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bumetanide

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https://www.readbyqxmd.com/read/28213919/diuretic-sensitive-electroneutral-na-movement-and-temperature-effects-on-central-axons
#1
Meneka Kanagaratnam, Christopher Pendleton, Danilo Almeida Souza, Joseph Pettit, James Howells, Mark D Baker
Raising the temperature of optic nerve from room temperature to near physiological has effects on the threshold, refractoriness and superexcitability of the shortest latency (fast, F) nerve fibres, consistent with hyperpolarization. The temperature dependence of peak impulse latency was weakened at temperatures above 30°C suggesting a temperature sensitive process that slows impulse propagation. The amplitude of the supramaximal compound action potential gets larger on warming, whereas in the presence of bumetanide and amiloride (blockers of electroneutral Na(+) movement), the action potential amplitude consistently falls...
February 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28192112/multiple-blood-brain-barrier-transport-mechanisms-limit-bumetanide-accumulation-and-therapeutic-potential-in-the-mammalian-brain
#2
Kerstin Römermann, Maren Fedrowitz, Philip Hampel, Edith Kaczmarek, Kathrin Töllner, Thomas Erker, Douglas H Sweet, Wolfgang Löscher
There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28161194/bumetanide-reduce-the-seizure-susceptibility-induced-by-pentylenetetrazol-via-inhibition-of-aberrant-hippocampal-neurogenesis-in-neonatal-rats-after-hypoxia-ischemia
#3
Jiang-Jian Hu, Xing-Liang Yang, Wen-Di Luo, Song Han, Jun Yin, Wan-Hong Liu, Xiao-Hua He, Bi-Wen Peng
Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na(+)-K(+)-Cl(-)-co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR...
February 2, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28159275/a-graphene-tip-coupled-with-liquid-chromatography-tandem-mass-spectrometry-for-the-determination-of-four-synthetic-adulterants-in-slimming-supplements
#4
Renyao Jin, Linqiu Li, Lianxian Guo, Weiqiao Li, Qing Shen
Slimming supplements were popularly sold online driven by the increasement of obesity and the development of social networking platform. However, events of drug abuse in slimming supplements were also frequently reported. In this study, a graphene tip solid-phase extraction (Gtip SPE) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for determining fenfluramine, phenolphthalein, bumetanide, and sibutramine in slimming supplements. It was validated in terms of linearity (0...
June 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28152000/bumetanide-increases-cl-dependent-short-circuit-current-in-late-distal-colon-evidence-for-the-presence-of-active-electrogenic-cl-absorption
#5
Lieqi Tang, Xiefan Fang, Steven P Winesett, Catherine Y Cheng, Henry J Binder, Scott A Rivkees, Sam X Cheng
Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current...
2017: PloS One
https://www.readbyqxmd.com/read/28111749/progress-report-on-new-antiepileptic-drugs-a-summary-of-the-thirteenth-eilat-conference-on-new-antiepileptic-drugs-and-devices-eilat-xiii
#6
REVIEW
Meir Bialer, Svein I Johannessen, René H Levy, Emilio Perucca, Torbjörn Tomson, H Steve White
The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689)...
January 23, 2017: Epilepsia
https://www.readbyqxmd.com/read/28110691/is-insulin-growth-factor-1-the-future-for-treating-autism-spectrum-disorder-and-or-schizophrenia
#7
Rami Bou Khalil
To date, no curative psychopharmacologic treatment exists for the core symptoms of autism spectrum disorder (ASD) as well as for schizophrenia. Bumatenide is a specific antagonist of the first isoform of the Na-K-Cl cotransporter (NKCC1). It is usually used as a diuretic but may also promote a decrease in intraneuronal chloride ion concentration leading to hyperpolarization in neuronal membrane and subsequent decrease in neuronal hyperexcitability. This physiologic effect has been considered to be behind the relative efficacy of bumetanide in improving symptoms of ASD and, to a lesser extent, schizophrenia...
February 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28105769/renal-tubular-resistance-is-the-primary-driver-for-loop-diuretic-resistance-in-acute-heart-failure
#8
Jozine M Ter Maaten, Veena S Rao, Jennifer S Hanberg, F Perry Wilson, Lavanya Bellumkonda, Mahlet Assefa, J Sam Broughton, Julie D'Ambrosi, W H Wilson Tang, Kevin Damman, Adriaan A Voors, David H Ellison, Jeffrey M Testani
BACKGROUND: Loop diuretic resistance is a common barrier to effective decongestion in acute heart failure (AHF), and is associated with poor outcome. Specific mechanisms underlying diuretic resistance are currently unknown in contemporary AHF patients. We therefore aimed to determine the relative importance of defects in diuretic delivery vs. renal tubular response in determining diuretic response (DR) in AHF. METHODS AND RESULTS: Fifty AHF patients treated with intravenous bumetanide underwent a 6-h timed urine collection for sodium and bumetanide clearance...
January 19, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28087701/the-ubiquitin-ligase-nedd4l-regulates-the-na-k-2cl-co-transporter-nkcc1-slc12a2-in-the-colon
#9
Chong Jiang, Hiroshi Kawabe, Daniela Rotin
The ubiquitin ligase Nedd4-like (Nedd4L, or Nedd4-2) binds to and regulates stability of the epithelial Na+ channel (ENaC) in salt absorbing epithelia in the kidney, lung, and other tissues. Its role in the distal colon, which also absorbs salt and fluid and expresses ENaC, is unknown. Using conditional knockout approach to knockout Nedd4L in mice intestinal epithelium (Nedd4Lf/f;Vil-CreERT2) we show here that Nedd4L depletion leads to a higher steady-state short circuit current (Isc) in mouse distal colon tissue relative to controls...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28074534/depolarizing-gaba-contributes-to-glutamatergic-network-rewiring-in-epilepsy
#10
Nazim Kourdougli, Christophe Pellegrino, Juho-Matti Renko, Stanislav Khirug, Geneviève Chazal, Tiina-Kaisa Kukko-Lukjanov, Sari E Lauri, Jean-Luc Gaiarsa, Liang Zhou, Angélique Peret, Eero Castrén, Raimo Kalevi Tuominen, Valérie Crépel, Claudio Rivera
OBJECTIVE: Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy. Besides the rewiring of excitatory circuit, an abnormal depolarizing GABAergic drive has been hypothesized to participate in the epileptogenic processes. However, a remaining clinically relevant question is whether early post Status Epilepticus (SE) evoked chloride dysregulation is important for the remodeling of aberrant glutamatergic neuronal circuit. METHODS: Osmotic mini-pumps were used to infuse intracerebrally a specific inhibitor of depolarizing GABAergic transmission as well as a functionally blocking antibody towards the pan-neurotrophin receptor p75 (p75(NTR) )...
January 11, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28066142/participation-of-central-gabaa-receptors-in-the-trigeminal-processing-of-mechanical-allodynia-in-rats
#11
Min Ji Kim, Young Hong Park, Kui Ye Yang, Jin Sook Ju, Yong Chul Bae, Seong Kyu Han, Dong Kuk Ahn
Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28057537/the-chloride-co-transporters-nkcc1-and-kcc2-in-experimental-autoimmune-encephalomyelitis-eae
#12
Muhammad Saad Yousuf, Kasia Zubkow, Gustavo Tenorio, Bradley Kerr
Patients with multiple sclerosis (MS) often complain of neuropathic pain. According to the Gate Control Theory of Pain, spinal networks of GABAergic inhibitory interneurons are important in modulating nociceptive inputs from the periphery. Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. In this study, we investigated the role of NKCC1 and KCC2 in neuropathic pain observed in the animal model, experimental autoimmune encephalomyelitis (EAE), a commonly used model to study the pathophysiology of MS...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28007722/physical-compatibility-of-isavuconazonium-sulfate-with-select-i-v-drugs-during-simulated-y-site-administration
#13
Wonhee So, Liz Kim, Abrar K Thabit, David P Nicolau, Joseph L Kuti
PURPOSE: The physical compatibility of isavuconazonium sulfate with 95 i.v. drugs during simulated Y-site administration was studied. METHODS: Isavuconazonium sulfate for injection and all other drugs were reconstituted according to the manufacturer's recommendation and further diluted with 0.9% sodium chloride injection or 5% dextrose injection to a final concentration (1.5 mg/mL for isavuconazonium sulfate and standard concentrations used clinically for other drugs)...
January 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27986254/inhibition-of-na-k-cl-cotransporter-isoform-1-reduces-lung-injury-induced-by-ischemia-reperfusion
#14
Chou-Chin Lan, Chung-Kan Peng, Shih-En Tang, Hsueh-Ju Lin, Sung-Sen Yang, Chin-Pyng Wu, Kun-Lun Huang
OBJECTIVES: Ischemia-reperfusion acute lung injury is characterized by increased vascular permeability, lung edema, and neutrophil sequestration. Ischemia-reperfusion acute lung injury occurs in lung transplantation and other major surgical procedures. Effective regulation of alveolar fluid balance is critical for pulmonary edema. Sodium-potassium-chloride co-transporter regulates alveolar fluid and is associated with inflammation. We hypothesized that sodium-potassium-chloride co-transporter is important in ischemia-reperfusion acute lung injury...
January 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27926982/trpv4-channels-mediate-na-k-cl-co-transporter-induced-brain-edema-after-traumatic-brain-injury
#15
Kwok-Tung Lu, Tai-Chun Huang, Ya-Hsin Tsai, Yi-Ling Yang
Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the mitogen-activated protein kinases (MAPK) cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27900370/a-patient-with-multisystem-dysfunction-carries-a-truncation-mutation-in-human-slc12a2-the-gene-encoding-the-na-k-2cl-cotransporter-nkcc1
#16
Eric Delpire, Lynne Wolfe, Bianca Flores, Rainelli Koumangoye, Cara C Schornak, Salma Omer, Barbara Pusey, Christopher Lau, Thomas Markello, David R Adams
This study describes a 13-yr-old girl with orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency, and multiorgan failure involving the gut and bladder. Exome sequencing revealed a de novo, loss-of-function allele in SLC12A2, the gene encoding the Na-K-2Cl cotransporter-1. The 11-bp deletion in exon 22 results in frameshift (p.Val1026Phefs*2) and truncation of the carboxy-terminal tail of the cotransporter. Preliminary studies in heterologous expression systems demonstrate that the mutation leads to a nonfunctional transporter, which is expressed and trafficked to the plasma membrane alongside wild-type NKCC1...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27881573/intestinal-na-k-2cl-cotransporter-2-plays-a-crucial-role-in-hyperosmotic-transitions-of-a-euryhaline-teleost
#17
Andrew J Esbaugh, Brett Cutler
Euryhaline fishes, such as the red drum (Sciaenops ocellatus), must quickly transition between hyperosmotic and hypoosmotic physiological strategies. When freshwater individuals transition to seawater they are exposed to increased diffusive water loss and ion gain. To maintain osmoregulatory balance these animals must drink and absorb seawater through the intestine, followed by ion excretion at the gills. The ability of fishes to transition between strategies can limit the magnitude of osmotic shock that can be tolerated...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27881572/the-roles-of-the-na-k-atpase-nkcc-and-k-channels-in-regulating-local-sweating-and-cutaneous-blood-flow-during-exercise-in-humans-in%C3%A2-vivo
#18
Jeffrey C Louie, Naoto Fujii, Robert D Meade, Glen P Kenny
Na(+)/K(+)-ATPase has been shown to regulate the sweating and cutaneous vascular responses during exercise; however, similar studies have not been conducted to assess the roles of the Na-K-2Cl co-transporter (NKCC) and K(+) channels. Additionally, it remains to be determined if these mechanisms underpinning the heat loss responses differ with exercise intensity. Eleven young (24 ± 4 years) males performed three 30-min semirecumbent cycling bouts at low (30% VO2peak), moderate (50% VO2peak), and high (70% VO2peak) intensity, respectively, each separated by 20-min recovery periods...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27871891/long-term-alcohol-exposure-elicits-hippocampal-nonsynaptic-epileptiform-activity-changes-associated-with-expression-and-functional-changes-in-nkcc1-kcc2-co-transporters-and-na-k-atpase
#19
Luiz E C Santos, Antônio M Rodrigues, Mariana R Lopes, Victor D C Costa, Carla A Scorza, Fulvio A Scorza, Esper A Cavalheiro, Antônio-Carlos G Almeida
Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression in the dentate gyrus (DG) after 4weeks of ethanol consumption, motivate the present work, in which rats were submitted to a period of chronic consumption (12weeks). Four groups of six animals (6-week-old male Wistar rats) were formed, including the control (C), ethanol 1 (E1), ethanol 2 (E2) and ethanol 3 (E3) groups. The rats in the E1, E2 and E3 groups were treated daily with a 30% v/v solution of ethanol, administered via oral gavage (1...
January 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/27865855/intestinal-response-to-salinity-challenge-in-the-senegalese-sole-solea-senegalensis
#20
I Ruiz-Jarabo, A Barany, I Jerez-Cepa, J M Mancera, J Fuentes
Fish are continuously forced to actively absorb or expel water and ions through epithelia. Most studies have focused on the gill due to its role in Na(+) and Cl(-) trafficking. However, comparatively few studies have focused on the changing function of the intestine in response to external salinity. Therefore, the present study investigated the main intestinal changes of long-term acclimation of the Senegalese sole (Solea senegalensis) to 5, 15, 38 and 55ppt. Through the measurement of short-circuit current (Isc) in Ussing chambers and biochemical approaches, we described a clear anterior/posterior functional regionalization of the intestine in response to salinity...
February 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
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