Riboflavin-UV--a crosslinking for fixation of biosynthetic corneal collagen implants.

PURPOSE: To evaluate riboflavin-UV-A crosslinking as an alternative suture-free fixation method for biosynthetic corneal collagen implants. METHODS: A range of cell-free corneal implants consisting of recombinant human collagen type III were examined. In vitro, the implants were crosslinked with different riboflavin solutions and irradiations. Ex vivo, the biosynthetic corneal implants were placed on the anterior cornea of porcine and rabbit eyes after performing deep anterior lamellar keratoplasty with a trephine, femtosecond laser, or excimer laser. UV-A crosslinking was performed with isotonic or hypotonic riboflavin at either standard or rapid procedure. The corneas were excised, fixed in PFA 4%, and embedded in paraffin. Crosslinking effects on the implants and the adhesion between implant and corneal bed were evaluated by slit-lamp biomicroscopy, optical coherence tomography (OCT) images, and histologically. RESULTS: After the crosslinking procedure, the implants showed different degrees of thinning. The accuracy of cutting the corneal bed was highest with the excimer laser. Good adhesion of the implant in the corneal bed could be demonstrated in OCT images. This was more accurate in porcine eyes than in rabbit eyes. Histologically, crosslinks between implant and corneal stroma were demonstrated. There was no difference between standard and rapid crosslinking procedures. CONCLUSIONS: Riboflavin-UV-A crosslinking as a fixation method for biosynthetic corneal collagen implants was demonstrated to be promising. It can reduce suture-related complications such as haze formation and surface irregularity. Stability of the implants, especially shrinkage after riboflavin-UV-A crosslinking, needs to be further evaluated. Biostability, integration, and long-term outcome are further evaluated in in vivo animal experiments.

Comparison of the maximum applicable stretch force after femtosecond laser-assisted and manual anterior capsulotomy.

PURPOSE: To objectively measure the strength of the capsulotomy performed with a femtosecond laser-assisted technique or performed manually in a pig-eye laboratory study. SETTING: International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. DESIGN: Experimental study. METHODS: Ten fresh pig eyes were randomly assigned to femtosecond laser-assisted capsulotomy or manual capsulotomy. The capsule was immersed in hyaluronic acid, and retractors were fixed in the capsule opening with a pull-force measuring device. The force necessary to break the capsulotomy was measured in millinewtons (mN); the maximum stretching ratio was also assessed. RESULTS: The observed mean rupture force (ie, maximum amount of force measured immediately before tissue rupture) was 113 mN ± 12 (SD) in the laser-assisted procedure and 73 ± 22 mN in the manual procedure (P<.05). The stretching ratios were 1.60 ± 0.10 (femtosecond) and 1.35 ± 0.04 (manual) (P<.05). CONCLUSION: In this laboratory pig-eye study, femtosecond laser-assisted capsulotomy resulted in a significantly stronger anterior capsule opening than the standard manually performed capsulotomy.

Assessment of nonoccupational exposure to DDT in the tropics and the north: relevance of uptake via inhalation from indoor residual spraying.

BACKGROUND: People who live in dwellings treated with indoor residual spraying (IRS) of DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] for disease-vector control in the tropics and indigenous populations in the Arctic who consume marine mammals experience high nonoccupational exposure to DDT. Although the use of DDT in IRS is rising, the resulting nonoccupational exposure is poorly characterized. OBJECTIVES: We have provided a comparative assessment of exposure to DDT and its metabolites in the general population of the tropical and northern regions and in highly exposed populations in these regions. METHODS: We compiled > 600 average or median DDT concentrations from the peer-reviewed literature, representing > 23,000 individual measurements in humans, food, air, soil, and dust. We use Monte Carlo sampling of distributions based on these data to estimate distributions of population- and route-specific uptake. We evaluate our exposure estimates by comparing them with biomonitoring data. RESULTS: DDT concentrations are highest in people living in IRS-treated houses and lowest in the northern general population, differing by a factor of about 60. Inuits and the general population in the tropics have similar concentrations. Inhalation exposure explains most of the difference in concentration between the highly exposed and the general population in the Tropics. Calculated exposure levels are consistent with human biomonitoring data. CONCLUSIONS: Nonoccupational inhalation exposure is a relevant exposure pathway for people living in homes treated by IRS of DDT. Continued monitoring of time trends and DDE to DDT ratios in the Tropics and in the North is needed to identify a possible slowdown in concentration decline and the influence of ongoing DDT use.

Intrinsic human elimination half-lives of polychlorinated biphenyls derived from the temporal evolution of cross-sectional biomonitoring data from the United Kingdom.

BACKGROUND: Most empirical estimates of human elimination kinetics for persistent chemicals reflect apparent elimination half-lives that represent the aggregated effect of intrinsic elimination, ongoing exposure, and changes in body weight. However, estimates of intrinsic elimination at background levels are required for risk assessments for the general population. OBJECTIVE: To estimate intrinsic human elimination half-lives at background levels for nine polychlorinated biphenyl (PCB) congeners, we used a novel approach based on population data. METHODS: We used a population pharmacokinetic model to interpret two sets of congener-specific cross-sectional age-concentration biomonitoring data of PCB concentrations measured in lipid and blood samples that were collected from 229 individuals in 1990 and 2003. Our method is novel because it exploits information about changes in concentration in the human population along two dimensions: age and calendar time. RESULTS: Our approach extracted information about both elimination kinetics and exposure trends from biomonitoring data. The longest intrinsic human elimination half-lives estimated in this study are 15.5 years for PCB-170, 14.4 years for PCB-153, and 11.5 years for PCB-180. CONCLUSIONS: Our results are further evidence that a maximum intrinsic elimination half-life for persistent chemicals such as PCBs exists and is approximately 10-15 years. A clear conceptual distinction between apparent and intrinsic half-lives is required to reduce the uncertainty in elimination half-lives of persistent chemicals. The method presented here estimates intrinsic elimination half-lives and the exposure trends of persistent pollutants using cross-sectional data available from a large and growing number of biomonitoring programs.

A multi-individual pharmacokinetic model framework for interpreting time trends of persistent chemicals in human populations: application to a postban situation.

BACKGROUND: Human milk and blood are monitored to detect time trends of persistent organic pollutants (POPs) in humans. It is current practice to use log-linear regression to fit time series of averaged cross-sectional biomonitoring data, here referred to as cross-sectional trend data (CSTD). OBJECTIVE: The goals of our study are to clarify the interpretation of half-lives derived from fitting exponential functions to declining CSTD and to provide a method of estimating human elimination half-lives from CSTD collected in a postban situation. METHODS: We developed a multi-individual pharmacokinetic model framework and present analytical solutions for a postban period. For this case, the framework quantitatively describes the relationships among the half-life for reduction of body burdens of POPs derived from CSTD, the half-life describing decline in daily intake, and the half-life of elimination from the human body. RESULTS: The half-life derived from exponential fitting of CSTD collected under postban conditions describes the exposure trend and is independent of human elimination kinetics. We use a case study of DDT (dichlorodiphenyltrichloroethane) to show that CSTD can be combined with exposure data obtained from total diet studies to estimate elimination kinetics of POPs for humans under background exposure conditions. CONCLUSIONS: CSTD provide quantitative information about trends in human exposure and can be combined with exposure studies to estimate elimination kinetics. The full utility of these data has not been exploited so far. An efficient and informative monitoring strategy for banned POPs in humans would coordinate sampling of consistent sets of CSTD from young adults with total diet studies.