Use of Bromoergocryptine in the Validation of Protocols for the Assessment of Mechanisms of Early Pregnancy Loss in the Rat

Use of Bromoergocryptine in the Validation of Protocols forthe Assessment of Mechanisms of Early Pregnancy Loss in theRat. CUMMINGS, A. M., PERREAULT, S. D., AND HARRIS, S. T. (1991).Fundam. Appl. Toxicol 17, 563–574. Validated protocolsfor evaluating maternally mediated mechanisms of early pregnancyfailure in rodents are needed for use in the risk assessmentprocess. To supplement previous efforts in the validation ofa panel of protocols assembled for this purpose, bromoergocryptine(BEC) was used as a model compound because it is known to inhibitpituitary prolactin secretion. BEC was tested using the earlypregnancy protocol (EPP), the decidual cell response technique(DCR), the pre- vs postimplantation protocol (PPP), and embryotransport rate analysis (ETRA). These protocols evaluate theeffects of chemicals on multiple endpoints following exposureduring (a) the first 8 days of pregnancy, (b) early pseudopregnancyaccompanied by decidual induction, (c) the pre- and postimplantationintervals of early pregnancy, or (d) the period of embryo transport.In the EPP, dosing with BEC during Days 1–8 of pregnancyreduced the number of implantation sites found on Day 9 as wellas serum progesterone. The DCR technique revealed a dose-dependentinhibition of decidual growth concomitant with decreased serumprogesterone as a result of BEC treatment. A modified DCR techniqueusing hormone-supplemented ovariectomized rats demonstratedthat BEC did not impair decidual growth in the presence of adequateprogestogenic support. Pie- vs postimplantation dosing indicatedthat implantation is vulnerable to BEC effects at least throughDay 4. BEC had no effect on embryo transport rate. Data fromthese protocols identified BEC as having adverse maternal effectsduring early pregnancy. While the pituitary was not identifiedby these protocols as the site of BECs's primary action, theprotocols did identify a reduction in serum progesterone andimpaired uterine function as toxicological mechanisms mediatingthe reduced fertility seen following BEC exposure.     

Interferon-γ signal transduction during parasite infection: modulation of MAP kinases in the infection of human monocyte cells (THP1) by Toxoplasma gondii

We assayed mitogen-activated protein (MAP) kinase phosphorylation in a human monocyte cell line (THP1) during their infection by Toxoplasma gondii . In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increased in the cytosol and membrane fractions of THP1 infected with T. gondii . The MAP kinase phosphorylation of uninfected THP1 cells was not significantly modified by incubation for 20 h with 1000 U/ml of IFN-γ. However, IFN-γ treatment of infected cells significantly reduces the increase in phosphorylation caused by parasite infection. There was also MAP kinase activity in the cytosol and membrane fractions of extracellular T. gondii tachyzoites. IFN-γ altered the distribution of activity in subcellular fractions of extracellular T. gondii tachyzoites. This indicates that IFN-γ directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and that the decrease in MAP kinase activity in infected cells caused by IFN-γ may be involved in mediating their protective signals .     

LIMITATIONS IN THE USE OF {gamma}-GLUTAMYL TRANSFERASE ESTIMATIONS IN ALCOHOL-DEPENDENT SUBJECTS

This paper studies a cohort of randomly selected attenders ata district alcohol treatment service and examines the relationshipbetween clinical assessments and laboratory markers currentlyin use in the Unit. It measures in particular the rate of changeof serial     

The value of bacteriology and serology in the diagnosis of necrotizing fasciitis

Fourteen patients with necrotizing fasciitis are described. In thirteen the cause was Streptococcus pyogenes [Group A beta haemolytic streptococcus (BHS)]; in the fourteenth, Staphylococcus aureus was responsible. In the acute fulminating form of the disease, BHS can be cultured from the affected tissues. In the less acute form, particularly when the patient has been previously treated with antibiotics, other bacteria colonize the tissues and the BHS cannot be isolated. Serological evidence of infection with Streptococcus pyogenes can be ascertained in all such patients by finding high levels of anti-desoxyribonuclease B and anti-hyaluronidase. Measurement of the anti-streptolysin O titre is not helpful. Once the diagnosis is made, surgical removal of all necrotic tissue is still the treatment of choice.