Olanzapine therapy in anorexia nervosa: psychobiological effects

Dopamine impairments occur in anorexia nervosa. The aim of this study was to see whether treatment with the atypical dopamine antagonist antipsychotic olanzapine improves the disorder. Thirty anorexics, 18 restricted and 12 bingeing-purging, underwent a 3-month course of cognitive behavioral therapy, plus at random and double-blinded oral olanzapine (2.5 mg for 1 month, 5 mg for 2 months) in half and oral placebo in the other half of them. BMI, psychopathological aspects (eating disorder inventory, Hamilton Rating Scale, Buss-Durkee Rating Scale, Yale Brown Cornell for Eating Disorders Rating Scale, temperament-character inventory), and homovanillic acid blood concentrations for dopamine secretion, were monitored at baseline and then monthly during the trial. At the end of the trial BMI, total eating disorder inventory, total Yale Brown Cornell for Eating Disorders Rating Scale, Buss-Durkee Rating Scale, Hamilton Rating Scale scores and in olanzapine-treated patients the subitems of eating disorder inventory ineffectiveness and maturity fear, of Buss-Durkee Rating Scale direct aggressiveness, of temperament-characteristic inventory persistence had improved significantly. When stratified for anorexia nervosa subtype, BMI changes were significant among anorexia nervosa bingeing-purging patient, 'depression' (Hamilton Rating Scale) and 'direct aggressiveness' (Buss-Durkee Rating Scale) among anorexia nervosa bingeing-purging patients, 'persistence' (temprerament-characteristic inventory), among anorexics restricted patients, with a trend toward significance for obsessivity-compulsivity (Yale Brown Cornell for Eating Disorders Rating Scale). homovanilic acid blood levels increased significantly in the cognitive behavioral therapy+olanzapine group. No correlations were observed between homovanilic acid concentrations and psychopathological parameters. The pharmacological treatment can significantly improve specific aspects of anorexia nervosa.     

Experimental phage therapy against Staphylococcus aureus in mice

The present study describes a bacteriophage (M(Sa)) active against Staphylococcus aureus, including methicillin-resistant staphylococcal strains. When inoculated into mice simultaneously with S. aureus A170 (10(8) CFU/mouse), phage (10(9) PFU) rescued 97% of the mice; when applied to nonlethal (5 x 10(6) CFU/mouse) 10-day infections, the phage also fully cleared the bacteria. The phage M(Sa), delivered inside macrophages by S. aureus, kills the intracellular staphylococci in vivo and in vitro. The phage can also prevent abscess formation and reduce the bacterial load and weight of abscesses. These results suggest a potential use of the phage for the control of both local and systemic human S. aureus infections.     

fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis

Functional magnetic resonance imaging (fMRI) data on motor function have shown adaptive functional changes related to brain injury in multiple sclerosis (MS). We investigated whether patients with MS have altered fMRI activation patterns during attention and memory tasks, and whether functional changes in the brain correlate with the extent of overall tissue damage on conventional MRI. Twenty-two right-handed patients with relapsing-remitting MS (RRMS) and no or only mild deficits at neuropsychological testing and 22 matched healthy subjects were scanned during the Paced Auditory Serial Addition Test (PASAT) and a recall task. fMRI data were analyzed using Statistical Parametric Mapping (SPM99). The relation between fMRI changes during both tasks and T2 lesion load was investigated. During both tasks, patients exhibited significantly greater brain activation than controls and recruited additional brain areas. Task-related functional changes were more significant in patients whose performance matched that of controls than in patients with a lower performance. During the PASAT, brain functional changes involved the right supplementary motor area and cingulate, the bilateral prefrontal, temporal and parietal areas, whereas during the recall task they involved the prefrontal and temporal cortex and basal ganglia bilaterally, and the left thalamus. In patients, activation in specific brain areas during performance of both tasks positively correlated with T2 brain lesions. Patients with RRMS exhibit altered patterns of activation during tasks exploring sustained attention, information processing and memory. During these tasks, fMRI activity is greater in patients with better cognitive function than in those with lower cognitive function. Functional changes in specific brain areas increase with increasing tissue damage suggesting that they may also represent adaptive mechanisms that reflect underlying neural disorganization or disinhibition, possibly associated with MS.     

Heterogeneity in responses by primary adult human colonic epithelial cells to purified enterotoxin of Bacteroides fragilis

Background—Enterotoxigenic strains ofBacteroides fragilis (ETBF) have been implicated indiarrhoeal illness in livestock and children, but their role in adulthuman colonic disease is unknown.
Aims—To investigate responses by primary adulthuman colonic epithelial cells to purified B fragilistoxin (BFT).
Methods—BFT was purified from culture supernatantof a highly toxigenic strain of ETBF. Morphological changes to primarycolonic epithelial cells, in response to purified BFT, were studied in organ culture of colonic biopsy specimens from 15adults.
Results—BFT induced epithelial cell cytotoxicityin colonic biopsy specimens from 12/15 subjects. The BFT inducedmorphological changes were characterised by epithelial cell rounding,separation from adjacent cells, and detachment from the basementmembrane. In severely affected specimens, almost all the epithelialcells were affected. There was heterogeneity between subjects in the rate at which BFT induced epithelial cell cytotoxicity occurred. Furthermore, in colonic biopsy specimens from three subjects, exposureto BFT did not induce any significant morphological changes toepithelial cells.
Conclusion—BFT is capable of inducingcytotoxicity in primary adult human colonic epithelial cells. Such aneffect of ETBF derived BFT on epithelial cells in the colon in vivowould be expected to lead to mucosal inflammation and diarrhoea.Heterogeneity in responses by primary colonocytes probably reflects theoutcome of host-BFT interactions. Such interactions in vivo coulddetermine the occurrence of colonic disease in some individuals but not others.

Keywords:Bacteroides fragilis; enterotoxin; epithelial cells; apoptosis

     

Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology

Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes.