Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation, characterization, and in vitro drug release study.

CONTEXT: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. OBJECTIVE: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. METHODS: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. RESULTS AND DISCUSSION: Nanocapsules showed mean particle size and zeta potential of 201 +/- 6 and -5.73 +/- 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 +/- 2.96 mg/cm(2)/h(1/2)) compared to the hydrogels containing the free drug (k = 26.65 +/- 2.09 mg/cm(2)/h(1/2)). CONCLUSION: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.

High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1.

UNLABELLED: Although it is known that neurofibromatosis 1 (NF1) patients suffer from vitamin D deficiency and display decreased bone mineral density (BMD), a systematic clinical and histomorphometrical analysis is absent. Our data demonstrate that NF1 patients display high bone turnover and accumulation of osteoid and that supplementation of vitamin D has a beneficial effect on their BMD. INTRODUCTION: Neurofibromatosis 1 results in a wide range of clinical manifestations, including decreased BMD. Although it has been reported that NF1 patients have decreased vitamin D serum levels, the manifestation of the disease at the bone tissue level has rarely been analyzed. METHODS: Thus, we performed a clinical evaluation of 14 NF1 patients in comparison to age- and sex-matched control individuals. The analysis included dual X-ray absorptiometry osteodensitometry, laboratory parameters, histomorphometric and quantitative backscattered electron imaging (qBEI) analyses of undecalcified bone biopsies. RESULTS: NF1 patients display significantly lower 25-(OH)-cholecalciferol serum levels and decreased BMD compared to control individuals. Histomorphometric analysis did not only reveal a reduced trabecular bone volume in biopsies from NF1 patients, but also a significantly increased osteoid volume and increased numbers of osteoblasts and osteoclasts. Moreover, qBEI analysis revealed a significant decrease of the calcium content in biopsies from NF1 patients. To address the question whether a normalization of calcium homeostasis improves BMD in NF1 patients, we treated four patients with cholecalciferol for 1 year, which resulted in a significant increase of BMD. CONCLUSION: Taken together, our data provide the first complete histomorphometric analysis from NF1 patients. Moreover, they suggest that low vitamin D levels significantly contribute to the skeletal defects associated with the disease.

Incorporation of beta-selenolo[3,2-b]pyrrolyl-alanine into proteins for phase determination in protein X-ray crystallography.

beta-Selenolo[3,2-b]pyrrolyl-L-alanine that mimics tryptophan with the benzene ring of the indole moiety replaced by selenophene, was incorporated into human annexin V and barstar. This was achieved by fermentation and expression in a Trp-auxotrophic Escherichia coli host strain using the selective pressure incorporation method. The seleno- proteins were obtained in yields comparable to those of the wild-type proteins and exhibit full crystallographic isomorphism to the parent proteins, but expectedly show altered absorbance profiles and quenched tryptophan fluorescence. Since the occurrence of tryptophan residues in proteins is rare, incorporation of the electron-rich selenium-containing tryptophan surrogate into proteins represents a useful supplementation and even a promising novel alternative to selenomethionine for solving the phase problem in protein X-ray crystallography.

In vitro toxicity assessment of mouthwashes in the pollen tube growth test: first results.

Mouthwashes are widespread used to treat halitosis or minor oral infections. Adverse effects of mouthwashes were recognized, e.g. desquamation of the oral mucosa and stomatitis. The acute toxicity of mouthwashes was tested in an in vitro system, the pollen tube growth test (PTG-test). In the PTG-test the acute toxicity of mouthwashes exceeds the toxic effect of alcohol. Consumers should be informed about the number and amounts of mouthwash ingredients, and their toxic potential. These declarations would provide the basis for testing the carcinogenic effects of mouthwashes.

Genetic analysis of vertebrate sensory hair cell mechanosensation: the zebrafish circler mutants.

The molecular basis of sensory hair cell mechanotransduction is largely unknown. In order to identify genes that are essential for mechanosensory hair cell function, we characterized a group of recently isolated zebrafish motility mutants. These mutants are defective in balance and swim in circles but have no obvious morphological defects. We examined the mutants using calcium imaging of acoustic-vibrational and tactile escape responses, high resolution microscopy of sensory neuroepithelia in live larvae, and recordings of extracellular hair cell potentials (microphonics). Based on the analyses, we have identified several classes of genes. Mutations in sputnik and mariner affect hair bundle integrity. Mutant astronaut and cosmonaut hair cells have relatively normal microphonics and thus appear to affect events downstream of mechanotransduction. Mutant orbiter, mercury, and gemini larvae have normal hair cell morphology and yet do not respond to acoustic-vibrational stimuli. The microphonics of lateral line hair cells of orbiter, mercury, and gemini larvae are absent or strongly reduced. Therefore, these genes may encode components of the transduction apparatus.

[Alternatives to steroid therapy in chronic uveitis]. / Alternativen zur Steroidtherapie bei der chronischen Uveitis.

In a search for alternative therapeutic methods other than corticosteroids and cytostatics, the effect of a dialyzable leukocyte extract (DLE), the antimetabolite 5-fluorouracil and the immunosuppressive agent cyclosporin A in corticosteroid-resistant idiopathic uveitis was studied. When DLE was administered to 26 patients who had uveitis forms with exogenous triggering (e.g., infection), as well as forms with an autoimmune background, there was a reduction in the number and duration of recurrences and a statistically proven prolongation of the inflammation-free intervals. This was particularly true in anterior and posterior uveitis and to a lesser extent in the intermediate form. No side effects were observed. 5-Fluorouracil, injected subconjunctivally, is indicated in intermediate uveitis with marked vitreous infiltration and beginning proliferation. Corneal erosion occurs relatively often. During treatment with cyclosporin A (low dose, 5 mg/kg of body weight per day), 14 of 17 patients (9 with intermediate uveitis, 6 with retinal vasculitis, 1 with sympathetic ophthalmia, 1 with panuveitis) showed improved results; in 2 cases the findings remained stationary and only 1 case had low-grade deterioration. If one takes into consideration the fact that in this patient any therapy would have failed, the results are convincing. This is particularly true of retinal vasculitis. There is no effect in cases of central hemorrhagic chorioretinopathy. So far, there have been no serious side effects.

Teaching communication skills in an integrated curriculum.

During the seven weeks students showed growth in empathic responding. In addition, many students were able to move beyond beginning empathy to identifying underlying feelings experienced by the patient. Progress in concreteness was noted as irrelevant questioning decreased and selective, open-ended questioning increased. There seemed to be a positive correlation between self-awareness and growth in communication skills. Initially, use of behaviorally specific feedback helped the students identify strengths and weaknesses. As the sessions progressed, students became more independent in critiquing their own interpersonal style. For example, one student identified her abrasive manner in a taped interaction and recognized her need to maintain control. She modified her approach and became more caring and empathic. Initially, Stage II skills were difficult for the students. Some students who expected to see change occur quickly, became impatient with relationship building, and used challenging skills prematurely. Other students had difficulty taking the risk to challenge the patient to focus on problem exploration. Role playing in the training sessions and faculty feedback in the clinical settings helped the students begin to use skills more appropriately. Observing the positive effects on patient behavior reinforced continued use. Students and faculty were enthusiastic about the workshop format and outcome. Student reactions reinforced the value of the systematic approach. Through verbal and written evaluations they identified the small group practice and clinical audiotaping as the most valuable activities. Many liked being able to practice and receive immediate feedback from their peers and instructors. Faculty found that the four components-description, demonstration, practice and application-provided direction for teaching.(ABSTRACT TRUNCATED AT 250 WORDS)