Reduction in grey matter volume and its correlation with clinical symptoms in Chinese boys with low functioning autism spectrum disorder.

BACKGROUND: Previous studies have reported changes within grey matter (GM) volume in children with autism spectrum disorder (ASD); however, little is known about GM volume changes and the relation with symptom severity in Chinese boys with low functioning autism spectrum disorder (LFASD). METHOD: GM volume was analysed using SPM 8 and compared between 16 boys with LFASD as well as 16 typically developing (TD) boys (using REST 1.8). Additionally, the correlation between GM volume and clinical symptoms was analysed, using subscales within the Autism Behaviour Checklist (ABC). RESULTS: The comparison showed a reduced volume of GM in 11 clusters in the boys with LFASD (i.e., the left inferior frontal gyrus, orbital part; right superior temporal gyrus, superior frontal gyrus, dorsolateral; precuneus and postcentral; bilateral rectus and middle temporal gyrus) and 1 area with increased GM volume (right caudate) compared to the TD group. Additionally, the GM volume of the left inferior frontal gyrus, orbital part was negatively correlated with the Social subscale score of the ABC (r = -0.765, P = 0.002), and the GM volume of the left Rectus was negatively associated with the Language, Body concept and Self-care subscale scores and the total score on the ABC(r = -0.624, P = 0.023; r = -0.657, P = 0.011; r = -0.618, P = 0.025; r = -0.625, P = 0.022). Further, the GM volume of the right Caudate was negatively correlated with the Sensory subscale on the ABC (r = -0.593, P = 0.033). CONCLUSION: In conclusion, the current study's findings display that the GM volume was widely reduced in Chinese boys with LFASD compared to TD boys and negatively correlated with the clinical symptoms, indicating a possible pathological mechanism of LFASD.

Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis.

BACKGROUND: The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD). H4R antagonists have already been tested in several animal models of AD, but these studies have yielded conflicting results. MATERIAL AND METHODS: The development of ovalbumin-induced AD-like skin lesions was analysed in H4R(-/-) mice and in H4R antagonist (JNJ28307474)-treated mice. RESULTS: H4R(-/-) mice showed a clear amelioration of the skin lesions, with a diminished influx of inflammatory cells and a reduced epidermal hyperproliferation at lesional skin sites. H4R(-/-) mice had a reduced amount of ovalbumin-specific IgE, a reduced number of splenocytes and lymph node cells with a decreased number of CD4+ T cells. The H4R modulated the cytokine secretion of CD4+ T cells and splenocytes and altered the cellular profile in the lymph nodes. The anti-inflammatory effect could only partially be mimicked by JNJ28307474 and only when the H4R antagonist was given during sensitization and challenge and not when JNJ28307474 was only given during the provocation phase of the allergic reaction. CONCLUSION: The H4R modulates inflammation in a chronic allergic dermatitis setting. However, results of this study indicate that it is necessary to block the H4R during ontogeny and development of the allergic inflammation.

Histamine H1, H3 and H4 receptors are involved in pruritus.

Histamine has long been recognised as a classical inducer of pruritus. However, the specific mechanism of histamine-induced itch has still not been fully understood. The H1 and H4 receptor appear to be key components in the induction of itch. The specific role of the H3 receptor in histamine-induced itch remains unclear. The aim of our study was to investigate the role of the four known histamine receptors (H1-4) in acute itch in mice. Intradermal injection of the selective H3R inverse agonist pitolisant induced strong itch in mice. Pitolisant (50 nmol/injection)-induced pruritus could be completely blocked by a combined treatment with the H1R antagonist cetirizine (15 mg/kg) and the H4R antagonist JNJ 7777120 (15 mg/kg), whereas the H2R antagonist ranitidine (15 mg/kg) failed to inhibit the scratch response. Next, expression and function of histamine receptors on sensory neurons isolated from dorsal root ganglia of mice were investigated. As the itch sensation results from the excitation of sensory nerves in the skin, we further focused on skin specific sensory neurons. Therefore, neurons were retrograde labelled from the skin by means of a fluorescent tracer. Expression of H1R, H3R and H4R on skin innervating sensory neurons was detected. By single-cell calcium imaging, it was demonstrated that histamine induces a calcium increase in a subset of (skin-specific) sensory neurons via activation of the H1R and H4R as well as inhibition of the H3R. It is assumed that the decreased threshold in response to H3R antagonism activates H1R and H4R on sensory neurons, which in turn results in the excitation of histamine-sensitive afferents and therefore elicits the sensation of itch.

Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function.

BACKGROUND: Histamine is an important mediator of allergic reactions, and recent studies indicated that the function of different types of antigen presenting cells (APC) can be modulated by histamine, in particular via the newly described histamine H(4) receptor (H(4)R). Therefore, we investigated possible interactions of histamine via the H(4)R on Langerhans cells (LC), which represent the professional APC in the skin and therefore have an important role in the initiation and maintenance of allergic skin diseases. METHODS: The expression of the H(4)R was evaluated by real-time PCR, flow cytometry and immunofluorescence staining. The function of the H(4)R was determined by intracellular flow cytometric measurement of chemokine production and LC migration assays. RESULTS: Here, we show H(4)R expression on in vitro generated monocyte-derived LC (mRNA and protein) and on primary LC from murine and human skin samples (protein). The immunofluorescence staining in murine and human skin samples clearly proved that LC express the H(4)R in situ. Stimulation with histamine or a H(4)R agonist downregulated the chemokine (C-C motif) ligand 2 (CCL2) in human monocyte-derived LC and primary LC. Prestimulation with a selective H(4)R antagonist abolished this effect. Moreover, migration of LC from the epidermis was increased after H(4)R agonist stimulation in ex vivo migration assays using human epidermis and murine in vivo assays. CONCLUSION: Our findings show that LC express a functional H(4)R and point towards a possible pathogenic relevance of the H(4)R in inflammatory and allergic diseases.

Bone-dust in autopsies: reduction of spreading.

During autopsies, an open oscillating saw produces large quantities of respirable bone-dust, which is able to carry microbes over several metres. Experiments were done using a modified (open) undulation saw (spray tube to moisten the saw-blade with water). Saw-dust was asservated with culture media. Colonies were identified macroscopically. Microbes in the air were quantified (per unit of time). A remarkable reduction of saw-dust is done by an integrated spray tube using water. There remains a contamination at the head of the autopsy table in the level of the table top. We found a complete decontamination 150 cm above the floor. No spreading of particles carrying microbes was seen over distances of more than 1.5 m. The risk of an airborne infection is minimal when using a manual saw (absence of grinding-dust). The modified type of an 'oscillating saw with a spray-tube' may be considered a practicable compromise between a manual saw and an unprotected undulation saw. It is necessary to complete the precautions against airborne infections by breath masks and safety-goggles.