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Dental health in children with phenylketonuria PKU and other inborn errors of amino acid metabolism managed by diet /

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Physical enhancement of transdermal drug application: is delivery technology keeping up with pharmaceutical development?

Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities.

A theoretical exploration of catchment-scale sediment delivery

This paper proposes a theoretical explanation of the variations of the sediment delivery ratio (SDR) versus catchment area relationships and the complex patterns in the behavior of sediment transfer processes at catchment scale. Taking into account the effects of erosion source types, deposition, and hydrological controls, we propose a simple conceptual model that consists of two linear stores arranged in series: a hillslope store that addresses transport to the nearest streams and a channel store that addresses sediment routing in the channel network. The model identifies four dimensionless scaling factors, which enable us to analyze a variety of effects on SDR estimation, including (1) interacting processes of erosion sources and deposition, (2) different temporal averaging windows, and (3) catchment runoff response. We show that the interactions between storm duration and hillslope/channel travel times are the major controls of peak-value-based sediment delivery and its spatial variations. The interplay between depositional timescales and the travel/residence times determines the spatial variations of total-volume-based SDR. In practical terms this parsimonious, minimal complexity model could provide a sound physical basis for diagnosing catchment to catchment variability of sediment transport if the proposed scaling factors can be quantified using climatic and catchment properties.

Impact of an intensive nursing education course on nurses' knowledge, confidence, attitudes, and perceived skills in the care of patients with cancer

Purpose/Objectives: To evaluate the impact of a cancer nursing education course on RNs. Design: Quasi-experimental, longitudinal, pretest/post-test design, with a follow-up assessment six weeks after the completion of the nursing education course. Setting: Urban, nongovernment, cancer control agency in Australia. Sample: 53 RNs, of whom 93% were female, with a mean age of 44.6 years and a mean of 16.8 years of experience in nursing; 86% of the nurses resided and worked in regional areas outside of the state capital. Methods: Scales included the Intervention With Psychosocial Needs: Perceived Importance and Skill Level Scale, Palliative Care Quiz for Nurses, Breast Cancer Knowledge, Preparedness for Cancer Nursing, and Satisfaction With Learning. Data were analyzed using multiple analysis of variance and paired t tests. Main Research Variables: Cancer nursing-related knowledge, preparedness for cancer nursing, and attitudes toward and perceived skills in the psychosocial care of patients with cancer and their families. Findings: Compared to nurses in the control group, nurses who attended the nursing education course improved in their cancer nursing-related knowledge, preparedness for cancer nursing, and attitudes toward and perceived skills in the psychosocial care of patients with cancer and their families. Improvements were evident at course completion and were maintained at the six-week follow-up assessment. Conclusions: The nursing education course was effective in improving nurses' scores on all outcome variables. Implications for Nursing: Continuing nursing education courses that use intensive mode timetabling, small group learning, and a mix of teaching methods, including didactic and interactive approaches and clinical placements, are effective and have the potential to improve nursing practice in oncology.

Drug delivery strategies for the treatment of Helicobacter pylori infections

Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. © 2005 Bentham Science Publishers Ltd.

Comparison and characterisation of ribozyme delivery in cultured glial and neuronal cells in vivo and in vitro

Ribozymes are short strands of RNA that possess a huge potential as biological tools for studying gene expression and as therapeutic agents to down-regulate undesirable gene expression. Successful application of ribozymes requires delivery to the target site in sufficient amounts for an adequate duration. However, due to their large size and polyanionic character ribozymes are not amenable to transport across biological membranes. In this study a chemically modified ribozyme with enhanced biological stability, targeted against the EGFR mRNA has been evaluated for cellular delivery to cultured glial and neuronal cells with a view to developing treatments for brain tumours. Cellular delivery of free ribozyme was characterised in cultured glial and neuronal cells from the human and rat. Delivery was very limited and time dependent with no consistent difference observed between glial and neuronal cells in both species. Cellular association was largely temperature and energy-dependent with a small component of non-energy dependent association. Further studies showed that ribozyme cellular association was inhibited with self and cross competition with nucleic and non-nucleic acid polyanions indicating the presence of cell surface ribozyme-binding molecules. Trypsin washing experiments further implied that the ribozyme binding surface molecules were protein by nature. Dependence of cellular association on pH indicated that interaction of ribozyme with cell surface molecules was based on ionic interactions. Fluoresence studies indicated that, post cell association, ribozymes were sequestered in sub-cellular vesicles. South-Western blots identified several cell surface proteins which bind to ribozymes and could facilitate cellular association. The limited cellular association observed with free ribozyme required the development and evaluation of polylactide-co-glycolide microspheres incorporating ribozyme for enhanced cellular delivery. Characterisation of microsphere mediated delivery of ribozyme in cultured glial and neuronal cells showed that association increased by 18 to 27-fold in all cell types with no differences observed between cell lines and species. Microsphere mediated delivery was temperature and energy dependent and independent of pH. In order to assess the potential of PLGA micro spheres for the CNS delivery of ribozyme the distribution of ribozyme entrapping microspheres was investigated in rat CNS after intracerebroventricular injection. Distribution studies demonstrated that after 24 hours there was no free ribozyme present in the brain parenchyma, however microsphere entrapped ribozyme was found in the CNS. Microspheres remained in the ventricular system after deposition and passed from the lateral ventricles to the third and fourth ventricle and in the subarachnoid space. Investigation of the influence of microsphere size on the distribution in CNS demonstrated that particles up to 2.5 and O.5f.lm remained in the ventricles around the choroid plexus and ependymal lining.

Novel formulations for antigen delivery using biodegradable polymers: new approaches for the use of new and established adjuvants

The use of immunological adjuvants has been established since 1924 and ever since many candidates have been extensively researched in vaccine development. The controlled release of vaccine is another area of biotechnology research, which is advancing rapidly with great potential and success. Encapsulation of peptide and protein drugs within biodegradable microspheres has been amongst the most successful of approaches within the past decade. The present studies have focused on combining the advantages of microsphere delivery systems composed of biodegradable polylactide (PLLA) and polylactide-co-glycolide (PLGA) polymers with that of safe and effective adjuvants. The research efforts were directed to the development of single-dose delivery vehicles which, can be manufactured easily, safely, under mild and favourable conditions to the encapsulated antigens. In pursuing this objective non ionic block copolymers (NIBCs) (Pluronics@ LI01 and L121) were incorporated within poly-dl-lactide (PDLA) micorospheres prepared with emulsification-diffusion method. LI0I and L121 served both as adjuvants and stabilising agents within these vaccine delivery vehicles. These formulations encapsulating the model antigens lysozyme, ovalbumin (OVA) and diphtheria toxoid (DT) resulted in high entrapment efficiency (99%), yield (96.7%) and elicited high and sustained immune response (IgG titres up to 9427) after one single administration over nine months. The structural integrity of the antigens was preserved within these formulations. In evaluating new approaches for the use of well-established adjuvants such as alum, these particles were incorporated within PLLA and PLGA microspheres at much lesser quantities (5-10 times lower) than those contained within conventional alum-adsorbed vaccines. These studies focused on the incorporation of the clinically relevant tetanus toxoid (TT) antigen within biodegradable microspheres. The encapsulation of both alum particles and TT antigen within these micropheres resulted in preparations with high encapsulation efficiency (95%) and yield (91.2%). The immune response to these particles was also investigated to evaluate the secretion of serum IgG, IgG1, IgG2a and IgG2b after a single administration of these vaccines. The Splenic cells proliferation was also investigated as an indication for the induction of cell mediated immunity. These particles resulted in high and sustained immune response over a period of 14 months. The stability of TT within particles was also investigated under dry storage over a period of several months. NIBC microspheres were also investigated as potential DNA vaccine delivery systems using hepatitis B plasmid. These particles resulted in micro spheres of 3-5 μm diameter and were shown to preserve the integrity of the encapsulated (27.7% entrapment efficiency) hepatitis B plasmid.

Unified model for performance analysis of IEEE 802.11 ad hoc networks in unsaturated conditions

IEEE 802.11 standard has achieved huge success in the past decade and is still under development to provide higher physical data rate and better quality of service (QoS). An important problem for the development and optimization of IEEE 802.11 networks is the modeling of the MAC layer channel access protocol. Although there are already many theoretic analysis for the 802.11 MAC protocol in the literature, most of the models focus on the saturated traffic and assume infinite buffer at the MAC layer. In this paper we develop a unified analytical model for IEEE 802.11 MAC protocol in ad hoc networks. The impacts of channel access parameters, traffic rate and buffer size at the MAC layer are modeled with the assistance of a generalized Markov chain and an M/G/1/K queue model. The performance of throughput, packet delivery delay and dropping probability can be achieved. Extensive simulations show the analytical model is highly accurate. From the analytical model it is shown that for practical buffer configuration (e.g. buffer size larger than one), we can maximize the total throughput and reduce the packet blocking probability (due to limited buffer size) and the average queuing delay to zero by effectively controlling the offered load. The average MAC layer service delay as well as its standard deviation, is also much lower than that in saturated conditions and has an upper bound. It is also observed that the optimal load is very close to the maximum achievable throughput regardless of the number of stations or buffer size. Moreover, the model is scalable for performance analysis of 802.11e in unsaturated conditions and 802.11 ad hoc networks with heterogenous traffic flows. © 2012 KSI.

The design of contact lens based ocular drug delivery systems for single-day use:part (I) structural factors, surrogate ophthalmic dyes and passive diffusion studies

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effects of nursing interventions for fever in acutely ill adults

Fever has both beneficial and detrimental effects. There is evidence that antipyretics and physical cooling methods, when used in combination, are more effective than antipyretics alone. This randomized controlled study examined 45 acutely ill adults with fever ${\ge}102.5\sp\circ\rm F$ where three nursing interventions were used. Group I received acetaminophen 650 mgs., Group II received acetaminophen 650 mgs. and tepid sponging, and Group III received acetaminophen 650 mgs. and hypothermia blanket. The purpose of this study was to evaluate which nursing intervention reduced temperature most effectively with respect to eight biobehavioral variables. Research hypotheses were tested statistically using the chi-square test and repeated measures analysis of variance. The study found statistically significant results for fever reduction overall, but no difference for the groups. Therefore, we suggest that acetaminophen alone be used in the treatment of fever in order to decrease cost, nursing time, and increase patient comfort. ^