PDLA a potential new potent topical analgesic: a case report.

Polymer D-lactic acid (PDLA) is a hydrogel that has been shown to sequester L-lactate (lactate). This reaction is rapid, spontaneous, and non-enzymatic. Lactate has been shown to have many functions within the nervous system including its use as a secondary fuel to sustain neural activity and as a neuromodulator. In the central nervous system, lactate is produced in glial cells and shuttled to neurons to be used mostly as a fuel. Lactate dehydrogenase (LDH)1 is the predominant LDH isoform within neurons and unlike LDH5, it preferentially converts lactate to pyruvate which can be used to produce adenosine triphosphate (ATP). Considering that lactate is intimately involved in the sustenance of neural activity, PDLA was applied to an open wound and its effects were examined. The results showed that the application of PDLA induced topical analgesia. This may be the first report to demonstrate that sequestering lactate, a source of energy required to sustain the firing of action potentials in neurons, may produce analgesia.

Analgésicos Tópicos

Background and objectives: Pain treatment involves the usage of common and opioid analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and adjuvant analgesics. Traditionally, these drugs are administered systemically or into the neuraxis. However, when analgesics are applied through these pathways, they are associated with significant side effects, which can hinder its use. Topical administration of analgesics is an alternative. The objective of this paper is to discuss topical analgesics, the mechanisms of action and clinical efficacy. Content: This is a review paper addressing the usage of the topical local anesthetics: capsaicin, clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids, discussing mechanism of action and effectiveness. Conclusions: Topical analgesics are promising as a strategy for pain treatment, as they are associated with lower incidence of side effects. The benefit of local anesthetics, NSAID's and capsaicin is well established. However, the efficacy of clonidine, tricyclic antidepressants, ketamine, opioids and cannabinoids is still questionable. Studies have shown that the multimodal approach is an alternative, but studies are needed to confirm this hypothesis. © 2012 Elsevier Editora Ltda.

Comparative efficacy of 2 topical anesthetics for the placement of orthodontic temporary anchorage devices.

This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P < .05) and success rate (P < .01) between drugs were seen, but no significant difference in pulse rate change between the topical anesthetics was observed (P > .05). It was concluded that when the efficacy of topical benzocaine and of a combination product was compared as the sole anesthetic to facilitate acceptable pain control for placement of orthodontic temporary anchorage devices, the combination product was considerably more efficacious.

Should topical opioid analgesics be regarded as effective and safe when applied to chronic cutaneous lesions?

Objectives: The induction of analgesia for many chronic cutaneous lesions requires treatment with an opioid analgesic. In many patients suffering with these wounds such drugs are either contraindicated or shunned because of their association with death. There are now case reports involving over 100 patients with many different types of chronic superficial wounds, which suggest that the topical application of an opioid in a suitable gel leads to a significant reduction in the level of perceived pain. Key findings: Some work has been undertaken to elucidate the mechanisms by which such a reduction is achieved. To date there have been no proven deleterious effects of such an analgesic system upon wound healing. Although morphine is not absorbed through the intact epidermis, an open wound provides no such barrier and for large wounds drug absorption can be problematic. However, for most chronic cutaneous lesions, where data has been gathered, the blood levels of the drug applied ranges from undetectable to below that required for a systemic effect. Summary If proven, the use of opioids in this way would provide adequate analgesia for a collection of wounds, which are difficult to treat in patients who are often vulnerable. Proof of this concept is now urgently required. © 2011 Royal Pharmaceutical Society.

Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

Challenges of tracking topical discussion networks online

Attempts to map online networks, representing relationships between people and sites, have covered sites including Facebook, Twitter, and blogs. However, the predominant approach of static network visualization, treating months of data as a single case rather than depicting changes over time or between topics, remains a flawed process. As different events and themes provoke varying interactions and conversations, it is proposed that case-by-case analysis would aid studies of online social networks by further examining the dynamics of links and information flows. This study uses hyperlink analysis of a population of French political blogs to compare connections between sites from January to August 2009. Themes discussed in this period were identified for subsequent analysis of topic-oriented networks. By comparing static blogrolls with topical citations within posts, this research addresses challenges and methods in mapping online networks, providing new information on temporal aspects of linking behaviors and information flows within these systems.

Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF

Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form of immunization to protect mice against genital tract and respiratory tract chlamydial infection. Protection was associated with local antibody responses in the vagina, uterus and lung as well as strong Th1 responses in the lymph nodes draining the reproductive tract and lungs respectively. In this study we show that topical application of GM-CSF to skin enhances the numbers and activation status of epidermal dendritic cells. Topical application of GM-CSF also increased the immune responses elicited by TCI. GM-CSF supplementation greatly increased cytokine (IFNgamma and IL-4) gene expression in lymph node and splenic cells compared to cells from animals immunized without GM-CSF. IgG responses in serum, uterine lavage and bronchoalveolar lavage and IgA responses in vaginal lavage were also increased by topical application of GM-CSF. The studies show that TCI induces protection against genital and respiratory tract chlamydial infections and that topical application of cytokines such as GM-CSF can enhance TCI-induced antibody and cell-mediated immunity.

Mapping intermedia news flows : topical discussions in the Australian and French political blogospheres

The growth of technologies and tools branded as =new media‘ or =Web 2.0‘ has sparked much discussion about the internet and its place in all facets of social life. Such debate includes the potential for blogs and citizen journalism projects to replace or alter journalism and mainstream media practices. However, while the journalism-blog dynamic has attracted the most attention, the actual work of political bloggers, the roles they play in the mediasphere and the resources they use, has been comparatively ignored. This project will look at political blogging in Australia and France - sites commenting on or promoting political events and ideas, and run by citizens, politicians, and journalists alike. In doing so, the structure of networks formed by bloggers and the nature of communication within political blogospheres will be examined. Previous studies of political blogging around the world have focussed on individual nations, finding that in some cases the networks are divided between different political ideologies. By comparing two countries with different political representation (two-party dominated system vs. a wider political spectrum), this study will determine the structure of these political blogospheres, and correlate these structures with the political environment in which they are situated. The thesis adapts concepts from communication and media theories, including framing, agenda setting, and opinion leaders, to examine the work of political bloggers and their place within the mediasphere. As well as developing a hybrid theoretical base for research into blogs and other online communication, the project outlines new methodologies for carrying out studies of online activity through the analysis of several topical networks within the wider activity collected for this project. The project draws on hyperlink and textual data collected from a sample of Australian and French blogs between January and August 2009. From this data, the thesis provides an overview of =everyday‘ political blogging, showing posting patterns over several months of activity, away from national elections and their associated campaigns. However, while other work in this field has looked solely at cumulative networks, treating collected data as a static network, this project will also look at specific cases to see how the blogospheres change with time and topics of discussion. Three case studies are used within the thesis to examine how blogs cover politics, featuring an international political event (the Obama inauguration), and local political topics (the opposition to the =Création et Internet‘, or HADOPI, law in France, the =Utegate‘ scandal in Australia). By using a mixture of qualitative and quantitative methods, the study analyses data collected from a population of sites from both countries, looking at their linking patterns, relationship with mainstream media, and topics of interest. This project will subsequently help to further develop methodologies in this field and provide new and detailed information on both online networks and internet-based political communication in Australia and France.

Should athletes return to sport after applying Ice? A systematic review of the effect of local 3 cooling on functional performance

Applying ice or other forms of topical cooling is a popular method of treating sports injuries. It is commonplace for athletes to return to competitive activity, shortly or immediately after the application of a cold treatment. In this article, we examine the effect of local tissue cooling on outcomes relating to functional performance and to discuss their relevance to the sporting environment. A computerized literature search, citation tracking and hand search was performed up to April, 2011. Eligible studies were trials involving healthy human participants, describing the effects of cooling on outcomes relating to functional performance. Two reviewers independently assessed the validity of included trials and calculated effect sizes. Thirty five trials met the inclusion criteria; all had a high risk of bias. The mean sample size was 19. Meta-analyses were not undertaken due to clinical heterogeneity. The majority of studies used cooling durations >20 minutes. Strength (peak torque/force) was reported by 25 studies with approximately 75% recording a decrease in strength immediately following cooling. There was evidence from six studies that cooling adversely affected speed, power and agility-based running tasks; two studies found this was negated with a short rewarming period. There was conflicting evidence on the effect of cooling on isolated muscular endurance. A small number of studies found that cooling decreased upper limb dexterity and accuracy. The current evidence base suggests that athletes will probably be at a performance disadvantage if they return to activity immediately after cooling. This is based on cooling for longer than 20 minutes, which may exceed the durations employed in some sporting environments. In addition, some of the reported changes were clinically small and may only be relevant in elite sport. Until better evidence is available, practitioners should use short cooling applications and/or undertake a progressive warm up prior to returning to play.

Intrapleural analgesia following endoscopic scoliosis correction

Endoscopic (thoracoscopic) scoliosis correction plays an important part in the surgical options available for treating adolescent idiopathic scoliosis. However, there is a paucity of literature examining optimum methods of analgesia following this type of surgery. Intra-pleural analgesia has been successfully used following cardiothoracic procedures [1-3]. The role of intra-pleural analgesia after keyhole anterior selective thoracic scoliosis correction is examined and described.