Proteinase inhibition using small Bowman-Birk-type structures.

Bowman-Birk inhibitors (BBIs) are cysteine-rich and highly cross-linked small proteins that function as specific pseudosubstrates for digestive proteinases. They typically display a "double-headed" structure containing an independent proteinase-binding loop that can bind and inhibit trypsin, chymotrypsin and elastase. In the present study, we used computational biology to study the structural characteristics and dynamics of the inhibition mechanism of the small BBI loop expressing a 35-amino acid polypeptide (ChyTB2 inhibitor) which has coding region for the mutated chymotrypsin-inhibitory site of the soybean BBI. We found that in the BBI-trypsin inhibition complex, the most important interactions are salt bridges and hydrogen bonds, whereas in the BBI-chymotrypsin inhibition complex, the most important interactions are hydrophobic. At the same time, ChyTB2 mutant structure maintained the individual functional domain structure and excellent binding/inhibiting capacities for trypsin and chymotrypsin at the same time. These results were confirmed by enzyme-linked immunosorbend assay experiments. The results showed that modeling combined with molecular dynamics is an efficient method to describe, predict and then obtain new proteinase inhibitors. For such study, however, it is necessary to start from the sequence and structure of the mutant interacting relatively strongly with both trypsin and chymotrypsin for designing the small BBI-type inhibitor against proteinases.

Proteinase inhibition using small Bowman-Birk-type structures

Bowman-Birk inhibitors (BBIs) are cysteine-rich and highly cross-linked small proteins that function as specific pseudosubstrates for digestive proteinases. They typically display a "double-headed" structure containing an independent proteinase-binding loop that can bind and inhibit trypsin, chymotrypsin and elastase. In the present study, we used computational biology to study the structural characteristics and dynamics of the inhibition mechanism of the small BBI loop expressing a 35-amino acid polypeptide (ChyTB2 inhibitor) which has coding region for the mutated chymotrypsin-inhibitory site of the soybean BBI. We found that in the BBI-trypsin inhibition complex, the most important interactions are salt bridges and hydrogen bonds, whereas in the BBI-chymotrypsin inhibition complex, the most important interactions are hydrophobic. At the same time, ChyTB2 mutant structure maintained the individual functional domain structure and excellent binding/inhibiting capacities for trypsin and chymotrypsin at the same time. These results were confirmed by enzyme-linked immunosorbend assay experiments. The results showed that modeling combined with molecular dynamics is an efficient method to describe, predict and then obtain new proteinase inhibitors. For such study, however, it is necessary to start from the sequence and structure of the mutant interacting relatively strongly with both trypsin and chymotrypsin for designing the small BBI-type inhibitor against proteinases.

Baerveldt drainage implants in eyes with a preexisting scleral buckle.

OBJECTIVE: To describe the surgical insertion of a Baerveldt drainage implant and postoperative visual acuity and intraocular pressure (IOP) outcomes in patients with a preexisting scleral buckle. METHODS: Medical records of all patients with a preexisting scleral buckle who underwent insertion of a Baerveldt drainage implant at Bascom Palmer Eye Institute, Miami, Fla, from January 1, 1994, through December 31, 1998, were reviewed. Outcome measures included visual acuity and IOP at 1 year. RESULTS: At 1 year postoperatively, 14 (88%) of 16 patients had stable or improved visual acuity. Preoperatively, mean IOP was 30.9 mm Hg and the mean number of antiglaucoma medications was 3.4; at 1 year postoperatively, mean IOP was 12.0 mm Hg and the mean number of antiglaucoma medications was 0.8 (P<.001). Nine patients (56%) achieved an IOP of greater than 5 and no greater than 21 mm Hg without medication, and an additional 7 (44%) achieved this level of IOP control with medication. No patient required further surgery for uncontrolled IOP during the follow-up interval, which ranged from 19. 1 to 45.5 months. CONCLUSION: Baerveldt drainage device insertion behind or over a preexisting encircling band is often successful in managing refractory glaucoma in patients who have undergone previous scleral buckling procedures. Arch Ophthalmol. 2000;118:1509-1513

Surgical management and outcomes of dislocated intraocular lenses.

OBJECTIVE: To evaluate the surgical management and visual acuity outcomes in a large series of patients with dislocated intraocular lenses (IOLs). DESIGN: Retrospective consecutive noncomparative case series. PARTICIPANTS: All patients who underwent surgical management of dislocated IOLs by two vitreoretinal surgeons at one institution between January 1, 1991, and March 31, 1998. METHODS: Demographic and clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURES: Visual acuity at final follow-up and surgical complications. RESULTS: The study population consisted of 110 patients, with a median follow-up interval of 50 weeks after dislocated IOL management. Surgical techniques included IOL repositioning in 93 (84.5%) eyes, IOL exchange in 16 (14.5%) eyes, and IOL removal in 1 (1 %) eye. Final visual acuity was > or =20/40 in 63 patients (57%) patients, 20/50-20/200 in 34 (31%) patients, and <20/200 in 13 (12%) patients. Ninety-nine (90%) patients had stable or improved final vision. Observed complications included postoperative retinal detachment in 7 (6.3%) eyes, chronic cystoid macular edema in 19 (17%) eyes, and suprachoroidal hemorrhage in 1 (1%) eye. CONCLUSIONS: Surgical management of dislocated IOLs usually results in satisfactory visual outcomes. Pre-existing ocular pathology and postoperative complications may limit final vision.

Emerging ciprofloxacin-resistant Pseudomonas aeruginosa.

PURPOSE: To report a clinical series of ciprofloxacin-resistant ocular isolates of Pseudomonas aeruginosa from a tertiary care ophthalmic center. METHODS: Review of in vitro sensitivities of all ocular isolates of P. aeruginosa be tween July 1991 and September 1998. In vitro resistance was defined as a minimum inhibitory concentration of 4 or more microg per ml. RESULTS: Nine of 423 ocular isolates of P. aeruginosa showed in vitro resistance to ciprofloxacin. From 1991 to 1994, 0.44% (1/227) of ocular isolates were resistant to ciprofloxacin, whereas from 1995 to 1998, 4.1% (8/ 196) of ocular isolates showed in vitro resistance (P = .014). CONCLUSIONS: Ciprofloxacin-resistant P. aeruginosa has been identified in recent clinical ocular specimens. Ciprofloxacin resistance among ocular isolates of P. aeruginosa is a local and worldwide concern.