Papers by Brian Tomlinson
The Open Nutraceuticals Journal, 2010
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Atherosclerosis, 2014
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Current opinion in investigational drugs (London, England: 2000)
HIV-associated lipodystrophy characterized by body composition changes and associated metabolic a... more HIV-associated lipodystrophy characterized by body composition changes and associated metabolic abnormalities, including dyslipidemia and insulin resistance, is a major challenge in the treatment of HIV infection. Growth hormone-releasing factor (GRF) analogs with greater stability than the natural hormone can induce growth hormone secretion in a physiological manner, and appear to be promising candidate therapies for these conditions. The most promising GRF agonist in development is tesamorelin (EMD Serono/Theratechnologies), which has exhibited efficacy for the treatment of excess visceral adipose tissue in patients with HIV infection in two recent phase III, randomized, placebo-controlled clinical trials. Additional long-term outcome trials are required to determine the long-term safety of tesamorelin and to evaluate whether this agent, or other GRF agonists, could reduce the cardiovascular risk associated with lipodystrophy-related metabolic complications and help to maintain a more normal distribution of body fat.
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Circulation
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Circulation
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Clinical nephrology
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Atherosclerosis Supplements, 2008
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Clinical and experimental pharmacology & physiology, Jan 18, 2015
Ursodeoxycholic acid (UDCA), a natural, dihydroxy bile acid, promotes gallstone dissolution and h... more Ursodeoxycholic acid (UDCA), a natural, dihydroxy bile acid, promotes gallstone dissolution and has been attributed with several other beneficial effects. The farnesoid X receptor (FXR) may influence the pharmacokinetics of UDCA by modulating the expression of bile acid transporters. This exploratory study examined whether common functional polymorphisms in FXR and in bile acid transporter genes affect the pharmacokinetics of exogenous UDCA. Polymorphisms in genes for transporters involved in bile acid transport, solute carrier organic anion 1B1 (SLCO1B1) 388A>G and 521T>C, solute carrier 10A1 (SLC10A1) 800 C>T and ATP-binding cassette B11 (ABCB11) 1331T>C, and the FXR -1G>T polymorphism were genotyped in 26 male Chinese subjects who ingested single oral 500-mg doses of UDCA. Plasma concentrations of UDCA and its major conjugate metabolite glycoursodeoxycholic acid (GUDCA) were determined. The mean systemic exposure of UDCA was higher in the 5 subjects with one copy o...
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Atherosclerosis
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Atherosclerosis
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Pharmacogenomics, 2015
Cutaneous flushing with niacin varies between individuals and is substantially reduced by concomi... more Cutaneous flushing with niacin varies between individuals and is substantially reduced by concomitant laropiprant. We investigated associations between baseline phenotypes and selected genotypes and flushing symptoms with niacin/laropiprant combination. Flushing symptoms were quantified in 196 Chinese dyslipidaemic patients treated with niacin/laropiprant, and associations with phenotypes and selected polymorphisms were analyzed. Moderate or severe flushing was associated with lower body mass index and the rs2279238 polymorphism in the LXRα on multivariate regression analysis and these factors accounted for 18.9% of the total variance. Lower body mass index and the LXRα polymorphism appear to be associated with flushing symptoms with niacin/laropiprant. Whether these findings can be applicable to other niacin formulations without laropiprant needs to be verified.
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The Journal of Clinical Pharmacology
The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has be... more The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro-oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT(1)) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double-blind, placebo-controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD-mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration-dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The ...
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Atherosclerosis
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Medical & biological engineering & computing, Jan 6, 2015
Despite increasing demand and research efforts, currently there is no consensus on the protocol f... more Despite increasing demand and research efforts, currently there is no consensus on the protocol for automated and reliable quantification of adipose tissue (AT) and visceral adipose tissue (VAT) using MRI. The purpose of this study was to propose a novel computational method with enhanced objectiveness for the quantification of AT and VAT in fat-water separation MRI. 3T data from IDEAL were acquired for the fat-water separation. Fat tissues were separated from nonfat regions (background air, bone, water, and other nonfat tissues) using K-means clustering (K = 2). From the binary fat mask, arm regions were separated from body based on the relative size of connected component. AT was obtained from the binary body fat mask. With the initial contour as the outer boundary of body fat, the subcutaneous adipose tissue (SAT) and VAT were separated using deformable model driven by a specifically generated deformation field pointing to the inner boundary of SAT. The proposed method was tested...
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American Journal of Hypertension, 1997
A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to... more A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem, in a sustained release preparation, and the angiotensin converting enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with mild-to-moderate hypertension. In addition to the hypotensive effects of combinations of both drugs compared with monotherapy, all given once
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European journal of clinical nutrition, Jan 18, 2015
Although observational studies suggest that soy foods or isoflavones are cardio-protective, clini... more Although observational studies suggest that soy foods or isoflavones are cardio-protective, clinical trials on whole soy or isoflavone daidzein (one major isoflavone and the precursor of equol) on blood pressure (BP) and endothelial function (EF) are few and have not been specifically conducted among equol producers, a population most likely to benefit from soy treatment. We performed a 6-month double-blind, randomized, placebo-controlled trial to examine the effect of whole soy (soy flour) or purified daidzein on BP and EF in prehypertensive or untreated hypertensive postmenopausal women verified to be equol producers. A total of 270 eligible women were recruited and randomized to either one of the three treatment groups, 40 g soy flour (whole soy group), 40 g low-fat milk powder+63 mg daidzein (daidzein group) or 40 g low-fat milk powder (active control group) daily, each given as a solid beverage powder for 6 months. The primary outcome measures were 24 h ambulatory BP (ABP) and ...
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Expert opinion on investigational drugs, Jan 21, 2015
Introduction: The fibrates have been used for many years to treat dyslipidemias and have also rec... more Introduction: The fibrates have been used for many years to treat dyslipidemias and have also recently been shown to have anti-inflammatory effects. They are relatively weak PPAR-α agonists and do have some adverse effects. Novel compounds are in development, which are selective PPAR modulators (SPPARMs) and have more potent PPAR-α agonist activity. These may prove to have advantages in the treatment of dyslipidemia, insulin resistance and non-alcoholic fatty liver disease (NAFLD). Areas covered: This review focuses on PPAR-α agonists or SPPARMs in development describing the preclinical and early clinical studies. The information was obtained by searching the published literature and abstracts from recent meetings. Ongoing clinical trials were identified using the Clinicaltrial.gov database. Expert opinion: There is still a need for new drugs to treat atherogenic dyslipidemia. The highly potent and selective PPAR-α agonist K-877 has shown beneficial effects on atherogenic dyslipidem...
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Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2014
Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may... more Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β-OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200, 400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and following GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from 0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P <0.05) and the ratio of cortisol to cortisone (P <0.005) and reducing 6β-OHC excretion (P <0.05) and the ratio of 6β-OHC to cortisol (P <0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated dos...
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Clinical pharmacology and therapeutics, 2005
Although cytochrome P450 (CYP) 2C9 was thought to be the main pathway for glyburide (INN, glibenc... more Although cytochrome P450 (CYP) 2C9 was thought to be the main pathway for glyburide (INN, glibenclamide) metabolism in vivo, studies in vitro indicated that CYP2C19 had a more dominant effect. This study investigated the relative influence of CYP2C9 and CYP2C19 genotypes on the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. Three groups of healthy male Chinese subjects (n=6 per group) were enrolled, as follows: group I, CYP2C9*1/*1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C9*1/*1 and CYP2C19 poor metabolizers (PMs); and group III, CYP2C9*1/*3 and CYP2C19 EMs. Subjects received single oral doses of 5 mg glyburide. Multiple blood samples were collected, and the plasma glyburide concentrations were determined by an HPLC method. The plasma glucose and insulin concentrations were also measured up to 2 hours after dosing. No significant differences in glyburide pharmacokinetics were observed between CYP2C19 EM and PM subjects who had the CYP2C9*1/*1...
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Papers by Brian Tomlinson