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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
#1
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/28698250/clinical-relevance-of-intraperitoneal-pressure-in-peritoneal-dialysis-patients
#2
Loreley A Betancourt
INTRODUCTION: Intraperitoneal pressure (IPP) in peritoneal dialysis (PD) increases in sitting and upright positions and is related to some individual characteristics. Adverse effects can appear with IPP > 20 cm H2O. Few studies about peritoneal transport or abdominal wall problems have directly measured IPP. We measured IPP in our prevalent PD patients to identify the clinical factors related to its variability and its possible association with peritoneal transport and abdominal wall complications...
July 11, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28658175/association-between-periodontal-disease-and-non-communicable-diseases-a-12-year-longitudinal-health-examinee-cohort-study-in-south-korea
#3
Jae-Hong Lee, Jin-Young Oh, Tae-Mi Youk, Seong-Nyum Jeong, Young-Taek Kim, Seong-Ho Choi
The National Health Insurance Service-Health Examinee Cohort during 2002 to 2013 was used to investigate the associations between periodontal disease (PD) and the following non-communicable diseases (NCDs): hypertension, diabetes mellitus, osteoporosis, cerebral infarction, angina pectoris, myocardial infarction, and obesity.Univariate and multivariate logistic regression analyses adjusting for potential confounders during the follow-up period-including age, sex, household income, insurance status, residence area, health status, and comorbidities-were used to estimated odds ratios (ORs) with 95% confidence intervals (CIs) in order to assess the associations between PD and NCDs...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28628147/-association-between-social-support-and-self-management-behaviors-among-patients-with-diabetes-in-community
#4
(no author information available yet)
OBJECTIVE: To study the status quo of directive and nondirective support from family or friends among patients with diabetes in community and to explore the association between directive, nondirective support from family or friends and self-management behaviors. METHODS: The data of the subjects were from the "Community Diagnosis in Tongzhou District, Beijing" survey. Questionnaire-based investigation, physical examination and glycated hemoglobin test were conducted on 474 eligible patients in community...
June 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28627418/alterations-in-neuronal-control-of-body-weight-and-anxiety-behavior-by-glutathione-peroxidase-4-deficiency
#5
Sonja C Schriever, Annemarie Zimprich, Katrin Pfuhlmann, Peter Baumann, Florian Giesert, Valentina Klaus, Dhiraj G Kabra, Ulrich Hafen, Artem Romanov, Matthias H Tschöp, Wolfgang Wurst, Marcus Conrad, Sabine M Hölter, Daniela Vogt Weisenhorn, Paul T Pfluger
Elevated levels of oxidative stress and neuronal inflammation in the hypothalamus or ventral midbrain, respectively, represent common denominators for obesity and Parkinson's Disease (PD). However, little is known about defense mechanisms that protect neurons in these regions from oxidative damage. Here, we aimed to assess whether murine Gpx4, a crucial antioxidant enzyme that protects neurons from membrane damage and ferroptosis, is critical for the protection from neuronal inflammation in two distinct pathophysiologic diseases, namely metabolic dysfunction in diet-induced obesity or PD...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28571972/discovery-of-novel-and-potent-stearoyl-coenzyme-a-desaturase-1-scd1-inhibitors-as-anticancer-agents
#6
Keisuke Imamura, Naoki Tomita, Youichi Kawakita, Yoshiteru Ito, Kouji Ono, Noriyuki Nii, Tohru Miyazaki, Kazuko Yonemori, Michiko Tawada, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Ikuo Miyahisa, Masako Sasaki, Yoshinori Satomi, Megumi Hirayama, Ryuichi Nishigaki, Hironobu Maezaki
A lead compound A was identified previously as an stearoyl coenzyme A desaturase (SCD) inhibitor during research on potential treatments for obesity. This compound showed high SCD1 binding affinity, but a poor pharmacokinetic (PK) profile and limited chemical accessibility, making it suboptimal for use in anticancer research. To identify potent SCD1 inhibitors with more promising PK profiles, we newly designed a series of 'non-spiro' 4, 4-disubstituted piperidine derivatives based on molecular modeling studies...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28546369/the-utility-of-sonographic-assessment-in-selecting-patients-for-percutaneous-insertion-of-peritoneal-dialysis-catheter
#7
Renuka Shanmugalingam, Angela Makris, Hicham Hassan, Yan Li, Imelda DeGuzman, Hareeshan Nandakoban, Ananthakrishnapuram Aravindan, Govind Narayanan, Jeffrey Wong
♦Background: Percutaneous insertion of peritoneal dialysis (PD) catheters by nephrologists is a safe and effective alternative to open surgical techniques. These patients are usually carefully selected due to anatomical considerations and medical comorbidities, with the current literature suggesting exclusion of patients with prior abdominal surgery. ♦ Method: We conducted a retrospective cohort study of pre-dialysis patients who attended a preprocedural clinic in a tertiary center over 6 years. Procedural complications and catheter survival were assessed...
May 25, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28528793/comparison-of-dual-energy-x-ray-absorptiometry-and-bioimpedance-in-assessing-body-composition-and-nutrition-in-peritoneal-dialysis-patients
#8
Velena Popovic, Bo Zerahn, James Goya Heaf
OBJECTIVE: Peritoneal dialysis (PD) patients are characterized by protein malnutrition and muscle wasting. Reliable, easy, and cheap methods for evaluating nutrition are desirable. Three methods are commonly available: dual-energy X-ray absorptiometry (DXA), bioimpedance (BI), and subjective global assessment (SGA).The objective of the study was to compare the previously mentioned methods for assessment of body composition and nutritional status in PD patients. DESIGN: The study is cross-sectional and consisted of 72 PD patients from a single center PD ambulatorium...
May 18, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/28509343/the-influence-of-vascular-risk-factors-on-cognitive-function-in-early-parkinson-s-disease
#9
Maxime Doiron, Mélanie Langlois, Nicolas Dupré, Martine Simard
OBJECTIVES: Hypertension, dyslipidemia, diabetes, and obesity are well-established risk factors for cognitive impairment and dementia in older adults. In contrast, previous studies that have assessed the impact of vascular risk factors (VRFs) on cognition in Parkinson's disease (PD) have had methodological limitations and reported conflicting findings. We address this question in a large well-characterized cohort of de novo PD patients. METHODS: A total of 367 untreated and non-demented patients aged 50 years and older with early PD (H&Y = 1...
May 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28508609/oral-health-in-children-with-obesity-or-diabetes-mellitus
#10
Fima Lifshitz, Patricia Lucia Casavalle, Noemí Bordoni, Patricia Noemi Rodriguez, Silvia Maria Friedman
Oral health status must be considered in the care of children with obesity (OB) and diabetes mellitus (DM). The health of these patients' mouths may have significant effects on their overall health and evolution of their disease. Here we address periodontal disease (PD) and dental caries (DC), since these are two of the most common chronic diseases affecting OB and DM patients. OB plays a plausible role in the development of PD. Both overall OB and central adiposity are associated with increased hazards of gingivitis and its progression to PD...
December 2016: Pediatric Endocrinology Reviews: PER
https://www.readbyqxmd.com/read/28508538/prognostic-value-of-predialysis-indices-for-technique-failure-and-mortality-in-peritoneal-dialysis-patients
#11
Masaru Matsui, Yasuhiro Akai, Ken-Ichi Samejima, Hideo Tsushima, Kaori Tanabe, Katsuhiko Morimoto, Miho Tagawa, Yoshihiko Saito
Technique failure remains a frequent cause of peritoneal dialysis (PD) withdrawal. Many post-commencement predictors of PD technique failure have been identified, while predialysis predictors have remained unclear. The aim of this study was to identify predialysis indices for technique failure in PD patients. We recruited 206 consecutive PD patients who were treated at Nara Medical University Hospital between 1 April 1997 and 31 December 2012. Forty-eight patients were excluded because of transition from hemodialysis (HD) or withdrawal from PD within 3 months, leaving 158 patients for analysis...
May 15, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28461146/impact-of-obesity-on-short-and-long-term-results-following-a-pancreatico-duodenectomy
#12
Awad Shamali, Vishal Shelat, Bashar Jaber, Aisha Wardak, Mohamed Ahmed, Martina Fontana, Thomas Armstrong, Mohammed Abu Hilal
BACKGROUND: The impact of obesity on short and long term outcomes following a pancreatico-duodenectomy (PD) is still unclear and needs further clarification. METHODS: Demographic, operative and outcomes data in 524 patients undergoing PD were analysed. RESULTS: Ninety-seven patients (18.5%) had BMI greater than or equal to 30 kg/m(2) (group A) and 427 patients (81.5%) had BMI less than 30 kg/m(2) (group B). Group A had a significantly greater operative duration, (375 vs 360 min, p = 0...
June 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28447069/long-term-calorie-restriction-in-humans-is-not-associated-with-indices-of-delayed-immunologic-aging-a-descriptive-study
#13
A Janet Tomiyama, Jeffrey M Milush, Jue Lin, James M Flynn, Pankaj Kapahi, Eric Verdin, Elizabeth Sinclair, Simon Melov, Elissa S Epel
BACKGROUND: Delayed immunologic aging is purported to be a major mechanism through which calorie restriction (CR) exerts its anti-aging effects in non-human species. However, in non-obese humans, the effect of CR on the immune system has been understudied relative to its effects on the cardiometabolic system. OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in non-obese humans. METHODS: We tested whether long-term CR practitioners (average 10.03 years of CR) evidenced decreased expression of T cell immunosenescence markers and longer immune cell telomeres compared to gender-, race/ethnicity-, age-, and education-matched "healthy" Body Mass Index (BMI) and "overweight"/"obese" BMI groups...
March 31, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/28428879/a-systems-biology-approach-to-investigating-the-influence-of-exercise-and-fitness-on-the-composition-of-leukocytes-in-peripheral-blood
#14
Michael P Gustafson, Ara Celi DiCostanzo, Courtney M Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A Gastineau, Bruce D Johnson, Allan B Dietz
BACKGROUND: Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy. METHODS: We investigated the effects of acute exercise on the composition of peripheral blood leukocytes over time in a male population of varying fitness...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28356069/broad-induction-of-immunoregulatory-mechanisms-after-a-short-course-of-anti-il-7r%C3%AE-antibodies-in-nod-mice
#15
Cristina Vazquez-Mateo, Justin Collins, Michelle Fleury, Hans Dooms
BACKGROUND: Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of the insulin-producing β-cells in the pancreas. Therefore, approaches that effectively halt the pathogenic T cell response are predicted to have preventive or therapeutic benefit for type 1 diabetes patients. We previously demonstrated that long-term blocking of IL-7 signaling, which is critical for the survival and function of T cells, prevented and reversed type 1 diabetes in non-obese diabetic mice...
March 29, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28343398/an-anti-programmed-death-1-antibody-%C3%AE-pd-1-fusion-protein-that-self-assembles-into-a-multivalent-and-functional-%C3%AE-pd-1-nanoparticle
#16
Peng Zhao, Djordje Atanackovic, Shuyun Dong, Hideo Yagita, Xiao He, Mingnan Chen
Cancer immune checkpoint therapy has achieved remarkable clinical successes in various cancers. However, current immune checkpoint inhibitors block the checkpoint of not only the immune cells that are important to cancer therapy but also the immune cells that are irrelevant to the therapy. Such an indiscriminate blockade limits the efficacy and causes the autoimmune toxicity of the therapy. It might be beneficial to use a carrier to target immune checkpoint inhibitors to cancer-reactive immune cells. Here, we explore a method to load the inhibitors into carriers...
April 19, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28289180/beneficial-effects-of-apelin-on-vascular-function-in-patients-with-central-obesity
#17
Francesca Schinzari, Augusto Veneziani, Nadia Mores, Angela Barini, Nicola Di Daniele, Carmine Cardillo, Manfredi Tesauro
Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr(1))apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients...
May 2017: Hypertension
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-up-regulates-programmed-cell-death-protein-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#18
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the T-cell receptor complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo...
June 2017: Immunology
https://www.readbyqxmd.com/read/28207885/the-association-between-body-mass-index-and-mortality-among-asian-peritoneal-dialysis-patients-a-meta-analysis
#19
Jing Liu, Xiaoxi Zeng, Hyokyoung G Hong, Yi Li, Ping Fu
BACKGROUND: Previous studies have revealed that increased body mass index (BMI) is associated with decreased mortality among hemodialysis patients. However, few studies have dealt with the association between BMI and mortality among patients undergoing peritoneal dialysis (PD) and even fewer studies have focused on the Asian PD patients. The reported studies were often non-conclusive and some even yielded contradictory results. This paper, to our best knowledge, registers the first attempt to systematically review the current literature and summarize new results on the association between BMI and mortality among the Asian PD population...
2017: PloS One
https://www.readbyqxmd.com/read/28126541/pharmacokinetics-of-levonorgestrel-and-ulipristal-acetate-emergency-contraception-in-women-with-normal-and-obese-body-mass-index
#20
Piyapa Praditpan, Angie Hamouie, Cale N Basaraba, Renu Nandakumar, Serge Cremers, Anne R Davis, Carolyn L Westhoff
OBJECTIVE: This study compares the pharmacokinetics (PK) of levonorgestrel (LNG) emergency contraceptive (EC) and ulipristal acetate (UPA)-EC between normal-body mass index (BMI) and obese-BMI women. STUDY DESIGN: This prospective, randomized crossover study evaluates the PK of women after single doses of LNG-EC (1.5mg) and UPA-EC (30mg). Study procedures took place during clinical research unit admissions, where participants received a standardized meal and each study drug, in random order, during two separate 24-h admissions...
January 23, 2017: Contraception
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