Oxidative Modification of Peroxiredoxin Is Associated with Drug-induced Apoptotic Signaling in Experimental Models of Parkinson Disease

Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.

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Association between diabetes and subsequent Parkinson disease

Neurology ◽

10.1212/wnl.0000000000005771 ◽

2018 ◽

Vol 91 (2) ◽

pp. e139-e142 ◽

Cited By ~ 65

Author(s):

Eduardo De Pablo-Fernandez ◽

Raph Goldacre ◽

Julia Pakpoor ◽

Alastair J. Noyce ◽

Thomas T. Warner

Keyword(s):

Cohort Study ◽

Parkinson Disease ◽

Cox Regression ◽

Normal Pressure ◽

Relative Increase ◽

Mortality Data ◽

Drug Induced ◽

Therapeutic Implications ◽

Large Cohort Study ◽

Reference Cohort

ObjectiveTo investigate the association between type 2 diabetes mellitus (T2DM) and subsequent Parkinson disease (PD).MethodsLinked English national Hospital Episode Statistics and mortality data (1999–2011) were used to conduct a retrospective cohort study. A cohort of individuals admitted for hospital care with a coded diagnosis of T2DM was constructed, and compared to a reference cohort. Subsequent PD risk was estimated using Cox regression models. Individuals with a coded diagnosis of cerebrovascular disease, vascular parkinsonism, drug-induced parkinsonism, and normal pressure hydrocephalus were excluded from the analysis.ResultsA total of 2,017,115 individuals entered the T2DM cohort and 6,173,208 entered the reference cohort. There were significantly elevated rates of PD following T2DM (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.29–1.35; p < 0.001). The relative increase was greater in those with complicated T2DM (HR 1.49, 95% CI 1.42–1.56) and when comparing younger individuals (HR 3.81, 95% CI 2.84–5.11 in age group 25–44 years).ConclusionsWe report an increased rate of subsequent PD following T2DM in this large cohort study. These findings may reflect shared genetic predisposition and/or disrupted shared pathogenic pathways with potential clinical and therapeutic implications.

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Experimental Models and New, Emerging Therapies for Parkinson Disease

Principles and Practice of Movement Disorders ◽

10.1016/b978-0-443-07941-2.50012-7 ◽

2007 ◽

pp. 205-231

Author(s):

Stanley Fahn ◽

Joseph Jankovic ◽

Mark Hallett ◽

Peter Jenner

Keyword(s):

Parkinson Disease ◽

Experimental Models ◽

Emerging Therapies

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Tremor pattern differentiates drug-induced resting tremor from Parkinson disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2016.02.002 ◽

2016 ◽

Vol 25 ◽

pp. 100-103 ◽

Cited By ~ 7

Author(s):

R. Nisticò ◽

A. Fratto ◽

B. Vescio ◽

G. Arabia ◽

G. Sciacca ◽

...

Keyword(s):

Parkinson Disease ◽

Drug Induced ◽

Resting Tremor

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Mechanistic Research for the Student or Educator (Part I of II)

10.20944/preprints202009.0481.v1 ◽

2020 ◽

Author(s):

Rehana Leak

Keyword(s):

Biological Sciences ◽

Drug Testing ◽

Therapeutic Potential ◽

Physiological Mechanism ◽

Experimental Models ◽

Preclinical Research ◽

Drug Induced ◽

Therapeutic Outcomes ◽

Biological Target ◽

Full Factorial

Many discoveries in the biological sciences have emerged from observational studies, but student researchers also need to learn how to design experiments that distinguish correlation from causation. For example, identifying the physiological mechanism of action of drugs with therapeutic potential requires the establishment of causal links. Only by specifically interfering with the purported mechanisms of action of a drug can the researcher determine how the drug “causes” its physiological effects. Typically, pharmacological or genetic approaches are employed to modify the expression and/or activity of the biological drug target or downstream pathways, to test if the salutary properties of the drug are thereby abolished. However, experimental techniques have caveats that tend to be underappreciated, particularly for the newer methods. In this two-part series, the caveats and strengths of mechanistic preclinical research are described, using the intuitive example of pharmaceutical drug testing in experimental models of human diseases. This series is not intended to tackle the perpetual clash between the frequentist approach to statistics and other schools of thought. Rather, Part I focuses on technical practicalities and common pitfalls of cellular and animal models designed for drug testing, and Part II describes in simple terms how to leverage a full-factorial three-way ANOVA, to test for causality in the link between drug-induced activation (or inhibition) of a biological target and therapeutic outcomes. Upon completion of this series, the student is expected to appreciate the strengths as well as limitations of mechanistic research and to avoid some of its pitfalls.

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Nephrotoxicity Biomarkers: Role and Significance in the Diagnosis of Drug-Induced Kidney Injury

Safety and Risk of Pharmacotherapy ◽

10.30895/2312-7821-2021-9-4-173-184 ◽

2021 ◽

Vol 9 (4) ◽

pp. 173-184

Author(s):

O. V. Muslimova ◽

V. A. Evteev ◽

I. A. Mazerkina ◽

E. A. Sokova ◽

A. B. Prokofiev ◽

...

Keyword(s):

Kidney Injury ◽

Experimental Models ◽

Injury Incidence ◽

Drug Induced ◽

Blood Concentrations ◽

Incidence And Mortality ◽

Hospital Patients

Drug-induced kidney injury (DIKI) accounts for 8 to 60% of episodes of acute kidney injury (AKI) among hospital patients. Early DIKI detection and timely adjustment of therapy will help reduce the kidney injury incidence and mortality. The aim of the study was to analyse scientific literature on the biomarkers used in DIKI diagnosis. The study revealed that the use of such kidney damage markers as serum creatinine, urinary output, urea nitrogen, sodium excretion, urinary sediment microscopy is limited because they do not give a full picture of the kidney injury degree and progression and do not allow for early AKI diagnosis. It was demonstrated that some of the most promising biomarkers are KIM-1, L-FABP, NAG, NGAL, cystatin C, clusterin, β2-microglobulin, МСР-1, IGFBP7, and TIMP-2. However, recommendations for determination of these biomarkers’ urine or blood concentrations for AKI diagnosis are somewhat preliminary, because there have been insufficient clinical and preclinical studies to establish validity of such tests. No precise algorithms based on determination of the biomarkers levels in urea and/or blood serum have been developed for AKI risk assessment, diagnosis, monitoring, and treatment. Thus, further research is necessary to investigate different AKI biomarkers and improve experimental models (both in vivo and in vitro), which will support assessment of potential nephrotoxic properties of existing and new medicinal products.

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Parkinsonism and Related Disorders

10.2310/tywc.1178 ◽

2019 ◽

Author(s):

Elizabeth J. Slow ◽

Anthony E. Lang

Keyword(s):

Differential Diagnosis ◽

Parkinson Disease ◽

Lewy Bodies ◽

Corticobasal Degeneration ◽

Normal Pressure ◽

Vascular Parkinsonism ◽

Drug Induced ◽

Clinical Criteria ◽

The Core ◽

Lewy Neurite

Parkinsonism describes the core clinical criteria of tremor, bradykinesia, rigidity, and postural instability. There is a large differential diagnosis, but the most common cause of parkinsonism is due to Parkinson disease. This review details the epidemiology, etiology/genetics, pathogenesis, diagnosis and differential diagnosis, management, and prognosis of Parkinson disease, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, vascular parkinsonism, normal pressure hydrocephalus, and drug-induced parkinsonism. This review contains 8 figures, 32 tables, and 73 references. Keywords: Parkinson disease, parkinsonism, levodopa, cogwheel ridigity, multiple system atrophy, dementia, substantia nigra, palsy, neurodegenerative disease, hydrocephalus, Lewy body, Lewy neurite

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