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https://www.readbyqxmd.com/read/28438697/predicting-drug-loading-in-pla-peg-nanoparticles
#1
M Meunier, A Goupil, P Lienard
Polymer nanoparticles present advantageous physical and biopharmaceutical properties as drug delivery systems compared to conventional liquid formulations. Active pharmaceutical ingredients (APIs) are often hydrophobic, thus not soluble in conventional liquid delivery. Encapsulating the drugs in polymer nanoparticles can improve their pharmacological and bio-distribution properties, preventing rapid clearance from the bloodstream. Such nanoparticles are commonly made of non-toxic amphiphilic self-assembling block copolymers where the core (poly-[D,L-lactic acid] or PLA) serves as a reservoir for the API and the external part (Poly-(Ethylene-Glycol) or PEG) serves as a stealth corona to avoid capture by macrophage...
April 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28414302/increased-salt-consumption-induces-body-water-conservation-and-decreases-fluid-intake
#2
Natalia Rakova, Kento Kitada, Kathrin Lerchl, Anke Dahlmann, Anna Birukov, Steffen Daub, Christoph Kopp, Tetyana Pedchenko, Yahua Zhang, Luis Beck, Bernd Johannes, Adriana Marton, Dominik N Müller, Manfred Rauh, Friedrich C Luft, Jens Titze
BACKGROUND: The idea that increasing salt intake increases drinking and urine volume is widely accepted. We tested the hypothesis that an increase in salt intake of 6 g/d would change fluid balance in men living under ultra-long-term controlled conditions. METHODS: Over the course of 2 separate space flight simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3 salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained constant...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28411157/the-separate-effects-of-lipids-and-proteins-on-brain-mri-contrast-revealed-through-tissue-clearing
#3
Christoph Leuze, Markus Aswendt, Emily Ferenczi, Corey W Liu, Brian Hsueh, Maged Goubran, Qiyuan Tian, Gary Steinberg, Michael M Zeineh, Karl Deisseroth, Jennifer A McNab
Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY...
April 12, 2017: NeuroImage
https://www.readbyqxmd.com/read/28352627/treatment-of-cirrhosis-associated-hyponatremia-with-midodrine-and-octreotide
#4
Sharad Patel, Dai-Scott Nguyen, Anjay Rastogi, Minh-Kevin Nguyen, Minhtri K Nguyen
BACKGROUND: Hyponatremia in the setting of cirrhosis is a common electrolyte disorder with few therapeutic options. The free water retention is due to non-osmotic vasopressin secretion resulting from the cirrhosis-associated splanchnic vasodilatation. Therefore, vasoconstrictive therapy may correct this electrolyte abnormality. The aim of this study was to assess the efficacy of midodrine and octreotide as a therapeutic approach to increasing urinary electrolyte-free water clearance (EFWC) in the correction of cirrhosis-associated hyponatremia...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28288570/effect-of-tolvaptan-on-renal-water-and-sodium-excretion-and-blood-pressure-during-nitric-oxide-inhibition-a-dose-response-study-in-healthy-subjects
#5
Safa Al Therwani, Jeppe Bakkestrøm Rosenbæk, Frank Holden Mose, Jesper Nørgaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist. Nitric Oxide (NO) promotes renal water and sodium excretion, but the effect is unknown in the nephron's principal cells. In a dose-response study, we measured the effect of tolvaptan on renal handling of water and sodium and systemic hemodynamics, during baseline and NO-inhibition with L-NMMA (L-NG-monomethyl-arginine). METHODS: In a randomized, placebo-controlled, double blind, cross over study, 15 healthy subjects received tolvaptan 15, 30 and 45 mg or placebo...
March 13, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28272337/impact-of-isotonic-beverage-on-the-hydration-status-of-healthy-chinese-adults-in-air-conditioned-environment
#6
Phei Ching Siow, Wei Shuan Kimberly Tan, Christiani Jeyakumar Henry
People living in tropical climates spend much of their time in confined air-conditioned spaces, performing normal daily activities. This study investigated the effect of distilled water (W) or isotonic beverage (IB) on the hydration status in subjects living under these conditions. In a randomized crossover design, forty-nine healthy male subjects either consumed beverage or IB over a period of 8 h (8 h) in a controlled air-conditioned environment. Blood, urine, and saliva samples were collected at baseline and after 8 h...
March 7, 2017: Nutrients
https://www.readbyqxmd.com/read/28247754/small-sized-mpeg-plga-nanoparticles-of-schisantherin-a-with-sustained-release-for-enhanced-brain-uptake-and-anti-parkinsonian-activity
#7
Tongkai Chen, Chuwen Li, Ye Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson's disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (mPEG-PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of ∼91% and drug loading of ∼28%...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28195741/behavior-of-ppi-g2-dendrimer-in-a-microemulsion
#8
Shifra Rokach, Maria Francesca Ottaviani, Alexander I Shames, Abraham Aserin, Nissim Garti
Dendrimer nanostructures are of eminent interest in biomedical applications because of their uniform and well-defined molecular size and shape, and their ability to cross cell membranes and reduce the risk of premature clearance from the human body. Dendrimers perform as gene and drug carriers and have also shown significant therapeutic properties for treating cancer and neurodegenerative diseases. A complex drug delivery system, based on a dendrimer solubilized in the aqueous core of a water-in-oil (W/O) microemulsion (ME) along with the drug may combine the advantages of both dendrimers and MEs to provide better control of drug release...
March 1, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28063291/glucogenic-treatment-creates-an-optimal-metabolic-milieu-for-the-conception-period-in-ewes
#9
C Porcu, V Pasciu, S Succu, E Baralla, M E Manca, E Serra, G G Leoni, M Dattena, G C Bomboi, G Molle, S Naitana, F Berlinguer
This study determined the influence of a short-term glucogenic nutritional treatment on circulating concentrations of glucose, insulin, insulin-like growth factor 1 (IGF-1), nonesterified fatty acids (NEFA), and urea, and on their correspondent levels in follicular fluid (FF) collected 12 h after the end of the treatment. After estrous synchronization with intravaginal progestagen-impregnated sponges, 20 Sarda ewes were randomly allocated into two experimental groups (GLU and WAT) and, from day 7 to day 10 (day 0 = day of sponge removal), the GLU group was gavaged with a glycogenic mixture, whereas the WAT group was gavaged with water (control group)...
December 11, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28039404/free-radical-scavenging-decreases-endothelin-1-excretion-and-glomerular-albumin-permeability-during-type-1-diabetes
#10
Mohamed A Saleh, Carmen De Miguel, David I Stevens, Pamela K Carmines, David M Pollock, Jennifer S Pollock
Increased renal endothelin-1 (ET-1) production and an ETA receptor-dependent increase in glomerular albumin permeability (Palb) accompany type 1 diabetes mellitus (T1D). We hypothesized that T1D-induced oxidative stress contributes to renal ET-1 production and glomerular Palb Male rats with streptozotocin-induced T1D were provided free access to drinking water without additives (T1D rats) or containing the free radical scavenger tempol (1 mmol/L; T1D+Tempol). After 3 weeks, T1D+Tempol rats displayed lower urinary excretion of thiobarbituric acid reactive substances and glomerular superoxide production (dihydroethidium staining) compared to T1D rats...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28012395/regulatory-mechanism-of-mineral-balanced-deep-sea-water-on-hypocholesterolemic-effects-in-hepg2-hepatic-cells
#11
Kyu-Shik Lee, Yun-Suk Kwon, Soyoung Kim, Deok-Soo Moon, Hyeon Ju Kim, Kyung-Soo Nam
Several previous studies have shown the benefits of deep sea water (DSW) in lipid metabolism. However, the effects of DSW on cellular cholesterol accumulation and synthesis induced by high glucose or free fatty acid plus high glucose [4.5g/L] (FFA/glucose) have not been fully elucidated to date. Herein, we showed the effects of mineral-balanced DSW [magnesium (Mg):calcium (Ca)=3:1] (MB-DSW) on cholesterol metabolism induced by high glucose or FFA/glucose in HepG2 hepatic cells. Moreover, the effects of high ratio Mg DSW [Mg:Ca=40:1] (Mg40) were also investigated...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27940284/alamethicin-for-using-in-bioavailability-studies-re-evaluation-of-its-effect
#12
Maren Vollmer, Mirko Klingebiel, Sascha Rohn, Ronald Maul
A major pathway for the elimination of drugs is the biliary and renal excretion following the formation of more hydrophilic secondary metabolites such as glucuronides. For in vitro investigations of the phase II metabolism, hepatic microsomes are commonly used in the combination with the pore-forming peptide alamethicin, also to give estimates for the in vivo situation. Thus, alamethicin may represent a neglected parameter in the characterization of microsomal in vitro assays. In the present study, the influence of varying alamethicin concentrations on glucuronide formation of selected phenolic compounds was investigated systematically...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27849390/adverse-effects-of-tempol-on-hidrosaline-balance-in-rats-with-acute-sodium-overload
#13
N M Kouyoumdzian, Nl Rukavina Mikusic, G Cao, M R Choi, Sl Della Penna, B E Fernández, J E Toblli, M I Rosón
We studied the effects of tempol, an oxygen radical scavenger, on hydrosaline balance in rats with acute sodium overload. Male rats with free access to water were injected with isotonic (control group) or hypertonic saline solution (0.80 mol/l NaCl) either alone (Na group) or with tempol (Na-T group). Hydrosaline balance was determined during a 90 min experimental period. Protein expressions of aquaporin 1 (AQP1), aquaporin 2 (AQP2), angiotensin II (Ang II) and endothelial nitric oxide synthase (eNOS) were measured in renal tissue...
November 2016: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/27845866/a-canola-oil-supplemented-diet-prevents-type-i-diabetes-caused-lipotoxicity-and-renal-dysfunction-in-a-rat-model
#14
Edgar Cano-Europa, Rocio Ortiz-Butron, Estela Melendez Camargo, María Miriam Esteves-Carmona, Rosa Maria Oliart-Ros, Vanessa Blas-Valdivia, Margarita Franco-Colin
We investigated the effect of a canola oil-supplemented diet on the metabolic state and diabetic renal function of a type I diabetes experimental model. Male Sprague-Dawley rats were randomly divided into four groups: (1) normoglycemic+chow diet, (2) normoglycemic+a canola oil-supplemented chow diet, (3) diabetic+chow diet, and (4) diabetic+a canola oil-supplemented chow diet. For 15 weeks, animals were fed a diet of Purina rat chow alone or supplemented with 30% canola oil. Energetic intake, water intake, body weight, and adipose tissue fat pad were measured; renal function, electrolyte balance, glomerular filtration rate, and the plasmatic concentration of free fatty acids, cholesterol, triglycerides, and glucose were evaluated...
November 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/27845599/n-acetylcysteine-protects-against-star-fruit-induced-acute-kidney-injury
#15
Maria Heloisa Massola Shimizu, Pedro Henrique França Gois, Rildo Aparecido Volpini, Daniele Canale, Weverton Machado Luchi, Leila Froeder, Ita Pfeferman Heilberg, Antonio Carlos Seguro
BACKGROUND: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect. MATERIALS AND METHODS: Male Wistar rats received SF juice (4 mL/100 g body weight) by gavage after a 12 h fasting and water deprivation...
2017: Renal Failure
https://www.readbyqxmd.com/read/27823925/application-of-a-lc-ms-ms-method-for-evaluating-lung-penetration-of-tobramycin-in-rats-by-microdialysis
#16
P M Bernardi, F Barreto, T Dalla Costa
A bioanalytical LC-MS/MS method was developed and validated to determine tobramycin in plasma and lung microdialysate samples. Tobramycin was separated using a C18 column and a mobile phase consisting of water and acetonitrile, both with 10mM of heptafluorobutyric acid, eluted as gradient. Apramycin was used as internal standard (IS) for plasma samples. Drugs were monitored using electrospray ionization operating on positive mode (ESI+) monitoring the transitions 468.2>163.3 m/z for tobramycin and 540.3>217...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27789808/elevation-of-arginine-vasopressin-levels-following-loop-diuretic-therapy-as-a-prognostic-indicator-in-heart-failure
#17
Shuichi Kitada, Shohei Kikuchi, Hiroo Sonoda, Atsuhiro Yoshida, Nobuyuki Ohte
Objective To investigate the association between arginine vasopressin (AVP) levels and loop diuretic (LD) therapy in patients with heart failure and to determine if AVP levels are a prognostic indicator of treatment failure. Methods Patients with stable heart failure and reduced (< 40%) left ventricular ejection fraction (LVEF) were divided into those treated with (LD) or without LD (NLD). The LD group was separated into subgroups of high (> 6.5 pg/dl) and low (≤ 6.5 pg/dl) AVP levels. The clinical and biochemical characteristics of the two groups were compared and the prognostic value of AVP levels in heart failure evaluated...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27760292/bioimaging-of-intravenous-polymeric-micelles-based-on-discrimination-of-integral-particles-using-an-environment-responsive-probe
#18
Haisheng He, Jian Zhang, Yunchang Xie, Yi Lu, Jianping Qi, Ejaj Ahmad, Xiaochun Dong, Weili Zhao, Wei Wu
One of the biggest challenges in bioimaging of nanoparticles is how to identify integral particles from bulk signals of probes. Signals of free probes are always mistakenly counted into total signals of particles. In this study, in vivo fate of intravenous polymeric micelles (PMs, mPEG2.5k-PDLLA2.5k) was explored using a highly sensitive near-infrared environment-responsive fluorescent probe. This probe is able to emit fluorescence when embedded in nanocarriers but quench spontaneously and absolutely upon release into water, based on the aggregation-caused quenching effect, which means that the interference generated by free probes can be completely diminished...
November 7, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27729196/cyclen-based-gd-3-complexes-as-mri-contrast-agents-relaxivity-enhancement-and-ligand-design
#19
Haroon Ur Rashid, Marco Antonio Utrera Martines, Juliana Jorge, Paula Martin de Moraes, Muhammad Naveed Umar, Kamin Khan, Hanif Ur Rehman
Magnetic Resonance Imaging (MRI) is a noninvasive radiology technique used to examine the internal organs of human body. It is useful for the diagnosis of structural abnormalities in the body. Contrast agents are used to increase the sensitivity of this technique. 1,4,7,10-Tetraazacyclododecane (cyclen) is a macrocyclic tetraamine. Its derivatives act as useful ligands to produce stable complexes with Gd(3+) ion. Such chelates are investigated as MRI contrast agents. Free Gd(3+) ion is extremely toxic for in vivo use...
October 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27595820/the-mechanism-of-glucagon-like-peptide-1-participation-in-the-osmotic-homeostasis
#20
Yu V Natochin, A S Marina, A V Kutina, E V Balbotkina, T A Karavashkina
We have found the physiological mechanism of intensification of the excessive fluid removal from the body under the action of glucagon-like peptide-1 and its analog exenatide. Under the water load in rats, exenatide significantly increased the clearance of lithium, reduced fluid reabsorption in the proximal tubule of the nephron and intensified reabsorption of sodium ions in the distal parts, which contributed to the formation of sodium-free water and faster recovery of osmotic homeostasis. Blocking this pathway with a selective antagonist of glucagon-like peptide-1 receptors slowed down the elimination of excessive water from the body...
July 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
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