Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Topical photodynamic therapy (PDT) has been applied to almost all types of nonmelanoma skin cancer and numerous superficial benign skin disorders. Strategies to improve the accumulation of photosensitizer in the skin have been studied in recent years. Although the hydrophilic phthalocyanine zinc compound, zinc phthalocyanine tetrasulfonate (ZnPcSO4) has shown high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain tumors and eye conditions, its use in topical skin treatment is currently limited by its poor skin penetration. In this study, nanodispersions of monoolein (MO)-based liquid crystalline phases were studied for their ability to increase ZnPcSO4 uptake by the skin. Lamellar, hexagonal and cubic crystalline phases were prepared and identified by polarizing light microscopy, and the nanodispersions were analyzed by dynamic light scattering. In vitro skin penetration studies were performed using a Franz's cell apparatus, and the skin uptake was evaluated in vivo in hairless mice. Aqueous dispersions of cubic and hexagonal phases showed particles of nanometer size, approximately 224 +/- 10 nm and 188 +/- 10 nm, respectively. In vitro skin retention experiments revealed higher fluorescence from the ZnPcSO4 in deeper skin layers when this photosensitizer was loaded in the hexagonal nanodispersion system when compared to both the cubic phase nanoparticles and the bulk crystalline phases (lamellar, cubic and hexagonal). The hexagonal nanodispersion showed a similar penetration behavior in animal tests. These results are important findings, suggesting the development of MO liquid crystal nanodispersions as potential delivery systems to enhance the efficacy of topical PDT.

The use of nasal dilator strips as a placebo for trials evaluating continuous positive airway pressure

OBJECTIVES: The aim of the current study was to compare the objective and subjective effects of continuous positive airway pressure to the use of nasal dilator strips in patients with acromegaly and moderate to severe obstructive sleep apnea. METHODS: We studied 12 patients with acromegaly and moderate to severe obstructive sleep apnea (male/females = 8/4, age = 52 +/- 8 ys, body mass index = 33.5 +/- 4.6 Kg/m(2), apnea-hypopnea index = 38 +/- 14 events/h) who had been included in a randomized, crossover study to receive three months of treatment with continuous positive airway pressure and nasal dilator strips. All patients were evaluated at study entry and at the end of each treatment by polysomnography, and Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and treatment satisfaction questionnaires. ClinicalTrials.gov: NCT01265121 RESULTS: The apnea-hypopnea index values decreased significantly with continuous positive airway pressure treatment but did not change with the use of nasal dilator strips. All of the subjective symptoms improved with both treatments, but these improvements were significantly greater with continuous positive airway pressure than with the nasal dilator strips. CONCLUSION: The use of nasal dilator strips had a much smaller effect on the severity of obstructive sleep apnea in patients with acromegaly and moderate to severe obstructive sleep apnea in comparison to the use of continuous positive airway pressure. Moreover, the improvement in several subjective parameters without any significant objective improvement in obstructive sleep apnea resulting from the use of nasal dilator strips is compatible with a placebo effect.

The dialogic life-death in care delivery to adolescents with cancer

This study aims to understand the experience of adolescents with cancer, family and the health team regarding death in the healthcare context, in the light of Edgar Morin's proposed theoretical framework of complexity. Participants were 12 adolescents, 14 relatives and 25 health professionals. The interview was used for data collection. The discussion of data was guided by the dialogic life-death in the context of care to adolescents with cancer. It was observed that the singularity in the way the adolescent experiences time and faces death and the possibility that the family will lose a loved one may not be in accordance with the care the health team offers, considering structural, organizational and affective aspects. It is not enough for the team just to rationally make choices on the use of diagnostic-therapeutic devices, in line with predefined moments in the disease. Instead, a contextualized and sensitive understanding of each situation is needed.

Practices of use of nasal intermittent positive pressure ventilation (NIPPV) in neonatology in northeastern Brazil

Objective: To investigate the use of nasal intermittent positive pressure ventilation (NIPPV) in level three neonatal intensive care units (NICU) in northeastern Brazil. Methods: This observational cross-sectional survey was conducted from March 2009 to January 2010 in all level three NICUs in northeastern Brazil that are registered in the Brazilian Registry of Health Establishments (Cadastro Nacional de Estabelecimentos de Saude, CNES) of the Ministry of Health. Questionnaires about the use of NIPPV were sent to the NICU directors in each institution. Statistical analysis was conducted using the software Epi-Info 6.04 and double data entry. A chi-square test was used to compare variables, and the level of statistical significance was set at p <= 0.05. Results: This study identified 93 level three NICUs in northeastern Brazil registered in CNES, and 87% answered the study questionnaire. Most classified themselves as private institutions (30.7%); 98.7% used NIPPV; 92.8 % adapted mechanical ventilators for NIPPV and used short binasal prongs as the interface (94.2%). Only 17.3% of the units had a protocol for the use of NIPPV. Mean positive inspiratory pressure and positive end-expiratory pressure were 20.0 cmH(2)O (standard deviation [SD]: 4.47) and 5.0 cmH(2)O (SD: 0.84). Conclusion: NICUs in northeastern Brazil use nasal intermittent positive pressure ventilation, but indications and ventilation settings are not the same in the different institutions.

Extraoral Implants in the Rehabilitation of Craniofacial Defects: Implant and Prosthesis Survival Rates and Peri-Implant Soft Tissue Evaluation

Purpose: Few reports have evaluated cumulative survival rates of extraoral rehabilitation and peri-implant soft tissue reaction at long-term follow-up. The objective of this study was to evaluate implant and prosthesis survival rates and the soft tissue reactions around the extraoral implants used to support craniofacial prostheses. Materials and Methods: A retrospective study was performed of patients who received implants for craniofacial rehabilitation from 2003 to 2010. Two outcome variables were considered: implant and prosthetic success. The following predictor variables were recorded: gender, age, implant placement location, number and size of implants, irradiation status in the treated field, date of prosthesis delivery, soft tissue response, and date of last follow-up. A statistical model was used to estimate survival rates and associated confidence intervals. We randomly selected 1 implant per patient for analysis. Data were analyzed using the Kaplan-Meier method and log-rank test to compare survival curves. Results: A total of 150 titanium implants were placed in 56 patients. The 2-year overall implant survival rates were 94.1% for auricular implants, 90.9% for nasal implants, 100% for orbital implants, and 100% for complex midfacial implants (P = .585). The implant survival rates were 100% for implants placed in irradiated patients and 94.4% for those placed in nonirradiated patients (P = .324). The 2-year overall prosthesis survival rates were 100% for auricular implants, 90.0% for nasal implants, 92.3% for orbital implants, and 100% for complex midfacial implants (P = .363). The evaluation of the peri-implant soft tissue response showed that 15 patients (26.7%) had a grade 0 soft tissue reaction, 30 (53.5%) had grade 1, 6 (10.7%) had grade 2, and 5 (8.9%) had grade 3. Conclusions: From this study, it was concluded that craniofacial rehabilitation with extraoral implants is a safe, reliable, and predictable method to restore the patient's normal appearance. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:1551-1557, 2012

Quality of life assessment septoplasty in patients with nasal obstruction

Naasal obstruction is a common complaint in the population. When caused by a deviated nasal septum, septoplasty is the procedure of choice for treating these patients. NOSE is a tool for assessing the disease-specific quality of life related to nasal obstruction. Aim: To assess the impact of septoplasty on patients with nasal obstruction secondary to deviated nasal septum based on the disease-specific quality-of-life questionnaire. Design: Prospective. Methods: Patients undergoing septoplasty with/without turbinectomy after no clinical improvement with medical treatment were assessed by the NOSE questionnaire before and 3 months after surgery. We evaluated the surgical improvement based on total score, the magnitude of the surgery in the disease-specific quality of life and the correlation between the preoperative score and postoperatively improvement. Results: Fourty-six patients were included in the study. There was a statistically significant improvement in the preoperative NOSE score (md = 75, IQR = 26) and after three months (md = 10, IQR = 20) (p < 0.001.T-Wilcoxon). The standardized response mean was 3.07. We found a strong correlation between the preoperative score in the NOSE questionnaire and improvements in the postoperative period (r = -0.789, p < 0.001, Spearman). No difference was found in improvement scores by gender. (p = 0.668, U-Mann-Whitney). Conclusion: Septoplasty resulted in a statistically significant improvement in the disease-specific QOL questionnaire.

Modified technique to increase nostril cross-sectional area after using rib and septal cartilage graft over alar nasal cartilages

PURPOSE: Describe a modified technique to increase nostril cross-sectional area using rib and septal cartilage graft over alar nasal cartilages. METHODS: A modified surgical technique was used to obtain, carve and insert cartilage grafts over alar nasal cartilages. This study used standardized pictures and measured 90 cadaveric nostril cross-sectional area using Autocad (c); 30 were taken before any procedure and 60 were taken after grafts over lateral crura (30 using costal cartilage and 30 using septal cartilage). Statistical analysis were assessed using a model for repeated measures and ANOVA (Analysis of Variance) for the variable "area". RESULTS: There's statistical evidence that rib cartilage graft is more effective than septal cartilage graft. The mean area after the insertion of septal cartilage graft is smaller than the mean area under rib graft treatment (no confidence interval for mean difference contains the zero value and all P-values are below the significance level of 5%). CONCLUSIONS: The technique presented is applicable to increase nostril cross section area in cadavers. This modified technique revealed to enhance more nostril cross section area with costal cartilage graft over lateral crura rather than by septal graft.

Delivery Levels of Support Competencies to Organizational Eco-efficiency: a case study in an electro-electronics sector industry

This article aims to develop and implement a search tool which, through the perception of its respondents, allows assessing how eco-efficient an organization is based on the identification of delivery levels of support competencies to organizational eco-efficiency. A mixed (qualitative and quantitative) exploratory-descriptive research was conducted, from a case study in an 'ISE Company'. A semi-structured interview and pictures of verification were used as data collection instruments. The data were analyzed via documentary analysis and triangulation of information collected. It was inferred that at the 'ISE Company' professionals at the high-level of the organizational hierarchy recognize, in part, the growth of organizational actions that contribute to sustainability, which is not fully consistent with national publications on the subject. The result of the research showed that organizational strategies addressing eco-efficiency are partially aligned with the professional performance of the organization.

EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also propose definitions for 'difficult to treat' rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between the upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists.

Orthodontic measurements and nasal respiratory function after surgically assisted rapid maxillary expansion: an acoustic rhinometry and rhinomanometry study

The present study sought to assess nasal respiratory function in adult patients with maxillary constriction who underwent surgically assisted rapid maxillary expansion (SARME) and to determine correlations between orthodontic measurements and changes in nasal area, volume, resistance, and airflow. Twenty-seven patients were assessed by acoustic rhinometry, rhinomanometry, orthodontic measurements, and use of a visual analogue scale at three time points: before surgery; after activation of a preoperatively applied palatal expander; and 4 months post-SARME. Results showed a statistically significant increase (p < 0.001) in all orthodontic measurements. The overall area of the nasal cavity increased after surgery (p < 0.036). The mean volume increased between assessments, but not significantly. Expiratory and inspiratory flow increased over time (p < 0.001). Airway resistance decreased between assessments (p < 0.004). Subjective analysis of the feeling of breathing exclusively through the nose increased significantly from one point in time to the next (p < 0.05). There was a statistical correlation between increased arch perimeter and decreased airway resistance. Respiratory flow was the only variable to behave differently between sides. The authors conclude that the SARME procedure produces major changes in the oral and nasal cavity; when combined, these changes improve patients' quality of breathing.

Influence of treatment with intranasal corticosteroids on the nasal mucosa, weight, and corticosteroid concentration in rats

Background: The effect of intranasal corticosteroids on the nasal epithelium mucosa is an important parameter of treatment safety. This study was designed to examine whether treatment with topical corticosteroids in patients with allergic rhinitis causes atrophic nasal mucosal changes, when compared with systemic corticosteroids, in rats. Methods: Male Wistar rats were treated daily during 7 weeks with topical administration with 10 microliters of normal saline (control group), 10 microliters of mometasone furoate group, 10 microliters of triamcinolone acetonide (T group), and 8 mg/kg of daily subcutaneous injections of methylprednisolone sodium succinate (MP group). Body weight was evaluated weekly. At the end of the treatment, rats were killed by decapitation to collect blood for determination of corticosterone levels and nasal cavities were prepared for histological descriptive analyses. Results: Treatment with T and MP decreased body weight. Plasma corticosterone concentration was significantly reduced by MP treatment and presented a clear tendency to decrease after T treatment. Histological changes observed in group T included ripples, cell vacuolization, increase in the number of nuclei, and decrease in the number of cilia in the epithelial cells. Conclusion: Growth and corticosterone concentration were impaired by T and MP at the same proportion, suggesting a role of this hormone in body gain. With the exception of T, intranasal or systemic treatment with the corticosteroids evaluated in this study did not affect nasal mucosa. (Am J Rhinol Allergy 26, e46-e49, 2012; doi: 10.2500/ajra.2012.26.3702)

Suppression of Inflammatory Cytokine Secretion by an NF-kappa B Inhibitor DHMEQ in Nasal Polyps Fibroblasts

Background: NF-kappa B is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-kappa B inhibitor that has been previously described with a greatpotential indecreasing inflammation in diseases other than CRSwNP. The aim of study isto evaluate the ability of DHMEQ to reducethe inflammatory recruiters on CRSwNP and to compare its anti-inflammatory profile as a single-agent or in association with fluticasone propionate (FP). Methods: nasal polyp fibroblasts were cultured in TNF-alpha enriched media. Cells were submitted to three different concentrations (1, 10 and 100nM) of either FP, DHMEQ or both. Inflammatory response was accessed by VCAM-1, ICAM-1 and RANTES expression (by RTQ-PCR) and protein levels by ELISA. Nuclear translocation of NF-kappa B was also evaluated. Results: both FP and DHMEQ inhibited inflammatory recruiters' production and NF-kappa B nuclear translocation. Interestingly, the anti-inflammatory effect from the association steroids plus DHMEQ was more intense than of each drug in separate. Conclusion: DHMEQ seems efficient in modulating the inflammatory process in CRSwNP. The synergic anti-inflammatory effect of DHMEQ and steroids may be a promising strategy to be explored, particularly in the setting of steroid-resistant NP. Copyright (c) 2012 S. Karger AG, Basel

Counter-ion effect on surfactant-DNA gel particles as controlled DNA delivery systems

The ability to entrap drugs within vehicles and subsequently release them has led to new treatments for a number of diseases. Based on an associative phase separation and interfacial diffusion approach, we developed a way to prepare DNA gel particles without adding any kind of cross-linker or organic solvent. Among the various agents studied, cationic surfactants offered particularly efficient control for encapsulation and DNA release from these DNA gel particles. The driving force for this strong association is the electrostatic interaction between the two components, as induced by the entropic increase due to the release of the respective counter-ions. However, little is known about the influence of the respective counter-ions on this surfactant-DNA interaction. Here we examined the effect of different counter-ions on the formation and properties of the DNA gel particles by mixing DNA (either single-(ssDNA) or double-stranded (dsDNA)) with the single chain surfactant dodecyltrimethylammonium (DTA). In particular, we used as counter-ions of this surfactant the hydrogen sulfate and trifluoromethane sulfonate anions and the two halides, chloride and bromide. Effects on the morphology of the particles obtained, the encapsulation of DNA and its release, as well as the haemocompatibility of these particles are presented, using counter-ion structure and DNA conformation as controlling parameters. Analysis of the data indicates that the degree of counter-ion dissociation from the surfactant micelles and the polar/hydrophobic character of the counter-ion are important parameters in the final properties of the particles. The stronger interaction with amphiphiles for ssDNA than for dsDNA suggests the important role of hydrophobic interactions in DNA.

In Vitro Characterization of Chitosan Gels for Buccal Delivery of Celecoxib: Influence of a Penetration Enhancer

Celecoxib (Cx) shows high efficacy in the treatment of osteoarthritis and rheumatoid arthritis as a result of its high specificity for COX-2, without gastrolesivity or interference with platelet function at therapeutic concentrations. Besides of anti-inflammatory effects, Cx also has a potential role for oral cancer chemoprevention. For these conditions, oral administration in long-term treatment is a concern due to its systemic side effects. However, local application at the site of injury (e.g., buccal inflammation conditions or chemoprevention of oral cancer) is a promising way to reduce its toxicity. In this study, the in vitro characterization of mucoadhesive chitosan (CHT) gels associated to AzoneA (R) was assessed to explore the potential buccal mucosal administration of Cx in this tissue. Rheological properties of gels were analyzed by a rheometer with cone-plate geometry. In vitro Cx release and permeability studies used artificial membranes and pig cheek mucosa, respectively. Mucoadhesion were measured with a universal test machine. CHT gels (3.0%) containing 2.0% or 3.0% Az showed more appropriate characteristics compared to the others: pH values, rheology, higher amount of Cx retained in the mucosa, and minimal permeation through mucosa, besides the highest mucoadhesion values, ideal for buccal application. Moreover, the flux (J) and amounts of drug released decreased with increased CHT and Az concentrations. CHT gels (3.0%) associated with 2.0% or 3.0% Az may be considered potential delivery systems for buccal administration of Cx.

Development of a recombinant fusion protein based on the dynein light chain LC8 for non-viral gene delivery

The low efficiency of gene transfer is a recurrent problem in DNA vaccine development and gene therapy studies using non-viral vectors such as plasmid DNA (pDNA). This is mainly due to the fact that during their traffic to the target cell's nuclei, plasmid vectors must overcome a series of physical, enzymatic and diffusional barriers. The main objective of this work is the development of recombinant proteins specifically designed for pDNA delivery, which take advantage of molecular motors like dynein, for the transport of cargos from the periphery to the centrosome of mammalian cells. A DNA binding sequence was fused to the N-terminus of the recombinant human dynein light chain LC8. Expression studies indicated that the fusion protein was correctly expressed in soluble form using E. coli BL21(DE3) strain. As expected, gel permeation assays found the purified protein mainly present as dimers, the functional oligomeric state of LC8. Gel retardation assays and atomic force microscopy proved the ability of the fusion protein to interact and condense pDNA. Zeta potential measurements indicated that LC8 with DNA binding domain (LD4) has an enhanced capacity to interact and condense pDNA, generating positively charged complexes. Transfection of cultured HeLa cells confirmed the ability of the LD4 to facilitate pDNA uptake and indicate the involvement of the retrograde transport in the intracellular trafficking of pDNA: LD4 complexes. Finally, cytotoxicity studies demonstrated a very low toxicity of the fusion protein vector, indicating the potential for in vivo applications. The study presented here is part of an effort to develop new modular shuttle proteins able to take advantage of strategies used by viruses to infect mammalian cells, aiming to provide new tools for gene therapy and DNA vaccination studies. (C) 2012 Elsevier B.V. All rights reserved.