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Drug dosing in obesity

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https://www.readbyqxmd.com/read/29026148/exclusive-and-combined-use-of-statins-and-aspirin-and-the-risk-of-pancreatic-cancer-a-case-control-study
#1
Livia Archibugi, Matteo Piciucchi, Serena Stigliano, Roberto Valente, Giulia Zerboni, Viola Barucca, Michele Milella, Patrick Maisonneuve, Gianfranco Delle Fave, Gabriele Capurso
Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024559/comparative-efficacy-of-five-long-term-weight-loss-drugs-quantitative-information-for-medication-guidelines
#2
REVIEW
Z Dong, L Xu, H Liu, Y Lv, Q Zheng, L Li
Quantitative information is scarce in current obesity medication guidelines, and they do not clearly reflect the differences in the efficacy characteristics among various drugs. This study quantitatively assessed the efficacy characteristics of five FDA-approved long-term weight loss drugs. Potentially eligible studies were obtained from public databases. Using the differences in the weight change from baseline between the drug group and the corresponding placebo group as the major indicator of efficacy, a time-effect model was established, and crucial pharmacodynamic parameters, such as the maximal efficacy, drug onset time and rate of body weight regain after the maximal efficacy point, were used to reflect the differences in efficacy among the five drugs...
October 10, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28958851/effects-of-liraglutide-on-weight-satiation-and-gastric-functions-in-obesity-a-randomised-placebo-controlled-pilot-trial
#3
Houssam Halawi, Disha Khemani, Deborah Eckert, Jessica O'Neill, Hoda Kadouh, Karen Grothe, Matthew M Clark, Duane D Burton, Adrian Vella, Andres Acosta, Alan R Zinsmeister, Michael Camilleri
BACKGROUND: Liraglutide, a long-acting GLP-1 receptor agonist, is approved for treatment of obesity; however, the mechanisms of action of liraglutide are incompletely understood. We compared effects of liraglutide versus placebo on gastric motor functions, satiation, satiety, and weight in obese individuals over 16 weeks. METHODS: We did a randomised, double-blind, placebo-controlled pilot trial at a single centre (Mayo Clinic, Rochester, MN, USA). Participants were randomly allocated (1:1) by a computer generated randomisation schedule with no stratification to receive subcutaneous liraglutide (3·0 mg) or placebo, with standardised nutritional and behavioural counselling...
September 25, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28948605/influence-of-body-composition-on-disposition-of-the-highly-fat-distributed-compound-as-analyzed-by-physiologically-based-pharmacokinetic-pbpk-modeling-and-simulation
#4
Akihiko Goto, Yoshihiko Tagawa, Yuu Moriya, Sho Sato, Masami Yamamoto, Takeshi Wakabayashi, Tetsuya Tsukamoto, Joost DeJongh, Tamara J van Steeg, Toshiya Moriwaki, Satoru Asahi
A recent study suggested that the pharmacokinetics (PK) of highly-fat distributed compounds can be affected by acute changes in the volume of adipose tissue. The present study investigates possible influences of body composition on the disposition of the highly lipophilic compound TAK-357 in two rat strains. Physiologically-based PK (PBPK) modeling and simulation was applied on single and multiple dose PK data of TAK-357 in obese Wistar fatty rats and Wistar lean rats having approximately 45% and 13% body fat, respectively...
September 25, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28932989/predictors-of-response-to-glucagon-like-peptide-1-receptor-agonists-a-meta-analysis-and-systematic-review-of-randomized-controlled-trials
#5
Matteo Monami, Ilaria Dicembrini, Besmir Nreu, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
AIMS: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs...
September 20, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28921681/anti-obesity-activity-of-saringosterol-isolated-from-sargassum-muticum-yendo-fensholt-extract-in-3t3-l1-cells
#6
Jung A Lee, Young-Rak Cho, Seong Su Hong, Eun-Kyung Ahn
Saringosterol, a steroid isolated from Sargassum muticum, a brown edible alga widely distributed on the seashores of southern and eastern Korea, has been shown to exhibit anti-obesity effect. In this study, we investigated the anti-obesity activity of saringosterol through various experiments. The inhibitory effect of saringosterol on adipogenesis was evaluated via Oil Red O staining in 3T3-L1 preadipocytes. After confirming that saringosterol is not cytotoxic to these cells by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, the effect of saringosterol on the expression of various adipogenesis-related genes was analyzed via quantitative real-time polymerase chain reaction and western blotting...
September 18, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28921641/pharmacokinetic-guided-dosing-of-new-oral-cancer-agents
#7
Catherine J Lucas, Jennifer H Martin
Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28914170/the-investigation-of-the-effects-of-topiramate-on-the-hypothalamic-levels-of-fat-mass-obesity-associated-protein-and-neuropeptide-y-in-obese-female-rats
#8
Işınsu Alkan, Berrin Zuhal Altunkaynak, Gamze Altun, Erkan Erener
OBJECTIVE: The aim of the present study is to investigate the effects of topiramate on the fat mass/obesity-associated protein (FTO) and on the neuropeptide Y (NPY) level in the hypothalamus depending on the recently increased prevalence of obesity. METHOD: In this study, twenty-four female rats were divided into four equal groups: Non-obese control, obese control, non-obese topiramate, and obese topiramate. Obese groups were fed with a 40% high-fat diet. At the end of the 9th week, the drug treatment started and the subjects were treated with topiramate once a day for 6 weeks...
September 15, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28901521/adiponectin-receptor-agonist-adiporon-suppresses-adipogenesis-in-c3h10t1-2-cells-through-the-adenosine-monophosphate%C3%A2-activated-protein-kinase-signaling-pathway
#9
Shu-Juan Wang, Wen-Yi Lu, Kai-Yan Liu
The aim of the present study was to investigate the effects of AdipoRon, an adiponectin receptor agonist, on adipogenesis in C3H10T1/2 cells and to explore the underlying mechanisms. C3H10T1/2 cells were treated with increasing doses of AdipoRon for 8 days, and Oil Red O staining was used to assess lipid accumulation. The protein and mRNA expression levels of adipogenic transcription factors and adipocyte‑specific genes were examined by western blotting and reverse transcription quantitative polymerase chain reaction, respectively...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899715/the-relationship-between-25-hydroxyvitamin-d-concentration-and-liver-enzymes-in-overweight-or-obese-adults-cross-sectional-and-interventional-outcomes
#10
Negar Naderpoor, Aya Mousa, Maximilian de Courten, Robert Scragg, Barbora de Courten
Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease...
September 9, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28895785/preclinical-pharmacokinetic-characterization-of-an-adipose-tissue-targeting-monoclonal-antibody-in-obese-and-non-obese-animals
#11
Sharmila Rajan, Danielle Mandikian, Amos Baruch, Thomas R Gelzleichter, Dale Stevens, Junichiro Sonoda, Kyra Cowan, C Andrew Boswell, Eric Stefanich
Target receptor levels can influence pharmacokinetics (PK) or pharmacodynamics (PD) of monoclonal antibodies (mAbs), and can affect drug development of this class of molecules. We generated an effector-less humanized bispecific antibody that selectively activates fibroblast growth factor receptor (FGFR)1 and βKlotho receptor, a FGF21 receptor complex highly expressed in both white and brown adipocytes. The molecule shows cross-species binding with comparable equilibrium binding affinity (Kd) for human, cynomolgus monkey, and mouse FGFR1/βKlotho...
September 12, 2017: MAbs
https://www.readbyqxmd.com/read/28894050/compounds-of-psoriasis-with-obesity-and-overweight
#12
Agnieszka Owczarczyk-Saczonek, Waldemar Placek
Many epidemiological studies have confirmed the relationship of obesity and psoriasis, and it is believed that obesity is an independent risk factor for its development and is associated with a worse prognosis. Furthermore, the reduction of body weight, using low-calorie diet combined with exercise, reduces the severity of psoriasis.Visceral adipose tissue is the largest endocrine organ, producing proinflammatory cytokines (TNF-α, IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin). They participate in the development of dyslipidemia, insulin resistance, diabetes, and consequently of the cardiovascular diseases...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28874443/amelioration-of-diet-induced-steatohepatitis-in-mice-following-combined-therapy-with-aso-fsp27-and-fenofibrate
#13
Ananthi Rajamoorthi, Noemi Arias, Jeannine Basta, Richard G Lee, Ángel Baldán
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD progresses from benign steatosis to steatohepatitis (NASH) to cirrhosis, and is linked to hepatocellular carcinoma. No targeted treatment is currently approved for NAFLD/NASH. We showed that fat-specific protein 27 (FSP27), a lipid droplet-associated protein that controls triglyceride turnover in the hepatocyte, is required for fasting- and diet-induced triglyceride accumulation in the liver. However, silencing Fsp27 with antisense oligonucleotides (ASOs) did not improve hepatosteatosis in genetic nor nutritional mouse models of obesity...
September 5, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28869666/comprehensive-guidance-for-antibiotic-dosing-in-obese-adults
#14
Lina Meng, Emily Mui, Marisa K Holubar, Stan C Deresinski
BACKGROUND: Physiologic alterations seen in obesity commonly impact the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics and may result in suboptimal dosing in this expanding but understudied population. Much of the published clinical and PK evidence to date consists of small patient populations and are retrospective with, not infrequently, heterogenous results that, in some cases, are contradictory. In the last 10 years, additional antimicrobial PK/PD and clinical data encompassing prolonged infusion strategies and examination of critically ill populations has emerged to inform antimicrobial dosing in obesity...
September 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28864983/epigenetic-influences-during-the-periconception-period-and-assisted-reproduction
#15
Akwasi A Amoako, Tamer M Nafee, Bolarinde Ola
The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28861414/continuous-spinal-anesthesia-for-obstetric-anesthesia-and-analgesia
#16
REVIEW
Ivan Veličković, Borislava Pujic, Charles W Baysinger, Curtis L Baysinger
The widespread use of continuous spinal anesthesia (CSA) in obstetrics has been slow because of the high risk for post-dural puncture headache (PDPH) associated with epidural needles and catheters. New advances in equipment and technique have not significantly overcome this disadvantage. However, CSA offers an alternative to epidural anesthesia in morbidly obese women, women with severe cardiac disease, and patients with prior spinal surgery. It should be strongly considered in parturients who receive an accidental dural puncture with a large bore needle, on the basis of recent work suggesting significant reduction in PDPH when intrathecal catheters are used...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28844874/cannabinoid-cb1-receptor-inverse-agonist-mj08-stimulates-glucose-production-via-hepatic-sympathetic-innervation-in-rats
#17
Wei Chen, Hongying Liu, Hua Guan, Nina Xue, Lili Wang
As a key insulin target tissue for maintaining systemic glucose homeostasis, the liver plays important roles in improving obesity-associated insulin intolerance via selective cannabinoid CB1 receptor antagonism/inverse agonism. However, it is unclear whether this receptor inverse agonism affects hepatic glucose metabolism. MJ08 is a novel cannabinoid CB1 receptor antagonist/inverse agonist that has superior inverse agonism over the well-known antagonist/inverse agonist, SR141716 (rimonabant). MJ08 remarkably elevates fasting blood glucose independent of inhibition of insulin release in mice...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28842267/medicinal-properties-of-mangosteen-garcinia-mangostana-l-a-comprehensive-update
#18
REVIEW
Berenice Ovalle-Magallanes, Dianelena Eugenio-Pérez, José Pedraza-Chaverri
Garcinia mangostana L. (Clusiaceae) is a tropical tree native to Southeast Asia known as mangosteen which fruits possess a distinctive and pleasant taste that has granted them the epithet of "queen of the fruits". The seeds and pericarps of the fruit have a long history of use in the traditional medicinal practices of the region, and beverages containing mangosteen pulp and pericarps are sold worldwide as nutritional supplements. The main phytochemicals present in the species are isoprenylated xanthones, a class of secondary metabolites with multiple reports of biological effects, such as antioxidant, pro-apoptotic, anti-proliferative, antinociceptive, anti-inflammatory, neuroprotective, hypoglycemic and anti-obesity...
August 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28803880/vitamin-d-and-symptoms-of-depression-in-overweight-or-obese-adults-a-cross-sectional-study-and-randomized-placebo-controlled-trial
#19
Aya Mousa, Negar Naderpoor, Maximilian P J de Courten, Barbora de Courten
Recent evidence suggests that vitamin D deficiency may contribute to increased risk of depression. However, previous studies are limited by variability in participant characteristics including vitamin D deficiency status and presence of existing diseases, use of low doses of vitamin D supplementation for short durations, and use of co-interventions or psychotropic drugs. We examined whether 25-hydroxyvitamin D (25(OH)D) concentrations were associated with symptoms of depression, as well as whether vitamin D supplementation reduced symptoms of depression in overweight or obese and vitamin D-deficient, but otherwise healthy adults...
August 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#20
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
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