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https://www.readbyqxmd.com/read/29154977/polymer-nitric-oxide-donors-potentiate-the-treatment-of-experimental-solid-tumours-by-increasing-drug-accumulation-in-the-tumour-tissue
#1
M Studenovsky, L Sivak, O Sedlacek, R Konefal, V Horkova, T Etrych, M Kovar, B Rihova, M Sirova
The delivery of nitric oxide (NO) specifically to solid tumours was explored in this study as a strategy to augment the passive accumulation of nanomedicines in tumours induced by the Enhanced Permeability and Retention (EPR) effect. An increase in accumulation was achieved by the binding of the chemical precursor of NO, based on an organic nitrate, to a water-soluble synthetic polymer drug carrier. Four structurally different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer NO donors were synthesized...
November 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29130954/effects-of-tolvaptan-addition-to-furosemide-in-normo-and-hyponatremia-patients-with-heart-failure-and-chronic-kidney-disease-stages-g3b-5-a-subanalysis-of-the-k-star-study
#2
Naoto Tominaga, Keisuke Kida, Takayuki Inomata, Naoki Sato, Tohru Izumi, Yoshihiro J Akashi, Yugo Shibagaki
BACKGROUND: Tolvaptan increases free water clearance (aquaresis) and thereby improves hyponatremia. Although hyponatremia on admission is common in patients with congestive heart failure (CHF), little is known regarding the response to tolvaptan in those who also have chronic kidney disease (CKD) with or without hyponatremia. The aim of this subanalysis was to investigate the differences in treatment response between normo- and hyponatremia patients with CHF and CKD stages G3b-5. METHODS: The Kanagawa Aquaresis Investigators Trial of Tolvaptan on HF Patients with Renal Impairment (K-STAR) was a multicenter, open-label, randomized, controlled prospective clinical trial that included 81 Japanese patients with CHF and residual signs of congestion despite oral furosemide treatment (≥40 mg/day)...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29107179/uptake-and-metabolism-of-water-borne-progesterone-by-the-mussel-mytilus-spp-mollusca
#3
Tamar I Schwarz, Ioanna Katsiadaki, Benjamin H Maskrey, Alexander P Scott
Previous studies have shown that mussels can pick up 17β-estradiol [E2] and testosterone [T] from water, metabolize them and conjugate them to fatty acids (esterification), leading to their accumulation in tissue. A key requirement for the esterification process is that a steroid must have a 'reactive' hydroxyl group to conjugate to a fatty acid (which in T, and probably E2, is the β-hydroxyl group on carbon 17). Progesterone (P) lacks any hydroxyl groups and theoretically cannot be esterified and hence should not accumulate in mussels in the same way as E2 or T...
October 26, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29106785/n-terminal-pro-b-type-natriuretic-peptide-in-three-different-mechanisms-of-dysnatremia-onset-after-a-child-s-craniopharyngioma-surgery
#4
(no author information available yet)
Craniopharyngioma, due to its sellar location, can be perioperatively complicated by different types of dysnatremia. We present a rare postoperative onset of a combination of three different mechanisms of dysnatremia with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and renal function parameters in a boy with a good outcome after craniopharyngioma surgery: 1/ Central diabetes insipidus (CDI) onset immediately after the operation, hypernatremia with peak serum sodium (SNa) 158 mmol/l) caused by free water polyuria (electrolyte-free water clearance, EWC 0...
October 6, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/29065098/effects-of-sodium-nitrite-on-renal-function-and-blood-pressure-in-hypertensive-vs-healthy-study-participants-a-randomized-placebo-controlled-crossover-study
#5
Jeppe B Rosenbæk, Bodil G Hornstrup, Andreas N Jørgensen, Jesper Mortensen, Erling B Pedersen, Jesper N Bech
OBJECTIVE: Nitric oxide is a key player in regulating vascular tone. Impaired endothelial nitric oxide synthesis plays an important role in hypertension. Replenishing of nitric oxide by sodium nitrite (NaNO2) has not been investigated in patients with essential hypertension (EHT). We aimed to determine the effects of NaNO2 on blood pressure (BP) and renal sodium and water regulation in patients with EHT compared with healthy control study participants (CON). METHODS: In a placebo-controlled, crossover study, we infused 240 μg NaNO2/kg/h or isotonic saline for 2 h in 14 EHT and 14 CON...
October 23, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29061124/dapagliflozin-acutely-improves-endothelial-dysfunction-reduces-aortic-stiffness-and-renal-resistive-index-in-type-2-diabetic-patients-a-pilot-study
#6
Anna Solini, Livia Giannini, Marta Seghieri, Edoardo Vitolo, Stefano Taddei, Lorenzo Ghiadoni, Rosa Maria Bruno
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms. METHODS: Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12...
October 23, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29057582/an-exploratory-pilot-study-with-copeptin-as-a-biomarker-for-individualizing-treatment-for-nocturnal-polyuria
#7
Elke Bruneel, An-Sofie Goessaert, Marie-Astrid Denys, Kristian V Juul, Jens P Nørgaard, Karel Everaert
OBJECTIVE: The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). METHODS: In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile...
October 23, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/29024278/why-do-sglt2-inhibitors-reduce-heart-failure-hospitalization-a-differential-volume-regulation-hypothesis
#8
REVIEW
K Melissa Hallow, Gabriel Helmlinger, Peter J Greasley, John J V McMurray, David W Boulton
The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28861607/glomerular-and-tubular-effects-of-nitric-oxide-no-are-regulated-by-angiotensin-ii-ang-ii-in-an-age-dependent-manner-through-activation-of-both-angiotensin-receptors-at1rs-and-at2rs-in-conscious-lambs
#9
Angela E Vinturache, Francine G Smith
Renin-angiotensin (RAS) and nitric oxide (NO) systems and the balance and interaction between them are considered of primary importance in maintaining fluid and electrolyte homeostasis. It has been suggested that the effects of NO may be modulated at least in part by the angiotensin (Ang) II, yet the roles of angiotensin receptor type 1 (AT1R) and type 2 (AT2R) are not well understood. Even though both Ang II and NO are elevated at birth and during the newborn period, their contribution to the adaptation of the newborn to life after birth as well as their physiological roles during development are poorly understood...
August 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28857279/self-perceived-mouthfeel-and-physico-chemical-surface-effects-after-chewing-gums-containing-sorbitol-and-magnolia-bark-extract
#10
Stefan W Wessel, Henny C van der Mei, Anje M Slomp, Betsy van de Belt-Gritter, Michael W J Dodds, Henk J Busscher
The European Food Safety Authority recognizes the contribution of sugar-free chewing gum to oral health through increased salivation, clearance of food debris, and neutralization of biofilm pH. Magnolia bark extract is a gum additive shown to reduce the prevalence of bad-breath bacteria but its effects on self-perceived mouthfeel are unknown. This paper aims to relate the effects of sorbitol-containing chewing gum, with and without Magnolia bark extract, on tooth-surface hydrophobicity and salivary-film composition with self-perceived mouthfeel...
August 31, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/28815743/pathophysiology-of-nocturnal-lower-urinary-tract-symptoms-in-older-patients-with-urinary-incontinence
#11
Marie-Astrid Denys, Veerle Decalf, Candy Kumps, Mirko Petrovic, An-Sofie Goessaert, Karel Everaert
OBJECTIVES: To explore the mismatch between functional bladder capacity and nocturnal urine production, and to study the pathophysiology of an increased nocturnal urine production in older patients with urinary incontinence. METHODS: The present prospective observational study included adults aged ≥65 years with urinary incontinence. Participants completed questionnaires, frequency volume charts and renal function profiles. The nocturnal lower urinary tract symptom index was defined as nocturnal urine output/maximum voided volume; the nocturnal polyuria index as nocturnal/24 h urine output...
November 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28810844/effect-of-tolvaptan-on-renal-handling-of-water-and-sodium-gfr-and-central-hemodynamics-in-autosomal-dominant-polycystic-kidney-disease-during-inhibition-of-the-nitric-oxide-system-a-randomized-placebo-controlled-double-blind-crossover-study
#12
Safa Al Therwani, My Emma Sofie Malmberg, Jeppe Bakkestroem Rosenbaek, Jesper Noergaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis. Nitric oxide (NO) stimulates natriuresis and diuresis, but its role is unknown during tolvaptan treatment in ADPKD. METHODS: Eighteen patients with ADPKD received tolvaptan 60 mg or placebo in a randomized, placebo-controlled, double blind, crossover study. L-NMMA (L-NG-monomethyl-arginine) was given as a bolus followed by continuous infusion during 60 min...
August 15, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28777197/elabela-improves-cardio-renal-outcome-in-fatal-experimental-septic-shock
#13
David Coquerel, Frédéric Chagnon, Xavier Sainsily, Lauralyne Dumont, Alexandre Murza, Jérôme Côté, Robert Dumaine, Philippe Sarret, Éric Marsault, Dany Salvail, Mannix Auger-Messier, Olivier Lesur
OBJECTIVES: Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown...
November 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28688582/net-k-secretion-in-the-thick-ascending-limb-of-mice-on-a-low-na-high-k-diet
#14
Bangchen Wang, Donghai Wen, Huaqing Li, Jun Wang-France, Steven C Sansom
Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance...
October 2017: Kidney International
https://www.readbyqxmd.com/read/28633516/synthesis-of-curcumin-glycosides-with-enhanced-anticancer-properties-using-one-pot-multienzyme-glycosylation-technique
#15
Rit Bahadur Gurung, So Youn Gong, Dipesh Dhakal, Tuoi Thi Le, Na Rae Jung, Hye Jin Jung, Tae Jin Oh, Jae Kyung Sohng
Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDP- α-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed...
September 28, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28540204/advanced-wasting-in-peritoneal-dialysis-patients
#16
Zhi Xu, Glen H Murata, Robert H Glew, Yijuan Sun, Darlene Vigil, Karen S Servilla, Antonios H Tzamaloukas
AIM: To identify patients with end-stage renal disease treated by peritoneal dialysis (PD) who had zero body fat (BF) as determined by analysis of body composition using anthropometric formulas estimating body water (V) and to compare nutritional parameters between these patients and PD patients whose BF was above zero. METHODS: Body weight (W) consists of fat-free mass (FFM) and BF. Anthropometric formulas for calculating V allow the calculation of FFM as V/0.73, where 0...
May 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#17
RANDOMIZED CONTROLLED TRIAL
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28490529/effect-of-sodium-nitrite-on-renal-function-and-sodium-and-water-excretion-and-brachial-and-central-blood-pressure-in-healthy-subjects-a-dose-response-study
#18
RANDOMIZED CONTROLLED TRIAL
Jeppe Bakkestroem Rosenbaek, Safa Al Therwani, Janni Majgaard Jensen, Frank Holden Mose, Christine Wandall-Frostholm, Erling Bjerregaard Pedersen, Jesper Noergaard Bech
Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2 on hemodynamics, sodium excretion, and glomerular filtration rate (GFR). In a single-blinded, placebo-controlled, crossover study, we infused placebo (0.9% NaCl) or 0.58, 1.74, or 3.48 μmol NaNO2·kg-1·h-1 for 2 h in 12 healthy subjects, after 4 days of a standard diet. Subjects were supine and water loaded. We measured brachial and central blood pressure (BP), plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma nitrite (P-[Formula: see text]), GFR by Cr-EDTA clearance, fractional excretion of sodium (FENa) free water clearance (CH2O), and urinary excretion rate of guanosine 3',5'-cyclic monophosphate (U-cGMP)...
August 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28438697/predicting-drug-loading-in-pla-peg-nanoparticles
#19
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
#20
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...
May 1, 2017: Journal of Clinical Investigation
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