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https://www.readbyqxmd.com/read/27925239/physiologically-based-pharmacokinetic-modeling-revealed-minimal-codeine-intestinal-metabolism-in-first-pass-removal-in-rats
#1
Keumhan Noh, Shu Chen, Qi J Yang, K Sandy Pang
The physiologically-based model with segregated flow to the intestine (SFM-PBPK; partial, lower flow to enterocyte region vs. greater flow to serosal region) was found to describe first-pass glucuronidation of morphine (M) to morphine-3β-glucuronide (MG) in rats after intraduodenal (ID) and intravenous (IV) administration better than the traditional model (TM), for which a single intestinal flow perfused the whole of the intestinal tissue. The SFM described a greater extent of intestinal M glucuronidation for ID vs...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27924154/early-diagnosis-of-brain-metastases-using-a-biofluids-metabolomics-approach-in-mice
#2
James R Larkin, Alex M Dickens, Timothy D W Claridge, Claire Bristow, Kleopatra Andreou, Daniel C Anthony, Nicola R Sibson
Over 20% of cancer patients will develop brain metastases. Prognosis is currently extremely poor, largely owing to late-stage diagnosis. We hypothesized that biofluid metabolomics could detect tumours at the micrometastatic stage, prior to the current clinical gold-standard of blood-brain barrier breakdown. Metastatic mammary carcinoma cells (4T1-GFP) were injected into BALB/c mice via intracerebral, intracardiac or intravenous routes to induce differing cerebral and systemic tumour burdens. B16F10 melanoma and MDA231BR-GFP human breast carcinoma cells were used for additional modelling...
2016: Theranostics
https://www.readbyqxmd.com/read/27924041/exposome-explorer-a-manually-curated-database-on-biomarkers-of-exposure-to-dietary-and-environmental-factors
#3
Vanessa Neveu, Alice Moussy, Héloïse Rouaix, Roland Wedekind, Allison Pon, Craig Knox, David S Wishart, Augustin Scalbert
Exposome-Explorer (http://exposome-explorer.iarc.fr) is the first database dedicated to biomarkers of exposure to environmental risk factors. It contains detailed information on the nature of biomarkers, their concentrations in various human biospecimens, the study population where measured and the analytical techniques used for measurement. It also contains correlations with external exposure measurements and data on biological reproducibility over time. The data in Exposome-Explorer was manually collected from peer-reviewed publications and organized to make it easily accessible through a web interface for in-depth analyses...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27922496/metabolic-myopathies
#4
Mark A Tarnopolsky
PURPOSE OF REVIEW: Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. RECENT FINDINGS: The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27921456/capillary-electrophoresis-mass-spectrometry-as-a-tool-for-untargeted-metabolomics
#5
Antonia García, Joanna Godzien, Ángeles López-Gonzálvez, Coral Barbas
Highly polar and ionic metabolites, such as sugars, most amino acids, organic acids or nucleotides are not retained by conventional reversed-phase LC columns and polar stationary phases and hydrophilic-interaction LC lacks of robustness, which is still limiting their applications for untargeted metabolomics where reproducibility is a must. Biological samples such as blood, urine or even tissues include many hydrophilic compounds secreted from cells, their analysis is essential for biomarker discovery, disease progression or treatment effects...
January 2017: Bioanalysis
https://www.readbyqxmd.com/read/27920983/bacteremic-renal-stone-associated-urinary-tract-infection-caused-by-nontypable-haemophilus-influenzae-a-rare-invasive-disease-in-an-immunocompetent-patient
#6
Masanao Fujii, Harumi Gomi, Haruhiko Ishioka, Noriko Takamura
Haemophilus species are known to colonize the upper respiratory tract and can cause infections. However Haemophilus influenzae has been rarely described as a cause of genitourinary tract infection. We report a 44-year-old nonimmunocompromised Japanese man with bacteremic pyelonephritis caused by a nontypable H. influenzae associated with a left ureteral calculus. The organism was isolated from both blood and urine cultures. Treatment consisted of 14 days of intravenous ceftriaxone and oral amoxicillin one after than other and insertion of a left ureteral stent...
2017: IDCases
https://www.readbyqxmd.com/read/27919963/expression-levels-of-piwi-interacting-rna-pir-823-are-deregulated-in-tumor-tissue-blood-serum-and-urine-of-patients-with-renal-cell-carcinoma
#7
Robert Iliev, Michal Fedorko, Tana Machackova, Hana Mlcochova, Marek Svoboda, Dalibor Pacik, Jan Dolezel, Michal Stanik, Ondrej Slaby
BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919185/modeling-the-effect-of-succimer-dmsa-dimercaptosuccinic-acid-chelation-therapy-in-patients-poisoned-by-lead
#8
Jan C H van Eijkeren, J Daniël N Olie, Sally M Bradberry, J Allister Vale, Irma de Vries, Harvey J Clewell, Jan Meulenbelt, Claudine C Hunault
CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. MATERIALS AND METHODS: We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model...
December 5, 2016: Clinical Toxicology
https://www.readbyqxmd.com/read/27918992/investigation-of-the-metabolites-of-the-hif-stabilizer-fg-4592-roxadustat-in-five-different-in-vitro-models-and-in-a-human-doping-control-sample-using-high-resolution-mass-spectrometry
#9
Annelie Hansson, Mario Thevis, Holly Cox, Geoff Miller, Daniel Eichner, Ulf Bondesson, Mikael Hedeland
FG-4592 is a hypoxia-inducible factor (HIF) stabilizer, which can increase the number of red blood cells in the body. It has not been approved by regulatory authorities, but is available for purchase on the Internet. Due to its ability to improve the oxygen transportation mechanism in the body, FG-4592 is of interest for doping control laboratories, but prior to this study, little information about its metabolism was available. In this study, the metabolism of FG-4592 was investigated in a human doping control sample and in five in vitro models: human hepatocytes and liver microsomes, equine liver microsomes and S9 fraction and the fungus Cunninghamella elegans...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27918253/placental-growth-factor-alone-or-in-combination-with-soluble-fms-like-tyrosine-kinase-1-as-an-aid-to-the-assessment-of-women-with-suspected-pre-eclampsia-systematic-review-and-economic-analysis
#10
Geoff K Frampton, Jeremy Jones, Micah Rose, Liz Payne
BACKGROUND: Pre-eclampsia (PE) prediction based on blood pressure, presence of protein in the urine, symptoms and laboratory test abnormalities can result in false-positive diagnoses. This may lead to unnecessary antenatal admissions and preterm delivery. Blood tests that measure placental growth factor (PlGF) or the ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to PlGF could aid prediction of PE if either were added to routine clinical assessment or used as a replacement for proteinuria testing...
November 2016: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/27918198/ppar%C3%AE-dependent-increase-of-mouse-urine-output-by-gemfibrozil-and-fenofibrate
#11
Danjun Song, Min Luo, Manyun Dai, Shizhong Bu, Weihua Wang, Burong Zhang, Frank J Gonzalez, Aiming Liu
While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity...
September 6, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27917897/blood-borne-phagocytes-internalize-urate-microaggregates-and-prevent-intravascular-netosis-by-urate-crystals
#12
Elmar Pieterse, Ivica Jeremic, Christine Czegley, Daniela Weidner, Mona H C Biermann, Susan Veissi, Christian Maueröder, Christine Schauer, Rostyslav Bilyy, Tetiana Dumych, Markus Hoffmann, Luis E Munoz, Anders A Bengtsson, Georg Schett, Johan van der Vlag, Martin Herrmann
Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation. Little is known on the mechanism(s) that prevent nsMSU formation within hyperuricemic blood, which would potentially cause detrimental consequences for the host...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917313/open-surgery-versus-retroperitoneal-laparoscopic-nephrectomy-for-renal-tuberculosis-a-retrospective-study-of-120-patients
#13
Su Zhang, You Luo, Cheng Wang, Hu Xiong, Sheng-Jun Fu, Li Yang
BACKGROUND: Laparoscopic renal surgery has been widely used in the treatment of renal diseases. However, there is still little research about its application in addressing renal tuberculosis. The purpose of this study is to retrospectively investigate the surgical results of laparoscopic and open surgery for nonfunctional tuberculous kidneys. METHODS: Between May 2011 and June 2016, 120 nephrectomies were performed in patients with a nonfunctional tuberculous kidney...
2016: PeerJ
https://www.readbyqxmd.com/read/27915431/time-dependent-postmortem-redistribution-of-morphine-and-its-metabolites-in-blood-and-alternative-matrices-application-of-ct-guided-biopsy-sampling
#14
Sandra N Staeheli, Dominic Gascho, Lars C Ebert, Thomas Kraemer, Andrea E Steuer
Interpretation of postmortem morphine concentrations in forensic toxicology provides several pitfalls such as missing information on tolerance, analyte stability, or postmortem redistribution (PMR). Recently, it had been shown that computed tomography (CT)-guided collection of biopsies using a robotic arm (virtobot) provides a valuable strategy for systematic studies on time-dependent PMR. Using this technique, time-dependent PMR of morphine and its metabolites was investigated in 12 cases. At admission to the institute (t1), femoral and heart blood (right ventricle) as well as biopsies from the right lung, the right kidney, liver, spleen, and muscle tissue were collected...
December 3, 2016: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/27915394/timelines-of-the-free-particle-and-fixed-particle-models-of-stone-formation-theoretical-and-experimental-investigations
#15
REVIEW
D J Kok, W Boellaard, Y Ridwan, V A Levchenko
Two major theories on renal stone formation will be reviewed, the "free-particle" and "fixed-particle" mechanisms. These theories combine data on intrinsic factors (inborn metabolic errors), extrinsic factors (diet), renal cell responses and the physico-chemistry and biochemistry of urine into mechanisms of stone formation. This paper describes the specific role of time in both mechanisms. The timeline of crystal- and stone formation was deducted from literature data and was measured for two stones using radioisotope decay analysis...
December 3, 2016: Urolithiasis
https://www.readbyqxmd.com/read/27914867/new-hbm-values-for-emerging-substances-inventory-of-reference-and-hbm-values-in-force-and-working-principles-of-the-german-human-biomonitoring-commission
#16
REVIEW
Petra Apel, Jürgen Angerer, Michael Wilhelm, Marike Kolossa-Gehring
The German Human Biomonitoring Commission (HBM Commission) derives health-related guidance values (Human Biomonitoring assessment values, HBM values) according to the procedures described in the HBM Commission's position papers. Since the last adaption of the methodology in 2014, the HBM Commission has established a series of new HBM values, mainly on the basis of internationally agreed TDI/RfD values, or of toxicologically well- founded points of departure observed in animal studies. The derivation of these new HBM values for HBCDD, triclosan, 2-MBT, PFOA and PFOS as well as for the metabolites of glycol ethers, of Hexamoll(®) DINCH(®), DPHP, DEHTP, NMP, NEP, and 4-MBC is specified, and the HBM values are presented together with already established HBM values for other substances...
September 17, 2016: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/27914708/generation-and-phenotypic-analysis-of-mice-lacking-all-urea-transporters
#17
Tao Jiang, Yingjie Li, Anita T Layton, Weiling Wang, Yi Sun, Min Li, Hong Zhou, Baoxue Yang
Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian kidney. UT inhibitors have diuretic activity and could be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27914612/dexamethasone-induced-diuresis-is-associated-with-inhibition-of-the-renin-angiotensin-aldosterone-system-in-rats
#18
Chao Liu, Ning Ge, Jian-Long Zhai, Jian-Xin Zhang
In heart failure (HF) patients, diuretics remain the cornerstone of therapy to relieve fluid retention. However, the resulting volume loss activates the renin-angiotensin-aldosterone system (RAAS), which blunts the decline in volume depletion and blood pressure. RAAS activation, in turn, compromises the diuretic decongesting effect. Although corticosteroids can induce potent diuresis in HF patients, the effects of corticosteroids on RAAS activation remain unclear. Therefore, we assessed the effects of dexamethasone (Dex) on urine output and plasma angiotensin II and aldosterone levels in rats following water deprivation-induced dehydration, following induction of chronic HF (CHF), and following induction of CHF and volume expansion therapy...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27914528/food-advanced-glycation-end-products-aggravate-the-diabetic-vascular-complications-via-modulating-the-ages-rage-pathway
#19
Xing Lv, Gao-Hong Lv, Guo-Ying Dai, Hong-Mei Sun, Hui-Qin Xu
The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27913748/a-3-year-follow-up-of-a-patient-with-acute-renal-failure-caused-by-thrombotic-microangiopathy-related-to-antiphospholipid-syndrome-case-report
#20
X-J Zhou, M Chen, S-X Wang, F-D Zhou, M-H Zhao
BACKGROUND: Microvascular manifestations of antiphospholipid antibody syndrome in the kidneys include acute renal failure, thrombotic microangiopathy and hypertension. Therapy has been largely empiric. CASE REPORT: A 49-year-old Chinese man presented with anuric acute renal failure without abundant proteinuria and heavy haematuria, but markedly low levels of urinary sodium, potassium and chlorine upon admission. On day 1 of hospitalization, his thrombocytopenia, anaemia and renal failure showed rapid progression...
December 2, 2016: Lupus
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