Interaction of mucosal microbiota with the innate immune system

Organisms live in continuos interaction with their environment; this interaction is of vital importance but at the same time can be life threatening. The largest and most important interface between the organism and its environment is represented by surfaces covered with epithelial cells. Of these surfaces, mucosae comprise in humans approximately 300 m2, and the skin covers approximately 1.8 m2 surface of the human body. Mucosal tissues contain two effector arms of the immune system, innate and adaptive, which operate in synergy. Interaction with commensal bacteria, which outnumber the nucleated cells of our body, occurs physiologically on epithelial surfaces; this interaction could pose the risk of inflammation. The mucosal immune system has developed a complex network of regulatory signalling cascades that is a prerequisite for proper activation but also for a timely inactivation of the pathway. As demonstrated in gnotobiotic animal models of human diseases, impaired regulation of mucosal responses to commensal bacteria plays an important role in the development of several inflammatory and autoimmune diseases.     

Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects.

BACKGROUND: The aim of our study was to test the hypothesis that amygdala volumes are reduced in patients with recurrent major depression compared with first episode patients. METHODS: Using structural magnetic resonance imaging, we compared 30 inpatients with first-episode depression and 27 inpatients with recurrent major depression (DSM-IV) with healthy volunteer subjects from the local community matched for age, gender, and handedness. RESULTS: Patients with first-episode depression showed enlarged amygdala volumes compared with patients with recurrent major depression and healthy control subjects. No significant differences were found between patients with recurrent depression and healthy control subjects. No significant correlations were found between amygdala volumes and age of onset, illness duration, or severity of depression. CONCLUSIONS: Larger amygdala volumes in patients with first-episode depression may result from higher amygdala metabolism and blood flow. Additionally, disease progression with stress-related excitotoxic processes during recurrent depressive episodes might result in decreased amygdala volumes. Prospective investigations to investigate amygdala changes during the course of depression are needed.     

Alumina‐reinforced zirconia implants: survival rate and fracture strength in a masticatory simulation trial

Background: Alumina‐toughened zirconia (ATZ) is a possible alternative material to titanium for oral implants. No data are available on the fracture strength of ATZ oral implants. Purpose: The purpose of this study was to examine one‐piece implants made of ATZ ceramic under artificial loading conditions and to compare the fracture strength of these implants with implants fabricated from tetragonal zirconium dioxide poylcrystal (TZP)‐A. Materials and methods: A total of 72 implants, 48 ATZ implants (groups A and B) and 24 TZP‐A implants (group C), were investigated. A chamfer preparation at the implant heads was performed on all implants of groups B and C. Eight implants of each group underwent 1.2 or five million thermomechanical loading cycles in the chewing simulator (load value: 98 N). Further eight implants of each group were not cyclic loaded. Finally, the fracture strength of all implants was determined using a universal testing machine. Results: No implant fractured during loading in the chewing simulator. All implants were placed in the universal testing machine to evaluate fracture strength. The mean fracture strength values±standard deviations for the implants without artificial loading were 1734±165 N (ATZ, no preparation), 1220±85 N (ATZ, with preparation), and 578±49 N (TZP‐A, with preparation); 1489±190 N (ATZ, no preparation), 1064±121 N (ATZ, with preparation), and 607±57 N (TZP‐A, with preparation) with 1.2 million loading cycles; and 1358±187 N (ATZ, no preparation), 1098±97 N (ATZ, with preparation), and 516±45 N (TZP‐A, with preparation) with five million cycles. The ATZ implants showed significantly higher mean fracture strengths compared with the TZP‐A implants. Modification of the implant head using diamond burs and increased loading time also led to a significant decrease in fracture strength. Conclusions: The ATZ implants showed an increased mechanical stability compared with the TZP‐A. Modification of the implant head resulted in a decrease in fracture strength. However, within the limits of this in vitro investigation it can be concluded that ATZ implants will withstand functional loading over an estimated period of 20 years. To cite this article:
Kohal R‐J, Wolkewitz M, Mueller C. Alumina‐reinforced zirconia implants: survival rate and fracture strength in a masticatory simulation trial.
Clin. Oral Impl. Res. 21 , 2010; 1345–1352.
doi: 10.1111/j.1600‐0501.2010.01954.x     

Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms,psychometric variables and mercury levels

Weidenhammer W, Bornschein S, Zilker T, Eyer F, Melchart D, Hausteiner C. Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms, psychometric variables and mercury levels. Community Dent Oral Epidemiol 2010. © 2010 John Wiley & Sons A/S Abstract – Objective: This analysis aimed to study predictors of different treatment outcomes and associations between subjective symptoms, psychometric variables and mercury levels in patients who subjectively attributed their health problems to dental amalgam. Material and methods: A secondary and retrospective analysis of data of a recently published randomized clinical trial was performed. Seventy‐eight patients [44% female, mean (SD) age 35 (6) years, randomly assigned to either amalgam removal or a health promotion program] were included into statistical analysis. Prior to intervention and 12 months later, questionnaires for assessing symptoms, psychological distress and health status were presented, and mercury levels in blood and urine were determined. Results: The patients’ personality profile at study onset was characterized by slightly reduced extraversion and slightly elevated emotional instability. Overall, subjective symptoms decreased slightly and there were no statistically significant differences in the decrease of symptoms after intervention between both groups. Decrease of mercury levels after intervention was closely associated with removal of amalgam fillings (r_mult = 0.64 in regression analysis). Statistically significant correlations could be found between mercury levels and subjective symptoms with respect to baseline (r = 0.29–0.39) and to changes after intervention (r = 0.24–0.42), but not for psychological distress (r = 0.05–0.25) and health related quality of life (r = ?0.03–0.18). Prediction of symptom improvement after intervention was poor (r_mult = 0.44). Conclusions: Results contribute some new aspects to the inconsistent findings in the literature with respect to associations between symptoms and subtoxic mercury levels. More emphasis should be placed on exploring individual vulnerability for amalgam sensitivity.     

Elastomechanical properties of bovine veins

Veins have historically been discussed in qualitative, relative terms: “more compliant” than arteries, subject to “lower pressures”. The structural and compositional differences between arteries and veins are directly related to the different functions of these vessels. Veins are often used as grafts to reroute flow from atherosclerotic arteries, and venous elasticity plays a role in the development of conditions such as varicose veins and valvular insufficiency. It is therefore of clinical interest to determine the elastomechanical properties of veins. In the current study, both tensile and vibration testing are used to obtain elastic moduli of bovine veins. Representative stress–strain data are shown, and the mechanical and failure properties reported. Nonlinear and viscoelastic behavior is observed, though most properties show little strain rate dependence. These data suggest parameters for constitutive modeling of veins and may inform the design and testing of prosthetic venous valves as well as vein grafts.     

The antihistamine fexofenadine does not affect I(Kr) currents in a case report of drug-induced cardiac arrhythmia

1. The human HERG gene encodes the cardiac repolarizing K(+) current I(Kr) and is genetically inactivated in inherited long QT syndrome 2 (LQTS2). The antihistamine terfenadine blocks HERG channels, and can cause QT prolongation and torsades de pointes, whereas its carboxylate fexofenadine lacks HERG blocking activity. 2. In the present study the ability of fexofenadine to block the K897T HERG channel variant was investigated. The underlying single nucleotide polymorphism (SNP) A2960C was identified in a patient reported to develop fexofenadine-associated LQTS. 3. K897T HERG channels produced wild-type-like currents in Xenopus oocytes. Even at a concentration of 100 micro M, fexofenadine did not inhibit wild-type or K897T HERG channels. Coexpression of wild-type and K897T HERG with the ss-subunit MiRP1, slightly changed current kinetics but did not change sensitivity to terfenadine and fexofenadine. 4. Western blot analysis and immunostaining of transiently transfected COS-7 cells demonstrated that overall expression level, glycosylation pattern and subcellular localization of K897T HERG is indistinguishable from wild-type HERG protein, and not altered in the presence of 1 micro M fexofenadine. 5. We provide the first functional characterization of the K897T HERG variant. We demonstrated that K897T HERG is similar to wild-type HERG, and is insensitive to fexofenadine. Although the polymorphism changes PKA and PKC phosphorylation sites, regulation of K897T HERG by these kinases is not altered. 6. Our results strongly indicate that QT lengthening and cardiac arrhythmia in the reported case of drug-induced LQT are not due to the K897T exchange or to an inhibitory effect of fexofenadine on cardiac I(Kr) currents. British Journal of     

Psychiatric morbidity and low self-attentiveness in patients with environmental illness

Controversy surrounds the origin of symptoms attributed to environmental pollutants or widely used chemicals, and the authors believed that a psychiatric evaluation could advance understanding of this contentious condition. They assessed psychiatric morbidity, somatization, and self-attentiveness in patients seen in their Environmental Clinic. Two hundred ninety-five consecutive patients underwent SCID-I and -II interviews and were investigated with self-rating scales for self-attentiveness and somatization. The authors found a high prevalence of mental disorders (66% had a current SCID diagnosis, and 75% had a lifetime SCID diagnosis) and a low level of self-attentiveness, which was not necessarily associated with psychiatric disease. Among patients visiting an Environmental Clinic, mental disorders were common and needed to be diagnosed and treated by standard interventions. Patients who did not meet diagnostic criteria for a psychiatric disorder had relatively low somatization scores and low private self-attentiveness. These "externalizers" could benefit from an intervention that teaches them to focus on their internal and emotional lives. In these patients, the authors consider low self-attentiveness a major feature that may act as a pathogenic factor for environmental illness.     

Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia

OBJECTIVE: Abnormalities in the immune system in schizophrenia have been described. However, important findings such as high levels of activating cytokines in the CSF and signs of CNS inflammation have been controversial. The authors conducted a trial of the new selective cyclooxygenase-2 inhibitor celecoxib, an immunomodulatory drug, in schizophrenic patients to evaluate its therapeutic effects. METHOD: In a prospective, double-blind evaluation, 50 patients with an acute exacerbation of schizophrenia were randomly assigned to either risperidone plus celecoxib or risperidone plus placebo. After a washout period, 25 patients received 2-6 mg/day of risperidone plus placebo and 25 received risperidone plus 400 mg/day of celecoxib for 5 weeks. The treatment effect was calculated by analysis of covariance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or risperidone dose or plasma level. RESULTS: Over 5 weeks, both groups of patients showed significant improvement in scores on the Positive and Negative Syndrome Scale and on all subscales. However, the celecoxib group showed significantly greater improvement in the total score. CONCLUSIONS: Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug showed beneficial effects on schizophrenia symptoms indicates that immune dysfunction in schizophrenia is not just an epiphenomenon but is related to the pathomechanism of the disorder. However, a nonimmunological therapeutic effect of celecoxib mediated by the N-methyl-D-aspartic acid receptor has to be taken into account.