Scavengome of an antioxidant.

The term "scavengome" refers to the chemical space of all the metabolites that may be formed from an antioxidant upon scavenging reactive oxygen or nitrogen species (ROS/RNS). This chemical space covers a wide variety of free radical metabolites with drug discovery potential. It is very rich in structures representing an increased chemical complexity as compared to the parent antioxidant: a wide range of unusual heterocyclic structures, new CC bonds, etc. may be formed. Further, in a biological environment, this increased chemical complexity is directly translated from the localized conditions of oxidative stress that determines the amounts and types of ROS/RNS present. Biomimetic oxidative chemistry provides an excellent tool to model chemical reactions between antioxidants and ROS/RNS. In this chapter, we provide an overview on the known metabolites obtained by biomimetic oxidation of a few selected natural antioxidants, i.e., a stilbene (resveratrol), a pair of hydroxycinnamates (caffeic acid and methyl caffeate), and a flavonol (quercetin), and discuss the drug discovery perspectives of the related chemical space.

Sublattice entanglement in an exactly solvable anyonlike spin ladder.

We introduce an integrable spin ladder model and study its exact solution, correlation functions, and entanglement properties. The model supports two particle types (corresponding to the even and odd sublattices), such that the scattering phases are constants: Particles of the same type scatter as free fermions, whereas the interparticle phase shift is a constant tuned by an interaction parameter. Therefore, the spin ladder bears similarities with anyonic models. We present exact results for the spectrum and correlation functions, and we study the sublattice entanglement by numerical means.

[Functional MRI investigation of brain activity triggered by taste stimulation]. / Ízstimulációval kiváltott agyi tevékenység funkcionális MR-vizsgálata elhízásban.

INTRODUCTION: Many factors contribute to the pathogenesis of morbid obesity, and the central nervous system - as one of those - also has an important role. Numerous studies focus on the central regulation of eating and metabolism, since associated problems like obesity, anorexia, diabetes or metabolic syndrome put an increasing burden on the health system of modern societies. Neither the pathophysiologic changes, nor the normal regulation of these systems are known adequately. Functional MR (fMRI) imaging, which has certainly gained popularity recently, aims to better understand these mechanisms. In this series we studied the brain fMRI activity changes of normal and obese persons, triggered by gustatory stimulation. METHODS: 10 obese and 10 normal weight healthy volunteers took part in the study, with comparable age and sex distribution. Gustatory stimulation was performed by 0.1 M sucrose (pleasant), 0.5 mM quinine HCl (unpleasant) and complex vanilla flavored (Nutridrink) solutions, which were administered through 0.5 mm PVC tubes, in 5-5 ml portions. For rinsing distilled water with neutral flavor was used. Imaging was performed in a 3T MRI, applying standard EPI sequences. Post processing of data was accomplished by FSL software package. RESULTS: Brain activation for gustatory stimuli was characteristically different between the two groups. There were high intensity activations in more cortical and subcortical regions of the obese volunteers compared to the normal ones. CONCLUSIONS: Our current fMRI investigations revealed different activations of numerous brain regions of normal and obese individuals, triggered by pleasant and unpleasant gustatory stimulation. Based on these results this method can help to recognize the role of the central nervous system in obesity, and may contribute to develop new therapies for weight loss.

Homeostatic alterations after IL-1beta microinjection into the nucleus accumbens of the rat.

The present study investigates the effects of direct administration of interleukin-1beta (IL-1beta) into the nucleus accumbens (NAcc) on homeostatic regulation. Short- and long-term food intakes (FI), water intakes (WI) and body temperature (BT) were measured before and after bilateral microinjection of IL-1beta (with or without paracetamol pretreatment) into the NAcc of Wistar rats, and the effects were compared with those found in vehicle treated control animals. In addition, blood glucose levels, along with a glucose tolerance test (GTT), and plasma concentrations of metabolic parameters, such as total cholesterol, triglycerides, HDL, LDL and uric acid were determined in cytokine treated and control rats. Short-term FI and WI were suppressed after intraaccumbens application of IL-1beta. A significant increase of BT was also observed after the cytokine microinjection. Pretreatment with paracetamol failed to influence the anorexigenic, adipsogenic, and pyrogenic effects of IL-1beta. A definite glucose intolerance of the cytokine treated animals and their pathologically elevated blood glucose levels became obvious in the acute GTT. Following IL-1beta microinjection, plasma levels of triglycerides, total cholesterol and LDL were found increased. Our present findings show that the NAcc is an important site of action of IL-1beta mediated processes in central homeostatic regulation.

Taste reactivity deficit in anorexia nervosa.

AIM: Anorexia nervosa is a complex psychiatric disorder posing a rapidly increasing burden on modern societies. Our purpose was to clarify perceptual-motivational aspects of gustatory disturbances in the disease. METHODS: A taste reactivity test, with the use of all five primary qualities in two concentrations, was performed in restrictive-type anorexic patients, and their hedonic evaluations were compared to those of age-matched healthy control subjects. RESULTS: The patients gave significantly lower pleasantness scores for pleasant taste stimuli compared with controls. The differences were the greatest for the lower concentration sucrose, umami and sodium chloride. Ratings given for the aversive taste stimuli were similar in both experimental groups. CONCLUSION: Our findings contribute to a better understanding of complex symptoms of anorexia nervosa, and may also help to develop more effective cognitive-behavioral therapies.

Taste reactivity alterations after IL-1beta microinjection into the ventromedial hypothalamic nucleus of the rat.

The ventromedial hypothalamic nucleus (VMH) is a central site of action of interleukin-1beta (IL-1beta) induced feeding disturbances. This study was designed to elucidate taste-related perceptual and motivational processes potentially contributing to the anorexia and adipsia seen after bilateral IL-1beta microinjection into the VMH. A saccharin conditioned taste aversion (CTA) paradigm was tested after the central IL-1beta administration. To further investigate whether gustatory deficits are involved in development of the feeding alterations, IL-1beta induced changes of taste responsiveness were also studied in taste reactivity tests. Administration of the cytokine into the VMH did not cause the development of CTA. During taste reactivity tests, however, IL-1beta treated rats displayed significantly poorer ingestive reactions to pleasant taste stimuli than did animals of the control group. In addition, the aversive responses of IL-1beta injected rats to pleasant tastes were significantly more robust than those of control animals. The cytokine treated animals also showed stronger aversion than ingestion to hedonically positive tastes. The present findings indicate that (1) anorexigenic and adipsogenic consequences of IL-1beta microinjection into the VMH are not due to development of cytokine induced CTA; and (2) hedonic responsiveness to palatable tastes is processed by IL-1beta mediated neural mechanisms in the VMH.

Glucose-monitoring neurons in the nucleus accumbens.

The nucleus accumbens, a key structure of the limbic circuitry, is involved in the regulation of motivated behaviors. The accumbens performs its roles via interconnections with brain areas where glucose-monitoring neurons have been localized. To search for such integrative chemosensory cells here, extracellular single neuron activity was recorded in the nucleus accumbens of Wistar rats by means of multibarreled glass microelectrodes during microelectrophoretic administration of D-glucose and other chemicals. Every fourth neuron tested changed in activity in response to glucose. Accumbens cells also displayed distinct gamma-amino-n-butyric acid type sensitivity. It is suggested that differential distribution of the chemosensory units, demonstrated between subdivisions of the nucleus accumbens, has particular significance with respect to functional dichotomy of the shell and core subregions.

Identification and evaluation of drug-supplement interactions in Hungarian hospital patients.

BACKGROUND: The increasing number of patients taking supplementary products together with prescribed medicines has become a new challenge for health care systems. These products may influence therapy outcomes by inducing unwanted effects. Particularly concerning is the potential for harmful interactions between prescribed medicines and supplementary products. OBJECTIVE: The aims of the study were to evaluate supplement use, to identify and analyse potential interactions, and to assess the efficiency of computerised interaction screening. SETTING: Participants of the study were inpatients and outpatients of a Hungarian university hospital. METHOD: A cross-sectional point-of-care survey of 200 patients was carried out. Data was collected through personal interviews and a review of the medical records. Drug-drug, drug-supplement and supplement-supplement interactions were analysed with three interaction databases (Lexi-Interact Online, Medscape Drug Interaction Checker and Mediris). MAIN OUTCOME MEASURE: Prevalence of supplementary product use, number of medicines and supplementary products per patient, procurement sources of products, number of potentially severe interactions. RESULTS: There was a marked difference between data obtained from patient interviews and the medical records. 85.5 % of the surveyed patients took supplementary products during the 2 weeks prior to the interview. The average number of prescribed medicines and supplementary products were 7.8 and 2.5, respectively. Women were more likely to take supplements than men. There was no significant difference in supplement use between patients under or over 60 years, between inpatients and outpatients and among patients in various wards. 39.4 % of supplementary products were purchased outside a regulated pharmacy environment. Potentially severe drug-supplement interactions were detected with 45.2 % of supplement users; however the majority of interactions were not included in one or the other of the three databases. In addition to that the risk ratings of the same interactions varied greatly between databases. CONCLUSION: A significant number of patients are exposed to potential drug interactions with supplementary products; however interagreement among interaction databases is poor. Our data suggest that a full medication history should specifically address the intake of supplements.

Taste reactivity alterations after streptozotocin microinjection into the mediodorsal prefrontal cortex.

The mediodorsal prefrontal cortex (mdPFC), as an integrant part of the forebrain glucose-monitoring neural network, plays important roles in neural control of feeding. Previous studies suggested that streptozotocin (STZ) causes selective destruction of forebrain glucose-monitoring (GM) neurons leading to development of feeding disturbances. The goal of this research was to evaluate gustatory consequences of bilateral streptozotocin microinjection into the mediodorsal prefrontal cortex of male Wistar rats during conditioned taste avoidance (CTA) acquisition, as well as during taste reactivity tests. Bilateral streptozotocin microinjection failed to impair CTA learning, tested in a saccharin CTA paradigm. However, taste reactivity deficit was found by a modified version of the protocol introduced by Grill and Norgren. The streptozotocin treated animals displayed significantly poorer ingestive reactions to pleasant taste stimuli than did rats of the control group. The unpleasant taste stimuli elicited ingestive and rejective taste reactivity patterns in a comparable manner in rats of the STZ vs. vehicle microinjected groups. The glucose-monitoring neurons of the mdPFC and their distinct role in the gustatory perception may have particular significance in the adaptive control of feeding.

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control.

Insulin and leptin plasma levels after the microinjection of interleukin-1ß into the nucleus accumbens of the rat.

The nucleus accumbens (NAcc), an important basal forebrain structure, has a central integratory function in the control of feeding and metabolism. The primary cytokine interleukin-1ß (IL-1ß) exerts its neuromodulatory effects on the endocrine functions both centrally and peripherally. The present study was designed to elucidate the possible consequences of direct administration of IL-1ß into the NAcc on the endocrine regulation of metabolism. Plasma concentrations of insulin and leptin, two key hormones in the homeostatic control were determined 15 minutes after a single bilateral microinjection of IL-1ß into the NAcc of adult male Wistar rats, and the effects were compared with those found in vehicle treated control animals. Insulin plasma levels of the cytokine treated animals were significantly higher than those parameters of the control rats. No differences were found in leptin plasma concentrations between the two groups. Our findings show that IL-1ß mediated processes in the NAcc have important roles in the central neuroendocrine control.

Gustatory perception alterations in obesity: an fMRI study.

The background of feeding associated and metabolic diseases is not sufficiently understood yet. Since gustatory alterations may be of particular significance in the above illnesses, in the present experiments, cerebral activation was detected by fMRI in twelve obese patients and twelve, age and gender matched healthy subjects. The gustatory stimulus solutions were delivered via intraorally positioned polyvinyl tubes. Each session consisted of three runs. Sucrose was used as a pleasant; quinine HCl as an aversive; and a high-calorie, vanilla flavored nourishment solution as a complex taste of high palatability. In each run, only one taste was used as a stimulus. During all runs, distilled water served as a neutral stimulus. Group analysis was made by using the FSL software package. The taste stimuli elicited characteristic and distinct activity changes of the two groups. In contrast to the controls, in the obese patients, stronger activation was detected in various cortical (anterior cingulate cortex, insular and opercular cortices, orbitofrontal cortex) and subcortical (amygdala, nucleus accumbens, putamen and pallidum) structures in case of all three stimuli. The present examinations elucidated differential activation of various brain structures to pleasant and unpleasant gustatory stimuli in obese patients compared to control subjects. These taste alterations are supposed to be of particular significance in obesity, and our findings may contribute to develop better strategies for prevention and effective therapies in the future.