A low inflammatory, Langerhans cell-targeted microprojection patch to deliver ovalbumin to the epidermis of mouse skin

In a low inflammatory skin environment, Langerhans cells (LCs) - but not dermal dendritic cells (dDCs) - contribute to the pivotal process of tolerance induction. Thus LCs are a target for specific-tolerance therapies. LCs reside just below the stratum corneum, within the skin's viable epidermis. One way to precisely deliver immunotherapies to LCs while remaining minimally invasive is with a skin delivery device such as a microprojection arrays (MPA). Today's MPAs currently achieve rapid delivery (e.g. within minutes of application), but are focussed primarily at delivery of therapeutics to the dermis, deeper within the skin. Indeed, no MPA currently delivers specifically to the epidermal LCs of mouse skin. Without any convenient, pre-clinical device available, advancement of LC-targeted therapies has been limited. In this study, we designed and tested a novel MPA that delivers ovalbumin to the mouse epidermis (eMPA) while maintaining a low, local inflammatory response (as defined by low erythema after 24 h). In comparison to available dermal-targeted MPAs (dMPA), only eMPAs with larger projection tip surface areas achieved shallow epidermal penetration at a low application energy. The eMPA characterised here induced significantly less erythema after 24 h (p = 0.0004), less epidermal swelling after 72 h (p

GATA3 haploinsufficiency causes a rapid deterioration of distortion product otoacoustic emissions (DPOAEs) in mice

Human HDR (hypoparathyroidism, deafness and renal dysplasia)-syndrome is caused by haploinsufficiency of zinc-finger transcription factor GATA3. The hearing loss due to GATA3 haploinsufficiency has been shown to be peripheral in origin, but it is unclear to what extent potential aberrations in the outer hair cells (OHCs) contribute to this disorder. To further elucidate the pathophysiological mechanism underlying the hearing defect in HDR-syndrome, we investigated the OHCs in heterozygous Gata3-knockout mice at both the functional and morphological level. While the signal-to-noise ratios of distortion product otoacoustic emissions (DPOAE) in wild type mice did not change significantly during the first half-year of live, those in the heterozygous Gata3 mice decreased dramatically. In addition, both light microscopic and transmission electron microscopic analyses showed that the number of OHCs containing vacuoles was increased in the mutants. Together, these findings indicate that outer hair cell malfunctioning plays a major role in the hearing loss in HDR-syndrome

Roken tijdens de zwangerschap: Trends in de periode 2001-2010

Doel. Het vaststellen van trends in de rookprevalentie onder zwangeren in de periode 2001-2010 en deze prevalentie relateren aan verschillen naar opleidingsniveau. Opzet. Beschrijvend; landelijke peilingen. Methode. In 2001, 2002, 2003, 2005, 2007 en 2010 werden via organisaties voor jeugdgezondheidszorg tijdens het periodiek gezondheidsonderzoek 28.720 vragenlijsten uitgedeeld aan moeders van kinderen ≤ 6 maanden. In totaal vulden 16.358 moeders (57%) de vragenlijst in. Resultaten. In de periode 2001-2010 is het aantal zwangeren dat rookte tijdens de zwangerschap gehalveerd (p < 0,001). In 2010 rookte 6,3% (95%-BI: 5,0-7,6) van de zwangeren dagelijks gedurende de hele zwangerschap. De rookprevalentie was het hoogst onder laagopgeleide zwangeren (13,8% in 2010; 95%-BI: 9,3-18,4) en het laagst onder hoogopgeleiden (2,4% in 2010; 95%-BI: 1,2-3,6). Tijdens de zwangerschap stopte 4% van de rokende vrouwen. De mediaan van het aantal gedurende de zwangerschap gerookte sigaretten was 5 per dag, tegenover 10 in het laatste half jaar vóór de zwangerschap. In 2001 was de het verschil in rookprevalentie tussen laag- en hoogopgeleide zwangeren 18,9%, in 2010 was dat 11,4%. Het verschil tussen middelbaar- en hoogopgeleide zwangeren was 6,5 en 5,4% in respectievelijk 2001 en 2010. Conclusie. Het percentage vrouwen dat gedurende de gehele zwangerschap rookt is tussen 2001 en 2010 gehalveerd, maar in 2010 rookte nog steeds 6,3% van de zwangeren. De rookprevalentie verschilde sterk tussen de opleidingsniveaus; de absolute verschillen veranderden niet gedurende het onderzoek

Precursor B-cell development in bone marrow of Good syndrome patients

Good syndrome is an immunodeficiency presenting with thymoma, hypogammaglobulinemia and almost absent B cells. To investigate the origin of the B-cell lymphopenia in these patients, we studied B cell differentiation in the bone marrow of Good syndrome patients. We found very low numbers of precursor B cells in bone marrow of Good syndrome patients and a differentiation arrest after the pro-B-cell stage; this is different from other agammaglobulinemia patients with a defect in pre B-cell receptor signaling

Autofluorescent flavoprotein imaging of spinal nociceptive activity

Pain arises from activation of peripheral nociceptors, and strong noxious stimuli may cause an increase in spinal excitability called central sensitization, which is likely involved in many pathological pain states. So far, it has not been achieved to simultaneously visualize in vivo both the temporal and spatial aspects of spinal activity, including central sensitization. Using autofluorescent flavoprotein imaging (AFI), an optical technique suitable for mapping activity in nervous tissue, we demonstrate a close temporal and spatial correlation of electrically evoked nociceptive input with the spinal AFI signal, representing spinal neuronal activity. The AFI signal increases linearly with stimulation intensity. Furthermore, we found that the AFI signal was much larger in intensity and size when the same electrical stimulation was applied after the induction of central sensitization by a subcutaneous capsaicin injection. Finally, innocuous palpation of the hindpaw did not evoke an AFI response in naive animals, but after capsaicin injection a strong response was obtained. This is the first report demonstrating simultaneously the temporal and spatial propagation of spinal nociceptive activity in vivo. Copyrigh