Investigations of the assessment of bioequivalence of topical clotrimazole products using a dermatopharmacokinetic approach

The specialised nature of the stratum corneum makes it an efficient barrier to foreign substances, including drug molecules. Therefore, cutaneous drug absorption is a slow and complex process of which stratum corneum penetration is the rate limiting step. The rate and extent of stratum corneum penetration by a drug compound depends greatly on the presence of penetration enhancing/retarding excipients and therefore the clinical outcomes of a product rely greatly on the components and quality of the formulation. Hence, establishing bioequivalence between topical products is crucial to ensure that patients receiving multisource drug products are assured of the same efficacy and safety as the brand product. Since locally acting topical formulations do not target the systemic circulation, conventional methods of assessing bioequivalence using plasma levels are not appropriate. Consequently, the current regulatory guidelines require comparative clinical trials to be carried out to show bioequivalence between topical products. As these studies are very expensive and time consuming, the development of a more direct and relatively rapid and inexpensive method for determining bioequivalence between topical products is required. Clotrimazole is an anti-fungal agent where the target site of action is in the stratum corneum. In this work, tape stripping, which involves the sampling of stratum corneum, was investigated as a tool for the determination of bioequivalence between topical clotrimazole products. The tape stripping method involved the analysis of each tape strip individually and standardization of stratum corneum thickness between subjects was carried out using TEWL measurements. This approach provided detailed information regarding the amount of clotrimazole present in the stratum corneum as well as the extent of drug penetration. Prior to the tape stripping studies an HPLC method was developed for the quantitative analysis of clotrimazole from the tape strip samples. This method was shown to be accurate and reproducible across the required range. It was also shown to be selective for clotrimazole in the presence of possible interfering substances such as those present in the tape adhesive and also skin components. The bioequivalence studies were conducted using a single “uptake” time point. In order to determine an appropriate dose duration for these studies a novel approach was employed, involving a preliminary dose duration study. For the bioequivalence investigations, Canesten® Topical cream was used as both test and reference products to determine if the method was capable of showing bioequivalence. Subsequently, Canesten® Topical cream was also compared to a 1% gel formulation to determine if the method could detect formulation differences. The conventional BE limits of 0.8 – 1.25 were used for the assessment of BE, however, the clinical relevance of using these limits for dermal studies is debatable since they are derived from oral pharmacokinetic studies. Therefore, the data from the tape stripping investigations were also assessed using more realistic limits of 0.75 – 1.33 and even 0.7 – 1.44. In addition to the tape stripping studies a novel method of determining the amount of drug present in the stratum corneum, the “Residual Method”, was investigated. This method involved assaying the amount of clotrimazole found in the residual formulation after a specified dose duration had elapsed and subtracting that amount from the amount of clotrimazole initially applied. The results of tape stripping investigations showed that, if the study is sufficiently powered, tape stripping may be used to determine bioequivalence according to the conventional limits, as well as possibly detect formulation differences between different clotrimazole products. Bioequivalence assessment using the widened intervals showed that fewer subjects were required to achieve a sufficient statistical power. The variability associated with this method was acceptable and tape stripping may therefore have the potential to be used as a BE tool in a regulatory setting for clotrimazole or other antifungal topical formulations. The “Residual Method” also showed promising results as a bioequivalence tool, but further investigation and extensive validation of this method is required before it can be suggested as a regulatory method. The results of these studies have clearly indicated that tape stripping has the potential to be used as an alternative to comparative clinical trails for the assessment of bioequivalence between clotrimazole formulations and also to assess bioequivalence between other antifungal products

Ego functions in art therapy: Utilizing ego strengths and weaknesses in treatment

This study explores the artwork of three patients diagnosed with schizophrenia to determine if Leopold Bellak's demarcation of twelve ego functions are manifested in art therapy products and processes. Patient drawing and sculpting manifestations are examined as well as patient behavior, thought processes and affect in order to determine ego functioning. The artwork was collected over the course of a single hospitalization and the associations, behavioral responses and affect were all recorded and integrated with the artwork. Psychoanalytic and ego psychology theories of ego functions and ego maturation are presented. Bellak's definitions of twelve ego Junctions are presented and compared to other theorists' views. Some treatment issues in art therapy's application of ego functioning include symbol formation, the therapeutic relationship, regressed affective states and the neutralization of primary process material. The major findings of this study were that levels ego functioning were suggested by art manifestations, associations to artwork, behavior in art processes and thought processes during the discussions of artwork. An ego based framework utilized in art therapy can emphasize strengths in the ego of a patient for treatment practices in clinical art therapy.M.A., Creative Arts Therapy -- Hahnemann University, 199

Non-Additive Toxicity of Bi-Metal Mixtures to Fathead Minnows

Much research has been conducted to assess the toxicity of metals to aquatic organisms. Most of the research has focused on the toxicity of individual metals. Recently, attention has been paid to metal mixture toxicity because metals are usually present as mixtures in contaminated environments. The literature review indicates that metal mixtures may be additive, synergistic, or antagonistic to freshwater species. However, the data is not consistent and is dependent on the metal and organisms. The goal of this research is to use a systematic experimental design to characterize the toxicity of Cu, Zn, Cd and Ni mixtures to Pimephales promelas. Standard 96h toxicity tests were conducted with larval P. promelas based on the US EPA methods to determine metal mixture effects. All experiments were conducted in synthetic moderately hard water. Results of this study indicate that the toxicity of Cu-Zn, Cu-Ni, and Zn-Ni bi-mixtures was synergistic. These results suggest a joint mechanism of toxicity of these metal bi-mixtures in larval P. promelas. However, a biphasic dose response was found for Cd and Zn mixtures and P. promelas. The effect was antagonistic over all Zn concentrations. Results of this study are important for developing a Biotic Ligand Model for metal mixtures and useful for setting mixture water quality guidelines for metals

Digital Media Use in Art Therapy

This art-based, phenomenological inquiry investigated how four art therapists and five art therapy clients have used digital media. Polarities in how computer-mediated materials are experienced and the larger impacts of technology on clients, therapists, and the therapeutic encounter were exposed. New media have brought constant contradiction in characterization just as all previous technologies have reflected responses from unease to adaptation. Some key questions in the research are how digitized materials are being used in art therapy and by whom and when? Related questions are what effects can these materials have for clients and what learning, interests, and media adaptations have art therapists integrated to use the materials skillfully? The reflexive use of digital video recording and editing activities formed deeper levels of sustained inquiry for the researcher to create a two part written and video research investigation that distilled the following major themes and subthemes: 1) omnipresence of technology with the subtheme digital divides; 2) technology as a bridge between therapy and the everyday lives of clients; 3) openness to new generations and evolutions; 4) photography and video as access to memory and storytelling with related subthemes of veracity of the image and capture and documentation; 5) the ‘hybridness’ of the digital art therapist; 6) fluid parameters in digital media with a subtheme of fluid parameters in ethical boundaries; and 7) the inherent and sensory qualities of digital media to include: immediacy and playback, emotional distancing and pause, movability, mobility, re-presentation, ordering and winnowing, versatility, roadblocks, curious and playful, and predictable to unpredictable. Conclusions from this research include digital culture considerations for how growing numbers of clients and therapists are using digital media readily; how digital media can be characterized and dismissed through intuitive understanding of benefits and drawbacks and without sustained knowledge, experiential or creative application, or evaluation; and why interested, hybrid therapists are growing the applications of digital media use technically, creatively, and ethically. This researcher noted profound implications for future digital media use in therapy and how the conscious use, balancing with, and understanding of technology are not casual choices or behaviors but dynamic cultural shifts within growing media sphere contexts

Duration Differences in Different Vowel Classes of the Speech of the Elderly

The following study focused on the effects of aging on fricative durations in varying vowel contexts in the speech ofthe elderly

Soil characteristics and pedogenesis on sub-Antarctic Marion Island

Marion Island is a sub-Antarctic volcanic island with a cold, wet climate. Much of the interior of the island is bare, with vegetation only found at lower altitudes. No soil classification has yet been undertaken for the Island, and literature on its soils and pedogenesis is sparse. As part of a broader research project on Geomorphology and Climate Change the morphological, physical, chemical, mineralogical and biological properties of soils from seven terrestrial habitats on Marion Island were analysed. It was determined that pedogenesis has taken place on Marion Island. A relationship was observed between soils and terrestrial habitats. Soils were classified according to the World Reference Base (WRB) soil classification system as Histosols, Histic Andosols, Andosols and Regosols. Generalised soil profiles were constructed for each of the seven terrestrial habitats. The spatial distributions of soil types for the Island were predicted with the use of a GIS model and are presented, together with the implications of climate change for pedogenesis and soil distribution on Marion Island.Dissertation (MSc)--University of Pretoria, 2010.Geography, Geoinformatics and MeteorologyMScUnrestricte

Invasive Bush Honeysuckle Removal Coalition Proposal

Course Code: ENR 2367The objective of this paper is to communicate to the general public the importance of the removal of nonnative honeysuckle from Ohio ecosystems. With a cohesive plan that links together organizations that have already performed successful operations, and willing student volunteers, we believe we can create a lasting partnership that will keep Bush Honeysuckle under control.Academic Major: Criminology and Criminal Justice StudiesAcademic Major: Environment, Economy, Development, and SustainabilityAcademic Major: Environmental Policy and Decision MakingAcademic Major: Natural Resources Managemen

Pathology in skeletons of Peale's dolphin Lagenorhynchus australis from southern South America

Peale's dolphin Lagenorhynchus australis is frequently seen off the coast of southern South America, where it feeds among coastal kelp beds and occasionally strands. We searched for macroscopic evidence of skeletal lesions in 78 specimens of Peale's dolphin from 2 museum collections, which contain almost all of the species' skeletons known in collections worldwide. Thirtytwo specimens (41%) had some type of osteological abnormalities. In 21 cases (66%), congenital deformations were the most predominant abnormality found. Acquired lesions included (1) induced trauma: abnormal curvature (n = 5 specimens) and fractures (n = 2); (2) infectious diseases: spondylo-osteomyelitis (n = 3); and (3) degenerative diseases: exostoses (n = 8) and spondylosis deformans (n = 4). It is noteworthy that all of these animals died incidentally in gillnet entanglement and were presumably healthy at the time of death. The effect that different osseous lesions may have on an animal's quality of life may depend on the area of the spine affected and the number of vertebrae involved.Fil: San Martín, Analía Anahí. Museo Acatushún de Aves y Mamíferos Marinos Australes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Macnie, Silvina V.. Museo Acatushún de Aves y Mamíferos Marinos Australes; ArgentinaFil: Prosser Goodall, Rae Natalie. Museo Acatushún de Aves y Mamíferos Marinos Australes; ArgentinaFil: Boy, Claudia Clementina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentin

Universal and Programmable Thinning and Thickening of Topologically-Active DNA Fluids

Understanding and controlling the rheology of polymeric fluids that are out-of-equilibrium is a fundamental problem in biology and industry. For example, to package, repair, and replicate DNA, cells use enzymes to constantly manipulate DNA topology, length, and structure. Inspired by this impressive feat, we combine experiments with theory and simulations to show that complex fluids of entangled DNA display a rich range of non-equilibrium material properties when undergoing enzymatic reactions that alter their topology and size. We reveal that while enzymatically-active fluids of linear DNA display universal viscous thinning, circular DNA fluids - undergoing the same non-equilibrium process - display thickening with a rate and degree that can be tuned by the DNA and enzyme concentrations. Our results open the way for the topological functionalization of DNA-based materials via naturally occurring enzymes to create a new class of "topologically-active" materials that can autonomously alter their rheological properties in a programmable manner

Subdivisión funcional de la columna vertebral en cuatro delfines sudamericanos

Subdivisión funcional de la columna vertebral en cuatro delfines sudamericanos. La descripción e interpretación funcional de la variación morfológica en la columna de delfines pueden facilitarse mediante el reconocimiento de unidades estructurales a lo largo de toda la estructura de la columna. Esta información ofrece pistas importantes sobre la proporción de la columna involucrada en la oscilación y el desplazamiento de la aleta caudal, y cómo el estilo de natación puede variar entre las especies. Por lo tanto, la caracterización morfológica y la subdivisión funcional de la columna vertebral son de fundamental importancia para obtener información sobre el comportamiento locomotor de las especies de cetáceos que habitan ambientes diferentes. Se empleó morfometría tradicional para establecer la subdivisión funcional de la columna vertebral del delfín de la tonina overa (Cephalorhynchus commersonii), una especie costera, y el delfín oscuro (Lagenorhynchus obscurus), una especie de plataforma, realizando una primera caracterización morfológica de sus columnas vertebrales. Estas especies están estrechamente relacionadas y, en algunos casos, son parcialmente simpátricas. También comparamos los resultados obtenidos con información previamente reportada por Marchesi et al. (2017) para el delfín austral (Lagenorhynchus australis), una especie costera, y el delfín cruzado (Lagenorhynchus cruciger), una especie oceánica. Estos resultados apoyan nuestra hipótesis de que las especies costeras tienen rasgos morfológicos asociados con mayor flexibilidad, mientras que las especies oceánicas y de plataforma tienen características asociadas con una mayor estabilidad en una mayor proporción de su columna.Description and functional interpretation of morphological variation in the dolphin column can be facilitated by recognizing structural units. This information offers important clues to the proportion of the column involved in the oscillation and displacement of the flukes, and how swimming style can vary among species. Thus, the morphological characterization and functional subdivision of the vertebral column is of key importance to gain insights into the locomotor performance of cetacean species occurring in different environments. We employed traditional morphometrics to establish the functional subdivision of the vertebral column of Commerson’s dolphin (Cephalorhynchus commersonii), a coastal species, and the dusky dolphin (Lagenorhynchus obscurus), a shelf species. These species are closely related, and some of them are partially sympatric. We also compared the obtained results against information previously reported by Marchesi et al (2017) on Peale’s dolphin (Lagenorhynchus australis), a coastal species, and the hourglass dolphin (Lagenorhynchus cruciger), an oceanic species. These results bring further support to our hypothesis that coastal species have morphological traits associated with higher flexibility, whilst platform and oceanic species have features associated with higher stability in a greater proportion of their column.Fil: Marchesi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Mora, Matías Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Crespo, Enrique Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Boy, Claudia C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: González-José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; ArgentinaFil: Prosser Goodall, Rae Natalie. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Museo Acatushún de Aves y Mamíferos Marinos Australes; Argentin