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Drug dosing in obesity

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https://www.readbyqxmd.com/read/28531772/diet-induced-weight-loss-and-markers-of-endothelial-dysfunction-and-inflammation-in-treated-patients-with-type-2-diabetes
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28420586/impaired-oral-absorption-of-methylphenidate-after-roux-en-y-gastric-bypass
#13
REVIEW
Carmil Azran, Peter Langguth, Arik Dahan
The anatomic and physiologic changes in the gastrointestinal (GI) tract after bariatric surgery may significantly affect the pharmacokinetics of medications taken by the patients for various reasons. Unfortunately, there is little information regarding changes in drug absorption after bariatric surgeries, limiting the ability of medical professionals to produce clear recommendations on what changes should be made to the formulations and dosing regimens of drugs after bariatric surgery. In this article, we report and analyze a case of 52-year-old male patient with morbid obesity and attention-deficit/hyperactivity disorder (ADHD) who experienced lack of methylphenidate efficacy after Roux en-Y gastric bypass (RYGB), which was eventually resolved by using the transdermal patch instead of an oral product...
March 9, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28417575/effect-of-weight-reduction-on-hemoglobin-a1c-in-weight-loss-trials-of-type-2-diabetes-patients
#14
Anders Gummesson, Elisabeth Nyman, Mikael Knutsson, Martin Karpefors
AIMS: To quantify the effect of weight loss on HbA1c at group level based on data from published weight loss trials in overweight and obese type 2 diabetes patients. METHODS: A systematic literature search in MEDLINE, EMBASE and Cochrane CENTRAL (January 1990 through December 2012) was conducted to identify prospective trials of energy-reduced diets, obesity drugs or bariatric surgery conducted in adult, overweight and obese T2D patients. Based on clinical data from 3 to 24 months of follow-up, a linear model was developed to describe the effect of weight reduction on HbA1c...
April 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28413099/second-line-biologic-therapy-optimization-in-rheumatoid-arthritis-psoriatic-arthritis-and-ankylosing-spondylitis
#15
REVIEW
Fabrizio Cantini, Laura Niccoli, Carlotta Nannini, Emanuele Cassarà, Olga Kaloudi, Ennio Giulio Favalli, Andrea Becciolini, Maurizio Benucci, Francesca Li Gobbi, Serena Guiducci, Rosario Foti, Marta Mosca, Delia Goletti
OBJECTIVE: The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies...
March 22, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28411363/animal-models-of-alcoholic-liver-disease-pathogenesis-and-clinical-relevance
#16
Bin Gao, Ming-Jiang Xu, Adeline Bertola, Hua Wang, Zhou Zhou, Suthat Liangpunsakul
Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models that have been useful for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals...
April 14, 2017: Gene Expression
https://www.readbyqxmd.com/read/28398897/book-reviews-great-ormond-street-handbook-of-paediatrics-2nd-edn-edited-by-stephan-strobel-lewis-spitz-stephen-d-marks-crc-press-2016-price-%C3%A2-63-99-pp-736-isbn-9781482222791-stroke-medicine-2nd-edn-hugh-markus-anthony-pereira-geoffrey-cloud-oxford-university
#17
https://www.readbyqxmd.com/read/28395380/streptozotocin-treated-high-fat-fed-mice-a-new-type-2-diabetes-model-used-to-study-canagliflozin-induced-alterations-in-lipids-and-lipoproteins
#18
Tian Yu, Mitchell J Sungelo, Ira J Goldberg, Hong Wang, Robert H Eckel
The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism...
May 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28390958/discovery-of-liver-directed-glucokinase-activator-having-anti-hyperglycemic-effect-without-hypoglycemia
#19
Anil M Deshpande, Debnath Bhuniya, Siddhartha De, Bhavesh Dave, Vinod P Vyavahare, Santosh H Kurhade, Sachin R Kandalkar, Keshav P Naik, Balasaheb S Kobal, Rahul D Kaduskar, Sujay Basu, Vaibhav Jain, Pratima Patil, Sandhya Chaturvedi Joshi, Ganesh Bhat, Amol A Raje, Satyanarayana Reddy, Jayasagar Gundu, Vamsi Madgula, Suhas Tambe, Prasad Shitole, Dhananjay Umrani, Anita Chugh, Venkata P Palle, Kasim A Mookhtiar
Glucokinase activators (GKAs) are among the emerging drug candidates for the treatment of type 2 diabetes (T2D). Despite effective blood glucose lowering in clinical trials, many pan-GKAs "acting both in pancreas and liver" have been discontinued from clinical development mainly because of their potential to cause hypoglycemia. Pan-GKAs over sensitize pancreatic GK, resulting in insulin secretion even at sub-normoglycemic level which might be a possible explanation for hypoglycemia. An alternative approach to minimize the risk of hypoglycemia is to use liver-directed GKAs, which are reported to be advancing well in clinical development...
March 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28387458/anti-tumorigenic-potential-of-a-novel-orlistat-aicar-combination-in-prostate-cancer-cells
#20
Clayton Wright, Anand Krishnan V Iyer, Vivek Kaushik, Neelam Azad
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti-obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell-lines (DU145, PC3, and LNCaP)...
April 7, 2017: Journal of Cellular Biochemistry
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