Steroid-free medium discloses oestrogenic effects of the bisphosphonate clodronate on breast cancer cells

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis

The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing’s sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone

Antioxidant Action of the Antiarrhythmic Drug Mexiletine in Brain Membranes

Mexiletine is a class Ib antiarrhythmic drug used in the treatment of ventricular arrhythmias. The Naf channel blocker mexiletine inhibits calcium influx in cells via decreasing reverse operation of the Na+-Ca2+ exchanger. Thus this drug is shown to protect the CNS white matter against anoxic/ischemic injury. The aim of our study was to investigate if this drug could act as an antioxidant drug as well. The antioxidant action of this drug was studied under different oxidant conditions in vitro, and thiobarbituric acid-reactive substances were measured to follow lipid peroxidation. Mexiletine inhibited iron-ascorbate-H2O2-induced lipid peroxidation in brain membranes, liver microsomes and phospholipid liposomes, being most effective in brain membranes. The inhibition was dose- and time-dependent. Mexiletine also inhibited copper-ascorbate-H2O2 -induced lipid peroxidation but to a lesser extent. It is concluded that mexiletine has a dual effect toward oxidative injury in brain, both by inhibiting Na+-Ca2+ exchanger-dependent Ca2+ influx and by acting as an inhibitor of lipid peroxidation. However, as this drug is effective at millimolar concentrations, it should be considered less active than natural antioxidants that are effective at micromolar concentrations.WoSScopu

Role of nitric oxide in hypoxia-induced changes in newborn rats

In order to investigate the role of nitric oxide (NO) in hypoxic tissue damage in newborns, we studied the effects of systemic administration of an inhibitor of NO synthase, N-G-nitro-L-arginine (L-NNA), and the precursor for the synthesis of NO, L-arginine (L-ARG), on the biochemical and histological changes in brain, heart, lung, liver, kidney, intestine, and skeletal muscle tissues. Four groups of 1-day-old Wistar rat pups were used: control, hypoxic, L-ARG, and L-NNA groups. L-ARG 100 mg/kg or L-NNA 2 mg/kg was administered as a bolus intraperitoneally 1.5 h before hypoxia. Hypoxia increased lipid peroxidation in all tissues except muscle; this increase was prevented by L-NNA and L-ARG in brain, heart, lung, kidney, and liver tissues. L-NNA in intestine and L-ARG in muscle tissue increased lipid peroxidation. The tissue-associated myeloperoxidase activity was decreased in the liver by L-NNA and L-ARG. Histopathological changes in intestines were villous epithelial separation and hyperemia in hypoxic and L-NNA groups which were not observed in control and L-ARG groups. In lungs, pulmonary hemorrhage was observed only in the hypoxic group. These data suggest that NO acts both as a destructive and a protective agent in the pathogenesis of hypoxia-reoxygenation injuries. Copyright (C) 2000 S. Karger AG. Basel

Effects of intestinal ischemia-reperfusion on major conduit arteries

Intestinal ischemia-reperfusion (I-R) is a common and serious clinical condition associated with simultaneous remote organ dysfunction. The purpose of this study was to investigate the effects of intestinal I-R on the vasomotor functions of major conduit arteries. Anesthetized rabbits were randomly assigned to one of three groups: sham-operated controls (Group I), and one-hour intestinal ischemia with two-hour reperfusion (Group II) or four-hour reperfusion (Group III). The following mechanisms of vasomotor functions were studied in abdominal aorta, superior mesenteric, renal, pulmonary, and carotid arterial rings: (1) endothelial-dependent vasodilation response to acetylcholine, (2) endothelial-independent vasodilation response to nitroprusside, (3) beta-adrenergic vasodilation response to isoproterenol, and (4) phenylephrine-induced vasoconstriction. Intestinal injury was quantified using malondialdehyde (MDA) concentration and wet-to-dry intestine weight ratio. Intestinal I-R did not affect the maximal responsiveness or the sensitivity to acetylcholine, nitroprusside, and isoproterenol in all the vessels studied. The maximal contractile response to phenylephrine increased significantly in mesenteric artery in Group II, (227.1 +/- 15.1% vs 152.8 +/- 11.7% in controls) (p < 0.05). Intestinal MDA concentration, a marker of oxidant injury, increased from 39.87 +/- 9.41 nmol/g to 67.8 +/- 8.8 nmol/g in group II (p < 0.01), and to 94.8 +/- 7.56 nmol/g in Group III (p < 0.001). Wet-to-dry intestine weight ratio increased from 3.62 +/- 0.12 to 4.28 +/- 0.17 in Group II (p < 0.01), to 4.62 +/- 0.14 in Group III (p < 0.001). These data indicate that although the intestines of the animals subjected to intestinal I-R are seriously injured, the smooth muscle relaxation of major conduit arteries was not affected

Infracardiac total anomalous pulmonary venous drainage with unusual presentation

WOS: 000280075700018PubMed ID: 20589476Total anomalous pulmonary venous drainage (TAPVD) is a rare entity which forms approximately 0.4 to 2% of all congenital heart disease. The infracardiac type usually involve obstructions on pulmonary venous connections and comprising a quarter of all TAPVD cases. The clinical findings in patients with obstructed infracardiac TAPVD could mimic respiratuary distress of several different etiologies during first hours of life. In this article, we present a case of a neonate with infracardiac type of TAPVD presented with only distinct subcutaneous veins of abdominal and thoracic wall