Peroxisomicine A1, a potential antineoplastic agent, causes micropexophagy in addition to macropexophagy.

Peroxisomicine A1 (PA1) is a potential antineoplastic agent with high and selective toxicity toward peroxisomes of tumor cells. Pexophagy is a selective autophagy process that degrades damaged peroxisomes; this process has been studied mainly in methylotrophic yeasts. There are two main modes of pexophagy in yeast: macropexophagy and micropexophagy. Previous studies showed that peroxisomes damaged by a prolonged exposition to PA1 are eliminated by macropexophagy. In this work, Candida boidinii was grown in methanol-containing media, and PA1 was added to the cultures at 2 µg/mL after they reached the mid-exponential growth phase. Samples were taken at 5, 10, 15, 20, and 25 min after the addition of PA1 and processed for ultrastructural analysis. Typical morphological characteristics of micropexophagy were observed: the direct engulfment of peroxisomes by the vacuolar membrane and the presence of the micropexophagic membrane apparatus (MIPA), which mediates the fusion between the opposing tips of the vacuole to complete sequestration of peroxisomes from the cytosol. In conclusion, here we report that, in addition to macropexophagy, peroxisomes damaged by PA1 can be eliminated by micropexophagy. This information is useful to deepen the knowledge of the mechanism of action of PA1 and of that of pexophagy per se.

Antitumor activity of a hydrogel loaded with lipophilic bismuth nanoparticles on cervical, prostate, and colon human cancer cells.

The objective of this study was to analyze the antitumor activity of a hydrogel loaded with lipophilic bismuth nanoparticles on human cervical, prostate, and colon cancer cell lines. The effect of lipophilic bismuth nanoparticles on the viability of cancer cell lines (HeLa, DU145, and HCT-116) and non-cancer lung fibroblasts (HLF; LL 47[MaDo]) was determined with the MTT cell viability assay and compared with known antineoplastic drugs. The biocompatibility at an organismal level was verified in a murine model by histological examination. A lipophilic bismuth nanoparticle hydrogel at 50 µM time-dependently inhibited the growth of the three cancer cell lines, in a time-dependent way. A 1-hour exposure to 250 µM lipophilic bismuth nanoparticle hydrogel, inhibited the growth of the three cancer cell lines. The in-vitro efficacy of lipophilic bismuth nanoparticle was similar to the one of docetaxel and cisplatin, but without inhibiting the growth of non-cancer control cells. Histology confirmed the biocompatibility of lipophilic bismuth nanoparticles as there were no signs of cytotoxicity or tissue damage in any of the evaluated organs (kidney, liver, brain, cerebellum, heart, and jejunum). In conclusion, a lipophilic bismuth nanoparticle hydrogel is an innovative, low-cost alternative for the topical treatment of cervicouterine, prostate, and colon human cancers.

Submitral Aneurysm in a Patient with a Normal Electrocardiogram.

A ventricular aneurysm entails well-known risks for the patient such as heart failure, potentially lethal arrhythmias, and systemic embolic phenomena. The submitral or posterolateral ventricular aneurysm is a very rare variety, usually of congenital etiology, which may also have other causes, including ischemic heart disease. The present case is about a 76-year-old male with the antecedent of an acute myocardial infarction 3 years ago. He presented with intermittent, brief, and self-limiting episodes of severe dyspnea, intense desperation, and accelerated palpitations, with a nonspecific electrocardiogram. An echocardiography revealed a large submitral aneurysm, with a good clinical response to the specific treatment of heart failure, antiarrhythmics, and oral anticoagulation therapy. We analyze the implications of an aneurysm in the context of an ischemic etiology, with special attention to the limitations of the electrocardiogram in the diagnosis of occlusions of the circumflex artery that irrigates the posterolateral region of the heart. We suspect that a greater number of patients with a culprit circumflex artery could receive appropriate coronary interventionism or thrombolysis if decision-making in the emergency room would not depend mainly on the electrocardiogram. Better stratification tools are needed to prevent late complications of infarction, such as those observed in this patient.

Hydroxyapatite decreases cytotoxicity of a glass ionomer cement by calcium fluoride uptake in vitro.

BACKGROUND: Glass ionomer cements (GICs) are widely used in dentistry because of their remineralizing and cariostatic potential induced by fluoride. In vitro studies have reported cell toxicity triggered by GICs; however, the influence of hydroxyapatite (HAp) must be considered. The aim of this study was to evaluate the effect of HAp in decreasing the cytotoxicity of the GIC 3M Vitrebond in vitro. METHODS: Samples of 3M Vitrebond (powder, liquid and light-cured) were incubated in Dulbecco's modified Eagle's medium-Ham's F12 (DMEM-F12) for 24 hours at 37°C. Subsequently, the light-cured medium was treated with 100 mg/mL of HAp overnight. Toxicity of conditioned media diluted 1:2, 1:4, 1:8 and 1:20 was analyzed on human gingival fibroblasts (HGFs) using light microscopy and the fluorometric microculture cytotoxicity assay. The amounts of calcium fluoride (CaF2) were determined by the alizarin red S method. RESULTS: The exposure of HGFs to light-cured induced cell death and morphological changes such as chromatin condensation, pyknotic nuclei and cytoplasmic modifications. Exposure to light-cured treated with HAp, significantly increased cell viability leading to mostly spindle-shaped cells (p<0.001). The concentration of CaF2 released by the light-cured was 200 ppm, although, in the light-cured/HAp conditioned medium, this quantity decreased to 88 ppm (p<0.01). CONCLUSIONS: These data suggest that HAp plays a protective role, decreasing the cytotoxic effect of 3M Vitrebond induced by CaF2.

Análisis comparativo de angioplastia versus cirugía en la coronariopatía multivaso; perspectiva de un hospital comunitario / Comparative analysis of angioplasty versus surgery in multivessel coronary artery disease: A community hospital perspective

Introducción: Hasta 60% de los casos tratados con intervención coronaria percutánea (ICP) o cirugía (CRVC) tienen enfermedad coronaria de múltiples vasos (ECMV). Objetivo: Comparar la evolución clínica de estos pacientes después de su comparativo, de una cohorte tratada por ECMV con CRVC o ICP más stents farmacoactivos o bioactivos entre enero de 2004 a julio de 2011. Se utilizó expediente clínico, consignando eventos cardiovasculares adversos. Resultados: Ingresaron 134 pacientes, predominando varones con enfermedad trivascular y angina estable con un seguimiento de 35.7 ± 20.4 meses. El grupo quirúrgico tuvo más dislipidemia (41.9 vs 36.7%), diabetes (59.5 vs 38.3%), hipertensión arterial (67.6 vs 60%), infarto del miocardio antiguo (37.8 vs 23.3%) y lesión tipo C en la arteria descendente anterior (63.9 vs 30.4%), p < 0.05 para todas. Los tratados con ICP tuvieron más necesidad de revascularización repetida (30.50 vs 2.73%) p < 0.01, recurrencia de angina (44 vs 20%), ergometrías positivas (39 vs 18%), hospitalizaciones (25 vs 9%) y deterioro funcional según la New York Heart Association III o IV (22 vs 11%), p < 0.05 para todos. Conclusión: En pacientes de un hospital comunitario con ECMV, la ICP presenta una recurrencia superior de isquemia y revascularización repetida comparada con la CRVC.

Introduction: 60% of the patients treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) suffer from multivessel coronary artery disease. Objective: Our objective was to compare the clinical course of patients with this diagnosis after revascularization. Methods: We‚ consulted and compared the clinical records‚ of‚ a multivessel coronary artery disease cohort treated with either coronary artery bypass grafting or angioplasty with drug eluting stents or bioactive stents between January 2004 and July 2011, consigning adverse cardiovascular events. Results: 134 patients, mostly male, with‚ 3-vessel disease and stable angina, were followed up for‚ 35.7 ± 20.4 months. Dyslipidemia‚ (41.9 vs 36.7%),‚ diabetes mellitus type 2‚ (59.5 vs 38.3%), hypertension (67.6 vs 60%),‚ old myocardial infarction‚ (37.8 vs 23.3%) and type C lesion in left anterior descendent artery (63.9 vs 30.4%) were all more frequent in the surgery group (p < 0.05). On the other hand, the angioplasty treated patients needed more frequently revascularization (30.50 vs 2.73%; p < 0.01) and hospitalization (25 vs 9%) and had more often angina‚ (44 vs 20%), positive ergometry (39 vs 18%), and functional impairment type New York Heart Association III/IV‚ (22 vs 11%) (p < 0.05). Conclusion: In patients at a community hospital with multivessel coronary artery disease, PCI has a higher recurrence of ischemia and repeated revascularization compared to CABG.

Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections.

Rheumatoid arthritis is an autoimmune disease that affects human beings worldwide. Infections have been associated to autoimmune diseases because their ability to induce a dominant cytokine response. Joint inflammation has been related to Th1 response because they induce high expression of proinflammatory cytokines TNF-alpha, IL-1, IFN-gamma. MRL/lpr mice spontaneously develop an autoimmune disease affecting joints, kidneys, etc. We compared incidence and severity of arthritis, antibody response, cytokine production, in mice infected with bacteria or helminthes in the Murphy Roths Large (MRL)lpr mice. Infections with helminthes Heligmosomoides polygyrus, Nippostrongylus brasiliensis or bacteria Nocardia brasiliensis and Staphylococcus aureus were studied. IL-4, IFN-gamma and IgG1, IgG2a antibody productions were determined. IFN-gamma was increased in all groups, the highest production was observed after bacterial infection; IL-4 production was higher after helminthes infection. IgG1 sera levels were increased in the helminthes infected group. IgG2a sera concentration was stimulated by bacterial infection. The histopathology showed that 100% of bacterial infected mice developed arthritis and severe tissue damage such as cartilage erosion and bone destruction. Animals infected with parasites showed a decreased incidence and severity of arthritis. Severity of tissue damage in joints is correlated with increased numbers of lymphocytes and macrophages immunoreactive to proinflammatory cytokines.