Association of Nail Dystrophy With Accrued Damage and Capillaroscopic Abnormalities in Systemic Lupus Erythematosus.

BACKGROUND: There are some nail abnormalities described in systemic lupus erythematosus (SLE). OBJECTIVES: The aim of this study was to evaluate the association between nail dystrophy (ND) and disease activity, accrued organ damage, capillaroscopic abnormalities, autoantibodies, and some markers of endothelial cell activation in patients with SLE. METHODS: This was a cross-sectional study of SLE patients from a rheumatology clinic in a tertiary care hospital. Patients were allocated in groups, according to the presence or absence of ND. Demographics, clinical data, disease activity, accrued damage, serology, nailfold capillaroscopy characteristics, serum levels of anti-endothelial cell antibodies, and plasma levels of endothelin 1 were compared between groups. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 index and accrued organ damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. RESULTS: Sixty-one patients were included; 50 patients (82%) were female. Thirty-two patients (52.5%) showed ND, and 29 did not. Besides a more frequent use of cyclophosphamide (46.9% vs 20.7%; P = 0.03) in the ND group, clinical features were similar. A greater organ damage was found in patients with ND (median Systemic Lupus International Collaborating Clinics/American College of Rheumatology index = 0.5, minimum = 0, maximum = 6) than in patients without ND (0, 0, 3, respectively; P = 0.04); specifically, only the skin domain was associated with ND (P = 0.04). Onycholysis (40.6%) and longitudinal ridging (25%) were the most frequent nail changes. Nailfold capillaroscopy changes were more frequent in ND patients (40.6%) than in control subjects (13.8%) (P = 0.02). The most frequent nailfold capillaroscopy findings in the ND group were enlarged capillaries (40.6%) and microhemorrhages (12.5%). There was no association between ND and the autoantibody profile, plasma endothelin 1, or serum anti-endothelial cell antibodies. CONCLUSIONS: Nail dystrophy was associated with higher accrued organ damage and the presence of capillaroscopic abnormalities. This suggests that ND might be related to chronic microvascular damage.

Statin-induced inhibition of MCF-7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress.

Statins have antiproliferative and anti-tumoral effects in MCF-7 cells. We determined the effect of statins upon MCF-7 cell cycle, toxicity, cell death, reactive oxygen species (ROS) production and mitochondrial membrane potential. Fluvastatin, simvastatin and atorvastatin inhibited cell proliferation. Antiproliferation was associated with a decrease in the DNA synthesis and a cell cycle arrest in the G1 and G2/M phases. A loss in the mitochondrial membrane potential was observed with fluvastatin. Statins induced increase in ROS production that was associated with cell death, which was abrogated by the antioxidant NAC. Our results suggest that the cytotoxic effect observed is mediated by an oxidative stress.

Altered detection of molecules associated with leukocyte traffic in HUVECs derived from newborns with a strong family history of myocardial infarction.

Atherosclerosis is a chronic inflammatory disease. As such, recruitment of immune cells is a significant event. Tightly controlled signaling molecules regulate leukocyte adhesion and migration to the tissues. The aim of this study was to determine if human umbilical vein endothelial cells (HUVECs) derived from healthy newborns with a strong family history of myocardial infarction (FHMI) showed variations in the presence of molecules related with leukocyte traffic and migration, in comparison to control healthy newborns. For this purpose, we evaluated the labeling of sialic acid containing glycoproteins, tight junction claudins and the cytoskeleton, using lectin- and immunocytochemistry in HUVECs from individuals with and without a strong FHMI. Our results show important differences in the labeling of alpha-2,3 or alpha-2,6 sialic acid-containing glycoconjugates, a disarrangement of actin filaments secondary to the absence of cytoplasmic claudin-5 immunopositivity and an increase in the binding of FHMI HUVECs to CD3+ Jurkat cells. It is possible that these differences relate to a predisposition for early appearance of atherosclerotic lesions.

Increased expression of inflammation-related co-stimulatory molecules by HUVECs from newborns with a strong family history of myocardial infarction stimulated with TNF-alpha and oxLDL.

BACKGROUND: Recent findings indicate that atherosclerosis, a chronic inflammatory process, might start during childhood. Nevertheless, the expression of inflammation-related molecules of endothelial cell isolated from healthy neonates with a strong family history of myocardial infarction (SFHMI) has been rarely analyzed. METHODS: Human umbilical vein endothelial cells (HUVECs) from children with SFHMI were assessed for the expression of CD40 and CD40L, in the presence of TNF-alpha and oxLDL. The intracellular content of CD80, CXCL8 and tissue factor by HUVECs stimulated with a CD40 agonist monoclonal antibody as well as monocytes/lymphocyte adhesion to TNF-alpha-stimulated HUVECs was also evaluated. RESULTS: The basal expression of CD40 and CD40L was higher in SFHMI-positive HUVECs in comparison to controls. TNF-alpha and oxLDL upregulated the expression of CD40 and CD40L in SFHMI versus control HUVECs (p<0.001). The intracellular expression of CXCL8, tissue factor and CD80 was also higher than in controls, and the adhesion of lymphocyte- and monocyte-like cells augmented upon TNF-alpha stimulation. CONCLUSIONS: It is possible that the modifications observed in the SFHMI-positive HUVECs, all of them relevant to the atherosclerosis process, may lead to early inflammatory reactions, thus contributing to the premature initiation of atherosclerotic lesions in these children.

Isolation of a 19-kDa mycobacterium, bovis-specific antigen, different from MPB70/80, by chromatofocusing.

Two antigens, 19-kDa each, were purified from Mycobacterium bovis culture filtrate protein extract by chromatofocusing. Antigen I had a 4.5 pI, and its amino terminal (DPVDAVINTTCNYGQVVAALNATDP) showed a 100% homology with the hypothetical protein Rv1174c. Antigen II had a pI of 6.0 pI and its amino terminal (GDLVGPGCAEYAAANPTGPASVQGM) showed a 100% homology with M. bovis MPB70/80. Antigen I is a hetero-dimer formed by a glycosylated, 10.5-kDa, monomer and a non-glycosylated 8-kDa monomer with identical amino terminal sequences. Both antigens were recognized by the sera of PPD+ animals, but antigen I did not crossreact with sera of human PPD+ individuals. Antigen I was a weak inducer of lymphocyte proliferation and IFN-gamma production. Our results show that M. bovis expresses a 19 kDa glycoprotein, homologue to the product of M. tuberculosis gen Rv1174c, which may prove useful for bovine TB diagnostic assays.