A quantitative assessment of the risk of introducing foot and mouth disease virus into the United States via cloned bovine embryos.

The trade of livestock or their products between nations requires information on the risk of introducing infectious agents such as foot and mouth disease virus (FMDV). Although transmission pathways for FMDV vary, a recent concern in the United States (USA) is that it might enter via cloned embryos. A quantitative risk assessment model was developed to determine the scenarios (with mathematical probabilities) that could lead to the introduction and maintenance of FMDV via the importation of cloned bovine embryos. Using @RISK software with Monte Carlo simulation involving 50,000 iterations, the probability of introducing FMDV via cloned embryos was estimated to be 3.1 x 10(-7). Given the current cloning protocol, and assuming the annual importation of 250 to 1,700 (mean = 520) cloned embryos, the expected number of infected embryos ranges from 1.1 x 10(-7) to 4.4 x 10(-3) (mean = 1.6 x 10(-4)) per year. Critical pathway analysis showed that the risk of FMDV entering the USA by this route is extremely low.

The evaluation of a sexual assault risk reduction program: a multisite investigation.

This article summarizes the results of the Ohio University Sexual Assault Risk Reduction Project, which is a program designed to reduce college women's risk for sexual assault. The program was evaluated at 2 separate universities with 762 women. Participants were randomly assigned either to the program or to the no-treatment comparison group, and they completed measures that assessed sexual victimization, dating behaviors, sexual communication, and rape empathy at the pretest and at the 2-month and 6-month follow-ups. At the 2-month follow-up, there were no differences between the groups on any of the outcome measures. However, those women who were moderately victimized during the 2-month follow-up were significantly less likely to be revictimized during the 6-month follow-up period if they participated in the program.

Anti-inflammatory activity of phosphodiesterase (PDE)-IV inhibitors in acute and chronic models of inflammation.

Inhibitors of cyclic nucleotide phosphodiesterases are known to suppress lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production in vitro in human monocytes. The most potent of these have selectivity for type IV PDEs, suggesting that this class of PDE is the major type involved in the regulation of human TNF-alpha production. Using compounds of two distinct chemical structural classes, a quinazolinedione (CP-77059) and a 4 arylpyrrolidinone (rolipram), we show here that PDE-IV-specific inhibitors are also potent in suppressing LPS-induced TNF-alpha production in vitro in sodium periodate-elicited murine macrophages (IC50s of 1 and 33, respectively). We then report the in vivo anti-inflammatory effect of PDE-IV inhibition in five murine models of inflammation: (i) elevation of serum TNF-alpha induced by a sublethal LPS injection; (ii) LPS-induced endotoxic shock; (iii) LPS/galactosamine-induced endotoxic shock; (iv) carrageenan-induced paw oedema; and (v) adjuvant arthritis. Following a sublethal (5 micrograms/mouse) injection of LPS, serum TNF-alpha levels in mice peaked sharply, reaching concentrations of 3-12 ng/ml 90 min after injection. In this sublethal LPS assay, CP-77059 was about 30 times more potent than rolipram, with a minimum effective dose of 0.1 mg/kg versus 3 mg/kg for rolipram. This rank order is in keeping with the relative in vitro IC50s for CP-77059 and rolipram, as well as their relative Ki against the human PDE-IV enzyme (46 nM and 220 nM, respectively). In LPS-induced endotoxic shock, rolipram and CP-77059 at relatively high doses of 30 and 10 mg/kg, respectively, significantly reduced serum TNF-alpha levels, and also inhibited mortality 66%. In the LPS/galactosamine shock model, in which mice are rendered exquisitely sensitive to LPS by co-injection with galactosamine, only 0.1 microgram of LPS/mouse is necessary for serum TNF-alpha elevation and death. Both rolipram and the CP-77059 caused dose-dependent reduction of serum TNF-alpha and lethality. In the carrageenan-induced paw oedema model, in which there is a pronounced local TNF-alpha response (without a serum TNF-alpha elevation), rolipram significantly inhibited paw swelling as well as localized TNF-alpha levels in the paw. In the adjuvant arthritis model, a chronic model of inflammation also possessing localized TNF-alpha elevation in the inflamed paw, rolipram and CP-77059 suppressed ankle swelling and radiological evidence of joint damage. These data are consistent with a major role for PDE-IV in regulation of TNF-alpha production and inflammatory responses in murine systems.(ABSTRACT TRUNCATED AT 400 WORDS)

An assessment of the risk of foreign animal disease introduction into the United States of America through garbage from Alaskan cruise ships.

The United States Department of Agriculture, Animal and Plant Health Inspection Service (USDA-APHIS) has been exploring methods of quantitative risk assessment to support decision-making, provide risk management options and identify research needs. With current changes in world trade, regulatory decisions must have a scientific basis which is transparent, consistent, documentable and defensible. These quantitative risk assessment methods are described in an accompanying paper in this issue. In the present article, the authors provide an illustration by presenting an application of these methods. Prior to proposing changes in regulations, USDA officials requested an assessment of the risk of introduction of foreign animal disease to the United States of America through garbage from Alaskan cruise ships. The risk assessment team used a combination of quantitative and qualitative methods to evaluate this question. Quantitative risk assessment methods were used to estimate the amount of materials of foreign origin being sent to Alaskan landfills. This application of quantitative risk assessment illustrates the flexibility of the methods in addressing specific questions. By applying these methods, specific areas were identified where more scientific information and research were needed. Even with limited information, the risk assessment provided APHIS management with a scientific basis for a regulatory decision.

Recommendations of the International Roundtable Workshop on Bovine Spongiform Encephalopathy.

Recommendations of the working party were summarized as follows: Determine the status in all countries of their national cattle herds with respect to BSE. Attempt to develop a test to recognize BSE-infected animals before they become clinically ill. Establish procedures to prevent spread of BSE agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. Review the rendering processes, identify the sources and destinations of rendered products, and suggest appropriate changes if needed. Especially needed are standardized rendering procedures in regard to use of organic solvents, temperature, and duration of heat treatment. Review import and export regulations to reduce the risk of spreading BSE and to maximize opportunities for safe trading in cattle and cattle products. The scrapie-free certification program of the USDA was supported, and similar programs might be considered by other countries. If BSE/scrapie is diagnosed in a given country, determine baseline incidence of CJD in those countries and consider contributing to an international registry. The WHO should address the problems of BSE, formulate policy, participate in and coordinate research, and provide training opportunities for veterinary and human health care workers from eastern European countries and developing nations. Government and private agencies should consider increasing support for research on transmissibility and pathogenesis of CJD, BSE, CWD, scrapie, and transmissible mink encephalopathy. Prepare and publish a critical neuropathologic review of all spongiform encephalopathies, naturally and experimentally transmitted, defining the characteristics of each disease in the various species known to be susceptible. Consider producing guidelines for the biological and pharmaceutical industries with regard to sourcing, collecting, and processing bovine and ovine materials.(ABSTRACT TRUNCATED AT 250 WORDS)

Metastasis of Rous sarcoma tumors in chickens is influenced by the major histocompatibility (B) complex and sex.

Six-week-old second generation progeny from the cross of inbred Lines 6(1) and 15(1), segregating into three major histocompatibility (B) complex groups (B2/B2, B2/B5, and B5/B5), were inoculated subcutaneously in the wingweb with one of three pseudotypes of Rous sarcoma virus. Chickens that died during a 10-week period after inoculation were necropsied and scrutinized for gross metastasis and histological sections of at least one lesion per affected organ examined for Rous sarcoma-transformed cells. By definition, a metastatic tumor was one located in an organ or tissue other than the primary inoculation site and having the histological appearance of a Rous sarcoma. Sarcomas developed in 1144 chickens, 390 of which died with tumor. For B2/B2, compared to B5/B5 hosts, mortality was 8 vs. 93%, median days to death were 45 vs. 31, and metastatic frequency was significantly lower, 32 vs. 58%. Disseminated lesions were significantly less frequent in females than males and grew preferentially in the heart and pericardial sac. Because the frequency of metastasis was significantly lower in B2/B2 than in B5/B5 chickens, a gene(s) within, or closely linked to, the B complex sharply retards the spread of Rous sarcoma virus-induced tumors.

Effect of D,L-alpha-difluoromethylornithine on murine mammary carcinogenesis.

The development of chemically-induced mammary gland carcinomas in rats was dramatically suppressed by provision of a 1% solution of D,L-alpha-difluoromethylornithine (DFMO) in drinking water. Treatment with DFMO significantly reduced cancer incidence and the average size and number of cancers per rat and prolonged the cancer-free time. DFMO appears to be effective in blocking some aspect of the promotion stage of chemically induced mammary carcinogenesis in the rat.