Ian Musgrave - Academia.edu (original) (raw)

Papers by Ian Musgrave

Clinical and Experimental Pharmacology and Physiology, Aug 1, 1997

SUMMARY1. Protein kinase C (PKC) is an important second messenger‐activated enzyme. In noradrener... more SUMMARY1. Protein kinase C (PKC) is an important second messenger‐activated enzyme. In noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG) to facilitate transmitter release and the steps in this involve activation of phospholipase C, generation of DAG and activation of PKC. It is suggested that the subsequent facilitation of transmitter release is due to the phosphorylation of proteins involved in the release process distal to Ca2+entry, presumably those involved in vesicle dynamics.2. There are differences between central noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to be tonically active and its inhibition results in a decrease in noradrenaline release under most, if not all, conditions.3. In sympathetic nerves PKC inhibitors only decrease transmitter release during high‐frequency stimulation and not during low‐frequency stimulation. At high frequency there is a gradual increase in the effect of PKC inhibitors on transmitter release during the first 15 s of a stimulation train. It is suggested that this is due to a progressive rise in intracellular Ca2+ and a consequent activation of PKC.4. Activation of PKC by phorbol esters produces a large enhancement in action potential‐evoked noradrenaline release in both the central nervous system and in peripheral tissues. The structural requirements of the phorbol esters for maximal effect suggest that the phorbol esters must access the interior of the nerve terminal to activate PKC and the neural membrane acts as a barrier for highly lipophilic phorbol esters, thereby reducing their activity. Activation of PKC represents one of the most powerful ways to enhance transmitter release and may have therapeutic potential.

Annals of the New York Academy of Sciences, Aug 1, 1990

Forensic Science, Medicine and Pathology

Unexpected hepatic failure with liver necrosis is sometimes encountered during a forensic autopsy... more Unexpected hepatic failure with liver necrosis is sometimes encountered during a forensic autopsy. Determining the etiology may sometimes be difficult, although increasingly herbal medicines are being implicated. To determine whether such effects might also be caused by foodstuffs, the following in vitro study was undertaken. Four formulations of traditional herbal soup advertised as bak kut teh were prepared and added to cultures of liver carcinoma cells (HepG2). Cell viability was assessed using an MTT colorimetric assay at 48 h demonstrating that all formulations had significant toxicity prior to dilution (p < 0.05). Formulation #1 showed 21% cell death (p = 0.023), Formulation #2 30% (p = 0.009), and Formulation #3 41% (p < 0.0001). Formulations #1–3 showed no significant toxicity once diluted (p > 0.05). Formulation 4 showed approximately 83% cell death before dilution (p < 0.0001) and persistent toxicity even with dilutions at 1:10 (15% ± 3.7, p = 0.023) and 1:1000...

Forensic Science, Medicine and Pathology, 2018

Mahomet Allum was a flamboyant philanthropist and herbalist who worked in South Australia in the ... more Mahomet Allum was a flamboyant philanthropist and herbalist who worked in South Australia in the early part of last century, whose herbal therapies generated some controversy at the time. Two of his preparations have survived to the present day, a general tonic and a treatment for liver and kidney dysfunction. Given the frequent use of pharmaceutical drugs in "tonics" at the time, toxicological analysis was undertaken at Forensic Science SA, Adelaide with liquid chromatography/quadrupole-time-offlight mass-spectrometer (LC-QTOF MS), liquid-chromatography/ diode array detector (LC/UV) and gas chromatography/ nitrogen phosphorous-detector/mass-spectrometer (GC-NPD/MS), to look for common drugs. In addition DNA analysis was also undertaken at Trace and Environmental DNA (TrEnD) Laboratory (Curtin University) to evaluate the types of plant products used to make these remedies. The general tonic contained genera from the Triticeae (wheat) family as well as the Medicago family (includes alfalfa), possibly as fillers. Other genera found included Utrica (nettle) and Passiflora (passion flower). The preparation for liver and kidney disease also contained genera from the Medicago family as well as genera Arctostaphylos (bear berry) which has traditionally been used for the treatment of dysuria and bladder stones. No common drugs were found. Thus it appears that the two treatments prepared by Mahomet Allum contained only herbal substances and not adulterant pharmaceutical agents. The herbals identified provide an insight into herbalist practices in the early twentieth century.

ChemInform, Sep 12, 2006

This review covers the literature on the subject of biologically active peptides from the glands ... more This review covers the literature on the subject of biologically active peptides from the glands of amphibians. These include neuropeptides, antimicrobial and anticancer active peptides, antiviral agents, fungicides and peptides which complex with Ca 2+ calmodulin. Other topics covered include sex pheromones from amphibians, and the use of peptide profiling to differentiate between species and different populations of the same species. 1 Introduction 2 Antibacterial and anticancer active peptides 2.1 Introduction 2.2 Antibacterial and anticancer active peptides from the genera Litoria, Uperoleia and Crinia 2.2.1 Citropin 1 type antibiotic peptides 2.2.2 Caerin 1 and maculatin 1 peptides 2.2.3 Narrow-spectrum antibiotics 2.3 Antibiotic peptides from the genus Rana 2.4 Antimicrobial peptides from the genera Ascaphus,

Globally, there has been an increase in the use of herbal remedies including traditional Chinese ... more Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines

Cells

Clusterin is a glycoprotein present at high concentrations in many extracellular fluids, includin... more Clusterin is a glycoprotein present at high concentrations in many extracellular fluids, including semen. Its increased expression accompanies disorders associated with extracellular amyloid fibril accumulation such as Alzheimer’s disease. Clusterin is an extracellular molecular chaperone which prevents the misfolding and amorphous and amyloid fibrillar aggregation of a wide variety of unfolding proteins. In semen, amyloid fibrils formed from a 39-amino acid fragment of prostatic acid phosphatase, termed Semen-derived Enhancer of Virus Infection (SEVI), potentiate HIV infectivity. In this study, clusterin potently inhibited the in vitro formation of SEVI fibrils, along with dissociating them. Furthermore, clusterin reduced the toxicity of SEVI to pheochromocytoma-12 cells. In semen, clusterin may play an important role in preventing SEVI amyloid fibril formation, in dissociating SEVI fibrils and in mitigating their enhancement of HIV infection.

Forensic Science, Medicine and Pathology

Pharmacological Research - Modern Chinese Medicine

Herbal traditional Chinese medicines (TCMs) are an increasingly popular alternative therapy globa... more Herbal traditional Chinese medicines (TCMs) are an increasingly popular alternative therapy globally. Due to the complex chemical composition of herbal products, and with research showing that consumers from Western countries are more likely to take multiple herbal products at one time, the lack of understanding of the potential side effects of herbal TCM may pose a significant risk to health and wellbeing. This may be particularly so now that herbal preparations are being promoted for the prevention and treatment of COVID-19 symptoms, often in association with Western medicines such as paracetamol. Of interest are the potential adverse effects of herbal TCMs on the kidney. Many factors can lead to the development of renal injury including intrinsic toxicity, plant misidentification, adulteration, contamination, and of increasing importance, interactions with conventional drugs and other herbs. This review evaluates and summarises some of the key aspects of TCM-induced nephrotoxicity and the current scope of herb-drug and herb-herb interaction that may cause adverse effects.

heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional

Journal of Pharmaceutical and Biomedical Analysis, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Drug and chemical toxicology, 2022

Intestinal epithelial injury from herbal products has rarely been reported, despite the gut being... more Intestinal epithelial injury from herbal products has rarely been reported, despite the gut being the first point of contact for oral preparations. These products often consist of multiple herbs, thereby potentially exposing consumers to higher levels of reactive phytochemicals than predicted due to pharmacokinetic interactions. The phytochemical coumarin, found in many herbal products, may be taken in combination with herbal medicines containing astragalosides and atractylenolides, purported cytochrome P450 (CYP) modulators. As herbal use increases, the need to predict interactions in multiple at-risk organ systems is becoming critical. Hence, to determine whether certain herbal preparations containing coumarin may cause damage to the intestinal epithelium, Caco2 cells were exposed to common phytochemicals. Coumarin, astragaloside IV (AST-IV) or atractylenolide I (ATR-I) solutions were exposed to Caco2 cultures in increasing concentrations, individually or combined. Coumarin produc...

Pharmacology Research & Perspectives, 2021

Forensic Science, Medicine and Pathology, 2021

A recent series of deaths in previously healthy dogs in Victoria, Australia associated with the i... more A recent series of deaths in previously healthy dogs in Victoria, Australia associated with the ingestion of raw meat contaminated by indospicine derived from native Australian plants of the Indigofera species draws attention to the potential that exists for herbal toxicity in domestic animals. Although the efficacy of herbal remedies generally remains unproven in domestic animals, herbal preparations are being increasingly used as supplements and treatments. Issues with incorrect ingredients, inadequate processing, faulty, incomplete or inaccurate product labelling, contamination with toxins, adulteration with undeclared pharmaceutical agents and herb-herb interactions are well recognized as causes of adverse effects in humans. However, apart from of the effects of noxious weed species, the literature on herbal toxicity in domestic animals is sparse. Thus, the forensic evaluation of cases of suspected poisoning in domestic animals should also encompass an accurate description the type and dose of any herbal preparations that may have been recently administered.

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2014

Semen-derived enhancer of viral infection (SEVI) is the term given to the amyloid fibrils formed ... more Semen-derived enhancer of viral infection (SEVI) is the term given to the amyloid fibrils formed by a 39-amino acid fragment (PAP248-286) of prostatic acidic phosphatase (PAP) found in human semen. SEVI enhances human immunodeficiency virus (HIV) infectivity by four to five orders of magnitude (Münch et al., 2007). Here, we show by various biophysical techniques including Thioflavin T fluorescence, circular dichroism spectroscopy and transmission electron microscopy that fragments encompassing the central region of SEVI, i.e. PAP248-271 and PAP257-267, form fibrils of similar morphology to SEVI. Our results show that the central region, residues PAP267-271, is crucially important in promoting SEVI fibril formation. Furthermore, SEVI and fibrillar forms of these peptide fragments are toxic to neuronal pheochromocytoma 12 cells but not to epithelial colon carcinoma cells. These findings imply that although SEVI assists in the attachment of HIV-1 to immune cells, it may not facilitate HIV entry by damaging the epithelial cell layer that presents a barrier to the HIV.

Clinical and Experimental Pharmacology and Physiology, Aug 1, 1997

SUMMARY1. Protein kinase C (PKC) is an important second messenger‐activated enzyme. In noradrener... more SUMMARY1. Protein kinase C (PKC) is an important second messenger‐activated enzyme. In noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG) to facilitate transmitter release and the steps in this involve activation of phospholipase C, generation of DAG and activation of PKC. It is suggested that the subsequent facilitation of transmitter release is due to the phosphorylation of proteins involved in the release process distal to Ca2+entry, presumably those involved in vesicle dynamics.2. There are differences between central noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to be tonically active and its inhibition results in a decrease in noradrenaline release under most, if not all, conditions.3. In sympathetic nerves PKC inhibitors only decrease transmitter release during high‐frequency stimulation and not during low‐frequency stimulation. At high frequency there is a gradual increase in the effect of PKC inhibitors on transmitter release during the first 15 s of a stimulation train. It is suggested that this is due to a progressive rise in intracellular Ca2+ and a consequent activation of PKC.4. Activation of PKC by phorbol esters produces a large enhancement in action potential‐evoked noradrenaline release in both the central nervous system and in peripheral tissues. The structural requirements of the phorbol esters for maximal effect suggest that the phorbol esters must access the interior of the nerve terminal to activate PKC and the neural membrane acts as a barrier for highly lipophilic phorbol esters, thereby reducing their activity. Activation of PKC represents one of the most powerful ways to enhance transmitter release and may have therapeutic potential.

Annals of the New York Academy of Sciences, Aug 1, 1990

Forensic Science, Medicine and Pathology

Unexpected hepatic failure with liver necrosis is sometimes encountered during a forensic autopsy... more Unexpected hepatic failure with liver necrosis is sometimes encountered during a forensic autopsy. Determining the etiology may sometimes be difficult, although increasingly herbal medicines are being implicated. To determine whether such effects might also be caused by foodstuffs, the following in vitro study was undertaken. Four formulations of traditional herbal soup advertised as bak kut teh were prepared and added to cultures of liver carcinoma cells (HepG2). Cell viability was assessed using an MTT colorimetric assay at 48 h demonstrating that all formulations had significant toxicity prior to dilution (p < 0.05). Formulation #1 showed 21% cell death (p = 0.023), Formulation #2 30% (p = 0.009), and Formulation #3 41% (p < 0.0001). Formulations #1–3 showed no significant toxicity once diluted (p > 0.05). Formulation 4 showed approximately 83% cell death before dilution (p < 0.0001) and persistent toxicity even with dilutions at 1:10 (15% ± 3.7, p = 0.023) and 1:1000...

Forensic Science, Medicine and Pathology, 2018

Mahomet Allum was a flamboyant philanthropist and herbalist who worked in South Australia in the ... more Mahomet Allum was a flamboyant philanthropist and herbalist who worked in South Australia in the early part of last century, whose herbal therapies generated some controversy at the time. Two of his preparations have survived to the present day, a general tonic and a treatment for liver and kidney dysfunction. Given the frequent use of pharmaceutical drugs in "tonics" at the time, toxicological analysis was undertaken at Forensic Science SA, Adelaide with liquid chromatography/quadrupole-time-offlight mass-spectrometer (LC-QTOF MS), liquid-chromatography/ diode array detector (LC/UV) and gas chromatography/ nitrogen phosphorous-detector/mass-spectrometer (GC-NPD/MS), to look for common drugs. In addition DNA analysis was also undertaken at Trace and Environmental DNA (TrEnD) Laboratory (Curtin University) to evaluate the types of plant products used to make these remedies. The general tonic contained genera from the Triticeae (wheat) family as well as the Medicago family (includes alfalfa), possibly as fillers. Other genera found included Utrica (nettle) and Passiflora (passion flower). The preparation for liver and kidney disease also contained genera from the Medicago family as well as genera Arctostaphylos (bear berry) which has traditionally been used for the treatment of dysuria and bladder stones. No common drugs were found. Thus it appears that the two treatments prepared by Mahomet Allum contained only herbal substances and not adulterant pharmaceutical agents. The herbals identified provide an insight into herbalist practices in the early twentieth century.

ChemInform, Sep 12, 2006

This review covers the literature on the subject of biologically active peptides from the glands ... more This review covers the literature on the subject of biologically active peptides from the glands of amphibians. These include neuropeptides, antimicrobial and anticancer active peptides, antiviral agents, fungicides and peptides which complex with Ca 2+ calmodulin. Other topics covered include sex pheromones from amphibians, and the use of peptide profiling to differentiate between species and different populations of the same species. 1 Introduction 2 Antibacterial and anticancer active peptides 2.1 Introduction 2.2 Antibacterial and anticancer active peptides from the genera Litoria, Uperoleia and Crinia 2.2.1 Citropin 1 type antibiotic peptides 2.2.2 Caerin 1 and maculatin 1 peptides 2.2.3 Narrow-spectrum antibiotics 2.3 Antibiotic peptides from the genus Rana 2.4 Antimicrobial peptides from the genera Ascaphus,

Globally, there has been an increase in the use of herbal remedies including traditional Chinese ... more Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines

Cells

Clusterin is a glycoprotein present at high concentrations in many extracellular fluids, includin... more Clusterin is a glycoprotein present at high concentrations in many extracellular fluids, including semen. Its increased expression accompanies disorders associated with extracellular amyloid fibril accumulation such as Alzheimer’s disease. Clusterin is an extracellular molecular chaperone which prevents the misfolding and amorphous and amyloid fibrillar aggregation of a wide variety of unfolding proteins. In semen, amyloid fibrils formed from a 39-amino acid fragment of prostatic acid phosphatase, termed Semen-derived Enhancer of Virus Infection (SEVI), potentiate HIV infectivity. In this study, clusterin potently inhibited the in vitro formation of SEVI fibrils, along with dissociating them. Furthermore, clusterin reduced the toxicity of SEVI to pheochromocytoma-12 cells. In semen, clusterin may play an important role in preventing SEVI amyloid fibril formation, in dissociating SEVI fibrils and in mitigating their enhancement of HIV infection.

Forensic Science, Medicine and Pathology

Pharmacological Research - Modern Chinese Medicine

Herbal traditional Chinese medicines (TCMs) are an increasingly popular alternative therapy globa... more Herbal traditional Chinese medicines (TCMs) are an increasingly popular alternative therapy globally. Due to the complex chemical composition of herbal products, and with research showing that consumers from Western countries are more likely to take multiple herbal products at one time, the lack of understanding of the potential side effects of herbal TCM may pose a significant risk to health and wellbeing. This may be particularly so now that herbal preparations are being promoted for the prevention and treatment of COVID-19 symptoms, often in association with Western medicines such as paracetamol. Of interest are the potential adverse effects of herbal TCMs on the kidney. Many factors can lead to the development of renal injury including intrinsic toxicity, plant misidentification, adulteration, contamination, and of increasing importance, interactions with conventional drugs and other herbs. This review evaluates and summarises some of the key aspects of TCM-induced nephrotoxicity and the current scope of herb-drug and herb-herb interaction that may cause adverse effects.

heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional

Journal of Pharmaceutical and Biomedical Analysis, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Drug and chemical toxicology, 2022

Intestinal epithelial injury from herbal products has rarely been reported, despite the gut being... more Intestinal epithelial injury from herbal products has rarely been reported, despite the gut being the first point of contact for oral preparations. These products often consist of multiple herbs, thereby potentially exposing consumers to higher levels of reactive phytochemicals than predicted due to pharmacokinetic interactions. The phytochemical coumarin, found in many herbal products, may be taken in combination with herbal medicines containing astragalosides and atractylenolides, purported cytochrome P450 (CYP) modulators. As herbal use increases, the need to predict interactions in multiple at-risk organ systems is becoming critical. Hence, to determine whether certain herbal preparations containing coumarin may cause damage to the intestinal epithelium, Caco2 cells were exposed to common phytochemicals. Coumarin, astragaloside IV (AST-IV) or atractylenolide I (ATR-I) solutions were exposed to Caco2 cultures in increasing concentrations, individually or combined. Coumarin produc...

Pharmacology Research & Perspectives, 2021

Forensic Science, Medicine and Pathology, 2021

A recent series of deaths in previously healthy dogs in Victoria, Australia associated with the i... more A recent series of deaths in previously healthy dogs in Victoria, Australia associated with the ingestion of raw meat contaminated by indospicine derived from native Australian plants of the Indigofera species draws attention to the potential that exists for herbal toxicity in domestic animals. Although the efficacy of herbal remedies generally remains unproven in domestic animals, herbal preparations are being increasingly used as supplements and treatments. Issues with incorrect ingredients, inadequate processing, faulty, incomplete or inaccurate product labelling, contamination with toxins, adulteration with undeclared pharmaceutical agents and herb-herb interactions are well recognized as causes of adverse effects in humans. However, apart from of the effects of noxious weed species, the literature on herbal toxicity in domestic animals is sparse. Thus, the forensic evaluation of cases of suspected poisoning in domestic animals should also encompass an accurate description the type and dose of any herbal preparations that may have been recently administered.

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2014

Semen-derived enhancer of viral infection (SEVI) is the term given to the amyloid fibrils formed ... more Semen-derived enhancer of viral infection (SEVI) is the term given to the amyloid fibrils formed by a 39-amino acid fragment (PAP248-286) of prostatic acidic phosphatase (PAP) found in human semen. SEVI enhances human immunodeficiency virus (HIV) infectivity by four to five orders of magnitude (Münch et al., 2007). Here, we show by various biophysical techniques including Thioflavin T fluorescence, circular dichroism spectroscopy and transmission electron microscopy that fragments encompassing the central region of SEVI, i.e. PAP248-271 and PAP257-267, form fibrils of similar morphology to SEVI. Our results show that the central region, residues PAP267-271, is crucially important in promoting SEVI fibril formation. Furthermore, SEVI and fibrillar forms of these peptide fragments are toxic to neuronal pheochromocytoma 12 cells but not to epithelial colon carcinoma cells. These findings imply that although SEVI assists in the attachment of HIV-1 to immune cells, it may not facilitate HIV entry by damaging the epithelial cell layer that presents a barrier to the HIV.