Currently, conjunctivitis is treated using ofloxacin eye drop solution, which shows low bioavailability and patient non-compliance. Ofloxacin loaded contact lens can be used to overcome the issues related to eye drop solutions (i.e. low bioavailability and frequent instillation). However, the conventional soaking method shows poor ofloxacin uptake and significantly affect the swelling and optical properties of the contact lenses. The current research investigates the effect of microemulsion on the ofloxacin uptake and its effect on the physical properties of the contact lens along with ofloxacin-release kinetics. In comparison to the conventional soaking method (Of-SM, ofloxacin-packaging solution), the ofloxacin loaded microemulsion-soaked contact lenses (Of-ME) showed improved drug uptake and physical properties of the contact lenses. The in vitro release data of Of-ME contact lenses showed 72-120 h release profile, while Of-SM contact lenses showed 24-60 h. The in vivo drug release data in the tear fluid (New Zealand rabbit's eye) showed high ofloxacin retention in comparison to the eye drop solution. The efficacy study in the rabbit model showed equivalent healing effect with the Of-ME contact lens in comparison to the frequent high dose eye drop therapy. Thus, the study demonstrates the application of microemulsion system to improve the ofloxacin loading capacity in the contact lens along with improvement in the physical properties to treat conjunctivitis.
Abstract Background: Mammalian target of rapamycin (mTOR) is a downstream regulatory protein of PI3K/AKT signal transduction pathway. The activation of cell surface receptors including IGF-1R (Insulin-Growth Factor-1Receptor) and EGFR (Epidermal Growth Factor Receptor) signals through PI3K/AKT pathway and is essential in cell proliferation, angiogenesis and anti-apoptosis process. Over activation of PI3K/AKT is a potential mechanism of resistance to mTOR inhibitors. mTOR inhibition could be a potential novel strategy in the treatment of lung cancer. Docetaxel (D) is commonly used in lung cancer treatment. Previously, we demonstrated that the sequence of D followed by mTOR inhibitor temsirolimus (T) in lung cancer cell lines (LCCL) had increased suppression of cell proliferation as compared to reverse sequence of T→D. The reason for this difference in decrease in proliferation effect is unclear. We hypothesized that D→T sequence can suppress the over activation of PI3K/AKT mechanism of resistance. We studied the expression of pmTOR, AKT and PI3K expression in lung cancer cell lines treated with different sequences of D and T and at different time points. Methods: Adenocarcinoma LCCL H2122 and H1437 were treated with T 1000nM or D 100nM for 24, 48 and 72h. We then treated both LCCL with D exposed for 24h followed by addition of T and the reverse sequence in both LCCL and prepared cell lysate at 24, 48 and 72h time points. We determined the expression of pmTOR, pAKT and PI3K by western blot using antibody from Cell Signaling. Results: T alone suppressed pmTOR after 24h but not at 48 and 72h in both LCCL. AKT was not suppressed. PI3K increased after 48h in both LCCL. The sequence of D→T suppressed expression of pmTOR and decreased expression of pAKT and PI3K at 48 and 72h in the H1437. We observed suppression of mTOR and PI3K but not AKT in the H2122. The opposite sequence of T→D did not suppress the expression of pmTOR and did not suppress the expression of pAKT and PI3K. Conclusion: The combination of D → T has synergistic inhibition of mTOR and it is able to suppress the over activation of AKT/PI3K pathway when compared with reverse sequence. This suggests that sequence of D→T can overcome the over activation of PI3K/AKT mechanism of resistance and it would be the ideal treatment sequence when using D in combination with mTOR inhibitor in the treatment of lung cancer. Expression of AKT/PI3K could be used as a biomarker of response to this regimen. Citation Format: Chao H. Huang, Peter J. VanVeldhuizen, Stephen K. Williamson, Ayten Gadashova, Faris Farassati. Docetaxel followed by temsirolimus suppresses mTOR pathway and can overcome PI3K / AKT over activation mechanism of resistance in lung cancer cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5654. doi:10.1158/1538-7445.AM2013-5654
Minimally invasive surgery (MIS) has been the preferred surgery approach owing to its advantages over conventional open surgery. As a major limitation, the lack of tactile perception impairs the ability of surgeons in tissue distinction and maneuvers. Many studies have been reported on industrial robots to perceive various tactile information. However, only force data are widely used to restore part of the surgeon’s sense of touch in MIS. In recent years, inspired by image classification technologies in computer vision, tactile data are represented as images, where a tactile element is treated as an image pixel. Processing raw data or features extracted from tactile images with artificial intelligence (AI) methods, including clustering, support vector machine (SVM), and deep learning, has been proven as effective methods in industrial robotic tactile perception tasks. This holds great promise for utilizing more tactile information in MIS. This review aims to provide potential tactile perception methods for MIS by reviewing literatures on tactile sensing in MIS and literatures on industrial robotic tactile perception technologies, especially AI methods on tactile images.
LCNEC of the lung comprises a small proportion of pulmonary malignancies. Traditionally, they have been classified based on histologic and immunohistochemistry characteristics with features of small cell and non-small cell lung cancer. The treatment outcome of advanced-stage LCNEC of the lung is poor with response rates ranging from 34 to 46% with platinum doublets, median progression-free survival (mPFS) ranging between 4.4 and 5.8 m, and median overall survival (mOS) ranging from 8 to 12.6 m. The optimal treatment strategy for LCNEC is debated given limited data and different outcomes based on chemotherapy type reported in the available literature. Recently, genomic profiling with Next Generation Sequencing (NGS) has been able to sub-classify LCNEC as SCLC-like or NSCLC-like. Treatment based on this sub-classification has improved outcomes by using SCLC and NSCLC regimens based on their genomic profile in retrospective analysis. Future studies in LCNEC of the lung should incorporate this new molecular sub-classification as stratification and possibly include SCLC-like LCNEC into SCLC studies and NSCLC-like into NSCLC studies.
Brachial plexus avulsion (BPA), which commonly occurs in neonatal birth injuries and car accidents, severely disrupts spinal cord segments and nerve roots. Avulsion is usually located in the transitional zone at the junction of spinal nerve roots and starting point of the spinal cord, which places heavy disability burdens on patients due to sensory and motor function loss in the innervated areas. Primary mechanical injuries and secondary pathogenesis, such as inflammatory infiltration and oxidative stress, lead to inefficient management and poor prognosis. Astaxanthin (AST) has a strong ability to bleach singlet oxygen and capture free radicals, quench singlet oxygen and trap free radicals, and folic acid (FC) can effectively inhibit the inflammatory response. This study aimed to investigate the therapeutic effects of AST and FC on BPA. The 24 h after BPA was considered the acute phase of the injury, and the combination of AST and FC had the best therapeutic effect due to the synergistic effect of AST’s antioxidant and FC’s anti-inflammatory properties. At 6 weeks after BPA, AST-FC promoted the recovery of biceps motor functions, increased myofiber diameter, enlarged the amplitude of musculocutaneous nerve-biceps compound action potential, and improved Terzis grooming test (TGT) scores. Meanwhile, more functional ventral horn motor neurons in the spinal cord were maintained. In conclusion, AST-FC combined therapy has a potential role in the clinical management of BPA since it can effectively alleviate oxidative stress and the inflammatory response in the acute phase of BPA, increase the survival rate of neurons, and promote neuronal regeneration and recovery of motor functions in the late stage of BPA.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)