[Weight gain and treatment with psychotropic drugs : Background and management]. / Gewichtszunahme unter Therapie mit Psychopharmaka : Hintergründe und Management.

Psychotropic drug-induced weight gain (PIWG) is a well-known and frequent side effect which is relevant for the prognosis of patients. Individual medications have varying risks for the occurrence of PIWG, and at the same time there are individual risk factors on the part of patients, such as age, gender, metabolic and genetic factors. As the metabolic changes in the context of PIWG result in increased mortality in the long term, it is important to prevent PIWG by appropriate prevention and to intervene in a targeted manner if PIWG has already occurred. Appropriate monitoring is therefore essential. This article provides an overview of underlying mechanisms, risk constellations and possible countermeasures.

Attachment mediates the link between childhood maltreatment and loneliness in persistent depressive disorder.

BACKGROUND: A central concept of attachment theory is that early experiences with close attachment figures shape the way we interact with and relate to other social partners throughout life. As such, early experiences of childhood maltreatment (CM) have been suggested as a key precursor of adult insecure attachment representations. As CM has been linked to feelings of loneliness in adulthood, this study examines whether insecure attachment could explain the relationship between CM and loneliness. Also, the moderating role of a diagnosis of persistent depressive disorder (PDD) is investigated, a disorder characterized by high levels of CM and loneliness. METHOD: 60 patients with PDD (DSM-5) and 60 gender- and age-matched non-clinical control participants (NC) completed self-report questionnaires measuring attachment, loneliness, and CM. Mediation analyses (PDD as a moderator) were performed. RESULTS: PDD patients reported higher levels of CM, attachment anxiety, attachment avoidance, and loneliness than NC. CM was positively associated with loneliness in both groups. Mediation analyses demonstrated that the relationship between CM and loneliness was mediated by avoidant, but not anxious attachment, regardless of a diagnosis of PDD. LIMITATIONS: Caution when interpreting these results is crucial as the study lacked a clinical control group, relied on self-report measures, and the cross-sectional design limits the ability to draw causal inferences. CONCLUSIONS: All constructs studied were present to a greater degree in PDD. Above, findings provide initial evidence that avoidant attachment may explain the relationship between CM and loneliness. Potentially, adult avoidant attachment may lead to and maintain feelings of loneliness, regardless of PDD.

Dynamics of the immediate behavioral response to partial social exclusion.

Social rejection and exclusion (ostracism) represent main stressors in daily life and even threaten mental and physical health. Abundant data from subjective measures in social exclusion paradigms are available, but the dynamic behavioral response is largely unexplored. Here, we applied modified variants of the Cyberball paradigm in two consecutive experiments to investigate the adaptive behavioral and emotional reactions to partial social exclusion. In experiment 1, 68 healthy participants (females, mean age 24.76 ± 4.05 years) played 2 min inclusion, 5 min partial exclusion and 2 min total exclusion. In experiment 2, 94 healthy participants (48 females, mean age 34.50 ± 12.08 years) underwent an experimental condition (2 min inclusion, 10 min partial exclusion) and a control condition (12 min inclusion only) in randomized order. In experiment 1, behavioral responses to partial exclusion showed two characteristics: (1) an immediate increase in ball passes to the excluding player followed (2) by a later return of participants' behavior to baseline. This finding was replicated for both genders and in comparison to a control condition in experiment 2. The dynamic behavioral response observed here may point to overlapping principles of cooperation in this ball tossing paradigm and serves as a novel experimental proxy.

[The challenge of treating bipolar outpatients]. / Herausforderungen der ambulanten Behandlung von Patienten mit bipolar-affektiven Störungen.

The course of bipolar illness comprises a wide range, which may vary between one single episode once every five years and a severe ultra rapid cycling course with mood changes within days. Even with optimal pharmacological treatment the functional outcome in bipolar patients is still poor. Underlying pathomechanisms are not fully understood yet. This article addresses three possible illness specific-aspects: cognitive defects, high relapse frequency and poor adherence. Causes as well as therapeutic interventions for these therapeutic pitfalls are summarised.

[The White man's burden - a case study caught between bipolar affective disorder and Huntington's disease]. / White Man's Burden - Im Grenzgebiet zwischen bipolarer affektiver Störung und Huntington-Erkrankung.

We report upon a case of a 55 year old patient with a bipolar affective disorder, presenting herself with a depressive symptomatology in addition to a severe motor perturbation. The main emphasis upon admittance was perfecting and improving her latest medication. Four weeks prior to her stay at our clinic a thorough neurological examination had taken place in terms of an invalidity pension trial which did not result in any diagnostic findings. Therefore a neurological disease seemed at first highly unlikely. Even though the prior testing was negative, the ensuing neurological examination at our clinic resulted in movement disorders very much indicative of Huntington's Disease. A detailed investigation in regards to the particular family history of the patient was positive for Huntington's Disease. However, whether the patient's mother had also been a genetic carrier of Huntington's Disease was still unknown at the time the patient was admitted to our clinic. It was nevertheless discovered that her mother had also suffered from a bipolar affective disorder. A genetic testing that followed the neurological examination of the patient proved positive for Huntington's Disease. Neuro-imaging resulted in a bicaudate-index of 2.4 (the critical value is 1.8). In a clinical psychological test battery the ensuing results were highly uncommon for patients with solely a bipolar affective disorder people. Under the medical regimen of Quetiapine, Citalopram and Tiaprid the patient's mood could be stabilized and there was some improvement of her motor pertubation.

The relationship of Akathisia with treatment emergent suicidality among patients with first-episode schizophrenia treated with haloperidol or risperidone.

Akathisia as well as younger age, early illness onset and discharge are important risk factors for suicidality in patients with first-episode schizophrenia. The aim of the present study was to analyze on a single case basis the relationship between a sudden increase in suicidality, anxiety symptoms, medication dosing and clinician- and patient-rated akathisia. A small subsample of patients demonstrated a positive relationship between suicidality and akathisia scores within the titration period of the study medication.

Elevated macrophage migration inhibitory factor and decreased transforming growth factor-beta levels in major depression--no influence of celecoxib treatment.

OBJECTIVES: The involvement of an immune process in the pathophysiology of major depression disorder (MDD) was substantiated by studies demonstrating elevated levels of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Cyclooxygenase-2 (COX-2) inhibitors lead to a reduced production of PGE(2) and have been shown to improve depressive symptoms. We investigated the three immune parameters macrophage migration inhibitory factor (MIF), transforming growth factor-ß (TGF-ß) and soluble CD14 (sCD14) in a randomized, placebo-controlled trial of the COX-2 inhibitor celecoxib as add-on therapy in patients with MDD treated with reboxetine. METHODS: Thirty-two patients with depression and 20 healthy controls participated in the study. The patients were treated with reboxetine and celecoxib or placebo. Immune parameters were measured from serum at baseline, after three and five weeks using ELISA. RESULTS: Celecoxib as add-on strategy resulted in a significant reduction of Hamilton Depression Scale scores compared to placebo. Depressed patients showed significantly elevated MIF (p < 0.001) and reduced TGF-ß (p = 0.006) concentrations at baseline. There was no difference in sCD14-concentrations. There was no difference between the placebo and the celecoxib group and no change over time. LIMITATIONS: Limitations of the study are the relatively small sample size and lack of functional assessment of HPA axis in parallel. CONCLUSIONS: MIF is a promising new candidate in the neuro-immune interplay that may link depressive symptoms, altered immune state and HPA-axis dysregulation. Reduced levels of TGF-ß replicate previous findings and support the importance of this regulatory cytokine in major depressive disorder.

The RSM-scale: a pilot study on a new specific scale for self- and observer-rated quality of life in patients with schizophrenia.

PURPOSE: To develop and evaluate a self- and observer-rating scale on quality of life in patients suffering from schizophrenia with regard to the efficacy of atypical antipsychotics based on different dimensions and to apply within a pilot study. METHODS: Following review of existing scales and a prevalidation phase, the Riedel-Spellmann-Musil (RSM) scale was developed comprising 36 items assigned to different subscales. As reference scales, the Quality of Life Scale (QLS) and the Subjective Well-being Under Neuroleptic Treatment Scale-short version (SWN-K) were performed, psychopathology and adverse events were measured at all visits. Reliability was assessed using Cronbach's alpha, Pearson's correlation coefficients were used to assess construct validity, and Intraclass Correlation Coefficients (ICCs) were used for test-retest reliability. T tests were performed in normal distributed samples; otherwise Wilcoxon tests were used. RESULTS: One hundred and thirty-six patients were included in the study. Cronbach`s α was 0.917 for the self-rating and 0.915 for the interviewer-rating part. ICCs were >0.70 for all subscales. The self-rating part correlated strongly with the SWN-K and the observer part with the QLS. Changes in psychopathology over the study period and different levels of functioning were detected. CONCLUSION: The RSM-scale is a new scale to assess the quality of life in different dimensions of patients with schizophrenia treated with antipsychotics and shows good internal consistency, test-retest reliability, construct and discriminant validity.

Neurocognition and its influencing factors in the treatment of schizophrenia-effects of aripiprazole, olanzapine, quetiapine and risperidone.

BACKGROUND: To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. METHODS: Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. RESULTS: A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. CONCLUSION: The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine.

Effect of aripiprazole on cognition in the treatment of patients with schizophrenia.

BACKGROUND: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.

Phenotypic analysis of human immunodeficiency virus (HIV) type 1 cell-mediated immune responses after treatment with an HIV-1 immunogen.

It was hypothesized that immune recognition could be stimulated with combined immune-based and potent antiviral drug therapies. This study examined human immunodeficiency virus type 1 (HIV-1)-specific lymphocyte proliferation before and after treatment with an inactivated HIV-1 immunogen in 15 chronically infected HIV-1 seropositive subjects. Lymphocyte proliferation to the immunizing antigen (gp120-depleted HIV-1; P<.001), purified native p24 (P<.001), and recombinant p24 (P<.05) increased after treatment with the HIV-specific immune-based therapy. By HIV-1 antigen-specific flow cytometry, T helper CD4 lymphocytes, CD8 lymphocytes, and NK cells (all P<.001) were the predominant cell types proliferating in vitro after treatment. Additional phenotyping of proliferating cells revealed predominantly CD4 and CD8 memory (both P<.001) phenotypes. This study supports the concept that in vitro lymphocyte proliferation to HIV-1 antigens, augmented after treatment with an inactivated HIV-1 immunogen, involves primarily CD4 and CD8 cell memory immune responses.

Characterization of highly purified, inactivated HIV-1 particles isolated by anion exchange chromatography.

This report characterizes inactivated, gp120 depleted, HIV-1 particles purified by an anion exchange chromatography production process. This antigen formulated with incomplete Freund's adjuvant constitutes Remune, which is being evaluated in a phase III clinical endpoint trial to determine the effect of this immune-based therapy on clinical progression of HIV-1 seropositive patients. Multiple production lots of the inactivated HIV-1 antigen strain HZ321, isolated by anion exchange chromatography, exhibit purity of > 95% by gel filtration. These findings are corroborated by thin section electron microscopy showing a homogenous field of intact particles. Analyses of the purified virus particles for protein, lipid, carbohydrate and RNA show structural retention of the envelope proteins, lipid bilayer and core components after large scale processing. The qualitative identification of at least 85% of total HIV-1 protein is determined by ELISA, Western blot, HPLC and amino acid sequencing analyses. Quantitative values are assigned to 50% of these proteins. The data confirm the presence of virally encoded proteins p6, p7, pI15, p17, p24, p32, pI39Gag, gp41, pp55Gag, p66/51, Vpr, Vif and Nef. Excellent consistency between production lots and equivalency to HIV-1 preparations purified by sucrose density gradient sedimentation has been established for protein and lipid composition, and overall purity. These findings further establish that non-viral encoded proteins and lipids are integral structural components of the intact virion and are not contaminants unique to a particular isolation method. The data confirm the presence of multicomponent antigens in the viral particles for stimulating a broad HIV-1 specific immune response. Finally, the work demonstrates that the two inactivation procedures (beta-propiolactone and gamma irradiation), which achieve efficient viral inactivation meeting US FDA guidelines, do not damage the protein antigens of the viral particles.

Isolation and expression in Escherichia coli of hepB and hepC, genes coding for the glycosaminoglycan-degrading enzymes heparinase II and heparinase III, respectively, from Flavobacterium heparinum.

Upon induction with heparin, Flavobacterium heparinum synthesizes and secretes into its periplasmic space heparinase I (EC 4.2.2.7), heparinase II, and heparinase III (heparitinase; EC 4.2.2.8). Heparinase I degrades heparin, and heparinase II degrades both heparin and heparan sulfate, while heparinase III degrades heparan sulfate predominantly. We isolated the genes encoding heparinases II and III (designated hepB and hepC, respectively). These genes are not contiguous with each other or with the heparinase I gene (designated hepA). hepB and hepC were found to contain open reading frames of 2,316 and 1,980 bp, respectively. Enzymatic removal of pyroglutamate groups permitted sequence analysis of the amino termini of both mature proteins. It was determined that the mature forms of heparinases II and III contain 746 and 635 amino acids, respectively, and have calculated molecular weights of 84,545 and 73,135, respectively. The preproteins have signal sequences consisting of 26 and 25 amino acids. Truncated hepB and hepC genes were used to produce active, mature heparinases II and III in the cytoplasm of Escherichia coli. When these enzymes were expressed at 37 degrees C, most of each recombinant enzyme was insoluble, and most of the heparinase III protein was degraded. When the two enzymes were expressed at 25 degrees C, they were both present predominantly in a soluble, active form.

Processing of the papain precursor. The ionization state of a conserved amino acid motif within the Pro region participates in the regulation of intramolecular processing.

The cysteine protease papain is synthesized as a 40-kDa inactive precursor with a 107-amino-acid N-terminal pro region. Although sequence conservation in the pro region is lower than in the mature proteases, a conserved motif (Gly-Xaa-Asn-Xaa-Phe-Xaa-Asp-36, papain precursor numbering) was found within the pro region of cysteine proteases of the papain superfamily. To determinate the function to this conserved motif, we have mutagenized at random each of the 4 residues individually within the pro region of the papain precursor. Precursor mutants were expressed in yeast, screened according to their ability to be processed through either a cis or trans reaction, into mature active papain. Three classes of mutants were found. Non-functional propapain mutants of the first class are completely degraded by subtilisin indicating that they are not folded into a native state. Mutants of the second class were neutral with respect to cis and trans processing. The third class included mutants that mostly accumulated as mature papain in the yeast vacuole. They had mutations that had lost the negatively charged Asp-36 residues and a mutation that probably introduces a positive charge, Phe-38His. The precursor of the Phe-38His mutant could be recovered by expression in a vph1 mutant yeast strain which has a vacuolar pH of about 7. The Phe-38His propapain mutant has an optimum pH of autoactivation about one pH unit higher than the wild type molecule. These results indicate that the electrostatic status of the conserved motif participates in the control of intramolecular processing of the papain precursor.

[Experimental studies of electroplating-resin bonding systems]. / Experimentelle Untersuchungen an Galvano-Kunststoff-Verbunden.

Optimized conditioning of galvanically produced gold frameworks (Auro-Galva-Crown-System) by means of Silicoater, Silicoater MD and Rocatec techniques gives rise to a reliable bond to veneering resins. After experimental stress (thermocycling) the strength of the compound could be found between 17 and 26 MPa and SEM investigations of the contact zone showed no crevices.

[Microbiological studies of self-disinfecting alginate impression materials]. / Mikrobiologische Untersuchungen an selbstdesinfizierenden Alginatabformwerkstoffen.

Using microbiologically experimental methods and observations corresponding to praxis the efficiency of the addition of antiseptics to alginate is evaluated. The addition of chlorhexidine to the alginate leads to a considerable reduction of the amounts of germs, but an one hundred percent disinfection of the alginates is not always performed. An influence of the alginate materials and the water quality on the antimicrobial efficacy of chlorhexidine has been proved. The always occurring contamination of the impression tray rules out a complete stopping of infection between the patient and the laboratory staff.

Processing of the papain precursor. Purification of the zymogen and characterization of its mechanism of processing.

The precursor of the cysteine protease papain has been expressed and secreted as propapain from insect cells infected with a recombinant baculovirus expressing a synthetic gene coding for prepropapain. This 39-kDa secreted propapain zymogen molecule is glycosylated and can be processed in vitro into an enzymatically active authentic papain molecule of 24.5 kDa (Vernet, T., Tessier, D.C., Richardson, C., Laliberté, F., Khouri, H. E., Bell, A. W., Storer, A. C., and Thomas, D. Y. (1990) J. Biol. Chem. 265, 16661-16666). Recombinant propapain was stabilized with Hg2+ and purified to homogeneity using affinity chromatography, gel filtration, and ion-exchange chromatographic procedures. The maximum rate of processing in vitro was achieved at approximately pH 4.0, at a temperature of 65 degrees C and under reducing conditions. Precursor processing is inhibited by a variety of reversible and irreversible cysteine protease inhibitors but not by specific inhibitors of serine, metallo or acid proteases. Replacement by site-directed mutagenesis of the active site cysteine with a serine at position 25 also prevents processing. The inhibitor 125I-N-(2S,3S)-3-trans-hydroxycarbonyloxiran-2-carbonyl-L-tyrosine benzyl ester covalently labeled the wild type papain precursor, but not the C25S mutant, indicating that the active site is accessible to the inhibitor and is in a native conformation within the precursor. Based on biochemical and kinetic analyses of the activation and processing of propapain we have shown that the papain precursor is capable of autoproteolytic cleavage (intramolecular). Once free papain is released processing can then occur in trans (intermolecular).