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Biomedical subjects

Robert Greenwald

Publications and source records attributed to Robert Greenwald.

6 recordsLinked to original sources

Excretion of collagen derived peptides is increased in women with stress urinary incontinence.

AIMS: The objective of this study was to demonstrate that weakened pelvic floor support of the lower genitourinary tract in women with stress urinary incontinence (SUI) is due to increased collagenolysis. When fibrillar collagen is degraded, pyridinium (PYD) crosslinks are released and excreted in the urine. Degradation of collagen also results in peptide fragments of various lengths which are excreted in the urine. Degradation of mature fibrillar collagen and collagen which has not been crosslinked can be assessed independently by measurement of both PYD and collagen-derived peptides in the urine. METHODS: Twenty-four hour urine collections were obtained from women with SUI (n = 23) and women without urinary incontinence (n = 39). Urinary PYD concentration was assayed by ELISA. The urinary concentration of helical peptide alpha1 (I) 620-633 fragments derived from collagen was assayed by competitive enzyme immunoassay. Values were normalized to creatinine. RESULTS: The mean urine PYD concentration for women with SUI (110.8 +/- 19.7 nM/mM creatinine) was not significantly different than that for women without SUI (85.2 +/- 13.7 nM/mM creatinine). The mean urine concentration of helical peptide alpha1 (I) 620-633 for women with SUI (0.80 +/- 0.13 microg/mg creatinine) was significantly (P < 0.02) higher than that for women without SUI (0.49 +/- 0.06 microg/mg creatinine). CONCLUSIONS: These data suggest that collagenolytic activity in women with SUI is elevated compared to continent controls, as measured by urinary helical peptide alpha1 (I) 620-633 excretion. The lack of difference in urinary PYD excretion between the two populations suggests that the increased collagenolytic activity in women with SUI, compared to continent controls, is restricted to uncrosslinked collagen.

Aged↗

Inhibition of adjuvant-induced arthritis by systemic tissue inhibitor of metalloproteinases 4 gene delivery.

OBJECTIVE: An imbalance in the matrix metalloproteinase:tissue inhibitor of metalloproteinases (MMP:TIMP) ratio in favor of MMP appears to be an important determinant of tissue damage in arthritis. We undertook this study to explore whether reversal of this imbalance in favor of TIMP would alter this process and to examine the mechanism of this alteration. METHODS: We administered human TIMP-4 by electroporation-mediated intramuscular injection of naked DNA using the rat adjuvant-induced arthritis (AIA) model. RESULTS: Intramuscular naked TIMP-4 gene administration resulted in high circulating TIMP-4 levels and completely abolished arthritis development in the rat AIA model. This inhibition was associated with significantly decreased MMP activity in the joint tissue as well as with significantly decreased serum and tissue tumor necrosis factor alpha levels and serum interleukin-1alpha levels compared with animals with arthritis. The mutation of cysteine at position 1 of TIMP-4 failed to block the development of AIA. CONCLUSION: Our data indicate that TIMP-4 is a potent antiinflammatory agent, and that its antiarthritis function may be mediated by MMPs. Arthritis-inhibiting effects of TIMP-4 may suggest a unique application of this gene therapy method for arthritis.

Animals↗

Reducing long-term remedial costs by transport modeling optimization.

The Department of Defense (DoD) Environmental Security Technology Certification Program and the Environmental Protection Agency sponsored a project to evaluate the benefits and utility of contaminant transport simulation-optimization algorithms against traditional (trial and error) modeling approaches. Three pump-and-treat facilities operated by the DoD were selected for inclusion in the project. Three optimization formulations were developed for each facility and solved independently by three modeling teams (two using simulation-optimization algorithms and one applying trial-and-error methods). The results clearly indicate that simulation-optimization methods are able to search a wider range of well locations and flow rates and identify better solutions than current trial-and-error approaches. The solutions found were 5% to 50% better than those obtained using trial-and-error (measured using optimal objective function values), with an average improvement of approximately 20%. This translated into potential savings ranging from 600,000 dollars to 10,000,000 dollars for the three sites. In nearly all cases, the cost savings easily outweighed the costs of the optimization. To reduce computational requirements, in some cases the simulation-optimization groups applied multiple mathematical algorithms, solved a series of modified subproblems, and/or fit "meta-models" such as neural networks or regression models to replace time-consuming simulation models in the optimization algorithm. The optimal solutions did not account for the uncertainties inherent in the modeling process. This project illustrates that transport simulation-optimization techniques are practical for real problems. However, applying the techniques in an efficient manner requires expertise and should involve iterative modification to the formulations based on interim results.

Algorithms↗

Pharmacy syringe sale practices during the first year of expanded syringe availability in New York City (2001-2002).

OBJECTIVE: [corrected] To assess the role that customer characteristics, including race, age, and gender and pharmacy characteristics, including type and location, play on actual syringe-selling practice by pharmacies registered to sell syringes under the New York State Expanded Syringe Access Demonstration Program (ESAP). DESIGN: 89 syringe-purchasing visits were made in randomly selected ESAP-registered pharmacies, stratified by chain and independent status. SETTING: Visits were conducted in 14 New York City neighborhoods. Three neighborhoods (two with high need for human immunodeficiency virus [HIV] prevention services and one with low need) were selected in each of New York City's five boroughs (except Staten Island, where only two neighborhoods were visited, as only one exists with high need for HIV prevention services). PARTICIPANTS: Visits were conducted by syringe-purchasing testers with different demographic characteristics, including age (< or = 25 and > 25), race/ethnicity (white, black, Latino), and gender (men, women). RESULTS: Testers were able to purchase syringes in 69% of visits. Tester race, age, and gender did not significantly affect sales of syringe-selling practices. Location of pharmacy was statistically significant, with only 33% of the registered pharmacies selling syringes in the Bronx, but 67% to 89% selling in other four boroughs. CONCLUSIONS: ESAP has been widely implemented among registered pharmacies in four of New York City's five boroughs. The program's effectiveness could be enhanced through pharmacy-based efforts focused broadly on the ESAP goal of preventing the transmission of HIV and other blood-borne infections among injection drug users.

HIV Infections↗