In our ongoing search for new metal-based chemotherapeutic agents against leishmaniasis and Chagas disease, six new ruthenium-ketoconazole (Ru-KTZ) complexes have been synthesized and characterized, including two octahedral coordination complexes cis-fac-[RuIICl2(DMSO)3(KTZ)] (1) and cis-[RuIICl2(bipy)(DMSO)(KTZ)] (2), and four organometallic compounds [RuII(η6-p-cymene)Cl2(KTZ)] (3), [RuII(η6-p-cymene)(en)(KTZ)][BF4]2 (4), [RuII(η6-p-cymene)(bipy)(KTZ)][BF4]2 (5), and [RuII(η6-p-cymene)(acac)(KTZ)][BF4] (6); the crystal structure of (3) is described. The central hypothesis of our work is that combining a bioactive compound like KTZ and a metal in a single molecule results in a synergy that can translate into improved activity and/or selectivity against parasites. In agreement with this hypothesis, complexation of KTZ to RuII in compounds 3-5 produces a marked enhancement of the activity toward promastigotes and intracellular amastigotes of Leishmania major, when compared with uncomplexed KTZ, or with similar Ru compounds not containing KTZ. Importantly, the selective toxicity of compounds 3-5 toward the leishmania parasites, in relation to human fibroblasts and osteoblasts, or murine macrophages, is also superior to those of the individual constituents of the drug. When tested against Trypanosoma cruzi epimastigotes, some of the organometallic complexes displayed an activity and selectivity comparable to that of free KTZ. A dual-target mechanism is suggested to account for the antiparasitic properties of these complexes.

This study describes a new method (NM) for estimation of sinoatrial conduction time (SACT), which utilizes constant atrial pacing (AP) instead of the premature atrial beats (PABs) used in the method reported in 1973 by Strauss et al. The SACTs were obtained by both methods in 20 patients. The SACT by the Strauss method (SM) was calculated as A2A3 minus A1A1. The NM consists of high right AP for a train of eight consecutive beats at rates less than or equal to 10 beats/min faster than the sinus rhythm. The interval between the last paced atrial electrogram (Ap) and the first escape atrial electrogram (A) of sinus origin (Ap-A) was measured along with several post pacing sinus cycles. The SACT by the NM was calculated as follows: SACT = Ap-A minus A1A1. The effect of AP at higher rates was also analyzed. In two patients, the SACT with the SM could not be defined, as all the A2A3 intervals were fully compensatory; with the NM the SACT was 217 and 320 msec. In the remaining 18 patients the SACT was obtainable by both methods. With SM, the SACT ranged 105--452 msec (mean 219 +/- 102 SD) and with the NM it was 85--492 msec (mean 201 +/- 112 SD), and the difference was statistically significant (P = 0.0162). The coefficient of correlation between the two methods was r = 0.97. During AP at faster rates, a rate related increment in Ap-A intervals and also post pacing sinus cycles was noted. This study describes a new and simple method for measurement of SACT in man.

Lack of adventitial injury after atherectomy for femoropopliteal stenosis is strongly related to patency at 1 year.

Chronic total occlusion, in-stent restenosis, thrombotic, calcific lesions >40 mm, and atherosclerotic lesions >140 mm identified by peripheral angiography necessitate concomitant filter use during atherectomy to prevent embolic complications.

Directional atherectomy guided by IVUS reduces clinically driven target lesion revascularization for patients with femoropopliteal in-stent restenosis.

Background and aims Neointimal cellular proliferation of fibroblasts and myofibroblasts is documented in coronary artery restenosis, however, their role in peripheral arterial disease (PAD) restenosis remains unclear. Our aim was to investigate the role of fibroblasts, myofibroblasts, and collagens in restenotic PAD. Methods Nineteen PAD restenotic plaques were compared with 13 de novo plaques. Stellate cells (H&E), fibroblasts (FSP-1), myofibroblasts (α-actin/vimentin/FSP-1), cellular proliferation (Ki-67), and apoptosis (caspase-3 with poly ADP-ribose polymerase) were evaluated by immunofluorescence. Collagens were evaluated by picro-sirius red stain with polarization microscopy. Smooth muscle myosin heavy chain (SMMHC), IL-6 and TGF-β cytokines were analyzed by immunohistochemistry. Results Restenotic plaques demonstrated increased stellate cells (2.7 ± 0.15 vs. 1.3 ± 0.15) fibroblasts (2282.2 ± 85.9 vs. 906.4 ± 134.5) and myofibroblasts (18.5 ± 1.2 vs. 10.6 ± 1.0) p = 0.0001 for all comparisons. In addition, fibroblast proliferation (18.4% ± 1.2 vs. 10.4% ± 1.1; p = 0.04) and apoptosis (14.6% ± 1.3 vs. 11.2% ± 0.6; p = 0.03) were increased in restenotic plaques. Finally, SMMHC (2.6 ± 0.12 vs. 1.4 ± 0.15; p = 0.0001), type III collagen density (0.33 ± 0.06 vs. 0.17 ± 0.07; p = 0.0001), IL-6 (2.08 ± 1.7 vs. 1.03 ± 2.0; p = 0.01), and TGF-β (1.80 ± 0.27 vs. 1.11 ± 0.18; p = 0.05) were increased in restenotic plaques. Conclusions Our study suggests proliferation and apoptosis of fibroblast and myofibroblast with associated increase in type III collagen may play a role in restenotic plaque progression. Understanding pathways involved in proliferation and apoptosis in neointimal cells, may contribute to future therapeutic interventions for the prevention of restenosis in PAD.

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