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Structural, Conformational, and Spectroscopic Studies of Primary Amine Complexes of Iron(II) Porphyrins.

Three novel bis(primary amine)iron(II) porphyrins [Fe(TPP)(RNH(2))(2)], where RNH(2) = 1-butylamine, benzylamine, and phenethylamine, have been synthesized and characterized by X-ray crystallography and IR, electronic, and Mössbauer spectroscopy. The compounds provide unprecedented structural data for the coordination of primary amines by iron(II) porphyrins. The Fe-N(ax) distances of [Fe(TPP)(1-BuNH(2))(2)], [Fe(TPP)(BzNH(2))(2)], and [Fe(TPP)(PhCH(2)CH(2)NH(2))(2)] are 2.039(3), 2.043(3), and 2.028(2) Å, respectively. The Fe-N(p) distances of the three complexes average 1.990(2) Å. The zero-field Mössbauer spectra (5-300 K) show comparable isomer shifts (0.393(1)-0.493(1) mm/s) and quadrupole splittings (1.144(6)-1.204(3) mm/s) that are consistent with an S = 0 iron(II) assignment in each case. The bis(primary amine) complexes are structurally and spectroscopically similar to [Fe(TPP)(Py)(2)] derivatives, where Py = an unsubstituted pyridine. Molecular mechanics (MM) calculations with a force field parametrized for primary and secondary amine complexes of iron(II) porphyrins show that stable conformations arise when the alpha-CH(2) and NH(2) protons of the coordinated ligands are staggered relative to the Fe-N(p) bonds of the porphyrin core. The lowest energy conformations of the three [Fe(TPP)(RNH(2))(2)] complexes therefore have the ligand alpha-carbons positioned directly over the Fe-N(p) bonds of the porphyrin core. The X-ray structure of [Fe(TPP)(PhCH(2)CH(2)NH(2))(2)] lies close to the global minimum (phi(1), phi(2) = 0, 180 degrees ) on the potential surface, while [Fe(TPP)(BzNH(2))(2)] and [Fe(TPP)(1-BuNH(2))(2)] show deviations that may be attributed to packing interactions in the solid and intrinsically low barriers to axial ligand rotation (<0.5 kcal/mol). Three types of minimum energy conformation are accessible for [Fe(TPP)(Pip)(2)]. The lowest energy conformation has an S(4)-ruffled porphyrin core. The conformation which matches the X-ray structure (Radonovich, L. J.; Bloom, A.; Hoard, J. L. J. Am. Chem. Soc. 1972, 94, 2073-2078) is a local minimum (1.6 kcal/mol higher in energy than the global minimum) with exact inversion symmetry. Higher in vacuo strain energy barriers ( approximately 2.2 kcal/mol) separate the potential minima of [Fe(TPP)(Pip)(2)], consistent with the increased bulk of the secondary amine axial ligands.

Journal Article↗

Obsessive-compulsive features in pathological lottery and scratch-ticket gamblers.

The results of this study support the notion that pathological gamblers drawn from the community would score higher on all three scores from the YBOCS than light gamblers. Consistent with hypotheses, pathological gamblers (lottery and scratch ticket) reported more obsessions, compulsions, and avoidance behavior than the light gamblers, and also reported having more urges to engage in injurious behaviors to themselves and others. These findings provide evidence that pathological gambling falls in a spectrum or family of disorders which have obsessive-compulsive disorder at its core. These findings support McElroy, Hudson, Philips, et al.'s (1993) suggestions of similarities between OCD and Impulse Control Disorders, and extend Blaszczynski (1999) findings of overlap between pathological gamblers and OCD in a treatment population. Heavy gamblers also reported significantly more hoarding symptoms and compulsive buying than light gamblers. More research in this area may show further evidence of a spectrum of disorders with obsessive compulsive disorder at its core, and show further links between impulse control disorders (such as pathological gambling) and OCD.

Adult↗

Quantitative and qualitative aspects of obsessive-compulsive behaviour in children with attention-deficit hyperactivity disorder compared with tic disorder.

OBJECTIVE: Within the framework of associated psychopathology in child psychiatric disorders, this study focused on quantitative and qualitative aspects of obsessive-compulsive behaviour (OCB) in both attention-deficit hyperactivity disorder (ADHD) and chronic tic disorder/Tourette's disorder (TD). METHOD: Forty-two healthy controls, 41 children with ADHD and 38 children with TD, aged 9-13 years, were investigated using the Leyton Obsessional Inventory--Child Version (LOI-CV), the Child Behaviour Checklist (CBCL) and an expert-rated structured parent interview to reflect a cross-informant view of OCB. RESULTS: Unexpectedly, self-reports of children with ADHD rather than children with TD showed the highest OCB scores in the LOI-CV. Qualitatively, ADHD-related OCB focused on the item subsets concerning 'dirt and contamination', 'repetition', 'overconscientiousness', and 'hoarding'. In the parent-rated CBCL, similar levels of OCB were reported for ADHD and TD patients. In contrast, only children with TD showed clinically relevant OCB according to expert ratings. CONCLUSION: Not only young TD patients but also children with ADHD should be investigated and monitored carefully for quantitative and qualitative aspects of OCB comorbidity.

Adolescent↗

Reinforcement and the organization of behavior in golden hamsters: brain stimulation reinforcement for seven action patterns.

Golden hamsters were reinforced with intracranial electrical stimulation of the lateral hypothalamus (ICS) for spending time engaging in one of seven topographically defined action patterns (APs). The stimulation used as reinforcer elicited hoarding and/or feeding and supported high rates of bar pressing. In Experiment 1, hamsters were reinforced successively for digging, open rearing, and face washing. Digging increased most in time spent, and face washing increased least. Experiments 2-5 examined these effects further and also showed that "scrabbling," like digging, was performed a large proportion of the time, almost without interruption, for contingent ICS but that scratching the body with a hindleg and scent-marking showed relatively little effect of contingent ICS, the latter even in an environment that facilitated marking. In Experiment 6, naive hamsters received ICS not contingent on behavior every 30 sec (fixed-time 30-sec schedule). Terminal behaviors that developed on this schedule were APs that were easy to reinforce in the other experiments, but a facultative behavior, face washing, was one not so readily reinforced. Experiment 7 confirmed a novel prediction from Experiment 6--that wall rearing, a terminal AP, would be performed at a high level for contingent ICS. All together, the results point to both motivational factors and associative factors being involved in the considerable differences in performance among different reinforced activities.

Animals↗

Finding your way in the dark: the retrosplenial cortex contributes to spatial memory and navigation without visual cues.

Path integration is presumed to rely on self-motion cues to identify locations in space and is subject to cumulative error. The authors tested the hypothesis that rats use memory to reduce such errors and that the retrosplenial cortex contributes to this process. Rats were trained for 1 week to hoard food in an arena after beginning a trial from a fixed starting location; probe trials were then conducted in which they began a trial from a novel place in light or darkness. After control injections, rats searched around the training location, showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted this search preference. To assess accuracy during navigation, rats were then trained to perform multiple trials daily, with a fixed or a different starting location in light or darkness. Retrosplenial cortex inactivation impaired accuracy in darkness. The retrosplenial cortex may provide mnemonic information, which decreases errors when navigating in the dark.

Animals↗

Evidence for anatomical but not functional asymmetry in the hemidecorticate rat.

Rats with unilateral ablation of the left or right cerebral neocortex or left or right hippocampus were studied in a battery of tests of spatial orientation, motor coordination, and social behavior, including Morris water task, radial arm maze, feeding, narrow beam traversing, puzzle latches, hoarding, grooming, nest building, running wheel activity, male--male interaction, and shock-induced aggression. Comparison of the brains of operated and control rats confirmed previous suggestions that the right hemisphere of the rat is bigger and may have different connections than the left hemisphere. Despite the morphological asymmetries, comparison of the behavior of rats with right hemidecortication with that of rats with left hemidecortication, and of rats with right and of those with left hippocampal lesions, failed to show a single instance of functional asymmetry in the rat brain. These behavioral results stand in marked contrast to previous reports of functional asymmetry in the control of activity, orientation, and rotation.

Afferent Pathways↗

Neonatal frontal lesions in hamsters impair species-typical behaviors and reduce brain weight and neocortical thickness.

Syrian golden hamsters with removals of the medial or ventral subfields of the frontal cortex at 4 days of age were compared behaviorally and neuroanatomically with hamsters with similar removals in adulthood. The behavioral results showed that hamsters with neonatal lesions show little sparing of species-typical behaviors such as hoarding and nest building. Study of the development of animals with early lesions showed that although as young juveniles the operated hamsters did not appear to be different from their littermate controls, as they developed they failed to improve in their performance as their littermates did. As adults these early operates were thus severely impaired relative to their littermates. Nonetheless, under certain environmental conditions it was possible to show that the animals were capable of performing the behaviors nearly as proficiently as normal animals. Thus, in order to thoroughly assess the extent of behavioral sparing following early neonatal lesions, it is necessary to test animals under widely varying stimulus conditions. Finally, when the brains of neonatally operated hamsters were compared with those of animals operated on in adulthood, there were striking differences; although the area of cavity appeared smaller in the neonatal operates, their brains weighed less and the remaining neocortex was thinner.

Animals↗

Central-place foraging by Rattus norvegicus on a radial maze.

We studied central-place foraging in rats (Rattus norvegicus) by placing food items that varied in size and weight at the ends of a 4-arm radial maze. In Experiments 1-3, rats increasingly tended to carry food to the center of the maze as the size of those items increased. Very large food items often were hoarded in the center. Rats consumed food faster on the arms than in the center, and rats traveled faster when carrying food than when not. Blocking arm entrances increased travel time between the center and the arms and decreased food carrying at every item weight except the largest. In Experiments 4-6, important conditions that influence the degree of food-carrying behavior were discovered; these were the intersection of maze arms, the presence of a conspecific, and the use of open vs. closed maze arms.

Animals↗

Social transmission of flavor preferences in two species of hamsters (Mesocricetus auratus and Phodopus campbelli).

Golden hamsters (Mesocricetus auratus) and dwarf hamsters (Phodopus campbelli) interacted with a conspecific demonstrator that had recently consumed a flavored food. When given a choice between their demonstrator's flavor and another flavor, the dwarf hamsters preferred the flavor their demonstrator had eaten. Golden hamsters did not prefer their demonstrators' diets when the demonstrators were unrelated adults or littermates, but they did when the demonstrator was their mother. Videotaping the interactions between demonstrators and observers revealed that adult golden hamsters did not investigate foods hoarded by their demonstrators whereas dwarf hamsters did. These results are interpreted in terms of the stimuli that activate feeding behavior systems in these 2 hamster species.

Animals↗

Decision making and set shifting impairments are associated with distinct symptom dimensions in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The authors examined how specific OCD symptom dimensions were related to neuropsychological functions using multiple regression analyses. A total of 39 OCD patients and 40 controls completed the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994), which is a test of decision making, and the Wisconsin Card Sorting Test (R. K. Heaton, 1981), which is a test of set shifting. OCD patients and controls showed comparable decision making. However, patients with prominent hoarding symptoms showed impaired decision making on the IGT as well as reduced skin conductance responses. OCD patients had poorer set shifting abilities than controls, and symmetry/ordering symptoms were negatively associated with set shifting. These results help explain previous inconsistent findings in neuropsychological research in OCD and support recent neuroimaging data showing dissociable neural mechanisms involved in mediating the different OCD symptom dimensions.

Adolescent↗

Behavior of the rat after removal of the neocortex and hippocampal formation.

After surgical removal of the neocortex and hippocampal formation, rats retained most of the movement patterns of locomotion, climbing, grooming, feeding, and fighting. However, forepaw immobility during swimming was abolished. Feeding behavior was suppressed temporarily but recovered partially. The distinctive postures of sleep and walking and a circadian rhythm of motor activity were retained. However, behaviors were often not performed at the appropriate time and place. The normal sequence of grooming behavior was disrupted; food hoarding and social behavior were essentially abolished. Removal of the neocortex alone had much the same effect as removal of neocortex and hippocampus together. Removal of hippocampus alone produced only a mild disruption of behavior. It is suggested that ascending nonspecific projections to the cerebral cortex play an important role in the moment-to-moment control of behavior but are not essential for the sleep-waking cycle.

Aggression↗

Decortication of rats in infancy or adulthood produced comparable functional losses on learned and species-typical behaviors.

Rats with complete ablation of the neocortex at 1--8 days of age were compared behaviorally with rats with similar excisions at 120 days of age. Decortication at both ages produced (a) chronic deficits in feeding behaviors indicated by chronic reduction in body weight, chronic deficits in pattern of food ingestion, and abolition of food-hoarding behavior; (b) increased general activity as measured in running wheels; (c) several chronic abnormalities in grooming behavior; (d) chronic abnormalities in paddling during swimming; (e) abolition of male sexual behavior; (f) elimination of defensive burying of a shock prod; and (g) severe impairments in the acquisition of a spatial reversal task. In sum, complete removal of the neocortex in infancy does not allow convincing sparing of function, a result demonstrating that subcortical structures are unable to take over functions of the neocortex. Thus, sparing of function reported following subtotal decortication requires neocortical circuitry, either alone or in combination with subcortical structures.

Aging↗

Brain reward circuitry and the regulation of energy balance.

Reward signals contribute to the regulation of energy balance by influencing switching between feeding and competing behaviors. Properties of natural rewards are mimicked by electrical stimulation of certain brain regions. The rewarding effect produced by stimulating the perifornical region of the hypothalamus is modulated by body weight and is attenuated both by leptin and insulin. Research is reviewed concerning the dependence of the rewarding effect of perifornical stimulation on long-term energy stores and the effects of two neuropeptides implicated in the regulation of energy balance, neuropeptide Y and corticotropin-releasing hormone. It is proposed that the potentiating effect of weight loss on perifornical self-stimulation is not tied to an increased propensity to eat or to an enhancement of food reward per se, but resembles the influence of long-term energy stores on non-ingestive behaviors that defend body weight, such as hoarding.

Animals↗

Eating difficulties, need for assisted eating, nutritional status and pressure ulcers in patients admitted for stroke rehabilitation.

The aim of this study was to describe the types and extent of eating difficulties, the need for assistance when eating, the nutritional status and pressure ulcers in consecutive patients (n = 162) admitted for stroke rehabilitation over a period of 1 year. Structured observations and assessments of eating, nutritional status (subjective global assessment of nutritional status), pressure ulcers and activities in daily living (Katz ADL-index) were performed by a nurse who also trained the staff to perform these assessments. Difficulties in eating were found in 80%, and 52.5% were unable to eat without assistance. Eating difficulties were: 'eats three-quarters or less of served food' (60%), difficulties in 'manipulating food on the plate' (56%), 'transportation of food to the mouth' (46%), 'sitting position' (29%), 'aberrant eating speed' (slow or forced) (26%), 'manipulating food in the mouth' (leakage, hoarding, chewing difficulties) (24%), 'swallowing difficulties' (18%), 'opening and/or closing the mouth' (16%), and 'alertness' (9%). Thirty-two percent were undernourished (49% of patients needing assisted eating and 13% of those not needing assistance, P < 0.0005). Among patients who were dependent in one or more functions according to the Katz ADL-index, 15% had pressure ulcers. The strongest eating variables for predicting nutritional status were 'alertness', 'swallowing difficulties', 'eats three-quarters or less of served food', and 'aberrant eating speed'. Nutritional status could in turn significantly predict pressure ulcers. Eating difficulties among patients with stroke are complex and the patient's situation before stroke adds to this complexity, especially among those dependent on assisted eating. As difficulties occur both among patients needing and not needing assisted eating, all patients with stroke admitted for rehabilitation need to be systematically assessed for eating difficulties and action needs to be taken to facilitate eating, especially as patients with eating difficulties risk becoming undernourished and in turn developing pressure ulcers.

Activities of Daily Living↗

Diogenes' syndrome in patients with intellectual disability: 'a rose by any other name'?

Diogenes' syndrome is characterized by marked self-neglect, domestic squalor, social withdrawal and hoarding of rubbish (syllogomania). The syndrome has been reported to occur in association with a wide variety of conditions, but the present authors were unable to find any previous reports of Diogenes' syndrome in patients with intellectual disability.

Activities of Daily Living↗

The seasonal pattern of cell proliferation and neuron number in the dentate gyrus of wild adult eastern grey squirrels.

The dentate gyrus is one of two areas in the mammalian brain that produces neurons in adulthood. Neurogenesis (proliferation, survival, and differentiation of new neurons) is regulated by experience, and increased neurogenesis appears to be correlated with improved spatial learning in mammals and birds. We tested the hypothesis that in long-lived mammals that scatter-hoard food, seasonal variations in spatial memory processing (i.e. increased processing during caching season in the autumn) might correlate with changes in neurogenesis and neuron number in the granule cell layer of the dentate gyrus (gcl DG). We investigated the rate of cell proliferation and the total number of neurons in the granule cell layer of wild adult eastern grey squirrels (Sciurus carolinensis) at three different times of the year (October, January and June). We found no seasonal differences in cell proliferation rate or in total neuron number in the granule cell layer. Our findings are in agreement with those of previous studies in laboratory mice and rats, and in free-ranging, food-caching, black-capped chickadees, as well as with current hypotheses regarding the relationship between neurogenesis and learning. Our results, however, are also in agreement with the hypothesis that neurogenesis in the dentate gyrus represents a maintenance system that may be regulated by environmental factors, and that changes in total neuron number previously reported in rodents represent developmental changes rather than adult plasticity. The patterns observed in mature wild rodents, such as free-ranging squirrels, may represent more accurately the extent of hippocampal plasticity in adult mammals.

Animals↗

Metabolic signals, hormones and neuropeptides involved in control of energy balance and reproductive success in hamsters.

In the 'postgenome era', most research on the neuroendocrine control of energy homeostasis has focused on hormonal and neuropeptide control of food intake (i.e. the amount of food eaten) in rats and mice. The amount of food consumed is influenced by both the motivation to procure food and the consummatory act of ingestion. In some species, the rate of food intake remains relatively constant, while survival is maintained via changes in food procurement, external storage and internal expenditure. For example, in hamsters, metabolic signals, peripheral hormones and central neuropeptides influence hunger motivation, food hoarding and changes in energy expenditure without necessarily influencing the amount of food ingested. A similar suite of metabolic signals, hormones and neuropeptides is involved in optimizing reproductive success under fluctuating energetic conditions. Reproductive processes are inhibited or delayed when energy expenditure outstrips energy intake and mobilization from storage. Estrous cyclicity in Syrian hamsters is sensitive to the availability of oxidizable glucose, but the presence of central glucose alone is not sufficient for normal estrous cycles. Food deprivation-induced anestrus does not depend upon food deprivation-induced increases in concentrations of adrenal hormones such as glucocorticoids. If hormones such as insulin and leptin play a role, they might do so by modulating the availability of glucose detected at extra-hypothalamic sites, instead of or in addition to direct effects on the mechanisms that control gonadotropin releasing hormone secretion. Despite our ability to measure and manipulate gene transcription, understanding of fuel homeostasis requires examination of indirect effects of hormones and neuropeptides on peripheral metabolism, attention to the motivational as well as consummatory aspects of ingestion, and the study of behaviour in a natural or seminatural context.

Animals↗

[Kleptomania: clinical and legal aspects].

Kleptomania is characterized by repetitive and irresistible impulses to steal objects, with growing excitement before, and relief after the incidents. The thefts are not planned, carried out without confidants and regarded as illegal by the offenders who often feel guilty for it. The objects are stolen not for monetary gain or personal use, but are mostly discarded, given away or hoarded. Though there is a debate going on for more than 100 years, the nosological position of kleptomania remains unclear. On the one hand the clinical picture is observed as an isolated disorder in otherwise healthy persons, on the other hand it may also occur as an accompanying symptom of various other psychiatric disorders, e. g. impulse control disorders, acute psychoses, affective, or organic psychic disorders. The present article gives an overview of the most important aetiopathogenetic viewpoints about kleptomania and discusses their nosological, therapeutical and legal implications.

Crime↗