Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions

Many symptoms of human depressive disorders are also observed in animals after exposure to unpredictable stressors. The chronic mild stress (CMS) paradigm was developed in order to better model the human situation by using chronic mild stressors over a longer period. It is claimed that the model induces anhedonia in the animals, a core symptom of depression in humans. Despite the fact that the CMS model has a high degree of face validity, there are a number of laboratories in which the establishment of the model is less reliably observed. We have examined behavior (sexual activity and open field activity) together with hedonic measures (sucrose and saccharine intake) after exposure to CMS. CMS decreased male sexual activity (e.g. reduced capability to ejaculate) and increased activity in an open field test. The hedonic measures showed diverging results after CMS in our laboratory. Sucrose consumption was reduced, while saccharine consumption did not show a comparable change. It is concluded that CMS induces comparable alterations to some depression-like symptoms in humans. Saccharine consumption is not a reliable indicator of the hedonic responsiveness to CMS.     

Insomnia symptoms and mortality: a register‐linked study among women and men from Finland,Norway and Lithuania

Evidence on the association between insomnia symptoms and mortality is limited and inconsistent. This study examined the association between insomnia symptoms and mortality in cohorts from three countries to show common and unique patterns. The Finnish cohort comprised 6605 employees of the City of Helsinki, aged 40–60 years at baseline in 2000–2002. The Norwegian cohort included 6236 participants from Western Norway, aged 40–45 years at baseline in 1997–1999. The Lithuanian cohort comprised 1602 participants from the City of Palanga, aged 35–74 years at baseline in 2003. Mortality data were derived from the Statistics Finland and Norwegian Cause of Death Registry until the end of 2012, and from the Lithuanian Regional Mortality Register until the end of 2013. Insomnia symptoms comprised difficulties initiating sleep, nocturnal awakenings, and waking up too early. Covariates were age, marital status, education, smoking, alcohol, physical inactivity, obesity, diabetes, cardiovascular diseases, depression, shift work, sleep duration, and self‐rated health. Cox regression analysis was used. Frequent difficulties initiating sleep were associated with all‐cause mortality among men after full adjustments in the Finnish (hazard ratio 2.51; 95% confidence interval 1.07–5.88) and Norwegian (hazard ratio 3.42; 95% confidence interval 1.03–11.35) cohorts. Among women and in Lithuania, insomnia symptoms were not statistically significantly associated with all‐cause mortality after adjustments. In conclusion, difficulties initiating sleep were associated with mortality among Norwegian and Finnish men. Variation and heterogeneity in the association between insomnia symptoms and mortality highlights that further research needs to distinguish between men and women, specific symptoms and national contexts, and focus on more chronic insomnia.     

Next of kin’s experiences of involvement during involuntary hospitalisation and coercion

Background

Norway has extensive and detailed legal requirements and guidelines concerning involvement of next of kin (NOK) during involuntary hospital treatment of seriously mentally ill patients. However, we have little knowledge about what happens in practice. This study explores NOK’s views and experiences of involvement during involuntary hospitalisation in Norway.

Methods

We performed qualitative interviews-focus groups and individual-with 36 adult NOK to adults and adolescents who had been involuntarily admitted once or several times. The semi-structured interview guide included questions on experiences with and views on involvement during serious mental illness and coercion.

Results

Most of the NOK were heavily involved in the patient’s life and illness. Their conceptions of involvement during mental illness and coercion, included many important aspects adding to the traditional focus on substitute decision-making. The overall impression was, with a few exceptions, that the NOK had experienced lack of involvement or had negative experiences as NOK in their encounters with the health services. Not being seen and acknowledged as important caregivers and co sufferers were experienced as offensive and could add to their feelings of guilt. Lack of involvement had as a consequence that vital patient information which the NOK possessed was not shared with the patient’s therapists.

Conclusions

Despite public initiatives to improve the involvement of NOK, the NOK in our study felt neglected, unappreciated and dismissed. The paper discusses possible reasons for the gap between public policies and practice which deserve more attention: 1. A strong and not always correct focus on legal matters. 2. Little emphasis on the role of NOK in professional ethics. 3. The organisation of health services and resource constraints. 4. A conservative culture regarding the role of next of kin in mental health care. Acknowledging these reasons may be helpful to understand deficient involvement of the NOK in voluntary mental health services.

     

The Norwegian national project for ethics support in community health and care services

Background

Internationally, clinical ethics support has yet to be implemented systematically in community health and care services. A large-scale Norwegian project (2007–2015) attempted to increase ethical competence in community services through facilitating the implementation of ethics support activities in 241 Norwegian municipalities. The article describes the ethics project and the ethics activities that ensued.

Methods

The article first gives an account of the Norwegian ethics project. Then the results of two online questionnaires are reported, characterizing the scope, activities and organization of the ethics activities in the Norwegian municipalities and the ethical topics addressed.

Results

One hundred and thirty-seven municipal contact persons answered the first survey (55 % response rate), whereas 217 ethics facilitators from 48 municipalities responded to the second (33 % response rate). The Norwegian ethics project is vast in scope, yet has focused on some institutions and professions (e.g., nursing homes, home-based care; nurses, nurses’ aides, unskilled workers) whilst seldom reaching others (e.g., child and adolescent health care; physicians). Patients and next of kin were very seldom involved. Through the ethics project employees discussed many important ethical challenges, in particular related to patient autonomy, competence to consent, and cooperation with next of kin. The “ethics reflection group” was the most common venue for ethics deliberation.

Conclusions

The Norwegian project is the first of its kind and scope, and other countries may learn from the Norwegian experiences. Professionals have discussed central ethical dilemmas, the handling of which arguably makes a difference for patients/users and service quality. The study indicates that large (national) scale implementation of CES structures for the municipal health and care services is complex, yet feasible.

     

Dipyridamole synergizes with nitric oxide to prolong inhibition of thrombin-induced platelet shape change

We and others have previously demonstrated that nitric oxide (NO)-induced inhibition of platelet shape change is important in regulating platelet adhesion and aggregation, and therapeutic intervention of this pathway is clinically relevant for secondary prevention of stroke with dipyridamole. In the present study, we investigated whether dipyridamole affected the shape change of aspirinated platelets. Platelet shape change was inhibited using both authentic NO and sodium nitroprusside, as monitored by light scattering and mean platelet volume measurements. Dipyridamole synergized with NO, even at supra-therapeutic levels, to inhibit thrombin-induced shape change and further potentiated cAMP dependent protein kinase (PKA) mediated phosphorylation of vasodilator stimulated phosphoprotein (VASP) Ser157, even without altered levels of platelet cAMP. The effect of dipyridamole on NO-inhibited shape change depended on cGMP synthesis as evaluated by inhibition of soluble guanylyl cyclase. Measured increases in cGMP levels by dipyridamole and NO was assessed by mathematical modeling and found to be consistent with inhibition of phosphodiesterase 5 (PDE5). The model could explain the unexpected efficiency of dipyridamole in inhibiting PDE5 at the measured cGMP levels, by the majority of cGMP being bound to cGMP-dependent protein kinase (PKG). Still, selective activators of PKG failed to extend NO-mediated inhibition of the thrombin-induced platelet shape change, suggesting that PKG was not responsible for the inhibitory effect of NO and dipyridamole on shape change. The effects of dipyridamole were independent of the prostanoid and ADP pathways. Thus, the effect of dipyridamole on NO-mediated inhibition of platelet shape change may be an important and additional beneficial therapeutic effect of dipyridamole, which we suggest, is acting though localized amplification of the NO/cGMP/Phosphodiesterase3/cAMP/PKA-pathway. Probably, the efficiency of dipyridamole could be amplified clinically with NO donors.     

Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer's disease

Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of astrocyte polarization. Loss of astrocyte polarization is known to compromise astrocytic function and to be associated with impaired water and K+ homeostasis. Here we investigate by a combination of light and electron microscopic immunocytochemistry whether amyloid deposition is associated with a loss of astrocyte polarization, using AQP4 as a marker. We used the tg-ArcSwe mouse model of Alzheimer's disease, as this model displays perivascular plaques as well as plaques confined to the neuropil. 3D reconstructions were done to establish the spatial relation between plaques and astrocytic endfeet, the latter known to contain the perivascular pool of AQP4. Changes in AQP4 expression emerge just after the appearance of the first plaques. Typically, there is a loss of AQP4 from endfoot membranes at sites of perivascular amyloid deposits, combined with an upregulation of AQP4 in the neuropil surrounding plaques. By electron microscopy it could be verified that the upregulation reflects an increased concentration of AQP4 in those delicate astrocytic processes that abound in synaptic regions. Thus, astrocytes exhibit a redistribution of AQP4 from endfoot membranes to non-endfoot membrane domains. The present data suggest that the development of amyloid deposits is associated with a loss of astrocyte polarization. The possible perturbation of water and K+ homeostasis could contribute to cognitive decline and seizure propensity in patients with Alzheimer's disease.