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Biomedical subjects

Theo Rufli

Publications and source records attributed to Theo Rufli.

7 recordsLinked to original sources
PubMed2006

Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings, and itch behavior.

The mu- (MOR) and kappa- (KOR) opioid receptors have been implicated in the regulation of homeostasis of non-neuronal cells, such as keratinocytes, and sensations like pain and chronic pruritus. Therefore, we have studied the phenotype of skin after deletion of MOR and KOR. In addition, we applied a dry skin model in these knockout mice and compared the different mice before and after induction of the dermatitis in terms of epidermal thickness, epidermal peripheral nerve ending distribution, dermal inflammatory infiltrate (mast cells, CD4 positive lymphocytes), and scratching behavior. MOR knockout mice reveal as phenotype a significantly thinner epidermis and a higher density of epidermal fiber staining by protein gene product 9.5 than the wild-type counterparts. Epidermal hypertrophy, induced by the dry skin dermatitis, was significantly less developed in MOR knockout than in wild-type mice. Neither mast cells nor CD4 T(h)-lymphocytes are involved in the changes of epidermal nerve endings and epidermal homeostasis. Finally, behavior experiments revealed that MOR and KOR knockout mice scratch less after induction of dry skin dermatitis than wild-type mice. These results indicate that MOR and KOR are important in skin homeostasis, epidermal nerve fiber regulation, and pathophysiology of itching.

Animals↗
PubMed2006

Topical bioavailability of triamcinolone acetonide: effect of dose and application frequency.

The application frequency of topical corticosteroids is a recurrently debated topic. Multiple-daily applications are common, although a superior efficacy compared to once-daily application is not unequivocally proven. Only few pharmacokinetic studies investigating application frequency exist. The aim of the study was to investigate the effect of dose (Experiment 1) and application frequency (Experiment 2) on the penetration of triamcinolone acetonide (TACA) into human stratum corneum (SC) in vivo. The experiments were conducted on the forearms of 15 healthy volunteers. In Experiment 1, single TACA doses (300 microg/cm(2) and 100 microg/cm(2)) dissolved in acetone were applied on three sites per arm. In experiment 2, single (1 x 300 microg/cm(2)) and multiple (3 x 100 microg/cm(2)) TACA doses were similarly applied. SC samples were harvested by tape stripping after 0.5, 4 and 24 h (Experiment 1) and after 4, 8 and 24 h (Experiment 2). Corneocytes and TACA were quantified by UV/VIS spectroscopy and HPLC, respectively. TACA amounts penetrated into SC were statistically evaluated by a paired-sample t-test. In Experiment 1, TACA amounts within SC after application of 1 x 300 microg/cm(2) compared to 1 x 100 microg/cm(2) were only significantly different directly after application and similar at 4 and 24 h. In Experiment 2, multiple applications of 3 x 100 microg/cm(2) yielded higher TACA amounts compared to a single application of 1 x 300 microg/cm(2) at 4 and 8 h. At 24 h, no difference was observed. In conclusion, using this simple vehicle, considerable TACA amounts were retained within SC independently of dose and application frequency. A low TACA dose applied once should be preferred to a high dose, which may promote higher systemic exposure.

Adhesives↗
PubMed2006

Deletion of delta-opioid receptor in mice alters skin differentiation and delays wound healing.

In addition to their well-known antinociceptive action, opioids can modulate non-neuronal functions, such as immune activity and physiology of different cell types. Several findings suggest that the delta-opioid receptor (DOR) and its endogenous ligands (enkephalins) are important players in cell differentiation and proliferation. Here we show the expression of DOR in mouse skin and human skin cultured fibroblasts and keratinocytes using RT-PCR. In DOR knock-out (KO) mice, a phenotype of thinner epidermis and higher expression of cell differentiation marker cytokeratin 10 (CK 10) were observed compared with wild type (WT). Using a burn wound model, significant wound healing delay (about 2 days) and severe epidermal hypertrophy were shown at the wound margin of DOR KO mice. This wound healing delay was further investigated by immunohistochemistry using markers for proliferation, differentiation, re-epithelialization, and dermal repair (CK 6, CK 10, and collagen IV). The levels of all these markers were increased in wounds of KO mice compared with WT. During the wound healing, the epidermal thickness in KO mice augments faster and exceeds that of the WT by day 3. These results suggest an essential role of DOR in skin differentiation, proliferation, and migration, factors that are important for wound healing.

Animals↗
PubMedDate not supplied

Specific stimulation of migration of human keratinocytes by mu-opiate receptor agonists.

There are several indications that neuropeptides, especially the opiate receptor agonists, modulate the immune response by stimulating the formation of granulation tissue and enhancing the reepithelialization. We observed that the mu-opiate receptor ligand beta-endorphin stimulates the migration of cultured human foreskin keratinocytes. After 1 hour exposure to 1 microM beta-endorphin, the keratinocytes experienced an increase of cell diameter by cellular elongation and stimulation of migration. Dynorphin had a lesser effect under the same condition. The opiate receptor antagonist naltrexone significantly reduced the effect of beta-endorphin on keratinocyte migration. This migratory effect of mu-opiate receptor agonists in vitro indicates that the opioid peptides, released in wounds, could play a key role in the final reepithelialization and tissue regeneration in wound healing. This new knowledge will help us not only to understand the mechanism of wound healing but also to improve the therapeutic strategy in the healing of painful chronic wounds.

Cell Movement↗
PubMedDate not supplied

Unilateral aplasia cutis congenita on the leg.

We present the case of a newborn male with aplasia cutis congenita on the extensor side of the right leg, with unilateral absence of skin on the lower limb. There was no abnormality in pregnancy or birth and there was no associated malformation or skin disease such as blistering or nail pathology. The management of this large ulcer was conservative, using silver sulfadiazine ointment, and healing occurred within 3 months. The follow-up after 21 months showed little scar formation and no handicap regarding function and appearance. The psychomotor development was normal. According to the classification outlined by Frieden, we classified this condition as type VII aplasia cutis congenita.

Anti-Infective Agents, Local↗