Immunology of Dermatophytosis

The immune response to infection by dermatophytes ranges from a non-specific host mechanism to a humoral and cell-mediated immune response. The currently accepted view is that a cell-mediated immune response is responsible for the control of dermatophytosis. Indeed, some individuals develop a chronic or recurrent infection mediated by the suppression of a cell-mediated immune response. The immune response to Trichophyton is unusual in that this fungus can elicit both immediate hypersensitivity (IH) and delayed-type hypersensitivity (DTH) in different individuals when they are submitted to a skin test reaction. Understanding the nature and function of the immune response to dermatophytes is an exciting challenge that might lead to novel approaches in the treatment and immunological prophylaxis of dermatophytosis.

Human Airway Epithelial Cell Responses to Neisseria lactamica and Purified Porin via Toll-Like Receptor 2-Dependent Signaling

The human airway epithelium is constantly exposed to microbial products from colonizing organisms. Regulation of Toll-like receptor (TLR) expression and specific interactions with bacterial ligands is thought to mitigate exacerbation of inflammatory processes induced by the commensal flora in these cells. The genus Neisseria comprises pathogenic and commensal organisms that colonize the human nasopharynx. Neisseria lactamica is not associated with disease, but N. meningitidis occasionally invades the host, causing meningococcal disease and septicemia. Upon colonization of the airway epithelium, specific host cell receptors interact with numerous Neisseria components, including the PorB porin, at the immediate bacterial-host cell interface. This major outer membrane protein is expressed by all Neisseria strains, regardless of pathogenicity, but its amino acid sequence varies among strains, particularly in the surface-exposed regions. The interaction of Neisseria PorB with TLR2 is essential for driving TLR2/TLR1-dependent cellular responses and is thought to occur via the porin`s surface-exposed loop regions. Our studies show that N. lactamica PorB is a TLR2 ligand but its binding specificity for TLR2 is different from that of meningococcal PorB. Furthermore, N. lactamica PorB is a poor inducer of proinflammatory mediators and of TLR2 expression in human airway epithelial cells. These effects are reproduced by whole N. lactamica organisms. Since the responsiveness of human airway epithelial cells to colonizing bacteria is in part regulated via TLR2 expression and signaling, commensal organisms such as N. lactamica would benefit from expressing a product that induces low TLR2-dependent local inflammation, likely delaying or avoiding clearance by the host.

Fluorescent indication that nitric oxide formation in NTS neurons is modulated by glutamate and GABA

Nitric oxide (NO) in NTS plays an important role in regulating autonomic function to the cardiovascular system. Using the fluorescent dye DAF-2 DA, we evaluated the NO concentration in NTS. Brainstem slices of rats were loaded with DAF-2 DA, washed, fixed in paraformaldehyde and examined under fluorescent light. In different experimental groups, NTS slices were pre-incubated with 1 mM L-NAME (a non-selective NOS inhibitor), 1 MM D-NAME (an inactive enantiomere of L-NAME), 1 mM kynurenic acid (a nonselective ionotropic receptors antagonist) or 20 mu M bicuculline (a selective GABA(A) receptors antagonist) before and during DAF-2 DA loading. Images were acquired using a confocal microscope and the intensity of fluorescence was quantified in three antero-posterior NTS regions. In addition, slices previously loaded with DAF-2 DA were incubated with NeuN or GFAP antibody. A semi-quantitative analysis of the fluorescence intensity showed that the basal NO concentration was similar in all antero-posterior aspects of the NTS (rostral intermediate, 15.5 +/- 0.8 AU: caudal intermediate, 13.2 +/- 1.4 AU; caudal commissural, 13.8 +/- 1.4 AU, n = 10). In addition, the inhibition of NOS and the antagonism of glutamatergic receptors decreased the NO fluorescence in the NTS. On the other hand, D-NAME did not affect the NO fluorescence and the antagonism of GABAA receptors increased the NO fluorescence in the NTS. It is important to note that the fluorescence for NO was detected mainly in neurons. These data show that the fluorescence observed after NTS loading with DAF-2 DA is a result of NO present in the NTS and support the concept that NTS neurons have basal NO production which is modulated by L-glutamate and GABA. (C) 2009 Elsevier Inc. All rights reserved.

Preparation and characterization of chitosan-treated alginate microparticles incorporating all-trans retinoic acid

Chitosan treated alginate microparticles were prepared with the purpose of incorporating all-trans retinoic acid (ATRA) using an inexpensive, simple and fast method, enhancing dermal localization and sustaining the release of ATRA into the skin. Microparticles characterization, drug-polymer interaction, release profile and in vitro skin retention were investigated. Microparticles presented spherical shape and drug loading capacity of 47%. The drug content of these microparticles was affected by ATRA concentration and by the solvent used and it was more weakly affected by chitosan concentration. The release of ATRA was also affected by chitosan concentration. Microparticles prepared with 0.4% chitosan (w/w) resulted in drug release with a more sustained profile. The results of in vitro retention studies showed that chitosan treated alginate microparticles decreased the drug retention in the stratum corneum (SC), where occur the skin irritation, but maintained the ATRA concentration in the deeper skin layers, where occur the pathologies treated with ATRA. Then, the microparticles developed in this work can be a good candidate to improve the topical therapy with retinoid.

Precursor system of liquid crystalline phase containing propolis microparticles for the treatment of periodontal disease: Development and characterization

Precursor systems of liquid crystalline phase were prepared using the surfactant PPG-5-Ceteth-20, isopropyl myristate, and water; gelatin microparticles containing propolis were then added into these systems. Homogeneity of dispersion, the in-system microparticle morphology, and sedimentation behavior of each formulation were evaluated. The rheological and mechanical properties (hardness, compressibility, and adhesiveness), the work of syringing, and the propolis release profile were also evaluated. All the formulations exhibited pseudoplastic flow and thixotropy, and they displayed storage modulus, loss modulus, dynamic viscosity, and loss tangent that depended on temperature, frequency, and composition. Mechanical properties varied significantly among the formulations being affected by changes in the composition and temperature. Raising the concentration of surfactant and adding propolis microparticles significantly decreased the work of syringing. The drug release was non-Fickian (anomalous) and there was no significant difference between the tested systems in the times required for 10%, 30%, and 50% release of the initial drug loading.

Analysis of Liquid Crystalline Nanoparticles by Small Angle X-Ray Diffraction: Evaluation of Drug and Pharmaceutical Additives Influence on the Internal Structure

The goal of this work was to study the liquid crystalline structure of a nanodispersion delivery system intended to be used in photodynamic therapy after loading with photosensitizers (PSs) and additives such as preservatives and thickening polymers. Polarized light microscopy and light scattering were performed on a standard nanodispersion in order to determine the anisotropy of the liquid crystalline structure and the mean diameter of the nanoparticles, respectively. Small angle X-ray diffraction (SAXRD) was used to verify the influence of drug loading and additives on the liquid crystalline structure of the nanodispersions. The samples, before and after the addition of PSs and additives, were stable over 90 days, as verified by dynamic light scattering. SAXRD revealed that despite the alteration observed in some of the samples analyzed in the presence of photosensitizing drugs and additives, the hexagonal phase still remained in the crystalline phase. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2849-2857, 2011

In Vitro Antifungal Activity and Toxicity of Itraconazole in DMSA-PLGA Nanoparticles

Itraconazole (ITZ) is a drug used to treat various fungal infections and may cause side effects. The aim of this study was to develop and evaluate the in vitro activity of DMSA-PLGA nanoparticles loaded with ITZ against Paracoccidioides brasiliensis, as well as their cytotoxicity. Nanoparticles were prepared using the emulsification-evaporation technique and characterized by their encapsulation efficiency, morphology (TEM), size (Nanosight) and charge (zeta potential). Antifungal efficacy in P brasiliensis was determined by minimal inhibition concentration (MIC), and cytotoxicity using MU assay. ITZ was effectively incorporated in the PLGA-DMSA nanoparticles with a loading efficiency of 72.8 +/- 3.50%. The shape was round with a solid polymeric structure, and a size distribution of 174 +/- 86 nm (Average +/- SD). The particles were negatively charged. ITZ-NANO presented antifungal inhibition (MIC = 6.25 ug/mL) against P brasiliensis and showed lower in vitro cytotoxicity than free drug (ITZ).

Development of novel bioanodes for ethanol biofuel cell using PAMAM dendrimers as matrix for enzyme immobilization

This paper describes the preparation and application of a novel bioanode for use in ethanol/O(2) biofuel cells based upon immobilization of alcohol dehydrogenase (ADH) and polyamidoamine (PAMAM) dendrimers onto carbon cloth platforms. The power density measurements indicated a direct relationship between the amount of anchored ADH and the anode power values, which increased upon enzyme loading. The power density values ranged from 0.04 to 0.28 mW cm(-2), and the highest power density was achieved with the bioanode prepared with 28 U of ADH, which provided a power density of 0.28 mW cm(-2) at 0.3 V. The latter power output values were the maximum observed, even for higher enzyme concentrations. Stability of the bioanodes was quite satisfactory, since there was no appreciable reduction of enzymatic activity during the measurements. The method of bioanode preparation described here has proven to be very effective. The PAMAM dendrimer represents a friendly environment for the immobilization of enzymes, and it is stable and capable of generating high power density compared to other immobilization methods. (C) 2010 Elsevier B.V. All rights reserved.

Influence of ovariectomy and masticatory hypofunction on mandibular bone remodeling

Introduction: This study was designed to examine the effect of masticatory hypofunction and estrogen deficiency on mandible bone mass and compare this site with spine and femoral bone. Methods: Twenty-four rats were ovariectomized (OVX) or Sham-operated (Sham) and analyzed after feeding with hard diet (Hard) or soft diet (Soft). They were divided into four groups: (GI)Sham-Hard; (GII)OVX-Hard; (GIII)Sham-Soft and (GIV)OVX-Soft. Bone mineral density (BMD) was measured in the spine and femur in the baseline and at the end of the study, and Delta BMD (final BMD - baseline BMD) was calculated. In mandible bone, BMD and histomorphometry were analyzed at the end of the experiment. Results: Sham rats showed higher spine (GI: 13.5%vs GII: 0.74%, P < 0.01; GIII: 10.67%vs GIV: -4.36%, P < 0.001) and femur Delta BMD (GI: 14.43%vs GII: 4.42%, P < 0.01; GIII: 10.58%vs GIV: 0.49%, P < 0.001) than OVX, but no difference was observed in mandible BMD among these groups (P > 0.05). Soft-diet groups showed decreased mandible BMD compared with hard-diet groups (GIV vs GII, P < 0.01; GIII vs GI, P < 0.01). Similarly, mandibular condyle histomorphometry showed that soft-diet groups presented a significant decrease in trabecular thickness and volume (GIV vs GII, P < 0.05; GIII vs GI, P < 0.01) compared with hard diet. Conclusion: Our results suggest that mandibular bone loss resulted from decreased of mechanical loading during mastication, and was not affect by estrogen depletion.

Refractory cluster headache in a patient with bruxism and obstructive sleep apnea: a case report

Introduction This is a case report of a 39-year-old patient with a 14-year history of clinically refractory cluster headache (CH), also presenting obstructive sleep apnea (OSA) and complaining of tooth-grinding during sleep. Discussion Treatment of OSA with an intra-oral device allowed an immediate reduction in frequency and intensity of CH events. Furthermore, CH attacks did not occur during the 12-month follow-up period.

Episodic and semantic memory in children with mesial temporal sclerosis

The aim of this study was to analyze semantic and episodic memory deficits in children with mesial temporal sclerosis (MTS) and their correlation with clinical epilepsy variables. For this purpose, 19 consecutive children and adolescents with MTS (8 to 16 years old) were evaluated and their performance on five episodic memory tests (short- and long-term memory and learning) and four semantic memory tests was compared with that of 28 healthy volunteers. Patients performed worse on tests of immediate and delayed verbal episodic memory, visual episodic memory, verbal and visual learning, mental scanning for semantic clues, object naming, word definition, and repetition of sentences. Clinical variables such as early age at seizure onset, severity of epilepsy, and polytherapy impaired distinct types of memory. These data confirm that children with MTS have episodic memory deficits and add new information on semantic memory. The data also demonstrate that clinical variables contribute differently to episodic and semantic memory performance. (C) 2011 Elsevier Inc. All rights reserved.

Intimal dissection of the hepatic artery after thrombectomy as a cause of graft loss in pediatric living-related liver transplantation

HAT is the main cause of graft loss in pediatric living-related LTx. Revascularization of the graft by thrombectomy and re-anastomosis has been reported to be effective for graft salvage in cases of HAT and should be attempted when potential donors are not available for emergency re-transplantation. Immediate complications secondary to revascularization attempts in cases of HAT are not described. Late complications are mainly related to biliary tree ischemia. We report a case of child who experienced intimal hepatic artery dissection, which extended into intra-hepatic branches of the artery after a thrombectomy with a Fogarty balloon catheter in an attempt to restore arterial flow after HAT. This complication led to acute deterioration of the graft and the need for emergency re-transplantation.

Successful Endomyocardial Biopsy Guided by Transthoracic Two-Dimensional Echocardiography

Introduction. Two-dimensional (2-D) echocardiography is an excellent alternative method to perform endomyocardial biopsies (EB) in special situations, mainly when the patient is in a critical state and cannot go to the catheterization laboratory or when there are contraindications to the use of fluoroscopy as in the pregnancy. Objective. This single-center experience analyzed the last 25 years use of an EB technique guided by echocardiography realized at the bedside on critical patients. Methods. From 1985 to 2010, we performed 76 EB guided by 2-D echocardiography on 59 patients, among whom 38 (64.4%) were critically ill with examinations at the bedside; among 10 (16.9%) subjects, the procedure was carried out simultaneously with fluoroscopy for safety`s sake during the learning period. In addition, 8 (13.6%) were unavailable for fluoroscopy, and 3 (5.1%) required a hybrid method due to an intracardiac tumor. Results. The main adverse effects included local pain (n = 4, 5.6%); difficult out successful puncture due to previous biopsies (n = 4, 5.6%); local hematoma without major consequences (n = 3, 4.2%); failed but ultimately successful puncture on the first try due to previous biopsies or (n = 3, 4.2%); obesity and immediate postoperative period with impossibility to pass the bioptome into the right ventricle; however 2 days later the procedure was repeated successfully by echocardiography (n = 1, 1.4%). All myocardial specimens displayed suitable size. There were no undesirable extraction effects on the tricuspid valve tissue. In this series, there was no case of death, hemopericardium, or other major complication as a direct consequence of the biopsy. Conclusion. 2-D echocardiography is a special feature to guide EB is mainly in critically ill patients because it can be performed at the bedside without additional risk or disadvantages of fluoroscopy. The hybrid method associating 2-D echocardiography and fluoroscopy allows the procedure in different situations such as intracardiac tumor cases.

The role of micro-anchor devices in medial canthopexy

Telecanthus, the lateral displacement of the medial canthus, can be a congenital deformity or can occur after facial trauma or tumor resection. Treatment of telecanthus remains a challenge for plastic surgeons. For proper correction, it is necessary to shift the medial canthus medially, fixing its tendon to the bone. The ideal technique would allow easy, safe, and stable fixation of the tendon, permit a unilateral approach with minimal incisions, and be cost-effective. The purpose of this study was to evaluate the feasibility and results (immediate and long-term) of medial telecanthus repair using ipsilateral titanium microanchor fixation. Nine patients, 7 with unilateral telecanthus and 2 with bilateral telecanthus, underwent ipsilateral canthopexy involving a microanchor device. Anthropometric measurements of the orbital regions were taken before, immediately after, and at 1 year after surgery. Data for the affected sides were compared with those for the unaffected sides, and the evolution of those values was assessed throughout the 1-year follow-up period. For all patients, the final values were lower than those initially obtained. At 1 year after surgery, the intercanthal distance was reduced to age-adjusted normal values in all cases. On the operated side, stable improvement was observed in terms of the distance from the medial canthus to the midline, although some degree of recurrence was noted in most of the patients. The use of a microanchor system for medial canthopexy can be considered an easily performed and effective option for treating canthal dystopia, especially when an ipsilateral approach is preferred.

Meta-analysis of infrapopliteal angioplasty for chronic critical limb ischemia

Background: Percutaneous transluminal angioplasty has been used with increasing frequency in the treatment of infrainguinal arterial occlusive disease. This meta-analysis aimed to assess the middle-term outcomes after crural angioplasty in patients with chronic critical limb ischemia and compare results with a meta-analysis of popliteal-to-distal vein bypass graft. Methods: Data were retrieved from 30 articles published from 1990 through 2006 (63% of articles published between 2000 and 2006). All studies used survival analysis, reported a 12-month cumulative rate of patency or limb salvage, and included at least 15 infrapopliteal angioplasties. The outcome measures were immediate technical success, primary and secondary patency, limb salvage, and patient survival. Data from life-tables, survival curves, and texts were used. Results. The pooled estimate of success was 89.0% +/- 2.2% for immediate technical result. Results at 1 and 36 months were 77.4% +/- 4.1% and 48.6% +/- 8.0% for primary patency, 83.3% +/- 1.4% and 62.9% +/- 11.0% for secondary patency, 93.4% +/- 2.3% and 82.4% +/- 3.4% for limb salvage, and 98.3% +/- 0.7% and 68.4% +/- 5.5% for patient survival, respectively. Studies with >75% of the limbs with tissue loss fared worse than their respective comparative subgroup for technical success and patency but not for limb salvage or survival. No publication bias was detected. Conclusion: The technical success and subsequent durability of crural angioplasty are limited compared with bypass surgery, but the clinical benefit is acceptable because limb salvage rates are equivalent to bypass surgery. Further studies are necessary to determine the proper role of infrapopliteal angioplasty.