Claudio Maioli

Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease.

Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n=7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n=8); treated with TNBS enema plus oral CysN (TNBS–CysN group; n=8); treated with CysN (CysN group; n=7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-α (TNF-α) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS–CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43±0.78 vs 3.28±0.95, microscopic score 6.62±12.01 vs 19.25±6.04, P<0.05, respectively) associated with a decrease of TG activity, TG2 and isopeptide bond immunohistochemical expression, TNF-α and IL-6 levels. No statistically significant differences were found between CysN and CTR groups. The colonic immunolocalization of TG2 was comparable in humans affected by IBD and TNBS-administered animals. This is the first demonstration that treatment with a CysN has an anti-inflammatory effect, reducing severity of colitis in a rat model. CysN could be tested as a possible treatment or co-treatment in IBD therapeutic trials.

Removal of radioisotopes in solution and bactericidal/bacteriostatic sterilising power in activated carbon and metal silver filters

Activated carbon filters play an important role in water filtration and purification from contaminants of different origin. Their limit consists in bacterial proliferation, which may occur only during prolonged periods of non-use and in their ability to remove radioactive contaminants present in waste water from Industry or Nuclear Medicine departments. In this work we tested a commercially available activated carbon filter for water purification enriched with silver plated parts incubating in static condition at room temperature different micro organisms (Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Staphylococcus aureus, Aspergillum niger), up to 78 days. The microbial growth was in general more inhibited in the presence of metal silver into the activated carbon in respect to filters with the activated carbon alone: >4log inhibition of bacterial proliferation after 78 days of incubation the presence of silver vs. 2log without silver. When the filters were incubated empty of carbon, the sterilizing power of silver was confirmed further. The activated carbon filters proved also their ability in removing from water the principal radioisotopes used for residues liquid medical and research purposes ((131)I, (99m)Tc, (201)Tl, (67)Ga). These results contribute useful data for the use of the silver-enriched carbon filters in water filtration both for daily use at home, and professional use in a Nuclear Medicine laboratory.

Truncal fat determined by dual-energy X-ray absorptiometry is an independent predictor of coronary artery disease extension

Background Controversy prevails regarding the existence of a correlation between the severity of coronary artery disease (CAD) and the extent and distribution of obesity. Purpose To assess the correlation between total fat, truncal fat (TF), and lean mass, obtained with dual-energy X-ray absorptiometry (DEXA) and standard anthropomorphic indices (body mass index, waist circumference, waist-to-hip ratio) and to verify whether DEXA indices can predict the extent and severity of CAD. Materials and methods Fifty-eight patients (19 females) consecutively referred for coronary angiography underwent physical examination and DEXA assessment of body composition. Results Of the 58 patients enrolled, 22 were overweight and 13 were obese. Significant CAD was found in 39 (67%) patients. DEXA-derived total mass and fat mass enabled us to distinguish overweight from obese patients (P < 0.005), whereas just TF mass correlated with the number of diseased vessels after adjusting for body mass index, sex, age, and smoking habit (odds ratio, 8.68; 95% confidence interval: 1.02-74.10). Conclusion TF determined by DEXA is independently related with CAD extension. Eur J Cardiovasc Prev Rehabil 15:428-433

Quality control on radiochemical purity in Technetium-99m radiopharmaceuticals labelling: three years of experience on 2280 procedures

Objective: the purpose of this study was to offer an example of evaluations of the ISO9001 certified internal quality assurance (QA) system of 99mTc-radiopharmaceutical preparations and quality control in vivo use, using industrial kits and generators in order to identify possible sources of errors in the procedures labeling and quality control procedures. Methods: The study was performed at a single institution over a period of three years (July 1st, 2011 - July 1st, 2014), and included a total of 2280 radiopharmaceutical preparations prepared by four different technologists. All the radiopharmaceutical preparations and quality controls were performed according to each SPC provided by the manufacturer. The radiopharmaceutical preparations were the following (trade names are reported in brackets): 99mTc-albumin colloid [Nanocoll] (n=349), 99mTc-oxidronate [Technescan®hdp] (n=701), 99mTc-exametazime [Ceretec] (n=169), 99mTc-sestamibi [Cardiolite] (n=92), 99mTc-albumin aggregated [Technescan®lyomaa] (n=140), 99mTc-tetrofosmin [Myoview]) (n=567), 99mTc-diethylene triamine pentacetic acid [Technescan®dtpa] (n=254), and 99mTc-dimercapto succinic acid [Renocis®] (n=8). Data were analyzed to determine the number and type of radiopharmaceutical labelling failure and to derive the sources of these failures to define corrective actions and optimize the quality assurance program. Results: A total of 2280 procedures were performed and recorded. Following the quality control procedure six out of the 2280 preparations (0.26%) were non-conforming for clinical use with the RCP limits indicated in the SPC. Five of these were due to gross technical errors in measurements and manual procedures and were immediately repeated, returning within the limits of acceptability. The sixth failure was due to short incubation time, though compliant with the manufacturer’s instructions. Conclusions: We concluded that the quality of the final product depends on a controlled production system based on the implementation of specific standard operating procedures (ISO9001, SOP) for each radiopharmaceutical production, according to strict adherence to the SPC of each radiopharmaceutical. Based on these conclusions, in our opinion every quality control suggesting a possible error in the synthesis procedure recommended in the SPC should be immediately reported to the manufacturer, for a revision of the SPC, as well as to the regulatory agencies for an alert. This strategy may in fact allow the continuous improvement of the labelling procedures and therefore the optimization of the quality control procedures frequency to ensure both patients safety and a more rational management of resources for economic sustainability. (www.actabiomedica.it)