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  • 1
    ISSN: 1432-1238
    Keywords: Key words Acquired ATIII deficiency ; ATIII replacement therapy ; Septic shock
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study. Methods: 120 patients admitted to the ICU with an ATIII concentration 〈 70 % were randomized to receive ATIII (total dose 24 000 units) or placebo treatment for 5 days; 56 patients had septic shock. Results: ATIII concentrations in the treated group remained constant throughout the treatment period (range 97–102 %). The Kaplan- Meier analysis showed no difference in overall survival between the two groups: 50 and 46 % for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1 % increase in the ATIII plasma concentration at baseline. Conclusions: The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 23 (1998), S. 1485-1491 
    ISSN: 1573-6903
    Keywords: Cerebral cortex ; energy metabolism ; enzymes ; L-acetylcarnitine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The maximum rate (Vmax) of some mitochondrial enzymatic activities related to the energy transduction (citrate synthase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate-transaminase, glutamate-oxaloacetate-transaminase) was evaluated in non-synaptic (free) and intra-synaptic mitochondria from rat brain cerebral cortex. Three types of mitochondria were isolated from rats subjected to i.p. treatment with L-acetylcarnitine at two different doses (30 and 60 mg·kg−1, 28 days, 5 days/week). In control (vehicle-treated) animals, enzyme activities are differently expressed in non-synaptic mitochondria respect to intra-synaptic “light” and “heavy” ones. In fact, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, glutamate-pyruvate-transaminase and glutamate-oxaloacetate-transaminase are lower, while citrate synthase, cytochrome oxidase and glutamate dehydrogenase are higher in intra-synaptic mitochondria than in non-synaptic ones. This confirms that in various types of brain mitochondria a different metabolic machinery exists, due to their location in vivo. Treatment with L-acetylcarnitine decreased citrate synthase and glutamate dehydrogenase activities, while increased cytochrome oxidase and α-ketoglutarate dehydrogenase activities only in intra-synaptic mitochondria. Therefore in vivo administration of L-acetylcarnitine mainly affects some specific enzyme activities, suggesting a specific molecular trigger mode of action and only of the intra-synaptic mitochondria, suggesting a specific subcellular trigger site of action.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6903
    Keywords: Cerebral cortex ; ATP-ases ; synaptic plasma membranes ; naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Naloxone is a specific competitive antagonist of morphine, acting on opiate receptors, located on neuronal membranes. The effects of in vivo administration of naloxone on energy-consuming non-mitochondrial ATP-ases were studied in two different types of synaptic plasma membranes from rat cerebral cortex, known to contain a high density of opiate receptors. The enzyme activities of Na+, K+-ATP-ase, Ca2+, Mg2+-ATP-ase and Mg2+-ATP-ase and of acetylcholinesterase (AChE) were evaluated on synaptic plasma membranes obtained from control and treated animals with effective dose of naloxone (12μg · kg−1 i.m. 30 minutes). In control (vehicle-treated) animals specific enzyme activities assayed on these two types of synaptic plasma membranes are different, being higher on synaptic plasma membranes of II type than of I type, because the first fraction is more enriched in synaptic plasma membranes. The acute treatment with naloxone produced a significant decrease in Ca2+,Mg2+-ATP-ase activity and an increase in AChE activity, only in synaptic plasma membranes of II type. The decrease of Ca2+,Mg2+-ATP-ase enzymatic activity and the increased AChE activity are related to the interference of the drug on Ca2+ homeostasis in synaptosoplasm, that leads to the activation of calcium-dependent processes, i.e. the extrusion of neurotransmitter. These findings give further evidence that pharmacodynamic characteristics of naloxone are also related to increase [Ca2+] i , interfering with enzyme systems (Ca2+,Mg2+-ATP-ase) and that this drug increases acetylcholine catabolism in synaptic plasma membranes of cerebral cortex.
    Type of Medium: Electronic Resource
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