Prevention of insect-borne disease: an approach using transgenic symbiotic bacteria

Expression of molecules with antiparasitic activity by genetically transformed symbiotic bacteria of disease-transmitting insects may serve as a powerful approach to control certain arthropod-borne diseases. The endosymbiont of the Chagas disease vector, Rhodnius prolixus, has been transformed to express cecropin A, a peptide lethal to the parasite, Trypanosoma cruzi. In insects carrying the transformed bacteria, cecropin A expression results in elimination or reduction in number of T. cruzi. A method has been devised to spread the transgenic bacteria to populations of R. prolixus, in a manner that mimics their natural coprophagous route of symbiont acquisition.     

Efficient immunocastration of male piglets by immunoneutralization of GnRH using a new GnRH-like peptide

BACKGROUND: DTIC and interleukin-2 (IL-2), as single agents, have a limited anti-tumor activity in patients with metastatic melanoma. Experimentally, thymosin alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and immunological effects of a combination with these three agents. PATIENTS AND METHODS: Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3 weeks. RESULTS: Objective responses were obtained in 15 (36%) of 42 evaluable patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and stable disease was observed in five. The median time to progression was 5.5 months and median survival was 11 months. Side effects were predominantly caused by IL-2. Treatment was tolerated reasonably well, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Baseline sCD4 levels seem to correlate to tumor burden. Patients benefiting from treatment had lower sCD4 and higher sCD8 than did progressing patients. CONCLUSIONS: The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.     

Neuropharmacology of St. John''s Wort (Hypericum)

OBJECTIVE: A developmental-ecological model was used to explore the psychological adjustment and peer social competencies of maltreated preschool children. METHOD: Enhanced research methods were used that included verification of maltreatment status, multiple-variable matching of comparison children, and contextually relevant assessment. One hundred eight Head Start children, of whom 54 were maltreated, participated. Assessment of social functioning included measurement of peer play interactions, global social skills, peer sociometrics, and teacher and parent ratings of behavior problems. RESULTS: Findings indicated that maltreated children were significantly less interactive in peer play and overall exhibited less self-control and interpersonal skill in social interactions than nonmaltreated children. In addition, maltreated children were more likely than their nonmaltreated peers to receive low sociometric ratings and were found by both teachers and parents to display more internalizing behavior problems than comparison children. CONCLUSIONS: These findings indicate the importance of using developmentally sensitive research methods to inform contextually relevant interventions.     

Growth and subsequent feedlot performance of estradiol-implanted vs nonimplanted steers grazing fall-accumulated endophyte-infested or low-endophyte tall fescue

A growing-finishing study using Angus steer calves was conducted in three phases: 1) grazing stockpiled 'Kentucky-31' tall fescue (Festuca arundinacea Schreb.) with high (65%; HE KY-31) and low (0%; LE KY-31) infestation rates of Acremonium coenophialum Morgan-Jones and Gams and 'Kenhy' and 'Johnstone' tall fescue with low (< 1%) infestation rate of Acremonium coenophialum from October 24 to December 19; 2) drylot feeding of Johnstone and HE KY-31 haylage (December 19 to April 10); and 3) feedlot finishing on a common high-concentrate diet (April 11 to August 1). In Phase 1, ADG was greatest (P < .05) for Kenhy, intermediate for Johnstone and LE KY-31, and lowest (P < .05) for HE KY-31. Implantation with estradiol 17-beta increased ADG (P < .01) by 23, 27, 7, and 2% for steers grazing Johnstone, HE KY-31, LE KY-31, and Kenhy, respectively. Dry matter digestibility and DMI of stockpiled Johnstone and HE KY-31 were not different (P > .10). During Phase 2, steers consuming Johnstone haylage had greater (P < .01) DMI, ADG, and gain:feed ratio (G:F) than steers consuming HE KY-31 haylage. During Phase 3, steers previously consuming Johnstone had greater DMI (P < .10); however, steers previously fed HE KY-31 had greater ADG (P < .05) and G:F (P < .01). By the end of the study, steer body weights were not different (P > .10) between treatments. These data indicate that growth-decreasing effects of endophyte-infested fescue were evident at hypothermal-ambient temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Yeast MAK3 N-acetyltransferase recognizes the N-terminal four amino acids of the major coat protein (gag) of the L-A double-stranded RNA virus

The MAK3 gene of Saccharomyces cerevisiae encodes an N-acetyltransferase whose acetylation of the N terminus of the L-A double-stranded RNA virus major coat protein (gag) is necessary for viral assembly. We show that the first 4 amino acids of the L-A gag protein sequence, MLRF, are a portable signal for N-terminal acetylation by MAK3. Amino acids 2, 3, and 4 are each important for acetylation by the MAK3 enzyme. In yeast cells, only three mitochondrial proteins are known to have the MAK3 acetylation signal, suggesting an explanation for the slow growth of mak3 mutants on nonfermentable carbon sources.     

Lipoprotein lipase activity and plasma triglyceride clearance are elevated in endurance-trained women

Numerous studies have examined factors regulating high-density lipoprotein cholesterol (HDL-C) levels in male endurance athletes, but few studies have examined HDL-C regulation in female athletes. The present study compared lipid and lipoprotein concentrations, postheparin lipolytic activities, and the clearance rate (K2) of triglycerides following an intravenous fat infusion in 12 female distance runners (aged 33 +/- 9 years, mean +/- SD) and 13 sedentary women (33 +/- 9 years). Runners were leaner and had greater maximum oxygen uptake values than controls. Runners also had nonsignificantly lower triglyceride (53 +/- 15 v 65 +/- 13 mg/dL) and higher HDL-C (62 +/- 14 v 52 +/- 8 mg/dL, P = .06). Lipoprotein lipase activity (LPLA) was 33% greater (P < .05) and fat clearance (K2) was 27% faster (P < .01) in the trained women, and LPLA correlated directly with K2 (r = .61) and HDL-C (r = .62) in this group (P < .05 for both). K2 was directly related to HDL-C in the athletes (r = .57, P = .06), and also when the active and sedentary women were combined (r = .43, P < .05). These results suggest that increased LPLA and enhanced plasma triglyceride clearance may contribute to the HDL-C levels of physically active premenopausal women.     

Abnormal progression of a liquid meal through the stomach and small intestine in patients with Chagas' disease

This study describes the abnormal pattern of gastrointestinal progression of a liquid meal in patients with the digestive form of chronic Chagas' disease. This condition is known as a natural model of intramural denervation of the gut. Sixteen patients with clinical and radiographic evidence of esophageal and/or colonic involvement and 18 healthy volunteers were studied. Orocecal transit time after the ingestion of a 10% lactulose solution (180 ml) tagged with 99mtechnetium was measured by a conventional H2 breath technique. Gastric emptying and the arrival of the front of the meal to regions of interest corresponding to proximal and distal areas of the small intestine were assessed by abdominal scintigraphy. Orocecal transit time was significantly greater (P < 0.05) in Chagas' disease patients (N = 13) than in control subjects (N = 18) (mean +/- SD: 100.7 +/- 48.7 min vs 62.9 +/- 18.2 min). Half-time for gastric emptying of liquids in chagasic patients (N = 9) was significantly lower (P < 0.01) than in controls (N = 7) (9.7 +/- 2.7 min vs 26.4 +/- 3.4 min). The time of arrival of the liquid meal to the proximal small intestine was also significantly shorter (P < 0.02) in patients than in controls (5.6 +/- 3.7 vs 11.4 +/- 5.5 min), but there was no difference between the two groups concerning the time the meal first arrived to the distal small intestine (15.0 +/- 11.0 min vs 23.5 +/- 11.4 min, P > 0.05). These results indicate that patients with Chagas' disease have a combination of exceedingly rapid gastric emptying and abnormally delayed transit of liquids through the more distal segments of the small bowel.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological assessment of exposure to Echinococcus granulosus in a rural dog population in Uruguay

An ELISA was used to screen a dog population in Uruguay (Sarandi Del Yi, Durazno District) for the prevalence of specific serum antibodies (IgG, IgA and IgE) to Echinococcus granulosus. The sensitivity (61%) and specificity (97%) of the ELISA were determined using well-defined serum groups. A total of 408 dogs from Sarandi del Yi and environs were screened serologically, and 29.7% (8.6-13.8% for each antibody class) of dogs had positive levels of antibody to E. granulosus. This antibody prevalence (exposure) was significantly higher than the percentage of dogs found to be positive for E. granulosus worms by arecoline purgation (7.6%). This level of exposure to E. granulosus determined by ELISA is considered unacceptable from a public health perspective. Measures will now focus on obtaining data on the true prevalence of current infection in this dog population and on determining the transmission patterns of the disease in this endemic region.