Effect of reactive oxygen intermediaries on the viability and infectivity of Mycobacterium lepraemurium

Murine leprosy is a natural disease of the mouse, the most popular model animal used in biomedical research; the disease is caused by Mycobacterium lepraemurium (MLM), a successful parasite of macrophages. The aim of the study was to test the hypothesis that MLM survives within macrophages because it highly resists the toxic effects of the reactive oxygen intermediaries produced by these cells in response to infection by the microorganism. MLM cells were incubated in the presence of horseradish peroxidase (HRPO)-H(2)O(2)-halide for several periods of time. The peroxidative effect of this system was investigated by assessing the changes occurred in (a) lipid composition; (b) viability; and (c) infectivity of the microorganism. Changes in the lipid composition of peroxidated- vs. intact-MLM were analysed by thin layer chromatography. The effect of the peroxidative system on the viability and infectivity of MLM was measured by the alamar blue reduction assay and by its ability to produce an infection in the mouse, respectively. Peroxidation of MLM produced drastic changes in the lipid envelope of the microorganism, killed the bacteria and abolished their ability to produce an in vivo infection in the mouse. In vitro, MLM is highly susceptible to the noxious effects of the HRPO-H(2)O(2)-halide system. Although the lipid envelope of MLM might protect the microorganism from the peroxidative substances produced at 'physiological' concentrations in vivo, the success of MLM as a parasite of macrophages might rather obey for other reasons. The ability of MLM to enter macrophages without triggering these cells' oxidative response and the lack of granular MPO in mature macrophages might better explain its success as an intracellular parasite of these cells.     

Enfermedad indiferenciada del tejido conectivo y enfermedad pulmonar intersticial: intentando definir patrones

Objectives

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior.

European high-activity (32)P radioactive stent experience

Brachytherapy by implantation of a radioactive stent is an alternative approach to catheter-based systems to reduce restenosis. The pilot clinical trials using 32P radioactive b-emitting stents at low-to-intermediate activity (0.5Eth 3.0 mCi) showed that restenosis at 6 months was not different from that of currently available non-radioactive stents. The evaluation of the efficacy in reducing restenosis of radioactive stents with higher activities (3Eth 24 mCi) started in Europe (Milan, Rotterdam and Vienna) between 1998 and 1999. In the Milan and Rotterdam experience, 32P radioactive stents with an activity of 3Eth 12 mCi demonstrated a reduction of intra-stent restenosis to < 4%. However, a high-edge restenosis > 30% was observed in the first 1Eth 3 mm outside the stent margins. This edge effect might be due to a low dose of radiation at the stent margins combined with systematic balloon injury in the reference segments. The hypothesis that a further increase in stent activity (12Eth 21 mCi) associated with a reduced balloon injury outside the stent could solve the problem of edge restenosis was not confirmed by the Milan experience; edge restenosis still occurred in 26% of the lesions treated by a single 32P radioactive stent, even if a nonaggressive stent implantation strategy was used. Two approaches under investigation to solve the problem of edge restenosis are: 1) lengthening the stent with a non-radioactive stent (cold-ends stent) to prevent negative remodeling; and 2) extending the area of irradiation beyond the balloon-injured area by an increased activity at the stent ends (hot-ends stent).     

Characterization of total occlusions with intracoronary ultrasound: the importance of the duration of occlusion

OBJECTIVE: To assess the impact of the occlusion duration on the characteristics of coronary occlusive plaques. BACKGROUND: The percutaneous recanalization of chronic total coronary occlusions is a technically demanding and yet often unsuccessful procedure due to unfavorable morphological changes described by histology but not well defined in vivo. METHODS: Thirty-five consecutive total occlusions of > or = 1 month duration in previously untreated native coronary arteries were studied using intracoronary ultrasound following dilatation with a 1.5 mm balloon. Plaque characteristics of lesions with an occlusive duration of > or = 3 months (old occlusions) and those of < 3 months (recent occlusions) were then compared. The ultrasound cross-section where there was maximal plaque accumulation at the site of occlusion was analyzed for its qualitative and quantitative characteristics. The lesion remodeling index was defined as the vessel area at occlusion divided by the vessel area at a proximal reference. RESULTS: The old occlusion group comprised 11 lesions whereas 16 lesions were found in the recent occlusion group; the occlusion duration was undetermined in the remaining 8 lesions, and the mean occlusion duration was found to be 4.9 +/- 4.3 months, over a range of 1 36 months. The baseline clinical and angiographic characteristics were similar in the 2 groups. The lesion remodeling index was found to be significantly lower in older occlusions than in the more recent occlusions (0.75 +/- 0.14 vs. 1. 06 +/- 0.25; p = 0.007) and the duration of the occlusion also correlated with the length of calcified segment as determined by ultrasound (p = 0.040), and with a smaller angiographic proximal reference diameter (p = 0.043). CONCLUSION: Long-standing occlusions undergo lesion shrinkage and exhibit more extensive calcification.     

Lp(a) levels in patients undergoing aorto-coronary bypass surgery.

The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass surgery (BP) and to relate these parameters to the involvement of one or more vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls, matched for sex, age and body weight were studied. Higher triglyceride and apo B levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in comparison with the controls. Lp(a) levels were slightly, but not significantly, increased. Moreover BP patients presented a significantly higher prevalence of HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22.1%) and Lp(a) levels above 70 mg dl-1 (10.4% vs 1.3%) than the controls. When patients were divided according to the number of coronary vessels involved (one, two or three), no significant difference was found, with a trend to increase in Lp(a) mean levels and in prevalence of Lp(a) levels above 30 and 70 mg dl-1 in more severely diseased patients. These results suggest that patients with severe coronary artery disease undergoing aorto-coronary bypass surgery show low HDL-cholesterol levels with high triglyceride levels. Moreover Lp(a) levels above 70 mg dl-1 are highly associated with severe coronary vessel stenosis.     

Confocal Laser Scanning Microscopy Analysis of 10 Cases of Craniofacial Fibrous Dysplasia

Fibro-osseous lesions (FOL) represent a heterogeneous group of lesions that exhibit a variety of clinic-pathological features. Recently, based on the new World Health Organization classification system, these lesions were reclassified as follows: (1) fibrous dysplasia (FD), (2) osseous dysplasia, and (3) ossifying fibroma. Nevertheless, the nosologic placement of FOL may be problematic because of substantial overlap in the histopathological findings. In this study, we analyzed 10 cases of FD by both optical and confocal laser scanning microscopy, a research technique based on the laser light microscopic analysis of stained biological samples that allows improved tissue imaging and bidimensional pictures with high resolution at the cellular level to provide a better understanding of the diagnosis of this disease.     

Edge restenosis after implantation of high activity (32)P radioactive beta-emitting stents

BACKGROUND: A high restenosis rate has been reported at the edges ("edge restenosis") of (32)P radioactive stents with an initial activity level of 3 to 12 microCi. This edge effect might be due to balloon injury and to a low dose of radiation at the stent margins. The aim of this study was to evaluate whether the implantation of (32)P radioactive stents with a higher activity level (12 to 21 microCi) combined with a nonaggressive stent implantation strategy could solve the problem of edge restenosis. METHODS AND RESULTS: We compared the results of lesions treated with single radioactive BX stents with an activity of 12 to 21 microCi (group 2, n = 54 lesions) with the results of lesions treated by single radioactive BX stents with an initial activity level of 3 to 12 microCi (group 1, n = 42 lesions). There were no procedural events. At the 6-month follow-up, no myocardial infarctions, deaths, or stent thromboses had occurred. Intrastent binary restenosis was 0% in group 1 versus 4% in group 2 (n = 2, both at the ostium of the right coronary artery, P = NS). Intrastent neointimal hyperplasia was significantly lower in group 2 than in group 1. The intralesion (intrastent plus peri-stent) restenosis rate was 38% in group 1 versus 30% in group 2 (P = NS). Conclusions-Single (32)P radioactive stents with an initial activity level of 12 to 21 microCi reduced intrastent neointimal hyperplasia compared with stents of 3 to 12 microCi, but they did not solve the problem of edge restenosis, even if a nonaggressive stent implantation strategy was used.