Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions

Gene therapy is expected to open a new strategy for the treatment of refractory vascular diseases, so the development of appropriate gene vectors for vascular lesions is needed. To realize this requirement with a non-viral approach, cyclo(RGDfK) peptide (cRGD) was introduced to block copolymer, poly(ethylene glycol)-block-polycation carrying ethylenediamine units (PEG-PAsp(DET)). cRGD recognizes αvβ3 and αvβ5 integrins, which are abundantly expressed in vascular lesions. cRGD-conjugated PEG-PAsp(DET) (cRGD-PEG-PAsp(DET)) formed polyplex micelles through complexation with plasmid DNA (pDNA), and the cRGD-PEG-PAsp(DET) micelles achieved significantly more efficient gene expression and cellular uptake as compared with PEG-PAsp(DET) micelles in endothelial cells and vascular smooth muscle cells. Intracellular tracking of pDNA showed that cRGD-PEG-PAsp(DET) micelles were internalized via caveolae-mediated endocytosis, which is associated with a pathway avoiding lysosomal degradation, and that PEG-PAsp(DET) micelles were transported to acidic endosomes and lysosomes via clathrin-mediated endocytosis. Further, in vivo evaluation in rat carotid artery with a neointimal lesion revealed that cRGD-PEG-PAsp(DET) micelles realized sustained gene expression, while PEG-PAsp(DET) micelles facilitated rapid but transient gene expression. These findings suggest that introduction of cRGD to polyplex micelles might create novel and useful functions for gene transfer and contribute to the establishment of efficient gene therapy for vascular diseases

Improved subjective symptoms of conjunctivochalasis using bipolar diathermy method for conjunctival shrinkage

Tomoyuki Kashima1,2, Hideo Akiyama1, Fumihide Miura2, Shoji Kishi11Department of Ophthalmology, Gunma University School of Medicine, Gunma, Japan; 2Department of Ophthalmology, Saku Central Hospital, Nagano, JapanPurpose: To evaluate the improvement in subjective symptoms of conjunctivochalasis after bipolar coagulation.Methods: Forty-three eyes of 26 patients (average age, 75.7 ± 8.4 years) were included in this study. The inferior conjunctivas were cauterized between April 2009 and June 2010. Surgery involved pinching the excess conjunctiva and performing bipolar cauterization after subconjunctival injection of a local anesthetic agent. Patients were asked to describe the postoperative foreign-body sensation and change in subjective symptoms 1 month postoperatively, with the preoperative symptom score defined as 10.Results: Twenty-two patients (84.6%) reported symptom relief immediately after the procedure, though all patients had a mild gritty sensation for 1–2 weeks postoperatively. The mean postoperative symptom score obtained from the questionnaire was 3.27 ± 3.31, which was significantly lower than the preoperative score (P < 0.0001). No patients had experienced recurrent symptoms at the end of the follow-up period.Conclusion: Thermal cauterization can achieve conjunctival shrinkage and adherence to the subconjunctival tissues. Operation time is only a few minutes, postoperative pain is not severe, and the procedure can be performed in an outpatient clinic, all of which represent benefits to the patients.Keywords: coagulation, cauterization, conjunctival injection&nbsp

Life Estimation for IC Plastic Packages Under Temperature Cycling Based on Fracture Mechanics

Abstract---: The strength of plastic encapsuiaiIts is analyzed from the viewpoint of crack propagation. With a preexisting crack length a and a specific number of applied load cycles N, fatigue crack propagation rates da/dN of the encapsulants were measured with laboratory test specimens. It was found that the da/dN of encapsulants can tie expressed as functions of the stress intensity factor range 11K. The crack propagation behavior in the package was estimated from the data of da/dN and 11K at the lowest temperature of the test cycles. Reasonabie correlation is found between the estimated crack propagation behavior and the observed one; The applicability of fracture mechanics to the package cracking problem is demonstrated