3D‐printed Franz type diffusion cells

Abstract

Objective

Franz cells are routinely used to measure in vitro skin permeation of actives and must be inert to the permeant under study. The aim of the present work was to develop and manufacture transparent Franz‐type diffusion cells using 3D printing and test these using a range of model active compounds. The study also aims to identify the critical 3D printing parameters necessary for the process including object design, choice of printing resin, printout curing and post‐curing settings and introduction of model coatings.

Methods

Transparent Franz cells were constructed using an online computer aided design program and reproduced with different stereolithography 3D printers. The two acrylate‐based resins used for the fabrication process were a commercially available product and a polymer synthesised in‐house. Comparative studies between glass and 3D printed Franz cells were conducted with selected model actives: terbinafine hydrochloride (TBF), niacinamide (NIA), diclofenac free acid (DFA) and n‐methyl paraben (MPB). In preliminary studies, MPB showed the lowest recovery when exposed to the receptor compartment of 3D printed cells. Consequently, in vitro permeation studies were carried out using only MPB with polydimethylsiloxane (PDMS) membrane. RESULTS: A decrease in the amounts of selected compounds was observed for transparent 3D printed Franz cells compared to glass cells. MPB showed the lowest recovery (53.8 ± 13.1%) when compared with NIA (74.9 ± 4.0%), TBF (81.5 ± 12.0%) and DFA (90.2 ± 12.9%) after 72 h. Permeation studies conducted using 3D printed transparent cells with PDMS membrane also showed a decrease in MPB recovery of 51.4 ± 3.7% for the commercial resin and 94.4 ± 3.5% for the polymer synthesised in‐house, when compared to glass cells. Although hydrophobic coatings were subsequently applied to the 3D printed cells the same reduction in MPB concentration was observed in the receptor solution.

Conclusion

Transparent Franz cells were successfully prepared using 3D printing and were observed to be robust and leak‐proof. There are few resins currently available for preparation of transparent materials and incompatibilities between the actives investigated and the 3D printed cells were evident. Hydrophobic coatings applied as barriers to the printed materials did not prevent these interactions.

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Periostin concentrations in childhood-onset craniopharyngioma patients

Abstract

Purpose

Periostin is highly expressed in craniopharyngioma (CP)-associated fibroblasts and has been identified as a marker for non-alcoholic fatty liver disease (NAFLD). Half of CP patients with hypothalamic syndrome develop NAFLD. We hypothesized that periostin concentration is elevated in biological fluids of CP and associated with pathological hepatic parameters, indicating increased risk for NAFLD.

Methods

A cross-sectional study on 35 patients with sellar masses (SMP) recruited in the German Childhood Craniopharyngioma Registry (32 CP, 2 xanthogranuloma, 1 pilocytic astrocytoma), three short-statured patients with isolated growth hormone deficiency, five short-statured patients with normal findings in GH-stimulating tests and decreased insulin-like growth factor (IGF)-1 and seven healthy controls. Periostin was measured by Elisa in serum, urine and saliva.

Results

Periostin serum, urine and saliva concentrations in CP were similar to concentrations of the other groups. Hypothalamic involvement/hypothalamic lesions, degree of obesity as well as hepatic enzymes were not associated with elevated periostin concentrations. Due to low patient numbers with pathological hepatic parameters, missing imaging data on the degree of steatosis hepatis and the lack of histological proof of NAFLD, no definitive conclusions can be drawn from measured periostin concentrations in serum. Interestingly, the subgroup of patients with decreased IGF-1 levels showed elevated concentrations of serum periostin when compared with other groups.

Conclusions

In CP, periostin concentrations are not associated with known risk factors for NAFLD such as hepatic and metabolic parameters, obesity and hypothalamic lesions. Accordingly, periostin does not seem to be a suitable marker for NAFLD in CP.

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In memory of Anna Basso (1937–2018), one of the founders of aphasia therapy

Publication date: December 2018

Source: Cortex, Volume 109

Author(s): Stefano F. Cappa, Costanza Papagno

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Cover figure

Publication date: December 2018

Source: Cortex, Volume 109

Author(s):

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Editorial Board

Publication date: December 2018

Source: Cortex, Volume 109

Author(s):

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Regulatory and effector B cells: Friends or Foes?

Publication date: Available online 23 November 2018

Source: Journal of Dermatological Science

Author(s): Takashi Matsushita

Abstract

B cells have moved to the center stage in many autoimmune diseases including autoantibody-mediated diseases and T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. B cells play an important role for immune response beyond antibody production through mechanisms like antigen presentation and cytokine production. However, not all B cells positively regulate immune responses. Regulatory B cells negatively regulate immune responses by production of anti-inflammatory cytokines such as IL-10, IL-35, and TGF-β. Regulatory B cells have been found to be decreased and/or functionally impaired in various autoimmune diseases. In contrast, B cells also produce pro-inflammatory cytokines, such as IL-6, IFN-γ and GM ­ CSF. These effector B cells contribute to the pathogenesis of autoimmune diseases. Regulatory and effector B cell balance regulates immune response through the release of cytokines. Furthermore, a protocol that selectively depletes effector B cells while sparing regulatory B cells would represent a potent therapy for autoimmune diseases rather than pan-B cell depletion using anti-CD20 mAb.

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Stat3 activation in epidermal keratinocytes induces Langerhans cell activation to form an essential circuit for psoriasis via IL-23 production

Publication date: Available online 23 November 2018

Source: Journal of Dermatological Science

Author(s): Kimiko Nakajima, Sayo Kataoka, Kenji Sato, Mikiro Takaishi, Mayuko Yamamoto, Hideki Nakajima, Shigetoshi Sano

ABSTRACT

Background

Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial.

Objectives

To elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model.

Methods

Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer.

Results

LCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23.

Conclusions

Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.

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