AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with ac...AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain,and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma. METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases. RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0±2.7 pg/mL, n=26),primary biliary cirrhosis (12.1±3.2 pg/mL, n=21) and liver cirrhosis (12.8±4.0 pg/mL, n=15) compared to the healthy controls (9.2±1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found(105.9±14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9±14.9 pg/mL, n=-12) and without (107.7±14.5pg/mL, n=6). CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.展开更多
AIM: Although liver cirrhosis is a predisposing factor for hepatocellular carcinoma (HCC), relatively few reports are available on HCC in primary biliary cirrhosis. High plasma nodceptin (N/OFQ) level has been shown i...AIM: Although liver cirrhosis is a predisposing factor for hepatocellular carcinoma (HCC), relatively few reports are available on HCC in primary biliary cirrhosis. High plasma nodceptin (N/OFQ) level has been shown in Wilson disease and in patients with acute and chronic pain. METHODS: We report a follow-up case of HCC, which developed in a patient with primary biliary drrhosis. The tumor appeared 18 years after the diagnosis of PBC and led to death within two years. Alfa fetoprotein and serum nodceptin levelswere monitored before and during the development of HCC. Nociceptin content was also measured in the tumor tissue. RESULTS: The importance and the curiosity of the presented case was the novel finding of the progressive elevation of plasma nodceptin level up to 17-fold (172 pg/mL) above the baseline (9.2±1.8 pg/mL), parallel with the elevation of alpha fetoprotein (from 13 ng/mL up to 3 480 ng/mL) during tumor development. Nodceptin content was more than 15-fold higher in the neoplastic tissue (0.16 pg/mg) than that in the tumorfree liver tissue samples (0.01 pg/mg) taken during the autopsy. CONCLUSION: Results are in concordance with our previous observation that a very high plasma nociceptin level may be considered as an indicator for hepatocellular carcinoma.展开更多
Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,c...Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.展开更多
文摘AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain,and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma. METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases. RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0±2.7 pg/mL, n=26),primary biliary cirrhosis (12.1±3.2 pg/mL, n=21) and liver cirrhosis (12.8±4.0 pg/mL, n=15) compared to the healthy controls (9.2±1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found(105.9±14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9±14.9 pg/mL, n=-12) and without (107.7±14.5pg/mL, n=6). CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.
文摘AIM: Although liver cirrhosis is a predisposing factor for hepatocellular carcinoma (HCC), relatively few reports are available on HCC in primary biliary cirrhosis. High plasma nodceptin (N/OFQ) level has been shown in Wilson disease and in patients with acute and chronic pain. METHODS: We report a follow-up case of HCC, which developed in a patient with primary biliary drrhosis. The tumor appeared 18 years after the diagnosis of PBC and led to death within two years. Alfa fetoprotein and serum nodceptin levelswere monitored before and during the development of HCC. Nociceptin content was also measured in the tumor tissue. RESULTS: The importance and the curiosity of the presented case was the novel finding of the progressive elevation of plasma nodceptin level up to 17-fold (172 pg/mL) above the baseline (9.2±1.8 pg/mL), parallel with the elevation of alpha fetoprotein (from 13 ng/mL up to 3 480 ng/mL) during tumor development. Nodceptin content was more than 15-fold higher in the neoplastic tissue (0.16 pg/mg) than that in the tumorfree liver tissue samples (0.01 pg/mg) taken during the autopsy. CONCLUSION: Results are in concordance with our previous observation that a very high plasma nociceptin level may be considered as an indicator for hepatocellular carcinoma.
文摘Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.
