Autogenic Training in Mental Disorders: What Can We Expect?

Autogenic training (AT) is a well-established self-induced relaxation technique based on autosuggestion. From the past two decades, an increasing number of AT studies strongly suggests the practical usefulness of psychophysiological relaxation in the area of medicine. Despite this interest, to date, limited critical clinical reflection on the application and effects of AT in mental disorders exists. The present paper reviews psychophysiological, psychopathological, and clinical aspects of AT in persons with mental disorders with emphasis on implications for future research and practice. Based on a formal literature search, 29 reported studies (7 meta-analyses/systematic reviews) were identified that examined the effects and impact of AT on mental disorders. The main psychophysiological effects of AT include autonomic cardiorespiratory changes paralleled by central nervous system activity modifications and psychological outputs. Studies demonstrate consistent efficacy of AT in reducing anxiety and medium range positive effects for mild-to-moderate depression. The impact on bipolar disorders, psychotic disorders, and acute stress disorder remains unexplored. As an add-on intervention psychotherapy technique with beneficial outcome on psychophysiological functioning, AT represents a promising avenue towards expanding research findings of brain-body links beyond the current limits of the prevention and clinical management of number of mental disorders.

Author Correction: BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity.

This Article contains an error in the spelling of the author Kjeld Møllgård, which is incorrectly given as Kjeld Møllgaard. The error has not been fixed in the original PDF and HTML versions of the Article.

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity.

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM.

Age dependency on some physiological and biochemical parameters of male Wistar rats in controlled environment.

The aim of the study was to assess the age dependence on some physiological and serum chemistry parameters of male Wistar rats for the estimation of reference values in controlled environment. We are presenting values obtained from a large number of animals such as survival, average life span, body mass, food and water intake, serum chemistry parameters as total protein, albumin, transferrin and ferritin in serum. One part of this work compares the relationship between rat and human age. The maximal life span of our rats was determined to be about 4.4 years. The average life span was 3.75 years. The body weight quickly rose to the 85th week of life and then remained in the range of about 640-660 g up to the 163rd week when it began to decline. Food intake rose from the beginning to the maximum of about 39 g in the 33rd week and then decreased to about 20 g in the 163rd week. The water intake had a similar dynamics (about 43 mL in the 33rd week and 33 mL in the 163rd week). Levels of total protein in serum increased with age, in contrast, albumin levels decreased. Transferrin and ferritin decreased to approximately the 160th week of life and then increased.

Multigenerational lifetime low-dose exposure to heavy metals on selected reproductive parameters in rats.

The aim of the present investigation was to evaluate the effects of multigenerational (P, F1 and F2) exposure to low doses of lead, mercury and cadmium dissolved in tap water on the reproductive potency of Wistar rats and the physical health of their progeny. The animals were divided into 4 groups - control (C) and 3 groups intoxicated by metals (Pb, 100 µM; Hg, 1 µM; Cd, 20 µM, respectively). Females gave births from the 13th to the 78th week of experiment. Parameters of reprotoxicity such as number of litters, total number of neonates (assigned in the birth day), and number of weanlings (28th day after birth) were measured in 13-week intervals. Our data show an increase of most reproductive parameters in parental generation of rats exposed to lead and mercury and a decrease of reproductive parameters of exposed animals in subsequent F1 and F2 generations. Exposure to cadmium had no significant effect on the reproductive parameters in comparison with the control group.

Analysis of Snail-1, E-cadherin and claudin-1 expression in colorectal adenomas and carcinomas.

We report the expression of Snail-1, E-cadherin and claudin-1 by indirect immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription factor expressed in cells that already have undergone almost complete epithelial-mesenchymal transition (EMT) and have already evaded from the tumor. The main mechanism by which Snail induces EMT is downregulation of E-cadherin, of which expression was shown to be frequently downregulated in many different types of tumors, where it accompanies the invasiveness and metastatic behavior of malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1, a cell-cell adhesion protein which plays a likely role in progression and dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and adenoma cells with histologically normal epithelium in the mucosa, adjacent to the tumors, without significant differences, and predominant strong intensity of staining. Statistically significant differences were revealed between normal and tumorous epithelium (p = 0.003) at the subcellular level, where the shift of the protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic expression was observed. E-cadherin expression was present in 100% of cases of both adenocarcinomas and adenomas, with prevailing strong membranous immunoreactivity and no differences between protein expression in tumors and normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor cells of adenocarcinomas and adenomas. Marked differences were seen in protein localization, where membranous staining, typical for nontumorous epithelium, changed to combined membranous/cytoplasmic expression in adenocarcinomas (p = 0.0001) and adenomas (0.0002), in which cytoplasmic shift was associated with a higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was more frequent in the carcinoma group (87%) in comparison with adenomas (51%) (p = 0.0001). We conclude that dystopic subcellular localizations of Snail-1 and claudin-1 may participate in changes of cellular morphology and behavior which might be associated with altered effectory pathways of proteins and thus substantially contribute to the cancer development.

Identification of CD133+/nestin+ putative cancer stem cells in non-small cell lung cancer.

AIMS: No effective treatment for lung cancer exists currently. One reason for this, is the development of drug resistance, assumed to be associated with cancer stem cell (CSCs) emergence within the tumour. This pilot study aimed to identify CSCs in 121 non-small cell lung cancer (NSCLC) patient samples via detection of the expression of stem cell markers - CD133 and nestin. MATERIAL AND METHODS: Archived paraffin blocks of 121 patient samples were prepared as Tissue Microarrays (TMA). Indirect immunohistochemical staining was used to determine the level of expression of CD133 and nestin. Double immunofluorescence staining was used to investigate the co-expression of these two markers. To determine the correlation between expression of nestin and CD133 with the length of asymptomatic period and overall patient survival we used the Kaplan-Meyer analysis. RESULTS: CD133 expression was detected in 22 (19%), nestin in the epithelium in 74 (66%) and vasculature in 78 (70%) of patients. Co-expression of these two markers was found in 21 (17%) patients in less than 1% of positive cells without impact on disease free or overall survival. CONCLUSIONS: We identified CD133(+)/nestin(+) cells as novel potential markers of lung cancer CSCs.

Immunohistochemical assessment of E-cadherin and beta-catenin in trichofolliculomas and trichoepitheliomas.

BACKGROUND: Trichofolliculomas and trichoepitheliomas are benign skin neoplasms originating from hair follicle cells. They result from defects in the signaling pathways that regulate hair follicle morphogenesis and regeneration. Thus they seem to be an excellent model of these processes. It is known that the E-cadherin/beta-catenin system of adhesion molecules plays a crucial role in the maintenance of tissue architecture. AIM: The aim of the present study was to investigate their involvement in benign hair follicle tumor development. METHODS: Semiquantitative intensity of expression were examined in formalin-fixed and paraffin-embedded tissue sections of 53 trichoepitheliomas, 15 trichofolliculomas and 19 normal skin samples by indirect immunohistochemistry. RESULTS: The intensity of E-cadherin/beta-catenin expression in tumor cells did not differ from controls. However, normal hair follicles cells exhibited membranous E-cadherin/beta-catenin expression, whereas both types of tumors, particularly trichoepitheliomas, showed E-cadherin/beta-catenin expression with a predominantly cytoplasmic localization. CONCLUSIONS: We suggest that this dystopic distribution of the E-cadherin/beta-catenin complex in hair follicle tumor cells may be a marker of cell-cell adhesion disruption which may contribute to the tumor formation.

Molecular changes in PDEGF and bFGF in malignant melanomas in relation to the stromal microenvironment.

BACKGROUND: Aberrant expression of either growth factors or growth factor-receptors by stromal cells can be an important factor promoting the growth of solid tumours. It may also affect differentiation of malignant cells and support tumour spread. The aim of the present study was to investigate the hypothesis that basic-fibroblast growth factor (bFGF) and platelet-derived growth factor (PDEGF) may be involved in tumour-stromal microenvironment interactions in primary malignant melanomas. MATERIALS AND METHODS: PDEGF and bFGF expression in malignant cells and surrounding stromal elements was assessed using indirect immunohistochemistry. RESULTS: It was confirmed that PDEGF can be involved in the reciprocal interactions between tumour cells and stroma, including aberrant angiogenesis. Interestingly, bFGF was present both in malignant melanoma lesions and benign nevi accompanied by different intracellular localisation of the protein, suggesting its implication in regulation of nevus cell proliferation and maturation. CONCLUSION: The present results suggest that bFGF and PDEGF participate in malignant melanoma progression.

Expression of the hMLH1 and hMSH2 proteins in normal tissues: relationship to cancer predisposition in hereditary non-polyposis colon cancer.

The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.