Activation of metabotropic glutamate receptor 3 enhances interleukin (IL)-1beta-stimulated release of IL-6 in cultured human astrocytes

Previous studies have demonstrated that human astrocytes express mRNA and receptor protein for group I and II metabotropic glutamate receptors (mGluRs). Whether these receptors can influence the inflammatory and immune response and can modulate the capacity of astrocytes to produce inflammatory cytokines is still unclear. Inflammatory cytokines can be produced by activated glial cells and play a critical role in several neurological disorders. Astrocyte-enriched human cell cultures growing in a serum-free chemically defined medium were used to study the regulation of IL (interleukin)-1β and IL-6 in response to mGluR activation. Astrocytes cultured in the absence or in the presence of epidermal growth factor (EGF), did not secrete significant IL-1β and IL-6, as determined by specific enzyme-linked immunosorbent assay (ELISA). Activation of mGluRs using (S)-3,5-dihydroxyphenylglycine (DHPG; selective group I agonist) or DCG-IV (selective group II agonist) did not affect the production of interleukins under both growth conditions. On exposure to IL-1β high levels of IL-6 were detected. Activation of mGluR3 with DCG-IV (but not of mGluR5 with DHPG) enhanced, in the presence of IL-1β, the release of IL-6 in a dose dependent manner in astrocytes cultured under conditions (+EGF) in which the mGluR expression is known to be upregulated. The effect of mGluR3 activation on IL-1β stimulated release of IL-6 was prevented by selective group II mGluR antagonists. The capacity of mGluR3 to modulate the release of IL-6 in the presence of IL-1β supports the possible involvement of this receptor subtype in the regulation of the inflammatory and immune response under pathological conditions associated with glial cell activation.     

The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

Thermographic skin temperature measurement compared with cold sensation in predicting the efficacy and distribution of epidural anesthesia

Due to the high rates of epidural failure (3–32%), novel techniques are required to objectively assess the successfulness of an epidural block. In this study we therefore investigated whether thermographic temperature measurements have a higher predictive value for a successful epidural block when compared to the cold sensation test as gold standard. Epidural anesthesia was induced in 61 patients undergoing elective abdominal, thoracic or orthopedic surgery. A thermographic picture was recorded at 5, 10 and 15 min following epidural anesthesia induction. After 15 min a cold sensation test was performed. Epidural anesthesia is associated with a decrease in skin temperature. Thermography predicts a successful epidural block with a sensitivity of 54% and a PPV of 92% and a specificity of 67% and a NPV of 17%. The cold sensation test shows a higher sensitivity and PPV than thermography (97 and 93%), but a lower specificity and NPV than thermography (25 and 50%). Thermographic temperature measurements can be used as an additional and objective method for the assessment of the effectiveness of an epidural block next to the cold sensation test, but have a low sensitivity and negative predictive value. The local decrease in temperature as observed in our study during epidural anesthesia is mainly attributed to a core-to-peripheral redistribution of body heat and vasodilation.     

Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer: a prognostic model to guide treatment selection

BACKGROUND: Brachytherapy was found to be preferable to metal stent placement for the palliation of dysphagia because of inoperable esophageal cancer in the randomized SIREC trial. The benefit of brachytherapy, however, only occurred after a relatively long survival. The objective is to develop a model that distinguishes patients with a poor prognosis from those with a relatively good prognosis. METHODS: Survival was analyzed with Cox regression analysis. Dysphagia-adjusted survival (alive with no or mild dysphagia) was studied with Kaplan-Meier analysis. Patient data is from the multicenter, randomized, controlled trial (SIREC, n = 209) and a consecutive series (n = 396). Patients received a stent or single-dose brachytherapy. RESULTS: Significant prognostic factors for survival included tumor length, World Health Organization performance score, and the presence of metastases (multivariable p < 0.001). A simple score, which also included age and gender, could satisfactorily separate patients with a poor, intermediate, and relatively good prognosis within the SIREC trial. For the poor prognosis group, the difference in dysphagia-adjusted survival was 23 days in favor of stent placement compared with brachytherapy (77 vs. 54 days, p = 0.16). For the other prognostic groups, brachytherapy resulted in a better dysphagia-adjusted survival. CONCLUSIONS: A simple prognostic score may help to identify patients with a poor prognosis in whom stent placement is at least equivalent to brachytherapy. If further validated, this score can provide an evidence-based tool for the selection of palliative treatment in esophageal cancer patients.     

Association of Psychiatric History and Type D Personality with Symptoms of Anxiety, Depression, and Health Status Prior to ICD Implantation

Background

Personality factors and psychiatric history may help explain individual differences in risk of psychological morbidity and poor health outcomes in patients with an implantable cardioverter defibrillator (ICD).

Purpose

We examined associations between previous anxiety and depressive disorder, type D personality, anxiety or depressive symptoms, and health status in ICD patients prior to ICD implantation.

Method

Patients (N?=?278; 83 % men; mean age?=?62.2 years ±11) receiving a first ICD from September 2007 through April 2010 at the Medisch Spectrum Twente, The Netherlands completed validated questionnaires before implantation assessing type D personality (14-item Type D Scale), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), and health status (36-item Short Form Health Survey). History of anxiety or depressive disorder was assessed with the Mini International Neuropsychiatric Interview structural interview.

Results

Previous anxiety or depressive disorder was prevalent in 8 and 19 % of patients, respectively. Type D personality was present in 21 %, depressive symptoms in 15 %, and anxiety in 24 %. In adjusted analyses, type D personality was a dominant correlate of previous depressive disorder (odds ratio (OR) 6.2, p?<?0.001) and previous anxiety disorder (OR 3.9, p?=?0.004). Type D personality (OR 4.0, p?<?0.001), age (OR 1.03, p?=?0.043), and gender (OR 2.5, p?=?0.013) were associated with anxiety symptoms at baseline. Type D personality (OR 5.9. p?<?0.001) was also associated with increased depressive symptoms at baseline. Heart failure and type D personality were related to poorer health status.

Conclusion

In ICD patients, prior to ICD implantation, a previous anxiety or depressive disorder, type D personality, and anxiety and depressive symptoms were associated with poorer health status. Type D personality was also independently associated with increased anxiety and depression symptoms.