Substance misuse and psychiatric comorbidity: an overview of the OPCS National Psychiatric Morbidity Survey

There have been a number of national surveys of psychiatric morbidity which have included questions on drugs, alcohol and tobacco. These surveys have helped delineate the overlap between substance use and dependence and other psychological morbidity. There is a strong association reported between high substance consumption and other measures of psychological problems. This article provides an overview of a national household survey, a survey of institutional residents with psychiatric disorders and a national survey of a homeless population. All three surveys used comprehensive and complex sampling strategies and lay interviewers to conduct structured diagnostic interviews. The household survey included over 10,000 households, the institutional survey interviewed 755 individuals and the homeless survey of hostels, night-shelters, day centres and private-sector leased accommodation interviewed 1,061 individuals. This overview looks at patterns of nicotine, alcohol and other drug use in the different samples and examines interactions with other psychiatric morbidity. The survey reports that substance-related disorders are some of the commonest disorders in the community, with 5% of the household sample alcohol dependent, 7% alcohol dependent in the institutional sample and over 21% in the homeless sample recorded as alcohol dependent. Tobacco, alcohol and other drug use and dependence were dramatically higher in the homeless sample than in either of the other two samples. Substance use was significantly associated with higher rates of psychological morbidity as measured by the Clinical Interview Schedule Revised. Future service planning needs to take account of the striking disparity of prevalence of psychiatric disorders in different subsections of the population.     

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.     

Cloning and tissue expression of the mouse ortholog of AIM1, a betagamma-crystallin superfamily member

Fast tissue regeneration after therapeutic manipulations is a central problem of periodontology, oral surgery and trauma of the periodontal tissues, including bone. Several products, which augment tissue regeneration, have been manufactured and assayed in clinical practice with positive results. Emdogain is a recent addition in this field, as a tissue-regenerating product. The substance is a derivative of amelogenin, obtained from porcine embryonic tissues. At the present time, it is not known whether the substance can induce a local (due to the uptake of the substance) or systemic immune response. The aim of the present study was to evaluate, in vitro, the ability of Emdogain to influence, in vitro, the immune system. Peripheral blood lymphocytes, isolated for 10 healthy donors, were cultured in the presence of various concentrations of the substance, in order to determine the rate of cell proliferation, the expression of surface antigens and the production of cytokines and immunoglobulins. Under our experimental conditions, Emdogain produced a slight increase of the proliferation of lymphocytes, restricted to the CD25 (IL-2 receptor) fraction of the CD4 positive T-lymphocytes, and a concomitant decrease of CD19 positive B-lymphocytes. Other cell fractions (CD8 positive T-cells, B-cells and NK-cells) were not affected. Under our conditions too, immunoglobulin and cytokin (IL-2 and IL-6) production was not modified, even after a 3-day application of concentrations much higher than those used in clinical practice. Our data suggest that Emdogain slightly induce an immune response, restricted to the activated fraction of CD4 T-lymphocytes in vitro.     

Allosteric Regulation of Proteases

Allostery is a basic principle of control of enzymatic activities based on the interaction of a protein or small molecule at a site distinct from an enzyme's active center. Allosteric modulators represent an alternative approach to the design and synthesis of small‐molecule activators or inhibitors of proteases and are therefore of wide interest for medicinal chemistry. The structural bases of some proteinaceous and small‐molecule allosteric protease regulators have already been elucidated, indicating a general mechanism that might be exploitable for future rational design of small‐molecule effectors.     

Fish liver and seagull eggs,vitamin D‐rich foods with a shadow: Results from the Norwegian Fish and Game Study

Scope Fish liver, fish liver oil, oily fish and seagull eggs have been major sources of vitamin D for the coastal population of Norway. They also provide dioxin and polychlorinated dioxin‐like compounds (dl‐compounds), which may interfere with vitamin D homeostasis. We investigated whether serum 25‐hydroxyvitamin D (25(OH)D) might be compromised by concomitant intake of dl‐compounds. Methods and results We studied 182 adults participating in the Norwegian Fish and Game Study. Participants who consumed fish liver and/or seagull eggs had higher dl‐compound intake and blood concentrations than non‐consumers (p < 0.001). Vitamin D intake was higher (p < 0.001), whereas serum 25(OH)D was lower (p = 0.029) in consumers than in non‐consumers. Among non‐consumers, vitamin D intake was associated with serum 25(OH)D (β=1.06; 95% CI: 0.48, 1.63). This association was weaker among consumers (β = 0.52; 95% CI: ?0.05, 1.08), but strengthened when adjusted for retinol intake (β = 0.66; 95% CI: 0.12, 1.21). The association between vitamin D intake and serum 25(OH)D did not seem to be compromised by intake of dl‐compounds. Conclusion To secure adequate vitamin D status while keeping the intake of dioxins and dl‐polychlorinated biphenyls low, a healthy diet should include both supplemental vitamin D and oily fish. Despite high nutrient content, dietary fish liver and seagull eggs should be restricted, due to dl‐compounds and possible vitamin A‐D antagonism.     

Chemical biology approaches reveal conserved features of a C-terminal processing PDZ protease

Several proteases like the high temperature requirement A (HtrA) protein family containing internal or C-terminal PDZ domains play key roles in protein quality control in the cell envelope of Gram-negative bacteria. While several HtrA proteases have been extensively characterized, many features of C-terminal processing proteases such as tail-specific protease (Tsp) are still unknown. To fully understand these cellular control systems, individual domains need to be targeted by specific peptides acting as activators or inhibitors. Here, we describe the identification and design of potent inhibitors and activators of Tsp. Suitable synthetic substrates of Tsp were identified and served as a basis for the generation of boronic acid-based peptide inhibitors. In addition, a proteomic screen of E. coli cell envelope proteins using a synthetic peptide library was performed to identify peptides capable of amplifying Tsp's proteolytic activity. The implications of these findings for the regulation of PDZ proteases and for future mechanistic studies are discussed.     

Ratings of journals by and for personality psychologists.

Rank ordered reference sources used by the authors selected by editors of the Annual Review of Psychology to cover the field of personality during 1970–1976 and found the assessment to be more reliable than D. Koulack and H. J. Keselman's (see record 1976-24649-001) ratings based on responses of American Psychological Association members. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atopy and IgE in a pediatric allergy practice

In children under six years of age referred to a pediatric allergy practice the usefulness of serum IgE assay was evaluated in relation to age, symptoms, nasal eosinophilia, skin tests and family history. In more than 60% of the children the initial symptom, usually rhinorrhea, had occurred before one year of age. In infancy the diagnosis was more difficult, gastrointestinal complaints were more frequent and nasal eosinophilia less frequent than in the older children. Many infants had positive skin tests to foods and to environmental allergens. There was a significant correlation between elevated serum IgE level and age, nasaeosinophilia, the number of positive skin tests and the probability of immunotherapy being prescribed. Although no clear diagnostic level is seen, an IgE level above 100 micron/ml at any age and an IgE level above 20 micron/ml in infants strongly suggest the possibility of atopic disease. However, a low IgE level does not exclude atopic disease.