Envirovet Summer Institute: Integrating Veterinary Medicine into Ecosystem Health Practice

Since 1991, Envirovet Summer Institutes have provided an intensive educational program in wildlife and ecosystem health to approximately 225 animal health professionals. Envirovet provides knowledge, skills, and multiple mentors to catalyze ecosystem health-oriented careers for young veterinarians. It is a total immersion experience, with the students engaged in 60–70 hours a week of instruction, 6–7 days a week, for 6 weeks. The course is comprised of lecture, laboratory, and field experiences organized into three sessions: 1) terrestrial wildlife and ecosystem health; 2) aquatic wildlife and ecosystem health; and 3) an ecosystem health approach to international development. Sessions 1 and 2 take place in Florida and Georgia; Session 3 takes place in a developing country (e.g., Kenya, Brazil, South Africa). Ultimately, the goal of Envirovet is to increase the numbers and effectiveness of veterinarians in productive ecosystem health research and application teams around the world.     

Ecdysteroids and a sucrose phenylpropanoid ester from Froelichia floridana

Phytoecdysteroid glycosides (1-5) and a phenylpropanoid ester of sucrose (6) were isolated from the whole plant of Froelichia floridana, along with eight known compounds including three ecdysteroids (7-9), four flavonoids (10-13), and one phenolic compound (14). Structures were determined using a combination of spectroscopic techniques. Compounds 1, 2 and 6-14 were tested in vitro for their activity against human DNA topoisomerase I. Compound 13 (diosmetin) showed marginal inhibition against topoisomerase I with IC₅₀ of 130 μM in conjunction with low intercalation ability.     

Role of natriuretic factor in central nervous system (CNS)-induced natriuresis

The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling-water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF.     

Protein sorting in mitochondria.

Most polypeptides that are imported into the mitochondrial matrix use a common translocation machinery. By contrast, proteins of the other mitochondrial compartments are imported by a variety of different mechanisms. Some of these proteins completely bypass the common translocation machinery, others use only the outer membrane components of this machinery, and still others use components of this machinery from both the outer and inner membranes. Import to the intermembrane space compartment provides examples of all three possibilities.     

Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni

Background

Schistosoma flatworm parasites cause schistosomiasis, a chronic and debilitating disease of poverty in developing countries. Praziquantel is employed for treatment and disease control. However, its efficacy spectrum is incomplete (less active or inactive against immature stages of the parasite) and there is a concern of drug resistance. Thus, there is a need to identify new drugs and drug targets.

Methodology/Principal Findings

We show that RNA interference (RNAi) of the Schistosoma mansoni ortholog of human polo-like kinase (huPLK)1 elicits a deleterious phenotypic alteration in post-infective larvae (schistosomula or somules). Phenotypic screening and analysis of schistosomula and adult S. mansoni with small molecule inhibitors of huPLK1 identified a number of potent anti-schistosomals. Among these was a GlaxoSmithKline (GSK) benzimidazole thiophene inhibitor that has completed Phase I clinical trials for treatment of solid tumor malignancies. We then obtained GSKs Published Kinase Inhibitor Sets (PKIS) 1 and 2, and phenotypically screened an expanded series of 38 benzimidazole thiophene PLK1 inhibitors. Computational analysis of controls and PLK1 inhibitor-treated populations of somules demonstrated a distinctive phenotype distribution. Using principal component analysis (PCA), the phenotypes exhibited by these populations were mapped, visualized and analyzed through projection to a low-dimensional space. The phenotype distribution was found to have a distinct shape and topology, which could be elicited using cluster analysis. A structure-activity relationship (SAR) was identified for the benzimidazole thiophenes that held for both somules and adult parasites. The most potent inhibitors produced marked phenotypic alterations at 1–2 μM within 1 h. Among these were compounds previously characterized as potent inhibitors of huPLK1 in cell assays.

Conclusions/Significance

The reverse genetic and chemical SAR data support a continued investigation of SmPLK1 as a possible drug target and/or the prosecution of the benzimidazole thiophene chemotype as a source of novel anti-schistosomals.     

Blood Lead Levels in a Welsh Rural Community

In a study of the blood lead levels of 626 healthy blood donors no differences were found between men and women, but there was a significant increase with age. Resident donors had a higher blood lead than students, and the level in residents increased with living in the Aberystwyth area up to about 20 years. The levels in the students did not increase with residence in Aberystwyth. No differences were found in the blood lead of donors living in different wards of Aberystwyth and none between the blood lead of donors living in the rural area and those in the town. Almost half of the local resident donors had a level above the “normal” range.     

Pathological Response of the Chicken Embryo to an Agent Which Causes Acute Leukosis (Marek''s Disease)

A laboratory test system specific for Marek's disease was developed by using the pathological response of the chicken embryo. Chicken epidermal scales (dander) and feather calami from infected chickens contain an agent(s) which after a 3- to 4-day incubation period caused gross or microscopic pathological changes (or both) in the embryo. A cell-free inoculum was obtained from infectious dander by 5-min sonic treatment, differential centrifugation, and membrane filtering (0.45 mum). Evidence for the cell-free existence of this agent(s) was obtained when membrane filtrates of dander preparations were shown to cause Marek's disease in 10-day-old chickens and in chickens inoculated at 1 day of age.