Rapid radiosynthesis of [11C] and [14C]azelaic,suberic, and sebacic acids for in vivo mechanistic studies of systemic acquired resistance in plants

A recent report that the aliphatic dicarboxylic acid, azelaic acid (1,9‐nonanedioic acid) but not related acids, suberic acid (1,8‐octanedioic acid) or sebacic (1,10‐decanedioic acid) acid induces systemic acquired resistance to invading pathogens in plants stimulated the development of a rapid method for labeling these dicarboxylic acids with ¹¹C and ¹⁴C for in vivo mechanistic studies in whole plants. ¹¹C‐labeling was performed by reaction of ammonium [¹¹C]cyanide with the corresponding bromonitrile precursor followed by hydrolysis with aqueous sodium hydroxide solution. Total synthesis time was 60 min. Median decay‐corrected radiochemical yield for [¹¹C]azelaic acid was 40% relative to trapped [¹¹C]cyanide, and specific activity was 15 GBq/µmol. Yields for [¹¹C]suberic and sebacic acids were similar. The ¹⁴C‐labeled version of azelaic acid was prepared from potassium [¹⁴C]cyanide in 45% overall radiochemical yield. Radiolabeling procedures were verified using ¹³C‐labeling coupled with ¹³C‐NMR and liquid chromatography–mass spectrometry analysis. The ¹¹C and ¹⁴C‐labeled azelaic acid and related dicarboxylic acids are expected to be of value in understanding the mode‐of‐action, transport, and fate of this putative signaling molecule in plants. Copyright © 2011 John Wiley & Sons, Ltd.     

Pulmonary Atresia with Ventricular Septal Defect and Multifocal Pulmonary Blood Supply: Does an Intensive Interventional Approach Improve the Outcome?

Introduction. Pulmonary atresia with ventricular septal defect (VSD) continues to be associated with significant morbidity and mortality, with significant institutional variation in therapeutic strategies. This study reports a single center experience utilizing an intensive transcatheter approach to promote pulmonary vascular growth. Methods. A retrospective analysis of 20 patients undergoing surgical and transcatheter treatment for pulmonary atresia with VSD between 2002 and 2010. Results. The median age at initial surgical palliation was 6.3 months (8 days to 2.5 years). Eleven patients (group 1) underwent initial surgical palliation without VSD closure and nine patients (group 2) underwent an initial complete repair with fenestrated or complete VSD closure. Group 1 had a smaller Nakata index (54 mm²/m² vs. 134 mm²/m², P= .04) and a smaller absolute native pulmonary artery diameter (2.7 mm vs. 4.5 mm, P= .01) than group 2. Intraoperative angiography was performed in 10 cases to evaluate if early transcatheter intervention was warranted. The median follow‐up during the study period was 2.3 years (1.6 months to 8.3 years). Of the 16 patients who survived the initial early postoperative period, 15 patients (94%) went on to receive surgical (n = 11) and/or interventional (n = 25) catheterization procedures. There was improvement in the mean Nakata index from the initial presurgical evaluation to the most recent catheterization data (38.4 mm²/m² vs. 169.7 mm²/m², P≤ .05). To date, two of 11 (18%) patients in group 1 ultimately underwent surgical VSD closure. Overall mortality was six of 20 (30%) with four deaths in group 1 and two deaths in group 2. There were no procedural deaths. Conclusions. Combining surgical unifocalization procedures with subsequent early and intensive catheter‐based pulmonary artery rehabilitation may improve vascular growth, ultimately rendering many patients suitable for fenestrated VSD closure. Risk stratification, including intraoperative exit angiography, is essential to determine the need for early transcatheter interventions.     

Anxiety,depression, traumatic stress and quality of life in colorectal cancer after different treatments: A study with Portuguese patients and their partners

PurposeThis study examines the impact of different modes of treatment on depression, anxiety, traumatic stress and quality of life in colorectal cancer patients and their partners.MethodsThe sample was comprised of 114 oncology patients and 67 partners. All patients were diagnosed with colorectal cancer. Participants were recruited from an Oncology Hospital in the North of Portugal and had been submitted to three modes of treatment: surgery, surgery plus chemotherapy or surgery followed by radiotherapy.ResultsThe results showed that patients who received only surgery, as treatment, had lower levels of depression, anxiety and traumatic stress symptoms when compared with patients who received surgery and chemotherapy or surgery plus radiotherapy. Partners of surgical patients presented lower levels of state anxiety and traumatic stress symptoms when compared with the other two groups. Patients with more depression had partners also more depressed. No relationship was found between anxiety and traumatic stress symptoms in patients and partners. Patients who received a diagnosis longer than 12 months had more traumatic stress, intrusion and hypervigilance. Patients with illness recurrence showed more traumatic symptoms. Anxiety and depression were the main predictors of patient’s quality of life. Traumatic stress was a predictor of symptom distress - pain/bowel pattern.ConclusionThis study highlights the importance of providing psychological interventions for cancer patients and their partners. Chemotherapy patients and those diagnosed over a year, as well as their partners, are more at risk.     

Impact of intratumoral heterogeneity of breast cancer tissue on quantitative metabolomics using high‐resolution magic angle spinning 1H NMR spectroscopy

High‐resolution magic angle spinning (HR MAS) nuclear magnetic resonance (NMR) spectroscopy is increasingly being used to study metabolite levels in human breast cancer tissue, assessing, for instance, correlations with prognostic factors, survival outcome or therapeutic response. However, the impact of intratumoral heterogeneity on metabolite levels in breast tumor tissue has not been studied comprehensively. More specifically, when biopsy material is analyzed, it remains questionable whether one biopsy is representative of the entire tumor. Therefore, multi‐core sampling (n = 6) of tumor tissue from three patients with breast cancer, followed by lipid (0.9‐ and 1.3‐ppm signals) and metabolite quantification using HR MAS ¹H NMR, was performed, resulting in the quantification of 32 metabolites. The mean relative standard deviation across all metabolites for the six tumor cores sampled from each of the three tumors ranged from 0.48 to 0.74. This was considerably higher when compared with a morphologically more homogeneous tissue type, here represented by murine liver (0.16–0.20). Despite the seemingly high variability observed within the tumor tissue, a random forest classifier trained on the original sample set (training set) was, with one exception, able to correctly predict the tumor identity of an independent series of cores (test set) that were additionally sampled from the same three tumors and analyzed blindly. Moreover, significant differences between the tumors were identified using one‐way analysis of variance (ANOVA), indicating that the intertumoral differences for many metabolites were larger than the intratumoral differences for these three tumors. That intertumoral differences, on average, were larger than intratumoral differences was further supported by the analysis of duplicate tissue cores from 15 additional breast tumors. In summary, despite the observed intratumoral variability, the results of the present study suggest that the analysis of one, or a few, replicates per tumor may be acceptable, and supports the feasibility of performing reliable analyses of patient tissue.