´╗┐Fiskerstrand EJ, Svaasand LO, Kopstad G, Ryggen K, Aase S

´╗┐Fiskerstrand EJ, Svaasand LO, Kopstad G, Ryggen K, Aase S. system as described in legend (as indicated in legend. Each represents entire patient population of Naspm study, referenced on left side Naspm of chart, whereby patient percentages are provided on bottom on right side of chart indicates type of classification system, which has been color coded according to level of cl as provided behind every legend entry. Each represents entire patient population of study, referenced on left side of chart, whereby patient percentages are provided on bottom ) at increasing vacuum pressures and suction times (B). A, Healthy volunteers with Fitzpatrick skin types II and III were subjected to laser irradiation at radiant exposure as indicated in legend, and extent of purpura was imaged at indicated times after laser irradiation. Purpura induced without use of suction device (and em dots /em )153 in vicinity of laser-induced, semiobstructive thermal coagulum. Release of prothrombotic and antifibrinolytic brokers promotes hyperthrombosis and deterrence of fibrinolysis, culminating in thrombotic occlusion and hemostasis of blood vessel that otherwise would have remained incompletely photo-occluded (X). Because this damage profile is comparable to completely photocoagulated vasculature, 24 SSPLT may prove promising in improving lesional clearance rates. There Naspm are numerous classes of pharmaceuticals that modulate the hemodynamic response via induction of hyperthrombosis (eg, platelet activators, coagulation agonists) and deterrence of fibrinolysis (eg, plasmin inhibitors). Because such drugs may produce undesirable adverse effects, the pharmaceuticals are to be encapsulated in a thermosensitive liposomal drug delivery system and specifically targeted to PDL-irradiated vasculature. Liposomes are nanoscopic fat droplets that can encapsulate water-soluble and lipophilic drugs. Moreover, liposomal encapsulation restricts the biological activity of the drugs until they are released from the liposomes. Drug release Naspm can be systematically brought on via thermal, oxidative, enzymatic, or chemical processes. The liposomes for SSPLT are selectively targeted to the thrombus (ie, via antibodies specific only to receptors on activated platelets involved in thrombosis) (Fig 5, step 2 2). Once the liposomes have accumulated in the thrombus, drug release will be brought on by local generation of heat using a heating pad or near infrared light (Fig 5, step 3 3). This will lead to site-specific hyperthrombosis and complete Naspm occlusion of the target vasculature (Fig 5, step 4 4), effecting the removal of blood vessels that would have otherwise remained partially patent. SSPLT may be combined with immunomodulatory and/or antiangiogenic modalities as described above to further modulate the chronic responses to laser therapy.24 Currently, the prothrombotic and antifibrinolytic liposomal formulations have been developed and characterized in vitro152 and will be tested in vivo before the end of 2011. Once proof of concept has been established as to their targeting specificity and pharmacodynamics, and toxicological testing has been completed, clinical Rabbit Polyclonal to SCARF2 phase II trials will be initiated. CONCLUSION Despite innovations in various laser techniques, our retrospective analysis shows that the number of patients with PWS who do not achieve complete lesion removal with current treatment modalities remains substantial. Consequently, the exploration and implementation of alternative therapies is necessary for improvement of therapeutic efficacy. Treatment failure has largely been attributed to lesional variation, posttreatment angiogenesis, and limitations in optical penetration depth. Several promising approaches have been presented that may improve therapeutic efficacy, including PDT, immunomodulation, antiangiogenesis therapy, hypobaric pressure devices, and SSPLT. ? CAPSULE SUMMARY The pulsed dye laser currently remains the treatment of choice for port wine stain (PWS) lesions. Despite innovations in various laser techniques and applications, the number of PWS refractory to current treatment modalities remains substantial. New experimental modalities are currently under investigation, including the use of photodynamic therapy, immune modulators, angiogenesis inhibitors, hemodynamic alterations in PWS vasculature, and site-specific pharmacolaser therapy. Alternative therapies will be required to increase the efficacy of PWS treatment. Supplementary Material 01Click here to view.(170K, pdf) Acknowledgments Dr Aguilar was funded by grant HD042057from the National Institutes of Health (NIH). Dr Kelly was funded by the NIH (AR51443 and HD065536), the American Society for Laser Medicine and Surgery, and a research grant from.

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