Rat behavior after chronic variable stress and partial lesioning of 5-HT-ergic neurotransmission: effects of citalopram

Deficits in serotonergic (5-HT-ergic) neurotransmission and stressful life events have been implicated in affective disorders, and chronic variable stress (CVS) can elicit behavioral changes reminiscent of increased emotionality, anxiety and atypical depression after partial 5-HT depletion. This study examined the effect of chronic citalopram treatment (10 mg/kg daily) on these changes. Parachloroamphetamine (PCA) (2 mg/kg) reduced the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex, increased anxiety in the social interaction test, and increased activity in the open field. CVS reduced social activity in the social interaction test and immobility time in the forced swimming test. Reduction of excrements left during immobilization indicated partial adaptation with the CVS. Specific stressors had different effects on body weight gain, shorter lasting stressors having a smaller effect in general than those that lasted longer. Combination of CVS and PCA increased sucrose intake after two weeks of stress. In addition, combination of the two treatments reduced diving in the forced swimming test. Citalopram prevented the increase in sucrose consumption in the PCA+CVS rats, and in 5-HT-depleted animals blocked the increase in struggling and reduced the number of defecations in the forced swim test. In conclusion, citalopram treatment prevented several effects of either 5-HT depletion or combined PCA+CVS treatment, suggesting that these behavioral changes could be used in studies on the neural mechanisms underlying emotional behavior that may have relevance to the neurobiology of depression.     

The effect of serotonin transporter gene promoter polymorphism on adolescent and adult ADHD symptoms and educational attainment: A longitudinal study

IntroductionThe purpose of this longitudinal study was to investigate the relationship between the 5-HTTLPR genotype, symptoms of ADHD in adolescence and adulthood, and educational attainment in a population representative sample. Neuroticism, depressive symptoms and general mental abilities were controlled for as possible confounding factors.MethodsADHD symptoms were reported at age 15 and 18 by teachers using the Hyperactivity Scale of af Klinteberg and SNAP-IV, and self-reported at age 25 using the ASRS. Data about education were reported at age 25.ResultsAt age 15, subjects with the l/l genotype had more concentration difficulties compared to s-allele carriers, and they also had more inattention symptoms according to SNAP-IV at age 18. These results were not altered by taking neuroticism or depressive symptoms into account. No 5-HTTLPR genotype effect on self-reported ADHD symptoms at age 25 was found. Inattention symptoms in adolescence were associated with lower education in young adulthood. The proportion of subjects with higher education at age 25 was significantly larger among s/s genotype compared to the l/l or s/l genotype.ConclusionsThe l/l genotype of the 5-HTTLPR is associated with inattentive symptoms during adolescence in the general population, and increases the likelihood of inferior educational level in young adulthood.     

Cardiorespiratory fitness relates more strongly than physical activity to cardiovascular disease risk factors in healthy children and adolescents: the European Youth Heart Study.

BACKGROUND: Physical activity and cardiorespiratory fitness are closely related to health variables in adults, especially those considered to be among risk factors for cardiovascular diseases. The possible tracking of cardiovascular disease risk factors from childhood to adulthood makes it important to increase our understanding of the complex relationships between physical activity, cardiorespiratory fitness and cardiovascular risk factors early in life. DESIGN: A cross-sectional, school-based study on healthy children and adolescents, aged 9-10 years (295 girls, 295 boys) and 15-16 years (302 girls, 233 boys) was performed during a school year in Sweden and Estonia, as part of the European Youth Heart Study. METHODS: Total physical activity, and minutes spent in inactivity and activity of moderate or higher intensity were measured by accelerometry. A maximal ergometer bike test was used for estimation of cardiorespiratory fitness. The risk factors included blood pressure and fasting blood levels of insulin, glucose, triglycerides, total cholesterol and high-density lipoprotein cholesterol. RESULTS: Canonical correlations between physical activity and cardiorespiratory fitness versus cardiovascular disease risk factors showed significant associations in both age and sex groups (rc=0.46-0.61, P<0.0001). The cardiorespiratory fitness was found to be the strongest contributor to these relationships. In girls high values of the physical activity variables were also associated with a favourable cardiovascular profile. CONCLUSIONS: Cardiorespiratory fitness relates more strongly to cardiovascular risk factors than components of objectively measured physical activity in children and adolescents. Physical activity becomes more important in the 15-year-old adolescents, indicating that these modifiable lifestyle factors increase in importance with age.     

Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food‐borne bacterial pathogens

Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron‐deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron‐ and infection‐induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin‐2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron‐deficient diet after infection. Next, mice on the iron‐deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host–pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.     

Bone mass development and bone metabolism in juvenile idiopathic arthritis: treatment with growth hormone for 4 years

OBJECTIVE: To study the acquisition of bone mass and changes in bone mineral density (BMD) related to age, bone age, pubertal status, and growth hormone (GH) therapy in 11 children with juvenile idiopathic arthritis (JIA) longitudinally over 4 years, in comparison to healthy children. METHODS: Bone mineral content (BMC), BMD, and vertebral area were measured by dual energy x-ray absorptiometry. Since BMC and BMD increase with size, BMD was converted to volumetric BMD (vBMD) after adjustment for vertebral size. RESULTS: At inclusion all patients (7 female, 4 male, mean age 10.3 +/- 2.1 yrs) had low BMD, with a mean z-score for area BMD (aBMD) of -2.04 +/- 0.8 SD. After adjustment for size, vBMD was 0.198 g/cm3, and after 4 years of GH treatment it increased significantly to 0.232 g/cm3 (p < 0.03), expressed as SD scores that increased from -2.97 +/- 0.81 SD to -2.83 +/- 0.67 SD. In relation to bone age, vBMD SD increased from -2.53 +/- 0.85 to -2.41 +/- 0.79. Compared to pretreatment values, bone formation and resorption markers increased significantly during treatment. CONCLUSION: Our results reflect an increase in bone turnover under GH therapy in these patients. Despite biochemical changes there was a stabilization of vBMD for age and bone age, with a percentage increase comparable to healthy children. Longterm GH treatment will be necessary to evaluate a potential positive effect of GH on bone density and metabolism in patients with JIA.     

Identification of the affected ear in lateral canal benign paroxysmal positional vertigo

Background:

The effective management of lateral canal benign paroxysmal positional vertigo (LC-BPPV) is dependent upon the accurate identification of the affected ear. The supine roll test is the gold standard for diagnosing LC-BPPV. However, in some cases, the elicited nystagmus has a similar intensity when the head is rolled to the right or to the left.

Objectives:

The purpose of this systematic review was to determine the effectiveness of accessory diagnostic procedures, used in conjunction with the supine roll test, at accurately identifying the affected ear in individuals with LC-BPPV.

Methods:

The following databases were searched: (1) CINAHL Plus with Full Text, (2) ProQuest Medical Library, and (3) MEDLINE. The following search terms were used: (1) ‘lateral canal’ OR ‘horizontal canal’ AND (2) ‘positional vertigo’ OR ‘positioning vertigo’ OR ‘positional nystagmus’ OR ‘positioning nystagmus’. Evidence level was examined with the Oxford Centre for Evidence-Based Medicine 2011 levels of evidence method, and methodological rigour was examined with the QUADAS method.

Results:

A database search originally identified 1348 records, and nine studies were ultimately included in the qualitative synthesis. This systematic review revealed four index tests that, when used in conjunction with the supine roll test, were able to accurately identify the affected ear in a majority of individuals with LC-BPPV.

Conclusions:

The pseudo-spontaneous test was found to be slightly superior to the other three index tests in terms of eliciting nystagmus during its administration and identifying the same affected ear as the supine roll test.     

Toxic effects of ophthalmic preservatives on cultured rabbit corneal epithelium

We investigated the effects of the ophthalmic preservatives thimerosal and sorbic acid on the proliferation and survival of rabbit corneal epithelial cells in tissue culture. Normally, explants of corneal epithelium grow vigorously during the first 7 days in culture. With 0.004% thimerosal present in the culture medium, the normal proliferation of corneal cells is suppressed completely. When 0.1% sorbic acid is present, proliferation is delayed and the lifespan of the corneal cells is reduced. After a 1-h exposure to concentrations of thimerosal of 0.0005% or greater, virtually all corneal cells present in established cultures are killed. These results suggest that use of ophthalmic preparations containing these chemicals may affect the metabolic and proliferative capacity of the corneal epithelium adversely.     

Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review

Frontotemporal dementia (FTD) is the second most common young-onset dementia and is clinically characterised by progressive behavioural change, executive dysfunction and language difficulties. Three clinical syndromes, behavioural variant FTD, semantic dementia and progressive non-fluent aphasia, form part of a clinicopathological spectrum named frontotemporal lobar degeneration (FTLD). The classical neuropsychological phenotype of FTD has been enriched by tests exploring Theory of Mind, social cognition and emotional processing. Imaging studies have detailed the patterns of atrophy associated with different clinical and pathological subtypes. These patterns offer some diagnostic utility, while measures of progression of atrophy may be of use in future trials. 30-50% of FTD is familial, and mutations in two genes, microtubule associated protein tau and Progranulin (GRN), account for about half of these cases. Rare defects in VCP, CHMP2B, TARDP and FUS genes have been found in a small number of families. Linkage to chromosome 9p13.2-21.3 has been established in familial FTD with motor neuron disease, although the causative gene is yet to be identified. Recent developments in the immunohistochemistry of FTLD, and also in amyotrophic lateral sclerosis (ALS), have led to a new pathological nomenclature. The two major groups are those with tau-positive inclusions (FTLD-tau) and those with ubiquitin-positive and TAR DNA-binding protein of 43 kDa (TDP-43) positive inclusions (FTLD-TDP). Recently, a new protein involved in familial ALS, fused in sarcoma (FUS), has been found in FTLD patients with ubiquitin-positive and TDP-43-negative inclusions. In this review, the authors discuss recent clinical, neuropsychological, imaging, genetic and pathological developments that have changed our understanding of FTD, its classification and criteria. The potential to establish an early diagnosis, predict underlying pathology during life and quantify disease progression will all be required for disease-specific therapeutic trials in the future.