Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways

Combustion-derived and manufactured nanoparticles (NPs) are known to provoke oxidative stress and inflammatory responses in human lung cells; therefore, they play an important role during the development of adverse health effects. As the lungs are composed of more than 40 different cell types, it is of particular interest to perform toxicological studies with co-cultures systems, rather than with monocultures of only one cell type, to gain a better understanding of complex cellular reactions upon exposure to toxic substances. Monocultures of A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte-derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of all three cell types were exposed to combustion-derived NPs (diesel exhaust particles) and to manufactured NPs (titanium dioxide and single-walled carbon nanotubes). The penetration of particles into cells was analysed by transmission electron microscopy. The amount of intracellular reactive oxygen species (ROS), the total antioxidant capacity (TAC) and the production of tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 were quantified. The results of the monocultures were summed with an adjustment for the number of each single cell type in the triple cell co-culture. All three particle types were found in all cell and culture types. The production of ROS was induced by all particle types in all cell cultures except in monocultures of MDDCs. The TAC and the (pro-)inflammatory reactions were not statistically significantly increased by particle exposure in any of the cell cultures. Interestingly, in the triple cell co-cultures, the TAC and IL-8 concentrations were lower and the TNF-alpha concentrations were higher than the expected values calculated from the monocultures. The interplay of different lung cell types seems to substantially modulate the oxidative stress and the inflammatory responses after NP exposure.

Structural differences between the bladder dome and trigone revealed by mRNA expression analysis of cold-cut biopsies

To establish the mRNA expression profiles of selected genes involved in bladder contractility and epithelial permeability in the bladder dome and trigone in order to evaluate the use of cold-cut biopsies for comparative quantitative studies into the anatomical differences between these two bladder regions.

Similarities and differences between physician and non-physician acupuncturists in using diagnostic methods - an explorative study

Purpose: Acupuncture is one of the complementary medicine therapies with the greatest demand in Switzerland and many other countries in the West and in Asia. Over the past decades, the pool of scientific literature in acupuncture has markedly increased. The diagnostic methods upon which acupuncture treatment is based, have only been addressed sporadically in scientific journals. The goal of this study is to assess the use of different diagnostic methods in the acupuncture practices and to investigate similarities and differences in using these diagnostic methods between physician and non-physician acupuncturists. Methods: 44 physician acupuncturists with certificates of competence in acupuncture – traditional chinese medicine (TCM) from ASA (Assoziation Schweizer Ärztegesellschaften für Akupunktur und Chinesische Medizin: the Association of Swiss Medical Societies for Acupuncture and Chinese Medicine) and 33 non-physician acupuncturists listed in the EMR (Erfahrungsmedizinisches Register: a national register, which assigns a quality label for CAM therapists in complementary and alternative medicine) in the cantons Basel-Stadt and Basel-Land were asked to fill out a questionnaire on diagnostic methods. The responder rate was 46.8% (69.7% non-physician acupuncturists and 29, 5% physician acupuncturists). Results: The results show that both physician and non-physician acupuncturists take patients’ medical history (94%), use pulse diagnosis (89%), tongue diagnosis (83%) and palpation of body and ear acupuncture points (81%) as diagnostic methods to guide their acupuncture treatments. Between the two groups, there were significant differences in the diagnostic tools being used. Physician acupuncturists do examine their patients significantly more often with western medical methods (p<.05) than this is the case for nonphysician acupuncturists. Non-physician acupuncturists use pulse diagnosis more often than physicians (p<.05). A highly significant difference was observed in the length of time spent with collecting patients’ medical history, where nonphysician acupuncturists clearly spent more time (p<.001). Conclusion: Depending on the educational background of the acupuncturist, different diagnostic methods are used for making the diagnosis. Especially the more time consuming methods like a comprehensive anamnesis and pulse diagnosis are more frequently employed by non-physician practitioners. Further studies will clarify if these results are valid for Switzerland in general, and to what extent the differing use of diagnostic methods has an impact on the diagnosis itself and on the resulting treatment methods, as well as on the treatment success and the patients’ satisfaction.

Is the allegiance effect an epiphenomenon of true efficacy differences between treatments? a meta-analysis

Many meta-analyses of comparative outcome studies found a substantial association of researcher allegiance (RA) and relative treatment effects. Therefore, RA is regarded as a biasing factor in comparative outcome research (RA bias hypothesis). However, the RA bias hypothesis has been criticized as causality might be reversed. That is, RA might be a reflection of true efficacy differences between treatments (true efficacy hypothesis). Consequently, the RA-outcome association would not be indicative of bias but an epiphenomenon of true efficacy differences. This meta-analysis tested the validity of the true efficacy hypothesis. This was done by controlling the RA-outcome association for true efficacy differences by restricting analysis to direct comparisons of treatments with equivalent efficacy. We included direct comparisons of different versions of trauma-focused therapy (TFT) in the treatment of posttraumatic stress disorder (PTSD). RA was measured from the research reports. Relative effect sizes for symptoms of PTSD were calculated. Random effects meta-regression was conducted. Twenty-nine comparisons of TFTs from 20 studies were identified. Initial heterogeneity among relative effect sizes was low. RA was a significant predictor of outcome and explained 12% of the variance in outcomes. The true efficacy hypothesis predicted the RA-outcome association to be zero; however, a substantial association was found. Thus, this study does not support the true efficacy hypothesis. Given findings from psychotherapy research and other fields that support a biasing influence of researcher preferences, RA should be regarded as a causal factor and conceptualized as a threat to the validity of conclusions from comparative outcome studies.

Differences between first episode schizophrenia and schizoaffective disorder

Background The diagnostic and clinical overlap between schizophrenia and schizoaffective disorder is an important nosological issue in psychiatry that is yet to be resolved. The aim of this study was to compare the clinical and functional characteristics of an epidemiological treated cohort of first episode patients with an 18-month discharge diagnosis of schizophrenia (FES) or schizoaffective disorder (FESA). Methods This study was part of the larger First Episode Psychosis Outcome Study (FEPOS) which involved a medical file audit study of all 786 patients treated at the Early Psychosis Prevention and Intervention Centre between 1998 and 2000. Of this cohort, 283 patients had an 18-month discharge diagnosis of FES and 64 had a diagnosis of FESA. DSM-IV diagnoses and clinical and functional ratings were derived and validated by two consultant psychiatrists. Results Compared to FES patients, those with FESA were significantly more likely to have a later age of onset (p=.004), longer prodrome (p=.020), and a longer duration of untreated psychosis (p<.001). At service entry, FESA patients presented with a higher illness severity (p=.020), largely due to the presence of more severe manic symptoms (p<.001). FESA patients also had a greater number of subsequent inpatient admissions (p=.017), had more severe depressive symptoms (p=.011), and higher levels of functioning at discharge. Discussion The findings support the notion that these might be considered two discernable disorders; however, further research is required to ascertain the ways and extent to which these disorders are discriminable at presentation and over time.

Differences between RNA and DNA due to RNA editing in temporal lobe epilepsy

To investigate whether alterations in RNA editing (an enzymatic base-specific change to the RNA sequence during primary transcript formation from DNA) of neurotransmitter receptor genes and of transmembrane ion channel genes play a role in human temporal lobe epilepsy (TLE), this exploratory study analyzed 14 known cerebral editing sites in RNA extracted from the brain tissue of 41 patients who underwent surgery for mesial TLE, 23 with hippocampal sclerosis (MTLE+HS). Because intraoperatively sampled RNA cannot be obtained from healthy controls and the best feasible control is identically sampled RNA from patients with a clinically shorter history of epilepsy, the primary aim of the study was to assess the correlation between epilepsy duration and RNA editing in the homogenous group of MTLE+HS. At the functionally relevant I/V site of the voltage-gated potassium channel Kv1.1, an inverse correlation of RNA editing was found with epilepsy duration (r=-0.52, p=0.01) but not with patient age at surgery, suggesting a specific association with either the epileptic process itself or its antiepileptic medication history. No significant correlations were found between RNA editing and clinical parameters at other sites within glutamate receptor or serotonin 2C receptor gene transcripts. An "all-or-none" (≥95% or ≤5%) editing pattern at most or all sites was discovered in 2 patients. As a secondary part of the study, RNA editing was also analyzed as in the previous literature where up to now, few single editing sites were compared with differently obtained RNA from inhomogenous patient groups and autopsies, and by measuring editing changes in our mouse model. The present screening study is first to identify an editing site correlating with a clinical parameter, and to also provide an estimate of the possible effect size at other sites, which is a prerequisite for power analysis needed in planning future studies.

Genomic differences between type strain PG1 and field strains of Mycoplasma mycoides subsp. mycoides small-colony type

The recently accomplished complete genomic sequence analysis of the type strain PG1 of Mycoplasma mycoides subsp. mycoides small-colony type revealed four large repeated segments of 24, 13, 12, and 8 kb that are flanked by insertion sequence (IS) elements. Genetic analysis of type strain PG1 and African, European, and Australian field and vaccine strains revealed that the 24-kb genetic locus is repeated only in PG1 and not in other M. mycoides subsp. mycoides SC strains. In contrast, the 13-kb genetic locus was found duplicated in some strains originating from Africa and Australia but not in strains that were isolated from the European outbreaks. The 12- and 8-kb genetic loci were found in two and three copies, respectively, in all 28 strains analyzed. The flanking IS elements are assumed to lead to these tandem duplications, thus contributing to genomic plasticity. This aspect must be considered when designing novel diagnostic approaches and recombinant vaccines.

Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines

Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients.

The 14-bp deletion polymorphism in the HLA-G gene displays significant differences between ulcerative colitis and Crohn's disease and is associated with ileocecal resection in Crohn's disease

HLA-G is a non-classical MHC class Ib molecule predominantly expressed in cytotrophoblasts and under pathological conditions also in chronically inflamed and in malignant tissues. Recently an increased expression of HLA-G was found in ulcerative colitis (UC), but not in Crohn's disease (CD). The HLA-G gene is located in IBD3, a linkage region for inflammatory bowel disease (IBD). A 14-bp deletion polymorphism (Del+/Del-) within exon 8 of the HLA-G gene might influence transcription activity and is therefore of potential functional relevance. To investigate whether the 14-bp deletion polymorphism is associated with IBD, 371 patients with CD, 257 patients with UC and 739 controls were genotyped. The heterozygous genotype (P = 0.031) and the Del+ phenotype (P = 0.038) were significantly increased, whereas the homozygous Del- phenotype (P = 0.038) was significantly decreased in UC when compared with CD. Thus, the 14-bp deletion polymorphism within the HLA-G gene displayed significant differences between UC and CD. Moreover, a significant increase of the Del+ allele (P = 0.002) and the Del+/Del+ genotype (P = 0.013) and a consecutive decrease of the Del-/- genotype (P = 0.024) were observed in those CD cases positive for ileocecal resection. Thus, a potential effect of the HLA-G gene in IBD may affect both UC and CD. Other polymorphisms linked to the 14-bp deletion polymorphism might also contribute to immunopathogenesis. As there are several partly functional polymorphisms within the promoter region potentially influencing HLA-G expression, further studies in IBD are necessary in the context of differential expression of HLA-G between UC and CD.