Striatal adenosine A2A receptor involvement in normal and large nest building deer mice: Perspectives on compulsivity and anxiety.

Obsessive-compulsive disorder (OCD) is characterized by recurring obsessive thoughts and repetitive behaviors that are often associated with anxiety and perturbations in cortico-striatal signaling. Given the suboptimal response of OCD to current serotonergic interventions, there is a need to better understand the psychobiological mechanisms that may underlie the disorder. In this regard, investigations into adenosinergic processes might be fruitful. Indeed, adenosine modulates both anxiety- and motor behavioral output. Thus, we aimed to explore the potential associations between compulsive-like large nest building (LNB) behavior in deer mice, anxiety and adenosinergic processes. From an initial pool of 120 adult deer mice, 34 normal nest building (NNB)- and 32 LNB-expressing mice of both sexes were selected and exposed to either a normal water (wCTRL) or vehicle control (vCTRL), lorazepam (LOR) or istradefylline (ISTRA) for 7- (LOR) or 28 days after which nesting assessment was repeated and animals screened for anxiety-like behavior in an anxiogenic open field. Mice were then euthanized, the striatal tissue removed on ice and the adenosine A2A receptor expression quantified. Our findings indicate that NNB and LNB behavior are not distinctly associated with measures of generalized anxiety and that ISTRA-induced changes in nesting expression are dissociated from changes in anxiety scores. Further, data from this investigation show that nesting in deer mice is directly related to striatal adenosine signaling, and that LNB is founded upon a lower degree of adenosinergic A2A stimulation.

Dopaminergic and serotonergic modulation of social reward appraisal in zebrafish (Danio rerio) under circumstances of motivational conflict: Towards a screening test for anti-compulsive drug action.

Cognitive flexibility, shown to be impaired in patients presenting with compulsions, is dependent on balanced dopaminergic and serotonergic interaction. Towards the development of a zebrafish (Danio rerio) screening test for anti-compulsive drug action, we manipulated social reward appraisal under different contexts by means of dopaminergic (apomorphine) and serotonergic (escitalopram) intervention. Seven groups of zebrafish (n = 6 per group) were exposed for 24 days (1 h per day) to either control (normal tank water), apomorphine (50 or 100 µg/L), escitalopram (500 or 1000 µg/L) or a combination (A100/E500 or A100/E1000 µg/L). Contextual reward appraisal was assessed over three phases i.e. Phase 1 (contingency association), Phase 2 (dissociative testing), and Phase 3 (re-associative testing). We demonstrate that 1) sight of social conspecifics is an inadequate motivational reinforcer under circumstances of motivational conflict, 2) dopaminergic and serotonergic intervention lessens the importance of an aversive stimulus, increasing the motivational valence of social reward, 3) while serotoninergic intervention maintains reward directed behavior, high-dose dopaminergic intervention bolsters cue-directed responses and 4) high-dose escitalopram reversed apomorphine-induced behavioral inflexibility. The results reported here are supportive of current dopamine-serotonin opponency theories and confirm the zebrafish as a potentially useful species in which to investigate compulsive-like behaviors.

[Hepcidin and Plasmodium falciparum malaria in anemic school children in Mali]. / Hepcidine et infection due a Plasmodium falciparum chez un groupe d'ecoliers anémiés du Mali.

Hepcidin is a peptide produced by hepatocytes and detectable in blood and urine. Urinary hepcidin excretion appeared to be significantly increasing in humans with acute and chronic infections or inflammatory diseases. However, the effects of common tropical parasitic infections on hepcidin have not been sufficiently examined. We carried out a study in school children from Mali living in a neighborhood where Plasmodium falciparum malaria and Schistosoma haematobium infections are prevalent. Anemia (hemoglobin < 120 g/l) prevalence was very high among these children (68%); 24% had iron deficiency anemia. The prevalence of infections was also high (65% had at least one infection and 41% had C-reactive protein (CRP) levels > 10 mg/L). S. haematobium was diagnosed in 64%. We assessed first morning urine hepcidin excretion in a sub-sample of 15 children with either S. haematobium, P. falciparum malaria or none; 14 of these 15 children were included in the analyses. Children with P. falciparum malaria excreted significantly higher levels of hepcidin than those with S. haematobium (chi2 = 3.86; p = 0.05) or without any infection (chi2 = 5.95; p = 0.01). Urinary hepcidin correlated significantly with CRP (Spearman's r = 0.59; p = 0.001) and serum ferritin (Spearman's r = 0.73; p = 0.003). Our study confirms the still limited evidence of an association between human malaria and increased urinary hepcidin and points out the need for further studies to define the contribution of hepcidin to anemia associated with this disease.

Early interactions between neuronal adaptation and voluntary control determine perceptual choices in bistable vision.

At the onset of bistable stimuli, the brain needs to choose which of the competing perceptual interpretations will first reach awareness. Stimulus manipulations and cognitive control both influence this choice process, but the underlying mechanisms and interactions remain poorly understood. Using intermittent presentation of bistable visual stimuli, we demonstrate that short interruptions cause perceptual reversals upon the next presentation, whereas longer interstimulus intervals stabilize the percept. Top-down voluntary control biases this process but does not override the timing dependencies. Extending a recently introduced low-level neural model, we demonstrate that percept-choice dynamics in bistable vision can be fully understood with interactions in early neural processing stages. Our model includes adaptive neural processing preceding a rivalry resolution stage with cross-inhibition, adaptation, and an interaction of the adaptation levels with a neural baseline. Most importantly, our findings suggest that top-down attentional control over bistable stimuli interacts with low-level mechanisms at early levels of sensory processing before perceptual conflicts are resolved and perceptual choices about bistable stimuli are made.

Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee.

OBJECTIVE: Although knee malalignment is assumed to correlate with knee osteoarthritis (OA), it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA. The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA. METHODS: A total of 1,501 participants in the Rotterdam study were randomly selected. Knee OA at baseline and at followup (mean followup 6.6 years) was scored according to the Kellgren/Lawrence (K/L) grading system. Alignment was measured by the femorotibial angle on radiographs at baseline. Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA. RESULTS: Of 2,664 knees, 1,012 (38%) were considered to have normal alignment, 693 (26%) had varus alignment, and 959 (36%) had valgus alignment. A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 0.97-2.44), and varus alignment was associated with a 2-fold increased risk (OR 2.06, 95% CI 1.28-3.32). Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non-overweight persons. The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment (OR 2.90, 95% CI 1.07-7.88). CONCLUSION: An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA. However, this association seems particularly applicable to overweight and obese persons.

Voluntary control and the dynamics of perceptual bi-stability.

Voluntary control and conscious perception seem to be related: when we are confronted with ambiguous images we are in some cases and to some extent able to voluntarily select a percept. However, to date voluntary control has not been used in neurophysiological studies on the correlates of conscious perception, presumably because the dynamic of perceptual reversals was not suitable. We exposed the visual system to four ambiguous stimuli that instigate bi-stable perception: slant rivalry, orthogonal grating rivalry, house-face rivalry, and Necker cube rivalry. In the preceding companion paper [van Ee, R. (2005). Dynamics of perceptual bi-stability for stereoscopic slant rivalry and a comparison with grating, house-face, and Necker cube rivalry. Vision Research] we focussed on the temporal dynamics of the perceptual reversals. Here we examined the role of voluntary control in the dynamics of perceptual reversals. We asked subjects to attempt to hold percepts and to speed-up the perceptual reversals. The investigations across the four stimuli revealed qualitative similarities concerning the influence of voluntary control on the temporal dynamics of perceptual reversals. We also found differences. In comparison to the other rivalry stimuli, slant rivalry exhibits: (1) relatively long percept durations; (2) a relatively clear role of voluntary control in modifying the percept durations. We advocate that these aspects, alongside with its metrical (quantitative) aspects, potentially make slant rivalry an interesting tool in studying the neural underpinnings of visual awareness.

Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers.

Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l(-1) ozone (CF+25), non-filtered air (NF), non-filtered air plus 25 nl l(-1) ozone (NF+25) and non-filtered air plus 50 nl l(-1) ozone (NF+50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species.

Iopamidol myelography in the horse.

The use of the non-ionic, water-soluble contrast agent iopamidol for myelography in seven horses is described. Contrast columns of diagnostic quality were produced in all seven cases and the procedure did not invoke any adverse reactions in the five cases which were recovered from general anaesthesia. It is concluded that iopamidol is a safe and effective contrast agent for myelography in the horse.

Fresh gas flow economics of the Waters (to-and-fro) system in small animal anaesthetic practice.

The Waters (to-and-fro) system is a commonly used anaesthetic system in small animal clinical practice. Although it may be used as a totally closed system, it has been recommended that it be used as a semi-closed system with relatively high fresh gas flow rates. The performance of the Waters system was studied with reference to wastage of neat, unused fresh gas flow. The results were compared with the performance of a modified Waters system. Using a fresh gas flow rate of 2 litres/minute considerable wastage of fresh gas flow and volatile agent was noted using the Waters system; the wastage was less with the modified system. Marked savings of fresh gas flow and volatile agent could result by reducing the fresh gas flow to 0.5 litres/minute. The findings are discussed in the light of current small animal clinical anaesthetic practice.

Use of guaiacol glycerine ether in clinical anaesthesia in the horse.

A total of 103 anaesthetic inductions were performed in horses for a variety of elective procedures. All cases were premedicated with acepromazine maleate (0.02 to 0.05 mg/kg body weight [bwt] intramuscularly [im]). In 50 cases (Group A) anaesthesia was induced by a single intravenous (iv) bolus of thiopentone sodium (11.1 mg/kg bwt or 1 g/90 kg bwt) followed immediately by a bolus of suxamethonium chloride (0.1 mg/kg bwt). In 53 cases (Group B) anaesthesia was induced using iv guaiacol glycerine ether (GGE) (approximately 50 mg/kg bwt) followed by a bolus of thiopentone at half the usual dose rate (5.6 mg/kg bwt or 1 g/180 kg bwt). Induction of anaesthesia was uneventful in both groups although in Group B it was particularly smooth. Following endotracheal intubation anaesthesia was maintained with halothane in oxygen administered via a circle system. The duration of anaesthesia was comparable between the two groups; however, the mean (+/- sd) time to standing in Group B, 35 +/- 22 mins, was significantly shorter than in Group A, 48 +/- 25 mins. The use of the GGE/thiopentone technique is discussed.

Persistent right aortic arch in a kitten.

Oesophageal obstruction as a result of persistence of the right aortic arch was diagnosed in a nine--and-a-half week old kitten. Thoracotomy was performed and corrective surgery successfully carried out. This uncommon condition is discussed.

Clinical, biochemical, and hormonal aspects of treatment with Des-tyr1-gamma-endorphin in schizophrenia.

Des-tyr1-gamma-endorphin (DT gamma E) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT gamma E led to a decrease of plasma prolactin levels in patients treated with DT gamma E in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylglycol were affected by DT gamma E. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DT gamma E. These data confirm and extend previous findings that DT gamma E has antipsychotic properties in a number of schizophrenic patients.

Ceruletide resembles antipsychotics in rats and schizophrenic patients. Preliminary report.

Peptides related to the C-terminal part of cholecystokinin, including ceruletide, were found to be active in a number of behavioral test procedures in rats, predicting antipsychotic action. In a subsequent clinical trial ceruletide was administered intramuscularly in a dose of 40 micrograms twice for 2 consecutive weeks to 6 neuroleptic-treated schizophrenic patients following a single-blind design. In 3 patients, a pronounced long-lasting antipsychotic effect was observed, while in the other 3 the response was less marked. It is suggested that ceruletide may be a potential antipsychotic peptide.

No evidence for a peripheral effect of L-DOPA on plasma prolactin in the rat.

Male and female rats with two permanently indwelling intravenous catheters were infused for 2 hours with ovine prolactin. During equilibrium conditions the effects of intravenously injected L-DOPA and benzerazide (a blocker of dopa-decarboxylase) on steady state levels of ovine prolactin were measured. A dose of 4.5 mg L-DOPA per 100 gr body weight (b.w.) caused a transient increase of plasma ovine prolactin. A dose of 0.3 mg L-DOPA/100 gr b.w. had no effect, neither in males nor in females, while benzerazide (20 mg/100 gr b.w.) had only a slight effect. The experiments suggest that L-DOPA does not affect the peripheral uptake of prolactin from the plasma.

Isolation and partial characterization of insulin-glucagon liberin from bovine hypothalamus.

A tridecapeptide that enhances insulin and glucagon release from isolated islets of Langerhans was extracted from bovine hypothalami. Following the recommendation of the IUPAC-IUB Commission on Biological Nomenclature, the name Insulin-Glucagon Liberin (IGL) is proposed. The extraction, purification and partial characterization of the peptide is reported. The biological significance of hypothalamic IGL is still unknown but it could be a neurohumoral link between the hypothalamus and islet function, related to the regulation of fool intake and body weight.