Hypovitaminosis D and osteopenia/osteoporosis in a haemophilia population: a study in HCV/HIV or HCV infected patients.

Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co-infections. Seventy-eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV-HCV co-infected, HCV mono-infected and uninfected). The BMD was measured by dual energy X-ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F-BMD reduction in all the three groups, whereas L-BMD was significantly lower in co-infected patients (P < 0.05). The clinical score was higher in co-infected (P < 0.002) and mono-infected (P < 0.006). The radiological score was higher in mono-infected than in the other two groups (P < 0.001). Overall 25-hydroxyvitamin D (25-OH Vit D) was reduced (87%). Bone-specific alkaline phosphatase (b-ALP) and telopeptide were increased in co-infected (P < 0.001 and P < 0.01) and mono-infected (P < 0.001 and P < 0.02). The result of the homogeneous F-BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L-BMD in co-infected and the increase of b-ALP and telopeptide in co-infected and mono-infected groups suggest faster bone metabolism in case of infections.

Oscillatory shear stress and reduced compliance impair vascular functions.

Shear stress has been shown to influence endothelial cell gene expression and morphology. In particular, low and bi-directional shear stress, mimicking conditions at plaque-prone areas, down-regulates the expression of several atheroprotective genes, and up-regulates that of other genes considered as pro-inflammatory. Another mechanical situation thought to have a negative influence on vascular functions is arterial stiffness. Loss of arterial compliance occurs during ageing, in diabetic as well as in hypertensive patients. In this work we investigated the effects of these two particular hemodynamic environments (bi-directional shear stress and reduced compliance), using a recently developed perfusion system allowing to expose native arteries in vitro to complex hemodynamic environments. We were able to show that both plaque-prone shear stress and reduced compliance trigger endothelial dysfunction, but via different mechanisms. Only reduced compliance affected vascular contractility, inducing a dedifferentiation of smooth muscle cells and a consequent loss of norepinephrine sensitivity.

Geometrical, functional, and histomorphometric adaptation of rat carotid artery in induced hypertension.

Acute and long-term (up to 56 days) evolution of geometry, structural properties, vascular smooth muscle (VSM) tone and histomorphometric properties of the rat common carotid arteries under induced hypertension were investigated. Hypertension was induced in 8-week old male Wistar rats by total ligation of the aorta between the two kidneys. Rats were sacrificed 2, 4, 8 and 56 days postsurgery. The arterial wall layers thicken non-uniformly during the adaptation process, the inner layers thicken more in the acute phase of hypertension, whereas the outer layers of the wall are thicker than the inner layers at the end of the adaptation phase. Collagen content in the wall media exhibits a non-linear evolution, with a rapid increase in the acute hypertension phase followed by a slower increase at long-term. The elastin content increase is slight and steady, whereas VSM shows a steady but considerable increase which outdoes the collagen increase in long-term phase. VSM tone increases rapidly in the acute phase of remodelling (0-8 days) and this increase in tone contributes to a considerable increase in arterial compliance in the operating pressure range. At long-term (56 days) VSM tone returns to near control level, but compliance is even further increased, which suggests that at long-term the compliance increase is attributed primarily to structural remodelling.

nodD2 of Rhizobium sp. NGR234 is involved in the repression of the nodABC operon.

Transcriptional regulators of the lysR family largely control the expression of bacterial symbiotic genes. Rhizobium sp. NGR234 contains at least four members of this family: two resemble nodD, while two others are more closely related to syrM. Part of the extremely broad host range of NGR234 can be attributed to nodD1, although the second gene shares a high degree of DNA sequence homology with nodD2 of R. fredii USDA191. A nodD2 mutant of NGR234 was constructed by insertional mutagenesis. This mutant (NGR omega nodD2) was deficient in nitrogen fixation on Vigna unguiculata and induced pseudonodules on Tephrosia vogelii. Several other host plants were tested, but no correlation could be drawn between the phenotype and nodule morphology. Moreover, nodD2 has a negative effect on the production of Nod factors: mutation of this gene results in a fivefold increase in Nod factor production. Surprisingly, while the structure of Nod factors from free-living cultures of NGR omega nodD2 remained unchanged, those from V. unguiculata nodules induced by the same strain are non-fucosylated and have a lower degree of oligomerization. In other words, developmental regulation of Nod factor production is also abolished in this mutant. Competitive RNA hybridizations, gene fusions and mobility shift assays confirmed that nodD2 downregulates expression of the nodABC operon.