West Nile virus quantification in feces of experimentally infected American and fish crows.

To better understand the potential environmental health risk presented by West Nile virus (WNV)-contaminated feces, we quantified the amount of WNV present in the feces of experimentally infected American crows (Corvus brachyrhynchos) and fish crows (Corvus ossifragus). Peak fecal titers ranged from 10(3.5) to 10(8.8) plaque-forming units (PFU)/g for 10 American crows and from 10(2.3) to 10(6.4) PFU/g for 10 fish crows. The presence of infectious WNV in bird feces indicates a potential for direct transmission of WNV. Thus, handlers of sick or dead birds should take appropriate precautions to avoid exposure to fecal material.     

Peptidomimetic thrombin inhibitors

The central position of thrombin in the coagulation cascade has made it a popular target for discovery of novel antithrombotic agents. Starting with hirudin, a natural peptide isolated from the medicinal leech, its shorter synthetic analogue hirulog, and argatroban,the first therapeutically used synthetic small-molecule thrombin active site inhibitor, hundreds of direct thrombin inhibitors have been discovered over the last 20 years. Most of them are peptidomimetic compounds,based on the amino acid sequence of fibrinogen which binds into the thrombin active site. Since elucidation of the crystal structure of human thrombin in 1989, the structure-based design of low-molecular-weight peptidomimetic thrombin inhibitors has been greatly aided by the use of x-ray crystallographic analysis of thrombin-inhibitor complexes. The ultimate goal of most research programmes and drug optimization strategies is to develop an orally bioavailable, small-molecule,direct thrombin inhibitor that would be suitable for once or twice daily dosing. An overview of the most advanced peptidomimetic direct thrombin inhibitors bivalirudin, argatroban, ximelagatran and dabigatran is presented.     

Immunoglobulins and their relative neutralizing efficiency in cattle immunized with infectious bovine rhinotracheitis — Parainfluenza-3 (IBR-PI-3) virus vaccine

The localization of anti-IBR and anti-PI-3 activity in the serum and nasal secretory immunoglobulins following intranasal immunization of cattle with a mixed vaccine (IBR-PI-3, MLV, TCO) was studied and was found to reside in the nasal secretory IgA, serum IgM and IgG fractions. The computation of their relative virus neutralizing efficiencies from kinetic data revealed their order of neutralizing efficiencies to be IgM greater than IgA greather than IgG.     

Effects of DFMO-induced polyamine depletion on human tumor cell sensitivity to antineoplastic DNA-crosslinking drugs

Summary We investigated the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to two alkylating and crosslinking agents: chlorambucil and N,N,N-triethylenethio-phosphoramide (thiotepa). The cell lines studied included HuTu-80 (duodenum), HT-29 (colon), ME-180 (cervix), and A-427 (lung). A 48- to 72-h pretreatment with DFMO reduced intracellular putrescine and spermidine contents to <10% and <1% of control levels. This treatment also caused a 30%–70% decline in spermine content. Survival of control and DFMO-pretreated cells after treatment with chlorambucil or thiotepa was measured by a plating efficiency assy. For three of the four lines studied, the DFMO-induced partial polyamine depletion significantly protected cells from the lethal effects of chlorambucil. In ME-180 cultures alone, DFMO pretreatment did not alter the cytocidal efficacy of chlorambucil. Addition of exogenous putrescine to cultures of HuTu-80, HT-29, or A-427 24 h after DFMO addition but 24 h before treatment with chlorambucil reversed the polyamine depletion and its protective effects on chlorambucil-induced cell kill. In contrast to the above observations, DFMO and partial polyamine depletion had no effect on cell survival after thiotepa treatment for any of the cell lines investigated.Abbreviations BCNU 1,3-bis (2-chloroethyl)-1-nitrosourea - CENU chloroethylnitrosourea - cis-Pt (II) cis-diamminedichloroplatinum (II) - DFMO difluoromethylornithine - ODC ornithine decarboxylase - PU putrescine - SD spermidine - SP spermine thiotepa - N,N,N triethylenethiophosphoramide This investigation was supported in part by PHS grant no. CA-32758 awarded by the National Cancer Institute, DHHS; by grant no. 82-6 from the American Cancer Society, Ill. Div., Inc.; and by a Biomedical Research Support Grant to Northwestern University Medical School from the US PHS, NIH (RR-05370)     

Bupivacaine 0.1% does not improve postoperative epidural fentanyl analgesia after abdominal or thoracic surgery

Epidural infusions of fentanyl, in a 10 micrograms.ml-1 concentration, combined with bupivacaine 0.1% were compared with epidural infusions of fentanyl alone for postoperative analgesia following abdominal or thoracic surgery. There were no detectable differences between the two groups in analgesia (mean visual analogue scale pain scores ranging between 15-35 mm), average infusion rates of 7-9 ml.hr-1, and serum fentanyl concentrations which reached 1-2 ng.ml-1. There was no difference in postoperative pulmonary function (pH, PaCO2, SaO2), or bowel function (time to flatus or po fluids). The incidence of side-effects including somnolence, nausea and vomiting, pruritus and postural hypotension was also similar. Of the patients receiving fentanyl and bupivacaine 0.1%, three developed a transient unilateral sensory loss to pinprick and ice, and two of these patients had unilateral leg weakness equal to a Bromage 1 score. The addition of bupivacaine 0.1% does not improve epidural infusions of fentanyl using a 10 micrograms.ml-1 concentration following abdominal or thoracic surgery.     

Serologic evidence of West Nile virus and St. Louis encephalitis virus infections in white-tailed deer (Odocoileus virginianus) from New Jersey, 2001

Serum samples from 689 hunter-killed white-tailed deer (Odocoileus virginianus) collected during the 2001 fall hunting season in New Jersey were tested for neutralizing antibodies to West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) by plaque-reduction neutralization tests. WNV-neutralizing antibodies were detected in six (0.9%) of the samples, and SLEV-neutralizing antibodies were found in 11 (1.6%) of the samples. We provide the first report of WNV infection in white-tailed deer.