A5028161543- Intensive Care Unit Cognitive Disorders
- Health Systems, Economic Evaluations, Quality of Life
- Frailty in Older Adults
- Drug-Induced Hepatotoxicity and Protection
- Pharmaceutical Practices and Patient Outcomes
- Anesthesia and Sedative Agents
- Nutrition and Health in Aging
- Geriatric Care and Nursing Homes
- Pharmacogenetics and Drug Metabolism
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Cardiovascular and exercise physiology
- Pharmacological Effects and Assays
- Dementia and Cognitive Impairment Research
- Liver Disease Diagnosis and Treatment
- Palliative Care and End-of-Life Issues
- Anesthesia and Neurotoxicity Research
- Chronic Disease Management Strategies
- Liver Disease and Transplantation
- Aluminum toxicity and tolerance in plants and animals
- Lipoproteins and Cardiovascular Health
- Cardiac, Anesthesia and Surgical Outcomes
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
The University of Sydney
2013-2024
Northern Sydney Local Health District
2020-2024
Royal North Shore Hospital
2013-2022
Keogh Institute for Medical Research
2020-2021
UNSW Sydney
2010
University of Minnesota, Duluth
2007
UnitedHealth Group (United States)
2001
Geriatric Research Education and Clinical Center
1988-1998
Harvard University
1998
University of Minnesota
1988-1997
Obesity is a top public health concern, and molecule that safely treats obesity urgently needed. Disulfiram (known commercially as Antabuse), an FDA-approved treatment for chronic alcohol addiction, exhibits anti-inflammatory properties helps protect against certain types of cancer. Here, we show in mice disulfiram prevented body weight gain abrogated the adverse impact obesogenic diet on insulin responsiveness while mitigating liver steatosis pancreatic islet hypertrophy. Additionally,...
We aimed to develop a mouse model of polypharmacy, primarily establish whether short-term exposure polypharmacy causes adverse geriatric outcomes. also investigated old age increased susceptibility any outcomes polypharmacy. Young (n= 10) and 21) male C57BL/6 mice were administered control diet or containing therapeutic doses five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, citalopram). Mice assessed before after the 2- 4-week intervention. Over intervention...
While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary changes in muscle, the liver also plays a key role whole-body handling its homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' essential for transfer across sinusoidal endothelium loss of fenestrations causes an impaired clearance hyperinsulinemia, induces hepatic resistance, impairs signaling, deranges glucose homeostasis. To further define signaling without...
Abstract Polypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure person’s total exposure to anticholinergic/sedative are associated with impaired physical function in observational studies older adults. Deprescribing, the supervised withdrawal medications for which harms outweigh benefits an individual, may be a useful intervention. Current knowledge is limited clinical that unable determine causality. Here, we establish preclinical model investigates...
OBJECTIVE: To evaluate the relationship between total serum anticholinergic activity (SAA) and presence or absence of delirium in older hospitalized persons on general medical wards. DESIGN: Case‐control study within‐subjects repeated‐measures recovered delirious patients. SETTING: Minneapolis Veterans Affairs Medical Center PARTICIPANTS: Eleven male patients ( DSM‐III‐R criteria) aged 60 11 comparably nondelirious controls. MEASUREMENTS: Radioreceptor bioassay SAA using tritiated...
Serotonin (5-HT) is released from the enterochromaffin cells and plays an important role in regulating intestinal function. Although release of 5-HT well documented, contribution serotonin reuptake transporter (SERT) to levels actions intestine unclear. This study aimed demonstrate real-time SERT activity ileal mucosa assess effects inhibition using fluoxetine. Electrochemical recordings were made full-thickness preparations rat ileum a carbon fiber electrode measure oxidation current force...
The mouse clinical frailty index and the phenotype assessment are two recently developed tools used to assess in mice. objectives of this study were investigate whether same mice identified as frail with both examine association each age frailty-related outcomes. Frailty was measured using old (~24 months; n = 36) C57BL/6 male After 2 weeks, blood pressure heart rate serum samples collected for analysis alanine aminotransferase, creatinine, albumin levels. no but modification tool six frail....
Aging, medication use, and global function are associated with changes in the microbiome. However, their interrelationships over time require further characterization. In a longitudinal aging mouse study, we investigated effects of aging, chronic polypharmacy high Drug Burden Index (DBI, measure total anticholinergic sedative exposure) gradual cessation (deprescribing) on microbiome, exploring any association outcomes. Chronic administration DBI attenuated aging-related reduction alpha...
Abstract Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly aging. This study aimed assess effect high Drug Burden Index (DBI) treatment compared control on physical function behavior young old, male female mice. We studied whether age sex play a role following they are paralleled by differences serum drug levels. Young (2.5 months) old (21.5 months), C57BL/6 mice were randomized or DBI...
Abstract Functional independence is an important aspect of successful aging and differs with age by sex in humans. Physical performance often declines earlier than other age-associated functional impairments. Rodent models are used to study pharmacological/toxicological effects human therapies. However, physical outcomes mice usually assessed for short periods, limited information on the influence sex. Here, we investigated how affected murine over 23 hours continuous observation. Young (3...
Aging, polypharmacy (concurrent use of ≥ 5 medications), and functional impairment are global healthcare challenges. However, knowledge the age/sex-specific effects is limited, particularly on daily physical activities. Using continuous monitoring, we demonstrated how with high Drug Burden Index (DBI-cumulative anticholinergic/sedative exposure) affected behaviors over 23 h in male/female, young/old mice. For comparison, also evaluated different drug regimens (polypharmacy/monotherapy)...
This study compared serum pyridine levels (NAD+ /NADH) in trained (n = 6) and untrained 7) subjects after continuous progressive exercise at 50%, 70% then 95% of physical work capacity until fatigue (TTF) consuming a placebo or antioxidant (AO) cocktail (Lactaway©). An increase 17% TTF was observed AO as to (p 0.032). accompanied by significant NAD+ 0.037) the supplemented group post exercise. The increases improved endurance reflect lower oxidative stress-induced suppression aerobic respiration.
Isoniazid is the first-line treatment for tuberculosis; however, its use limited by hepatotoxicity. Age-related differences in isoniazid pharmacokinetics and hepatotoxicity are uncertain. We aimed to investigate these young (3 ± 0 months, n = 26) old (23.0 0.2 27) male Fischer 344 rats following a low- or high-dose toxic regimen of vehicle (4 doses/day over 2 days; low: 100, 75, 75 mg/kg; high: 150, 105, 105 mg/kg i.p. every 3 h). Fifteen hours after last dose, animals were euthanized sera...
Abstract Background Ageing, sex and polypharmacy affect physical function. Objectives This mouse study investigates how ageing, interact grip strength, balance beam wire hang, correlating comparing the different test results between within subgroups. Methods Young (2.5 months) old (21.5 C57BL/6 J male female mice ( n = 10–6/group) were assessed for function at baseline on hang with three trials of 60 s (WH60s) one trial 300 (WH300s). Mice randomised to control or diet containing a high Drug...
We investigated the effect of aging on hepatic pharmacokinetics and degree hepatotoxicity following a toxic dose acetaminophen. Young old male Fischer 344 rats were treated with 800 mg/kg acetaminophen (young n = 8, 5) or saline 9, 9). Serum measurements showed had significantly lower serum alanine aminotransferase higher glucuronide levels creatinine, compared young (p < .05). Immunoblotting activity assays saline-treated twofold cytochrome P450 2E1 threefold NAD(P)H quinone oxireductase 1...
Abstract There is an unmet need and urgency to find safe effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency led a decrease body weight increase energy expenditure. The intervention improved glucose tolerance insulin sensitivity, mitigated metabolic dysfunctions various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic proteomic data...