Contextual emotion-regulation therapy for childhood depression: description and pilot testing of a new intervention

OBJECTIVE: To pilot test the acceptability and efficacy of contextual emotion-regulation therapy (CERT), a new, developmentally appropriate intervention for childhood depression, which focuses on the self-regulation of dysphoria. METHOD: Two samples of convenience (n = 29, n = 2) served to verify some CERT constructs; it was then operationalized in a treatment manual. To pilot test CERT, 20 children (ages 7-12; 35% girls) with DSM dysthymic disorder (mean duration 24.4 months) entered an open, 30-session, 10-month, 4-phase trial, with 6- and 12-month follow-up. Assessments included independent clinical evaluations and self-rated questionnaires. RESULTS: Fifteen children completed theraphy, four were administratively terminated and one dropped out. Completers did not clinically differ from the rest, but they were more likely to have better educated and less depressed mothers and intact families. At the end of treatment, 53% of the completers had full and 13% partial remission of dysthymia (remission from superimposed major depression was 80%). By 6- and 12-month follow-up, 79% and 92% had full remission of dysthymia (p < 0.0001). Self-reported depressive and anxiety symptoms significantly declined by the end of treatment (p < .001) and remained so throughout follow-up. CONCLUSIONS: CERT enables clinicians to "match" the intervention to children's emotion regulatory needs and symptoms and was readily accepted by families. The promising results suggest the need for a randomized trial.     

Presenilin 1 forms aggresomal deposits in response to heat shock

Aggresomes have been described as cytoplasmic membrane protein aggregates that are induced by proteasome inhibition or overexpression of certain proteins. Here, we characterized aggresomes formed by the Alzheimer's disease-associated presenilin 1 (PS1) protein. Proteasome inhibition induced accumulation of PS1 in the endoplasmic reticulum (ER) and retrotranslocation of the protein from the ER membrane into the cytoplasm. Aggresomes formed by PS1 modified the ER structure whereas proteasomes were inhibited. Therefore, clear visual identification of PS1 aggresomes required removal of the proteasome inhibitor followed by hours of recovery to redistribute the ER throughout the cells. Aggresomes formed by PS1 did not potentiate or attenuate apoptotic cell death induced by staurosporine treatment. Selective presence of the heat-shock proteins Hsp70 and HDJ-2/HSDJ, but not Hsp90, in aggresomes suggested chaperone-mediated transport of PS1 into these structures. Because proteasome inhibition and heat shock are both known to induce expression of heat shock proteins, we also demonstrated that heat shock alone was sufficient to induce PS1 aggresome formation and Hsp70 expression. These results indicate that aggresome formation by PS1 is chaperone-mediated and can be induced in response to heat-shock stress, a common cellular event in neurodegenerative diseases. Malfunctioning of the proteasome or heat-shock stress response in the brains of patients affected by Alzheimer's disease may lead to the accumulation of stable aggresomes of PS1, perhaps contributing to neurodegeneration.     

Amygdalohippocampal involvement in tinnitus and auditory memory

CONCLUSION: The preliminary results suggest that in chronic unilateral tinnitus the contralateral amygdalohippocampal complex does seem to be involved in tinnitus perception of pure tones. OBJECTIVES: Functional neuroimaging studies have revealed that the hippocampus and amygdala are involved in tinnitus perception. The amygdala and hippocampus are supplied by the anterior choroidal artery. Selective amobarbital injections in the anterior choroidal artery result in a non-functional amygdalohippocampal area for 10 min. The aim of this study was to assess the influence of this procedure on tinnitus perception. PATIENTS AND METHODS: Amobarbital (80 mg in total) was injected selectively in two sessions in the left and right anterior choroidal artery in six male patients with tinnitus: four with unilateral tinnitus, two with bilateral tinnitus. Of the patients with unilateral tinnitus, three had right-sided tinnitus and one had left-sided tinnitus. The average age was 57.3 years (range 43-69). Average tinnitus duration was 5.3 years (range 1-10). The differences in visual analogue scale (VAS) scores before and after the amytal tests were analysed. RESULTS: Amytal injection ipsilateral to the side where the tinnitus was perceived resulted in a maximum of 30% tinnitus suppression, whereas amytal injection contralateral to the tinnitus side yielded a 60-70% tinnitus suppression in three patients with unilateral chronic tinnitus (>4 years). Only pure tone tinnitus was suppressed, white noise was not. Two patients with bilateral tinnitus had no suppression, irrespective of the tinnitus type. A third patient without clinical tinnitus suppression had tinnitus of more recent origin (1.5 years).     

Continuous versus intermittent levofloxacin treatment in complicated urinary tract infections caused by urinary obstruction temporarily relieved by foreign body insertion

This study was one of the first to examine the in vivo levofloxacin adsorption to stent surfaces. The results demonstrated the ability of this antibiotic to adsorb to the conditioning film and to the surface of the inserted device, and showed that 1-2 weeks after the discontinuation of antibiotic administration some amount of the antibiotic still could be detected on them. The second aim of the investigation was to determine whether continuous or intermittent levofloxacin treatment is advantageous for the patients who have acute complicated urinary tract infection (UTI) caused by urinary obstruction. The results did not show any clinical or microbiological advantages of the continuous therapy.     

Critical role of PI3-kinase/Akt activation in the PARP inhibitor induced heart function recovery during ischemia-reperfusion

Poly(ADP-ribose) polymerase (PARP) inhibitors protect hearts from ischemia-reperfusion (IR)-induced damages by limiting nicotinamide adenine dinucleotide (NAD+) and ATP depletion, and by other, not yet elucidated mechanisms. Our preliminary data suggested that PARP catalyzed ADP-ribosylations may affect signaling pathways in cardiomyocytes. To clarify this possibility, we studied the effect of a well-characterized (4-hydroxyquinazoline) and a novel (carboxaminobenzimidazol-derivative) PARP inhibitor on the activation of phosphatidylinositol-3-kinase (PI3-kinase)/Akt pathway in Langendorff-perfused hearts. PARP inhibitors promoted the restoration of myocardial energy metabolism (assessed by 31P nuclear magnetic resonance spectroscopy) and cardiac function compared to untreated hearts. PARP inhibitors also attenuated the infarct size and reduced the IR-induced lipid peroxidation, protein oxidation and total peroxide concentration. Moreover, PARP inhibitors facilitated Akt phosphorylation and activation, as well as the phosphorylation of its downstream target glycogen synthase kinase-3beta (GSK-3beta) in normoxia and, more robustly, during IR. Blocking PI3-kinase by wortmannin or LY294002 reduced the PARP inhibitor-elicited robust Akt and GSK-3beta phosphorylation upon ischemia-reperfusion, and significantly diminished the recovery of ATP and creatine phosphate showing the importance of Akt activation in the recovery of energy metabolism. In addition, inhibition of PI3-kinase/Akt pathway decreased the protective effect of PARP inhibitors on infarct size and the recovery of heart functions. All these data suggest that contrary to the original view, which considered preservation of NAD+ and consequently ATP pools as the exclusive underlying mechanism for the cytoprotective effect of PARP inhibitors, the activation of PI3-kinase/Akt pathway and related processes are at least equally important in the cardioprotective effects of PARP inhibitors during ischemia-reperfusion.     

Interleukin-4 treatment restores cellular immunity after ethanol exposure and burn injury

BACKGROUND: Previous studies from this laboratory showed that the suppression of cell-mediated immunity after the combined injury of ethanol exposure and burn is mediated by increased presence of the proinflammatory cytokine interleukin (IL)-6. IL-4 is a T-helper cell type 2 lymphocyte-derived cytokine that serves to down-regulate the inflammatory response. Therefore, the goal of this study was to evaluate the effects of ethanol exposure and burn injury on lymphocyte production of IL-4 and to determine whether administration of IL-4 could improve cellular immunity after ethanol exposure and burn injury through modulation of IL-6 levels. METHODS: Mice were subjected to a 15% total body-surface area burn (or sham) injury 30 min after being given a single dose of alcohol (or saline) designed to achieve a blood alcohol level of 100 mg/dl. Thirty minutes after burn, mice were treated with IL-4 (or vehicle) and were killed 24 hr later. RESULTS: Lymphocytes from ethanol/burn mice secreted significantly less IL-4 in comparison to all other groups of mice (p < 0.05). Administration of IL-4 resulted in a complete restoration of the delayed-type hypersensitivity (p < 0.01) and splenocyte proliferative responses (p < 0.05) and a significant reduction in circulating and splenic macrophage-derived IL-6 (p < 0.05). Addition of IL-4 (100 or 300 pg/ml) to cultures generated from ethanol/burn and vehicle mice resulted in a complete restoration of splenocyte proliferation and a concomitant attenuation of macrophage IL-6 production. CONCLUSIONS: These studies suggest that the loss of lymphocyte production of IL-4 after ethanol exposure and burn injury may contribute to the exaggerated production of IL-6, a known mediator of immune suppression after injury. Moreover, the administration of IL-4 may be beneficial for patients with injuries that are characterized by a dysregulated inflammatory response.     

Ganglion cells in the posterior pituitary: result of ectopia or transdifferentiation?

Histologic examination revealed large ganglion cells within the posterior pituitary of an 80-year-old woman who died of myocardial infarction. Apparently fully mature, the cells were an incidental finding scattered within hyperplastic foci of pars intermedia (PI)-derived cells (basophil invasion) on histologic examination of the pituitary obtained at autopsy. Immunocytochemistry showed staining reactivity for neuron-specific enolase, synaptophysin, alpha subunit of the glycoprotein hormones and beta-endorphin. The presence of these ganglion cells with features similar to those of magnocellular hypothalamic neurons could be considered the result of abnormal migration during the early phase of embryonic life, or differentiation/maturation of neuroblasts, presumed to occur in the embryonic neurohypophysis. Alternatively, transdifferentiation from proliferating PI cells may explain the emergence of neurons; a hypothesis supported by the proximity and shared alpha subunit, and beta-endorphin immunoreactivities of the two cell types. Received: 31 August 1999 / Accepted: 12 October 1999