62 research outputs found
FDG-PET scan in patients with clinically and/or radiologically suspicious colorectal cancer recurrence but normal CEA
Italian Association of Clinical Endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms
Roles for mitochondria in pentamidine susceptibility and resistance in Leishmania donovani
Pentamidine resistant Leishmania donovani was raised in the laboratory by stepwise exposure to increasing drug pressure until a line capable of growth in 8 µM pentamidine (R8) had been selected. An IC50 value of 40 µM was determined for this line, some 50-fold higher than that recorded for the parental wild-type line. The pentamidine resistant promastigotes were cross-resistant to other toxic diamidine derivatives but not to antimonials or substrates of multidrug resistance pumps. Decreased mitochondrial transmembrane potential was observed in pentamidine resistant promastigotes. A substantial net decrease in accumulation of [3H]-pentamidine accompanied the resistance phenotype. Inhibitors of P-glycoprotein pumps, including prochlorperazine and trifluoperazine, did not reverse this decreased drug uptake, which distinguishes the L. donovani resistant line studied here from L. mexicana promastigotes previously studied for pentamidine resistance. Kinetic analysis identified a carrier with an apparent Km value of 6 µM for pentamidine. No significant difference between wild-type and resistant parasites could be detected with respect to this transporter in rapid uptake experiments. However, in longer-term uptake experiments and also using concentrations of pentamidine up to 1 mM, it was demonstrated that wild-type cells, but not resistant cells, could continue to accumulate pentamidine after apparent saturation via the measured transporter had been reached. Agents that diminish the mitochondrial membrane potential inhibited this secondary route. A fluorescent analogue of pentamidine, 2,5-bis-(4-amidophenyl)-3,4-dimethylfuran (DB99), accumulated in the kinetoplast of wild-type but not resistant parasites indicating that uptake of this cationic compound into mitochondria of wild-type cells was more pronounced than in the resistant line. These data together indicate that resistance to pentamidine in L. donovani is associated with alterations to the mitochondria of the parasites, which lead to reduced accumulation of drug
Early Bile Duct Cancer in a Background of Sclerosing Cholangitis and Autoimmune Pancreatitis
Subcutaneous Pneumocele Associated With Ventriculoperitoneal Shunt Migration Into the Mechanically Occluded Colon-Case Report-
Assessment of iodine uptake by pancreatic cancer following chemotherapy using dual-energy CT
Mapping of hepatic vasculature in potential living liver donors: comparison of gadoxetic acid-enhanced MR imaging using CAIPIRINHA technique with CT angiography
Altered gene expression and repressed markers of autophagy in skeletal muscle of insulin resistant patients with type 2 diabetes
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