Cobus Gerber

The Effect of Sampling Methods on the Apparent Constituents of Ink from the Squid Sepioteuthis australis

Publisher: Springer Science and Business Media LLC

Date: 07-10-2010

DOI: 10.1007/S10886-010-9869-0

Abstract: Results of experiments conducted on ink recovered from the squid Sepioteuthis australis indicate that there is no epinephrine or protein naturally present in the ink as it would be ejected in vivo. Protein content was effectively zero when ink was syringed from the duct end of the ink sac of freshly killed animals. By contrast, there were proteins in s les collected from dead specimens where ink was collected by a stripping method. From these s les, a single large molecular weight protein was identified as having tyrosinase activity. Digestion of syringed ink did not yield signs of melanin-bound proteins. Analysis of supernatants after centrifugation of squid ink consistently revealed the presence of DOPA, dopamine, and taurine, whereas epinephrine and nor-epinephrine were recorded from what was believed to be contaminated ink. Histological investigations of the ink sac revealed a compartmentalised glandular structure distal to the duct end. Closer observation of the glandular tissue showed that compartments increased in size as they matured and moved further into the lumen. It was concluded that the presence of epinephrine and tyrosinase (or a related protein) in the ink of S. australis could be attributed to rupturing of basal glandular compartments or contamination from other sources during the extraction process.

Qualitative and quantitative temporal analysis of licit and illicit drugs in wastewater in Australia using liquid chromatography coupled to mass spectrometry

Publisher: Springer Science and Business Media LLC

Date: 06-12-2018

DOI: 10.1007/S00216-017-0747-2

Abstract: The combination of qualitative and quantitative bimonthly analysis of pharmaceuticals and illicit drugs using liquid chromatography coupled to mass spectrometry is presented. A liquid chromatography-quadrupole time of flight instrument equipped with Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) was used to qualitatively screen 346 compounds in influent wastewater from two wastewater treatment plants in South Australia over a 14-month period. A total of 100 compounds were confirmed and/or detected using this strategy, with 61 confirmed in all s les including antidepressants (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine), illicit drugs (cocaine, meth hetamine, hetamine, 3,4-methylenedioxymeth hetamine (MDMA)), and known drug adulterants (lidocaine and tetramisole). A subset of these compounds was also included in a quantitative method, analyzed on a liquid chromatography-triple quadrupole mass spectrometer. The use of illicit stimulants (meth hetamine) showed a clear decrease, levels of opioid analgesics (morphine and methadone) remained relatively stable, while the use of new psychoactive substances (methylenedioxypyrovalerone (MDPV) and Alpha PVP) varied with no visible trend. This work demonstrates the value that high-frequency s ling combined with quantitative and qualitative analysis can deliver. Graphical abstract Temporal analysis of licit and illicit drugs in South Australia.

Pharmacokinetics of fexofenadine following LPS administration to rats

Publisher: Informa UK Limited

Date: 23-09-2010

DOI: 10.3109/00498254.2010.506929

Abstract: The function and expression of drug transporters, including P-glycoprotein (P-gp) and organic-anion transporting polypeptides (Oatps), have been investigated but it is not well established how variables such as disease processes affect them. Fexofenadine is a substrate of these transporters and it was previously shown that its clearance is reduced in the rat isolated perfused liver following treatment with E.coli lipopolysaccharide (LPS). However, whether this translates to altered fexofenadine pharmacokinetics in vivo is yet to be established. E.coli LPS at 5 mg/kg or sterile saline (control) was injected intraperitoneally in rats. Oral or intravenous (IV) fexofenadine (10 mg/kg) was administered 24 h later and plasma and urine s les collected for pharmacokinetic analysis. LPS treatment did not significantly change the pharmacokinetics of IV fexofenadine, although there was a good correlation between weight loss and clearance suggesting reduced clearance in more severely affected animals. However, AUC(0-∞) of oral fexofenadine was a significantly higher in LPS-treated animals (13.9 ± 9.76 min · µg/ml) compared to controls (5.53 ± 1.12 min · µg/ml). In conclusion, LPS treatment increased the bioavailability of fexofenadine but did not affect other pharmacokinetic parameters. This is consistent with a reduction in hepatic Oatp and/or P-gp for a high extraction ratio drug such as fexofenadine.

Investigating the appearance of new psychoactive substances in South Australia using wastewater and forensic data

Publisher: Wiley

Date: 12-09-2019

DOI: 10.1002/DTA.2484

Abstract: New psychoactive substances (NPS) have increased in use and popularity worldwide. Wastewater analysis has been successfully applied to evaluate illicit drugs use within a population. However, for NPS, such an approach may be limited due to low doses of NPS combined with their ever-changing composition and usage. The dynamic nature of the NPS market means use may be opportunistic, infrequent, and with few users. Hence, the use of complementary information sources is recommended to improve the knowledge on NPS consumption. The aim of this study was to investigate the changing landscape of NPS use on a community scale by combining wastewater analysis and forensic toxicology. Forensic analysis provided specific information on NPS prevalence in post-mortem blood s les in Adelaide, South Australia over five years, while wastewater analysis showed community use over the same period. A qualitative liquid chromatography--high resolution mass spectrometry method was initially used to screen the wastewater s les. A total of 24 NPS were found: 6 in wastewater only, 13 in forensic post-mortem toxicology s les only, and 5 in both. As these results showed the presence of NPS, a targeted method was subsequently employed to quantify levels of these NPS in wastewater. Temporal trends were found in wastewater with distinct tendencies for synthetic cathinones visible over the period studied.

Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder

Publisher: Springer Science and Business Media LLC

Date: 04-11-2013

DOI: 10.1186/2040-2392-4-42

Abstract: A recent report indicated that numbers of Sutterella spp. are elevated in gastrointestinal biopsies taken from children with autism spectrum disorder (ASD). We have recently reported changes in the numbers of some bacteria within the stool of ASD children, and now examine whether numbers of Sutterella spp. and some other mucosa-associated bacteria linked with gastrointestinal disease ( Ruminococcus gnavus and Ruminococcus torques ) are also altered in the stool of these children. We show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder. We show further evidence of changes in the gut microbiota of children with ASD and confirm that the abundance of Sutterella spp. is altered in stool.

A new LC-MS/MS bioanalytical method for atenolol in human plasma and milk

Publisher: Future Science Ltd

Date: 04-2017

DOI: 10.4155/BIO-2016-0304

Abstract: Aim: A new sensitive LC–MS/MS method for the quantification of atenolol in human plasma and milk has been developed for clinical lactation studies. Methods & results: Atenolol and the internal standard, phenazone, were extracted from biological matrices by protein precipitation. A Phenomenex ® C-18 column and gradient chromatographic conditions were used for separation of the analyte, followed by detection with MS. Stability of s les was confirmed for atenolol in human plasma and milk for up to 3 months. Linearity range of 1–800 ng/ml (r 2 = 0.9995), the precision within 15% CV and the recovery of the analyte (80–100% range) were achieved. Conclusion: A new validated analytical method for atenolol in plasma and milk was developed.

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1016/J.DRUGALCDEP.2018.02.030

Abstract: The societal impact of drug use is well known. An ex le is when drug-intoxicated drivers increase the burden on policing and healthcare services. This work presents the correlation of wastewater analysis (using UHPLC-MS/MS) and positive roadside drug testing results for meth hetamine, 3,4-methylenedioxymeth hetamine (MDMA) and cannabis from December 2011-December 2016 in South Australia. Meth hetamine and MDMA showed similar trends between the data sources with matching increases and decreases, respectively. Cannabis was relatively steady based on wastewater analysis, but the roadside drug testing data started to erge in the final part of the measurement period. The ability to triangulate data as shown here validates both wastewater analysis and roadside drug testing. This suggests that changes in overall population drug use revealed by WWA is consistent and proportional with changes in drug-driving behaviours. The results show that, at higher levels of drug use as measured by wastewater analysis, there is an increase in drug driving in the community and therefore more strain on health services and police.

Occurrence of illicit drugs in water and wastewater and their removal during wastewater treatment

Publisher: Elsevier BV

Date: 11-2017

DOI: 10.1016/J.WATRES.2017.07.068

Abstract: This review critically evaluates the types and concentrations of key illicit drugs (cocaine, hetamines, cannabinoids, opioids and their metabolites) found in wastewater, surface water and drinking water sources worldwide and what is known on the effectiveness of wastewater treatment in removing such compounds. It is also important to amass information on the trends in specific drug use as well as the sources of such compounds that enter the environment and we review current international knowledge on this. There are regional differences in the types and quantities of illicit drug consumption and this is reflected in the quantities detected in water. Generally, the levels of illicit drugs in wastewater effluents are lower than in raw influent, indicating that the majority of compounds can be at least partially removed by conventional treatment processes such as activated sludge or trickling filters. However, the literature also indicates that it is too simplistic to assume non-detection equates to drug removal and/or mitigation of associated risks, as there is evidence that some compounds may avoid detection via inadequate s ling and/or analysis protocols, or through conversion to transformation products. Partitioning of drugs from the water to the solids fraction (sludge/biosolids) may also simply shift the potential risk burden to a different environmental compartment and the review found no information on drug stability and persistence in biosolids. Generally speaking, activated sludge-type processes appear to offer better removal efficacy across a range of substances, but the lack of detail in many studies makes it difficult to comment on the most effective process configurations and operations. There is also a paucity of information on the removal effectiveness of alternative treatment processes. Research is also required on natural removal processes in both water and sediments that may over time facilitate further removal of these compounds in receiving environments.

Artificial Cell Encapsulation for Biomaterials and Tissue Bio-Nanoengineering: History, Achievements, Limitations, and Future Work for Potential Clinical Applications and Transplantation

Publisher: MDPI AG

Date: 30-11-2021

DOI: 10.3390/JFB12040068

Abstract: Pancreatic β-cell loss and failure with subsequent deficiency of insulin production is the hallmark of type 1 diabetes (T1D) and late-stage type 2 diabetes (T2D). Despite the availability of parental insulin, serious complications of both types are profound and endemic. One approach to therapy and a potential cure is the immunoisolation of β cells via artificial cell microencapsulation (ACM), with ongoing promising results in human and animal studies that do not depend on immunosuppressive regimens. However, significant challenges remain in the formulation and delivery platforms and potential immunogenicity issues. Additionally, the level of impact on key metabolic and disease biomarkers and long-term benefits from human and animal studies stemming from the encapsulation and delivery of these cells is a subject of continuing debate. The purpose of this review is to summarise key advances in this field of islet transplantation using ACM and to explore future strategies, limitations, and hurdles as well as upcoming developments utilising bioengineering and current clinical trials.

Estimation of atenolol transfer into milk and infant exposure during its use in lactating women

Publisher: SAGE Publications

Date: 05-06-2018

DOI: 10.1177/0890334418771308

Abstract: Atenolol lactation information is limited, and controversy exists over the safety of its use during breastfeeding. In this study, important parameters including milk-to-plasma ratio, ratio of infant plasma to maternal plasma, infant daily dosage, and relative infant dose were investigated. The findings from this study add information to existing data about atenolol transfer in human milk. This may help guide health professionals in decision making regarding the safety of beta blockers used by mothers during breastfeeding. The aims of the study were to quantify concentrations of atenolol in human plasma and milk, to evaluate atenolol pharmacokinetics in lactating women, and to investigate subsequent infant exposure to atenolol via mother’s milk. In this prospective, longitudinal observational study, participants were lactating mothers ( N = 3), 1 to 4 months postpartum, who had been taking atenolol for therapeutic reasons, and one 4-month-old breastfed infant. Eight milk s les were collected over 24 hr at different time points, together with a single blood s le from each lactating mother and the infant, and quantified using a new sensitive liquid chromatography mass spectrometry method developed for this study. Peak milk concentrations of atenolol were observed in the women at 4 hr (T max ) after oral administration. The dose-normalized maximum concentrations (C max ) of all patients were similar. The mean milk-to-plasma ratio of the patients who were taking 25 to 100 mg of atenolol was 8.57%. In the mother–infant pair study, the ratio (%) of infant plasma drug concentration to maternal plasma drug concentration observed (18.87%) was similar to the relative infant dose estimated (18.20%). The relative infant dose values (13.96%-18.20%) for all patients were within 10% to 25% of maternal dosage. Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred.

Changes in alcohol consumption associated with social distancing and self‐isolation policies triggered by COVID‐19 in South Australia: a wastewater analysis study

Publisher: Wiley

Date: 10-2020

DOI: 10.1111/ADD.15256

Abstract: To assess the effects of social distancing and social isolation policies triggered by COVID‐19 on alcohol consumption using wastewater analysis in Adelaide, South Australia. Longitudinal quantitative analysis of influent wastewater data for alcohol concentration. Adelaide, South Australia. Wastewater catchment area representative of 1.1 million inhabitants. Twenty‐four hour composite influent wastewater s les were collected from four wastewater treatment plants in Adelaide, South Australia for 7 consecutive days (Wednesday–Tuesday) every 2 months from April 2016–April 2020. The alcohol metabolite ethyl sulfate was measured in s les using chromatography–tandem mass spectrometry. Data were population‐weighted adjusted with consumption expressed as standard drinks/day/1000 people. Weekly consumption and weekend to mid‐week consumption ratios were analysed to identify changes in weekday alcohol use pattern. Estimated weekend alcohol consumption was significantly lower (698 standard drinks/day/1000 people) after self‐isolation measures were enforced in April 2020 compared with the preceding s ling period in February 2020 (1047 standard drinks/day/1000 people), P 0.05. Weekend to midweek consumption ratio was 12% lower than the average ratio compared with all previous s ling periods. April 2020 recorded the lowest alcohol consumption relative to April in previous years, dating back to 2016. Wastewater analysis suggests that introduction of social distancing and isolation policies triggered by COVID‐19 in Adelaide, South Australia, was associated with a decrease in population‐level weekend alcohol consumption.

A wastewater‐based assessment of the impact of a minimum unit price (MUP) on population alcohol consumption in the Northern Territory, Australia

Publisher: Wiley

Date: 20-07-2021

DOI: 10.1111/ADD.15631

Abstract: To test if there was a reduction in alcohol consumption in wastewater s les in the Northern Territory of Australia after the implementation of a minimum unit alcohol price policy (MUP) in October 2018. Between August 2016 and February 2020, wastewater s les were collected across 66 sites in the Northern Territory and all other states and territories in Australia. S les were collected every 2 months in capital cities and every 4 months in regional places during this period. Overall, 4917 s les were taken (2816 before MUP and 2101 after). The number of standard drinks per 1000 people per day in the respective catchment areas was estimated based on the concentration of an alcohol‐specific metabolite, ethyl sulphate in the s les (using the excretion factor of ethyl sulphate, the flow of wastewater entering the wastewater treatment plants and the population of each wastewater catchment). Results from a linear mixed model showed that there was a large drop in alcohol consumption immediately after the MUP in Northern Territory [estimated drop = 1231, 99% confidence interval (CI) = 830, 1633 38.75%]. There was no significant drop in all other states/territories except for Queensland, which showed a significant but much smaller drop (estimated drop: 310 99% CI = 114, 550). One year after the MUP, the drop narrowed to 520 (99% CI = 189, 851) and was no longer statistically significant in February 2020 (15 months after MUP estimated drop = 283, 99% CI = −114, 681). Per‐capita consumption of alcohol appears to have decreased substantially in the Northern Territory of Australia immediately after the implementation of a minimum unit price but consumption steadily recovered and almost returned to the pre‐MUP consumption level after 15 months.

A review of candidate urinary biomarkers for autism spectrum disorder

Publisher: Informa UK Limited

Date: 25-10-2020

DOI: 10.3109/1354750X.2011.598564

Disposition of isosteviol in the rat isolated perfused liver

Publisher: Wiley

Date: 16-04-2010

DOI: 10.1111/J.1440-1681.2010.05359.X

Abstract: 1. The aim of the present study was to investigate the mechanisms involved in the clearance of isosteviol using the rat isolated perfused liver. 2. Six livers from male Sprague‐Dawley rats were perfused with 15.7 μmol isosteviol in a recirculating system. Perfusate and bile s les were collected for 60 min and the liver was collected at the end of the perfusion. All s les collected were incubated with α‐glucuronidase. Isosteviol–glucuronide was determined as equivalent isosteviol. Isosteviol concentrations were determined using a previously developed liquid chromatography–tandem mass spectrometry method. The final isosteviol liver erfusate (L/P), bile/liver (B/L) and isosteviol‐glucuronide in bile/liver (B G /L G ) ratios were determined. 3. Isosteviol has a high clearance (21.4 ± 4.8 mL/min) from the perfusate, with a short half‐life (13 ± 4 min). α‐Glucuronidase incubation revealed that isosteviol is conjugated in the liver and excreted into the bile. There was no isosteviol‐glucuronide detected in perfusate s les. The total recovery of the rat isolated perfused liver system is 74 ± 14% and glucuronidated isosteviol accounted for 23 ± 4% of the administered dose. 4. In conclusion, we are the first to characterize the metabolism of isosteviol using rat isolated liver perfusion. Our results strongly suggest that the liver is the main organ of isosteviol elimination and that isosteviol is glucuronidated in the liver before it is excreted into the bile.

Transfer of rosuvastatin into breast milk: liquid chromatography–mass spectrometry methodology and clinical recommendations

Publisher: Informa UK Limited

Date: 10-2018

DOI: 10.2147/DDDT.S184053

Simultaneous determination of 24 opioids, stimulants and new psychoactive substances in wastewater

Publisher: Elsevier BV

Date: 2019

DOI: 10.1016/J.MEX.2019.04.016

Effect of Garlic, Gingko, and St. John's Wort Extracts on the Pharmacokinetics of Fexofenadine: A Mechanistic Study

Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)

Date: 10-02-2017

DOI: 10.1124/DMD.116.073528

Abstract: The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/organic anion-transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW 1000 mg/kg positive control), or Milli-Q water for 14 days. On day 15, rats either were administered fexofenadine (orally or i.v.), had their livers isolated and perfused with fexofenadine, or had their small intestines ided into four segments (SI-SIV) and analyzed for P-gp and Oatp1a5. In vivo, SJW increased the clearance of i.v. administered fexofenadine by 28%. Garlic increased the area under the curve

Determination of colistin in human plasma, urine and other biological samples using LC–MS/MS

Publisher: Elsevier BV

Date: 02-2008

DOI: 10.1016/J.JCHROMB.2007.12.009

Abstract: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed to quantify colistin in human plasma and urine, and perfusate and urine from the isolated perfused rat kidney (IPK). Solid phase extraction (SPE) preceded chromatography on a Synergi Fusion-RP column with a mobile phase of acetonitrile, water and acetic acid (80/19/1) at 0.2mL/min. Ions were generated using electrospray ionization and detected in the positive-ion mode. Multiple reaction monitoring was performed using precursor-product ion combinations. Calibration curves were linear from 0.028microg/mL (human plasma, IPK perfusate and urine)/0.056microg/mL (human urine) to 1.78microg/mL (all four media) for colistin A sulfate corresponding values for colistin B sulfate were 0.016/0.032 to 1.01microg/mL. Accuracy and precision were within 10%. The LLOQ for colistin A sulfate was 0.028microg/mL in human plasma, IPK perfusate and urine and 0.056microg/mL in human urine corresponding values for colistin B sulfate were 0.016 and 0.032microg/mL. The low s le volume, short analysis time and low LLOQ are ideal for pre-clinical and human pharmacokinetic studies of colistin.

Estimates of tobacco use by wastewater analysis of anabasine and anatabine

Publisher: Wiley

Date: 22-07-2015

DOI: 10.1002/DTA.1842

Abstract: Wastewater analysis, the chemical analysis of municipal sewage, is fast becoming the technique of choice to monitor changes in community consumption of a range of compounds over time. Currently wastewater analyses which estimate tobacco consumption focus on the major alkaloid nicotine and its urinary metabolite, cotinine. As nicotine is also present in replacement therapies such as nicotine gum and patches, this analysis is not specific and hence does not truly reflect the harmful consumption of tobacco. Two alkaloids - anabasine and anatabine - which are specific to dried tobacco, were assessed as biomarkers for tobacco consumption in wastewater, together with nicotine and cotinine. Consequently, solid phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS) methods for the detection of anabasine, anatabine, nicotine, and cotinine in municipal wastewater were validated. All compounds were detected in wastewater extracts and found to have satisfactory recovery, accuracy, precision, and stability in wastewater. Daily flow volume and catchment population of the wastewater facility were used to estimate normalized consumption figures of mg/day/1000 people for composite s les collected over one week, in an application of the method. Anabasine and anatabine were found to be suitable wastewater biomarkers of tobacco and can be used to assess tobacco consumption of communities via wastewater analysis. Application of this methodology can be used to collect temporal consumption data which could be used to determine the efficacy of tobacco reduction strategies. Copyright © 2015 John Wiley & Sons, Ltd.

Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism

Publisher: American Society for Microbiology

Date: 15-09-2011

DOI: 10.1128/AEM.05212-11

Abstract: Gastrointestinal disturbance is frequently reported for in iduals with autism. We used quantitative real-time PCR analysis to quantify fecal bacteria that could influence gastrointestinal health in children with and without autism. Lower relative abundances of Bifidobacteria species and the mucolytic bacterium Akkermansia muciniphila were found in children with autism, the latter suggesting mucus barrier changes.

Spatio‐temporal assessment of illicit drug use at large scale: evidence from 7 years of international wastewater monitoring

Publisher: Wiley

Date: 23-10-2019

DOI: 10.1111/ADD.14767

Is urinary indolyl-3-acryloylglycine a biomarker for autism with gastrointestinal symptoms?

Publisher: Informa UK Limited

Date: 12-2009

DOI: 10.3109/13547500903183962

Abstract: An autism spectrum disorder (ASD) diagnosis is based on clinical behaviours as there are no validated biological diagnostic tools. Indolyl-3-acryloylglycine (IAG) is a chemical produced by gut microflora and there are conflicting reports as to whether urinary levels are elevated in children with ASD compared with controls. Urinary IAG levels in morning urine s les were statistically significantly higher in children with ASD whose caregivers reported the presence of chronic gastrointestinal (GI) disturbance than children with ASD without chronic GI disturbance. Urinary IAG, however, was not statistically significantly higher in children with ASD, compared with siblings or unrelated controls without ASD.

Occurrence, removal and environmental risk of markers of five drugs of abuse in urban wastewater systems in South Australia

Publisher: Springer Science and Business Media LLC

Date: 09-06-2018

DOI: 10.1007/S11356-018-2464-6

Abstract: The occurrence and fate of five drugs of abuse in raw influent and treated effluent wastewater were investigated over a period of 1 year in the Adelaide region of South Australia. Four wastewater treatment plants were chosen for this study and monitored for five drugs which included cocaine in the form of its metabolite benzoylecgonine (BE), meth hetamine, 3,4-methylenedioxymeth hetamine (MDMA) and two opioids (codeine and morphine) during the period April 2016 to February 2017. Alongside concentrations in raw sewage, the levels of drugs in the treated effluent were assessed and removal efficiencies were calculated. Drug concentrations were measured by mixed-mode solid phase extraction and liquid chromatography coupled to a quadrupole mass spectrometer. Drug concentrations detected in the raw wastewater ranged from 7 to 6510 ng/L and meth hetamine > morphine > MDMA > BE. Results showed that all the targeted drugs were on average incompletely removed by wastewater treatment, with removal performance highest for morphine (94%) and lowest for MDMA (58%). A screening-level environmental risk assessment was subsequently performed for the drugs based on effluent wastewater concentrations. Based on calculated risk quotients, overall environmental risk for these compounds appears low, with codeine and meth hetamine likely to pose the greatest potential risk to receiving environments. Given the recognised limitations of current ecotoxicological models and risk assessment methods for these and other pharmaceutical drugs, the potential for environmental impacts associated with the continuous discharge of these compounds in wastewater effluents should not be overlooked.

Towards finding a population biomarker for wastewater epidemiology studies

Publisher: Elsevier BV

Date: 07-2014

DOI: 10.1016/J.SCITOTENV.2013.11.075

Abstract: Wastewater analysis has the potential to provide objective information on community drug use. Introducing a population biomarker (PB) in the s le analysis may significantly reduce errors in the back-calculation associated with population estimation and wastewater volume measurement. A number of potential PBs have been suggested but no systematic evaluation has been conducted so far. This study evaluated the eligibility of the previously suggested PB candidates (creatinine, cholesterol, coprostanol and cotinine) as well as three new ones (cortisol, androstenedione and 5-hydroxyindoleacetic acid (5-HIAA)) using five criteria. We assessed the quantification method, affinity to particulate matter and stability of candidates in wastewater, as well as the constancy of inter-day excretion and correlation between excretion and census population. All PB candidates were quantifiable in wastewater. Cholesterol and coprostanol were eliminated from further consideration due to affinity to particulate matters in the wastewater. Creatinine, cortisol and androstenedione were disqualified for stability reasons. On a population scale, both cotinine and 5-HIAA were excreted (RSD=8.01 ± 1.13% and 10.20 ± 0.89%, respectively) at a constant rate and concentrations of each correlated well with the census population (r=0.9809 and 0.9442, respectively). Overall, both cotinine and 5-HIAA are eligible PBs, but the neurotransmitter metabolite 5-HIAA may be more suitable for international comparisons.

Trends in stimulant use in Australia: A comparison of wastewater analysis and population surveys

Publisher: Elsevier BV

Date: 12-2015

DOI: 10.1016/J.SCITOTENV.2015.07.078

Abstract: Levels of community drug use are usually described by national surveys data relied upon by decision makers in health and law enforcement. In recent years the analysis of wastewater for drugs and their metabolites has become prominent. Both methods convey unique drug use information. This paper demonstrates differences arising from the two approaches, using meth hetamine, 3,4-methylenedioxymeth hetamine (MDMA) and cocaine data from the state of South Australia. The proportion of people using each drug, obtained from three prominent drug surveys, was compared with estimates of total community drug use derived by wastewater analysis. Temporal trends were compared for available years of the surveys and wastewater analysis from 2010 to 2013. Wastewater results showed meth hetamine to be the most prevalent stimulant in Adelaide, South Australia, with an average of 24.4±1.7 doses per day per 1000 inhabitants for 2013, while consumption of MDMA and cocaine were much lower at 0.52±0.12 and 0.42±0.06 doses per day per 1000 inhabitants, respectively. Survey data typically had MDMA as the most used stimulant on a proportion of the population basis. The difference in magnitude of drug use between MDMA and meth hetamine was also less apparent. Temporal trends of the proportion of the population using a drug by surveys did not generally reflect total use within the community which was observed by wastewater analysis. Survey data are excellent for describing users demographically. However, discrepancies between the proportion of the population who are users and the magnitude of drug use can lead to misrepresentation of the overall scale of use. The results from this study indicate meth hetamine was used to a much greater extent than suggested by the surveys. Together, wastewater analysis and survey data give a comprehensive view of the drug problem enabling more informed decisions on drug policy.

Physical factors affecting chloroquine binding to melanin

Publisher: Elsevier BV

Date: 10-2015

DOI: 10.1016/J.COLSURFB.2015.06.040

Abstract: Chloroquine is an antimalarial drug but is also prescribed for conditions such as rheumatoid arthritis. Long-term users risk toxic side effects, including retinopathy, thought to be caused by chloroquine accumulation on ocular melanin. Although the binding potential of chloroquine to melanin has been investigated previously, our study is the first to demonstrate clear links between chloroquine adsorption by melanin and system factors including temperature, pH, melanin type, and particle size. In the current work, two Sepia melanins were compared with bovine eye as a representative mammalian melanin. Increasing the surface anionic character due to a pH change from 4.7 to 7.4 increased each melanin's affinity for chloroquine. Although the chloroquine isotherms exhibited an apparently strong interaction with each melanin, isosteric heat analysis indicated a competitive interaction. Buffer solution cations competed effectively at low surface coverage chloroquine adsorption occurs via buffer cation displacement and is promoted by temperature-influenced secondary structure swelling.

Removal of emerging drugs of addiction by wastewater treatment and water recycling processes and impacts on effluent-associated environmental risk

Publisher: Elsevier BV

Date: 08-2019

DOI: 10.1016/J.SCITOTENV.2019.05.068

Abstract: Drugs of addiction, have been recognized as potential contaminants of concern to the environment. Effluent wastewater discharge is a major source of contamination to aquatic receiving environments. A year-long monitoring program was undertaken in Australia to characterise the fate of four emerging drugs of addiction: meth hetamine MDMA pharmaceutical opioids: codeine and morphine and a metabolite: benzoylecgonine in four wastewater treatment plants operating with different secondary treatment technologies: conventional activated sludge (CAS), membrane bioreactors (MBR), integrated fixed-film AS (IFAS) and sequencing batch reactor (SBR). The effect of subsequent tertiary treatment (coagulation/flocculation) on the removal efficiency was also assessed. Drugs were detected in influent and effluent s les (mean concentration ranged from 43-4777 and 17-1721 ng/L, respectively). Treated effluents had noticeably lower levels compared to raw influents. Removal efficiency of compounds depended on the secondary treatment employed, with IFAS and MBR performing the best with significant removal of compounds (≈90%) followed by CAS (54-96%) and lastly SBR (42-83%). Despite the low levels of drugs measured after the secondary treatment, near complete removal after tertiary treatment (≈99%) was recorded, which demonstrated the effectiveness of using the coagulation/flocculation process as an effective step for enhancing the removal efficiency. The levels of drugs were at a low level in the effluents released into the environment and used for recycling and all posed a low environmental risk in urban water courses based on the risk assessment. The information given here provides new and useful information to the water industry and regulators on the efficiency of drug removal in a range of wastewater treatment configurations.

LC-HRMS suspect screening to show spatial patterns of new psychoactive substances use in Australia

Publisher: Elsevier BV

Date: 02-2019

DOI: 10.1016/J.SCITOTENV.2018.09.348

Abstract: New Psychoactive Substances (NPS) are an ever-changing class of compounds designed to imitate the effects of current recreational drugs. Such a erse market is difficult to assess by traditional means, while collected information can become obsolete before it is available. Wastewater-based epidemiology is one technique which can capture information on where and when NPS appear at the community level. The aim of this study was to identify NPS in wastewater s les using a suspect screening approach. Weekend s les were collected from 50 wastewater treatment plants from Australian capital cities and regional areas across all eight States and Territories and screened against a database containing almost 200 NPS. A total of 22 different NPS were found across all regional and metropolitan wastewater treatment plants. Results showed that the most detected compounds were of the cathinone class, with both Alpha-PVP and methcathinone found in every region. In addition, five different synthetic cannabinoids were detected, at least once in half of the regions analysed. Herein, we report the first comprehensive nationwide analysis of NPS and show the utility of liquid chromatography-high resolution mass spectrometry screening for delivering spatial information of the NPS being consumed in communities.

Temporal trends in drug use in Adelaide, South Australia by wastewater analysis

Publisher: Elsevier BV

Date: 09-2016

DOI: 10.1016/J.SCITOTENV.2016.04.183

Abstract: Analysis of municipal wastewater for drug metabolites can reveal the scale of drug use within communities. An Australian city with a population of 1.2million inhabitants was assessed for 4 stimulants: cocaine, meth hetamine, 3.4-methylenedioxymeth hetamine (MDMA) and hetamine 6 opioids: codeine, morphine, heroin, fentanyl, oxycodone and methadone 11 new psychoactive substances (NPS) benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP), methcathinone, methylone, mephedrone, methylenedioxypyrovalerone (MDPV), alpha pyrrolidinopentiophenone (alpha-PVP), paramethoxy hetamine (PMA), 25C-NBOMe, 25B-NBOMe, 25I-NBOMe and cannabis, for up to four years between December 2011 and December 2015. Temporal trends revealed increasing usage rates of meth hetamine, cocaine, oxycodone, and fentanyl, while decreasing rates of use were observed for MDMA, BZP and methylone. Use of other opioids and cannabis was generally stable across years, while use of new psychoactive substances fluctuated without an apparent direction. Opioids and cannabis were used at a consistent level through the course of the week, while use of stimulants and some NPS increased on the weekend. Seasonal differences in use were observed for MDMA and cannabis (p$_ _$lt .05) where, on average, MDMA use was approximately 90% higher in December than in other months and cannabis use was approximately 45% lower in each February. Residual month-to-month variability measures on trend-free data showed NPS use had higher variability than the stimulants and opioids. Frequent wastewater s ling and analysis over prolonged periods has yielded valuable insights into long-term drug use trends, in some instances revealed important within-year trends, and demonstrated the differing patterns of use of drugs on weekends compared to weekdays.

Multi-year inter-laboratory exercises for the analysis of illicit drugs and metabolites in wastewater: Development of a quality control system

Publisher: Elsevier BV

Date: 06-2018

DOI: 10.1016/J.TRAC.2018.03.009

Wastewater analysis shows a large decrease in oxycodone use in Adelaide

Publisher: AMPCo

Date: 07-2017

DOI: 10.5694/MJA17.00137

A new LC-MS/MS bioanalytical method for perindopril and perindoprilat in human plasma and milk

Publisher: Springer Science and Business Media LLC

Date: 25-08-2017

DOI: 10.1007/S00216-017-0552-Y

Abstract: A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical s les. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL (r

Oral and i.v. pharmacokinetics of isosteviol in rats as assessed by a new sensitive LC–MS/MS method

Publisher: Elsevier BV

Date: 11-2008

DOI: 10.1016/J.JPBA.2008.06.015

Abstract: A sensitive liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed to investigate isosteviol pharmacokinetics in vivo. Isosteviol was extracted from plasma with hexane and 4% formic acid. A Phenomenex Synergi 2mu Fusion reversed phase analytical HPLC column (50 mm x 2.0 mm) equipped with a Synergi 2micro Fusion guard column was employed for chromatographic separations. The gradient mobile phase consisted of acetonitrile (ACN) and 20mM ammonium acetate at pH 6.5, starting at 20% ACN and r ing to 80% at 7 min, followed by 80% ACN for 1 min, then 20% ACN for 5 min. Negative SRM was used to monitor the m/z 317.1/317.1 and 317.3/317.3 transitions for isosteviol and 395.0/395.0 and 397.0/397.0 transitions for internal standard. The retention time of isosteviol was 9.2 min. The assay was linear over the range of 50-2,000 ng/mL. The accuracy of the method was in the range of 97-105%. Intra- and inter-day precisions were in the range of 1.5-4.6%. Isosteviol (4 mg/kg) was dosed intravenously and orally to Sprague-Dawley rats (n=6). Plasma s les were collected and analysed. Intravenous isosteviol has a distribution half-life of 35.7+/-9.0 min with the initial distribution volume of 68.1+/-9.4 mL. The total clearance, terminal half-life and steady-state volume of distribution were 1.25+/-0.12 mL/min, 150.6+/-50.5 min and 272.6+/-95.9 mL, respectively. The oral bioavailability of isosteviol was found to be 60.4+/-15.5%.

Measuring spatial and temporal trends of nicotine and alcohol consumption in Australia using wastewater-based epidemiology.

Publisher: Wiley

Date: 26-02-2018

DOI: 10.1111/ADD.14157

Abstract: Tobacco and alcohol consumption remain priority public health issues world-wide. As participation in population-based surveys has fallen, it is increasingly challenging to estimate accurately the prevalence of alcohol and tobacco use. Wastewater-based epidemiology (WBE) is an alternative approach for estimating substance use at the population level that does not rely upon survey participation. This study examined spatio-temporal patterns in nicotine (a proxy for tobacco) and alcohol consumption in the Australian population via WBE. Daily wastewater s les (n = 164) were collected at 18 selected wastewater treatment plants across Australia, covering approximately 45% of the total population. Nicotine and alcohol metabolites in the s les were measured using liquid chromatography-tandem mass spectrometry. Daily consumption of nicotine and alcohol and its associated uncertainty were computed using Monte Carlo simulations. Nation-wide daily average and weekly consumption of these two substances were extrapolated using ordinary least squares and mixed-effect models. Nicotine and alcohol consumption was observed in all communities. Consumption of these substances in rural towns was three to four times higher than in urban communities. The spatial consumption pattern of these substances was consistent across the monitoring periods in 2014-15. Nicotine metabolites significantly reduced by 14-25% (P = 0.001-0.008) (2014-15) in some catchments. Alcohol consumption remained constant over the studied periods. Strong weekly consumption patterns were observed for alcohol but not nicotine. Nation-wide, the daily average consumption per person (aged 15-79 years) was estimated at approximately 2.5 cigarettes and 1.3-2.0 standard drinks (weekday-weekend) of alcohol. These estimates were close to the sale figure and apparent consumption, respectively. Wastewater-based epidemiology is a feasible method for objectively evaluating the geographic, temporal and weekly profiles of nicotine and alcohol consumption in different communities nationally.

Is there a role for routinely screening children with autism spectrum disorder for creatine deficiency syndrome?

Publisher: Wiley

Date: 29-06-2010

DOI: 10.1002/AUR.145

Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that presents in the first three years of life. Currently, diagnosis of ASD is based on its behavioural manifestations, as laboratory diagnostic tests do not exist. Creatine deficiency syndrome (CDS) is one form of inborn error of metabolism where affected in iduals have similar clinical features to in iduals with ASD. Abnormal urinary creatine (CR) and guanidinoacetate (GAA) levels have been reported as biomarkers of CDS. We hypothesized that screening for abnormal levels of urinary CR and GAA in children with ASD may assist in identifying a subgroup of ASD in iduals who can be managed with dietary interventions. Morning urine s les were collected from children with and without autism and analyzed for CR and GAA levels. Results showed there was no statistically significant difference in urinary CR:creatinine and GAA:creatinine between the children with ASD and sibling or unrelated controls. In conclusion, routine screening for abnormal urinary CR and GAA could be considered in ASD diagnostic protocols however, in iduals positive for CDS are likely to be rare in an ASD cohort.

Role of saturated and unsaturated fatty acids on dicarbonyl-albumin derived advanced glycation end products in vitro.

Publisher: Springer Science and Business Media LLC

Date: 21-08-2022

DOI: 10.1007/S00726-021-03069-6

Abstract: Glycation is a non-enzymatic reaction that occurs between the free amino group of proteins and reducing sugars and/or lipids, leading to the formation of advanced glycation end products (AGEs). The reaction also produces reactive oxygen species that have detrimental effects on cellular and extracellular proteins. Aminoguanidine is a known inhibitor of AGEs, and some fatty acids are known to have a beneficial role in vivo by reducing inflammation and oxidative stress. However, the role of fatty acids on AGE formation has not been thoroughly reported. We investigated the role of a range of fatty acids in the formation of AGEs and their reactive intermediates using an in vitro BSA-dicarbonyl model. The model assessed a time-dependent (0-72 h) and dicarbonyl concentration (0-2 mM) -dependent studies for the optimal formation of AGEs. A 72 h time point was found to be optimal for the reaction of BSA with either methylglyoxal (MGO) or glyoxal (GO) to generate AGE-BSA complexes. When arachidonic, eicosapentaenoic or docosahexaenoic acids were included in the reaction, a significant decrease in protein-bound fluorescent AGEs was seen compared to the respective controls. In contrast, saturated and 18 carbon polyunsaturated fatty acids showed no significant activity. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis showed saturated fatty acids significantly decreased the production of N

Inhibition of indoleamine 2,3-dioxygenase activity by fatty acids and prostaglandins: A structure function analysis

Publisher: Elsevier BV

Date: 07-2017

DOI: 10.1016/J.PLEFA.2017.06.010

Abstract: Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation. As such, IDO-1 has become a target of intense interest for pharmacological inhibition, for the treatment of cancer. We have previously demonstrated that AA and the prostaglandin metabolite, PGD

Flavonoids from the leaves and stems of Dodonaea polyandra: A Northern Kaanju medicinal plant

Publisher: Elsevier BV

Date: 10-2011

DOI: 10.1016/J.PHYTOCHEM.2011.05.006

Abstract: Three prenylated flavonoids 5,7,4'-trihydroxy-3'(3-methylbut-2-enyl)-3-methoxy flavone, 5,7-dihydroxy-3'(3-methylbut-2-enyl)-3,4'-dimethoxy flavone and 5,7,4'-trihydroxy-3',5'(3-methylbuyt-2-enyl)-3-methoxy flavone together with three other known flavonoids were isolated from the medicinal plant Dodonaea polyandra. The plant is used in the traditional medicine system of Northern Kaanju people of Cape York Peninsula, Queensland, Australia. The extracts studied have previously been found to possess anti-inflammatory activity. Successive fractionation of leaf and stem extracts by column and high performance liquid chromatography led to the isolation of these compounds. Their structures were determined using a number of spectroscopic techniques including 1D and 2D NMR and high resolution mass spectroscopy. The structural elucidation is reported herein accompanied by full ¹H and ¹³C NMR spectroscopic data. Spectroscopic data of known compounds was in agreement with that previously reported in literature.

A reappraisal of Fe(III) adsorption by melanin

Publisher: Springer Science and Business Media LLC

Date: 21-05-2014

DOI: 10.1007/S00702-014-1236-9

Abstract: The adsorptive capacity of melanin for Fe(III) was investigated. Iron is involved in promoting the formation of reactive oxygen species which has consequently been associated with Parkinson's disease. Neuromelanin has been suggested to act as an iron scavenger and, therefore, determining the capacity of melanin to adsorb iron is relevant. Although a few reports have quantified the binding capacity, the current research examined the effect of solution pH on adsorption as well as considering physiologically relevant matrices. In addition, desorption is described for the first time. Our results indicated that adsorption over an acidic pH range was relatively constant and was not significantly affected by the presence of protein or lipid. This paper, therefore, goes beyond published reports by investigating a broader range of factors. It also highlights the importance of melanin in the brain through its homeostatic regulation of Fe(III), through the desorption profile of melanin, a novel result.

Using Sepia melanin as a PD model to describe the binding characteristics of neuromelanin – A critical review

Publisher: Elsevier BV

Date: 03-2015

DOI: 10.1016/J.JCHEMNEU.2015.02.001

Abstract: Parkinson's disease is characterised pathologically by a relatively selective death of dopaminergic neurons in the substantia nigra of the brain. The vulnerability of these neurons appears to be linked to the pigment neuromelanin. However, as yet there is limited understanding behind the mechanisms of this disease process. Complications arise due to the difficulty in obtaining appreciable quantities of neuromelanin. Furthermore, an appropriate model for studying neuromelanin has not been identified. To date there has been many studies looking at the binding and chemical characteristics of neuromelanin. However, a range of different synthetic and organic melanins have been used as models and leading to many varied conclusions being drawn. Therefore, the aim of this review is to present Sepia melanin as the most appropriate study model for the binding characteristics of neuromelanin. Considerations included chemical structure, surface characteristics and structural features of both synthetic and organic melanins.

Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies

Publisher: Elsevier BV

Date: 2014

DOI: 10.1016/J.TOXREP.2014.10.019

In vivo activity of benzoyl ester clerodane diterpenoid derivatives from dodonaea polyandra

Publisher: American Chemical Society (ACS)

Date: 07-03-2011

DOI: 10.1021/NP100701S

Abstract: Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8α-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8α-(benzoyloxy)methyl-2α-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8α-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2α-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses.

Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder

Publisher: Springer Science and Business Media LLC

Date: 26-04-2012

DOI: 10.1007/S10620-012-2167-7

Abstract: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder where a high frequency of gastrointestinal disturbance (e.g., constipation and diarrhea) is reported. As large bowel fermentation products can have beneficial or detrimental effects on health, these were measured in feces of children with and without ASD to examine whether there is an underlying disturbance in fermentation processes in the disorder. Fecal s les (48 h) were collected from children with ASD (n = 23), and without ASD (n = 31) of similar age. Concentrations of short chain fatty acids, phenols and ammonia were measured. Fecal total short chain fatty acid concentrations were significantly higher in children with ASD compared to controls (136.6 ± 8.7 vs. 111.1 ± 6.6 mmol/kg). Moreover, when concentrations of fecal acetic, butyric, isobutyric, valeric, isovaleric and caproic acids were measured, all were significantly higher in children with ASD compared with controls except for caproic acid. The concentration of fecal ammonia was also significantly greater in ASD participants than controls (42.7 ± 3.3 vs. 32.3 ± 1.9 mmol/kg). Fecal phenol levels and pH did not differ between groups. Macronutrient intake, as determined from dietary records kept by caregivers, also did not differ significantly between study groups. Our results suggest fermentation processes or utilization of fermentation products may be altered in children with ASD compared to children without ASD.

University Of South Australia

Location: Australia

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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100137

Start Date: 12-2021

End Date: 03-2023

Amount: $881,758.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP180100715

Start Date: 10-2019

End Date: 07-2023

Amount: $192,000.00

Funder: Australian Research Council

Linkage Projects - Grant ID: LP190101124

Start Date: 06-2021

End Date: 06-2025

Amount: $563,412.00

Funder: Australian Research Council