Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty

OBJECTIVE: To assess the effect of hypercholesterolemia on neointima formation and vascular remodelling after porcine coronary angioplasty. METHODS: Left anterior descending coronary angioplasty was carried out in five control and 16 age-matched hypercholesterolemic miniature pigs. Vascular remodelling was measured by intravascular ultrasound. Neointima size and composition were assessed by quantitative image analysis. Coronary smooth muscle cells (SMC) from control and diet pigs were collected 1 h after angioplasty for in vitro study of the effect of hypercholesterolemic serum on SMC migration and of macrophage-induced matrix degradation on SMC adhesion. RESULTS: Twenty-eight days after angioplasty, lumen increase was 0.08+/-1.7 mm(2) in diet and 2.7+/-2.7 mm(2) (P=0.016) in control pigs. Lumen increase correlated with vascular remodelling (IEL(post)/IEL(pre); R(2)=0.59; P<0.001) and with the circumferential gain relative to the neointima (R(2)=0.32; P<0.01) but not with neointimal area that was similar in control and diet pigs. Circumferential gain correlated with VSMC deposition at the site of the injury (R(2)=0.28; P<0.01) that correlated with organized collagen (R(2)=0.34; P<0.01). The VSMC and collagen content of neointima in diet pigs was lower whereas the macrophage content was higher. Hypercholesterolemic serum and oxidised LDL reduced migration of VSMC from diet pigs. Macrophage-induced degradation of VSMC extracellular matrix reduced VSMC adhesion (P=0.015). CONCLUSION: Hypercholesterolemia impairs vascular remodelling of balloon-treated coronary arteries. It decreases VSMC and collagen accumulation at the site of injury. Our in vitro data suggest that this decrease can be due to macrophage-induced matrix degradation and reduced VSMC adhesion and to impaired VSMC migration. Oxidised LDL mimics the inhibitory effect of hypercholesterolemic serum.     

La neurostimulation n’augmente pas le taux de succès du bloc du nerf saphène

PURPOSE: To evaluate neurostimulation of motor components of the vastus medialis muscle and the rectus femoris muscle, with a view to blocking the medial sensory fibres of the saphenous nerve. METHOD: First we dissected four femoral trigones, in order to select our puncture point. We were able to observe that, at the flexion crease of the thigh, the different fibers that make up the femoral nerve were clustered together and the saphenous nerve and the vastus medialis nerve had not yet separated from the femoral stem. Secondly, we conducted a prospective clinical study among 71 patients who had undergone surgery on the lower third of the leg with a sciatic block and a saphenous nerve block. The saphenous nerve block was performed using 10 mL of local anesthetic, by puncturing the flexion crease of the thigh in a bid to obtain one of two muscle responses: medial (contraction of the vastus medialis muscle) or anterior (contraction of the rectus femoris muscle and elevation of the patella). RESULTS: There was an overall success rate of 80% with the saphenous nerve block, with no statistical difference existing between the two response types. Average duration for the block to be completed was two minutes and it took an average of 15 min before the anesthesia took effect. No complications were encountered, apart from a puncture of the femoral artery, which was clinically inconsequential. CONCLUSION: Neurostimulation of the vastus medialis muscle has the same effect as neurostimulation of the rectus femoris muscle with respect to anesthesia of the saphenous nerve. Neurostimulation of the medial compartment of the femoral nerve saves local anesthetic, compared to a standard femoral block.     

Regression of hepatocellular carcinoma under Tamoxifen: report of one case and review of the literature

Hepatocellular carcinoma is a malignant tumor with a poor prognosis, particularly when it is unresectable. The results of tamoxifen treatment in hepatocellular carcinoma have been disappointing and randomized studies have shown conflicting results. We report the case of a 72-yr-old-man with histologically confirmed hepatocellular carcinoma on a normal liver, that regressed with tamoxifen treatment. Regression was confirmed by normalization of serum alpha-fetoprotein levels and a significant decrease in radiological lesions by 66%. The patient was alive in excellent clinical condition more than 30 months after the initial diagnosis.     

Loss of expression of the beta subunit of soluble guanylyl cyclase prevents nitric oxide-mediated inhibition of DNA synthesis in smooth muscle cells of old rats

We compared the effects of NO donors and cGMP analogues on the growth of aortic smooth muscle cells (SMCs) derived from newborn, adult (aged 3 months), and old (aged 2 years) rats. We found that the NO donor S-nitroso-N-acetylpenicillamine failed to block DNA synthesis in SMCs from old rats but was effective in SMCs from newborn and adult rats. However, cGMP analogues were inhibitory in all 3 SMC types. We demonstrated that in SMCs from old rats, NO was unable to increase the concentration of intracellular cGMP, suggesting that either cGMP synthesis was defective or cGMP degradation was enhanced. Western blot analysis revealed that SMCs from old rats do not express the beta subunit of soluble guanylyl cyclase. To confirm the importance of this observation in vivo, we balloon-injured the carotid arteries of adult and old rats. Whereas soluble guanylyl cyclase was expressed at the same level in the media of injured vessels and uninjured vessels of both groups, its expression in the intimas of old rats was reduced by 70% compared with intimas from adult animals. Furthermore, N(omega)-nitro-L-arginine, an inhibitor of NO synthesis, enhanced the intimal thickening in injured vessels in adult rats but not in old rats. We conclude that the loss of NO responsiveness in aged rats is due to the lack of the beta subunit of soluble guanylyl cyclase, and we speculate that this defect contributes to the enhanced intimal thickening in response to injury in old animals.     

Targeting connexin 43 prevents platelet-derived growth factor-BB-induced phenotypic change in porcine coronary artery smooth muscle cells

We previously reported that reducing the expression of the gap junction protein connexin (Cx)43 in mice restricts intimal thickening formation after acute vascular injury by limiting the inflammatory response and the proliferation and migration of smooth muscle cells (SMCs) toward the damaged site. SMC populations isolated from porcine coronary artery exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). S-SMCs are predominant in the normal media, whereas R-SMCs are recovered in higher proportion from stent-induced intimal thickening, suggesting that they participate in the restenotic process. Here, we further investigate the relationship between connexin expression and SMC phenotypes using porcine coronary artery SMCs. Cx40 was highly expressed in normal media of porcine coronary artery in vivo, whereas Cx43 was barely detectable. In contrast, Cx40 was downregulated and Cx43 was markedly upregulated in stent-induced intimal thickening. In vitro, S-SMCs expressed Cx40 and Cx43. In R-SMCs, Cx43 expression was increased and Cx40 was absent. We confirmed that S-SMCs treated with platelet-derived growth factor-BB acquire an R phenotype. This was accompanied by an upregulation of Cx43 and a loss of Cx40. Importantly, platelet-derived growth factor-BB-induced S-to-R phenotypic change was prevented by a reduction of Cx43 expression with antisense, ie, S-SMCs retained their typical elongated appearance and the expression of alpha-smooth muscle actin, a well-known SMC differentiation marker, whereas the expression of S100A4, a typical marker of R-SMCs, was prevented. In conclusion, limiting Cx43 expression in S-SMCs prevents platelet-derived growth factor-BB-induced S-to-R modulation. This suggests that Cx43 may be an additional target for local delivery strategies aimed at reducing restenosis.     

Combination of line immunoassays Mikrogen recomLine CMV IgG and recomLine CMV IgG Avidity helps to date the onset of CMV primary infection

CMV IgG avidity assays are widely used and can be helpful in pregnant women to date the onset of CMV primary infection; however, these tests are not standardized and sometimes give inconclusive results. We evaluated the performances of Mikrogen recomLine CMV IgG and IgG Avidity compared to the VIDAS CMV IgG Avidity. On a first sample set of 89 sequential sera collected from 40 women with precisely determined onset of CMV primary infection, the combination of Mikrogen recomLine CMV IgG and IgG Avidity showed an accurate interpretation in 83.1% (74/89), an incorrect result in 4.5% (4/89), and an inconclusive result in 12.4% (11/89) and showed a better sensitivity to diagnose infections <14?weeks compared to VIDAS (85.9% vs. 76.9%). On a second sample set of 89 sera with an intermediate VIDAS CMV IgG Avidity, the combination of line immunoassays provided additional information on the time of infection in 79% (70/89) of the samples. This combination of line assays is useful as additional confirmatory testing and can help to date more precisely the onset of CMV primary infection.