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Biomedical subjects

L Weimer

Publications and source records attributed to L Weimer.

5 recordsLinked to original sources

Angiostatic activity of steroids in the chick embryo CAM and rabbit cornea models of neovascularization.

Ocular neovascular diseases represent a major cause of blindness in the world. Angiostatic steroids are a unique class of compounds which inhibit the formation of new blood vessels in various models, including ocular models of angiogenesis. In search of potent new anti-angiogenic agents for the treatment of ocular neovascular disease, a large group of steroids were evaluated for angiostatic activity in the chick embryo CAM model. Angiostatic activity was found among all steroid classes included in the study. There was a good correlation between the angiostatic efficacies of 15 diverse steroids tested in the chick CAM and in the rabbit LPS-induced corneal pocket models of neovascularization (r=0.76, p=0.01). These studies show that potent angiostatic steroids inhibit neovascularization in two different animal models, suggesting a common mechanism of action. Glucocorticoid therapy is sometimes associated with ocular side effects. Two of the most potent angiostatic steroids, AL-3789 and AL-4940, were evaluated for glucocorticoid-mediated antiinflammatory activity in the in vitro U937 cell model of LPS-induced IL-1 induction and found to be devoid of glucocorticoid activity. Angiostatic steroids which lack glucocorticoid activity should be attractive drug candidates for treating ocular neovascular disease.

Angiogenesis Inhibitors↗

Model for the combined effects of temperature, initial pH, sodium chloride and sodium nitrite concentrations on anaerobic growth of Shigella flexneri.

A fractional factorial design was used to measure the effects and interactions of temperature (12-37 degrees C), initial pH (5.5-7.5), NaCl (0.5-4.0%) and NaNO2 (0-1000 ppm) on the anaerobic growth kinetics of Shigella flexneri in Brain-Heart Infusion broth. Anaerobic conditions were established by flushing the culture flasks with N2. A total of 375 cultures representing 124 variable combinations were analyzed, with growth curves being generated using the Gompertz equation. Growth rates decreased with decreasing temperature, decreasing pH and increasing NaCl level. NaNO2 in combination with low temperature, low pH and high NaCl content effectively inhibited S. flexneri. Response surface analysis was used to obtain models for estimating the growth of S. flexneri in terms of temperature, initial pH, and NaCl and NaNO2 concentrations. A third-order equation using the natural logarithm transformations for the Gompertz B and M terms gave reasonable estimates of bacterial growth in response to any combination of the variables studied within the specified ranges.

Anaerobiosis↗

A membrane vesicle/ribosome preparation from Serratia marcescens elicits peritoneal exudate cells expressing both tumoricidal and bactericidal activity.

A biological response modifier called ImuVert, derived from the bacterium Serratia marcescens, produced long-lasting elevation of peritoneal exudate cell (PEC) numbers after intraperitoneal injection into mice. These cells had enhanced ability to phagocytose both latex beads and opsonized Listeria monocytogenes. PEC harvested 2-14 days after a single injection of ImuVert killed L. monocytogenes, and ImuVert protected mice from infection by L. monocytogenes, measured both by LD50 and bacterial growth in vivo. Cells harvested 7 and 14 days after ImuVert injection also were tumoricidal, measured as killing of P815 mastocytoma cells, and ImuVert induced macrophages to express tumoricidal properties in vitro. These data suggest that ImuVert has a unique ability to induce a chronic inflammatory response, as other agents do not induce such a long-lasting influx of bactericidal inflammatory cells that also show tumoricidal activity. The consequences of this response appear to include protection from infection by certain bacteria.

Animals↗

Cognitive and behavioral findings in children taking theophylline.

In a prior pilot study involving six children, we noted improved memory and concentration and improved behavior when these children were switched from theophylline to cromolyn sodium therapy. We now report the findings in 29 children (24 boys and five girls), aged 7 to 12 years. In this study, a double-blind, double-dummy randomized design was used so that half the subjects continued to receive theophylline and the other half was actually switched from theophylline to cromolyn sodium therapy. Assessment again consisted of the revised Wechsler Intelligence Scale for Children, the Selective Reminding test, the Benton Visual Retention test, Stroop tests I and II, and the Child Behavior Checklist. The group receiving placebo theophylline/active cromolyn sodium therapy demonstrated greater improvement on all tests of memory and concentration, with greatest significance for the Stroop test (p less than 0.03 by analysis of covariance). There were also significant correlations between length of time theophylline was taken and scores on the depression (p less than 0.03) and the obsessive-compulsive (p less than 0.04) subscales of the Child Behavior Checklist. These results support the findings of the previous pilot study but, in addition, raise concern about depression and anxiety as possible long-term side effects of long-term theophylline therapy.

Asthma↗