At a dose as low as 1 microgram per kilogram of body weight, lysergic acid diethylamide (LSD) significantly decreased the suppressive effect of electric shock on licking behavior of the rat. Attenuation of punishment was also obtained with mescaline, but neither dimethyltryptamine nor delta9-tetrahydrocannabinol was active in this test. Cyproheptadine and alpha-propyldopacetamide, drugs that interfere with the function of neurons that contain serotonin, have a behavioral effect similar to that of LSD and mescaline, which suggests that the attenuation of punishment produced by these hallucinogens may result from decreased activity of such neurons.

The ruminant pathogen Listeria ivanovii differs from Listeria monocytogenes in that it causes strong, bizonal haemolysis and a characteristic shovel‐shaped co‐operative haemolytic (‘CAMP‐like’) reaction with Rhodococcus equi. We cloned the gene responsible for the differential haemolytic properties of L. ivanovii, smcL. It encodes a sphingomyelinase C (SMase) highly similar (> 50% identity) to the SMases from Staphylococcus aureus (β‐toxin), Bacillus cereus and Leptospira interrogans. smcL was transcribed monocistronically and was expressed independently of PrfA. Low‐stringency Southern blots demonstrated that, within the genus Listeria, smcL was present only in L. ivanovii. We constructed an smcL knock‐out mutant. Its phenotype on blood agar was identical to that of L. monocytogenes (i.e. weak haemolysis and no shovel‐shaped CAMP‐like reaction with R. equi ). This mutant was less virulent for mice, and its intracellular proliferation was impaired in the bovine epithelial‐like cell line MDBK. The role of SmcL in intracellular survival was investigated using an L. monocytogenes mutant lacking the membrane‐damaging determinants hly, plcA and plcB, being thus unable to grow intracellularly. Complementation of this mutant with smcL on a plasmid was sufficient to promote bacterial intracellular proliferation in MDBK cells. Transmission electron microscopy showed that SmcL mediates the disruption of the phagocytic vacuole and the release of bacteria into the cytosol. Therefore, L. ivanovii possesses a third phospholipase with membrane‐damaging activity that, together with PlcA and PlcB, may act in concert with the pore‐forming toxin Hly to mediate efficient escape from the vacuolar compartment. The 5′ end of smcL is contiguous with the internalin locus i‐inlFE, which is also specific to L. ivanovii and is required for full virulence in mice. Thus, smcL forms part of a novel virulence gene cluster in Listeria that is species specific.

Objective-Our study aims to determine the role of time of menopause on vascular inflammation biomarkers and how it affects their modulation by estrogen and raloxifene in postmenopausal women. Methods and Results-Uterine arteries from 68 postmenopausal women were divided into 3 segments and cultured for 24 hours in tissue culture media containing 17β-estradiol (100 nmol/L), raloxifene (100 nmol/L), or vehicle. Assessment of arterial concentration of 13 inflammatory biomarkers was performed by multiplex immunobead-based assay. Aging per se has a positive correlation with the generation of several proinflammatory markers. Although short-term estradiol exposure correlates with lower expression of tumor necrosis factor-α, vascular endothelial growth factor, and interleukin-1β in all age groups, for most biomarkers aging was associated with a switch from a beneficial anti-inflammatory action by estrogen, at earlier stages of menopause, to a proinflammatory profile after 5 years past its onset. Raloxifene has no significant effect on the expression of all proinflammatory markers. Western blot analysis of estrogen receptor expression (estrogen receptor-α and estrogen receptor-β) showed that estrogen receptor-β increases with aging, and this increase has a positive correlation with the generation of several proinflammatory markers. Women who have never been on hormone replacement therapy or selective estrogen receptor modulators (raloxifene and tamoxifen) were matched for body mass index, blood pressure, lipids, and lipoproteins. Exclusion criterion includes use of chronic anti-inflammatory therapy, statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor type 1 antagonist. At the moment of hysterectomy, arteries were cleaned, divided into 3 segments, and cultured for 24 hours in tissue culture media containing 17β-estradiol (100 nmol/L), raloxifene (100 nmol/L), or vehicle for further analysis of inflammation biomarkers and estrogen receptor (ER) expression. Detailed methods related to tissue culture and treatments, multiplex assay, and Western blot are shown in the online-only Data Supplement. Conclusion-Aging Data AnalysisTime since menopause was defined by the age at which a woman last had any menstrual bleeding and expressed as years passed since last menstruation until the day of hysterectomy. Inflammation biomarker concentration in each sample was expressed as mean concentration from triplicate measurements normalized by the amount of protein in each sample. The degree of linear relationship between time since menopause and biomarker concentration found in each group (ie, estrogen-treated, raloxifene-treated, and untreated groups), as well as the correlation between ER-α or ER-β expression (in untreated arteries) and biomarker concentration after treatments (estrogen or raloxifene), was expressed as regular linear regression compared with the use of Pearson correlation coefficient, expressed as Pearson r value, ranging from −1 (inverse correlation) to +1 (positive correlation). The proportion of...