Urgent endovascular ligature of a ruptured splenic artery pseudoaneurysm in a patient with acute pancreatitis: a case report

Introduction

We report on the successful endovascular treatment of a ruptured splenic artery pseudoaneurysm. Our patient had acute pancreatitis superimposed on chronic calcific pancreatitis and chronic renal impairment. Contrast-enhanced ultrasonography was used to assess post-embolization results.

Case presentation

Our patient was a 67-year-old white Caucasian man with recurrent pancreatitis. Computed tomography angiography showed a pancreatic pseudocyst with a ruptured pseudoaneurysm, which was successfully embolized using an endovascular percutaneous approach. At six months, persistent renal failure led to contrast-enhanced ultrasonography. This confirmed the absence of turbulent blood flow and extravasation of contrast medium in the pseudocyst.

Conclusion

Our experience with this case leads us to support the role of interventional radiology as a first-line treatment tool. Contrast-enhanced ultrasonography can be used to follow-up embolization procedures in patients with impaired renal function.     

Macrophages and antioxidant status in the NOD mouse pancreas

This study showed that citiolone (CIT), a free radical scavenger, significantly increased superoxide dismutase (P < 0.001 vs. untreated NOD, NMMA-treated, and silica-treated animals), catalase (P < 0.01 vs. untreated NOD), and glutathione peroxidase (P < 0.001 vs. untreated NOD and C57BL6/J) values. Silica treatment was capable of counteracting the plasma antioxidant capacity (TRAP) decrease observed in untreated NOD mice, although it did not block the blood glucose rise and insulitis progression in type 1 diabetes significantly. Conversely, early silica administration was able to deplete macrophages (as demonstrated by immunocytochemistry) and to block the rise in blood glucose levels and insulitis progression significantly. Silica-treated animals in this study showed the highest TRAP levels, demonstrating that depletion of macrophages also was able to improve the antioxidant status. This study suggested that macrophages are essential for type 1 diabetes development and showed that they also are involved when the antioxidant status is affected. The reported findings are significant in view of previous studies indicating that oxygen and/or nitrogen free radicals contribute to the islet β-cell destruction in type 1 diabetes animal models. J. Cell. Biochem. 71:479–490, 1998. © 1998 Wiley-Liss, Inc.     

Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities.Subject terms: Cancer models, Cell biology, Preclinical research     

Catechol(amine)s as probes of lactoperoxidase catalytic site structure: spectroscopic and modeling studies

 Binding affinities to lactoperoxidase (LPO) of a homologous series of substituted catechol(amine)s [such as catechol, 4-methylcatechol, 3,4-dihydroxybenzoic acid, 3,4-dihydroxyphenylacetic acid, 3-(3,4-dihydroxyphenyl)propionic acid; dopamine, noradrenaline, adrenaline;l-3,4-dihydroxyphenylalanine] were studied by UV-visible spectroscopy and docking simulations. Dissociation constant (K _d) values were calculated by direct fitting of the experimental data and fall in a range of 3–95 mM. Thermodynamic parameters are comparable with those reported for the interaction of LPO with p-substituted phenols, suggesting a similar general mode of binding. Furthermore, the relative contributions to binding energy, described by the unimolecular constant K _u, show that interaction between protein and ligands originates from a relatively large number of groups. Docking and molecular dynamics simulations, in agreement with experimental evidence, predict that the substrate is localized into the access channel in the vicinity of heme distal pocket. This channel is characterized by a hydrophobic patch (six Phe residues) and by a charged contribution (two Glu and one His residues). All of the substrates, except caffeic acid, may approach the protein active site. Positively charged Arg372 acts as a gate above the heme distal pocket and seems to address substrate orientation in relation to the side-chain terminal group. Received: 4 June 1998 / Accepted: 1 October 1998     

Pcr-based multiplex DNA fingerprinting techniques for the analysis of conifer genomes

We utilised fingerprinting techniques such as amplified restriction fragment polymorphism (AFLP) and selective amplification of microsatellite polymorphic loci (SAMPL) in order to identify molecular markers in the conifer species Norway spruce (Picea abies K). A total of 366 polymorphic AFLP and 20 polymorphic SAMPL bands were scored, with an average of 12.6 polymorphic bands obtained per primer combination. Of the bands, 94% segregated in a Mendelian fashion, and 14% of the AFLP bands behaved as codominant markers. Norway spruce, as well as other conifers, has a very large genome (1.5–2.5 × 10¹⁰ bp) which is thought to be largely composed of repetitive sequences of different origin, either organised in tandem or interspersed in the genome. The high complexity of these genomes has so far hindered the efficient use of multiplexed fingerprinting techniques for their analysis. The use of the methylation-sensitive restriction enzyme PstI as 6 bp cutter allows a reduction in pattern complexity as compared to EcoRI. We thus demonstrated that high-throughput PCR-based multiplex fingerprinting techniques such as AFLP and SAMPL, when opportunely modified, can be effectively applied also to these species and be useful for mapping purposes.     

ADMET rules of thumb II: A comparison of the effects of common substituents on a range of ADMET parameters

A systematic analysis of data generated in key in vitro assays within GSK has been undertaken to identify what impact a range of common substituents have on a range of ADMET parameters. These include; P450 1A2, 2C9, 2C19, 2D6 and 3A4 inhibition, hERG inhibition, phosphate buffer solubility and artificial membrane permeability. We do this by identifying all matched molecular pairs, differing by the replacement of a hydrogen atom with a list of predefined substituents.For each substituent we calculate the mean difference in the ADMET parameter for all the matched molecular pairs identified, making a statistical assessment of the difference, as well as assessing the diversity for each example to ensure that the results can be generalized. We also relate the change in activity observed for each substituent to differences in their molecular properties in an effort to identify any structural alerts.     

Reactivity of ubiquinones and ubiquinols with free radicals

The reactivity of quinones 1-4 and of the corresponding quinols 5-8 towards carbon- and oxygen-centred radicals were studied. All quinones bearing at least one nuclear position free, readily react with alkyl and phenyl radicals to afford the alkylated quinones 12-24; however, quinones 1 and 3 reacted with 2-cyano-2-propyl radical to yield products (the mono- and di-ethers 9-11) derived from the attack on the carbonylic oxygen. The reactions carried out on quinones with the benzoyloxy radical led to no reaction products and in the case of Q₁₀, the isoprenic chain also remained unchanged. Quinols 5-8 reacted only with oxygencentred radicals (benzoyloxy and 2-cyano-2-propylperoxy radicals) to give the corresponding quinones. The isoprenic chain of Q₁₀ did not undergo attack even with peroxy radicals. Carbon-centred radicals resulted unable to abstract hydrogen from the studied quinols.