Functional alterations of nicotinic neurotransmission in dopamine transporter knock-out mice

Mice lacking the dopamine (DA) transporter (DAT) gene exhibit a phenotype reminiscent of schizophrenia and attention deficit hyperactivity disorder (ADHD), including hyperDAergia, hyperactivity and deficits in cognitive performance, which are alleviated by antipsychotic agents. Numerous studies suggest a dysfunction of nicotinic neurotransmission in schizophrenia and show increased tobacco intake in schizophrenic and ADHD patients, possibly as a self-medication. Thus, we examined the potential alteration of nicotinic neurotransmission in DAT knock-out (KO) mice. We showed that constitutively hyperDAergic DAT KO mice exhibited modifications in nicotinic receptor density in an area- and subtype-dependent manner. In some DAergic areas, the small decrease in the beta2* nicotinic subunit (nAChR) density contrasted with the higher decrease and increase in the alpha6* and alpha7 nAChR densities, respectively. Mutant mice were hypersensitive to the stimulant locomotor effects of nicotine at low doses, probably due to enhanced nicotine-induced extracellular DA level. They also showed hypersensitivity to the hypolocomotion induced by nicotine. In contrast, no hypersensitivity was observed for other nicotine-induced behavioral effects, such as anxiety or motor activity in the elevated plus maze. Co-administration of nicotinic agonists at sub-active doses elicited opposite locomotor effects in wild-type and DAT KO mice, as reported previously for methylphenidate. Interestingly, such a co-administration of nicotinic agonists induced synergistic hypolocomotion in DAT KO mice. These findings show that a targeted increase of DA tone can be responsible for significant adaptations of the cholinergic/nicotinic neurotransmission. This study may provide potential leads for the use of nicotine or combined nicotinic agonists for the therapy of psychiatric disorders.     

Serum interleukin-6 is elevated in symptomatic carotid bifurcation disease

Introduction – The levels of circulating proinflammatory cytokines may express the extent of the inflammatory response and their participation in plaque progression and rupture needs to be evaluated. We aimed to investigate differences in circulating levels of proinflammatory cytokines and in plaque infiltration by macrophages between patients undergoing carotid endarterectomy for symptomatic and asymptomatic carotid atherosclerotic disease. Methods – One hundred nineteen patients (91 men and 28 women; mean age 66 ± 8 years; range 42–83 years) who underwent carotid endarterectomy for significant (>70%) carotid bifurcation stenosis were enrolled in this study. Patients were characterized as symptomatic (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), IL‐1β, serum amyloid A (SAA), and high‐sensitivity C‐reactive protein (hs‐CRP) were evaluated. Macrophage infiltration of the plaque was assessed quantitatively from endarterectomy specimens using the monoclonal antibody CD68. Results – Serum IL‐6 levels were significantly higher in patients with symptomatic compared with those with asymptomatic carotid disease (3.3 [2.0–6.5] pg/ml vs 2.5 [1.9–4.1] pg/ml, P = 0.02). TNF‐α, IL‐1β, SAA, and hs‐CRP levels did not differ significantly between the two groups. Symptomatic patients had also more intense macrophage accumulation in the carotid plaque compared with asymptomatic patients (0.6 ± 0.1% vs 0.4 ± 0.1%, P < 0.001). Although there were correlations between the levels of the different inflammatory markers, there were no correlation between any of them and the extent of plaque macrophage infiltration. Conclusion – Patients with symptomatic carotid atherosclerotic disease have elevated serum IL‐6 levels compared with asymptomatic patients. Symptomatic patients have also more intense macrophage infiltration of the atherosclerotic plaque suggesting that inflammatory process may contribute to the destabilization of the carotid plaque.     

Viscoelastic properties of bovine articular cartilage attached to subchondral bone at high frequencies

Background  

Articular cartilage is a viscoelastic material, but its exact behaviour under the full range of physiological loading frequencies is unknown. The objective of this study was to measure the viscoelastic properties of bovine articular cartilage at loading frequencies of up to 92 Hz.     

Rotating shift-related changes in hormone levels in intensive care unit nurses

Title.  Rotating shift-related changes in hormone levels in intensive care unit nurses.
Aim.  This paper is a report of a study to investigate if an irregular rotating shift system, including night shifts, can cause changes to the secretion of hormones in nurses.
Method.  In 2006, 32 healthy intensive care unit nurses completed the Standard Shiftwork Index (SSI) and blood samples were collected from each participant at the beginning and end of each shift. Change in hormone levels between the beginning and end of morning shifts were examined and compared between nurses on morning only and rotating shifts. Correlations between change in hormone concentrations and scores from the SSI are presented.
Results.  The mean reduction of cortisol level between the two measurements was statistically significantly greater for the 'rotating' than 'morning' shift group ( P  = 0·032). There were no statistically significant differences between the two groups in overall mean change from the first to the second measurement of prolactin, triiodothyronine and thyroid-stimulating hormone. Levels of thyroxine increased statistically significantly in the 'rotating' group ( P  = 0·049) but not in the 'morning' group. The morningness scale score was greater for the 'rotating' group, while greater job satisfaction levels were found in the 'morning' group. Statistically significant correlations were found between thyroid-stimulating hormone, triiodothyronine, thyroxine and prolactin changes and specific scales of the SSI questionnaire.
Conclusion.  Ergonomic shift schedules sympathetic to the body clock and nurses' preferences should be adopted to mitigate the adverse effects on health.     

When "no" might not quite mean "no"; the importance of informed and meaningful non-consent: results from a survey of individuals refusing participation in a health-related research project

Background  

Low participation rates can lead to sampling bias, delays in completion and increased costs. Strategies to improve participation rates should address reasons for non-participation. However, most empirical research has focused on participants' motives rather than the reasons why non-participants refuse to take part. In this study we investigated the reasons why older people choose not to participate in a research project.     

Normalization of thyroid hormone levels in patients with either hyper- or hypothyroidism results in a profound change of atrial natriuretic peptide (ANP) levels

Atrial Natriuretic Peptide (ANP) is a hormone produced by cardiac atrial myocytes. Thyroid hormones may affect its release. The aim of this study was to analyze the effect of hyper and hypothyroidism on the secretion of ANP and its relationship with the changes of the renin-angiotensin-aldosterone system. Plasma ANP concentration as well as plasma renin activity (PRA) and aldosterone (ALDO) were measured in 21 patients with hyperthyroidism, 12 patients with hypothyroidism and 29 normal controls. Moreover, in 5 hyperthyroid and 8 hypothyroid patients hormones measurements were performed at diagnosis and 15, 30, 45 and 60 days after starting the appropriate therapy. Statistical analysis was performed employing the Wilcoxon two sample test to compare the ANP levels in normal and hyper or hypothyroid patients while the pairwise comparisons were evaluated using the Spermans rank correlation. Partial correlation and regression models were used to examine the joint effects of multiple predictors on ANP. ANP levels were significantly higher in hyperthyroid (mean+/-SEM, 17+/-1.7 pmol/L, +/-<0.001) and lower in hypothyroid patients (6.18+/-1.14 pmol/L, p<0.01) compared to normals (10.35+/-0.59 pmol/L). In the hyperthyroid patients following treatment with antithyroid drugs plasma ANP levels reached normal values after 15 days and remained stable thereafter. In the hypothyroid patients, ANP levels increased gradually following initiation of treatment with thyroxine, reaching values comparable to controls at day 45. PRA was significantly higher only in hyperthyroid patients compared to controls. ALDO concentrations were not different in all groups studied. No correlation was found between plasma ANP levels and T3, T4, TSH, PRA and ALDO levels in the individual groups, while a positive correlation for T3 (r=0.610, p<0.01), T4 (r=0.653, p<0.01) and pulse rate (r=0.704, p<0.01) and negative correlation with TSH (r=-0.519, p<0.01) was found when all groups were pooled together. In conclusion, our data indicate that thyroid hormones affect positively ANP secretion from cardiac myocytes. This effect may be, at least in part, indirect via hemodynamic alterations.     

One versus two embryo transfer after IVF and ICSI: a randomized study

BACKGROUND: The main reason for adverse treatment outcome in assisted reproduction is the high rate of multiple pregnancies. The only strategy to avoid dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144 women, who had had at least four good quality embryos available after IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous failed treatment cycle, were randomized to have either one or two embryos transferred. The treatment outcomes including those after frozen embryo transfer were compared between these groups. RESULTS: The clinical pregnancy rate per transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo transfer group, the difference being not significant. Eleven twin deliveries (n = 39) occurred in the two embryo transfer group and there was one pair of monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate per patient after transfer of fresh and frozen embryos was 47.3% in the one embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS: Our results indicate that among women who have good quality embryos in their first IVF/ICSI, good treatment results can be achieved. They support the idea of changing embryo transfer policy towards one embryo transfer without any remarkable decrease in the success rate, while dizygotic twins can be avoided.     

Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo

The symptoms of major psychotic illness are diverse and vary widely across individuals. Furthermore, the prepsychotic phase is indistinct, providing little indication of the precise pattern of symptoms that may subsequently emerge. Likewise, although in some individuals who have affected family members the occurrence of disease may be predicted, the specific symptom profile may not. An important question, therefore, is whether predictive physiological markers of symptom expression can be identified. We conducted a placebo-controlled, within-subjects study in healthy individuals to investigate whether individual variability in baseline physiology, as assessed using functional magnetic resonance imaging, predicted psychosis elicited by the psychotomimetic drug ketamine and whether physiological change under drug reproduced those reported in patients. Here we show that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.