Rotational angiography (RA) and three-dimensional imaging (3-DRA): an available clinical tool

Being able to accurately choose an optimal view for stent positioning, non foreshortened length and to avoid side branches is imperative during therapeutic procedures. Traditional imaging limitations may include the selection of an incorrectly sized stent, inaccurate placement, and/or the need for additional stents. With the use of newer acquisition techniques and three-dimensional (3-D) modeling/reconstructions this can be minimized. We present a case in which with the assistance of 3-D and its computer derived optimal view, and optimal length, a significant amount of vessel foreshortening was eliminated therefore improving the procedural outcome.     

Porcine islet isolation outcome is not affected by the amount and distribution of collagen in the pancreas

Hilling DE, Rijkelijkhuizen JKRA, Töns HAM, Terpstra OT, Bouwman E. Porcine islet isolation outcome is not affected by the amount and distribution of collagen in the pancreas.
Xenotransplantation 2010; 17: 250–255. © 2010 John Wiley & Sons A/S. Abstract: Variable islet yields in porcine islet isolation may be caused by the collagen substrate within the pancreas. The aim of the present study was to determine the total amount and distribution of collagen within porcine pancreata and their relationship to islet isolation outcome. A total of 64 juvenile and 76 adult porcine pancreata of eight purebred breeds were histologically examined. The amount of collagen was quantitatively assessed in tissue samples stained with Sirius Red. Collagen distribution was semi‐quantitatively determined by assessing the presence of collagen in the endocrine–exocrine interface and within the islet, in tissue samples stained with Sirius Red and anti‐insulin. Islet isolation was performed in 58 pancreata of the adult group. Total collagen content and islet encapsulation ranged widely in both adult and juvenile pigs. However, the majority of islets in adult and juvenile pigs had no or only a limited collagen capsule. The difference in collagen content between adult and juvenile pigs could not be explained by age. Furthermore, no differences between adult and juvenile pigs were found in islet encapsulation or the amount of intra‐islet collagen. In adult pigs, no significant relationships were found between obtained islet yield and total collagen content, islet encapsulation or amount of collagen within the islet. Considering the limitations in experimental design (staining method) and study material, isolation outcome does not seem to be affected by the total collagen content or collagen distribution. The influence of other matrix elements and collagen subtypes should be investigated.     

Adenoviral transfer of murine oncostatin M elicits periosteal bone apposition in knee joints of mice,despite synovial inflammation and up-regulated expression of interleukin-6 and receptor activator of nuclear factor-kappa B ligand

Oncostatin M (OSM) has been described as a bone-remodeling factor either stimulating osteoblast activity or osteoclast formation in vitro. To elucidate the in vivo effect of OSM on bone remodeling, we injected an adenoviral vector encoding murine OSM in knee joints of mice. OSM strongly induced interleukin (IL)-6 gene expression, a known mediator of osteoclast development. We investigated the OSM effect in wild-type and IL-6-deficient mice and found a similar degree of OSM-induced joint inflammation. Within the first week of inflammation, the periosteum along the femur and tibia increased in cell number and stained positive for the osteoblast marker alkaline phosphatase. At these sites bone apposition occurred in both strains as demonstrated by Goldner and Von Kossa staining. In vitro OSM enhanced the effect of bone morphogenetic protein-2 on osteoblast differentiation. Immunohistochemistry demonstrated expression of receptor activator of nuclear factor-kappa B ligand (RANKL) and its receptor, receptor activator of nuclear factor-kappa B (RANK), in the periosteum but osteoclasts were not detected at sites of bone apposition. Induced mRNA expression for the receptor activator of nuclear factor-kappa B ligand inhibitor osteoprotegerin probably controlled osteoclast development during OSM overexpression. Our results show that OSM favors bone apposition at periosteal sites instead of resorption in vivo. This effect was not dependent on or inhibited by IL-6.     

The beta‐carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells

Multidrug resistance (MDR), mediated by highly expressed ABC transporters, is one of the most important mechanisms in tumor cells. Breast cancer resistance protein (BCRP) is a member of the ABC transporter family. This transporter expels different kinds of lipophilic anticancer drugs, which have diffused into the cells. In this study, 96‐well plate based assays and flow cytometry analysis were employed to screen natural products for BCRP inhibition. The beta‐carboline alkaloid harmine inhibited BCRP in a BCRP overexpressing breast cancer cell line (MDA‐MB‐231). Harmine reduced resistance to the anticancer drugs mitoxantrone and camptothecin mediated by BCRP and might be an interesting new reversal agent. Harmine did not inhibit P‐glycoprotein (P‐gp) mediated drug efflux. Copyright © 2009 John Wiley & Sons, Ltd.     

In vivo MRS and histochemistry of status epilepticus‐induced hippocampal pathology in a juvenile model of temporal lobe epilepsy

Childhood status epilepticus (SE) initiates an epileptogenic process that leads to spontaneous seizures and hippocampal pathology characterized by neuronal loss, gliosis and an imbalance between excitatory and inhibitory neurotransmission. It remains unclear whether these changes are a cause or consequence of chronic epilepsy. In this study, in vivo MRS was used in a post‐SE juvenile rat model of temporal lobe epilepsy (TLE) to establish the temporal evolution of hippocampal injury and neurotransmitter imbalance. SE was induced in P21 rats by injection of lithium and pilocarpine. Four and eight weeks after SE, in vivo ¹H and γ‐aminobutyric acid (GABA)‐edited MRS of the hippocampus was performed in combination with dedicated ex vivo immunohistochemistry for the interpretation and validation of MRS findings. MRS showed a 12% decrease (p < 0.0001) in N‐acetylaspartate and a 15% increase (p = 0.0226) in choline‐containing compound concentrations, indicating neuronal death and gliosis, respectively. These results were confirmed by FluoroJade and vimentin staining. Furthermore, severe and progressive decreases in GABA (?41%, p < 0.001) and glutamate (Glu) (?17%, p < 0.001) were found. The specific severity of GABAergic cell death was confirmed by parvalbumin immunoreactivity (?68%, p < 0.001). Unexpectedly, we found changes in glutamine (Gln), the metabolic precursor of both GABA and Glu. Gln increased at 4 weeks (+36%, p < 0.001), but returned to control levels at 8 weeks. This decrease was consistent with the simultaneous decrease in glutamine synthase immunoreactivity (?32%, p = 0.037). In vivo MRS showed gliosis and (predominantly GABAergic) neuronal loss. In addition, an increase in Gln was detected, accompanied by a decrease in glutamine synthase immunoreactivity. This may reflect glutamine synthase downregulation in order to normalize Gln levels. These changes occurred before spontaneous recurrent seizures were present but, by creating a pre‐epileptic state, may play a role in epileptogenesis. MRS can be applied in a clinical setting and may be used as a noninvasive tool to monitor the development of TLE. Copyright © 2012 John Wiley & Sons, Ltd.