6 research outputs found
Recommended from our members
Pseudotumor Cerebri Appearing With Unilateral Papilledema After Trabeculectomy
We describe a patient with papilledema due to pseudotumor cerebri that was seen unilaterally following normalization of intraocular pressure (IOP) and discontinuation of systemic acetazolamide therapy following trabeculectomy. We hypothesize that the lamina cribrosa sclerae serves as a flexible barrier between intracranial pressure (ICP) and IOP and that alterations of the normal ICP/IOP ratio may lead to papilledema. To our knowledge, there have been no reports describing the development of unilateral papilledema following surgical reduction in IOP. REPORT OF A CASE. A 41-year-old obese white woman with a 9-year history of juvenile primary open-angle glaucoma underwent uncomplicated trabeculectomy in the left eye with supplemental 5-mg subconjunctival injections of 5-fluorouracil (50 mg/mL) because of progressive glaucomatous cupping. Preoperative IOP was 23 mm Hg in the right eye and 35 mm Hg in the left eye while receiving acetazolamide sequels, 500 mg twice daily, plus a combination of timolol maleate 0.5% an
Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post-synthetic Modification with Hydrophilic Side Chains
Peptide nucleic acid (PNA) is a nucleic acid mimic in which the
deoxyribose–phosphate was replaced by a peptide-like backbone.
The absence of negative charge in the PNA backbone leads to several
unique behaviors including a stronger binding and salt independency
of the PNA–DNA duplex stability. However, PNA possesses poor
aqueous solubility and cannot directly penetrate cell membranes. These
are major obstacles that limit in vivo applications of PNA. In previous
strategies, the PNA can be conjugated to macromolecular carriers or
modified with positively charged side chains such as guanidinium groups
to improve the aqueous solubility and cell permeability. In general,
a preformed modified PNA monomer was required. In this study, a new
approach for post-synthetic modification of PNA backbone with one
or more hydrophilic groups was proposed. The PNA used in this study
was the conformationally constrained pyrrolidinyl PNA with prolyl-2-aminocyclopentanecarboxylic
acid dipeptide backbone (acpcPNA) that shows several advantages over
the conventional PNA. The aldehyde modifiers carrying different linkers
(alkylene and oligoÂ(ethylene glycol)) and end groups (−OH,
−NH<sub>2</sub>, and guanidinium) were synthesized and attached
to the backbone of modified acpcPNA by reductive alkylation. The hybrids
between the modified acpcPNAs and DNA exhibited comparable or superior
thermal stability with base-pairing specificity similar to those of
unmodified acpcPNA. Moreover, the modified apcPNAs also showed the
improvement of aqueous solubility (10–20 folds compared to
unmodified PNA) and readily penetrate cell membranes without requiring
any special delivery agents. This study not only demonstrates the
practicality of the proposed post-synthetic modification approach
for PNA modification, which could be readily applied to other systems,
but also opens up opportunities for using pyrrolidinyl PNA in various
applications such as intracellular RNA sensing, specific gene detection,
and antisense and antigene therapy
Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG