Pharmacokinetics of acute tryptophan depletion using a gelatin-based protein in male and female Wistar rats

The essential amino acid tryptophan is the precursor of the neurotransmitter serotonin. By depleting the body of tryptophan, brain tryptophan and serotonin levels are temporarily reduced. In this paper, several experiments are described in which dose and treatment effects of acute tryptophan depletion (ATD) using a gelatin-based protein–carbohydrate mixture were studied in male and female Wistar rats. Two or three doses of tryptophan depleting mixture resulted in 65–70% depletion after 2–4 h in males. ATD effects were similar in females, although females may return to baseline levels faster. Treatment effects after four consecutive days of ATD were similar to the effects of 1 day of treatment. Object recognition memory was impaired 2, 4, and 6 h after the first of two doses of ATD, suggesting that the central effects occurred rapidly and continued at least 6 h, in spite of decreasing treatment effects on plasma tryptophan levels at that time point. The method of acute tryptophan depletion described here can be used to study the relationship between serotonin and behaviour in both male and female rats

Lung cancer in HIV patients and their parents: A Danish cohort study

<p>Abstract</p> <p>Background</p> <p>HIV patients are known to be at increased risk of lung cancer but the risk factors behind this are unclear.</p> <p>Methods</p> <p>We estimated the cumulative incidence and relative risk of lung cancer in 1) a population of all Danish HIV patients identified from the Danish HIV Cohort Study (n = 5,053) and a cohort of population controls matched on age and gender (n = 50,530) (study period; 1995 - 2009) and 2) their parents (study period; 1969 - 2009). Mortality and relative risk of death after a diagnosis of lung cancer was estimated in both populations.</p> <p>Results</p> <p>29 (0.6%) HIV patients vs. 183 (0.4%) population controls were diagnosed with lung cancer in the observation period. HIV patients had an increased risk of lung cancer (adjusted incidence rate ratio (IRR); 2.38 (95% CI; 1.61 - 3.53)). The IRR was considerably increased in HIV patients who were smokers or former smokers (adjusted IRR; 4.06 (95% CI; 2.66 - 6.21)), male HIV patients with heterosexual route of infection (adjusted IRR; 4.19 (2.20 - 7.96)) and HIV patients with immunosuppression (adjusted IRR; 3.25 (2.01 - 5.24)). Both fathers and mothers of HIV patients had an increased risk of lung cancer (adjusted IRR for fathers; 1.31 (95% CI: 1.09 - 1.58), adjusted IRR for mothers 1.35 (95% CI: 1.07 - 1.70)). Mortality after lung cancer diagnose was increased in HIV patients (adjusted mortality rate ratio 2.33 (95%CI; 1.51 - 3.61), but not in the parents. All HIV patients diagnosed with lung cancer were smokers or former smokers.</p> <p>Conclusion</p> <p>The risk was especially increased in HIV patients who were smokers or former smokers, heterosexually infected men or immunosuppressed. HIV appears to be a marker of behavioural or family related risk factors that affect the incidence of lung cancer in HIV patients.</p

Contribution of parental and school personnel smoking to health risk behaviours among Finnish adolescents

This study compared parental smoking with school personnel smoking in relation to adolescents' smoking behaviours, alcohol use, and illicit drug use

Effects of acute tryptophan depletion on affective processing in first-degree relatives of depressive patients and controls after exposure to uncontrollable stress

Rationale Individuals with a family history of depression may be more likely to develop depression due to an innate vulnerability of their serotonergic system. However, even though serotonergic vulnerability may constitute a risk factor in the development of depression, it does not seem to be sufficient to cause a depressive episode. Based on previous data, it is suggested that stress may be a mediating factor. Objectives This study examined the role of serotonin (5-HT) in stress coping in individuals with or without a family history of depression. Materials and methods Nineteen healthy first-degree relatives of depressive patients (FH+) and 19 healthy controls without a family history of depression (FH-) were tested in a double-blind placebo-controlled design for affective processing under acute stress exposure, following acute tryptophan depletion (ATD) or placebo. Results Significant negative effects were found of stress on affective processing in FH- and FH+. In addition, FH- responded slower to positive words after stress only following ATD, whereas FH+ responded marginally slower under stress already after placebo and before stress following ATD. Conclusion Acute stress exposure reduces positive affective bias; supporting the role of stress as an important predecessor in the development of depression. Furthermore, FH+ may be more susceptible than FH- to the negative effects of stress as well as to the negative effects of ATD. The results support the assumption that the 5-HT system is involved in stress resilience and may be more vulnerable in first-degree relatives of depression

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression