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Drug dosing in obesity

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https://www.readbyqxmd.com/read/28612554/-the-preliminary-investigation-of-glp-1-receptor-agonist-on-liver-steatosis-in-obese-mice
#1
Xia Wang, He He, Li-Bo Liang, Mei Zhang, She-Yu Li, Shuang-Qing Li, Zhen-Mei An, Heng-Jian Huang
OBJECTIVES: To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, on liver function and steatosis in obese mice. METHODS: Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 μg/ (g·d) , high-fat-diet], low-dose exenatide group [L group, intraperitoneal injection 0...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28601546/influences-of-obesity-and-bariatric-surgery-on-the-clinical-and-pharmacologic-profile-of-rivaroxaban
#2
REVIEW
Kenneth Todd Moore, Dino Kröll
The health implications of obesity are myriad and multifaceted. Physiologic changes associated with obesity can affect the absorption, distribution, metabolism, and excretion of administered drugs, thereby altering their pharmacologic profiles. In 2016, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published recommendations regarding the use of direct oral anticoagulants (DOACs) in obese patients. This guidance provides uniform recommendations for all DOACs, yet data suggest that individual agents may be affected to different degrees by obesity...
June 7, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28592157/correlation-between-nasal-epithelial-injury-and-in-vitro-cytotoxicity-using-a-series-of-small-molecule-protein-tyrosine-phosphatase-1b-inhibitors-investigated-for-reversal-of-leptin-resistance-in-obesity
#3
Alan P Brown, Chandrassegar Saravanan, Patrick Devine, Maria Magnifico, Jiaping Gao, Valerie Beaulieu, Fupeng Ma, Kayo Yasoshima, David Barnes-Seeman, Ken Yamada
This research provides a cautionary example when evaluating changes in behavioral end points with respect to postulated pharmacologic activity. Various small molecule substrate mimetic protein tyrosine phosphatase 1B (PTP1B) inhibitors were investigated as pharmacologic agents for decreasing food consumption using intranasal (IN) dosing as a means for direct nose-to-brain delivery along the olfactory/trigeminal nerve pathways. Although food consumption was decreased in diet-induced obese (DIO) mice, nasal discharge was observed...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28590147/screening-of-cardiovascular-risk-factors-in-patients-with-schizophrenia-and-patients-treated-with-antipsychotic-drugs-are-we-equally-exhaustive-as-with-the-general-population
#4
Miguel Castillo-Sánchez, Mireia Fàbregas-Escurriola, Daniel Bergè-Baquero, MªIsabel Fernández-SanMartín, Albert Goday-Arno
Many studies have previously shown increased cardiovascular risk factors related to schizophrenia independently from the use of antipsychotic drugs. However, a poorer effort in clinical detection and management of cardiovascular risk in patients with severe mental illness could also explain these results. To test this hypothesis, we analyzed the differences in screening and incidence of cardiovascular risk factors between schizophrenia, non-schizophrenic patients on treatment with antipsychotic drugs (NS-TAD) and the general population...
June 7, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28587677/anti-obesity-activity-acute-toxicity-and-chemical-constituents-of-aqueous-and-ethanol-viola-mandshurica-extracts
#5
Yoon-Young Sung, Dong-Seon Kim, Seung-Hyung Kim, Ho Kyoung Kim
BACKGROUND: Viola mandshurica has traditionally been used as an expectorant, diuretic, and anti-inflammatory drug. The present study was designed to test the hypothesis that low doses of two different V. mandshurica extracts have anti-obesity effects. METHODS: We evaluated the effects of ethanol extract (VME) and aqueous extract (VMA) from V. mandshurica on high-fat diet (HFD)-induced obese mice as well as the acute oral toxicities and chemical compositions of both extracts...
June 6, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28579479/anti-obesogenic-and-hypolipidemic-effects-of-a-glucagon-like-peptide-1-receptor-agonist-derived-from-the-saliva-of-the-gila-monster
#6
Patricia Lucio Alves, Fernando Mauricio Francis Abdalla, Rafaela Fadoni Alponti, Paulo Flavio Silveira
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor (R) agonists are a class of incretin mimetic drugs that have been used for the treatment of type 2 diabetes mellitus and also considered strong candidates for the treatment of obesity. The original prototypical drug in this class is the exenatide, a synthetic peptide with the same structure as the native molecule, exendin-4, found in the saliva of the Gila monster (Heloderma suspectum suspectum lizard). OBJECTIVES: To identify and compare the anti-obesogenic, antidyslipidemic and antidiabetogenic effects of agonism in GLP-1R by exenatide on two distinct models of obesity: induced by hypothalamic injury (MSG) or high-calorie diet (DIO)...
June 1, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28575552/supervised-machine-learning-reveals-that-old-and-obese-people-achieve-low-dapsone-concentrations
#7
Ronald G Hall, Jotam G Pasipanodya, Mark A Swancutt, Claudia Meek, Richard Leff, Tawanda Gumbo
The human species is becoming increasingly obese. Dapsone, which is extensively used across the globe for dermatological disorders, arachnid bites, and for treatment of several bacterial, fungal and parasitic diseases, could be affected by obesity. We performed a clinical experiment, using optimal design, in volunteers weighing 44-150 kilograms, to identify the effect of obesity on dapsone pharmacokinetic parameters based on maximum-likelihood solution via the expectation-maximization algorithm. Artificial intelligence-based multivariate adaptive regression splines were used for covariate selection, and identified weight and/or age as predictors of absorption, systemic clearance and volume of distribution...
June 2, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28574870/dietary-supplementation-with-fish-oil-prevents-high-fat-diet-induced-enhancement-of-sensitivity-to-the-behavioral-effects-of-quinpirole
#8
Caroline Hernandez-Casner, Jeremiah Ramos, Katherine M Serafine
Eating a diet high in fat can lead to negative health consequences, including obesity and insulin resistance. Omega-3 polyunsaturated fatty acids (such as those found in fish oil) prevent high fat diet-induced obesity and insulin resistance in rats. Eating a high fat diet also enhances sensitivity of rats to the behavioral effects of drugs that act on dopamine systems (e.g. quinpirole, a dopamine D2/D3 receptor agonist). To test the hypothesis that dietary supplementation with fish oil prevents high fat diet-induced enhanced sensitivity to the behavioral effects of quinpirole (0...
June 1, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28531772/diet-induced-weight-loss-and-markers-of-endothelial-dysfunction-and-inflammation-in-treated-patients-with-type-2-diabetes
#9
K A Berk, T P Oudshoorn, A J M Verhoeven, M T Mulder, A J M Roks, W A Dik, R Timman, E J G Sijbrands
BACKGROUND & AIMS: Overweight and obesity increase cardiovascular mortality in patients with type 2 diabetes (T2D). In a recent trial, however, diet-induced weight loss did not reduce the cardiovascular risk of patients with T2D, possibly due to the parallel intensive medical treatment. We investigated the effect of diet-induced weight loss on cardiovascular risk factors in overweight and obese patients with T2D, and whether this effect was influenced by the use of statins, ACE inhibitors, metformin and duration of T2D...
October 2016: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/28531567/impact-of-body-composition-parameters-on-clinical-outcomes-in-patients-with-metastatic-castrate-resistant-prostate-cancer-treated-with-docetaxel
#10
Samantha J Cushen, Derek G Power, Kevin P Murphy, Ray McDermott, Brendan T Griffin, Marvin Lim, Louise Daly, Peter MacEneaney, Kathleen O' Sullivan, Carla M Prado, Aoife M Ryan
BACKGROUND: Body composition may influence clinical outcomes of certain chemotherapeutic agents. We examined the prognostic significance of skeletal muscle mass and adipose tissue on docetaxel toxicity and overall survival in patients with metastatic castrate resistant prostate cancer (mCRPC). METHODS: A retrospective review of patients medical records with mCRPC, treated with docetaxel was conducted. Body composition parameters (skeletal muscle mass, muscle attenuation [MA], visceral and subcutaneous adipose tissue) were measured at L3 by computed tomography (CT) and defined using previously established cut points...
June 2016: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#11
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28522911/study-of-the-effects-of-nesfatin-1-on-gastric-function-in-obese-rats
#12
Guo-Tao Yang, Hong-Ying Zhao, Yu Kong, Ning-Ning Sun, Ai-Qin Dong
AIM: To investigate the effects of nesfatin-1 on gastric function in obese rats. METHODS: The obese rat model was induced by a high-fat diet. The gastric emptying rate and gastric acid secretory capacity of the rats were determined after treatment with different drug concentrations of nesfatin-1 and administration routes. Based on this, the expression of H+/K+-ATPase was measured using RT-PCR and western blot to preliminarily explore the mechanism of gastric acid secretion changes...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28510797/influence-of-morbid-obesity-on-the-pharmacokinetics-of-morphine-morphine-3-glucuronide-and-morphine-6-glucuronide
#13
Sjoerd de Hoogd, Pyry A J Välitalo, Albert Dahan, Simone van Kralingen, Michael M W Coughtrie, Eric P A van Dongen, Bert van Ramshorst, Catherijne A J Knibbe
INTRODUCTION: Obesity is associated with many pathophysiological changes that may result in altered drug metabolism. The aim of this study is to investigate the influence of obesity on the pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a combined analysis in morbidly obese patients and non-obese healthy volunteers. METHODS: In this analysis, data from 20 morbidly obese patients [mean body mass index 49.9 kg/m(2) (range 37...
May 16, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28502674/evidence-based-drug-treatment-for-special-patient-populations-through-model-based-approaches
#14
REVIEW
Elke H J Krekels, J G Coen van Hasselt, John N van den Anker, Karel Allegaert, Dick Tibboel, Catherijne A J Knibbe
The majority of marketed drugs remain understudied in some patient populations such as pregnant women, paediatrics, the obese, the critically-ill, and the elderly. As a consequence, currently used dosing regimens may not assure optimal efficacy or minimal toxicity in these patients. Given the vulnerability of some subpopulations and the challenges and costs of performing clinical studies in these populations, cutting-edge approaches are needed to effectively develop evidence-based and individualized drug dosing regimens...
May 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28487951/berberine-activates-ampk-to-suppress-proteolytic-processing-nuclear-translocation-and-target-dna-binding-of-srebp-1c-in-3t3-l1-adipocytes
#15
Jaewoong Jang, Yoonju Jung, Seong Jun Seo, Seok-Min Kim, Yae Jie Shim, Soo Hyun Cho, Sang-In Chung, Yoosik Yoon
AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP)‑1c are major therapeutic targets in the treatment of metabolic diseases. In the present study, the fat‑reducing mechanisms of berberine (BBR), a natural isoquinoline, was investigated by examining the AMPK‑mediated modulation of SREBP‑1c in 3T3‑L1 adipocytes. BBR activated AMPK in a dose‑ and time‑dependent manner, and increased the phosphorylation of the 125‑kDa precursor form of SREBP‑1c, which suppressed its proteolytic processing into the mature 68‑kDa form and its subsequent nuclear translocation...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28456730/usefulness-of-pbpk-modeling-in-incorporation-of-clinical-conditions-in-personalized-medicine
#16
REVIEW
Niloufar Marsousi, Jules A Desmeules, Serge Rudaz, Youssef Daali
Personalized medicine aims to determine the most adequate treatment and dose regimen to obtain the maximum efficacy and minimum side effect by taking into account patients' characteristics. For numerous reasons one being ethical and methodological hurdles in including specific populations in clinical trials, innovative methods for optimization of drugs safety and efficacy in such patients have received increasing interest recently. Physiologically-Based PharmacoKinetic (PBPK) modeling has emerged as a promising approach in designing adequate clinical trials and quantifying anticipated changes in unknown clinical situations...
April 26, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28452063/risk-factors-of-adverse-health-outcomes-after-hospital-discharge-modifiable-by-clinical-pharmacist-interventions-a-review-with-a-systematic-approach
#17
REVIEW
B Morath, T Mayer, A F J Send, T Hoppe-Tichy, W E Haefeli, H M Seidling
AIM: This review assessed the evidence on risk factors for the occurrence of adverse health outcomes after discharge (i.e. unplanned readmission or adverse drug event after discharge) that are potentially modifiable by clinical pharmacist interventions. The findings were compared with patient characteristics reported in guidelines that supposedly indicate a high risk of drug-related problems. METHODS: First, guidelines and risk assessment tools were searched for patient characteristics indicating a high risk of drug-related problems...
April 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28440768/clinical-and-metabolic-profile-of-patients-with-latent-autoimmune-diabetes-in-adults-in-specialized-care-in-madrid
#18
Alfonso Arranz Martín, Edurne Lecumberri Pascual, Miguel Ángel Brito Sanfiel, Víctor Andía Melero, Lia Nattero Chavez, Iván Sánchez López, Gloria Cánovas Molina, Francisco Arrieta Blanco, Noemí González Perez Del Villar
OBJECTIVE: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. METHODS: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed...
January 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28434881/muramyl-dipeptide-based-postbiotics-mitigate-obesity-induced-insulin-resistance-via-irf4
#19
Joseph F Cavallari, Morgan D Fullerton, Brittany M Duggan, Kevin P Foley, Emmanuel Denou, Brennan K Smith, Eric M Desjardins, Brandyn D Henriksbo, Kalvin J Kim, Brian R Tuinema, Jennifer C Stearns, David Prescott, Philip Rosenstiel, Brian K Coombes, Gregory R Steinberg, Jonathan D Schertzer
Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28433925/low-dose-pollutant-mixture-triggers-metabolic-disturbances-in-female-mice-leading-to-common-and-specific-features-as-compared-to-a-high-fat-diet
#20
Emmanuel Labaronne, Claudie Pinteur, Nathalie Vega, Sandra Pesenti, Benoit Julien, Emmanuelle Meugnier-Fouilloux, Hubert Vidal, Danielle Naville, Brigitte Le Magueresse-Battistoni
Environmental pollutants are potential etiologic factors of obesity and diabetes that reach epidemic proportions worldwide. However, it is important to determine if pollutants could exert metabolic defects without directly inducing obesity. The metabolic disturbances triggered in nonobese mice lifelong exposed to a mixture of low-dose pollutants (2,3,7,8-tetrachlorodibenzo-p-dioxine, polychlorinated biphenyl 153, diethylhexyl-phthalate, and bisphenol A) were compared with changes provoked by a high-fat high-sucrose (HFHS) diet not containing the pollutant mixture...
April 8, 2017: Journal of Nutritional Biochemistry
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