Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition.

AIMS/HYPOTHESIS: Renal accumulation of AGEs may contribute to the progression of diabetic nephropathy. We evaluated the effect of ramipril (a pure ACE inhibitor) and AVE7688 (a dual inhibitor of ACE and neutral endopeptidase) on renal accumulation of the advanced glycation end-product (AGE) 3-deoxyglucosone-imidazolone, carboxymethyllysine (CML) and pentosidine, and on clearance of CML in type 2 diabetes. METHODS: Male Zucker diabetic fatty rats (ZDF, Gmi-fa/fa) rats were treated from age 10 to 37 weeks with ramipril (1 mg.kg(-1).day(-1)), AVE7688 (45 mg.kg(-1).day(-1)) or without drug. Ramipril and AVE7688 reduced albuminuria by 30 and 90%, respectively. RESULTS: ZDF rats showed increased renal accumulation of the AGE subtypes 3-deoxyglucosone-imidazolone, pentosidine and CML by about 40, 55 and 55%, respectively compared with heterozygous, non-diabetic control animals at the age of 37 weeks. AVE7688 but not ramipril attenuated the renal accumulation of 3-deoxyglucosone-imidazolone, pentosidine and CML and improved CML clearance in ZDF rats. During glycation reactions in vitro, AVE7688 also demonstrated potent chelating activity and inhibited metal-catalysed formation of pentosidine and CML. CONCLUSIONS/INTERPRETATION: Improved AGE clearance and direct inhibition of AGE formation by chelation may contribute to reduced accumulation of renal AGEs and to the nephroprotective effects of vasopeptidase inhibition in type 2 diabetes.

Noninvasive, optical detection of diabetes: model studies with porcine skin.

An in vitro study was performed to evaluate noninvasive spectroscopic measurement of advanced glycation endproducts (AGEs) in skin collagen. A porcine dermis preparation was incubated in solutions simulating normal and hyperglycemic conditions. The AGEs kinetics of increase were determined by HPLC and GC/MS assays, and compared to near-infrared (NIR) and ultraviolet/visible fluorescence skin spectra. Multivariate analysis indicated that, although NIR did not discriminate between collagen samples exposed to different glucose concentrations, fluorescence changes were readily detected and correlated strongly with skin concentration of AGEs. These results suggest that measurement of skin AGEs by fluorescence spectroscopy may be useful for detection and diagnosis of type II diabetes.

Evaluation of wheelchair sling seat and sling back crashworthiness.

Many wheelchairs are used as vehicle seats by those who cannot transfer to a vehicle seat. Although ANSI/RESNA WC-19 has been recently adopted as a standard to evaluate crashworthiness of the wheelchairs used as motor vehicle seats, replacement or after-market seats may not be tested to this standard. This study evaluated the crashworthiness of two specimens each of three unique sling backs and three unique sling seats using a static test procedure intended to simulate crash loading conditions. To pass the test, a sling back is required to withstand a 2290 lb load, and a sling seat should be capable of withstanding a 3750 lb load. All, but two sling back specimens which failed at 1567 lb and 1787 lb, withstood the test criterion load. Two of six tested sling seats failed to pass the test: one failed at 3123 lb and the other failed to sustain the load for 5 s although it reached the test criterion load. Most of the failures occurred at the seams of the side openings of upholsteries where the wheelchair frame inserts for attachment.

Computer simulation of stair falls to investigate scenarios in child abuse.

OBJECTIVES: To demonstrate the usefulness of computer simulation techniques in the investigation of pediatric stair falls. Since stair falls are a common falsely reported injury scenario in child abuse, our specific aim was to investigate the influence of stair characteristics on injury biomechanics of pediatric stair falls by using a computer simulation model. Our long-term goal is to use knowledge of biomechanics to aid in distinguishing between accidents and abuse. METHODS: A computer simulation model of a 3-year-old child falling down stairs was developed using commercially available simulation software. This model was used to investigate the influence that stair characteristics have on biomechanical measures associated with injury risk. Since femur fractures occur in unintentional and abuse scenarios, biomechanical measures were focused on the lower extremities. RESULTS: The number and slope of steps and stair surface friction and elasticity were found to affect biomechanical measures associated with injury risk. CONCLUSIONS: Computer simulation techniques are useful for investigating the biomechanics of stair falls. Using our simulation model, we determined that stair characteristics have an effect on potential for lower extremity injuries. Although absolute values of biomechanical measures should not be relied on in an unvalidated model such as this, relationships between accident-environment factors and biomechanical measures can be studied through simulation. Future efforts will focus on model validation.

Evaluation of wheelchair drop seat crashworthiness.

Wheelchair seating crash performance is critical to protecting wheelchair users who remain seated in their wheelchairs during transportation. Relying upon computer simulation and sled testing seat loads associated with a 20 g/48 kph (20 g/30 mph) frontal impact and 50th percentile male occupant were estimated to develop test criteria. Using a static test setup we evaluated the performance of various types of commercially available drop seats against the loading test criteria. Five different types of drop seats (two specimens each) constructed of various materials (i.e. plastics, plywood, metal) were evaluated. Two types of drop seats (three of the total 10 specimens) met the 16650 N (3750 lb) frontal impact test criteria. While additional validation of the test protocol is necessary, this study suggests that some drop seat designs may be incapable of withstanding crash level loads.

Evaluation of wheelchair seating system crashworthiness: "drop hook"-type seat attachment hardware.

OBJECTIVE: To evaluate the crashworthiness of commercially available hardware that attaches seat surfaces to the wheelchair frame. DESIGN: A low cost static crashworthiness test procedure that simulates a frontal impact motor vehicle crash. SETTING: Safety testing laboratory. SPECIMENS: Eleven unique sets of drop-hook hardware made of carbon steel (4), stainless steel (4), and aluminum (3). INTERVENTIONS: Replicated seat-loading conditions associated with a 20g/48 kph frontal impact. Test criterion for seat loading was 16,680 N (3750 lb). MAIN OUTCOME MEASURES: Failure load and deflection of seat surface. RESULTS: None of the hardware sets tested met the crashworthiness test criterion. All failed at less than 50% of the load that seating hardware could be exposed to in a 20g/48 kph frontal impact. The primary failure mode was excessive deformation, leading to an unstable seat support surface. CONCLUSIONS: Results suggest that commercially available seating drop hooks may be unable to withstand loading associated with a frontal crash and may not be the best option for use with transport wheelchairs.

Evaluation of wheelchair back support crashworthiness: combination wheelchair back support surfaces and attachment hardware.

Automotive seats are tested for compliance with federal motor vehicle safety standards (FMVSS) to assure safety during impact. Many wheelchair users rely upon their wheelchairs to serve as vehicle seats. However, the crashworthiness of these wheelchairs during impact is often unknown. This study evaluated the crashworthiness of five combinations of wheelchair back support surfaces and attachment hardware using a static test procedure simulating crash loading conditions. The crashworthiness was tested by applying a simulated rearward load to each seat-back system. The magnitude of the applied load was established through computer simulation and biodynamic calculations. None of the five tested wheelchair back supports withstood the simulated crash loads. All failures were associated with attachment hardware.