Non-convulsive status epilepticus of frontal origin in mucopolysaccharidosis type II successfully treated with ethosuximide

At 7 years of age, a female with mucopolysaccharidosis type II (MPS II) showed a sudden deterioration in neurological function, a sleep disorder, and progressive behavioural impairment. Electroencephalography was performed 1 year and 8 months after the onset of the neurological regression and revealed continuous ictal activity in the frontal regions. The female was diagnosed as having frontal non‐convulsive status epilepticus. After 5 weeks of therapy with ethosuximide, the ictal electroencephalographic activity disappeared. At the same time, her sleep and cognitive and behavioural functions were observed to improve. This is the first case of MPS type II reported in an individual with non‐convulsive status epilepticus. Two main forms of MPS II can be recognized: attenuated and severe. Severe MPS II is characterized by neurodegeneration. No study has explored the relationship between epilepsy and neurological deterioration in MPS II. Our observation shows that epilepsy may be a treatable cause of neurological regression in individuals with MPS II.     

Increased inflammation in mice deficient for the chemokine decoy receptor D6

Chemokines are chemotactic cytokines with a key role in the control of cell trafficking and positioning under homeostatic and inflammatory conditions. D6 is a promiscuous 7-transmembrane-domain receptor expressed on lymphatic vessels which recognizes most inflammatory, but not homeostatic, CC chemokines. In vitro experiments demonstrated that D6 is unable to signal after ligand engagement, and it is structurally adapted to sustain rapid and efficient ligand internalization and degradation. These unique functional properties lead to the hypothesis that D6 may be involved in the control of inflammation by acting as a decoy and scavenger receptor for inflammatory chemokines. Consistent with this hypothesis, here we report that D6(-/-) mice showed an anticipated and exacerbated inflammatory response in a model of skin inflammation. Moreover, the absence of D6 resulted in increase cellularity and inflammatory-chemokine levels in draining lymph nodes. Thus, D6 is a decoy receptor structurally adapted and strategically located to tune tissue inflammation and control transfer of inflammatory chemokines to draining lymph nodes.     

Antibiofilm activity of sandblasted and laser-modified titanium against microorganisms isolated from peri-implantitis lesions

Infections due to biofilm-producing microorganisms are one of the main causes for the failure of dental implants. Increasing efforts have been made in order to develop new strategies to prevent biofilm formation. In this study, the biofilm development on a newly designed laser-modified titanium implant surface was evaluated and compared to that on conventional sandblasted titanium used in implant dentistry. The amount of biofilm produced by Staphylococcus aureus, Pseudomonas aeruginosa and Porphyromonas gingivalis isolated from peri-implantitis was assessed by a semi-quantitative spectrophotometric method and by confocal laser scanning microscopy. Results showed a lower biofilm production on laser-modified surface compared to the sandblasted one. In particular, a significantly lower total volume of the biomass was observed on laser-modified surface, while no significant changes in live/dead bacteria percentages were noticed between materials. Modifying the topography of the conventional implant surface with laser ablation could represent a promising approach for inhibiting biofilm formation.     

Long-term effects of memory training in the elderly: a longitudinal study

The effects of different types of memory training in young and older adults reported in a previous study [Cavallini, E., Pagnin, A., Vecchi, T., 2003. Aging and everyday memory: the beneficial effect of memory training. Arch. Gerontol. Geriatr. 37, 241-257] were again investigated from a longitudinal perspective 2 years after the original memory training sessions. The authors retested the original participants to measure the long-term effectiveness of two mnemonic strategies: the loci technique and strategic training. Three groups of participants (13 adults, M=24.1, 13 younger elderly, M=64.2 and 13 older elderly, M=74.4) were tested using a battery of seven tasks and four questionnaires, to evaluate memory performance and metamemory variables. The three age groups and the two trainings showed similar results on memory performance. Long-term effects were found only on two memory tasks, both were highly related to everyday life showing that, without additional practice, memory performance tended to go back to the original level. Moreover, the beneficial effects of the previous training sessions were particularly evident for older adults in metamemory knowledge and for strategic training in memory complaints. Results partially support the durability of memory training in improving memory performance.     

Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis.

BACKGROUND & AIMS: The role of the interleukin (IL)-1 receptor antagonist (IL-1ra) in predisposing an individual to inflammatory bowel disease (IBD) is controversial. This study aimed to determine the association between intron 2 IL-1ra polymorphism and IBD by performing a multiethnic case-control study and to assess its functional significance. METHODS: A total of 236 patients with ulcerative colitis (UC), 196 patients with Crohn's disease (CD), and 338 ethnically matched control patients treated at LAC-USC and Cedars-Sinai Medical Centers and the University of Milan Medical Center were genotyped for a variable length polymorphism in intron 2 of the IL-1ra gene (IL-1RN). Total IL-1ra protein production rates in peripheral blood mononuclear cells (PBMCs) were correlated with carriage of allele 2 of the IL-1RN gene (IL-1RN*2). RESULTS: In the LAC-USC group, UC patients (n = 60) had an increased frequency of at least 1 copy of IL-1RN*2 compared with controls (n = 129) (70% vs. 33%; P < 0.01; odds ratio [OR], 4.7). The frequency of IL-1RN*2 carriage in the Cedars-Sinai group was 59% in UC, 45% in CD, and 42% in controls (P < 0.01; OR, 2.0). A significant difference was observed only in the Jewish subgroup (P = 0.003; OR, 5.0). The association was not detected in UC or CD patients treated at the University of Milan. The ORs of 4.7 and 5.0 appear to be the highest reported in any UC population for any genetic markers. Further, carriage of IL-1RN*2 was associated with decreased production of total IL-1ra protein in cultured PBMCs from both UC patients and controls. CONCLUSIONS: These results provide further evidence that IL-1ra is important in the predisposition to UC, there may be genetic or pathogenetic heterogeneity between different ethnic groups, and UC and CD are genetically distinct diseases.     

The role of chemokines in the regulation of dendritic cell trafficking.

The immunobiology of dendritic cells (DC) involves localization in tissues and trafficking via the lymph or blood to lymphoid organs. Appropriate assays representative of different steps of DC trafficking (e.g., reverse transmigration) provide the tools to dissect the migratory properties of these cells. Chemokines have emerged as important regulators of DC migration. DC are both the target and the source of chemokines. DC express receptors for and respond to a set of chemoattractants that overlap with, but are distinct from, those active on other leukocytes. Differential expression of the CCR6 receptor reveals heterogeneity among DC populations. Functional maturation is associated with loss of responsiveness to chemokines present at sites of inflammation and acquisition of a receptor repertoire that renders these cells responsive to signals that guide their localization in lymphoid organs. A better understanding of the molecular basis of DC trafficking may provide molecular and conceptual tools to direct and modulate DC traffic as a strategy to up-regulate and orient specific immunity.     

Anti-laminin auto antibodies in ANCA-associated vasculitis.

BACKGROUND: Endothelial cell damage occurs during vasculitic processes in vivo. With the alteration of the endothelium, exposure to basement membrane components may occur with induction of humoral immunity. METHODS: In the present study, we evaluated the prevalence of antibodies against the basement membrane antigen laminin (LMN) in patients with ANCA-associated systemic vasculitis (AASV), pathologic controls (systemic lupus erythematosus, mixed cryoglobulinaemia, Henoch-Sch?nlein purpura, primary glomerulonephritis) and normal individuals. RESULTS: By ELISA, 21.6% of AASV (16/74) and 10% of pathologic controls (3/30), but only one of the normal controls (2. 8%) had these antibodies (P=0.02). When AASV patients were divided into two groups according to diagnosis and ANCA antigen specificity, antibodies to LMN were found in 27.5% of MPO-ANCA positive microscopic polyangiitis patients (11/40) vs. only 14.7% of PR3-ANCA positive Wegener granulomatosis patients (5/34). There was no correlation between the presence or titre of anti-LMN antibodies and the main clinical and laboratory parameters. CONCLUSION: These results indicate that basement membrane antigens may become immunogenic in patients with AASV, especially in those with MPO-ANCA positivity. These antibodies are most likely the result of endothelial damage secondary to the initial inflammatory process but may well perpetuate further vascular damage in some patients.