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Circulating microRNA profiles in human drug-induced liver injury
S94
Abstracts / Toxicology Letters 229S (2014) S40–S252
P-2.4 TGF 1 codon-10 and codon-25 polymorphisms influence the spirometry parameters in the workers of sweet- and sour-gas refinery plants Aziz Eftekhari 1,∗ , Arasto Saeedi 4 , Ali Mandegary 2 , Elham Ahmadian 1,3 , Hamid Mohammadi 4 1
Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran, 2 Department of Toxicology & Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran, 3 Research Committee of Tabriz University of Medical Science, Tabriz, Iran, 4 Research Committee of Tabriz University of Medical Science, Shiraz, Iran
Out of 1805 miRNA species, 79 were >3 fold increased with APAP-ALI. A classifier model consisting of 16 miRNAs accurately separated APAP-ALI and APAP-noALI patients. Receiver operator curve analysis demonstrated that miR-122 predicted DILI at first presentation to hospital and was more accurate than ALT. The AUC (95% CI, P value, sensitivity at 95% specificity) values of miR-122 and ALT activity were 0.95 (0.90–1.00, P < 0.0001, 0.54) and 0.81 (0.65–0.97, P = 0.0006, 0.46), respectively. A novel panel of 16 miRNAs accurately diagnosed DILI with miR-122 reporting liver injury at first presentation to hospital with greater accuracy than current clinical biomarkers. With development, this panel of miRNAs may have significant utility in drug development and clinical medicine. http://dx.doi.org/10.1016/j.toxlet.2014.06.350
Objectives: Gene which encode inflammatory cytokine transforming growth factor-1 (TGF 1) is subject to polymorphisms in their regulatory regions that may effect both the level and ratio of cytokines produced in response to exogenous stimuli. The gene-environment interactions would effect the expression and/or progression of the disease including respiratory ones. Methods: After recruiting 120 and 110 workers respectively from the sour- and sweet-gas refinery plants, their pulmonary functions were assessed using spirometry. After extraction of DNA, the polymorphism of TGF 1 codon-10 (T to C) and codon-25 (G to C) was determined by the amplification refractory mutation system (ARMS)-PCR method. The multiple linear regression used to model the FVC, PEF, FEV1% and FEV1. Results: Exposure to H2S increased the FVC and PEF parameters. Subjects with codon-10C allele (CC and/or CT) and codon-25C allele (CC/GC) had higher FVC, FEV1% and FEV1 in comparison with wild types. The combination of both codons had different effect: subjects with at least one mutant allele of each codon had lower FVC and FEV1. These decrements were maximum for subjects who were C positive for both codons. Conclusion: High producing of TGF 1 can decrease the pulmonary functional tests. The effect of H2S on the spirometry parameters could be controversial. http://dx.doi.org/10.1016/j.toxlet.2014.06.349 P-2.5 Circulating microRNA profiles in human drug-induced liver injury Bastiaan Vliegenthart 1,∗ , Jonathan Shaffer 2 , Laura Peeters 1 , David Webb 1 , Nick Bateman 1 , Matthew Bailey 1 , Darren Craig 1 , Ken Simpson 1 , Eric Lader 2 , James Dear 1 1
Edinburgh University, Edinburgh, UK, 2 Qiagen, MD, USA
Acetaminophen (paracetamol – APAP) is the commonest cause of drug-induced liver injury (DILI). Circulating microRNAs (miRNAs) are promising DILI biomarkers, with miR-122 undergoing qualification in humans. For the first time, we comprehensively profiled the circulating miRNAome in humans with DILI. Plasma miRNAs were analysed using PCR-based arrays in ageand sex-matched APAP overdose patients with (N = 27) and without (N = 27) acute liver injury (APAP-ALI and APAP-noALI, respectively). Using random forest analysis a classifier miRNA model was developed that was tested in a second independent cohort (‘test cohort’ N = 82). MiRNAs that were most stable across patients were identified, then selected normalised miRNAs were compared to serum alanine transaminase (ALT) activity with regard to the stratification of patients at first presentation to hospital after overdose (N = 76).
P-2.6 Clinical interventions used in diminishing pain among patients with osteoarthritis: A mindfulness intervention Carolina Negrei 1,∗ , Luminita Claudia Miclea 2,4 , Octav Ginghina 5,6 , Florica Nicolescu 1 , Barbara Craciun 3 1
Department of Toxicology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, 2 Dresden University of Technology, Dresden, Germany, 3 Faculty of Psychology, Titu Maiorescu University, Bucharest, Romania, 4 Department of Biophysics and Cell Biotechnology “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, 5 “Sf. Ioan” Hospital, Bucharest, Romania, 6 Department for Oncological Surgery, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Objective: Pain is the most prominent symptom in the majority of people with osteoarthritis. Pain perception and the development of chronic pain is a complex process of neural integration. The concept and applicability of the mindfulness techniques have gained in the past years a continuously growing exposure both in the clinical and psychotherapeutic domains. Materials and methods: The trial included three groups, first group diagnosed with osteoarthritis (N = 42) mindfulness treatment applied, second group diagnosed with osteoarthritis (N = 38) treated with NSAIDS, and third, the control group (N = 37) which did not receive any kind of pharmacological and non-pharmacological treatment strategies. The instruments we used were the following: Visual analogue scale (VAS), Numerical rating scale (NRS) and Hospital Anxiety and Depression Scale (HADS). Results: The obtained results indicate an improvement of the state of patients suffering from osteoarthritis who benefited from applying mindfulness techniques and procedures specific to diminishing the pain. In the first group we registered significantly lower values of pain indicators and indicators of psychological distress caused by the osteoarthritis. Also, the level of depressive symptomatology has become lower in the group that received clinical treatment. Conclusions: The registered data suggest that compared to control group, the mindfulness technique reduce the level of pain reported by the patients and diminish the level of depressive symptomatology, also reducing the level of psychological distress. The findings in the present study are consistent with results from other studies which support the efficiency of mindfulness techniques when diminishing pain among patients with osteoarthritis. http://dx.doi.org/10.1016/j.toxlet.2014.06.351
Abstracts / Toxicology Letters 229S (2014) S40–S252
P-2.4 TGF 1 codon-10 and codon-25 polymorphisms influence the spirometry parameters in the workers of sweet- and sour-gas refinery plants Aziz Eftekhari 1,∗ , Arasto Saeedi 4 , Ali Mandegary 2 , Elham Ahmadian 1,3 , Hamid Mohammadi 4 1
Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran, 2 Department of Toxicology & Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran, 3 Research Committee of Tabriz University of Medical Science, Tabriz, Iran, 4 Research Committee of Tabriz University of Medical Science, Shiraz, Iran
Out of 1805 miRNA species, 79 were >3 fold increased with APAP-ALI. A classifier model consisting of 16 miRNAs accurately separated APAP-ALI and APAP-noALI patients. Receiver operator curve analysis demonstrated that miR-122 predicted DILI at first presentation to hospital and was more accurate than ALT. The AUC (95% CI, P value, sensitivity at 95% specificity) values of miR-122 and ALT activity were 0.95 (0.90–1.00, P < 0.0001, 0.54) and 0.81 (0.65–0.97, P = 0.0006, 0.46), respectively. A novel panel of 16 miRNAs accurately diagnosed DILI with miR-122 reporting liver injury at first presentation to hospital with greater accuracy than current clinical biomarkers. With development, this panel of miRNAs may have significant utility in drug development and clinical medicine. http://dx.doi.org/10.1016/j.toxlet.2014.06.350
Objectives: Gene which encode inflammatory cytokine transforming growth factor-1 (TGF 1) is subject to polymorphisms in their regulatory regions that may effect both the level and ratio of cytokines produced in response to exogenous stimuli. The gene-environment interactions would effect the expression and/or progression of the disease including respiratory ones. Methods: After recruiting 120 and 110 workers respectively from the sour- and sweet-gas refinery plants, their pulmonary functions were assessed using spirometry. After extraction of DNA, the polymorphism of TGF 1 codon-10 (T to C) and codon-25 (G to C) was determined by the amplification refractory mutation system (ARMS)-PCR method. The multiple linear regression used to model the FVC, PEF, FEV1% and FEV1. Results: Exposure to H2S increased the FVC and PEF parameters. Subjects with codon-10C allele (CC and/or CT) and codon-25C allele (CC/GC) had higher FVC, FEV1% and FEV1 in comparison with wild types. The combination of both codons had different effect: subjects with at least one mutant allele of each codon had lower FVC and FEV1. These decrements were maximum for subjects who were C positive for both codons. Conclusion: High producing of TGF 1 can decrease the pulmonary functional tests. The effect of H2S on the spirometry parameters could be controversial. http://dx.doi.org/10.1016/j.toxlet.2014.06.349 P-2.5 Circulating microRNA profiles in human drug-induced liver injury Bastiaan Vliegenthart 1,∗ , Jonathan Shaffer 2 , Laura Peeters 1 , David Webb 1 , Nick Bateman 1 , Matthew Bailey 1 , Darren Craig 1 , Ken Simpson 1 , Eric Lader 2 , James Dear 1 1
Edinburgh University, Edinburgh, UK, 2 Qiagen, MD, USA
Acetaminophen (paracetamol – APAP) is the commonest cause of drug-induced liver injury (DILI). Circulating microRNAs (miRNAs) are promising DILI biomarkers, with miR-122 undergoing qualification in humans. For the first time, we comprehensively profiled the circulating miRNAome in humans with DILI. Plasma miRNAs were analysed using PCR-based arrays in ageand sex-matched APAP overdose patients with (N = 27) and without (N = 27) acute liver injury (APAP-ALI and APAP-noALI, respectively). Using random forest analysis a classifier miRNA model was developed that was tested in a second independent cohort (‘test cohort’ N = 82). MiRNAs that were most stable across patients were identified, then selected normalised miRNAs were compared to serum alanine transaminase (ALT) activity with regard to the stratification of patients at first presentation to hospital after overdose (N = 76).
P-2.6 Clinical interventions used in diminishing pain among patients with osteoarthritis: A mindfulness intervention Carolina Negrei 1,∗ , Luminita Claudia Miclea 2,4 , Octav Ginghina 5,6 , Florica Nicolescu 1 , Barbara Craciun 3 1
Department of Toxicology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, 2 Dresden University of Technology, Dresden, Germany, 3 Faculty of Psychology, Titu Maiorescu University, Bucharest, Romania, 4 Department of Biophysics and Cell Biotechnology “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania, 5 “Sf. Ioan” Hospital, Bucharest, Romania, 6 Department for Oncological Surgery, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Objective: Pain is the most prominent symptom in the majority of people with osteoarthritis. Pain perception and the development of chronic pain is a complex process of neural integration. The concept and applicability of the mindfulness techniques have gained in the past years a continuously growing exposure both in the clinical and psychotherapeutic domains. Materials and methods: The trial included three groups, first group diagnosed with osteoarthritis (N = 42) mindfulness treatment applied, second group diagnosed with osteoarthritis (N = 38) treated with NSAIDS, and third, the control group (N = 37) which did not receive any kind of pharmacological and non-pharmacological treatment strategies. The instruments we used were the following: Visual analogue scale (VAS), Numerical rating scale (NRS) and Hospital Anxiety and Depression Scale (HADS). Results: The obtained results indicate an improvement of the state of patients suffering from osteoarthritis who benefited from applying mindfulness techniques and procedures specific to diminishing the pain. In the first group we registered significantly lower values of pain indicators and indicators of psychological distress caused by the osteoarthritis. Also, the level of depressive symptomatology has become lower in the group that received clinical treatment. Conclusions: The registered data suggest that compared to control group, the mindfulness technique reduce the level of pain reported by the patients and diminish the level of depressive symptomatology, also reducing the level of psychological distress. The findings in the present study are consistent with results from other studies which support the efficiency of mindfulness techniques when diminishing pain among patients with osteoarthritis. http://dx.doi.org/10.1016/j.toxlet.2014.06.351