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https://www.readbyqxmd.com/read/28213850/gamma-hydroxybutyrate-ghb-content-in-hair-samples-correlates-negatively-with-age-in-succinic-semialdehyde-dehydrogenase-deficiency
#1
S S Johansen, X Wang, D Sejer Pedersen, P L Pearl, J-B Roullet, G R Ainslie, K R Vogel, K M Gibson
Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD...
February 18, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28212631/anti-malarial-effect-of-novel-chloroquine-derivatives-as-agents-for-the-treatment-of-malaria
#2
Seon-Ju Yeo, Dong-Xu Liu, Hak Sung Kim, Hyun Park
BACKGROUND: The widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. In this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. RESULTS: Novel two derivatives (SKM13 and SKM14) were synthesized based on the chloroquine (CQ) template containing modified side chains such as α,β-unsaturated amides and phenylmethyl group. The selective index indicated that SKM13 was 1...
February 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#3
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212414/decline-in-infection-related-morbidities-following-drug-mediated-reductions-in-the-intensity-of-schistosoma-infection-a-systematic-review-and-meta-analysis
#4
Gisele Andrade, David J Bertsch, Andrea Gazzinelli, Charles H King
BACKGROUND: Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity...
February 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28210757/sildenafil-a-phosphodiesterase-type-5-inhibitor-downregulates-osteopontin-in-human-peripheral-blood-mononuclear-cells
#5
Beata Kaleta, Agnieszka Boguska
The aim of this study was to investigate the ability of sildenafil to regulate osteopontin (OPN) gene and protein in peripheral blood mononuclear cells (PBMCs) from healthy blood donors. OPN is expressed by a wide variety of cell types, including immune cells. OPN functions are linked to various physiological and pathological conditions. Sildenafil is a selective inhibitor of type 5 phosphodiesterase. Sildenafil has recently been found to have immunomodulatory effects in animal models and in studies performed in humans...
February 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28209220/very-low-density-lipoprotein-associated-apolipoproteins-predict-cardiovascular-events-and-are-lowered-by-inhibition%C3%A2-of%C3%A2-apoc-iii
#6
Raimund Pechlaner, Sotirios Tsimikas, Xiaoke Yin, Peter Willeit, Ferheen Baig, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Joseph L Witztum, Veronica J Alexander, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD. OBJECTIVES: This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome...
February 21, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28209132/urinary-tract-infection-among-fistula-patients-admitted-at-hamlin-fistula-hospital-addis-ababa-ethiopia
#7
Matifan Dereje, Yimtubezinesh Woldeamanuel, Daneil Asrat, Fekade Ayenachew
BACKGROUND: Urinary Tract Infection (UTI) causes a serious health problem and affects millions of people worldwide. Patients with obstetric fistula usually suffer from incontinence of urine and stool, which can predispose them to frequent infections of the urinary tract. Therefore the aim of this study was to determine the etiologic agents, drug resistance pattern of the isolates and associated risk factor for urinary tract infection among fistula patients in Addis Ababa fistula hospital, Ethiopia...
February 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28209006/a-comparative-evaluation-of-serum-magnesium-in-diabetes-mellitus-type-2-patients-with-and-without-periodontitis-a-clinico-biochemical-study
#8
Akshatha Shetty, Rahul Bhandary, Biju Thomas, Amitha Ramesh
INTRODUCTION: Magnesium is an essential cation playing a crucial role in many physiological functions and its imbalance is associated with greater number of pathological situations. Oxidative stress is usually increased due to decreased essential nutrients. Hence, any imbalance of essential nutrients like serum magnesium can significantly play a role in the pathobiology of periodontitis in the presence of diabetes, as diabetes and chronic periodontitis are two chronic diseases that have been biologically linked...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28207836/tmg-123-a-novel-glucokinase-activator-exerts-durable-effects-on-hyperglycemia-without-increasing-triglyceride-in-diabetic-animal-models
#9
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
https://www.readbyqxmd.com/read/28207540/different-dosages-of-mifepristone-versus-enantone-to-treat-uterine-fibroids-a-multicenter-randomized-controlled-trial
#10
Chongdong Liu, Qi Lu, Hong Qu, Li Geng, Meilu Bian, Minli Huang, Huilan Wang, Youzhong Zhang, Zeqing Wen, Shurong Zheng, Zhenyu Zhang
BACKGROUND: To evaluate the efficacy and safety of 10 mg and 25 mg mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids. METHODS: This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207493/treatment-of-lupus-nephritis-current-paradigms-and-emerging-strategies
#11
Maria Dall'Era
PURPOSE OF REVIEW: Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies. RECENT FINDINGS: Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity...
February 15, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#12
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205212/sarcoidosis-extent-relates-to-molecular-variability
#13
Calixte S Monast, Katherine Li, Marc A Judson, Robert P Baughman, Eric Wadman, Rosemary Watt, Philip E Silkoff, Elliot S Barnathan, Carrie Brodmerkel
The molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment of sarcoidosis have not been elucidated. Peripheral samples from sarcoidosis subjects who participated in a phase 2 study of golimumab (anti-TNFα) and ustekinumab (anti-IL12p40) were used to measure the whole blood transcriptome and levels of serum proteins. Differential gene and protein expression analyses were used to explore the molecular differences between sarcoidosis phenotypes as defined by extent of organ involvement...
February 16, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28202290/effect-of-psychotropic-drug-treatment-on-sterol-metabolism
#14
Željka Korade, Wei Liu, Emily B Warren, Kristan Armstrong, Ned A Porter, Christine Konradi
Cholesterol metabolism is vital for brain function. Previous work in cultured cells has shown that a number of psychotropic drugs inhibit the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the final steps in cholesterol biosynthesis. This leads to the accumulation of 7-dehydrocholesterol (7DHC), a molecule that gives rise to oxysterols, vitamin D, and atypical neurosteroids. We examined levels of cholesterol and the cholesterol precursors desmosterol, lanosterol, 7DHC and its isomer 8-dehydrocholesterol (8DHC), in blood samples of 123 psychiatric patients on various antipsychotic and antidepressant drugs, and 85 healthy controls, to see if the observations in cell lines hold true for patients as well...
February 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28201955/the-prevalence-of-metabolic-syndrome-and-different-obesity-phenotype-in-iranian-male-military-personnel
#15
Moloud Payab, Shirin Hasani-Ranjbar, Yaser Merati, Alireza Esteghamati, Mostafa Qorbani, Mahboobeh Hematabadi, Hoda Rashidian, Nooshin Shirzad
Obesity, especially when concentrated in the abdominal area, is often associated with the presence of metabolic syndrome. Stress, particularly occupational stress, is one of the most important factors contributing to the increased prevalence of metabolic syndrome components among different populations. This study aimed to investigate the prevalence of overweight and obesity as well as the criteria for metabolic syndrome and its risk factors and different obesity phenotype in a population of military personnel aged 20 to 65 years...
March 2017: American Journal of Men's Health
https://www.readbyqxmd.com/read/28197288/serum-triglyceride-lowering-effect-of-cilnidipine-in-patients-with-essential-hypertension
#16
Prakash Kumar, Arijit Das, Satish Chandra, Manju Gari, U S P Keshri, Kusum Kumari
BACKGROUND: Many epidemiological studies have established the relationship between hypertension and dyslipidemia. Calcium channel blockers (CCBs) are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine as a newer CCB acting by blocking both L- and N-type calcium channels possesses additional beneficial effects apart from lowering blood pressure (BP). The aim of this study was to evaluate the effectiveness of cilnidipine in patients with essential hypertension with borderline dyslipidemia and its effects on lipid profile...
October 2016: Cardiology Research
https://www.readbyqxmd.com/read/28196046/bioequivalence-of-a-new-oral-levosulpiride-formulation-compared-with-a-standard-one-in-healthy-volunteers
#17
Simona De Gregori, Laura Cipollina, Annalisa De Silvestri, Marianna Ventura, Roberta Michelini, Monica Morosini, Michela Montagna, Carmine Tinelli, Mario Regazzi, Mariadelfina Molinaro, Roberto Imberti
BACKGROUND: A monocentric, single-dose, open-label, two-way, crossover randomized study was conducted by the San Matteo Phase I Clinical Trial Unit and Experimental Therapy (Pavia, Italy) to assess the bioequivalence and the systemic tolerability of a new oral formulation of levosulpiride (tablet 25 mg: test) versus a commercially available formulation on the Italian market (tablet 25 mg: reference). METHODS: Thirty-five healthy adult volunteers, males (n = 19) and females (n = 16), aged between 18 and 55 years were screened and 32 of them were enrolled in the study...
February 11, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28195743/p-gp-protein-expression-and-transport-activity-in-rodent-seizure-models-and-human-epilepsy
#18
Anika M S Hartz, Anton Pekcec, Emma L B Soldner, Yu Zhong, Juli Schlichtiger, Bjoern Bauer
A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to anti-seizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of anti-seizure drugs, and thus, contribute to anti-seizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28194469/phenylephrine-induced-cardiac-hypertrophy-is-attenuated-by-a-histone-acetylase-inhibitor-anacardic-acid-in-mice
#19
Chang Peng, Xiaomei Luo, Shuo Li, Huichao Sun
Cardiac hypertrophy is a complex process involving highly coordinated but tight regulation of multiple elements, such as in epigenetics, which make an important contribution to myocardium remodeling and cardiac hypertrophy. Epigenetic regulations, particularly histone acetylation, have been implicated in cardiac hypertrophy, however, the exact mechanism is still largely unknown. In the present study, we explored the potential attenuating effects of Chinese herbal extract anacardic acid on phenylephrine-induced cardiac hypertrophy and the underlying mechanism...
February 14, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28193995/evaluating-the-effectiveness-of-gtm-1-rapamycin-and-carbamazepine-on-autophagy-and-alzheimer-disease
#20
Lijuan Zhang, Lina Wang, Run Wang, Yuan Gao, Haoyue Che, Yonghua Pan, Peng Fu
BACKGROUND This study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study. MATERIAL AND METHODS Firstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze...
February 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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