K. Sideris

Bio: K. Sideris is an academic researcher. The author has contributed to research in topics: Deoxyglucose. The author has an hindex of 1, co-authored 2 publications receiving 989 citations.

Noninvasive determination of local cerebral metabolic rate of glucose in man

Abstract: A method for the determination of local cerebral metabolic rates of glucose (LCMRGlc) in normal man is described. The method employs [18F]2-fluoro-2-deoxy-D-glucose (FDG) and emission-computed tomography (ECT). FDG was injected intravenously as a bolus. Radioactivities in separate brain regions were measured with ECT. Plasma FDG concentration following injection was measured from blood samples. A mathematical model that describes the kinetics of FDG transports was employed to determine the transport rate constants of FDG and to convert the radioactivity measurements to metabolic rates. The model has taken into account the possible dephosphorylation reaction from FDG-6-PO4 (FDG-6-P) to free FDG in brain tissues. Experiments were performed in 13 normal volunteers. The rate constants of FDG in man were found to be comparable to those of deoxyglucose in rat and in rhesus monkey. The average LCMRGlc in gray and in white matter were found to be 7.30 +/- 1.18 (SD) and 3.41 +/- 0.64 mg/min per 100 g brain tissue, respectively. The subject-to-subject variation of LCMRGlc as measured by the present method was comparable to those of other methods that measure whole-brain CMRGlc.

Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review

Abstract: The objective of this review article is to summarize current knowledge of blood flow and perfusion-related parameters, which usually go hand in hand and in turn define the cellular metabolic microenvironment of human malignancies. A compilation of available data from the literature on blood flow, oxygen and nutrient supply, and tissue oxygen and pH distribution in human tumors is presented. Whenever possible, data obtained for human tumors are compared with the respective parameters in normal tissues, isotransplanted or spontaneous rodent tumors, and xenografted human tumors. Although data on human tumors in situ are scarce and there may be significant errors associated with the techniques used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic blood supply to many tumors. As a result, O2-depleted areas develop in human malignancies which coincide with nutrient and energy deprivation and with a hostile metabolic microenvironment (e.g., existence of severe tissue acidosis). Significant variations in these relevant parameters must be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Furthermore, this synopsis will attempt to identify relevant pathophysiological parameters and other related areas future research of which might be most beneficial for designing individually tailored treatment protocols with the goal of predicting the acute and/or long-term response of tumors to therapy.

Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM.

Abstract: Apres l'ingestion de glucose, l'insulino-secretion du pancreas est stimulee et la combinaison de l'hyperglycemie et de l'hyperinsulinemie doit induire la captation de glucose dans les territoires splanchique (foie et tube digestif) et peripherique (muscles) et la suppression de la production hepatique du glucose. Le but de cette conference est de prouver que, bien que la perturbation du metabolisme hepatique du glucose joue un role dans le maintien de l'etat diabetique, le foie ne joue probablement pas de role majeur dans le developpement precoce de l'hyperglycemie a jeun des DNID

Pathogenesis of NIDDM: A balanced overview

Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal. With time, however, the beta-cell fails to maintain its high rate of insulin secretion and the relative insulinopenia (i.e., relative to the degree of insulin resistance) leads to the development of impaired glucose tolerance and eventually overt diabetes mellitus. The cause of pancreatic "exhaustion" remains unknown but may be related to the effect of glucose toxicity in a genetically predisposed beta-cell. Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered beta-cell function in NIDDM. Insulin resistance in NIDDM involves both hepatic and peripheral, muscle, tissues. In the postabsorptive state hepatic glucose output is normal or increased, despite the presence of fasting hyperinsulinemia, whereas the efficiency of tissue glucose uptake is reduced. In response to both endogenously secreted or exogenously administered insulin, hepatic glucose production fails to suppress normally and muscle glucose uptake is diminished. The accelerated rate of hepatic glucose output is due entirely to augmented gluconeogenesis. In muscle many cellular defects in insulin action have been described including impaired insulin-receptor tyrosine kinase activity, diminished glucose transport, and reduced glycogen synthase and pyruvate dehydrogenase. The abnormalities account for disturbances in the two major intracellular pathways of glucose disposal, glycogen synthesis, and glucose oxidation. In the earliest stages of NIDDM, the major defect involves the inability of insulin to promote glucose uptake and storage as glycogen. Other potential mechanisms that have been put forward to explain the insulin resistance, include increased lipid oxidation, altered skeletal muscle capillary density/fiber type/blood flow, impaired insulin transport across the vascular endothelium, increased amylin, calcitonin gene-related peptide levels, and glucose toxicity.

Reduction of prefrontal cortex glucose metabolism common to three types of depression.

Abstract: • Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, righthanded patients with unipolar depression (n =10), bipolar depression (n =10), obsessive-compulsive disorder (OCD) with secondary depression (n =10), OCD without major depression (n =14), and normal controls (n =12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non—sex-matched patients with mania. Mean ( ± SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 ±0.05; bipolar depression =1.04 ± 0.05), and were significantly lower than those in normal controls (1.12 ± 0.06) or OCD without depression (1.15 ± 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 ± on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n =12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem. These data support other findings that major depression is associated with a left ALPFC abnormality.