Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

Penicillin vs. erythromycin in the treatment of diphtheria

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.     

Recruitment strategies in the women's health trial: feasibility study in minority populations. WHT:FSMP Investigators Group. Women's Health Trial:Feasibility Study in Minority Populations

The Women's Health Trial:Feasibility Study in Minority Populations (WHT:FSMP) examined the feasibility of recruiting postmenopausal women from a broad range of racial and socioeconomic backgrounds into a primary prevention trial requiring marked reductions in dietary fat. Postmenopausal women aged 50-79 yr who had no history of cardiovascular disease or cancer and who consumed 36% or more total energy from fat qualified to participate. We randomized the women into dietary intervention (60%) or control (40%) groups; we aimed to randomize 750 women in 18 months in each of the three clinical centers. All centers achieved goals for randomization based on ethnicity, and two centers exceeded overall recruitment goals. The greatest source of randomized participants was mass mailing, followed by items in the media, referrals, and community outreach. Recruitment yields were generally similar for the ethnic groups but lower for less-educated participants. The experience of WHT:FSMP indicates that postmenopausal women from the African-American, Hispanic, and non-Hispanic white communities can be recruited into dietary intervention studies for the prevention of disease.     

Assessing terrestrial wildlife populations in the Toronto and Region Area of Concern

Beneficial use impairments (BUIs) under the Great Lakes Water Quality Agreement identify environmental issues requiring remedial action within the Great Lakes Areas of Concern (AOCs). We conducted this study to support the assessment of the wildlife component of BUI 3: degradation of fish and wildlife populations. We compared bird and amphibian (frogs and toads) data from the Toronto and Region Conservation Authority’s Terrestrial Long-term Monitoring Program in the Toronto and Region AOC to an adjacent, but otherwise similar, reference watershed, Duffins Creek. Twelve of 13 targets were met within the AOC for forest bird, wetland bird, meadow bird and amphibian populations based on averages of mean annual values at sites within the AOC that were within two standard deviations of averages at sites in the Duffins Creek reference watershed between 2008 and 2017. Even though wildlife populations within the AOC were within the normal range of variability expected from a reference watershed, they were often at lower levels than within the Duffins Creek reference watershed. In addition, forest bird and amphibian populations were negatively affected by urbanization within the AOC and meadow bird indices declined. We conclude that while wildlife populations within the AOC currently meet targets for BUI 3, they continue to be negatively impacted by numerous stressors that are primarily related to past and ongoing urbanization. Thus, continued restoration of wildlife habitat and protection of existing habitat within the AOC is highly recommended.     

The strength and stiffness of perimysial connective tissue isolated from cooked beef muscle

Thick transverse slices of bovine M. semitendinosus were cooked for 1 h at 50°–90° and then cooled. Perimysial connective tissue was dissected from the cooked meat and subjected to mechanical testing in a small-scale device. The initial ‘toe’ region of the J-shaped load-extension curve was progressively lost with increasing temperature, the curve becoming more nearly linear after cooking at 90°C. These effects are explained on the basis of the progressive straightening out of the crimps from the collagen fibres, the crimps becoming finally lost at approximately 70°C. The final stiffness of the perimysium at greater extensions was unchanged at higher temperatures. Breaking strength increased from raw to cooked at 50°C, thereafter decreasing at cooking temperatures up to 90°C. it is proposed that this technique of testing isolated perimysium gives a valuable means of directly measuring the effects of cooking, or other treatments, on the intrinsic properties of perimysial collagenous material. Quantitative knowledge of these will help to determine its contribution to the overall mechanical properties, and hence eating quality, of cooked meat.     

A theoretical approach for inverse filter design in ultrasonic applications

A comparison between simulation- and measurement-based characterization is provided for the design of one-dimensional, nonadaptive, inverse filters for ultrasonic applications. Both prefiltering and postfiltering are considered by means of two different filtering strategies performed in the time and frequency domains. The results clearly indicate that theoretical methods can be used successfully, provided that the physical limitations of the simulation process are fully appreciated. In some instances, the simulation-based approach is shown to provide superior results, and the reasons for this are explained.     

On the analysis of two-dimensional discrete singular systems

In contrast to 1-D systems, the 2-D systems have no natural notion of causality. An artificial restriction traditionally imposed to allow recursive solution of these systems is that of recursibility. In this paper we study 2-Dsingular systems, taking advantage of the nonoriented or noncausal nature of these systems to provide a solution even if the requirement of recursibility does not hold. It is shown thatnonrecursible masks may be described using singular 2-D systems. The analysis approach relies on thefundamental matrix.Research supported by the US Fulbright Foundation in Greece and NSF Grant ECS-8805932.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.