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Drug dosing in obesity

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https://www.readbyqxmd.com/read/28726640/c1q-tnf-related-protein-6-ctrp6-links-obesity-to-adipose-tissue-inflammation-and-insulin-resistance
#1
Xia Lei, Marcus M Seldin, Hannah C Little, Nicholas Choy, Thomas Klonisch, G William Wong
Obesity is associated with chronic low-grade inflammation, and metabolic regulators linking obesity to inflammation have therefore received much attention. Secreted C1q/TNF-related proteins (CTRPs) are one such group of regulators that regulate glucose and fat metabolism in peripheral tissues and modulate inflammation in adipose tissue. We have previously shown that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by the anti-diabetic drug, rosiglitazone. Here, we provide evidence for a novel role of CTRP6 in modulating both inflammation and insulin sensitivity...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28718949/high-dosage-of-vitamin-d-regulates-the-energy-metabolism-and-increases-insulin-sensitivity-but-are-associated-with-high-levels-of-kidney-damage
#2
Rafael Calais Gaspar, José Diego Botezelli, Gabriel Keine Kuga, Vitor Rosetto Muñoz, Andressa Coope, Rodrigo Martins Pereira, Adelino Sanchez Ramos da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle, José Rodrigo Pauli
Preclinical Research Metabolic disorders are responsible for more than 60% of all deaths worldwide. Calcitriol or vitamin D (vitD) deficiency is associated with a large proportion of these diseases is an important therapeutic target for exploration. This study evaluated the administration of high doses of vitD (3000 IU/kg) in obese and insulin-resistant C57BL/6J mice. Our results demonstrated that although high doses of vitD provided metabolic benefits such as increased insulin sensitivity and decreased body mass, this was associated with significant damage in the kidneys of obese mice...
July 18, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28718324/physical-health-and-drug-safety-in-individuals-with-schizophrenia
#3
Tamara Pringsheim, Martina Kelly, Doug Urness, Michael Teehan, Zahinoor Ismail, David Gardner
BACKGROUND: While antipsychotic medications are the mainstay of therapy for individuals with schizophrenia and psychotic disorders, their use is associated with adverse effects on physical health that require the attention and care of prescribers. METHODS: We used the ADAPTE process to adapt existing guideline recommendations from the National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the dosing of antipsychotics and antipsychotic polypharmacy, screening for adverse effects of antipsychotics, and management of metabolic and extrapyramidal side effects to the Canadian context...
January 1, 2017: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/28707286/intragastric-balloon-treatment-for-obesity-review-of-recent-studies
#4
REVIEW
Chinara M Tate, Allan Geliebter
INTRODUCTION: The FDA recently approved three intragastric balloon (IGB) devices, ReShape, ORBERA™, and Obalon for treatment of obesity. Given the high cost, complication risk, and invasiveness of bariatric surgery, IGB treatment may present a safer and lower cost option for weight reduction. IGBs are generally placed in the stomach endoscopically for up to 6 months to reduce gastric capacity, enhance feelings of fullness, and induce weight loss. The mechanism of action likely involves stimulation of gastric mechanoreceptors triggering short-acting vagal signals to brain regions implicated in satiety...
July 13, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-anti-obesity-effects-in-diet-induced-obese-mice
#5
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
Glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans in addition to their potent anti-diabetic effects. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their anti-obesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog, exenatide, for the development of promising new anti-obesity drugs...
July 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28690544/lotus-leaf-aqueous-extract-reduces-visceral-fat-mass-and-ameliorates-insulin-resistance-in-hfd-induced-obese-rats-by-regulating-ppar%C3%AE-2-expression
#6
Kemin Yan, Huijuan Zhu, Jian Xu, Hui Pan, Naishi Li, Linjie Wang, Hongbo Yang, Meijuan Liu, FengYing Gong
Objectives: Lotus leaf is a kind of traditional Chinese medicine. We aimed to explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome proliferative activated receptor γ2 (PPARγ2) expression in preadipocytes and adipocytes and further investigate its effects on high fat diet (HFD)-induced obese rats. Methods: pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reporter gene expression plasmid containing PPARγ2 promoter, was stably transfected into 3T3-L1 preadipocytes. PPARγ2 promoter activities were determined by assaying the luciferase activities...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28669771/antidiabetic-antioxidant-and-anti-inflammatory-properties-of-water-and-n-butanol-soluble-extracts-from-saharian-anvillea-radiata-in-high-fat-diet-fed-mice
#7
Chouaib Kandouli, Mathieu Cassien, Anne Mercier, Caroline Delehedde, Emilie Ricquebourg, Pierre Stocker, Mourad Mekaouche, Zineb Leulmi, Aicha Mechakra, Sophie Thétiot-Laurent, Marcel Culcasi, Sylvia Pietri
ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties...
July 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28666894/pharmacological-comparison-of-traditional-and-non-traditional-cannabinoid-receptor-1-blockers-in-rodent-models-in-vivo
#8
Balázs Varga, Ferenc Kassai, György Szabó, Péter Kovács, János Fischer, István Gyertyán
Cannabinoid receptor 1 (CB1R) antagonists have been proven to be effective anti-obesity drugs; however, psychiatric side effects have halted their pharmaceutical development worldwide. Despite the emergence of next generation CB1R blockers, a preclinical head to head comparison of the anti-obesity and psychiatric side effect profiles of the key compounds has not been performed. Here, we compared classical CB1R antagonists (rimonabant, taranabant, otenabant, ibipinabant, and surinabant) and non-traditional CB1R blockers (the partial agonist O-1269, the neutral antagonists VCHSR and LH-21 and the peripherally acting inverse agonist JD-5037) using an in vivo screening cascade...
June 27, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28660593/is-obesity-the-new-hypertension-parallels-in-the-evolution-of-obesity-and-hypertension-as-recognized-disease-states
#9
REVIEW
Devika Umashanker, Alpana P Shukla, Katherine H Saunders, Louis J Aronne
Obesity and hypertension are recognized disease states that share many similarities including complex physiology, therapeutic response to both lifestyle modification and pharmacotherapy, and the need for long-term management. Both were initially believed to be disorders of lifestyle rather than true disease entities, and initial efforts at developing medical and surgical therapies were criticized. Ultimately, both have proven to be amenable to treatments that control their underlying physiology. Both hypertension and obesity have complex pathophysiology involving multiple regulatory pathways that may require combination therapies in addition to lifestyle modification to reach therapeutic goals...
August 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28658801/hypolipidaemic-effects-of-gymnema-sylvestre-on-high-fat-diet-induced-dyslipidaemia-in-wistar-rats
#10
Dheeraj Kumar Singh, Narendra Kumar, Anjula Sachan, Preet Lakhani, Sachin Tutu, Rajendra Nath, Amod Kumar Sachan, Rakesh Kumar Dixit
INTRODUCTION: Hyperlipidaemia is a well known risk factor for cardiovascular diseases. Lifestyle modification can be the initial step to reduce cholesterol levels. There are various drugs which are used to control dyslipidaemia. Treatment of lipid abnormalities is a lifelong battle. Moreover, the safety and effectiveness of long term lipid lowering treatment are questionable. Gymnema Sylvestre (GS) is a well known herb with various medicinal properties. AIM: To explore the hypolipidaemic activity of GS leaves extract...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28647460/a-prospective-study-evaluating-tobramycin-pharmacokinetics-and-optimal-once-daily-dosing-in-burn-patients
#11
Colin Lee, Sandra A N Walker, Scott E Walker, Winnie Seto, Andrew Simor, Marc Jeschke
BACKGROUND: Once-daily aminoglycoside dosing (ODA) is used in most patient populations to optimize antibacterial activity and reduce toxicity. Unfortunately, burn patients are excluded from ODA due to concerns over altered pharmacokinetics resulting in a shortened half-life and low peak aminoglycoside concentrations. Retrospective studies suggest that ODA may be appropriate if higher milligram/kilogram doses are used. However, no prospective clinical trials in burn patients exist to confirm these findings...
June 21, 2017: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/28645996/treatment-of-suspected-pulmonary-embolism-in-a-morbidly-obese-patient
#12
Viviene Heitlage, Mary Beth Borgstadt, Lisa Carlson
PURPOSE: A case highlighting challenges with enoxaparin dosage and monitoring in obese patients is presented. SUMMARY: A morbidly obese 22-year-old Caucasian female (height, 168 cm; weight, 322 kg; body mass index [BMI], 114 kg/m(2)) who presented to the emergency department with acute-onset dyspnea and hypoxia was empirically initiated on enoxaparin for suspected pulmonary embolism at the institution's standard maximum dosage (160 mg subcutaneously every 12 hours)...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28612554/-the-preliminary-investigation-of-glp-1-receptor-agonist-on-liver-steatosis-in-obese-mice
#13
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
#14
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
#15
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
#16
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...
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
#17
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
#18
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
#19
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
#20
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
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