Preliminary assessment of fentanyl and synthetic opioids prevalence among addiction patients by means of hair analysis

Background Although the diffusion of novel synthetic opioids has become a worldwide phenomenon, their prevalence of use in Italy seems to be limited. Existing national data is mainly derived by anamnestic surveyslacking of toxicological validation and not always disclosing the use of these compounds, which might remain under-diagnosed. Methods an assessment of the metabolites of the main synthetic opioids on hair samples was carried out among patients admitted at the Addiction Treatment Unit of Trento. The analytical approach included: (a) screening by means of immunoenzymatic method for fentanyl, fentanyl analogs and oxicodone; (b) confirmation of the samples resulted positive for fentanyl and oxicodone by means of HPLC-MS/; (c) search and dosage detection of Tramadol by means of HPLC-MS/MS. Results 3 out of 309 analysed samples were found positive: one was positive to Fentanyl and two to 4-ANPP. In the same cohort, 6 samples were also found positive for Oxycodone . Tramadol was searched in 189 samples and 12 of them resulted positive. Discussion and conclusion Those found positive were mainly young adults engaging in dangerous patterns of use and lacking awareness of risks. The phenomenon requires further consideration by health professionals. Training and more evidence-based information on synthetic opioids as well as other Novel Psychoactive Substances (NPS) are urgently needed.Peer reviewe

The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer can be efficiently treated when found at early stages, thus the search for novel markers is of paramount importance. Since inflammation is associated with cancer progression and angiogenesis, we investigated expression of cytokines like IL-6 and other mediators that play a key role in the innate immune system, in particular toll like receptor 4 (TLR4), in the microenvironment of lesions from different stages of colon disease progression, from ulcerative colitis to adenoma and adenocarcinoma to find useful markers.</p> <p>Methods</p> <p>The presence of inflammatory cells and expression of key cytokines involved in the inflammation process were quantified by immunohistochemistry in specific tissue compartments (epithelial, stromal, endothelial) by immunohistochemistry. A murine azoxymethane/dextran sulfate model in which Tir8, a negative regulator of the inflammatory response, was ablated was used to confirm the clinical observations. 116 Archival tissue samples from patients with different stages of colorectal disease: 13 cases of ulcerative colitis (UC), 34 tubular or tubulo-villous adenomas (AD), and 53 infiltrating adenocarcinomas. 16 specimens of healthy mucosa surgically removed with the cancerous tissue were used as a control.</p> <p>Results</p> <p>The differences between healthy tissues and the diverse lesions was characterized by a marked inflammatory-angiogenic reaction, with significantly (P < 0.05) higher numbers of CD68, CD15, and CD31 expressing cells in all diseased tissues that correlated with increasing grade of malignancy. We noted down-regulation of a potential modulator molecule, Hepatocyte Growth Factor, in all diseased tissues (P < 0.05). TLR-4 and IL6 expression in the tumor microenvironment were associated with adenocarcinoma in human samples and in the murine model. We found that adenocarcinoma patients (pT1-4) with higher TLR-4 expression in stromal compartment had a significantly increased risk in disease progression. In those patients with a diagnosis of pT3 (33 cases) colon cancer, those with very high levels of TLR-4 in the tumor stroma relapsed significantly earlier than those with lower expression levels.</p> <p>Conclusions</p> <p>These data suggest that high TLR-4 expression in the tumor microenvironment represents a possible marker of disease progression in colon cancer.</p