Ahluwalia G.S.,Allergan, Inc.
The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research | Year: 2013
Few dermatologic conditions carry as much anxiety and emotional distress as hair loss resulting from a disease condition such as alopecia areata or as a result of cytotoxic drug treatment, e.g., after chemotherapy. Bimatoprost 0.03% solution is a Food and Drug Administration-approved prescription product indicated for the treatment of eyelash hypotrichosis. The product was investigated in a double-masked, randomized, and placebo-controlled study in patients who had significant eyelash loss or hypotrichosis as a result of chemotherapy. Once-daily treatment with bimatoprost ophthalmic solution 0.03% to the upper eyelid margin restored eyelash growth and prominence more quickly than the slower, natural course of recovery observed in the vehicle control subjects. The eyelash prominence measured using a validated Global Eyelash Assessment (GEA) scale demonstrated a statistically significant increase over placebo following 6 months of treatment. Efficacy was also demonstrated using a validated objective digital image analysis methodology to show significant increase in eyelash length, thickness/fullness, and darkness in these patients. Bimatoprost was found to be well tolerated over the 1-year treatment period.
Messina D.J.,Allergan, Inc.
Plastic and Reconstructive Surgery | Year: 2014
Background: Hyaluronic acid-based dermal fillers have gained rapid acceptance for treating facial wrinkles and deep tissue folds. Although their spacefilling properties are well understood, this study evaluates the cellular and molecular changes in skin, as a secondary effect, following injection of a commercially available, 24-mg/ml, cross-linked hyaluronic acid-based filler (HYC-24L+) in a rodent model. Methods: Sprague-Dawley rats, aged 2 to 4 months, were injected intradermally with 20 μl of HYC-24L+ using a linear threading technique and followed to 12 weeks after injection. Untreated skin and saline injection were used as study controls. Enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction methods were used to investigate changes in the expression of several extracellular matrix proteins and genes over time. Results: HYC-24L+ significantly increased the protein expression levels of collagen types I and III in rat dermal tissue for up to 12 weeks. The ratio of collagen type III to type I protein, however, remained unchanged, suggesting maintenance of collagen homeostasis. A significant increase in dermal elastin after HYC-24L+ injection was also observed. Gene expression analysis confirmed that several genes associated with extracellular matrix production and assembly were also transiently up-regulated, and that these changes temporally preceded those observed at the protein level. Conclusion: In addition to its well-understood space-filling function, as a secondary effect, the authors demonstrate that HYC-24L+ stimulates the production of several extracellular matrix components, including dermal collagen and elastin. Copyright © 2014 by the American Society of Plastic Surgeons.
Spear S.L.,Georgetown University |
Murphy D.K.,Allergan, Inc.
Plastic and Reconstructive Surgery | Year: 2014
Background:: Allergan's Natrelle round silicone-filled breast implants were approved by the U.S. Food and Drug Administration in 2006 based on interim results from the Core Study; final 10-year study results are now available. Methods:: Seven hundred fifteen subjects were implanted with smooth and Biocell textured Natrelle round silicone implants and attended clinic visits at 0 to 4 weeks, 6 months, 1 year, and annually through 10 years. Approximately one-third of subjects underwent magnetic resonance imaging at years 1, 3, 5, 7, and 9 to assess rupture. Results:: Complication rates showed modest increases over the previously published 6-year rates. The Kaplan-Meier capsular contracture rate was 18.9 percent for augmentation, 28.7 percent for revision-augmentation, and 24.6 percent for reconstruction. Among augmentation subjects, capsular contracture was significantly lower (p = 0.023) for submuscular (15.7 percent) versus subglandular (26.3 percent) placement. The overall rupture rate in the magnetic resonance imaging cohort was 13.0 percent for subjects and 7.7 percent for implants. By the end of the study, 81.8 percent of augmentation subjects still had an original implant in place. Using a five-point scale, 94.2 percent of augmentation, 83.8 percent of revision-augmentation, and 90.7 percent of reconstruction subjects reported being satisfied or definitely satisfied with their implants. Significant improvement over baseline was also seen in overall breast satisfaction and satisfaction with breast size, shape, feel, and how well they matched. Conclusion:: The 10-year data from the Natrelle Core Study, which can guide surgeons and patients in decision-making, demonstrate safety and high levels of patient satisfaction. Copyright © 2014 by the American Society of Plastic Surgeons.
Cunningham J.J.,Allergan, Inc. |
Ulbright T.M.,Indiana University |
Pera M.F.,Walter and Eliza Hall Institute of Medical Research |
Looijenga L.H.J.,Erasmus University Rotterdam
Nature Biotechnology | Year: 2012
The potential for the formation of teratomas or other neoplasms is a major safety roadblock to clinical application of pluripotent stem cell therapies. Preclinical assessment of the risk of tumor formation in this context poses considerable scientific and regulatory challenges, especially because animal xenograft models may not properly reflect the long-term tumorigenic potential of human cells. A better understanding of the biology of spontaneously occurring teratomas and related tumors in humans can help to guide efforts to assess and minimize the potential hazards of embryonic stem cell or induced pluripotent stem cell therapeutics. Here we review the features of teratomas derived experimentally from human pluripotent stem cells and argue that they most closely resemble spontaneous benign teratomas that occur early in both mouse and human life. The natural history and pathology of these spontaneously occurring teratomas provide important clues for preclinical safety assessment and patient monitoring in trials of stem cell therapies. © 2012 Nature America, Inc. All rights reserved.
Woodward D.F.,Allergan, Inc. |
Jones R.L.,University of Strathclyde |
Narumiya S.,Kyoto University
Pharmacological Reviews | Year: 2011
It is now more than 15 years since the molecular structures of the major prostanoid receptors were elucidated. Since then, substantial progress has been achieved with respect to distribution and function, signal transduction mechanisms, and the design of agonists and antagonists (http://www.iuphar-db.org/ DATABASE/FamilyIntroductionForward? familyId=58). This review systematically details these advances. More recent developments in prostanoid receptor research are included. The DP 2 receptor, also termed CRTH2, has little structural resemblance to DP 1 and other receptors described in the original prostanoid receptor classification. DP 2 receptors are more closely related to chemoattractant receptors. Prostanoid receptors have also been found to heterodimerize with other prostanoid receptor subtypes and nonprostanoids. This may extend signal transduction pathways and create new ligand recognition sites: prostacyclin/thromboxane A 2 heterodimeric receptors for 8-epi-prostaglandin E 2, wild-type/alternative (alt4) heterodimers for the prostaglandin FP receptor for bimatoprost and the prostamides. It is anticipated that the 15 years of research progress described herein will lead to novel therapeutic entities. © 2011 by The American Society for Pharmacology and Experimental Therapeutics.