Nicardipine improves myocardial perfusion in systemic sclerosis

Primary scleroderma myocardial disease may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. We evaluated the effect of the calcium channel blocker nicardipine on myocardial perfusion assessed by thallium-201 scanning in 16 patients with systemic sclerosis. Thallium-201 single photon emission computerized tomography was performed at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SD) number of left ventricular segments with perfusion defects significantly decreased from 6.0 +/- 2.0 at baseline to 4.1 +/- 2.3 after nicardipine (p less than 0.01). The mean global perfusion score significantly increased from 10.2 +/- 1.9 at baseline to 11.9 +/- 2.6 after nicardipine (p less than 0.02). Our study demonstrates short-term improvement in thallium-201 myocardial perfusion with nicardipine in patients with systemic sclerosis.     

Single-steep transformation of human breast epithelial cells by SV40 large T oncogene.

Normal human mammary epithelial cell (HMEC) cultures originating from 2 mammoplasty reduction surgical samples were transfected with replication-defective SV 40 DNA. Two independent cell lines designated as S2T2 and S1T3, selected for their increased proliferation potential and lifespan, were propagated for greater than 22 months in culture. They maintained a near-diploid karyotype with few chromosomal markers such as trisomy 1q (S1T3) and trisomy 8q (S2T2), which are most common in breast cancer in vivo. Immortalized S1T3 cells were not tumorigenic, whereas S2T2 cells produced slowly growing tumors in nude mice. One tumor was propagated in vitro and the transformed NS2T2 cell line subsequently raised 100% large tumors in the nude mouse. Rearrangement of the SV40 genome was observed in NS2T2 cells, which was not associated with increased expression of large T antigen. S1T3, S2T2 and transformed NS2T2 cell lines expressed cytokeratins CK18, CK19, the mammary-specific antigen DF3, and functional EGF receptors. Single-step immortalization and malignant transformation of human breast epithelial cells can thus occur upon transfection with SV40 large T oncogene. The chromosomal abnormalities observed in these cell lines suggest that they could offer a model for the study of breast-tumor progression in vitro.     

The pleiotropic functions of peroxisome proliferator-activated receptor γ

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for synthetic compounds that induce peroxisome proliferation. PPARgamma is the best characterized of the PPARs. The heterodimer of PPARgamma with the retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization. The RXR/PPARgamma heterodimer furthermore has been reported to have important immunomodulatory activities and to affect cell proliferation/differentiation pathways in various malignancies. PPARgamma is activated by a number of naturally occurring fatty acid derivatives and by several synthetic compounds, including the thiazolidinediones and L-tyrosine-based insulin sensitizers. This review gives an overview of the pleiotropic functions of PPARgamma and discusses the wide-ranging medical implications that modulation of PPARgamma activity might have for various diseases, ranging from obesity and type 2 diabetes to cancer and inflammation.     

Immune status and uptake of antiretroviral interventions to prevent mother-to-child transmission of HIV-1 in Africa

The aim of this study performed in Abidjan, C?te d'Ivoire, was to describe the distribution of CD4+ T-cell lymphocytes (CD4) in HIV-1-infected (HIV+) pregnant women diagnosed during prenatal voluntary counseling and testing and to assess whether HIV-related immunodeficiency influenced the acceptance of an antiretroviral (ARV) package (zidovudine beginning at 36 weeks of amenorrhea plus intrapartum nevirapine) to prevent mother-to-child transmission. Between April and June 2002, a CD4 count was systematically performed in all HIV+ women (n=221) in 5 antenatal clinics carrying out voluntary counseling and testing. No difference in CD4 count was found in HIV+ women who did not return for their test result (n=50) and those who were informed of their positive serostatus (n=171) (median CD4 count: 389/mm3 vs. 420/mm3; P=0.19). We also found a lack of difference in CD4 count in those who accepted ARV (n=72) and those who did not but knew their HIV status (n=99) (median CD4 count: 405/mm3 vs. 425/mm3; P=0.47). The overall uptake of the intervention (31.9%) appeared to be independent of the maternal immune status.     

Campylobacter fetus bloodstream infection: risk factors and clinical features

In this paper, we report 21 cases of Campylobacter fetus bloodstream infection observed in our institution over a 9-year period. The median age of the patients was 78 years. Most of them (62%) had a significant underlying disease, such as diabetes, immunodeficiency or cardiovascular disease. The main clinical features were fever with (62% of cases) or without (38%) extra-intestinal symptoms. These included mycotic aneurysm of the abdominal aorta (24%) and cellulitis (19%). Antibiotic treatment was mainly based on amoxicilline-clavulanate (57%) or imipenem (21%), for a median duration of 28 days. A favourable outcome was observed in 72% of cases. Death directly attributable to infection was observed for three patients, due to the rupture of an infected aneurysm or relapsing bloodstream infection with septic shock. All patients initially treated with imipenem had a favourable outcome. This report adds evidence that C. fetus bloodstream infection should be suspected in elderly patients with fever, immunodeficiency and cardiovascular damages. Imipenem seems to be the most active drug, especially in severe cases.     

Oxytocin localization and function in the A1 noradrenergic cell group: ultrastructural and electrophysiological studies

Antibodies to oxytocin and noradrenalin were utilized in an immunocytochemical study of the caudal ventrolateral medulla of the rat brainstem. Noradrenalin was visualized by using antibodies to noradrenalin and by means of a silver-gold intensification of diaminobenzidine, whereas oxytocin could be demonstrated in the same section by using the diaminobenzidine precipitate as a marker. At the light microscopic level, oxytocin fibers were densely distributed around the A1 cell bodies. At the ultrastructural level, oxytocin-containing fibers were seen to terminate synaptically onto noradrenalin-containing neurons. Previous studies have shown that electrical stimulation of A1 neurons selectively activates vasopressin-secreting neurons in the supraoptic nucleus. Therefore, separate electrophysiological studies were set up, in which we observed that oxytocin infusions (100-200 pg) into the A1 area enhanced the activity of 16 out of 19 putative vasopressin-secreting neurons and elicited no response from any of 10 oxytocin-secreting neurons. This finding suggests that some of the parvicellular neurons in the paraventricular nucleus of the hypothalamus, from which the A1 neurons derive their oxytocin innervation, can activate the A1 cell group via this peptidergic neurotransmitter. One of the consequences of A1 neuronal activation is enhanced firing of hypothalamic supraoptic (and paraventricular) vasopressin-secreting neurons, and a consequent rise in plasma vasopressin.