Alexithymia and suicidal ideation: a 12-month follow-up study in a general population

Alexithymic features are often associated with depression, which is the most important risk factor for suicidal behaviors. Nevertheless, little is known about the associations between alexithymia and suicidality. In this 12-month follow-up study we investigated the relationship between alexithymia and suicidal ideation in a sample of the general population (N = 1,563) using the 20-item Toronto Alexithymia Scale (TAS-20) and the 21-item Beck Depression Inventory (BDI). Suicidal ideation was more common among subjects with alexithymia than among nonalexithymic subjects (32% v 9% at baseline and 36% v 9% after 12 months). In cross-sectional analyses, alexithymia associated with the presence of suicidal ideation even after adjustment for sex, age, and several psychosocial and socioeconomic factors and the presence of depression. Moreover, after adjustment for depression at baseline, the decrease and increase in alexithymic features during the study period associated independently with recovery from and the occurrence of suicidal ideation, respectively. Nevertheless, these associations were no longer independent when adjusted for concomitant changes in the level of depressive symptoms. In conclusion, if depression presents alexithymic features the subject has an additive impact on the risk of suicidal ideation.     

Evaluation of exposure to man-made vitreous fibers by nasal lavage

The objectives of this study were to develop a biomonitoring method for the assessment of exposure to man-made vitreous fibers (MMVF), to examine the level of exposure to MMVF in the prefabricated house industry, and to study nasal inflammatory reactions and respiratory symptoms associated with MMVF among workers. Nasal lavage was performed on workers from two factories, and concentrations of MMVF were measured by electron microscopy. Cytokines (IL-6, IL-8, TNF-alpha, and IFN-gamma) were also assayed and inflammatory cells (lymphocytes, eosinophils, neutrophils, and macrophages) were counted microscopically. Concentrations of airborne fibers (longer than 5 microm) were measured for comparison. Moreover, the exposure to MMVF and the related symptoms were studied with a structured questionnaire. In nasal lavage samples, the mean concentration of MMVF (length >1.5 microm) was 3260 f/ mL in Factory 1, 1680 f/mL in Factory 2, and below 500 f/mL in the control group. About 52% of the retained fibers were longer than 100 microm. The group-specific mean concentrations of MMVF in nasal lavage samples correlated with production rates and airborne fiber levels in both plants. The airborne concentrations of MMVF both in the breathing zone and fixed-point samples were low (below 0.1 f/cm(3)). No significant differences in the biological response (inflammatory cells, cytokines) were found between the groups exposed and the control group. The workers complained of some irritation of the skin, eyes, and upper respiratory tract, which could be reduced by appropriate protective equipment. It is concluded that nasal lavage can be used as a biomonitoring method in the assessment of MMVF exposure.     

Suicide in alcohol-dependent individuals: epidemiology and management

The association of alcohol dependence with suicidal behaviour is well established although complex. On the basis of epidemiological and clinical evidence, alcohol dependence is known to increase the risk for suicidal ideation, suicide attempts and completed suicide. However, this risk is modulated by a wide variety of factors including sociodemographic, clinical, treatment-related and life situational characteristics as well as current drinking status and the effect of inebriation. Treatment and management of patients with alcohol dependence and concomitant suicidal communication or suicide attempts is crucial, as is the recognition of these patients in emergency and other healthcare service contacts. The treatment strategies cannot be based on evidence derived from randomised clinical trials as such data do not exist. They must rather be based on current knowledge of risk factors for suicidal behaviour, efficacy of treatment for alcohol dependence or relevant co-morbid conditions and problems known to be common in treatment settings. In this article, we review the essential literature on the epidemiological and clinical research in the areas of alcohol dependence and suicidal behaviour. On the basis of current data and clinical experience, we suggest the following principles be followed in the management of alcohol-dependent individuals: (i) suicidal threats or communication by alcohol-dependent individuals in emergency and other contacts should be taken seriously; (ii) other mental disorders should be well evaluated, a consequent treatment plan initiated and follow-up arranged; (iii) appropriate and up-to-date pharmacological treatment should focus on both reducing the amount of drinking and treating symptoms of other mental disorders; (iv) psychotherapeutic efforts should be focused on emerging symptoms of both alcohol use and other mental disorders; and (v) known epidemiological and clinical risk factors, adverse life events in particular, should be recognised and taken into account.     

Cancer cells as targets for lentivirus-mediated gene transfer and gene therapy

Lentiviruses have been used as gene transfer vectors for almost 10 years and their utility has been demonstrated in a variety of different applications. However, their value in cancer gene therapy has not been studied thoroughly. Here we show that VSV-G pseudotyped HIV-1-based lentiviruses are efficient vectors for human tumor cells in vitro and in vivo. Lentiviral gene transfer efficiency was demonstrated by transducing 42 different cell lines, representing 10 different human tumor types. It was shown that most of the cell lines were good or excellent targets for lentiviral transduction, allowing 50-95% gene transfer efficiency. These results were comparable to those obtained with an E1/E3 deleted, serotype 5 adenovirus vector. Analysis of lentivirus vector structure revealed that virus particles devoid of HIV-1 accessory proteins appeared to be more efficient, but the presence of enhancing elements cPPT and WPRE did not play a major role in transduction efficiency to four different human tumor cell lines. However, their effect on the gene expression level in these cells was apparent. To examine the impact of lentiviral gene expression level on suicide gene therapy approach, human osteosarcoma cells were transduced with lentivirus- or adenovirus vectors carrying the fusion gene HSV-TK-GFP and exposed to ganciclovir. Cell viability analysis after the treatment revealed that both vector types induced similar level of cytotoxicity, suggesting that lentiviral expression of a suicide gene is adequate for tumor cell destruction. Finally, in vivo transduction studies with subcutaneous tumors showed that lentivirus vectors can yield similar gene transfer efficiency than adenovirus vector, despite three orders of magnitude lower titer of the lentiviral preparation. In conclusion, these data show that lentiviruses are efficient gene transfer vehicles for human tumor cells and justify their use in further preclinical cancer gene therapy studies.     

Improved display of synthetic IgG-binding domains on the baculovirus surface

Improved display of foreign protein moieties in combination with beneficial alteration of the viral surface properties should be of value for targeted and enhanced gene delivery. Here, we describe a vector based on Autographa californica multiple nucleopolyhedrovirus (AcMNPV) displaying synthetic IgG-binding domains (ZZ) of protein A fused to the transmembrane anchor of vesicular stomatitis virus (VSV) G protein. This display vector was equipped with a GFP/EGFP expression cassette enabling fluorescent detection in both insect and mammalian cells. The virus construct displayed the biologically active fusion protein efficiently and showed increased binding capacity to IgG. As the display is carried out using a membrane anchor of foreign origin, gp64 is left intact for virus entry, which may increase gene expression in the transduced mammalian cells. In addition, the viral vector can be targeted to any desired cell type via binding of ZZ domains when an appropriate IgG antibody is available.     

Breast milk fatty acids,eicosanoids, and cytokines in mothers with and without allergic disease

Allergic disease (AD), including atopic eczema, asthma, allergic rhinitis, and food allergy, is characterized by an imbalance between cytokines produced by distinct T-helper cell subtypes. Whether this imbalance can be transferred from mother to breast milk remains to be established. The objective was to investigate the concentrations and interactions of nutritional and inflammatory factors in breast milk. Breast milk samples were collected from mothers with AD (n = 43) and without AD (n = 51). The concentrations of transforming growth factor (TGF)-beta2, tumor necrosis factor-alpha, IL-4, IL-10, prostaglandin E2, and cysteinyl leukotrienes were measured by immunoassays and fatty acid composition by gas chromatography. Mothers with AD had a lower concentration of TGF-beta2 in breast milk [median (interquartile range), 420 (278-701) ng/L] compared with those without AD [539 (378-1108) ng/L; p = 0.003], whereas other cytokines, prostaglandin E2, and cysteinyl leukotriene concentrations or fatty acid composition were not significantly different between the groups. The breast milk inflammatory factors and fatty acid composition were shown to be related. A positive association was observed between TGF-beta2 and the proportion of polyunsaturated fatty acids (p = 0.038) and a negative association between TGF-beta2 and the proportion of saturated fatty acids (p = 0.029) in breast milk. The reduced TGF-beta2 concentration in the breast milk of mothers with AD may interfere with the development of the mucosal immune system of the breast-fed infant. The observed associations between nutritional and inflammatory factors in breast milk suggest that it may be possible to influence the immunologic properties of breast milk by dietary intervention of the mother.     

Antioxidant defense mechanisms in human neutrophils

Neutrophils have a short half-life and high tendency to undergo apoptosis. One feature that may influence these characteristics is the antioxidant/oxidant balance of these cells. There are few studies on the levels of antioxidant enzymes in human neutrophils. We have analyzed by immunohistochemistry of paraffin-embedded cells and from cytospin preparations the most important antioxidant proteins in human neutrophils, and compared their levels with those in blood monocytes. Neutrophils showed moderate to high catalase, weak to moderate extracellular superoxide dismutase, and weak copper zinc superoxide dismutase and gamma-glutamylcysteine synthetase immunoreactivities. There were no detectable levels of manganese superoxide dismutase, thioredoxin, and heme oxygenase 1. Some differences were observed between the samples prepared by embedding in paraffin or by cytospin. These results, in combination with a recent study from this laboratory, suggest that a prominent feature in neutrophils is their high catalase activity but lower level of glutathione-dependent antioxidant enzymes. The differences in antioxidant profiles in neutrophils and monocytes may have important effects on the life span of human neutrophils, in both healthy and diseased tissues.     

Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala hantavirus infection than the tumor necrosis factor-alpha(-308) G/A polymorphism

The tumor necrosis factor (TNF)-alpha(-308) G/A polymorphism (TNF-2) is in linkage disequilibrium with the human leukocyte antigen (HLA)-B8-DR3 haplotype. Both factors have been associated with severe Puumala hantavirus-induced nephropathia epidemica (NE). To examine which part of this extended haplotype might show the strongest association with the outcome of NE, the HLA-B, HLA-DRB1, and TNF-alpha(-308) alleles in 116 hospital-treated patients with NE were analyzed. The findings pointing to clinically severe NE were strongly associated with HLA-B8-DR3 haplotype. There was a trend toward severe disease in persons positive for TNF-2. This was probably due to strong linkage disequilibrium with HLA-B8-DR3, since there were no differences in the clinical severity of NE when TNF-2-positive/B8-DR3-negative persons were compared with TNF-2-negative/B8-DR3-negative persons. It is concluded that the HLA-B8-DR3 haplotype is an important contributor to the course of NE. The data indicate that the TNF-2 allele is not an independent risk factor for severe NE but a passive component in the extended haplotype.     

The Mood Disorder Questionnaire improves recognition of bipolar disorder in psychiatric care

Background  

We investigated our translation of The Mood Disorder Questionnaire (MDQ) as a screening instrument for bipolar disorder in a psychiatric setting in Finland.     

Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease

We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer's disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean +/- SD rCMRgluc were 0.20 +/- 0.03 micromol/ml/min for the demented twins, 0.21 +/- 0.03 micromol/ml/min for their non-demented co-twins, and 0.23 +/- 0.02 micromol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean +/- SD rCMRgluc were 0.27 +/- 0.05, 0.28 +/- 0.04, and 0.32 +/- 0.02 micromol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.