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1.
Neurobiol Learn Mem ; 162: 36-46, 2019 07.
Article in English | MEDLINE | ID: mdl-31125611

ABSTRACT

In order to optimize outcomes in the face of uncertainty, one must recall past experiences and extrapolate to the future by assigning values to different choice outcomes. This behavior requires an interplay between memory and reward valuation, necessitating communication across many brain regions. At the anatomical nexus of this interplay is the perirhinal cortex (PRC). The PRC is densely connected to the amygdala and orbital frontal cortex, regions that have been implicated in reward-based decision making, as well as the hippocampus. Thus, the PRC could serve as a hub for integrating memory, reward, and prediction. The PRC's role in value-based decision making, however, has not been empirically examined. Therefore, we tested the role of the PRC in a spatial delay discounting task, which allows rats to choose between a 1-s delay for a small food reward and a variable delay for a large food reward, with the delay to the large reward increasing after choice of each large reward and decreasing after each small reward. The rat can therefore adjust the delay by consecutively choosing the same reward or stabilize the delay by alternating between sides. The latter has been shown to occur once the 'temporal cost' of the large reward is established and is a decision-making process termed 'exploitation'. When the PRC was bilaterally inactivated with the GABA(A) agonist muscimol, rats spent fewer trials successfully exploiting to maintain a fixed delay compared to the vehicle control condition. Moreover, PRC inactivation resulted in an increased number of vicarious trial and error (VTE) events at the choice point, where rats had to decide between the two rewards. These behavioral patterns suggest that the PRC is critical for maintaining stability in linking a choice to a reward outcome in the face of a variable cost.


Subject(s)
Choice Behavior/physiology , Delay Discounting/physiology , Perirhinal Cortex/physiology , Spatial Behavior/physiology , Animals , Choice Behavior/drug effects , Delay Discounting/drug effects , GABA-A Receptor Agonists/pharmacology , Male , Muscimol/pharmacology , Perirhinal Cortex/drug effects , Rats , Spatial Behavior/drug effects , Time Factors
2.
Pharmazie ; 52(6): 428-36, 1997 Jun.
Article in German | MEDLINE | ID: mdl-9324689

ABSTRACT

A series of 2-aryl-pyrrolobenzothiazoles with additional functional groups was synthesized and characterized. Mainly ring opening and less substitution of the pyrrole moiety was observed reacting the heterocyclic system with diazoethyl acetate. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase but one of them is a well balanced dual inhibitor. A structure-activity relationship and the enzyme selectivity are discussed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/pharmacology , Lipoxygenase Inhibitors/chemical synthesis , Lipoxygenase Inhibitors/pharmacology , Thiazoles/chemical synthesis , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Neutrophils/drug effects , Neutrophils/enzymology , Structure-Activity Relationship , Thiazoles/pharmacology
3.
Arch Pharm (Weinheim) ; 329(6): 301-10, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8767113

ABSTRACT

The delay of onset of irritation phenomena at the chorioallantoic membrane of incubated hen's eggs, a parameter for anti-inflammatory activity, was determined for the pharmaceutical substances diclofenac, flufenamic acid, ibuprofen, indomethacin, ketoprofen, piroxicam, phenylbutazone, salicylic acid, and sodium salicylate. Alongside questions relating to the dose-effect ratio, metabolisation, recovery, and diffusion of the substances to their site of action were investigated. The reproducibility of the procedure and its selectivity with regard to substances with a different mechanism of action is proven. The method allows classification of the substances according to their anti-inflammatory potency. However, correlation with the results of enzyme inhibition or in vivo results is only possible to a limited extent.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Toxicity Tests/methods , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Chickens , Chorion/metabolism , Diffusion , Dose-Response Relationship, Drug , Eggs , Molecular Structure , Time Factors
4.
Alcohol Clin Exp Res ; 16(5): 971-8, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1443438

ABSTRACT

Protein-energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol-binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients.


Subject(s)
Food, Formulated , Hospitalization , Insulin Resistance/physiology , Liver Cirrhosis, Alcoholic/physiopathology , Protein-Energy Malnutrition/physiopathology , Anthropometry , Blood Glucose/metabolism , Blood Proteins/metabolism , Humans , Liver Cirrhosis, Alcoholic/complications , Liver Function Tests , Nutrition Assessment , Protein-Energy Malnutrition/therapy
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