Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons

Dopamine is believed to contribute to the degeneration of dopamine-containing neurons in the brain. However, whether dopamine affects the survival of other neuronal populations has remained unclear. Here we document that mice with persistently elevated extracellular dopamine, resulting from inactivation of the dopamine transporter gene, sporadically develop severe symptoms of dyskinesia concomitant with apoptotic death of striatal dopamine-responsive gamma-aminobutyric acidergic neurons. Chronic inhibition of dopamine synthesis prevents the appearance of motor dysfunction. The neuronal death is associated with overactivation of dopaminergic signaling as evidenced by the robust up-regulation of striatal DeltaFosB, cyclin-dependent kinase 5, and p35. Moreover, hyperphosphorylation of the tau protein, a phenomenon associated with the activation of cyclin-dependent kinase 5 in several neurodegenerative disorders, is observed in symptomatic mice. These findings provide in vivo evidence that, in addition to its proposed role in the degeneration of dopamine neurons, dopamine can also contribute to the selective death of its target neurons via a previously unappreciated mechanism.     

Correlation between salivary and serum melatonin: dependence on serum melatonin levels

Saliva and serum samples were collected from eight healthy volunteers every two hours during a 26-hour period. Melatonin concentrations were measured by radioimmunoassay after chloroform extraction using radioiodinated melatonin as a tracer. Five of the subjects had high serum melatonin levels at night (peak levels higher than 75 pg/ml); in three subjects the highest serum melatonin concentration was 20-40 pg/ml. All subjects had low levels (less than 10 pg/ml) during the day. The correlations between salivary and serum levels were calculated. The regression line y = 0.33x + 3.7 pg/ml, r = 0.95, P less than 0.001, was obtained for all detectable value pairs (n = 73). The regression and correlation coefficients were almost equal for the peak values of melatonin and during the rising and descending phases of the secretion patterns. However, no significant correlation was found between low daytime salivary and serum concentrations when calculated separately. In the five high-secretors the melatonin levels in saliva reflected reliably the changes in serum, but in the three low-secretors the correlation between salivary and serum melatonin was not significant. The proportion of melatonin found in saliva decreased with increasing serum melatonin levels. Circadian rhythm parameters were estimated by single cosinor analysis. The acrophases did not differ significantly within a subject in the concomitant measurements of serum and salivary melatonin. The measurements of salivary melatonin levels seem valid for studies on melatonin rhythms, but the melatonin concentrations measured in saliva do not always consistently reflect the absolute concentrations in blood.     

Mortality from amyloidosis and renal diseases in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA), 500 men and 500 women, aged 40 years and over, together with a control population matched by age and sex, were observed over a 10 year period. The overall mortality was significantly higher in both men and women with rheumatoid arthritis than in the controls due to an excess mortality from infections and cardiovascular and renal diseases. During the follow up 31 patients with RA (12 male, 19 female) and one male control subject died from amyloidosis and 42 RA patients (19 male, 23 female) and one male control from renal diseases. The most important causes of renal deaths were chronic nephritis and renal infections.     

Motivational Orientation of People Participating in Vocational Rehabilitation

Purpose The task of vocational rehabilitation is to support the employee’s chances of continuing in working life. The study aimed to examine the motivational orientation of people participating in vocational rehabilitation and to find out what characteristics of the clients, their life situation, and their beliefs and perceptions were associated with it. Methods A mail questionnaire was answered by 839 rehabilitation clients who had received an affirmative rehabilitation decision under the earnings-related pension scheme 12 months earlier (response rate 67 %). Two variables depicting motivational orientation were formed, i.e., motivation for continuing in working life and motivation for participating in vocational rehabilitation. Logistic regression analyses were applied in examining the factors associated with each motivation variable. Results The results indicate that the two motivational orientations can be regarded as partly separate and partly overlapping constructs. The rehabilitation clients’ motivational orientations were associated with their experiences and their perceptions on environmental factors and future possibilities, both those that precipitated the application for rehabilitation and those that are important in their current life situation and their perceived future possibilities. Conclusions In the planning of individual rehabilitation processes there is a clear need to sort out what factors may hide behind the client’s weak contextual or situational motivation. In the course of the rehabilitation process, it is important to discuss these factors in order to alleviate the clients’ uncertainty towards change and enhance their motivation to participate in rehabilitation and re-think their future prospects of returning to work.     

Visual field findings after a ruptured intracranial aneurysm

Background

Visual field defects (VFDs) negatively affect activities of daily living and rehabilitation following aneurysmal subarachnoid haemorrhage (aSAH). The aim here was to assess VFDs in patients with aSAH and their associations with age, gender, aSAH severity, and clinical outcome.

Methods

Patients admitted to Helsinki University Central Hospital and treated during 2011 were participants in this prospective study. Findings obtained with the Octopus 900 perimeter (Haag-Streit Inc, Koenic, Switzerland), the Goldmann perimeter (Haag-Streit Inc, Bern, Switzerland), or the confrontation visual field test on admission and 3 days, 14 days, 2 to 4 months, and 6 months postoperatively were assigned to 16 classes. Associations between post-chiasmal VFDs and relevant clinical, radiological, and demographic data were analysed with uni- and multivariate logistic regression.

Results

Of 105 survivors at 6 months, 20 (19 %) had VFDs occurring for aneurysm- or operation-related reasons; homonymous hemianopias or quadrantanopias were the most common finding, occurring in 16 patients (15 %). Posterior ischaemic optic neuropathy presented in two patients (2 %). Ten survivors (10 %) no longer fulfilled visual field requirements for driving licences. Significant associations emerged between VFDs at 6 months and the Hunt and Hess (H&H), World Federation of Neurosurgical Societies (WFNS), and Fisher grades on admission, presence of intracerebral haemorrhage (ICH), hydrocephalus, or postoperative infarction, and higher modified Rankin Scale scores at 6 months. Multivariate logistic regression showed the H&H grade and presence of ICH to independently predict VFDs.

Conclusions

Assessing VFDs is advisable, especially among patients with poor-grade aSAH (H&H grade IV or V) and ICH.     

The degree of fetal metformin exposure does not influence fetal outcome in gestational diabetes mellitus

The purpose of the study was to examine in vivo placental transfer of metformin, its association with neonatal outcome in metformin-treated gestational diabetes (GDM) patients, and influence of metformin exposure on maternal glycemic control and weight gain. Two hundred and seventeen GDM patients were randomized to metformin or insulin in Turku University Hospital, Finland. Metformin concentrations were determined by mass spectrometry in maternal serum at 36 gestational weeks (gw) and at birth, and in umbilical cord blood. Main outcome measures were birth weight, gw at birth, umbilical artery pH and neonatal hypoglycemia, maternal weight gain, HbA1c and fructosamine concentration. Median umbilical cord/maternal serum metformin concentration ratio was 0.73. There were no differences in birth weight measured in grams or SD units (p = 0.49), or gw at birth (p always ≥0.49) between insulin- and metformin-treated patients stratified by trough metformin concentration tertiles measured at 36 gw. Rate of neonatal hypoglycemia (p = 0.92) and umbilical artery pH value (p = 0.78) was similar in insulin- and metformin-treated patients stratified by cord metformin concentration tertiles. Maternal glycemic control was similar in metformin concentration tertiles at 36 gw. Maternal weight gain was 223 g greater per week (p = 0.038) in the lowest metformin tertile compared to other tertiles combined. Maternal and fetal exposure to metformin is similar. Maternal or fetal metformin concentrations do not predict maternal glycemic control or neonatal outcome, but low maternal exposure may lead to greater maternal weight gain.     

Characterization of Organosolv Lignins and Their Application in the Preparation of Aerogels

The production of novel materials and value-added chemicals from lignin has received considerable attention in recent years. Due to its abundant occurrence in nature, there is a growing interest in utilizing lignin as a feedstock for functional materials production, for example aerogels. Much like in the synthesis of phenol-based resins, the vacant ortho positions of the aromatic rings in lignin can crosslink with formaldehyde and form polymeric gels. After drying the hydrogels with supercritical CO₂, highly porous aerogels are obtained. Current study focuses on the preparation and thorough parametrization of organosolv lignins from different types of lignocellulosic biomass (aspen, pine, and barley straw) as well as their utilization for the preparation of lignin-5-methylresorcinol-formaldehyde aerogels. The thorough structural characterization of the obtained aerogels was carried out by gas adsorption, IR spectroscopy, and scanning electron microscopy. The obtained lignin-based monolithic mesoporous aerogels had specific surface areas and total pore volumes in the upward ranges of 450 m²/g and 1.4 cm³/g, respectively.