Hydroxocobalamin to treat refractory vasoplegia following phaeochromocytoma resection in a child.

Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours that often secrete catecholamines, which can cause dramatic swings in blood pressure and end-organ damage. During surgical resection of these tumours, antihypertensive drug infusions are often required, but after resection patients may become vasoplegic, in part due to cessation of catecholamine secretion by the tumour in the context of pre-operative α1 adrenoceptor antagonism. Numerous medications have been used to treat vasoplegia in this setting, including noradrenaline, vasopressin and, more recently, angiotensin II. We report the case of a patient who experienced vasoplegia after phaeochromocytoma resection which was refractory to vasopressin and angiotensin II infusions but was successfully treated with high dose hydroxocobalamin.

Magnetic nanoparticle biodistribution following intratumoral administration.

Recently, heat generated by iron oxide nanoparticles (IONPs) stimulated by an alternating magnetic field (AMF) has shown promise in the treatment of cancer. To determine the mechanism of nanoparticle-induced cytotoxicity, the physical association of the cancer cells and the nanoparticles must be determined. We have used transmission electron microscopy (TEM) to define the time dependent cellular uptake of intratumorally administered dextran-coated, core-shell configuration IONP having a mean hydrodynamic diameter of 100-130 nm in a murine breast adenocarcinoma cell line (MTG-B) in vivo. Tumors averaging volumes of 115 mm3 were injected with iron oxide nanoparticles. The tumors were then excised and fixed for TEM at time 0.1-120 h post-IONP injection. Intracellular uptake of IONPs was 5.0, 48.8 and 91.1% uptake at one, 2 and 4 h post-injection of IONPs, respectively. This information is essential for the effective use of IONP hyperthermia in cancer treatment.

An in vivo transmission electron microscopy study of injected dextran-coated iron-oxide nanoparticle location in murine breast adenocarcinoma tumors versus time.

Investigators are just beginning to use hyperthermia generated by alternating magnetic field (AMF) activated iron oxide nanoparticles (IONPs) as a promising avenue for targeted cancer therapy. An important step in understanding cell death mechanisms in nanoparticle AMF treatments is to determine the location of these nanoparticles in relation to cellular organelles. In this paper, we report on transmission electron microscopy (TEM) studies designed to define the position of 100 nm diameter dextran-coated iron oxide nanoparticles in murine breast adenocarcinoma (MTG-B)and human colon adenocarcinoma tumors propagated in mice. METHODS: Iron oxide nanoparticles (5 mg/g tumor) were injected into intradermal MTG-B flank tumors on female C3H/HEJ mice and into HT-29 flank tumors on female Nu/Nu mice. The IONPs were allowed to incubate for various times. The tumors were then excised and examined using TEM. RESULTS: In the MTG-B tumors, most of the nanoparticles reside in aggregates adjacent to cell plasma membranes prior to three hours post-injection. By four hours post injection, however, most of the nanoparticles have been endocytosed by the cells. At time periods after four hours post injection, few visible extracellular nanoparticles remain and intracellular nanoparticles have densely aggregated within endosomes. In the HT-29 tumor, however, endocytosis of nanoparticles has not progressed to the same extent as in the MTG-B tumors by four hours post injection. CONCLUSIONS: The time at which most of the nanoparticles transition from being extracellular to intracellular in the MTG-B system appears to be between two and four hours. The HT-29 cells, however, display different and delayed uptake pattern. These data show that there are IONP uptake differences between tumor types (cell lines) and that, based on known uptake kinetics, nanoparticle hyperthermia can be employed as an extracellular or intracellular modality. These data will be important in guiding future nanoparticle hyperthermia cancer treatments.