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Article ; Online: A review of liquid biopsy as a tool to assess epigenetic, cfDNA and miRNA variability as methotrexate response predictors in patients with rheumatoid arthritis.

Daraghmeh, Dala N / King, Catherine / Wiese, Michael D

2021 Volume 173, Page(s) 105887

Abstract: Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease affecting 0.5-1% of adults worldwide. Achieving long term remission or low disease activity is possible through early diagnosis, rapid initiation of disease modifying anti-rheumatic ... ...

Abstract	Rheumatoid arthritis (RA) is a common autoimmune inflammatory disease affecting 0.5-1% of adults worldwide. Achieving long term remission or low disease activity is possible through early diagnosis, rapid initiation of disease modifying anti-rheumatic drugs (DMARDs) and implementation of a treat to target approach. Initial DMARD therapy usually involves methotrexate (MTX), either alone or in combination with other agents, however 40% of RA patients do not respond adequately, putting them at risk of disease progression and unnecessary exposure to MTX related adverse effects. Early predictors of MTX response would therefore enable a more personalized treatment strategy, ensuring timely access to MTX for those likely to respond and importantly, early initiation of alternative treatment for those in which MTX is unlikely to be efficacious. Predicting response to treatment will most likely require consideration of the clinical characteristics of the patient and interrogation of a number of factors including genetic, epigenetic, cell free DNA (cfDNA) and microRNA (miRNA), all of which can be investigated through blood derived liquid biopsies. This review will summarize the existing literature examining the use of epigenetic factors, cfDNA and miRNA as response predictors among RA patients treated with MTX.
MeSH term(s)	Antirheumatic Agents/pharmacology ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/genetics ; Cell-Free Nucleic Acids ; Epigenesis, Genetic ; Humans ; Liquid Biopsy ; Methotrexate/pharmacology ; Methotrexate/therapeutic use ; MicroRNAs ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; Cell-Free Nucleic Acids ; MicroRNAs ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2021-09-16
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.105887
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Zs.A 721: Show issues

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Article ; Online: Barriers and Enablers in the Use of Parenteral Methotrexate in Rheumatoid Arthritis Patients: A Scoping Review.

Tan, Jiun Ming / Reeve, Emily / Fraser, Lauren / Proudman, Susanna M / Wiese, Michael D

Arthritis care & research

2023 Volume 75, Issue 11, Page(s) 2306–2315

Abstract: Objective: Methotrexate (MTX) is effective in controlling disease activity in rheumatoid arthritis (RA). Parenteral MTX may have benefits over oral MTX, but it is rarely used in practice. To better understand this low usage rate, it is necessary to ... ...

Abstract	Objective: Methotrexate (MTX) is effective in controlling disease activity in rheumatoid arthritis (RA). Parenteral MTX may have benefits over oral MTX, but it is rarely used in practice. To better understand this low usage rate, it is necessary to explore the barriers and enablers of therapy from the perspective of RA patients. The objectives of this scoping review were to describe RA patients' perspectives on the barriers and enablers in the use of parenteral MTX and to identify the research gaps in this field. Methods: The search was performed in Medline, Embase, Scopus, and Cochrane Library from inception to May 2021. Data synthesis was conducted using the Theoretical Framework of Acceptability. This scoping review included any type of study that explored the use of parenteral MTX by adult RA patients from the patients' perspective, written in English. Results: Fifteen studies were included; findings related to the constructs "affective attitude," "burden," "intervention coherence," and "self-efficacy" were explored the most, while some were rarely ("opportunity cost" and "perceived effectiveness") or not ("ethicality") reported. RA patients were generally satisfied with MTX injections ("affective attitude"). From the burden construct, the requirement for dexterity for administering MTX by injection was considered a barrier, whereas the lack of significant pain from MTX injection was considered an enabler. Conclusion: The findings suggested that patients generally preferred parenteral MTX formulations with attributes that facilitate self-administration. However, much of the identified research focused on prefilled pen devices, and significant gaps were identified, such as a lack of qualitative research.
MeSH term(s)	Adult ; Humans ; Methotrexate/therapeutic use ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Treatment Outcome
Chemical Substances	Methotrexate (YL5FZ2Y5U1) ; Antirheumatic Agents
Language	English
Publishing date	2023-06-12
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.25141
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Zs.A 2446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 24: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Quantitation of methotrexate polyglutamates in human whole blood, erythrocytes and leukocytes collected via venepuncture and volumetric absorptive micro-sampling: a green LC–MS/MS-based method

Daraghmeh, Dala N. / Moghaddami, Mahin / Bobrovskaya, Larisa / Proudman, Susanna M. / Wiese, Michael D.

Analytical and bioanalytical chemistry. 2022 Aug., v. 414, no. 20

2022

Abstract: Low-dose methotrexate (MTX) plays a key role in treatment of rheumatoid arthritis. However, not all patients respond satisfactorily, and no therapeutic drug monitoring has been implemented in clinical practice, despite the fact that MTX therapy has now ... ...

Abstract	Low-dose methotrexate (MTX) plays a key role in treatment of rheumatoid arthritis. However, not all patients respond satisfactorily, and no therapeutic drug monitoring has been implemented in clinical practice, despite the fact that MTX therapy has now been available for decades. Analysis of individual intracellular MTX metabolites among rheumatoid arthritis (RA) patients is hampered by the low intracellular concentrations of MTX-PGs which require a highly sensitive method to quantify. Here, we present a rapid and highly sensitive LC (HILIC) MS/MS method with LLOQ 0.1 nM, 0.8 nmol/L for each metabolite of MTX-PG₁₋₅ and MTX-PG₆₋₇ respectively. Over a linear range of 0.1–100 nM, 0.8–100 nmol/L for each metabolite of MTX-PG₁₋₅ and MTX-PG₆₋₇, respectively, the inter- and intra- accuracy and precision were within 15% of the nominal value for all MTX metabolites. The presented assay was used to assess and compare MTX metabolite concentrations extracted from four different matrices: red blood cells, plasma, peripheral blood mononuclear cells, and whole blood that have been collected either using traditional venepuncture or volumetric absorptive micro-sampling (VAMS) sampling techniques. The presented method not only improves analyte coverage and sensitivity as compared to other published methods; it also improves the greenness.
Keywords	analytical chemistry ; erythrocytes ; humans ; metabolites ; methotrexate ; rheumatoid arthritis ; therapeutics
Language	English
Dates of publication	2022-08
Size	p. 6029-6046.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-022-04186-1
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Article ; Online: The efficacy of systemic administration of lipopolysaccharide in modelling pre-motor Parkinson's disease in C57BL/6 mice.

Deng, Isaac / Wiese, Michael D / Zhou, Xin-Fu / Bobrovskaya, Larisa

Neurotoxicology

2021 Volume 85, Page(s) 254–264

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease, characterised by the loss of dopaminergic neurons in the substantia nigra. Mounting evidence indicates a crucial role of inflammation and concomitant oxidative stress in the ... ...

Abstract	Parkinson's disease (PD) is the second most common neurodegenerative disease, characterised by the loss of dopaminergic neurons in the substantia nigra. Mounting evidence indicates a crucial role of inflammation and concomitant oxidative stress in the disease progression. Therefore, the aim of this study was to investigate the ability of systemically administered lipopolysaccharide (LPS) to induce motor and non-motor symptoms of PD, inflammation, oxidative stress and major neuropathological hallmarks of the disease in regions postulated to be affected, including the olfactory bulb, hippocampus, midbrain and cerebellum. Twenty-one male C57BL/6 mice, approximately 20 weeks old, received a dose of 0.3 mg/kg/day of LPS systemically on 4 consecutive days and behavioural testing was conducted on days 14-18 post-treatment, followed by tissue collection. Systemically administered LPS increased latency time in the buried food seeking test (indicative of olfactory impairment), and decreased time spent in central zone of the open field (anxiety-like behaviour). However, there was no change in latency time in the rotarod test or the expression of tyrosine hydroxylase (TH) in the midbrain. Systemically administered LPS induced increased glial markers GFAP and Iba-1 and oxidative stress marker 3-nitrotyrosine (3-NT) in the olfactory bulb, hippocampus, midbrain and cerebellum, and there were region specific changes in the expression of NFκB, IL-1β, α-synuclein, TH and BDNF proteins. The model could be useful to further elucidate early non-motor aspects of PD and the possible mechanisms contributing to the non-motor deficits.
MeSH term(s)	Affect/drug effects ; Affect/physiology ; Animals ; Disease Models, Animal ; Lipopolysaccharides/toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Motor Activity/physiology ; Parkinsonian Disorders/chemically induced ; Parkinsonian Disorders/metabolism ; Parkinsonian Disorders/psychology ; Smell/drug effects ; Smell/physiology
Chemical Substances	Lipopolysaccharides
Language	English
Publishing date	2021-06-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	800820-6
ISSN	1872-9711 ; 0161-813X
ISSN (online)	1872-9711
ISSN	0161-813X
DOI	10.1016/j.neuro.2021.05.015
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Zs.A 1547: Show issues

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Article ; Online: Quantitation of methotrexate polyglutamates in human whole blood, erythrocytes and leukocytes collected via venepuncture and volumetric absorptive micro-sampling: a green LC-MS/MS-based method.

Daraghmeh, Dala N / Moghaddami, Mahin / Bobrovskaya, Larisa / Proudman, Susanna M / Wiese, Michael D

Analytical and bioanalytical chemistry

2022 Volume 414, Issue 20, Page(s) 6029–6046

Abstract	Low-dose methotrexate (MTX) plays a key role in treatment of rheumatoid arthritis. However, not all patients respond satisfactorily, and no therapeutic drug monitoring has been implemented in clinical practice, despite the fact that MTX therapy has now been available for decades. Analysis of individual intracellular MTX metabolites among rheumatoid arthritis (RA) patients is hampered by the low intracellular concentrations of MTX-PGs which require a highly sensitive method to quantify. Here, we present a rapid and highly sensitive LC (HILIC) MS/MS method with LLOQ 0.1 nM, 0.8 nmol/L for each metabolite of MTX-PG
MeSH term(s)	Arthritis, Rheumatoid ; Chromatography, Liquid/methods ; Erythrocytes/chemistry ; Humans ; Leukocytes/chemistry ; Leukocytes, Mononuclear ; Methotrexate/analogs & derivatives ; Polyglutamic Acid/analogs & derivatives ; Tandem Mass Spectrometry/methods
Chemical Substances	Polyglutamic Acid (25513-46-6) ; methotrexate polyglutamate (82334-40-5) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-07-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-022-04186-1
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Article ; Online: Population Pharmacokinetic Model for Tramadol and O-desmethyltramadol in Older Patients.

Al-Qurain, Aymen A / Upton, Richard N / Tadros, Rami / Roberts, Michael S / Wiese, Michael D

European journal of drug metabolism and pharmacokinetics

2022 Volume 47, Issue 3, Page(s) 387–402

Abstract: Background and objectives: Tramadol is commonly prescribed to manage chronic pain in older patients. However, there is a gap in the literature describing the pharmacokinetic parameters for tramadol and its active metabolite (O-desmethyltramadol [ODT]) ... ...

Abstract	Background and objectives: Tramadol is commonly prescribed to manage chronic pain in older patients. However, there is a gap in the literature describing the pharmacokinetic parameters for tramadol and its active metabolite (O-desmethyltramadol [ODT]) in this population. The objective of this study was to develop and evaluate a population pharmacokinetic model for tramadol and ODT in older patients. Methods: Twenty-one patients who received an extended-release oral tramadol dose (25-100 mg) were recruited. Tramadol and ODT concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. The performance of the model was assessed by visual predictive check. Results: A two-compartment, first-order absorption model with linear elimination best described the tramadol concentration data. The absorption rate constant was 2.96/h (between-subject variability [BSV] 37.8%), apparent volume of distribution for the central compartment (V Conclusion: Exposure to tramadol increased with increased frailty and reduced CrCL. Prescribers should consider patients frailty status and CrCL to minimise the risk of tramadol toxicity in such cohort of patients.
MeSH term(s)	Aged ; Chromatography, Liquid/methods ; Female ; Frailty ; Half-Life ; Humans ; Male ; Tramadol/analogs & derivatives
Chemical Substances	O-demethyltramadol (2WA8F50C3F) ; Tramadol (39J1LGJ30J)
Language	English
Publishing date	2022-02-15
Publishing country	France
Document type	Journal Article
ZDB-ID	196729-0
ISSN	2107-0180 ; 0398-7639 ; 0378-7966
ISSN (online)	2107-0180
ISSN	0398-7639 ; 0378-7966
DOI	10.1007/s13318-022-00756-x
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Zs.A 1236: Show issues

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Article ; Online: Maternal-placental-fetal drug metabolism is altered by late gestation undernutrition in the pregnant ewe.

Meakin, Ashley S / Darby, Jack R T / Holman, Stacey L / Wiese, Michael D / Morrison, Janna L

Life sciences

2022 Volume 298, Page(s) 120521

Abstract: Background: Maternal undernutrition during pregnancy disrupts both fetal growth and development with perturbations to certain physiological processes within the maternal-fetal-placental unit, including metabolic function. However, it is unknown if ... ...

Abstract	Background: Maternal undernutrition during pregnancy disrupts both fetal growth and development with perturbations to certain physiological processes within the maternal-fetal-placental unit, including metabolic function. However, it is unknown if hypoglycemia during pregnancy alters maternal-fetal-placental drug metabolism as mediated by cytochrome P450 (CYP) enzymes. Despite this, hypoglycemia reduces CYP enzyme activity in non-pregnant animals. We therefore hypothesised that in a sheep model of hypoglycemia induced by late gestation undernutrition (LGUN), maternal-fetal-placental CYP activity would be reduced, and that fetal glucose infusion (LGUN+G) would rescue reduced CYP activity. Methods: At 115d gestation (term, 150d), ewes were allocated to control (100% metabolic energy requirement (MER); n = 11), LGUN (50% MER; n = 7) or LGUN+G (50% MER + fetal glucose infusion; n = 6) and maintained on their diets until post-mortem. Maternal-fetal-placental CYP activity assays were performed at 131-133d gestation. Microsomes were isolated from placenta and fetal liver collected at 139-142d gestation and incubated with CYP-specific probe drugs. Metabolite concentrations were measured using Liquid Chromatography - tandem mass spectrometry (LC-MS/MS). Results: CYP2C19 and CYP3A were undetectable in placenta or fetal liver, and CYP1A2 was undetectable in the fetal liver. Placental-specific CYP1A2 and CYP2D6 activity and hepatic-specific CYP2D6 activity were unaffected by LGUN. Maternal-fetal-placental CYP1A2 activity was reduced in response to LGUN in the maternal compartment only. Conclusions: Reduced maternal-fetal-placental CYP1A2 activity, but not placental-specific CYP1A2 activity, may lead to the developing fetus being exposed to increased concentrations of CYP1A2-specific substrates and suggests further consideration of drug dosing is required in instances of late gestation maternal undernutrition.
MeSH term(s)	Animals ; Chromatography, Liquid ; Cytochrome P-450 CYP1A2/metabolism ; Cytochrome P-450 CYP2D6/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Female ; Fetus/metabolism ; Glucose/metabolism ; Hypoglycemia/metabolism ; Malnutrition/metabolism ; Maternal-Fetal Exchange ; Placenta/metabolism ; Pregnancy ; Sheep ; Tandem Mass Spectrometry
Chemical Substances	Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-03-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120521
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Article ; Online: The development of Jack Jumper ant venom immunotherapy: our 25 years' experience.

Wanandy, Troy / Le, Thanh-Thao A / Lau, Wun Y / Wiese, Michael D / Heddle, Robert J / Brown, Simon G A

Internal medicine journal

2023 Volume 53, Issue 9, Page(s) 1716–1721

Abstract: Jack Jumper ant venom allergy is a uniquely Australian medical issue. The stinging ant is a leading cause of insect venom allergy in south-eastern Australia. An effective venom immunotherapy-based treatment was successfully developed by the Tasmanian ... ...

Abstract	Jack Jumper ant venom allergy is a uniquely Australian medical issue. The stinging ant is a leading cause of insect venom allergy in south-eastern Australia. An effective venom immunotherapy-based treatment was successfully developed by the Tasmanian Jack Jumper Allergy Research group. This paper provides a synopsis of our 25 years' research journey in developing this evidence-based treatment modality.
MeSH term(s)	Humans ; Animals ; Ants ; Australia ; Desensitization, Immunologic ; Hypersensitivity/therapy ; Pain
Language	English
Publishing date	2023-09-24
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2045436-3
ISSN	1445-5994 ; 1444-0903
ISSN (online)	1445-5994
ISSN	1444-0903
DOI	10.1111/imj.16217
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Zs.A 792: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Maternal obesity impacts fetal liver androgen signalling in a sex-specific manner.

Meakin, Ashley S / Nathanielsz, Peter W / Li, Cun / Clifton, Vicki L / Wiese, Michael D / Morrison, Janna L

Life sciences

2023 Volume 337, Page(s) 122344

Abstract: Background: Maternal obesity (MO) increases fetal androgen concentrations, the prevalence of macrosomia, and predisposes offspring to metabolic dysfunction in later life, especially males. These risks may be, in part, the result of increased liver- ... ...

Abstract	Background: Maternal obesity (MO) increases fetal androgen concentrations, the prevalence of macrosomia, and predisposes offspring to metabolic dysfunction in later life, especially males. These risks may be, in part, the result of increased liver-specific androgen signalling pathway activity in utero. Androgen signalling activity can be suppressed by androgen metabolism via cytochrome P450 (CYP) isoenzymes (CYP2B6, CYP3A) or through inhibition of the full-length androgen receptor (AR-FL) via the antagonistic isoform, AR-45. We hypothesised MO impairs CYP enzyme activity and AR-45 expression in male fetal livers, thereby enhancing activity of androgen signalling pathways. Methods: Nine months prior to pregnancy, nulliparous female baboons were assigned to either ad libitum control or high fat diet. At 165 day (d) gestation (term, 180 d) fetal liver was collected (n = 6/sex/group). CYP activity was quantified using functional assays; subcellular AR expression was measured using Western blot. Results: CYP2B6 and CYP3A activity, and nuclear expression of AR-45, was reduced in MO males only. Nuclear AR-45 expression was inversely related with fetal body weight of MO males only. Conclusions: Reduced CYP2B6 and CYP3A activity in conjunction with decreased nuclear AR-45 expression may enhance liver androgen signalling in males from MO pregnancies, thereby increasing the risk of macrosomia, as well as metabolic dysfunction in later life.
MeSH term(s)	Humans ; Female ; Pregnancy ; Male ; Androgens/metabolism ; Obesity, Maternal/metabolism ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 CYP2B6/metabolism ; Fetal Macrosomia/metabolism ; Receptors, Androgen/metabolism ; Liver/metabolism ; Isoenzymes
Chemical Substances	Androgens ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Cytochrome P-450 CYP2B6 (EC 1.14.14.1) ; Receptors, Androgen ; Isoenzymes
Language	English
Publishing date	2023-12-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.122344
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Article ; Online: Treating rheumatoid arthritis to target: physician and patient adherence issues in contemporary rheumatoid arthritis therapy.

Wabe, Nasir / Wiese, Michael D

Journal of evaluation in clinical practice

2017 Volume 23, Issue 3, Page(s) 486–493

Abstract: Development of the treat-to-target (T2T) strategy, the process whereby drug therapy is adjusted until the therapeutic goal is achieved, has revolutionized how rheumatoid arthritis (RA) patients are treated. With the advent of T2T, the management of RA is ...

Abstract	Development of the treat-to-target (T2T) strategy, the process whereby drug therapy is adjusted until the therapeutic goal is achieved, has revolutionized how rheumatoid arthritis (RA) patients are treated. With the advent of T2T, the management of RA is more effective than ever, with the possibility of remission and other favorable clinical and patient-reported outcomes. Effective implementation of a T2T strategy in routine clinical practice mainly depends on the long-term commitment of physician and patient to T2T treatment recommendations. However, as T2T is a complex process involving aggressive early management with several steps of therapy modifications requiring frequent close monitoring of disease activity and drug toxicities, it may be more liable to suboptimal adherence in real-life clinical practice. The aim of the review is to present key issues related to patient medication adherence and physician adherence to the current RA treatment recommendations and their importance in optimizing the outcome of treatment in RA treated according to T2T strategy.
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1327355-3
ISSN	1365-2753 ; 1356-1294
ISSN (online)	1365-2753
ISSN	1356-1294
DOI	10.1111/jep.12620
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