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https://www.readbyqxmd.com/read/28928659/brain-pharmacokinetics-and-the-pharmacological-effects-on-striatal-neurotransmitter-levels-of-pueraria-lobata-isoflavonoids-in-rat
#1
Bingxin Xiao, Zengxian Sun, Fangrui Cao, Lisha Wang, Yonghong Liao, Xinmin Liu, Ruile Pan, Qi Chang
Isoflavonoids are putatively active components of Pueraria lobata and has been demonstrated prominent neuro-protection effect against cerebrovascular disorders, hypertension or Parkinson's disease (PD). However, the molecular basis for the beneficial effect of Pueraria lobata on nervous systems has not been well revealed. The present study aims to assess striatum exposure to main active isoflavonoids and changes of striatal extracellular neurotransmitters levels in rat brain after intravenous administration of Pueraria lobata isoflavonoids extracts (PLF), to further elucidate its' substantial bases for neuro activities...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28891201/predicting-drug-concentration-time-profiles-in-multiple-cns-compartments-using-a-comprehensive-physiologically-based-pharmacokinetic-model
#2
Yumi Yamamoto, Pyry A Välitalo, Dymphy R Huntjens, Johannes H Proost, An Vermeulen, Walter Krauwinkel, Margot W Beukers, Dirk-Jan van den Berg, Robin Hartman, Yin Cheong Wong, Meindert Danhof, Johan G C van Hasselt, Elizabeth C M de Lange
Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically-based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System-specific and drug-specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration-time profiles from 10 drugs in rat plasma, brain extracellular fluid, two cerebrospinal fluid sites, and total brain tissue...
September 11, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28890943/trial-of-amiloride-in-type-2-diabetes-with-proteinuria
#3
Mark L Unruh, V Shane Pankratz, John E Demko, Evan C Ray, Rebecca P Hughey, Thomas R Kleyman
INTRODUCTION: Renal Na(+) retention and extracellular fluid volume expansion are hallmarks of nephrotic syndrome, which occurs even in the absence of activation of hormones that stimulate renal Na(+) transporters. Plasmin-dependent activation of the epithelial Na(+) channel (ENaC) has been proposed to have a role in renal Na(+) retention in the setting of nephrotic syndrome. We hypothesized that the ENaC inhibitor amiloride would be an effective therapeutic agent in inducing a natriuresis and lowering blood pressure in individuals with macroscopic proteinuria...
September 2017: KI Reports
https://www.readbyqxmd.com/read/28887906/sphingosine-1-phosphate-and-renal-vasoconstriction
#4
EDITORIAL
Boye L Jensen
In the present issue of Acta Physiologica, Guan et al. in their article "Mechanisms of sphingosine-1-phosphate-mediated vasoconstriction of rat afferent arterioles" (1) address the signaling events associated with sphingosine-1-phosphate (S1P)-mediated renal afferent vasoconstriction and show in, technically demanding, blood-perfused juxtamedullary nephron preparation that S1P signaling relies predominantly on transmembrane calcium influx from the extracellular fluid through L-type calcium channels with contribution from oxidative stress metabolites(1) ...
September 9, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28887501/voluntary-liquorice-ingestion-increases-blood-pressure-via-increased-volume-load-elevated-peripheral-arterial-resistance-and-decreased-aortic-compliance
#5
Elina J Hautaniemi, Anna M Tahvanainen, Jenni K Koskela, Antti J Tikkakoski, Mika Kähönen, Marko Uitto, Kalle Sipilä, Onni Niemelä, Jukka Mustonen, Ilkka H Pörsti
We investigated the haemodynamic effects of two-week liquorice exposure (glycyrrhizin dose 290-370 mg/day) in 22 healthy volunteers during orthostatic challenge. Haemodynamics were recorded during passive 10-minute head-up tilt using radial pulse wave analysis, whole-body impedance cardiography, and spectral analysis of heart rate variability. Thirty age-matched healthy subjects served as controls. Liquorice ingestion elevated radial systolic (p < 0.001) and diastolic (p = 0.018) blood pressure and systemic vascular resistance (p = 0...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884936/dietary-cation-and-anion-difference-effects-on-milk-production-and-body-fluid-distribution-in-lactating-dairy-goats-under-tropical-conditions
#6
Thiet Nguyen, Narongsak Chaiyabutr, Somchai Chanpongsang, Sumpun Thammacharoen
This study aimed to determine the effect of dietary cation and anion difference (DCAD) on milk production and body fluid distribution in lactating dairy goats. Ten dairy goats were selected and divided into two groups, five animals each. Animals received either control DCAD (control, 22.81 mEq/100 g dry matter (DM)) or high DCAD (DCAD, 39.08 mEq/100 g DM). The results indicated that rectal temperature (Tr), respiration rate, milk yield and compositions did not differ between groups. But the percentage change of Tr from the DCAD group was lower than the control group between 09...
September 8, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28846776/nonarteritic-anterior-ischemic-optic-neuropathy-induced-retinal-folds-and-deformations
#7
Mark J Kupersmith, Patrick A Sibony, Sarita Dave
Purpose: We hypothesized that the edema/swelling in the retina due to acute nonarteritic anterior ischemic optic neuropathy (NAION) can induce retinal folds (RF). We determined the pattern and frequency of folds in NAION at presentation and in follow-up, and the relationship between folds and a number of functional and structural parameters over time. Methods: We prospectively studied eyes with acute NAION by spectral-domain optic coherence tomography (SD-OCT). We used transaxial and en face views to evaluate the presence of peripapillary fluid (PPF), peripapillary wrinkles (PPW), RF, choroidal folds (CF), creases, macular edema, and vitreous traction on the optic disc...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28842313/a-facile-approach-to-functionalizing-cell-membrane-coated-nanoparticles-with-neurotoxin-derived-peptide-for-brain-targeted-drug-delivery
#8
Zhilan Chai, Xuefeng Hu, Xiaoli Wei, Changyou Zhan, Linwei Lu, Kuan Jiang, Bingxia Su, Huitong Ruan, Danni Ran, Ronnie H Fang, Liangfang Zhang, Weiyue Lu
The blood brain barrier separates the circulating blood from the extracellular fluid in the central nervous system and thus presents an essential obstacle to brain transport of therapeutics. Herein, we report on an effective brain-targeted drug delivery system that combines a robust red blood cell membrane-coated nanoparticle (RBCNP) with a unique neurotoxin-derived targeting moiety. The RBCNPs retain the complex biological functions of natural cell membranes while exhibiting physicochemical properties that are suitable for effective drug delivery...
August 24, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28829810/extracellular-overhydration-linked-with-endothelial-dysfunction-in-the-context-of-inflammation-in-haemodialysis-dependent-chronic-kidney-disease
#9
Nicos Mitsides, Tom Cornelis, Natascha J H Broers, Nanda M P Diederen, Paul Brenchley, Frank M van der Sande, Casper G Schalkwijk, Jeroen P Kooman, Sandip Mitra
BACKGROUND: Haemodialysis (HD) patients are predisposed to dysregulated fluid balance leading to extracellular water (ECW) expansion. Fluid overload has been closely linked with outcome in these patients. This has mainly been attributed to cardiac volume overload, but the relation between abnormalities in fluid status with micro- and macrovascular dysfunction has not been studied in detail. We studied the interaction of macro- and microvascular factors in states of normal and over- hydration in HD-dependent CKD...
2017: PloS One
https://www.readbyqxmd.com/read/28814497/extracellular-acid-base-balance-and-ion-transport-between-body-fluid-compartments
#10
REVIEW
Julian L Seifter, Hsin-Yun Chang
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment...
September 2017: Physiology
https://www.readbyqxmd.com/read/28812111/syndrome-of-inappropriate-anti-diuresis-induces-volume-dependent-hypercalciuria
#11
J Grellier, A Jaafar, A Martin, M El Alaoui, C Lebely, I Tack, M Vallet
Hyponatremia is associated with bone demineralization. We hypothesized that, during hyponatremia, calciuria and calcium balance depend on volemic status. We evaluated calciuria in patients with hyponatremia, secondary to SIAD or hypovolemia. Patients with SIAD exhibited a volemic expansion that was associated with hypercalciuria. Calciuria was proportional to markers of volemia. INTRODUCTION: Chronic mild hyponatremia has been associated with bone demineralization of unknown mechanisms...
August 15, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28811499/the-role-of-dermcidin-isoform-2-in-the-occurrence-and-severity-of-diabetes
#12
Suman Bhattacharya, Md Mobidullah Khan, Chandradipa Ghosh, Sarbashri Bank, Smarajit Maiti
Diabetes is now epidemic worldwide. Several hundred-million peoples are presently suffering from this disease with other secondary-disorders. Stress, hypertension, sedentary life-style, carbohydrate/lipid metabolic-disorders due to genetic or environmental factors attributes to type-1 and/or type-2 diabetes. Present investigation demonstrates that stress-induced protein dermcidin isoform-2 (DCN-2) which appears in the serum of diabetic-patients play a key-role in this disease pathogenesis/severity. DCN-2 suppresses insulin production-release from liver/pancreas...
August 15, 2017: Scientific Reports
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
#13
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/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#14
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28803831/localization-of-connexin-43-gap-junctions-and-hemichannels-in-tanycytes-of-adult-mice
#15
Anett Szilvásy-Szabó, Edina Varga, Zsuzsa Beliczai, Ronald M Lechan, Csaba Fekete
Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes...
August 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28795486/a-reassessment-of-the-blood-brain-barrier-transport-of-large-neutral-amino-acids-during-acute-systemic-inflammation-in-humans
#16
Rasmus H Dahl, Ronan M G Berg, Sarah Taudorf, Damian M Bailey, Carsten Lundby, Fin S Larsen, Kirsten Møller
We reassessed data from a previous study on the transcerebral net exchange of large neutral amino acids (LNAAs) using a novel mathematical model of blood-brain barrier (BBB) transport. The study included twelve healthy volunteers who received a 4-h intravenous lipopolysaccharide (LPS) infusion (total dose: 0·3 ng/kg), a human experimental model of the systemic inflammatory response during the early stages of sepsis. Cerebral blood flow and arterial-to-jugular venous LNAA concentrations were measured prior to and after LPS, and the BBB transport and brain extracellular concentrations of LNAAs were calculated...
August 9, 2017: Clinical Physiology and Functional Imaging
https://www.readbyqxmd.com/read/28768552/a-mild-form-of-adenylosuccinate-lyase-deficiency-in-absence-of-typical-brain-mri-features-diagnosed-by-whole-exome-sequencing
#17
Marina Macchiaiolo, Sabina Barresi, Francesco Cecconi, Ginevra Zanni, Marcello Niceta, Emanuele Bellacchio, Giacomo Lazzarino, Angela Maria Amorini, Enrico Silvio Bertini, Salvatore Rizza, Benedetta Contardi, Marco Tartaglia, Andrea Bartuli
BACKGROUND: Adenylosuccinate lyase (ADSL) deficiency is a defect of purine metabolism affecting purinosome assembly and reducing metabolite fluxes through purine de novo synthesis and purine nucleotide recycling pathways. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The most severe form is characterized by neonatal encephalopathy, absence of spontaneous movement, respiratory failure, intractable seizures, and early death within the first weeks of life...
August 2, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28766715/hypertonic-nacl-versus-osmotic-stimuli-distinct-ovlt-neurones-can-sense-the-difference-to-control-sympathetic-outflow-and-blood-pressure
#18
V R Antunes
No abstract text is available yet for this article.
September 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28761086/serotonin-hormonally-regulates-lacrimal-gland-secretory-function-via-the-serotonin-type-3a-receptor
#19
Toshihiro Imada, Shigeru Nakamura, Ryuji Hisamura, Yusuke Izuta, Kai Jin, Masataka Ito, Naoki Kitamura, Kenji F Tanaka, Masaru Mimura, Izumi Shibuya, Kazuo Tsubota
Tears are extracellular fluid secreted from the lacrimal gland (LG). Tears consist of a dynamic tri-layered film composed of secretions from the LG, Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous component of the tear, the Meibomian gland secretes the lipid component, and conjunctival goblet cells secrete mucin. The regulation of LG activity via the autonomic nervous system has been recognized as fundamental to maintaining aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin, in tear secretion...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28756226/specific-packaging-and-circulation-of-cytochromes-p450-especially-2e1-isozyme-in-human-plasma-exosomes-and-their-implications-in-cellular-communications
#20
Santosh Kumar, Namita Sinha, Kelli A Gerth, Mohammad A Rahman, Murali M Yallapu, Narasimha M Midde
Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are mainly found in hepatic and some extra-hepatic cells. However, their presence and functional role in exosomes, small extracellular vesicles that are secreted from various cells into extracellular fluids including plasma, is unknown. In this study, we analyzed the expression and biological activity of CYP enzymes in human plasma exosomes. First, we optimized isolation of plasma exosomes and characterized them for their physical properties and quality...
September 23, 2017: Biochemical and Biophysical Research Communications
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