methyl nitrate failed to alter the hyperglycemic responses to CDP-choline and its metabolites whereas hexamethonium, the ganglionic nicotinic receptor antagonist which blocks nicotinic cholinergic neurotransmission at the autonomic ganglionic level, blocked completely the hyperglycemia induced by CDP-choline, phosphocholine and choline, and attenuated the hyperglycemic response to cytidine monophosphate and cytidine. Increased blood glucose following CDP-choline, phosphocholine and choline was accompanied by elevated plasma catecholamine concentrations. Hyperglycemia elicited by CDP-choline and its metabolites was entirely blocked either by pretreatment with a nonselective -adrenoceptor antagonist phentolamine or by the 2-adrenoceptor antagonist, yohimbine. Hyperglycemic responses to CDP-choline, choline, cytidine monophosphate and cytidine were not affected by chemical sympathectomy, but were prevented by bilateral adrenalectomy. Phosphocholine-induced hyperglycemia was attenuated by bilateral adrenalectomy or by chemical sympathectomy. These data show that CDP-choline and its metabolites induce hyperglycemia which is mediated by activation of ganglionic

  1. Acute mitral regurgitation in Takotsubo cardiomyopathy.

    PubMed

    Bouabdallaoui, Nadia; Wang, Zhen; Lecomte, Milena; Ennezat, Pierre V; Blanchard, Didier

    2015-04-01

    Takotsubo cardiomyopathy (TTC) is a well-recognised entity that commonly manifests with chest pain, ST segment abnormalities and transient left ventricular apical ballooning without coronary artery obstructive disease. This syndrome usually portends a favourable outcome. In the rare haemodynamically unstable TTC patients, acute mitral regurgitation (MR) related to systolic anterior motion (SAM) of the mitral valve and left ventricular outflow tract obstruction (LVOTO) is to be considered. Bedside echocardiography is key in recognition of this latter condition as vasodilators, inotropic agents or intra-aortic balloon counter-pulsation worsen the patient's clinical status. We discuss here a case of TTC where nitrate-induced subaortic obstruction and mitral regurgitation led to haemodynamic instability.

  2. Acute bacterial sinusitis in children.

    PubMed

    DeMuri, Gregory; Wald, Ellen R

    2013-10-01

    On the basis of strong research evidence, the pathogenesis of sinusitis involves 3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of sinus secretions. On the basis of studies of the microbiology of otitis media, H influenzae is playing an increasingly important role in the etiology of sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase production by H influenzae is increasing in respiratory isolates in the United States. On the basis of some research evidence and consensus,the presentation of acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent, severe, and worsening symptoms. On the basis of some research evidence and consensus,the diagnosis of sinusitis should be made by applying strict clinical criteria. This approach will select children with upper respiratory infection symptoms who are most likely to benefit from an antibiotic. On the basis of some research evidence and consensus,imaging is not indicated routinely in the diagnosis of sinusitis. Computed tomography or magnetic resonance imaging provides useful information when complications of sinusitis are suspected. On the basis of some research evidence and consensus,amoxicillin-clavulanate should be considered asa first-line agent for the treatment of sinusitis.

  3. Acute Vestibulopathy

    PubMed Central

    Cha, Yoon-Hee

    2011-01-01

    The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan. PMID:23983835

  4. Acute Blindness.

    PubMed

    Meekins, Jessica M

    2015-09-01

    Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed.

  5. Impetigo presenting as an acute necrotizing swelling of the lower lip in an adult patient.

    PubMed

    Ghafoor, Mohammed; Halsnad, Moorthy; Fowell, Christopher; Millar, Brian G

    2012-06-01

    The authors present an unusual case of an acute swelling of the lower lip and septicemia in a 35-year-old, recent immigrant male arriving from India. The patient presented in our emergency department with a 48-hour history of a worsening, painful swelling of the lower lip. On presentation, he was pyrexial and the lip was found to be acutely inflamed with honey-colored crusting, pustular lesions, and induration . A diagnosis of impetigo leading to necrosis of the lip was established, a rare phenomenon potentially resulting in significant tissue destruction. Appropriate medical management achieved a good outcome and prevented disabling tissue loss of the orofacial region.

  6. Antecedent thermal injury worsens split-thickness skin graft quality: A clinically relevant porcine model of full-thickness burn, excision and grafting.

    PubMed

    Carlsson, Anders H; Rose, Lloyd F; Fletcher, John L; Wu, Jesse C; Leung, Kai P; Chan, Rodney K

    2017-02-01

    Current standard of care for full-thickness burn is excision followed by autologous split-thickness skin graft placement. Skin grafts are also frequently used to cover surgical wounds not amenable to linear closure. While all grafts have potential to contract, clinical observation suggests that antecedent thermal injury worsens contraction and impairs functional and aesthetic outcomes. This study evaluates the impact of antecedent full-thickness burn on split-thickness skin graft scar outcomes and the potential mediating factors. Full-thickness contact burns (100°C, 30s) were created on the backs of anesthetized female Yorkshire Pigs. After seven days, burn eschar was tangentially excised and covered with 12/1000th inch (300μm) split-thickness skin graft. For comparison, unburned wounds were created by sharp excision to fat before graft application. From 7 to 120days post-grafting, planimetric measurements, digital imaging and biopsies for histology, immunohistochemistry and gene expression were obtained. At 120days post-grafting, the Observer Scar Assessment Scale, colorimetry, contour analysis and optical graft height assessments were performed. Twenty-nine porcine wounds were analyzed. All measured metrics of clinical skin quality were significantly worse (p<0.05) in burn injured wounds. Histological analysis supported objective clinical findings with marked scar-like collagen proliferation within the dermis, increased vascular density, and prolonged and increased cellular infiltration. Observed differences in contracture also correlated with earlier and more prominent myofibroblast differentiation as demonstrated by α-SMA staining. Antecedent thermal injury worsens split-thickness skin graft quality, likely by multiple mechanisms including burn-related inflammation, microscopically inadequate excision, and dysregulation of tissue remodeling. A valid, reliable, clinically relevant model of full-thickness burn, excision and skin replacement therapy has been

  7. Measures of Hip Morphology are Related to Development of Worsening Radiographic Hip Osteoarthritis Over 6 to 13 Year Follow-Up: The Johnston County Osteoarthritis Project

    PubMed Central

    Nelson, Amanda E.; Stiller, Jamie L.; Shi, Xiaoyan A.; Leyland, Kirsten M.; Renner, Jordan B.; Schwartz, Todd A.; Arden, Nigel K.; Jordan, Joanne M.

    2015-01-01

    Objectives We sought to describe the effect of alterations in hip morphology with respect to worsening hip OA in a community-based sample including African American (AA) and white men and women. Methods This nested case-control study defined case hips as Kellgren Lawrence grade (KLG)<3 on baseline supine pelvis radiographs and KLG≥3 or THR for OA at the 1st or 2nd follow-up visit (mean 6 and 13 years, respectively); control hips had KLG<3 at both visits, with gender/race distribution similar to cases. Hip morphology was assessed using HipMorf software (Oxford, UK). Descriptive means and standard errors were obtained from generalized estimating equation (GEE) models. Sex-stratified GEE regression models (accounting for within-person correlation), adjusted for age, race, BMI, and side were then employed. Results A total of 120 individuals (239 hips; 71 case/168 control) were included (25% male, 26% AA, mean age 62 years, BMI 30 kg/m2). Case hips tended to have greater baseline AP alpha angles, smaller minimum joint space width (mJSW) and more frequent triangular index signs. Adjusted results among men revealed that higher AP alpha angle, Gosvig ratio, and acetabular index were positively associated with case hips; coxa profunda was negatively associated. Among women, greater AP alpha angle, smaller mJSW, protrusio acetabuli, and triangular index sign were associated with case hips. Conclusions We confirmed an increased risk of worsening hip OA due to baseline features of cam deformity among men and women, as well as protrusio acetabuli among women, and provide the first estimates of these measures in AAs. PMID:26497609

  8. Therapeutic Effect of Vagus Nerve Stimulation on Depressive-Like Behavior, Hyperglycemia and Insulin Receptor Expression in Zucker Fatty Rats

    PubMed Central

    Rong, Peijing; McCabe, Michael F.; Wang, Xing; Zhao, Jingjun; Ben, Hui; Wang, Shuxing

    2014-01-01

    Depression and type 2 diabetes (T2D) are common comorbid diseases and highly prevalent in the clinical setting with an unclarified mechanism. Zucker diabetic fatty (ZDF, fa/fa) rats natively develop T2D with hyperglycemia and hyperinsulinemia. Here we studied whether ZDF rats also innately develop depression, what a correlation is between depression and T2D, whether insulin receptor (IR) expression is involved in, and whether transcutaneous auricular vagus nerve stimulation (taVNS) would be beneficial in amelioration of the comorbidity. Six week old male ZDF and Zucker lean (ZL, fa/+) littermates were randomly divided into naïve (ZDF, n = 6; ZL, n = 7) and taVNS (ZDF-taVNS, n = 8; ZL-taVNS, n = 6) groups. Once daily 30 min-taVNS sessions were administrated under anesthesia for 34 consecutive days in taVNS groups. Blood glucose levels were tested weekly, and plasma glycosylated hemoglobin (HbAlc) level and immobility time in forced swimming test were determined on day 35 in all groups. The expression of insulin receptor (IR) in various tissues was also detected by immunostaining and Western blot. We found that naïve ZDF rats developed hyperglycemia steadily. These ZDF rats showed a strong positive correlation between longer immobility time and higher plasma HbAlC level. Long term taVNS treatment simultaneously prevented the development of depression-like behavior and progression of hyperglycemia in ZDF rats. The expression of IR in various tissues of naïve ZDF rats is lower than in naïve ZL and long-term taVNS treated ZDF rats. Collectively, our results indicate that in ZDF rats, i) depression and T2D develop simultaneously, ii) immobility time and HbAlc concentrations are highly and positively correlated, iii) a low expression of IR may be involved in the comorbidity of depression and T2D, and iv) taVNS is antidiabetic and antidepressive possibly through IR expression upregulation. PMID:25365428

  9. Effects of hyperglycemia on lonidamine-induced acidification and de-energization of human melanoma xenografts and sensitization to melphalan.

    PubMed

    Nath, Kavindra; Nelson, David S; Heitjan, Daniel F; Zhou, Rong; Leeper, Dennis B; Glickson, Jerry D

    2015-03-01

    We seek to exploit the natural tendency of melanomas and other tumors to convert glucose to lactate as a method for the selective intracellular acidification of cancer cells and for the potentiation of the activity of nitrogen-mustard antineoplastic agents. We performed this study to evaluate whether the induction of hyperglycemia (26 mM) could enhance the effects of lonidamine (LND, 100 mg/kg; intraperitoneally) on the induction of intracellular acidification, bioenergetic decline and potentiation of the activity of melphalan (LPAM) against DB-1 melanoma xenografts in mice. Intracellular pH (pHi ), extracellular pH (pHe ) and bioenergetics (β-nucleoside triphosphate to inorganic phosphate ratio, β-NTP/Pi) were reduced by 0.7 units (p < 0.001), 0.3 units (p > 0.05) and 51.4% (p < 0.05), respectively. The therapeutic response to LPAM (7.5 mg/kg; intravenously) + LND (100 mg/kg; intraperitoneally) was reduced by about a factor of three under hyperglycemic conditions relative to normoglycemia, producing a growth delay of 7.76 days (tumor doubling time, 5.31 days; cell kill, 64%) compared with LND alone of 1.70 days and LPAM alone of 0.29 days. Under normoglycemic conditions, LND plus LPAM produced a growth delay of 17.75 days, corresponding to a cell kill of 90% at the same dose for each of these agents. The decrease in tumor cell kill under hyperglycemic conditions correlates with an increase in tumor ATP levels resulting from increased glycolytic activity. However, hyperglycemia substantially increases lactic acid production in tumors by a factor of approximately six (p < 0.05), but hyperglycemia did not increase the effects of LND on acidification of the tumor, most probably because of the strong buffering action of carbon dioxide (the pKa of carbonic acid is 6.4). Therefore, this study demonstrates that the addition of glucose during treatment with LND diminishes the activity of this agent.

  10. Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung

    PubMed Central

    Grasemann, C; Herrmann, R; Starschinova, J; Gertsen, M; Palmert, M R; Grasemann, H

    2017-01-01

    Background/Objectives: Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. Methods: We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. Results: Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. Conclusions: These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring. PMID:28218737

  11. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America.

    PubMed

    Ranilla, Lena Galvez; Kwon, Young-In; Apostolidis, Emmanouil; Shetty, Kalidas

    2010-06-01

    Traditionally used medicinal plants, herbs and spices in Latin America were investigated to determine their phenolic profiles, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension. High phenolic and antioxidant activity-containing medicinal plants and spices such as Chancapiedra (Phyllantus niruri L.), Zarzaparrilla (Smilax officinalis), Yerba Mate (Ilex paraguayensis St-Hil), and Huacatay (Tagetes minuta) had the highest anti-hyperglycemia relevant in vitro alpha-glucosidase inhibitory activities with no effect on alpha-amylase. Molle (Schinus molle), Maca (Lepidium meyenii Walp), Caigua (Cyclanthera pedata) and ginger (Zingiber officinale) inhibited significantly the hypertension relevant angiotensin I-converting enzyme (ACE). All evaluated pepper (Capsicum) genus exhibited both anti-hyperglycemia and anti-hypertension potential. Major phenolic compounds in Matico (Piper angustifolium R.), Guascas (Galinsoga parviflora) and Huacatay were chlorogenic acid and hydroxycinnamic acid derivatives. Therefore, specific medicinal plants, herbs and spices from Latin America have potential for hyperglycemia and hypertension prevention associated with Type 2 diabetes.

  12. Comparison of the efficacy of cardamom (Elettaria cardamomum) with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats.

    PubMed

    Nitasha Bhat, G M; Nayak, Nagendra; Vinodraj, K; Chandralekha, N; Mathai, Paul; Cherian, J

    2015-01-01

    To evaluate the efficacy of cardamom with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats. There were four groups of 6 rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received cardamom suspension 1 g/kg/10 mL of 2% gum acacia orally 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load, liver weight, liver volume were recorded, and histopathological analysis was done. The effects of cardamom were compared with that of pioglitazone. Dexamethasone caused hepatomegaly, dyslipidemia and hyperglycemia. Both pioglitazone and cardamom significantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone in comparison to cardamom (P < 0.01). Cardamom has comparable efficacy to pioglitazone in preventing dexamethasone-induced hepatomegaly, dyslipidemia, and fasting hyperglycemia.

  13. Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs

    SciTech Connect

    Chen Haibing; Jia Weiping; Xu Xun; Fan Ying; Zhu Dongqing; Wu Haixiang; Xie Zhenggao; Zheng Zhi

    2008-05-02

    Poly(ADP-ribose)polymerase (PARP) inhibitors decrease angiogenesis through reducing vascular endothelium growth factor (VEGF) induced proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In contrast to VEGF, pigment epithelium-derived factor (PEDF) has been demonstrated to act as a strong endogenous inhibitor of angiogenesis. Here, we show that PARP inhibition with a specific inhibitor PJ-34 or specific PARP antisense oligonucleotide upregulates hyperglycemia-induced PEDF expression in HUVECs in a dose-dependent manner. This results in the retard of activation of p38 MAP kinase and the concomitant decrease in cell apoptosis. These results give the first direct demonstration that PEDF might represent a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent.

  14. Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3-36 in healthy overweight/obese humans.

    PubMed

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

    2014-01-15

    Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial, glucose, insulin, PYY3-36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h) of PYY3-36 were lower (meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05), whereas insulin (meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and ghrelin (meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0-0.5, 4-4.5, and 8-8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P < 0.05). Also, meal-induced fullness was prevented (meal 1, P = 0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia. Furthermore, trends in ghrelin, PYY3-36, and fullness were described by different polynomial functions between the trials. In conclusion, hyperglycemia abolishes meal-induced satiety and dysregulates postprandial responses of the gut hormones PYY3-36 and ghrelin in overweight/obese healthy humans.

  15. Inflammatory Mediators and Glucose in Pregnancy: Results from a Subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

    PubMed Central

    Lowe, Lynn P.; Metzger, Boyd E.; Lowe, William L.; Dyer, Alan R.; McDade, Thomas W.; McIntyre, H. David

    2010-01-01

    Context: Inflammatory mediators are associated with type 2 and gestational diabetes. It is unknown whether there are associations with glucose in pregnant women with lesser degrees of hyperglycemia. Objective: The objective of the study was to examine associations of inflammatory mediators with maternal glucose levels and neonatal size in a subset of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Design: Eligible pregnant women underwent a 75-g oral glucose tolerance test between 24 and 32 wk gestation, and levels of C-peptide, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), and resistin were measured in fasting serum samples. Associations of inflammatory mediators with maternal glucose and with birth size were assessed using multiple linear regression analyses, adjusting for maternal body mass index (BMI), fasting C-peptide, and other potential confounders. Results: Mean levels of adiponectin declined, and PAI-1 and CRP increased across increasing levels of maternal glucose, BMI, and C-peptide. For example, for fasting plasma glucose less than 75 mg/dl and fasting plasma glucose of 90 mg/dl or greater, adiponectin was 22.5 and 17.4 μg/ml and PAI-1 was 30.9 and 34.2 ng/ml, respectively. Associations with 1- and 2-h plasma glucose remained significant for adiponectin (P < 0.001), PAI-1 (P < 0.05), and CRP (P < 0.01) after adjustment for BMI and C-peptide. Adiponectin and CRP were inversely associated with birth weight, sum of skinfolds and percent body fat, and PAI-1 with sum of skinfolds (all P < 0.05) after adjustment for confounders. Resistin was not associated with 1- or 2-h glucose or birth size. Conclusion: Levels of inflammatory mediators are associated with levels of maternal glucose in pregnant women without overt diabetes. PMID:20843942

  16. Fluctuations of Hyperglycemia and Insulin Sensitivity Are Linked to Menstrual Cycle Phases in Women With T1D

    PubMed Central

    Brown, Sue A.; Jiang, Boyi; McElwee-Malloy, Molly; Wakeman, Christian; Breton, Marc D.

    2015-01-01

    Background: Factors influencing glycemic variability in type 1 diabetes (T1D) may play a significant role in the refinement of closed loop insulin administration. Phase of menstrual cycle is one such factor that has been inadequately investigated. We propose that unique individual patterns can be constructed and used as parameters of closed loop systems. Method: Women with T1D on continuous subcutaneous insulin infusion and continuous glucose monitoring were studied for 3 consecutive menstrual cycles. Ovulation prediction kits and labs were used to confirm phase of menstrual cycle. Glycemic risks were assessed using the low- and high blood glucose indices (LBGI and HBGI). Insulin sensitivity (SI) was estimated using a Kalman filtering method from meal and insulin data. Overall change significance for glycemic risks was assessed by repeated measures ANOVA, with specific phases emphasized using contrasts. Results: Ovulation was confirmed in 33/36 cycles studied in 12 subjects (age = 33.1 ± 7.0 years, BMI = 25.7 ± 2.9 kg/m2, A1c = 6.8 ± 0.7%). Risk for hyperglycemia changed significantly during the cycle (P = .023), with HBGI increasing until early luteal phase and returning to initial levels thereafter. LBGI was steady in the follicular phase, decreasing thereafter but not significantly. SI was depressed during the luteal phase when compared to the early follicular phase (P ≤ .05). Total daily insulin, carbohydrates, or calories did not show any significant fluctuations. Conclusions: Women with T1D have glycemic variability changes that are specific to the individual and are linked to phase of cycle. An increased risk of hyperglycemia was observed during periovulation and early luteal phases compared to the early follicular phase; these changes appear to be associated with decreased insulin sensitivity during the luteal phase. PMID:26468135

  17. Pectinase-Processed Ginseng Radix (GINST) Ameliorates Hyperglycemia and Hyperlipidemia in High Fat Diet-Fed ICR Mice

    PubMed Central

    Yuan, Hai-Dan; Kim, Jung Tae; Chung, Sung Hyun

    2012-01-01

    To develop a ginseng product possessing an efficacy for diabetes, ginseng radix ethanol extract was treated with pectinase and obtained the GINST. In the present study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced hyper-glycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice were randomly divided into five groups: regular diet group (RD), high fat diet group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300 mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the glucose tolerance after glucose challenge. Fasting plasma glucose and insulin levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150, and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma triglyceride, total cholesterol and non-esterified fatty acid levels in the GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared to those in HFD control group. Enlarged adipocytes of HFD control group were markedly decreased in GINST-treated groups, and shrunken islets of HFD control mice were brought back to near normal shape in GINST300 group. Furthermore, GINST enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4 pathways, and could be a potential therapeutic agent for type 2 diabetes. PMID:24116299

  18. Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

    SciTech Connect

    Xu, Ying; Nie, Ling; Yin, Yang-Guang; Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan; Zhou, Shi-Wen

    2012-03-15

    Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

  19. Mild Gestational Hyperglycemia in Rat Induces Fetal Overgrowth and Modulates Placental Growth Factors and Nutrient Transporters Expression

    PubMed Central

    Cisse, Ouma; Fajardy, Isabelle; Dickes-Coopman, Anne; Moitrot, Emmanuelle; Montel, Valérie; Deloof, Sylvie; Rousseaux, Jean; Vieau, Didier; Laborie, Christine

    2013-01-01

    Mild gestational hyperglycemia is often associated with fetal overgrowth that can predispose the offspring to metabolic diseases later in life. We hypothesized that unfavorable intrauterine environment may compromise the development of placenta and contribute to fetal overgrowth. Therefore, we developed a rat model and investigated the effects of maternal dysglycemia on fetal growth and placental gene expression. Female rats were treated with single injection of nicotinamide plus streptozotocin (N-STZ) 1-week before mating and were studied at gestational day 21. N-STZ pregnant females displayed impaired glucose tolerance that is associated with a lower insulin secretion. Moderate hyperglycemia induced fetal overgrowth in 40% of newborns, from pregnancies with 10 to 14 pups. The incidence of macrosomia was less than 5% in the N-STZ pregnancies when the litter size exceeds 15 newborns. We found that placental mass and the labyrinthine layer were increased in macrosomic placentas. The expression of genes involved in placental development and nutrient transfer was down regulated in the N-STZ placentas of macrosomic and normosomic pups from pregnancies with 10 to 14 ones. However, we observed that lipoprotein lipase 1 (LPL1) gene expression was significantly increased in the N-STZ placentas of macrosomic pups. In pregnancies with 15 pups or more, the expression of IGFs and glucose transporter genes was also modulated in the control placentas with no additional effect in the N-STZ ones. These data suggest that placental gene expression is modulated by gestational conditions that might disrupt the fetal growth. We described here a new model of maternal glucose intolerance that results in fetal overgrowth. We proposed that over-expression of LPL1 in the placenta may contribute to the increased fetal growth in the N-STZ pregnancies. N-STZ model offers the opportunity to determinate whether these neonatal outcomes may contribute to developmental programming of metabolic

  20. Effects of metformin on hyperglycemia in an experimental model of tacrolimus- and sirolimus-induced diabetic rats

    PubMed Central

    Jin, Jian; Lim, Sun Woo; Jin, Long; Yu, Ji Hyun; Kim, Hyun Seon; Chung, Byung Ha; Yang, Chul Woo

    2017-01-01

    Background/Aims Metformin (MET) is a first-line drug for type 2 diabetes mellitus (DM); its effect on new-onset diabetes after transplantation caused by immunosuppressant therapy is unclear. We compared the effects of MET on DM caused by tacrolimus (TAC) or sirolimus (SRL). Methods DM was induced by injection of TAC (1.5 mg/kg) or SRL (0.3 mg/kg) for 2 weeks in rats, and MET (200 mg/kg) was injected for 2 more weeks. The effects of MET on DM caused by TAC or SRL were evaluated using an intraperitoneal glucose tolerance test (IPGTT) and by measuring plasma insulin concentration, islet size, and glucose-stimulated insulin secretion (GSIS). The effects of MET on the expression of adenosine monophosphate-activated protein kinase (AMPK), a pharmacological target of MET, were compared between TAC- and SRL-treated islets. Results IPGTT showed that both TAC and SRL induced hyperglycemia and reduced plasma insulin concentration compared with vehicle. These changes were reversed by addition of MET to SRL but not to TAC. Pancreatic islet cell size was decreased by TAC but not by SRL, but addition of MET did not affect pancreatic islet cell size in either group. MET significantly increased GSIS in SRL- but not in TAC-treated rats. AMPK expression was not affected by TAC but was significantly decreased in SRL-treated islets. Addition of MET restored AMPK expression in SRL-treated islets but not in TAC-treated islets. Conclusions MET has different effects on hyperglycemia caused by TAC and SRL. The discrepancy between these drugs is related to their different mechanisms causing DM. PMID:27688296

  1. Physical Activity, TV Watching Time, Sleeping, and Risk of Obesity and Hyperglycemia in the Offspring of Mothers with Gestational Diabetes Mellitus

    PubMed Central

    Zhang, Tao; Wang, Peng; Liu, Huikun; Wang, Leishen; Li, Weiqin; Leng, Junhong; Li, Nan; Zhang, Shuang; Qi, Lu; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Hu, Gang

    2017-01-01

    We investigated the association of physical activity, TV watching time, sleeping time with the risks of obesity and hyperglycemia among 1263 offspring aged 1–5 years of mothers with gestational diabetes (GDM) in a cross-sectional study. Logistic regression models were used to obtain the odd ratios (ORs) (95% confidence intervals [CI]) of childhood obesity and hyperglycemia associated with different levels of indoor activity, outdoor activity, TV watching, and sleeping time. The multivariable-adjusted ORs of obesity based on different levels of TV watching time (0, <1.0, and ≥1.0 hour/day) were 1.00, 1.21 (95% CI 0.72–2.05), and 2.20 (95% CI 1.33–3.63) (Ptrend = 0.003), respectively. The multivariable-adjusted ORs of hyperglycemia based on different levels of indoor activity (<5.0, 5.0–6.9, and ≥7.0 hours/day) were 1.00, 0.74 (95% CI 0.45–1.21), and 0.49 (95% CI 0.28–0.84) (Ptrend = 0.034), respectively. The multivariable-adjusted ORs of hyperglycemia associated with different levels of sleeping time (<11.0, 11.0–11.9, and ≥12.0 hours/day) were 1.00, 0.67 (95% CI 0.42–1.05), and 0.39 (95% CI 0.23–0.67) (Ptrend = 0.003), respectively. The present study indicated a positive association of TV watching with the risk of obesity, and an inverse association of either indoor activity or sleeping time with the risk of hyperglycemia among offspring born to GDM mothers in Tianjin, China. PMID:28120866

  2. Impact of Hyperglycemia and Low Oxygen Tension on Adipose-Derived Stem Cells Compared with Dermal Fibroblasts and Keratinocytes: Importance for Wound Healing in Type 2 Diabetes

    PubMed Central

    Lafosse, Aurore; Dufeys, Cécile; Beauloye, Christophe; Horman, Sandrine; Dufrane, Denis

    2016-01-01

    Aim Adipose-derived stem cells (ASC) are currently proposed for wound healing in those with type 2 diabetes mellitus (T2DM). Therefore, this study investigated the impact of diabetes on adipose tissue in relation to ASC isolation, proliferation, and growth factor release and the impact of hyperglycemia and low oxygen tension (found in diabetic wounds) on dermal fibroblasts, keratinocytes, and ASC in vitro. Methods Different sequences of hypoxia and hyperglycemia were applied in vitro to ASC from nondiabetic (n = 8) or T2DM patients (n = 4) to study cell survival, proliferation, and growth factor release. Comparisons of dermal fibroblasts (n = 8) and keratinocytes (primary lineage) were made. Results No significant difference of isolation and proliferation capacities was found in ASC from nondiabetic and diabetic humans. Hypoxia and hyperglycemia did not impact cell viability and proliferation. Keratinocyte Growth Factor release was significantly lower in diabetic ASC than in nondiabetic ASC group in each condition, while Vascular Endothelial Growth Factor release was not affected by the diabetic origin. Nondiabetic ASC exposition to hypoxia (0.1% oxygen) combined with hyperglycemia (25mM glucose), resulted in a significant increase in VEGF secretion (+64%, p<0.05) with no deleterious impact on KGF release in comparison to physiological conditions (5% oxygen and 5 mM glucose). Stromal cell-Derived Factor-1α (-93%, p<0.001) and KGF (-20%, p<0.05) secretion by DF decreased in these conditions. Conclusions A better profile of growth factor secretion (regarding wound healing) was found in vitro for ASC in hyperglycemia coupled with hypoxia in comparison to dermal fibroblasts and keratinocytes. Interestingly, ASC from T2DM donors demonstrated cellular growth rates and survival (in hypoxia and hyperglycemic conditions) similar to those of healthy ASC (from normoglycemic donors); however, KGF secretion was significantly depleted in ASC obtained from T2DM patients. This

  3. Physical Activity, TV Watching Time, Sleeping, and Risk of Obesity and Hyperglycemia in the Offspring of Mothers with Gestational Diabetes Mellitus

    NASA Astrophysics Data System (ADS)

    Zhang, Tao; Wang, Peng; Liu, Huikun; Wang, Leishen; Li, Weiqin; Leng, Junhong; Li, Nan; Zhang, Shuang; Qi, Lu; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Hu, Gang

    2017-01-01

    We investigated the association of physical activity, TV watching time, sleeping time with the risks of obesity and hyperglycemia among 1263 offspring aged 1–5 years of mothers with gestational diabetes (GDM) in a cross-sectional study. Logistic regression models were used to obtain the odd ratios (ORs) (95% confidence intervals [CI]) of childhood obesity and hyperglycemia associated with different levels of indoor activity, outdoor activity, TV watching, and sleeping time. The multivariable-adjusted ORs of obesity based on different levels of TV watching time (0, <1.0, and ≥1.0 hour/day) were 1.00, 1.21 (95% CI 0.72–2.05), and 2.20 (95% CI 1.33–3.63) (Ptrend = 0.003), respectively. The multivariable-adjusted ORs of hyperglycemia based on different levels of indoor activity (<5.0, 5.0–6.9, and ≥7.0 hours/day) were 1.00, 0.74 (95% CI 0.45–1.21), and 0.49 (95% CI 0.28–0.84) (Ptrend = 0.034), respectively. The multivariable-adjusted ORs of hyperglycemia associated with different levels of sleeping time (<11.0, 11.0–11.9, and ≥12.0 hours/day) were 1.00, 0.67 (95% CI 0.42–1.05), and 0.39 (95% CI 0.23–0.67) (Ptrend = 0.003), respectively. The present study indicated a positive association of TV watching with the risk of obesity, and an inverse association of either indoor activity or sleeping time with the risk of hyperglycemia among offspring born to GDM mothers in Tianjin, China.

  4. Early onset acute tubular necrosis following single infusion of zoledronate

    PubMed Central

    Yachoui, Ralph

    2016-01-01

    Summary Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent. PMID:27920815

  5. [Acute pulmonary embolism: beware of the wolf in sheep's clothing].

    PubMed

    Klok, Frederikus A; Vahl, Jelmer E; Huisman, Menno V; van Dijkman, Paul R M

    2012-01-01

    Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoea. In one patient, the general practitioner had previously adopted an expectative policy because of a clean chest X-ray. At presentation after 4 weeks, the patient was diagnosed with and treated for acute coronary syndrome because of minor ECG abnormalities. Additional CT scanning showed a large saddle embolus. Despite adequate treatment, the patient suffered an electrical asystole and died. The other patient underwent ECG, bicycle ergometry, MRI adenosine, echocardiography and lung function tests over a period of 5 weeks before pulmonary embolism (PE) was diagnosed. As the signs and symptoms of PE are largely non-specific, diagnostic delay is common, with risk of poor clinical outcome. PE should at least be considered whenever a patient presents with acute or worsening breathlessness, chest pain, circulatory collapse or coughing, particularly in the presence of known thrombotic risk factors or when there is no clear alternative.

  6. A rare case of acute on chronic gastric volvulus with Borchardt's triad.

    PubMed

    Senior, Andrew; Hari, Churunal

    2014-11-20

    Gastric volvulus is a rare condition with two forms of presentation, either acute or chronic. Since its discovery, there have been no cases of acute on chronic volvulus discussed in the literature. Its vague presentation makes diagnosis and subsequent management difficult. The diagnosis of acute gastric volvulus is made on clinical grounds via Borchardt's triad; however, barium swallow and oesophagogastroduodenoscopy have been shown to play a role. We describe a case of a 95-year-old Caucasian woman who presented with worsening dysphagia, epigastric pain, retching without vomiting and hiccups of 5 months. Initially diagnosed as a hiatus hernia, the patient subsequently died following an acute on chronic gastric volvulus. This rare, life-threatening diagnosis provides an opportunity to discuss characteristics of gastric volvulus and the difficulties in management.

  7. Pharmacologic strategies to preserve renal function in acute decompensated heart failure.

    PubMed

    Kumar, Sachin; Taylor, David O

    2015-02-01

    Over a million patients get hospitalized with the diagnosis of acute decompensated heart failure which poses an insurmountable financial burden on the health care system. Heart failure alone incurs over 30 billion dollars with half the cost spent towards acute hospitalizations. Majority of the treatment strategies have focused towards decongesting patients which often comes with the cost of worsening renal function. Renal dysfunction in the setting of acute decompensated heart failure portends worse morbidity and mortality. Recently, there has been a change in the focus with shift towards therapies attempting to conserve renal function. In the past decade, we have witnessed several large randomized controlled trials testing the established as well as emerging therapies in this subset of population with mixed results. This review intends to provide a comprehensive overview of the pharmacologic therapies commonly utilized in the management of acute decompensated heart failure and the body of evidence supporting these strategies.

  8. Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease

    PubMed Central

    Squiers, John J.; Edwards, Anthony G.; Parra, Alberto; Hofmann, Sandra L.

    2016-01-01

    A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient’s peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined. PMID:27047980

  9. A man with worsening weakness.

    PubMed

    Proietti, G; Puliti, M; Tulli, F; Silvestri, M

    1999-01-01

    The contemporary presence of organomegaly, skin manifestations, polyneuropathy, endocrinopathy and monoclonal component characterises the POEMS syndrome, often associated with osteosclerotic myeloma and Castelman's disease and more frequent in the Japanese. Clinical manifestations seem to be related to the production of many interleukins, mainly IL-1, IL-6 and TNF. Several endocrinopathies have been described, the most frequent being diabetes. Only one previous case of hypoparathyroidism associated with the syndrome has been described in medical reviews. Polyneuropathy is often sensitivo-motory and skin disease accounts for Raynaud phenomenon, skin pigmentation, hypertricosis and others. We describe the case of a 74-year-old man who underwent clinical examination for weakness mainly in the legs. Clinical and instrumental data showed rhabdomyolysis due to hypoparathyroidism. The contemporary presence of a monoclonal band of light chains on proteic electrophoresis, organomegaly and distal leg neuropathy allowed us to make a diagnosis of POEMS syndrome.

  10. [Therapeutic strategies in acute decompensated heart failure and cardiogenic shock].

    PubMed

    Buerke, M; Lemm, H; Russ, M; Schlitt, A; Werdan, K

    2010-08-01

    As the population of elderly people is increasing, the number of patients requiring hospitalization for acute exacerbations is rising. Traditionally, these episodes of hemodynamic instability were viewed as a transient event characterized by systolic dysfunction, low cardiac output, and fluid overload. Diuretics, along with vasodilator and inotropic therapy, eventually became elements of standard care. In a multicenter observational registry (ADHERE--Acute Decompensated Heart Failure National Registry) of more than 275 hospitals, patients with acute decompensated heart failure were analyzed for their characteristics and treatments options. These data have shown that this population consists of multiple types of heart failure, various forms of acute decompensation, combinations of comorbidities, and varying degrees of disease severity. The challenges in the treatment require multidisciplinary approaches since patients typically are elderly and have complex combinations of comorbidities. So far only a limited number of drugs is currently available to treat the different groups. Over the past years it was shown that even "standard drugs" might be deleterious by induction of myocardial injury, worsening of renal function or increasing mortality upon treatment. Therefore, based on pathophysiology, different types of acute decompensated heart failure require specialized treatment strategies.

  11. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

    PubMed Central

    Filippatos, Gerasimos; Anker, Stefan D.; Böhm, Michael; Gheorghiade, Mihai; Køber, Lars; Krum, Henry; Maggioni, Aldo P.; Ponikowski, Piotr; Voors, Adriaan A.; Zannad, Faiez; Kim, So-Young; Nowack, Christina; Palombo, Giovanni; Kolkhof, Peter; Kimmeskamp-Kirschbaum, Nina; Pieper, Alexander; Pitt, Bertram

    2016-01-01

    Aims To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. Methods and results Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized. Patients received oral, once-daily finerenone (2.5, 5, 7.5, 10, or 15 mg, uptitrated to 5, 10, 15, 20, or 20 mg, respectively, on Day 30) or eplerenone (25 mg every other day, increased to 25 mg once daily on Day 30, and to 50 mg once daily on Day 60) for 90 days. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to Day 90. A key exploratory endpoint was a composite clinical endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentation for worsening HF until Day 90. Mean age ranged from 69.2 to 72.5 years in different treatment groups (standard deviation 9.7–10.6 years). Decreases in NT-proBNP of >30% from baseline occurred in 37.2% of patients in the eplerenone group and 30.9, 32.5, 37.3, 38.8, and 34.2% in the 2.5→5, 5→10, 7.5→15, 10→20, and 15→20 mg finerenone groups, respectively (P = 0.42–0.88). Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred numerically less frequently in finerenone-treated patients compared with eplerenone; this difference reached nominal statistical significance in the 10→20 mg group (hazard ratio 0.56, 95% confidence interval, CI, 0.35; 0.90; nominal P = 0.02), despite the fact that this phase 2 study was not designed to detect statistical significant differences. A potassium level increase to ≥5.6 mmol/L at any time point occurred in 4.3% of patients, with a balanced

  12. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

    PubMed Central

    Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

    2015-01-01

    Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

  13. Acute laminitis.

    PubMed

    Baxter, G M

    1994-12-01

    Laminitis is an inflammation of the sensitive laminae along the dorsal aspect of the digit and is considered to be a secondary complication of several predisposing or primary factors. Affected horses are usually very lame, have increased digital pulses, are painful to hoof testers along the toe of the foot, and have evidence of downward rotation or distal displacement of the distal phalanx present on radiographs. Treatments for acute laminitis include anti-inflammatory drugs, anti-endotoxin therapy, vasodilators, antithrombotic therapy, corrective trimming and shoeing, and surgical procedures. Treatment regimens are very controversial and the true efficacy of these treatments is unknown. The quality of laminae damage that occurs with laminitis, however, probably has greater influence on the success of treatment and outcome of the horse than the treatment regimen itself.

  14. Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE(-/-) mice.

    PubMed

    Busnelli, Marco; Manzini, Stefano; Hilvo, Mika; Parolini, Cinzia; Ganzetti, Giulia S; Dellera, Federica; Ekroos, Kim; Jänis, Minna; Escalante-Alcalde, Diana; Sirtori, Cesare R; Laaksonen, Reijo; Chiesa, Giulia

    2017-03-14

    The PLPP3 gene encodes for a ubiquitous enzyme that dephosphorylates several lipid substrates. Genome-wide association studies identified PLPP3 as a gene that plays a role in coronary artery disease susceptibility. The aim of the study was to investigate the effect of Plpp3 deletion on atherosclerosis development in mice. Because the constitutive deletion of Plpp3 in mice is lethal, conditional Plpp3 hepatocyte-specific null mice were generated by crossing floxed Plpp3 mice with animals expressing Cre recombinase under control of the albumin promoter. The mice were crossed onto the athero-prone apoE(-/-) background to obtain Plpp3(f/f)apoE(-/-)Alb-Cre(+) and Plpp3(f/f)apoE(-/-)Alb-Cre(-) offspring, the latter of which were used as controls. The mice were fed chow or a Western diet for 32 or 12 weeks, respectively. On the Western diet, Alb-Cre(+) mice developed more atherosclerosis than Alb-Cre(-) mice, both at the aortic sinus and aorta. Lipidomic analysis showed that hepatic Plpp3 deletion significantly modified the levels of several plasma lipids involved in atherosclerosis, including lactosylceramides, lysophosphatidic acids, and lysophosphatidylinositols. In conclusion, Plpp3 ablation in mice worsened atherosclerosis development. Lipidomic analysis suggested that the hepatic Plpp3 deletion may promote atherosclerosis by increasing plasma levels of several low-abundant pro-atherogenic lipids, thus providing a molecular basis for the observed results.

  15. Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE−/− mice

    PubMed Central

    Busnelli, Marco; Manzini, Stefano; Hilvo, Mika; Parolini, Cinzia; Ganzetti, Giulia S.; Dellera, Federica; Ekroos, Kim; Jänis, Minna; Escalante-Alcalde, Diana; Sirtori, Cesare R.; Laaksonen, Reijo; Chiesa, Giulia

    2017-01-01

    The PLPP3 gene encodes for a ubiquitous enzyme that dephosphorylates several lipid substrates. Genome-wide association studies identified PLPP3 as a gene that plays a role in coronary artery disease susceptibility. The aim of the study was to investigate the effect of Plpp3 deletion on atherosclerosis development in mice. Because the constitutive deletion of Plpp3 in mice is lethal, conditional Plpp3 hepatocyte-specific null mice were generated by crossing floxed Plpp3 mice with animals expressing Cre recombinase under control of the albumin promoter. The mice were crossed onto the athero-prone apoE−/− background to obtain Plpp3f/fapoE−/−Alb-Cre+ and Plpp3f/fapoE−/−Alb-Cre− offspring, the latter of which were used as controls. The mice were fed chow or a Western diet for 32 or 12 weeks, respectively. On the Western diet, Alb-Cre+ mice developed more atherosclerosis than Alb-Cre− mice, both at the aortic sinus and aorta. Lipidomic analysis showed that hepatic Plpp3 deletion significantly modified the levels of several plasma lipids involved in atherosclerosis, including lactosylceramides, lysophosphatidic acids, and lysophosphatidylinositols. In conclusion, Plpp3 ablation in mice worsened atherosclerosis development. Lipidomic analysis suggested that the hepatic Plpp3 deletion may promote atherosclerosis by increasing plasma levels of several low-abundant pro-atherogenic lipids, thus providing a molecular basis for the observed results. PMID:28291223

  16. Quetiapine-induced hypertriglyceridaemia causing acute pancreatitis.

    PubMed

    Franco, John Mark; Vallabhajosyula, Saraschandra; Griffin, Timothy John

    2015-05-14

    Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients.

  17. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction

    PubMed Central

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients’ medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  18. Pleotropic Acute and Chronic Effects of Leptin to Reverse Type 1 Diabetes

    PubMed Central

    Perry, Rachel J.

    2017-01-01

    Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin’s chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin’s ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats. Thus current evidence suggests that leptin’s acute, insulin-independent effect to reverse DKA by suppressing HPA axis activity occurs through a different mechanism from its chronic, pleotropic, insulin-dependent effect to reverse hyperglycemia and prolong survival in rodents with T1D. Leptin may therefore represent an attractive therapeutic target to improve glycemic control in humans with poorly-controlled T1D. PMID:28239611

  19. Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism.

    PubMed

    Lau, Yeh Siang; Tian, Xiao Yu; Huang, Yu; Murugan, Dharmani; Achike, Francis I; Mustafa, Mohd Rais

    2013-02-01

    Increased oxidative stress is involved in the pathogenesis and progression of diabetes. Antioxidants are therapeutically beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1,10-dimethoxyaporphine) is a major alkaloid present in the leaves and bark of the boldo tree (Peumus boldus Molina), with known an antioxidant activity. This study examined the protective effects of boldine against high glucose-induced oxidative stress in rat aortic endothelial cells (RAEC) and its mechanisms of vasoprotection related to diabetic endothelial dysfunction. In RAEC exposed to high glucose (30 mM) for 48 h, pre-treatment with boldine reduced the elevated ROS and nitrotyrosine formation, and preserved nitric oxide (NO) production. Pre-incubation with β-NAPDH reduced the acetylcholine-induced endothelium-dependent relaxation; this attenuation was reversed by boldine. Compared with control, endothelium-dependent relaxation in the aortas of streptozotocin (STZ)-treated diabetic rats was significantly improved by both acute (1 μM, 30 min) and chronic (20mg/kg/daily, i.p., 7 days) treatment with boldine. Intracellular superoxide and peroxynitrite formation measured by DHE fluorescence or chemiluminescence assay were higher in sections of aortic rings from diabetic rats compared with control. Chronic boldine treatment normalized ROS over-production in the diabetic group and this correlated with reduction of NAD(P)H oxidase subunits, NOX2 and p47(phox). The present study shows that boldine reversed the increased ROS formation in high glucose-treated endothelial cells and restored endothelial function in STZ-induced diabetes by inhibiting oxidative stress and thus increasing NO bioavailability.

  20. Evidence That Multiple Defects in Lipid Regulation Occur before Hyperglycemia during the Prodrome of Type-2 Diabetes

    PubMed Central

    Banerjee, Moulinath; Brown, Marie; Broadhurst, David I.; Goodacre, Royston; Cooper, Garth J. S.; Kell, Douglas B.; Cruickshank, J. Kennedy

    2014-01-01

    Background Blood-vessel dysfunction arises before overt hyperglycemia in type-2 diabetes (T2DM). We hypothesised that a metabolomic approach might identify metabolites/pathways perturbed in this pre-hyperglycemic phase. To test this hypothesis and for specific metabolite hypothesis generation, serum metabolic profiling was performed in young women at increased, intermediate and low risk of subsequent T2DM. Methods Participants were stratified by glucose tolerance during a previous index pregnancy into three risk-groups: overt gestational diabetes (GDM; n = 18); those with glucose values in the upper quartile but below GDM levels (UQ group; n = 45); and controls (n = 43, below the median glucose values). Follow-up serum samples were collected at a mean 22 months postnatally. Samples were analysed in a random order using Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap mass spectrometer. Statistical analysis included principal component (PCA) and multivariate methods. Findings Significant between-group differences were observed at follow-up in waist circumference (86, 95%CI (79–91) vs 80 (76–84) cm for GDM vs controls, p<0.05), adiponectin (about 33% lower in GDM group, p = 0.004), fasting glucose, post-prandial glucose and HbA1c, but the latter 3 all remained within the ‘normal’ range. Substantial differences in metabolite profiles were apparent between the 2 ‘at-risk’ groups and controls, particularly in concentrations of phospholipids (4 metabolites with p≤0.01), acylcarnitines (3 with p≤0.02), short- and long-chain fatty acids (3 with p< = 0.03), and diglycerides (4 with p≤0.05). Interpretation Defects in adipocyte function from excess energy storage as relatively hypoxic visceral and hepatic fat, and impaired mitochondrial fatty acid oxidation may initiate the observed perturbations in lipid metabolism. Together with evidence from the failure of glucose-directed treatments to improve

  1. SIRT1 activator ameliorates the renal tubular injury induced by hyperglycemia in vivo and in vitro via inhibiting apoptosis.

    PubMed

    Wang, Xue-Ling; Wu, Li-Yan; Zhao, Long; Sun, Li-Na; Liu, Hai-Ying; Liu, Gang; Guan, Guang-Ju

    2016-10-01

    We aimed to explore the role of SIRT1 in apoptosis in human kidney proximal tubule epithelial (HK-2) cells, and to determine whether resveratrol (RSV, a SIRT1 activator) could ameliorate apoptosis in rats with streptozotocin-induced diabetes mellitus (DM) and/or in high glucose (HG, 30mM) - stimulated HK-2 cells. Rats were distributed randomly into three groups: 1) control group, 2) DM group, and 3) DM with RSV group (DM+RSV; rats treated with 30mg/kg/d of RSV for 16 weeks). The physical, biochemical, and morphological parameters were then examined. Additionally, the deacetylase activity of SIRT1, and the expression levels of SIRT1 and of representative apoptosis markers, such as p53, acetylated p53, cleaved caspase-3, caspase-9, and cleaved PARP, were measured. HK-2 cells were stimulated by HG for different lengths of time to study the effect of HG on apoptosis. HK-2 cells were treated with or without RSV (25μM) to investigate if RSV has a protective effect on HG-induced apoptosis. A gene-specific small interfering RNA against SIRT1 was used to study the role of SIRT1 in apoptosis. More apoptosis was found in the DM rats than in the control rats. Similarly, the expression levels of cleaved caspase-3, cleaved PARP, and acetylated p53 were significantly higher, and the level of SIRT1 was significantly lower, in the HK-2 cells that were cultured under HG conditions than those in the HK-2 cells that were cultured under low glucose (5.5mM) conditions. Notably, treatment with RSV lessened the HG-induced changes in the levels of apoptosis indicators, and this inhibition of HG-induced apoptosis in HK-2 cells by RSV treatment was abolished by SIRT1 silencing. Our study showed that hyperglycemia contributes to apoptosis in rat kidney and HK-2 cells. SIRT1 activation by RSV can reduce urinary albumin excretion and proximal tubule epithelial apoptosis both in vitro and in vivo. Based on our study, SIRT1/p53 axis played an important role in the hyperglycemia induced apoptosis

  2. Selected tea and tea pomace extracts inhibit intestinal α-glucosidase activity in vitro and postprandial hyperglycemia in vivo.

    PubMed

    Oh, Jungbae; Jo, Sung-Hoon; Kim, Justin S; Ha, Kyoung-Soo; Lee, Jung-Yun; Choi, Hwang-Yong; Yu, Seok-Yeong; Kwon, Young-In; Kim, Young-Cheul

    2015-04-21

    Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by postprandial hyperglycemia, which is an early defect of T2DM and thus a primary target for anti-diabetic drugs. A therapeutic approach is to inhibit intestinal α-glucosidase, the key enzyme for dietary carbohydrate digestion, resulting in delayed rate of glucose absorption. Although tea extracts have been reported to have anti-diabetic effects, the potential bioactivity of tea pomace, the main bio waste of tea beverage processing, is largely unknown. We evaluated the anti-diabetic effects of three selected tea water extracts (TWE) and tea pomace extracts (TPE) by determining the relative potency of extracts on rat intestinal α-glucosidase activity in vitro as well as hypoglycemic effects in vivo. Green, oolong, and black tea bags were extracted in hot water and the remaining tea pomace were dried and further extracted in 70% ethanol. The extracts were determined for intestinal rat α-glucosidases activity, radical scavenging activity, and total phenolic content. The postprandial glucose-lowering effects of TWE and TPE of green and black tea were assessed in male Sprague-Dawley (SD) rats and compared to acarbose, a known pharmacological α-glucosidase inhibitor. The IC50 values of all three tea extracts against mammalian α-glucosidase were lower or similar in TPE groups than those of TWE groups. TWE and TPE of green tea exhibited the highest inhibitory effects against α-glucosidase activity with the IC50 of 2.04 ± 0.31 and 1.95 ± 0.37 mg/mL respectively. Among the specific enzymes tested, the IC50 values for TWE (0.16 ± 0.01 mg/mL) and TPE (0.13 ± 0.01 mg/mL) of green tea against sucrase activity were the lowest compared to those on maltase and glucoamylase activities. In the animal study, the blood glucose level at 30 min after oral intake (0.5 g/kg body wt) of TPE and TWE of both green and black tea was significantly reduced compared to the control in sucrose-loaded SD rats. The TPE

  3. Dammarane-type triterpene extracts of Panax notoginseng root ameliorates hyperglycemia and insulin sensitivity by enhancing glucose uptake in skeletal muscle.

    PubMed

    Kitamura, Kumiko; Takamura, Yusuke; Iwamoto, Taku; Nomura, Mitsuru; Iwasaki, Hideaki; Ohdera, Motoyasu; Murakoshi, Michiaki; Sugiyama, Keikichi; Matsuyama, Kazuki; Manabe, Yasuko; Fujii, Nobuharu L; Fushiki, Tohru

    2017-02-01

    Skeletal muscle is an important organ for controlling the development of type 2 diabetes. We discovered Panax notoginseng roots as a candidate to improve hyperglycemia through in vitro muscle cells screening test. Saponins are considered as the active ingredients of ginseng. However, in the body, saponins are converted to dammarane-type triterpenes, which may account for the anti-hyperglycemic activity. We developed a method for producing a dammarane-type triterpene extract (DTE) from Panax notoginseng roots and investigated the extract's potential anti-hyperglycemic activity. We found that DTE had stronger suppressive activity on blood glucose levels than the saponin extract (SE) did in KK-A(y) mice. Additionally, DTE improved oral glucose tolerance, insulin sensitivity, glucose uptake, and Akt phosphorylation in skeletal muscle. These results suggest that DTE is a promising agent for controlling hyperglycemia by enhancing glucose uptake in skeletal muscle.

  4. Italian Society for the Study of Diabetes (SID)/Italian Endocrinological Society (SIE) guidelines on the treatment of hyperglycemia in Cushing's syndrome and acromegaly.

    PubMed

    Baroni, M G; Giorgino, F; Pezzino, V; Scaroni, C; Avogaro, A

    2016-02-01

    Hyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. The purpose of these guidelines is to assist clinicians and other health care providers to take evidence-based therapeutic decisions for the treatment of hyperglycemia in patients with growth hormone and corticosteroid excess. Both the SID and SIE appointed members to represent each society and to collaborate in Guidelines writing. Members were chosen for their specific knowledge in the field. Each member agreed to produce-and regularly update-conflicts of interest. The authors of these guidelines prepared their contributions following the recommendations for the development of Guidelines, using the standard classes of recommendation shown below. All members of the writing committee provided editing and systematic review of each part of the manuscript, and discussed the grading of evidence. Consensus was guided by a systematic review of all available trials and by interactive discussions.

  5. Worsening of Health and a Cessation or Reduction in Alcohol Consumption to Special Occasion Drinking Across Three Decades of the Life Course

    PubMed Central

    Ng Fat, Linda; Cable, Noriko; Shelton, Nicola

    2015-01-01

    Background Ex-drinkers suffer from worse health than drinkers; however, whether a worsening of health is associated with a change in drinking status from early adulthood has not been previously investigated. We assess whether a worsening of health is associated with a cessation in consumption or reduction to special occasion drinking from early adulthood to middle age. Methods Multinomial logistic regression assessing whether a change in self-reported limiting longstanding illness (LLI) was associated with ceasing alcohol consumption, or a reduction to special occasion drinking compared with being a persistent drinker from age 23 in separate models at ages 33, 42, and 50. All models adjusted for sex, poor psychosocial health, education, marital status, and children in the household. Sample included participants from Great Britain followed longitudinally in the National Child Development Study from ages 23 to 33 (N = 5,529), 42 (N = 4,787), and 50 (N = 4,476). Results Developing an LLI from the previous wave was associated with ceasing alcohol consumption at ages 33 (odds ratio [ORs] = 2.71, 95% confidence interval [CI] = 1.16–4.93), 42 (OR = 2.44, 95%CI = 1.24–4.81), and 50 (OR = 3.33, 95%CI = 1.56–7.12) and a reduction to special occasion drinking at ages 42 (OR = 2.04, 95%CI = 1.40–2.99) and 50 (OR = 2.04, 95%CI = 1.18–3.53). Having a persistent LLI across 2 waves increased the odds of ceasing consumption at ages 42 (OR = 3.22, 95%CI = 1.06–9.77) and 50 (OR = 4.03, 95%CI = 1.72–9.44) and reducing consumption to special occasion drinking at ages 33 (OR = 3.27, 95%CI = 1.34–8.01) and 42 (OR = 2.25, 95%CI = 1.23–4.50). Persistent drinkers at older ages had the best overall health suffering less from previous poor health compared with those who reduced or ceased consumption at an earlier time point. Conclusions Developing an LLI was associated with a cessation in alcohol consumption and a reduction in

  6. Hyperglycemia Induces a Dynamic Cooperativity of Histone Methylase and Demethylase Enzymes Associated With Gene-Activating Epigenetic Marks That Coexist on the Lysine Tail

    PubMed Central

    Brasacchio, Daniella; Okabe, Jun; Tikellis, Christos; Balcerczyk, Aneta; George, Prince; Baker, Emma K.; Calkin, Anna C.; Brownlee, Michael; Cooper, Mark E.; El-Osta, Assam

    2009-01-01

    OBJECTIVE Results from the Diabetes Control Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) Study and more recently from the U.K. Prospective Diabetes Study (UKPDS) have revealed that the deleterious end-organ effects that occurred in both conventional and more aggressively treated subjects continued to operate >5 years after the patients had returned to usual glycemic control and is interpreted as a legacy of past glycemia known as “hyperglycemic memory.” We have hypothesized that transient hyperglycemia mediates persistent gene-activating events attributed to changes in epigenetic information. RESEARCH DESIGN AND METHODS Models of transient hyperglycemia were used to link NFκB-p65 gene expression with H3K4 and H3K9 modifications mediated by the histone methyltransferases (Set7 and SuV39h1) and the lysine-specific demethylase (LSD1) by the immunopurification of soluble NFκB-p65 chromatin. RESULTS The sustained upregulation of the NFκB-p65 gene as a result of ambient or prior hyperglycemia was associated with increased H3K4m1 but not H3K4m2 or H3K4m3. Furthermore, glucose was shown to have other epigenetic effects, including the suppression of H3K9m2 and H3K9m3 methylation on the p65 promoter. Finally, there was increased recruitment of the recently identified histone demethylase LSD1 to the p65 promoter as a result of prior hyperglycemia. CONCLUSIONS These studies indicate that the active transcriptional state of the NFκB-p65 gene is linked with persisting epigenetic marks such as enhanced H3K4 and reduced H3K9 methylation, which appear to occur as a result of effects of the methyl-writing and methyl-erasing histone enzymes. PMID:19208907

  7. Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

    SciTech Connect

    Al-Kafaji, Ghada; Malik, Afshan N.

    2010-01-22

    During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as {mu}-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 {+-} 50 vs 147 {+-} 54, p < 0.05), and hearts (1583 {+-} 277 vs 191 {+-} 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 {+-} 37 vs 18 {+-} 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

  8. Repetitive Concussive Traumatic Brain Injury Interacts with Post-Injury Foot Shock Stress to Worsen Social and Depression-Like Behavior in Mice

    PubMed Central

    Klemenhagen, Kristen C.; O’Brien, Scott P.; Brody, David L.

    2013-01-01

    The debilitating effects of repetitive concussive traumatic brain injury (rcTBI) have been increasingly recognized in both military and civilian populations. rcTBI may result in significant neurological, cognitive, and affective sequelae, and is often followed by physical and/or psychological post-injury stressors that may exacerbate the effects of the injury and prolong the recovery period for injured patients. However, the consequences of post-injury stressors and their subsequent effects on social and emotional behavior in the context of rcTBI have been relatively little studied in animal models. Here, we use a mouse model of rcTBI with two closed-skull blunt impacts 24 hours apart and social and emotional behavior testing to examine the consequences of a stressor (foot shock fear conditioning) following brain injury (rcTBI). rcTBI alone did not affect cued or contextual fear conditioning or extinction compared to uninjured sham animals. In the sucrose preference test, rcTBI animals had decreased preference for sucrose, an anhedonia-like behavior, regardless of whether they experienced foot shock stress or were non-shocked controls. However, rcTBI and post-injury foot shock stress had synergistic effects in tests of social recognition and depression-like behavior. In the social recognition test, animals with both injury and shock were more impaired than either non-shocked injured mice or shocked but uninjured mice. In the tail suspension test, injured mice had increased depression-like behavior compared with uninjured mice, and shock stress worsened the depression-like behavior only in the injured mice with no effect in the uninjured mice. These results provide a model of subtle emotional behavioral deficits after combined concussive brain injury and stress, and may provide a platform for testing treatment and prevention strategies for social behavior deficits and mood disorders that are tailored to patients with traumatic brain injury. PMID:24058581

  9. The impact of neutralizing antibodies on the risk of disease worsening in interferon β-treated relapsing multiple sclerosis: a 5 year post-marketing study.

    PubMed

    Paolicelli, D; D'Onghia, M; Pellegrini, F; Direnzo, V; Iaffaldano, P; Lavolpe, V; Trojano, M

    2013-06-01

    The impact of neutralizing antibodies (NAbs) on interferon β (IFNβ) efficacy in MS patients is still an object of controversy. To evaluate the clinical response to IFNβ during NAb-positive (NAb+) and NAb-negative (NAb-) statuses on a large population of relapsing remitting (RR) MS patients were followed up to 5 years. Sera from 567 RR MS patients treated with IFNβ for 2-5 years were collected every 6-12 months and evaluated for NAb presence by a cytopathic effect assay. The relapse rate and expanded disability status scale (EDSS) score were assessed at baseline and every 6 months for each patient. A NAb+ status was defined after two consecutive positive titers of NAbs >/= 20 neutralizing units (NU)/mL. Multivariate models were used to analyze the relapse rate, the time to first relapse, the time to confirmed EDSS score 4 during NAb+ and NAb- statuses. A propensity score (PS) matching analysis was performed to assess the robustness of the multivariate models. Fourteen percent of patients became NAb+ during the follow-up. A significant increase of the relapse rate (IRR = 1.38; p = 0.0247) and decrease of the time to 1st relapse (IRR = 1.51; p = 0.0111) were found during NAb+ periods. The PS matching analysis, in a selected cohort of patients, demonstrated a negative trend of NAbs on the time to reach the milestone EDSS 4 (IRR = 2.94; p = 0.0879). This long-term post-marketing observational study further confirms that the occurrence of NAbs significantly affects the risk of disease worsening in IFNβ- treated RRMS.

  10. Low albumin levels and high impedance ratio as risk factors for worsening kidney function during hospitalization of decompensated heart failure patients

    PubMed Central

    Valdespino-Trejo, Adrian; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Keirns-Davis, Candace; Montañez-Orozco, Álvaro; Ortíz-Suárez, Gerson; Delgado-Pérez, D Alejandro; Marquez-Zepeda, Bianka

    2013-01-01

    BACKGROUND: Patients hospitalized for decompensated heart failure (DHF) frequently experience worsening of renal function (WRF), leading to volume overload and resistance to diuretics. OBJECTIVE: To investigate whether albumin levels and whole-body impedance ratio, as an indicator of water distribution, were associated with WRF in patients with DHF. Methods: A total of 80 patients hospitalized for DHF were consecutively included in the present longitudinal study. WRF during hospitalization was defined as an increase of ≥0.3 mg/dL (≥26.52 μmol/L) or 25% of baseline serum creatinine. Clinical and echocardiographic characteristics were assessed at baseline. Whole-body bioelectrical impedance was measured using tetrapolar and multiple-frequency equipment to obtain the ratio of impedance at 200 kHz to that at 5 kHz. Serum albumin levels were also evaluated. Baseline characteristics were compared between patients with and without deteriorating renal function using a t test or χ2 test. Subsequently, a logistic regression analysis was performed to obtain the independent variables associated with WRF. RESULTS: The incidence of WRF during hospitalization was 26%. Independent risk factors associated with WRF were low serum albumin (RR=0.11; P=0.04); impedance ratio >0.85 (RR=5.3; P=0.05), systolic blood pressure >160 mmHg (RR=12; P=0.02) and maximum dose of continuous intravenous furosemide required >80 mg/day during hospitalization (RR=5.7, P=0.015). CONCLUSIONS: WRF is frequent in patients with DHF. It results from the inability to effectively regulate volume status because hypoalbuminemia induces water loss from the vascular space (high impedance ratio), and high diuretic doses lower circulatory volumes and reduce renal blood flow, leading to a decline in renal filtration function. PMID:23940434

  11. Polychlorinated Biphenyl 153 Is a Diet-dependent Obesogen Which Worsens Nonalcoholic Fatty Liver Disease In Male C57BL6/J Mice

    PubMed Central

    Wahlang, Banrida; Falkner, K. Cameron; Gregory, Bonnie; Ansert, Douglas; Young, David; Conklin, Daniel J.; Bhatnagar, Aruni; McClain, Craig J.; Cave, Matt

    2013-01-01

    Background Polychlorinated biphenyls (PCBs) are persistent environmental pollutants which are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies. Objective The purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high fat diet (HFD). Methods Male C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 co-exposure (50 mg/kg i.p. × 4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression. Results In control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, co-exposure reduced expression of hepatic genes implicated in β-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels. Conclusion PCB 153 is an obesogen which exacerbates hepatic steatosis; alters adipocytokines; and disrupts normal hepatic lipid metabolism when administered with HFD, but not control diet. Because all U.S. adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity/NAFLD. PMID:23618531

  12. The Clinical Relevance of Self-Reported Premenstrual Worsening of Depressive Symptoms in the Management of Depressed Outpatients: A STAR*D Report

    PubMed Central

    Haley, Charlotte L.; Rush, A. John; Trivedi, Madhukar H.; Wisniewski, Stephen R.; Luther, James F.; Kornstein, Susan G.

    2013-01-01

    Abstract Objective To determine the incidence, clinical and demographic correlates, and relationship to treatment outcome of self-reported premenstrual exacerbation of depressive symptoms in premenopausal women with major depressive disorder who are receiving antidepressant medication. Method This post-hoc analysis used clinical trial data from treatment-seeking, premenopausal, adult female outpatients with major depression who were not using hormonal contraceptives. For this report, citalopram was used as the first treatment step. We also used data from the second step in which one of three new medications were used (bupropion-SR [sustained release], venlafaxine-XR [extended release], or sertraline). Treatment-blinded assessors obtained baseline treatment outcomes data. We hypothesized that those with reported premenstrual depressive symptom exacerbation would have more general medical conditions, longer index depressive episodes, lower response or remission rates, and shorter times-to-relapse with citalopram, and that they would have a better outcome with sertraline than with bupropion-SR. Results At baseline, 66% (n=545/821) of women reported premenstrual exacerbation. They had more general medical conditions, more anxious features, longer index episodes, and shorter times-to-relapse (41.3 to 47.1 weeks, respectively). Response and remission rates to citalopram, however, were unrelated to reported premenstrual exacerbation. Reported premenstrual exacerbation was also unrelated to differential benefit with sertraline and bupropion-SR. Conclusions Self-reported premenstrual exacerbation has moderate clinical utility in the management of depressed patients, although it is not predictive of overall treatment response. Factors that contribute to a more chronic or relapsing course may also play a role in premenstrual worsening of major depressive disorder (MDD). PMID:23480315

  13. Maternal Iron Deficiency Worsens the Associative Learning Deficits and Hippocampal and Cerebellar Losses in a Rat Model of Fetal Alcohol Spectrum Disorders

    PubMed Central

    Huebner, Shane M.; Tran, Tuan D.; Rufer, Echoleah S.; Crump, Peter M.; Smith, Susan M.

    2015-01-01

    Background Gestational alcohol exposure causes lifelong physical and neurocognitive deficits collectively referred to as fetal alcohol spectrum disorders (FASDs). Micronutrient deficiencies are common in pregnancies of alcohol-abusing women. Here we show the most common micronutrient deficiency of pregnancy, iron deficiency without anemia, significantly worsens neurocognitive outcomes following perinatal alcohol exposure. Methods Pregnant rats were fed iron-deficient (ID) or iron-sufficient diets from gestational day 13 to postnatal day (PD) 7. Pups received alcohol (0, 3.5, 5.0 g/kg) from PD 4–9, targeting the brain growth spurt. At PD 32, learning was assessed using delay or trace eyeblink classical conditioning (ECC). Cerebellar interpositus nucleus (IPN) and hippocampal CA1 cellularity was quantified using unbiased stereology. Results Global ANOVA revealed that ID and alcohol separately and significantly reduced ECC learning with respect to amplitude (p’s ≤0.001) and CR percentage (p’s ≤0.001). Iron and alcohol interacted to reduce CR percentage in the trace ECC task (p = 0.013). Both ID and alcohol significantly reduced IPN (p’s <0.001) and CA1 cellularity (p’s < 0.005). CR amplitude correlated with IPN cellularity (Delay 0.871, Trace 0.703, p’s <0.001) and CA1 cellularity (Delay 0.792, Trace 0.846, p’s <0.001) across both tasks. The learning impairments persisted even through the offsprings’ iron status had normalized. Conclusion Supporting our previous work, gestational ID exacerbates the associative learning deficits in this rat model of FASD. This is strongly associated with cellular reductions within the ECC neurocircuitry. Significant learning impairments in FASD could be the consequence, in part, of pregnancies in which the mother was also iron-inadequate. PMID:26399568

  14. Verbal Dominant Memory Impairment and Low Risk for Post-operative Memory Worsening in Both Left and Right Temporal Lobe Epilepsy Associated with Hippocampal Sclerosis

    PubMed Central

    KHALIL, Amr Farid; IWASAKI, Masaki; NISHIO, Yoshiyuki; JIN, Kazutaka; NAKASATO, Nobukazu; TOMINAGA, Teiji

    2016-01-01

    Post-operative memory changes after temporal lobe surgery have been established mainly by group analysis of cognitive outcome. This study investigated individual patient-based memory outcome in surgically-treated patients with mesial temporal lobe epilepsy (TLE). This study included 84 consecutive patients with intractable TLE caused by unilateral hippocampal sclerosis (HS) who underwent epilepsy surgery (47 females, 41 left [Lt] TLE). Memory functions were evaluated with the Wechsler Memory Scale-Revised before and at 1 year after surgery. Pre-operative memory function was classified into three patterns: verbal dominant memory impairment (Verb-D), visual dominant impairment (Vis-D), and no material-specific impairment. Post-operative changes in verbal and visual memory indices were classified into meaningful improvement, worsening, or no significant changes. Pre-operative patterns and post-operative changes in verbal and visual memory function were compared between the Lt and right (Rt) TLE groups. Pre-operatively, Verb-D was the most common type of impairment in both the Lt and Rt TLE groups (65.9 and 48.8%), and verbal memory indices were lower than visual memory indices, especially in the Lt compared with Rt TLE group. Vis-D was observed only in 11.6% of Rt and 7.3% of Lt TLE patients. Post-operatively, meaningful improvement of memory indices was observed in 23.3–36.6% of the patients, and the memory improvement was equivalent between Lt and Rt TLE groups and between verbal and visual materials. In conclusion, Verb-D is most commonly observed in patients with both the Lt and Rt TLE associated with HS. Hippocampectomy can improve memory indices in such patients regardless of the side of surgery and the function impaired. PMID:27250575

  15. Monacolin K and monascin attenuated pancreas impairment and hyperglycemia induced by advanced glycation endproducts in BALB/c mice.

    PubMed

    Hsu, Wei-Hsuan; Lu, Si-Shi; Lee, Bao-Hong; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-12-01

    Several lines of evidence have implicated high levels of advanced glycation endproducts (AGEs) in diabetes. Pancreas impairment caused by AGEs has been found in recent studies. Monascin (MS) and monacolin K (MK) are active compounds identified from Monascus-fermented products, which have been reported to inhibit inflammation and improve insulin resistance. In order to confirm the protective effects of MS and MK on pancreatic function, BALB/c mice were treated with AGEs via intraperitoneal injection for 22 weeks to induce hyperglycemia, and the pancreas-protecting mechanism of MS and MK from AGE-induced damage was investigated. We found that the expression of pancreatic and duodenal homeobox-1 (PDX-1) and glucose transporter 2 (GLUT2) was recovered by MS or MK administration to AGE-treated mice. In addition, MS strongly improved performance in the oral glucose tolerance test (OGTT) and the insulin tolerance test (ITT), suggesting that MS sensitized to insulin in AGE-treated mice. Both MS and MK elevated pancreatic insulin expression when compared to the AGE-treated group, suggesting that MS and MK attenuated AGE-induced pancreatic dysfunction. Histopathology studies showed that intraperitoneal injection of AGEs did not result in pancreas damage. These findings confirm that the potential mechanism of AGEs on pancreatic dysfunction involves the induction of inflammation and the suppression of PDX-1 and GLUT2 expression. Taken together, MS and MK may be developed as an anti-diabetic agent in the future.

  16. Hyperglycemia and hypercapnia suppress BDNF gene expression in vulnerable regions after transient forebrain ischemia in the rat.

    PubMed

    Uchino, H; Lindvall, O; Siesjö, B K; Kokaia, Z

    1997-12-01

    Preischemic hyperglycemia or superimposed hypercapnia exaggerates brain damage caused by transient forebrain ischemia. Because high regional levels of brain-derived neurotrophic factor (BDNF) protein correlate with resistance to ischemic damage, we studied the expression of BDNF mRNA using in situ hybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, hyperglycemic, or hypercapnic conditions. Compared with normoglycemic animals, the increase of BDNF mRNA using in situ hybridization in rats subjected to 10 minutes of forebrain ischemia under normoglycemic, or hypercapnic conditions. Compared with normoglycemic animals, the increase of BDNF mRNA in dentate granule cells was attenuated and that in CA3 pyramidal neurons completely prevented in hyperglycemic rats. No ischemia-induced increases of BDNF mRNA levels in the hippocampal formation were detected in hypercapnic animals. Hyperglycemic and hypercapnic rats showed transiently decreased expression of BDNF mRNA levels in the cingulate cortex, which was not observed in normoglycemic animals. The results suggest that suppression of the BDNF gene might contribute to the increased vulnerability of the CA3 region and cingulate cortex in hyperglycemic and hypercapnic animals.

  17. Hyperglycemia, oxidative stress, liver damage and dysfunction in alloxan-induced diabetic rat are prevented by Spirulina supplementation.

    PubMed

    Gargouri, Manel; Magné, Christian; El Feki, Abdelfattah

    2016-11-01

    Medicinal plants have long been used against life-threatening diseases including diabetes, with more or less success. Some of these plants have been shown to possess antioxidant activities, which could help improving diabetes inconveniences. In that context, we investigated the effects of spirulina supplementation on alloxan-induced diabetic rats, hypothesizing that co-administration of spirulina with rat diet could ameliorate diabetes complications and provide as benefits as the common antidiabetic insulin. Following alloxan treatment, male Wistar rats were fed daily with 5% spirulina-enriched diet or treated with insulin (0.5 IU/rat) for 21 days. Both spirulina and insulin treatments of diabetic rats resulted in a significant reduction in fasting blood glucose and an increase of glycogen level. Spirulina supplementation also impeded loss of body weight and ameliorated hepatic toxicity indices, i.e. alkaline phosphatases and transaminases activities, bilirubin levels and lipid peroxidation. Besides, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels decreased in the serum. Moreover, diabetic rats fed with spirulina exhibited sig changes in antioxidant enzyme activities in the liver (ie, decrease in superoxide dismutase and increase in catalase and glutathione peroxidase activities). The beneficial effects of spirulina or insulin were confirmed by histological study of the liver of diabetic rats. Overall, this study indicates that treatment with spirulina decreased hyperglycemia and oxidative stress in diabetic rats, this amelioration being even more pronounced than that provided by insulin injection. Therefore, administration of this alga would be very helpful in the prevention of diabetic complications.

  18. Lipid droplet accumulation is associated with an increase in hyperglycemia-induced renal damage: prevention by liver X receptors.

    PubMed

    Kiss, Eva; Kränzlin, Bettina; Wagenblaβ, Katja; Bonrouhi, Mahnaz; Thiery, Joachim; Gröne, Elisabeth; Nordström, Viola; Teupser, Daniel; Gretz, Norbert; Malle, Ernst; Gröne, Hermann-Josef

    2013-03-01

    Dyslipidemia is a frequent component of the metabolic disorder of diabetic patients contributing to organ damage. Herein, in low-density lipoprotein receptor-deficient hyperlipidemic and streptozotozin-induced diabetic mice, hyperglycemia and hyperlipidemia acted reciprocally, accentuating renal injury and altering renal function. In hyperglycemic-hyperlipidemic kidneys, the accumulation of Tip47-positive lipid droplets in glomeruli, tubular epithelia, and macrophages was accompanied by the concomitant presence of the oxidative stress markers xanthine oxidoreductase and nitrotyrosine, findings that could also be evidenced in renal biopsy samples of diabetic patients. As liver X receptors (LXRα,β) regulate genes linked to lipid and carbohydrate homeostasis and inhibit inflammatory gene expression in macrophages, the effects of systemic and macrophage-specific LXR activation were analyzed on renal damage in hyperlipidemic-hyperglycemic mice. LXR stimulation by GW3965 up-regulated genes involved in cholesterol efflux and down-regulated proinflammatory/profibrotic cytokines, inhibiting the pathomorphology of diabetic nephropathy, renal lipid accumulation, and improving renal function. Xanthine oxidoreductase and nitrotyrosine levels were reduced. In macrophages, GW3965 or LXRα overexpression significantly suppressed glycated or acetylated low-density lipoprotein-induced cytokines and reactive oxygen species. Specifically, in mice, transgenic expression of LXRα in macrophages significantly ameliorated hyperlipidemic-hyperglycemic nephropathy. The results demonstrate the presence of lipid droplet-induced oxidative mechanisms and the pathophysiologic role of macrophages in diabetic kidneys and indicate the potent regulatory role of LXRs in preventing renal damage in diabetes.

  19. Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase - enzymes related to hyperglycemia.

    PubMed

    Su, Chun-Han; Lai, Min-Nan; Ng, Lean-Teik

    2013-04-25

    In Asia, medicinal mushrooms have been popularly used as folk medicine and functional foods. In this study, our aim was to examine the inhibitory effects of six medicinal mushrooms on key enzymes (α-amylase and α-glucosidase) related to hyperglycemia; chemical profiles of bioactive extracts were also examined. The results showed that the n-hexane extract of Coriolus versicolor had the strongest anti-α-amylase activity, while the n-hexane extract of Grifola frondosa showed the most potent anti-α-glucosidase activity. Compared with acarbose, the anti-α-amylase activity of all mushroom extracts was weaker, however a stronger anti-α-glucosidase activity was noted. GC-MS analysis showed that the magnitude of potency of inhibiting α-glucosidase activity varied with the levels of oleic acid and linoleic acid present in the extracts. These findings were consistent with the IC50 values of these free fatty acids on inhibiting α-glucosidase activity. Taken together, this study suggests that oleic acid and linoleic acid could have contributed to the potent anti-α-glucosidase activity of selected medicinal mushrooms.