Lecithin/chitosan nanoparticles for transdermal delivery of melatonin

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as colloidal nanosystem for transdermal melatonin delivery was investigated. Mean diameter and zeta-potential of NPs differing in lecithin type (Lipoid S45 and S100) and chitosan content ranged between 113.7 and 331.5?nm and 4.6 and 31.2?mV, respectively. Melatonin loadings were up to 7.2%. The potential of lecithin/chitosan NPs to enhance transdermal melatonin delivery was investigated by determining the drug flux across dermatomed porcine skin and its skin deposition. Lecithin/chitosan NPs provided 1.3-2.3-fold higher flux compared to melatonin solution. The highest flux, 9.0?±?0.21?μg/cm2/h, was observed for S45 lecithin/chitosan NPs with lecithin/chitosan weight ratio of 20:1. NP possible cytotoxicity in vitro was evaluated using human skin keratinocytes and fibroblasts. It was demonstrated that lecithin/chitosan NPs can be applied to skin cells at concentrations up to 200?μg/mL without inducing plasma membrane damage or cell viability decrease.     

Latex-allergic patients sensitized to the major allergen hevein and hevein-like domains of class I chitinases show no increased frequency of latex-associated plant food allergy

Allergies to certain fruits such as banana, avocado, chestnut and kiwi are described in 30-70% of latex-allergic patients. This association is attributed to the cross-reactivity between the major latex allergen hevein and hevein-like domains (HLDs) from fruit class I chitinases. We aimed to assess the extent of cross-reactivity between hevein and HLDs using sera from latex-allergic patients with and without plant food allergy. Hevein and HLDs of latex, banana, and avocado chitinases were expressed in Escherichia coli as fusion proteins with the maltose-binding protein and purified by affinity chromatography. IgE binding to these proteins was studied in sera from 59 latex-allergic patients and 20 banana-allergic patients without latex allergy by ELISA and ELISA inhibition. Additionally, 16,408 allergic patients’ sera were tested for IgE binding to hevein, latex chitinase, and wheat germ agglutinin using an allergen microarray. Hevein-specific IgE was detected in 34/59 (58%) latex-allergic patients’ sera. HLDs of latex, banana, and avocado chitinases were recognized by 21 (36%), 20 (34%), and 9 (15%) sera, respectively. In contrast, only one of 20 banana-allergic patients without latex allergy was sensitized to chitinase HLDs. In most tested latex-allergic patients’ sera, IgE binding to hevein was only partially reduced by preincubation with HLDs. Among hevein-sensitized, latex-allergic patients, the percentage of plant food allergy (15/34 = 44%) was equal to latex-allergic patients without hevein sensitization (11/25 = 44%). In the general allergic population, 230 of 16,408 sera (1.4%) reacted to hevein and/or a hevein-like allergen. Of these, 128 sera showed an isolated sensitization to hevein, whereas only 17 bound to latex chitinase or wheat germ agglutinin without hevein sensitization. In conclusion, the IgE response to HLDs is elicited by hevein as sensitizing allergen in most cases. Despite considerable cross-reactivity between these allergens, no correlation between latex-associated plant food allergy and sensitization to hevein or HLDs was found.     

Multiple oncogenic mutations and clonal relationship in spatially distinct benign human epidermal tumors

Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about the genetic changes in benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal tumors without malignant potential. We performed a comprehensive mutational screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT pathways from 175 SK, including multiple lesions from each patient. SK commonly harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK and PI3K pathway signaling, we did not find induction of senescence or a DNA damage response. Array comparative genomic hybridization (aCGH) analysis revealed that SK are genetically stable. The pattern of oncogenic mutations and X chromosome inactivation departs significantly from randomness and indicates that spatially independent lesions from a given patient share a clonal relationship. Our findings show that multiple oncogenic mutations in the major signaling pathways involved in cancer are not sufficient to drive malignant tumor progression. Furthermore, our data provide clues on the origin and spread of oncogenic mutations in tissues, suggesting that apparently independent (multicentric) adult benign tumors may have a clonal origin.     

Bcl-2 and bcl-xL antisense oligonucleotides induce apoptosis in melanoma cells of different clinical stages

Recent clinical studies have shown the promise of bcl-2 antisense therapy in patients with melanoma. To further demonstrate the importance of bcl-2 and validate the related antiapoptotic protein bcl-xL as targets for antisense therapy in melanoma, their implication as survival factors in melanoma cells of different clinical stages as well as in normal melanocytes was investigated. Primary cell cultures derived from 17 melanomas, the cell line A375, and normal melanocytes from healthy donors were treated with antisense oligonucleotides targeting either the bcl-xL mRNA or the bcl-2 and the bcl-xL mRNAs simultaneously. Bcl-2 and bcl-xL expression in cells was analyzed by real-time polymerase chain reaction and Western blotting. Cell viability was assessed in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and apoptosis assays. Bcl-2 expression was low in melanoma cells of stages I, II, and III, hardly detectable in A375 cells, but high in normal melanocytes. Bcl-xL expression was high in all cell types tested. As shown in A375 cells and the stage III melanoma cells 0513, both the bcl-xL monospecific oligonucleotide 4259 and the bcl-2/bcl-xL bispecific oligonucleotide 4625 effectively reduced tumor cell viability by induction of apoptosis with IC50 values ranging from 200 to 350 nM. Oligonucleotide 4625 proved to be superior to 4259, as it significantly reduced the viability of cells from all melanoma stages. Both oligonucleotides reduced also the viability of normal melanocytes. Our data suggest that bcl-2 and bcl-xL are promising targets for antisense therapy of melanoma, and that the simultaneous downregulation of their expression may provide additional clinical benefit.     

Dapson bei granulomatöser Rosazea

Die Dermatologie - Wir berichten über zwei Patienten mit granulomatöser Rosazea und eine Patientin mit granulomatöser perioraler Dermatitis, welche auf eine Behandlung mit Dapson gut...     

Airborne irritant contact dermatitis from metal dust adhering to semisynthetic working suits

2 workers at an aircraft factory were employed in a plasma sparying unit. Soon after they were equipped with new semisynthetic working suits, they started to complain of pruritic eruptions after heavy exposure to metal dust. They noted that the dust was not as easily blown off the clothes by pressurized air as previously. Clinical findings consisted of discrete macular and papular lesions, partly follicular, on the ventral and medial thighs. Atopy score, IgE level and a standard series of prick tests ruled out atopic disposition. Patch tests revealed no reactions. A diagnosis of occupational airborne irritant contact dermatitis from metal dust was therefore made. To elucidate the role of the working suit, extensive physical investigations of the physical properties of the textile were performed. Microscopic pictures at low magnification showed more dust particles on the semisynthetic working suit, compared to the former pure cotton suit. This impression could not be confirmed by particle count because of too uneven particle distribution at higher magnification. Hairiness of the 2 textiles was low and ruled out irritation by the semisynthetic textile itself. No difference in electrostatic properties between the 2 working suits could be established either. Both textiles showed high static electrical propensity. When use of the semisynthetic overall was discontinued, the patients reported no recurrence. The 2 reported cases show that the physical properties of the textiles of working suits can be of interest and should be considered in the management of dust-induced irritant contact dermatitis. Extended physical examinations of textile failed to explain the clinical observation; further investigations might establish physical characteristics of textiles for such adhesion qualities.     

A psychogeriatric community outreach service: Description and evaluation

The structure and function of a small psychogeriatric community outreach team is outlined, together with the results of intervention in 100 consecutive cases. Patients in residential or nursing home care were rated for level of behavioural disturbance at entry to the study and after three months. Patients with dementia and psychotic disorders showed clinically and statistically significant improvement, whereas the improvement of patients with major depression was not statistically significant. The usefulness of the outreach service was evaluated independently by carers and by referring agents. Eighty per cent of carers and 87% of referring agents rated the service as useful or very useful. It was concluded that a small outreach team (comprising the equivalent of only six full-time staff) is an effective and acceptable supplement to the overall care of psychogeriatric patients.