Inhibition of Corneal and Retinal Angiogenesis by Organic Integrin Antagonists After Intrascleral or Intravitreal Drug Delivery
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The choice of using air or saline in epidural syringes during the loss-of-resistance technique, for identifying the epidural space, has been based largely on personal preference of the anesthesia provider. A survey of practice in the United Kingdom, thought to be similar to practice in the United States, revealed that the majority of anesthesia providers use air. Case reports have appeared in the literature suggesting that air may be harmful to patients or, at the very least, impede the onset and quality of epidural analgesia. Two studies have evaluated air vs saline to determine whether one may lead to more rapid or better quality epidural analgesia in laboring parturients. Results are mixed. However, they seem to indicate that the use of saline for the loss-of-resistance may result in more rapid and satisfactory quality of pain relief in laboring parturients. Current anesthesia literature suggests using saline with an air bubble in the loss-of-resistance syringe. Many anesthesia training programs continue to teach the use of air, saline, and saline with an air bubble. Further studies may help to determine whether there is a scientific or safety basis for using air vs saline.
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Developing more effective ocular drug delivery systems is essential to improving the treatment of posterior segment eye disease. The large target area provided by the sclera and potentially less vision threatening complications are advantages of transscleral administration compared to more traditional modalities of drug delivery to the posterior segment. We aimed to determine the permeability coefficient for the in vitro diffusion of a small, single-stranded, oligonucleotide across human sclera. Transscleral permeability was measured by placing 100 μL of 2.96 × 10-4 mol single-stranded, fluorescein-labeled oligonucleotide (MW = 7998.3) on the episcleral surface of sclera mounted in a perfusion chamber. Fractions of choroidal perfusate were collected hourly for 24 hours. The permeability constant or Ktrans for the transscleral diffusion of the naked, single-stranded, fluorescein-labeled oligonucleotide was 7.67 ± 1.8 × 10-7 cm/s (mean ± SEM, N = 7). The permeability constant or Ktrans after intrascleral injection of the same fluorescein-labeled oligonucleotide was 1.32 ± 0.42 × 10-7 (mean ± SEM, N = 4). This analysis demonstrates that diffusion of a naked, 24-base, single-stranded, fluorescein-labeled oligonucleotide can be accomplished by both of the described methods. The ability to deliver single-stranded oligonucleotides across the sclera may prove to be advantageous given the development of several novel therapeutic strategies that use similar molecules.
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