Intimate stimuli result in fronto-parietal activation changes in anorexia nervosa.

BACKGROUND: Intimacy is a key psychological problem in anorexia nervosa (AN). Empirical evidence, including neurobiological underpinnings, is however, scarce. OBJECTIVE: In this study, we evaluated various emotional stimuli including intimate stimuli experienced in patients with AN and non-patients, as well as their cerebral response. METHODS: Functional magnetic resonance imaging was conducted using stimuli with positive, neutral, negative and intimate content. Participants (14 AN patients and 14 non-patients) alternated between passive viewing and explicit emotion regulation. RESULTS: Intimate stimuli were experienced less positively in AN patients compared to non-patients. AN patients showed decreased cerebral responses in superior parietal cortices in response to positive and intimate stimuli. Intimate stimuli led to stronger activation of the orbitofrontal cortex, and lower activation of the bilateral precuneus in AN patients. Orbitofrontal responses decreased in AN patients during explicit emotion regulation. CONCLUSIONS: These results show that intimate stimuli are of particular importance in AN patients, who show experiential differences compared to non-patients and altered activation of orbitofrontal and parietal brain structures. This supports that AN patients have difficulties with intimacy, attachment, self-referential processing and body perception. LEVEL OF EVIDENCE: Level III, case-control study.

How do patients with anorexia nervosa "process" psychotherapy between sessions? A comparison of cognitive-behavioral and psychodynamic interventions.

OBJECTIVE: Patients' processing of psychotherapy between sessions ("inter-session process" (ISP)) has been repeatedly shown to be related to outcome. The aim of this study was to compare ISP characteristics of cognitive-behavioral vs. psychodynamic psychotherapy in the treatment of anorexia nervosa (AN) and their relation to outcome. METHODS: Data of 106 patients participating in a randomized-controlled trial who received either 40 sessions of enhanced cognitive-behavioral therapy (CBT-E) or focal psychodynamic therapy (FPT) were analyzed. The ISP was measured with the Inter-session Experience Questionnaire (IEQ). Three outcome classes were distinguished: full recovery, partial recovery, and still fulfilling all AN criteria. RESULTS: Patients receiving CBT-E reported more on "applying therapy" in the initial and the final treatment phase compared to FPT patients. In terms of process-outcome relations, higher levels of "recreating the therapeutic dialogue between sessions," "recreating the therapeutic dialogue with negative emotions" as well as "applying therapy with negative emotions" in the final phase of treatment predicted negative outcome in FPT, whereas overall higher levels of negative emotions predicted negative outcome in CBT-E. CONCLUSIONS: In outpatient treatment in AN, the processing of therapy as measured by the IEQ showed surprisingly few differences between CBT-E and FPT. However, different ISP patterns were predictive of outcome, pointing to different mechanisms of change.

Cost-effectiveness of focal psychodynamic therapy and enhanced cognitive-behavioural therapy in out-patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious illness leading to substantial morbidity and mortality. The treatment of AN very often is protracted; repeated hospitalizations and lost productivity generate substantial economic costs in the health care system. Therefore, this study aimed to determine the differential cost-effectiveness of out-patient focal psychodynamic psychotherapy (FPT), enhanced cognitive-behavioural therapy (CBT-E), and optimized treatment as usual (TAU-O) in the treatment of adult women with AN. METHOD: The analysis was conducted alongside the randomized controlled Anorexia Nervosa Treatment of OutPatients (ANTOP) study. Cost-effectiveness was determined using direct costs per recovery at 22 months post-randomization (n = 156). Unadjusted incremental cost-effectiveness ratios (ICERs) were calculated. To derive cost-effectiveness acceptability curves (CEACs) adjusted net-benefit regressions were applied assuming different values for the maximum willingness to pay (WTP) per additional recovery. Cost-utility and assumptions underlying the base case were investigated in exploratory analyses. RESULTS: Costs of in-patient treatment and the percentage of patients who required in-patient treatment were considerably lower in both intervention groups. The unadjusted ICERs indicated FPT and CBT-E to be dominant compared with TAU-O. Moreover, FPT was dominant compared with CBT-E. CEACs showed that the probability for cost-effectiveness of FTP compared with TAU-O and CBT-E was ⩾95% if the WTP per recovery was ⩾€9825 and ⩾€24 550, respectively. Comparing CBT-E with TAU-O, the probability of being cost-effective remained <90% for all WTPs. The exploratory analyses showed similar but less pronounced trends. CONCLUSIONS: Depending on the WTP, FPT proved cost-effective in the treatment of adult AN.

Severity of bulimia nervosa. Measurement and classification into health or pathology.

AIMS: In order to identify the most important components of the severity of bulimia nervosa (as well as identifying clinical cases), we explored the relation between dimensional and categorical assessment. This was achieved by studying the performance of variables from standard instruments (measuring specific and general psychopathology) in predicting an expert rating of overall syndrome severity. METHOD: In total, 213 cases were selected (across the whole range of severity). We applied regression with optimal scaling to model nonlinear relations in the data, and the lasso method with bootstrapping for predictor selection. The best model contained 2 scales of the Eating Disorders Inventory ('bulimia' and 'drive for thinness') and the frequency of the binges. The sensitivity and specificity of case classification using the obtained model was determined. RESULTS: The model can predict the probability of being a clinical case at a rate of 88%. The presented statistical methods are innovative and promising approaches that can help researchers and clinicians to better define sets of variables for treatment evaluation and outcome studies. CONCLUSION: The results indicate that severity and outcome in bulimia nervosa should be determined by measuring both cognitive and behavioral aspects of the symptoms.

Symptom severity and treatment course of bulimic patients with and without a borderline personality disorder.

There are contradictory results concerning the frequency of borderline personality disorder (BPD) in bulimic patients and its impact on eating pathology and treatment outcome. We evaluated 240 patients with bulimia nervosa using EDI-2, SIAB and SCL-90-R. Only a minority of patients had a BPD (13.8%). There were no differences in binging or purging behaviour between patients with and without BPD, but borderline patients had significantly more feelings of ineffectiveness and more disturbances in interoceptive awareness. Bulimic patients with BPD showed significantly more general psychopathology. Although, BPD patients started with higher levels of pathology, there were similar reductions of symptoms over the course of treatment in both groups. Psychotherapy in bulimic patients with a BPD has to focus not only on eating pathology but also on aspects that are caused by the severe personality disturbance.

[Cytotoxic compounds from the marine actinobacterium].

We isolated a bioactive streptomycete from marine sediment samples collected at Bay of Bengal, India, during our systematic study of marine actinobacteria. The taxonomic studies indicated that the isolate is related to Strepomyces corchorusii. However, it differed in certain aspects, and, hence, was designated as S. corchorusii AUBN(1)/7. A solvent extraction followed by a chromatographic purification helped obtain from the isolate two cytotoxic compounds, which were identified as resistomycin, a quinone-related antibiotic, and tetracenomycin D, an anthraquinone antibiotic, on the basis of spectral data of pure compounds. They demonstrated in vitro a potent cytotoxic activity against cell lines HMO2 (gastric adenocarcinoma) and HepG2 (hepatic carcinoma) and also exhibited weak antibacterial activities against Gram-positive and Gram-negative bacteria. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

[Bulimia nervosa]. / Bulimia nervosa.

Bulimia nervosa is characterized by episodes of binge eating and compensatory behaviours (self-induced vomiting, laxative misuse, dietary restriction). It has a complex aetiology and is mostly found in young women. Bulimia leads to substantial physical and psychosocial morbidity. Bulimia nervosa needs specialized psychotherapeutic treatment. In most cases outpatient treatment is sufficient, but comorbidity with other psychiatric disturbances has to be taken into account. Additional psychopharmacological interventions might be helpful. After 5 to 10 years about 50% of the patients show complete remissions, 30% partial remissions and about 20% a chronic course of the illness. General practitioners, dentists and gynaecologists should be informed about typical signs of the disorder that is often hidden by the patients.

Enterobactin: the characteristic catecholate siderophore of Enterobacteriaceae is produced by Streptomyces species.(1).

Enterobactin is described in the literature as the typical iron-chelating compound (siderophore) produced by bacteria of the family Enterobacteriaceae. In the course of a HPLC with diode array detection screening programme for detection of novel secondary metabolites, enterobactin, its biosynthetic precursor 2,3-dihydroxy-N-benzoylserine and its linear dimer and trimer condensation products were found to be produced by two Streptomyces strains besides the trihydroxamate-type siderophores desferri-ferrioxamine B and E.

UV mutagenesis and enzyme inhibitors as tools to elucidate the late biosynthesis of the spirobisnaphthalenes.

The metabolite pattern of UV mutants of the spirobisnaphthalene producing fungus F-24'707 by TLC and HPLC analysis has been investigated. Mutants with differences in colony morphology or colour compared to the parent strain were isolated. Cultivation in shaking flasks and P flasks showed differences in the metabolite pattern of some of the strains. Furthermore, enzyme inhibitors were used to block the spirobisnaphthalene biosynthesis of the parent strain at different steps. Feeding of precursors and intermediates of cladospirone bisepoxide (15) led to a two-fold increase of the production of 15. From these data and preceding biosynthetic studies we deduced a general pathway for the biosynthesis of all spirobisnaphthalenes of the fungus F-24'707. This enables us to present the hypothesis that all bisnaphthalenes described so far are produced using a common pathway with only a few intermediates as central branching points.

Sphaerolone and dihydrosphaerolone, two bisnaphthyl-pigments from the fungus Sphaeropsidales sp. F-24'707.

Two new bisnaphthalene compounds, sphaerolone (1) and dihydrosphaerolone (2), together with 2-hydroxyjuglone (9), were isolated from the culture broth of a Sphaeropsidales sp. (strain F-24'707) after inhibition of the regular proceeding 1,8-dihydroxynaphthalene (DHN) biosynthesis with tricyclazole. The structures of 1 and 2 were established by detailed spectroscopic analysis and present novel bisnaphthalenes. The biosynthetic origin of 1 and 2 as dimerization products of 1,3,8-trihydroxynaphthalene, an intermediate of the DHN biosynthesis, is discussed.

Five naphthalene glycosides from the roots of Rumex patientia.

Three novel and two known naphthalene glycosides were isolated from the roots of Rumex patientia L. (Polygonaceae). The structures of the new compounds were established, respectively as 2-acetyl-3-methyl-6-carboxy-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranoside, 4,4"-binaphthalene-8,8"-O,O-di-beta-D-glucopyranoside and 2-acetyl-3-methyl-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranosyl (1-->3) beta-D-glucopyranoside on the basis of spectral analysis. The other napthalene glycosides were determined as nepodin-8-O-beta-D-glucopyranoside and torachrysone-8-O-beta-D-glucopyranoside by comparison of their spectral data with those previously reported.

The structures of antioxidant and cytotoxic agents from natural source: anthraquinones and tannins from roots of Rumex patientia.

A new anthraquinone glycoside, emodin-6-O-beta-D-glucopyranoside, and a new simple halogenated flavan-3-ol, 6-chlorocatechin, have been isolated from the roots of Rumex patientia L. together with seven known phenolic compounds. Their structures were elucidated on the basis of spectroscopic methods. Cytotoxic effects and radical scavenging properties of the isolated compounds have been demonstrated.

Metabolic products of microorganisms. 240. Urdamycins, new angucycline antibiotics from Streptomyces fradiae. II. Structural studies of urdamycins B to F.

The structures of the angucycline antibiotics urdamycin B (5), E (2) and F (9) were established by comparing of their spectra with those of urdamycin A (1). The structures of urdamycins C and D, the largest compounds of this series, are still incomplete (10 and 11). The aglycones urdamycinone C, D and E can be liberated by methanolysis of the corresponding urdamycins. The liberation of urdamycinone B (6) requires an alcohol-free medium, to prevent its rearrangement to the naphthacenequinone 7 or 8. The urdamycins differ from other O-glycoside series in their variety of aglycones.

Derivatives of saquayamycins A and B. Regio- and diastereoselective addition of alcohols to the L-aculose moiety.

In continuation of our structure-activity investigations on angucycline antibiotics we prepared derivatives of saquayamycins A (1) and B (4) by regio- and diastereoselective nucleophilic addition of different alcohols to the L-aculose moiety. Reversible protection of the 4'-hydroxy group in 1 by silylation allowed a derivatization at both L-aculose moieties without cyclization towards cinerulose B. The in vitro cytotoxic activity remained almost unchanged after variation at the L-aculose moieties whereas a change in the aglycone structure led to a total loss of the biological activity.

Structure-activity relationships of elloramycin and tetracenomycin C.

The structure-activity relationships of the anthracycline-related antibiotics of the tetracenomycin C/elloramycin-type were investigated by derivatization of elloramycin (1) and elloramycinone (2). During hydrolysis experiments a unique transglycosylation reaction was discovered, converting elloramycin (1) into isoelloramycin (10) by treatment with anhydrous trifluoroacetic acid. Following the proposed structure-activity relationship concept, 8-O-methylelloramycinone (14) was synthesized from elloramycinone (2), and was shown to be the most active derivative according to the proliferation inhibition assay against murine L1210 leukemia cells.

Secondary metabolites by chemical screening. I. Calcium 3-hydroxyquinoline-2-carboxylate from a Streptomyces.

Streptomyces griseoflavus subsp. (Gö 3592) was investigated by chemical screening methods. The mycelium contained gilvocarcin V (1). The culture filtrate contained the calcium salt of 3-hydroxyquinoline-2-carboxylic acid (2) confirmed by spectroscopic methods and by a 5-step partial synthesis of the free acid (3).

New biologically active rubiginones from Streptomyces sp.

Four new polyketides, named rubiginone D2 (2), 4-O-acetyl-rubiginone D2 (3), rubiginone H (6) and rubiginone I (7) were isolated from the cultures of Streptomyces sp. (strain Gö N1/5). Their structures were established by a detailed spectroscopic analysis. The absolute configuration of 3 was determined by derivatization with chiral acids (Helmchen's method). The rubiginones inhibit the growth of some Gram-positive bacteria and are cytostatically active against different tumor cell lines.

Cineromycins, gamma-butyrolactones and ansamycins by analysis of the secondary metabolite pattern created by a single strain of Streptomyces.

The antifungal and antibacterial properties of the crude extract from Streptomyces sp. (strain Gö 40/10) encouraged us to perform a detailed analysis of its secondary metabolite pattern by chemical screening, which revealed the presence of at least 30 different compounds. Ten of the isolated 18 metabolites proved to be new. Remarkable are hydrogenated (3, 4) and glucosylated (5, 6, 7) 14-membered macrolides derived from cineromycin B, two gamma-butyrolactones (8, 9), the so far unknown naphthomycin K (14) and the collinolactones A and B. The constitution and relative stereochemistry of these metabolites were deduced from spectroscopic data. Finally the concept of our one strain/many compounds (OSMAC) method for exploring new microbial secondary metabolites is discussed.

The structure of manumycin. III. Absolute configuration and conformational studies.

Chromic acid oxidation of manumycin (1), an antibiotic produced by Streptomyces parvulus (strain Tü 64), led to the isolation of 2-(2-methyl-4-oxo-2-pentenoylamino)-5,6-epoxy-1,4-benzoquinone (3) and (-)-(R)-2-methylhexanoic acid (4). From the absolute configuration of 4, determined by comparing its optical rotation with published data, follows the absolute configuration at the center of chirality in the diene side chain of manumycin (1) to be (6'R). Based on the direct comparison of the CD spectra of the two chromic acid oxidation products 2 and 3 with those of the antibiotic G7063-2 (5) and (-)-terreic acid (6) the stereochemistry at C-5 and C-6 of 1 was determined as (5R, 6S). From the negative CD-couplet of manumycin (1) its stereochemistry at C-4 was assigned as (4R).

Metabolic products of microorganisms. 234. Urdamycins, new angucycline antibiotics from Streptomyces fradiae. I. Isolation, characterization and biological properties.

The colored urdamycins A to F, six new angucycline antibiotics produced by Streptomyces fradiae strain Tü 2717, were detected by chemical screening. They are biologically active against Gram-positive bacteria and stem cells of murine L1210 leukemia. The urdamycins are glycosides and differ in their aglycones, which can be liberated by acidic hydrolysis besides the sugars D-olivose and L-rhodinose. The structure of the main compound, urdamycin A, follows from the spectroscopic and chemical data in connection with an X-ray analysis. The aglycone urdamycinone A is identical with aquayamycin. The structures of urdamycin B, E, F and partial structures of urdamycin C and D, will be presented in a subsequent paper. The new term "angucycline/angucyclinone" is used for an increasing group of related antibiotics.