Home About us Contact
|
Home About us Contact | ||
|
|
||
Metabolic Derangement (metabolic + derangement)
Selected AbstractsRanolazine Attenuates Palmitoyl- l -carnitine-induced Mechanical and Metabolic Derangement in the Isolated, Perfused Rat HeartJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2000KAZUYASU MARUYAMA The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl- l -carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl- l -carnitine (4 ,m) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl- l -carnitine were attenuated by ranolazine (5, 10, and 20 ,m) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mm) did not attenuate palmitoyl- l -carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl- l -carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl- l -carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase. [source] New prospects for immunotherapy at diagnosis of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Paolo Pozzilli Immune intervention at diagnosis of type 1 diabetes (T1D) aims to prevent or reverse the disease by blocking autoimmunity, thereby preserving/restoring ,-cell mass and function. Recent clinical trials of non-specific and of antigen-specific immune therapies have demonstrated the feasibility of modulation of islet-specific autoimmunity in patients with partial prevention of loss of insulin secretion. In a series of review articles published in this issue of the journal, some of the most promising approaches of immune intervention in T1D are presented. Here we outline the rationale of such interventions and future prospects in this area. Copyright © 2009 John Wiley & Sons, Ltd. Insulin therapy in type 1 diabetes (T1D) rescues the patient from a certain death but not cure the disease. The goal of any therapeutic intervention in T1D is the preservation of insulin-secreting cells; this is achieved by the abrogation of pathogenic reactivity to beta cell autoantigens while preserving full capacity to generate a normal immune response against foreign antigens. Although several therapeutic candidates have been investigated in experimental models of T1D many of which showed promising results, a successful extrapolation of these findings to human T1D has proved to be difficult. In part, this failure results from the considerable disease heterogeneity associated with diverse genetic and non-genetic disease determinants and the spectrum of clinical phenotype at diagnosis. Thus, a younger age at onset is associated with stronger genetic susceptibility, more intense immune response to ,-cell antigens, shorter duration of symptoms, more severe metabolic derangement at diagnosis and a more rapid rate of ,-cell-destruction 1,3. Therefore, designing therapies that would be effective in all clinical settings is definitely challenging. In this issue five different approaches are discussed ranging from antigen-specific therapies [DiaPep277 and glutamic acid decarboxylase(GAD)], to non-antigen-specific immunoregulation (anti-CD3) and to anti-inflammatory (anti-IL1 receptor antagonist). These approaches are currently being tested in large international multicenter trials, and all of them use very similar outcome in terms of a beneficial effect (C-peptide secretion as evidence of a therapeutic effect on restoration of ,-cell function). The authors have been asked to follow a similar format in presenting their approaches so that the reader can easily compare them in terms of rationale and therapeutic goals. [source] Agreement between bicarbonate measured on arterial and venous blood gasesEMERGENCY MEDICINE AUSTRALASIA, Issue 5-6 2004Anne-Maree Kelly Abstract Objective:, This study aims to determine the extent of agreement between venous and arterial bicarbonate for a group of emergency department patients with respiratory or metabolic illness requiring blood gas analysis as part of their evaluation. Methods:, This prospective study of patients who were deemed by their treating doctor to require an arterial blood gas analysis to determine their ventilatory or acid-base status, compared bicarbonate on an arterial and a venous sample taken as close to simultaneously as possible. Data were analysed using bias (Bland-Altman) methods. Subgroup analyses were performed for the metabolic, respiratory, chronic obstructive airways disease and acidotic subgroups. Results:, Two hundred and forty-six patients were entered into the study; 195 with acute respiratory disease and 51 with suspected metabolic derangement. The values of bicarbonate on arterial and venous samples showed close agreement with an average difference between the samples of 1.20 mmol/L (95% limits of agreement being ,2.73 to +5.13 mmol/L). Similar agreement was found for all subgroups. Conclusion:, Venous bicarbonate estimation shows a high level of agreement with the arterial value, with acceptably narrow 95% limits of agreement. These results suggest that venous bicarbonate estimation may be an acceptable substitute for arterial measurement. [source] Troglitazone prevents fatty changes of the liver in obese diabetic ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2000Dong Mei Jia Abstract Background and Aims: Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats. Methods: A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age. Results: Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue. Conclusion: Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes. [source] Ranolazine Attenuates Palmitoyl- l -carnitine-induced Mechanical and Metabolic Derangement in the Isolated, Perfused Rat HeartJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2000KAZUYASU MARUYAMA The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl- l -carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl- l -carnitine (4 ,m) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl- l -carnitine were attenuated by ranolazine (5, 10, and 20 ,m) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mm) did not attenuate palmitoyl- l -carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl- l -carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl- l -carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase. [source] The severity of clinical presentation of type 1 diabetes in children does not significantly influence the pattern of residual ,-cell function and long-term metabolic controlPEDIATRIC DIABETES, Issue 1 2003Silvana Salardi Abstract: Aim:, The purpose of the present study was to compare relationships between the clinical presentation of type 1 diabetes in children and residual ,-cell secretion and long-term metabolic control. Methods:, This retrospective study was conducted in 66 diabetic children with age at diagnosis ranging from 0.7 to 14.8 yr. The patients showed contrasting characteristics at diagnosis: either diabetic ketoacidosis (DKA) (group 1, n = 29) or absence of metabolic derangement (group 2, n = 37) associated with marked (group 2A, n = 12) or mild hyperglycemia (group 2B, n = 25). A regular follow-up was available for at least 10 yr (10,32 yr) in all cases and for 20 yr in 23 cases. C-peptide levels were measured from diagnosis and thereafter at intervals for the first years of disease until becoming permanently undetectable. Results:, C-peptide levels at diagnosis were undetectable in about 20% of the cases both with and without DKA. C-peptide levels at diagnosis, the duration of measurable C-peptide levels and the maximum value found during follow-up were not significantly different in the three groups and were not correlated with glycated hemoglobin (GHb) calculated throughout the whole period. No differences were found between the groups of patients concerning GHb values and insulin dose at 10, 15 and 20 yr of disease. The patients of group 2A, characterized by an extremely high glycemic level without ketoacidosis, had a significantly higher prevalence of HLA DR3/4 heterozygosity. Conclusions:, The severity of clinical presentation at diagnosis does not significantly influence residual ,-cell function, and long-term metabolic control. [source] Recommendation for a definition of acute symptomatic seizureEPILEPSIA, Issue 4 2010Ettore Beghi Summary Purpose:, To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies. Methods:, Systematic review of the literature and of epidemiologic studies. Results:, An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs. Discussion:, Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification. [source] Androgen receptor gene polymorphism and the metabolic syndrome in 60,80 years old Norwegian menINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2010Paal André Skjærpe Summary The metabolic syndrome (MS) includes a clustering of metabolic derangements. Low testosterone levels have been shown to be associated with both components of MS and MS per se. As most androgen-related effects are mediated thorough the androgen receptor (AR), we wanted to investigate to which degree the AR CAG and GGN repeat polymorphisms might be related to MS. Sixty-eight men, 60,80 years old, with subnormal total testosterone levels (,11.0 nmol/L) and 104 men with normal levels (>11.0 nmol/L), participating in a nested case,control study were investigated in this study. Body weight, height, waist circumferences and blood pressure were measured. Fasting blood samples were drawn and an oral glucose tolerance test (OGTT) was performed. The CAG and GGN polymorphisms in the AR gene were determined by direct sequencing of leucocyte DNA. Men with MS had lower CAG repeat number than healthy men (p = 0.007). There were, however, no difference in CAG or GGN repeats length between the groups with subnormal or normal testosterone concentrations. In cross-sectional analyses, men with CAG repeat lengths , 21 had significantly higher fasting glucose, C-peptide and glycosylated haemoglobin (HbA1c) levels (all p < 0.05). In multiple regression analyses, CAG repeat length was an inverse and independent predictor of glucose after an OGTT and of HbA1c levels. We also found that men with more than one component of MS had shorter CAG repeat number (p for trend 0.013) than those with only one component. In conclusion, there were no associations with GGN repeat length, while short CAG repeat length seems to be associated with increased risk of MS. [source] Tumor lysis under anesthesia in a childACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009R. SINHA Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency characterized by metabolic derangements caused by massive lysis and release of cellular components. TLS has been reported to occur under various circumstances. There have however, been only two reports of precipitation of TLS by anesthesia in the current medical literature. We report on the development of TLS in a 7-year-old child with a pelvic neuroectodermal tumor following induction of anesthesia and discuss the peri-operative concerns while dealing with patients with high tumor burdens. [source] A Segmental Polynomial Model of Ventricular Electrograms as a Simple and Efficient Morphology Discriminator for Implantable DevicesANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2006Jeffrey L. Williams M.D. Background: The goal of this study is to construct a polynomial model of the ventricular electrogram (EGM) that faithfully reproduces the EGM and can be implemented in current, low computational power implantable devices. Such a model of ventricular EGMs is still lacking. Methods: New Zealand White rabbits underwent chronic implantation of pacemakers through a left thoracotomy approach. Unipolar ventricular EGMs sampled at a frequency of 1 kHz were stored digitally in 1-minute segments before and after intravenous injection of isoproterenol or procainamide. Each cardiac cycle was divided into a QR and an RQ segment which were modeled separately using a 6th order polynomial equation. Results: The 14 coefficients of each cardiac cycle were reproducible throughout the baseline recordings (r , 0.94, P < 0.002). Isoproterenol caused no changes in the coefficients of the QR segment but significantly altered all but one of the seven coefficients of the RQ segment (p6= 0.0039, p5= 0.017, p4= 0.00007, p3= 0.112, p2= 0.00016, p1= 0.0086, pa= 0.00003). Procainamide caused statistically significant changes in both QR segment (p6= 0.018, p5= 0.287, p4= 0.019, p3= 0.176, p2= 0.016, p1= 0.362, pa= 0.000044) and RQ segment (p6= 0.0028, p5= 0.036, p4= 0.002, p3= 0.058, p2= 0.022, p1= 0.718, pa= 0.0018) coefficients. Conclusion: Our data demonstrate the feasibility of a segmental polynomial equation that reproduces the phases of depolarization and repolarization of the rabbit EGM. This model is reproducible and demonstrates the expected changes with antiarrhythmic drug administration. If reproduced in humans, these findings can have wide applications in patients with implantable devices, ranging from morphologic discrimination of arrhythmias to early detection of metabolic derangements or drug effects. [source] Seizures in HIV/AIDS: a southern African perspectiveACTA NEUROLOGICA SCANDINAVICA, Issue 2005A. I. Bhigjee South Africa, with a population of 44.8 million, has over 5 million human immunodeficiency virus (HIV)-infected individuals. Over 70% of HIV-infected patients will present with clinically relevant neurologic disease at some stage during the course of their disease. New onset seizures occur in 3,11% of these patients. The mechanism of seizure production in HIV-positive patients includes incidental association, HIV itself, opportunistic infections (OIs), neoplasia, cerebrovascular disease, drug toxicity, and metabolic derangements. In developing countries, OIs constitute the largest group presenting with seizures. Seizure management in HIV-positive patients presents special problems, especially with respect to drug,disease and drug,drug interactions. The older antiepileptic drugs (AEDs) are protein-bound and largely depend on the cytochrome p450 system for their metabolism. The newer AEDs may be safer in patients on antiretroviral drugs. However, they are expensive, an important consideration in developing countries. [source] | |||||||||||||||||||