Life-threatening cardiac toxicity is rare after BMT, occurring in less than 2% of all patients. Although the occurrence of cardiac toxicity is correlated with a reduction of EF before BMT, life-threatening cardiac toxicity cannot be predicted in individual patients.
Morphine exhibits important pharmacological effects for which it has been used in medical practice for quite a long time. However, it has a high addictive potential and can be abused. Long-term use of this drug can be connected with some pathological consequences including neurotoxicity and neuronal dysfunction, hepatotoxicity, kidney dysfunction, oxidative stress and apoptosis. Therefore, most studies examining the impact of morphine have been aimed at determining the effects induced by chronic morphine exposure in the brain, liver, cardiovascular system and macrophages. It appears that different tissues may respond to morphine diversely and are distinctly susceptible to oxidative stress and subsequent oxidative damage of biomolecules. Importantly, production of reactive oxygen/nitrogen species induced by morphine, which have been observed under different experimental conditions, can contribute to some pathological processes, degenerative diseases and organ dysfunctions occurring in morphine abusers or morphine-treated patients. This review attempts to provide insights into the possible relationship between morphine actions and oxidative stress.
This study was a retrospective analysis of patients with CLI who underwent infrapopliteal percutaneous transluminal angioplasty (PTA). The main goal was to evaluate clinical and morphological factors that influence the clinical outcome of PTA in long-term follow-up. A total of 1,445 PTA procedures were performed in 1,268 patients. Main indications for PTA included gangrene, nonhealing ulcers, or rest pain. The mean number of treated arteries was 1.77 artery/limb, and the majority of lesions were type TASC D. The technical success rate of PTA was 89% of intended-to-treat arteries. The main criterion of clinical success was functional limb salvage (LS). One-year follow-up involved 1,069 limbs. Primary and secondary 1-year LS rates were 76.1 and 84.4%, respectively. The effect of clinical and morphological parameters on the 1-year LS was that the only associated disease with an adverse effect on LS rate was DM combined with dialysis. Regarding limb preprocedural status, gangrene was clearly a negative predictor. The most important factor affecting LS was the number of patent arteries post-PTA: patients with 0, 1, 2, and 3 patent arteries had 1-year primary LS rates of 56.4, 73.1, 80.4, and 83%, respectively. Long-term follow-up of LS rates demonstrated secondary LS rates of 84.4, 78.8, and 73.3% at 1, 5, and 10 years. Every effort should be made to perform PTA for as many arteries as possible, even if TASC D type, to improve clinical outcome. Our study shows that repeat PTA is capable of keeping the long-term LS rate close to 75%.
After Endurant stent grafting, the incidence of limb occlusion was low. Classifying patients as high risk vs low risk according to the algorithm used in this study may help define specific strategies to prevent limb occlusion and improve the overall results of endovascular aneurysm repair using the latest generation of stent grafts.
Using a combination of confocal immunofluorescence microscopy and subcellular fractionation, we demonstrate for the first time active internalization, trafficking, and down-regulation of a G protein alpha subunit subsequent to agonist occupation of a receptor. This proceeds on a much slower time scale than internalization of the corresponding receptor. In intact E2M11 HEK293 cells that express high levels of murine G11alpha and the rat thyrotropin-releasing hormone (TRH) receptor, the immunofluorescence signal of G11alpha was restricted almost exclusively to the plasma membrane. Exposure to TRH (10 microM) resulted first in partial relocation of G11alpha to discrete, segregated patches within the plasma membrane (10-60 min). Further exposure to TRH caused internalization of G11alpha to discrete, punctate, intracellular bodies (2-4 h) and subsequently to a virtually complete loss of G11alpha from plasma membranes and the cells (8-16 h). Short-term treatment with TRH followed by wash-out of the ligand allowed G11alpha immunofluorescence to be restored to the plasma membrane within 12 h. In subcellular membrane fractions, G11alpha was centered on plasma membranes, and this was not altered by up to 1-2 h of incubation with TRH. Further exposure to TRH (2-4 h) resulted in transfer of a significant portion of G11alpha to light-vesicular and cytosol fractions. At longer time intervals (4-16 h), an overall decrease in G11alpha content was observed.
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