Michael Coleman

Michael Coleman
Aston University · School of Life and Health Sciences

Ph.D., D.Sc.,

About

181
Publications
27,402
Reads
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2,872
Citations
Additional affiliations
September 1991 - present
Aston University
Position
  • Professor (Full)
Description
  • Hotel California (you can check out any time, but you can never leave)
September 1988 - September 1991
University of Liverpool
Position
  • Wellcome Fellow in Toxicology
Description
  • Got 6 months worth of soft money and then applied for the Fellowship (submission of grant) as well as an interview, in which I wore red shoes and was successful.
July 1986 - August 1988
Walter Reed Army Institute of Research
Position
  • Resident Research Associate
Description
  • I worked at the Silver Spring Annex, which was actually a condemned building, but it was on a road linked up to I-95 so we saw a couple of cool Police pursuits...
Education
October 1986 - July 2004
Aston University
Field of study
  • Biochemical Pharmacology of Antiparasitic Agents
October 1982 - April 1985
University of Liverpool
Field of study
  • Biochemical Pharmacology
October 1979 - July 1982
University of Liverpool
Field of study
  • Pharmacology

Publications

Publications (181)
Article
Full-text available
Brain inflammation generally accelerates neurodegeneration. Alzheimer’s disease (AD) triggers an innate immune response by activating a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Our study investigated patients with leprosy and AD. They were treated with dapsone (4,4’-diaminodipheny...
Preprint
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated inflammasome diseases. Moreover, its pathophysiology involves the angiotensin-converting enzyme 2 (ACE2) receptor, Toll-like receptor 4 (TLR4) pathway, neuropilin‑1 pathway, inflammasome activation pathway, sterile alpha motif (SAM) and histidine-aspartate domain (...
Preprint
Full-text available
This study investigated leprosy patients with Alzheimer's disease (AD) treated with dapsone (4,4’-diaminodiphenyl sulfone, DDS) as a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and neuroinflammasome competitor. We searched the Sorokdo National Hospital medical records and the National...
Preprint
Full-text available
Background: Dapsone is helpful in the molecular regulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3). Objective: To study the targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by Dapsone should be responsible for its observed preventive treatment effects, functioning as a competitor against Pandemic v...
Preprint
Background: Dapsone is helpful in the molecular regulation of inflammasome activation, ubiquitin, one/two-electron oxidation, ubiquitination cascade, and myeloperoxidase/halide system. Objective: To study whether lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response by dapsone are responsible for it...
Article
Full-text available
To reflect human development, it is critical to create a substrate that can support long-term cell survival, differentiation, and maturation. Hydrogels are promising materials for 3D cultures. However, a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell in...
Chapter
The need for human cell-based experimental platforms for the study of the brain’s most basic activity and function has never been greater. Initial progress was made through differentiation of the NT2.D1 platform, which facilitated the study of postmitotic but generic neuronal/astrocytic interactions both electrophysiologically and pharmacologically...
Article
Full-text available
We are being confronted with the most consequential pandemic since the Spanish flu of 1918‑1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS‑CoV2 structure and functions, immune responses and known tre...
Article
Full-text available
We are being confronted with the most consequen-tial pandemic since the Spanish flu of 1918-1920 to the extent that never before have 4 billion people quarantined simultaneously ; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS-CoV2 structure and functions, immune responses and known t...
Article
To change the physicochemical structure and properties of lipophilic molecules they must be conveyed somehow through a medium that is utterly hostile to them, i.e. a water‐based bloodstream, to a place where the biochemical systems of metabolism can physically attack and change the structure of these molecules. Cytochrome P450 (CYP) monooxygenase s...
Article
Glucuronidation is the largest capacity conjugative clearance system in humans and is accomplished by a set of enzymes known as uridine diphosphate glucuronosyl transferases (UGTs). UGTs use an activated glucose derivative (UDPGA) as a co‐factor to convert a huge number of chemicals to beta‐D‐glucopyranosiduronic acids, or glucuronides, by a nucleo...
Article
Drugs are tested at the preclinical stage in animal populations that are usually inbred and display little variation from animal to animal. Data from animal studies in one country are usually comparable with that of another, provided the animal species and strain are the same. This chapter discusses some of the major factors related to patient gene...
Article
It is important to see the role of metabolism in drug toxicity as one component of the bigger picture of all adverse reactions suffered by patients during drug therapy. Drug‐adverse effects are classified as either predictable (type A) or unpredictable (type B). Type A predictable effects can be reversible concerning pharmacological effects, but th...
Article
As many of the ‘threat chemicals’ so closely resemble endogenous signal molecules, it is entirely logical that the biotransforming enzyme systems such as the Cytochrome P450 (CYP) would evolve to dismantle these threat molecules as well as build and dismantle endogenous ones. It has long been known in folk medicine that many plants have hormone‐lik...
Chapter
This chapter discusses cytochrome P450 systems and presents some case studies with analysis for drug metabolism. To enter the circulation from an oral dose, the drugs must pass through the gut, the portal circulation and then into the liver itself. Since the liver's blood flow is not likely to undergo a sustained increase, then the only way such a...
Chapter
In contrast to enzyme induction, drug inhibition does not at first sight,seem to be a process where a logical adaptive response can be made by the patient's metabolism. Biotransforming systems can, to a limited degree, compensate for the sustained loss of a Cytochrome P450 (CYP), either through inhibition or polymorphism. CYPs are enzymes like any...
Article
Full-text available
The world biodiesel production is increasing at a rapid rate. Despite its perceived safety for the environment, more detailed toxicity studies are mandatory, especially in the field of aquatic toxicology. While considerable attention has been paid to biodiesel combustion emissions, the toxicity of biodiesel in the aquatic environment has been poorl...
Article
Full-text available
Abstract Microporous membranes support the growth of neurites into and through micro-channels, providing a different type of neural growth platform to conventional dish cultures. Microporous membranes are used to support various types of culture, however, the role of pore diameter in relation to neurite growth through the membrane has not been well...
Article
Full-text available
The brain is the most complex organ in the body, controlling our highest functions, as well as regulating myriad processes which incorporate the entire physiological system. The effects of prospective therapeutic entities on the brain and central nervous system (CNS) may potentially cause significant injury, hence, CNS toxicity testing forms part o...
Article
Full-text available
Periodontal disease, periodontitis as well as the preceding gingivitis, has been associated with both obesity and diabetes. Studies have shown that diet changes can lead to a lower incidence of such inflammation. The aim of the present case series over four weeks was to study the effects on medical and dental conditions in patients with type 2 diab...
Article
The present study aimed to elucidate the photosynthetic performance, antioxidant enzyme activities, anthocyanin contents, anthocyanin biosynthetic gene expression, and vanadium uptake in mustard genotypes (purple and green) that differ in photosynthetic capacity under vanadium stress. The results indicated that vanadium significantly reduced photos...
Article
The present study aimed to elucidate the photosynthetic performance, antioxidant enzyme activities, anthocyanin contents, anthocyanin biosynthetic gene expression, and vanadium uptake in mustard genotypes (purple and green) that differ in photosynthetic capacity under vanadium stress. The results indicated that vanadium significantly reduced photos...
Article
Full-text available
Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinal...
Article
Modern agriculture provides the potential for sustainable feeding of the world's increasing population. Up to the present moment, genetically modified (GM) products have enabled increased yields and reduced pesticide usage. Nevertheless, GM products are controversial amongst policy makers, scientists and the consumers, regarding their possible envi...
Article
Full-text available
Another important hormone is 17β-estradiol (E2), which, in addition to its multiple actions throughout the body and brain, exerts neuroprotective effects in both acute and chronic neurodegenerative diseases such as cerebral ischemia, traumatic brain injury, AD, and PD. R. Thakkar and colleagues investigated whether 17β-estradiol (E2), acting via th...
Chapter
Pressure from our aging population's vulnerability to neurodegenerative disease necessitates the development of experimental platforms to research brain pathology and new drug design, as well as the detection of toxic impact on both the adult and developing CNS. Although exciting human stem cell models are under development, the NT2.D1 teratocarcin...
Article
Aim: A causative relationship between acute coronary syndrome (ACS) and periodontitis has yet to be defined. The aim of this study was to assess differences in levels of serum cytokines between individuals with or without ACS or periodontal comorbidity. Material and methods: In a case-control study, individuals with ACS (78 individuals, 10.3% fe...
Article
Astrocytes are now increasingly acknowledged as having fundamental and sophisticated roles in brain function and dysfunction. Unravelling the complex mechanisms that underlie human brain astrocyte-neuron interactions is therefore an essential step on the way to understanding how the brain operates. Insights into astrocyte function to date, have alm...
Article
Full-text available
Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDSNHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mech...
Article
Full-text available
Bioactive molecules in berries may be helpful in reducing the risk of oral diseases. The aim of this study was to determine the effect of bilberry consumption on the outcome of a routine dental clinical parameter of inflammation, bleeding on probing (BOP), as well as the impact on selected biomarkers of inflammation, such as cytokines, in gingival...
Article
Alzheimer's disease (AD) is the most common form of dementia, affecting more than 35 million people worldwide. Brain hypometabolism is a major feature of AD, appearing decades before cognitive decline and pathologic lesions. To date, the majority of studies on hypometabolism in AD have used transgenic animal models or imaging studies of the human b...
Article
The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary...
Article
Mixtures of pesticides in foodstuffs and the environment are ubiquitous in the developed world, and although agents are usually exhaustively tested individually, the toxicological implications of pesticide mixtures are underreported. In this study, the effects of two fungicides, fenhexamid and myclobutanil were investigated individually and in comb...
Chapter
Aromatic amines are responsible for bladder cancer in smokers as well as in neoplasms of occupational origin. If individuals are suffering from bladder cancer and wish to claim injury benefits, the onus is on them to provide evidence that they were exposed to the prescribed aromatic amines which were, of course, banned decades previously. It is not...
Chapter
This chapter describes case histories where toxins have caused acute, as well as chronic acute effects on worker's health. The scale and variety of solvent usage are outlined, followed by their particular properties which promote their toxic effects, as well as the difficulties encountered in discerning the long-term impact of these chemicals on an...
Chapter
As mining became more industrialised in the Middle Ages, many debilitating conditions emerged, not least vibration ‘white finger’ and noise-related deafness, which were linked with cutting and boring machinery, as well as toxicity associated with the fumes of explosives and more recently, underground vehicles. Bernadino Ramazzini's work anticipated...
Chapter
It is important to investigate and curtail the sale of goods imported from developing countries which are unsafe, as they might injure or cause toxicity to consumers in the developed world. Concerns are raised by complaints from the public are investigated by Local Council Trading Standards Officers. The Officers may go as far as to institute court...
Article
Full-text available
This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For th...
Article
Summary — Recent changes to the legislation on chemicals and cosmetics testing call for a change in the paradigm regarding the current ‘whole animal’ approach for identifying chemical hazards, including the assessment of potential neurotoxins. Accordingly, since 2004, we have worked on the development of the integrated co-culture of post-mitotic, h...
Article
The NT2.D1 cell line is one of the most well-documented embryocarcinoma cell lines, and can be differentiated into neurons and astrocytes. Great focus has also been placed on defining the electrophysiological properties of the neuronal cells, and more recently we have investigated the functional properties of their associated astrocytes. We now sho...
Article
Full-text available
Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pha...
Data
Full list of genes differentially regulate by 1 mM LiCl in comparison to the RA treated control. Expression changes with a p-value <0.05 were considered significantly modulated (n = 3). (DOC)
Data
Full list of genes differentially regulate by 0.5 mM VPA in comparison to the RA treated control. Expression changes with a p-value <0.05 were considered significantly modulated (n = 3). (DOC)
Article
Full-text available
Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and n...
Article
Full-text available
Rose hips are popular in health promoting products as the fruits contain high content of bioactive compounds. The aim of this study was to investigate whether health benefits are attributable to ascorbic acid, phenols, or other rose-hip-derived compounds. Freeze-dried powder of rose hips was preextracted with metaphosphoric acid and the sample was...
Article
Full-text available
A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrop...
Article
Full-text available
Berries contain several bioactive compounds that can protect against oxidative stress. In this study we evaluated the protective effect of different sequential extracts (ethyl acetate, ethanol and water) of seven berry species: bilberry (Vaccinium myrtillus), blackcurrant (Ribes nigrum), elderberry (Sambucus nigra), lingonberry (Vaccinium vitis-ida...
Chapter
With growing regulatory emphasis on the evaluation of increasing numbers of possible neurotoxins in the environment, as well as for novel therapeutic agent testing, the need for relevant, high-throughput and human-based in vitro neurotoxicity assays has never been greater. Although current in vitro human neurotoxicity models, such as neuroblastoma...
Article
The timeline imposed by recent worldwide chemical legislation is not amenable to conventional in vivo toxicity testing, requiring the development of rapid, economical in vitro screening strategies which have acceptable predictive capacities. When acquiring regulatory neurotoxicity data, distinction on whether a toxic agent affects neurons and/or as...
Article
The in-vitro toxicities of sulphametrole and sulphamethoxazole have been compared in three in-vitro tests which involve a rat microsomal metabolite-generating system coupled to either a human mononuclear leucocyte toxicity assay, or a single and two-compartment methaemoglobin-generating assay.Mononuclear leucocyte cell death in the presence of sulp...
Article
N-hydroxylation of dapsone leads to the formation of the toxic hydroxylamines responsible for the clinical methaemoglobinaemia associated with dapsone therapy. Dapsone has been associated with decreased lifespan of erythrocytes, with consequences such as anaemia and morbidity in patients treated with dapsone for malaria. Here, we investigated how d...
Book
Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences. Completely revised and updated throughout, the new edition focuses only on essential chemical detail and includes patient case histories to i...
Chapter
Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences. Completely revised and updated throughout, the new edition focuses only on essential chemical detail and includes patient case histories to i...
Chapter
Therapeutic windowConsequences of drug concentration changesClearanceHepatic extraction and intrinsic clearanceFirst pass and plasma drug levelsDrug and xenobiotic metabolism
Chapter
IntroductionCapture of lipophilic moleculesCytochrome P450s classification and basic structureCYPs – main and associated structuresHuman CYP families and their regulationMain human CYP familiesCytochrome P450 catalytic cycleFlavin monooxygenases (FMOs)How CYP isoforms operate in vivoAromatic ring hydroxylationAlkyl oxidations‘Rearrangement’ reactio...
Chapter
IntroductionCauses of accelerated clearanceEnzyme inductionMechanisms of enzyme inductionInduction – general clinical aspects
Chapter
IntroductionGlucuronidationSulphonationThe GSH systemGlutathione S-transferasesEpoxide hydrolasesAcetylationMethylationEsterases/amidasesAmino acid conjugation (glycine or glutamate)Phase III transport processesBiotransformation-integration of processes
Chapter
IntroductionOpiatesCocaineHallucinogensAmphetaminesCannabisDissociative anaesthetics
Article
Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and inte...
Article
Three human astroglioma lines U251-MG, U373-MG and CCF-STTG1 have been evaluated further as possible models for astrocytotoxicity (GFAP and IL-6 release). The effects of bacterial lipopolysaccharide, chloroquine diphosphate and acrylamide were studied on GFAP expression and LPS, chloroquine diphosphate, ethanol, trimethyltin chloride (TMTC) and acr...
Article
Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyu...
Article
Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to...
Article
The effects of the alpha-diketone derivatives 2,3- and 3,4-hexanediones were investigated in three non-neuronal cell lines (MCF7, HepG(2) and CaCo-2) as well as in the neuroblastoma line, SH-SY5Y. The MTT reduction assay was employed to determine the necrotic effects of the alpha-diketones and the neurotoxin 2,5-hexanedione over 4, 24 and 48 hr exp...
Article
Recent developments within the National Health Service have led to an increase in personnel ‘qualified’ to prescribe a wide range of pharmacological agents. A short (38-day) Continuing Professional Development course in prescribing is deemed adequate to fully train individuals for practice. A sound understanding of prescribing medicines has importa...
Article
The astrogliotic responses of the CCF-STTG1, U251-MG, and U373-MG human astrocytoma lines were determined after exposure to ethanol, trimethyltin chloride (TMTC), and acrylamide over 4, 16, and 24h. Basal glial fibrillary acidic protein (GFAP) expression in the U-251MG and U373-MG cells was 10-fold greater than the CCF-STGG1 line. Ethanol treatment...
Article
Astrocytes are essential for neuronal function and survival, so both cell types were included in a human neurotoxicity test-system to assess the protective effects of astrocytes on neurons, compared with a culture of neurons alone. The human NT2.D1 cell line was differentiated to form either a co-culture of post-mitotic NT2.N neuronal (TUJ1, NF68 a...