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https://www.readbyqxmd.com/read/28577991/inhibition-of-na-k-2cl-cotransporter-attenuates-blood-brain-barrier-disruption-in-a-mouse-model-of-traumatic-brain-injury
#1
Jun Zhang, Hongjian Pu, Haiyue Zhang, Zhishuo Wei, Xiaoyan Jiang, Mingyue Xu, Lili Zhang, Wenting Zhang, Jialin Liu, Hengxing Meng, R Anne Stetler, Dandan Sun, Jun Chen, Yanqin Gao, Ling Chen
Traumatic brain injury (TBI) can lead to long-term motor and cognitive dysfunction, which can be at least partly attributed to blood-brain barrier (BBB) disruption. The mechanisms underlying post-TBI BBB disruption, however, are poorly understood thus far. Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1) is a universally expressed ion transporter that maintains intracellular ion homeostasis by increasing intracellular K(+) and Cl(-). Having been characterized in stroke models, NKCC1 is activated in various cell types in the ischemic brain, and is thought to mediate BBB disruption, brain edema, and neuronal cell death...
May 31, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28530501/palliative-care-for-advanced-heart-failure-in-a-department-of-veterans-affairs-regional-hospice-program-patient-selection-a-treatment-protocol-and-clinical-course
#2
George J Taylor, Dorothy M Lee, Catalin F Baicu, Michael R Zile
BACKGROUND: Palliative care for advanced heart failure (HF) is generally recommended. However, few reports have focused on the particulars of treatment, or the clinical course of HF on a specific treatment regimen. OBJECTIVE: Palliation adequate to allow patients to avoid HF admission and die at home. METHODS: Patients from a veterans administration regional practice with multiple, recent hospital admissions were enrolled in community hospice programs...
May 22, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28523460/evaluation-of-the-effect-of-torsemide-on-warfarin-dosage-requirements
#3
Sophia Lai, Jeremiah D Momper, Felix K Yam
Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014...
May 18, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28513167/quercetin-morin-luteolin-and-phloretin-are-dietary-flavonoid-inhibitors-of-monocarboxylate-transporter-6
#4
Robert S Jones, Mark D Parker, Marilyn E Morris
Monocarboxylate transporter 6 (MCT6; SLC16A5) has been recognized for its role as a xenobiotic transporter, with characterized substrates probenecid, bumetanide, and nateglinide. To date, the impact of commonly ingested dietary compounds on MCT6 function has not been investigated, and therefore, the objective of this study was to evaluate a variety of flavonoids for their potential MCT6-specific interactions. Flavonoids are a large group of polyphenolic phytochemicals found in commonly consumed plant-based products that have been recognized for their dietary health benefits...
May 31, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28490320/astaxanthin-protects-astrocytes-against-trauma-induced-apoptosis-through-inhibition-of-nkcc1-expression-via-the-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Mingkun Zhang, Zhenwen Cui, Hua Cui, Yong Wang, Chunlong Zhong
BACKGROUND: Astaxanthin (ATX) is a carotenoid pigment with pleiotropic pharmacological properties that is seen as a possible drug for treating cerebral ischemic injury and subarachnoid hemorrhage. Na(+)-K(+)-2Cl(-) co-transporter-1 (NKCC1), an intrinsic membrane protein expressed by many cell types, is activated by various insults, leading to the formation of cell swelling and brain edema. We previously established that ATX attenuated brain edema and improved neurological outcomes by modulating NKCC1 expression after traumatic brain injury in mice...
May 10, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28488084/loop-diuretics-diminish-hemolysis-induced-by-%C3%AE-hemolysin-from-escherichia-coli
#6
Carl Martin Söderström, Steen K Fagerberg, Mette B Brogaard, Jens Leipziger, Marianne Skals, Helle A Praetorius
Uropathogenic Escherichia coli often produce the virulence factor α-hemolysin (HlyA), and the more severe the infection, the likelier it is to isolate HlyA-producing E. coli from patients. HlyA forms pores upon receptor-independent insertion of the toxin into biological membranes and it has been substantiated that HlyA-induced hemolysis is amplified by toxin-induced ATP release and activation of P2X receptors. Thus, hemolysis inflicted by HlyA is a protracted process involving signal transduction. It consists of early, marked cell shrinkage followed by swelling and eventually lysis...
May 9, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28485727/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#7
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
No abstract text is available yet for this article.
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28473802/the-subiculum-a-potential-site-of-ictogenesis-in-a-neonatal-seizure-model
#8
Xin-Xin Wang, Yong-Hua Li, Hai-Qing Gong, Pei-Ji Liang, Pu-Ming Zhang, Qin-Chi Lu
Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg(2+) or high-K(+) artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28433802/role-of-environmental-stressors-in-determining-the-developmental-outcome-of-neonatal-anesthesia
#9
Ling-Sha Ju, Jiao-Jiao Yang, Nikolaus Gravenstein, Christoph N Seubert, Timothy E Morey, Colin Sumners, Terrie Vasilopoulos, Jian-Jun Yang, Anatoly E Martynyuk
BACKGROUND: The majority of studies evaluating neurocognition in humans who had procedures under anesthesia early in life found long-term deficits even though the typical anesthesia duration normalized to the human life span is much shorter than that shown to induce developmental abnormalities in rodents. Therefore, we studied whether subsequent environmental stressors contribute to deficiencies programmed by a brief neonatal etomidate exposure. METHODS: Postnatal days (P) 4, 5, or 6, Sprague-Dawley rats, pretreated with vehicle or the Na(+)-K(+)-2Cl(-) (NKCC1) inhibitor, bumetanide, received two injections of etomidate resulting in anesthesia for 2h...
April 7, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28417963/loop-diuretics-affect-skeletal-myoblast-differentiation-and-exercise-induced-muscle-hypertrophy
#10
Shintaro Mandai, Susumu Furukawa, Manami Kodaka, Yutaka Hata, Takayasu Mori, Naohiro Nomura, Fumiaki Ando, Yutaro Mori, Daiei Takahashi, Yuki Yoshizaki, Yuri Kasagi, Yohei Arai, Emi Sasaki, Sayaka Yoshida, Yasuro Furuichi, Nobuharu L Fujii, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28411035/altered-ion-transport-in-normal-human-bronchial-epithelial-cells-following-exposure-to-chemically-distinct-metal-welding-fume-particles
#11
Jeffrey S Fedan, Janet A Thompson, Terence G Meighan, Patti C Zeidler-Erdely, James M Antonini
Welding fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of fume toxicity, and investigated the effects of fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn...
July 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28291262/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#12
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl(-))i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I)...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28213919/diuretic-sensitive-electroneutral-na-movement-and-temperature-effects-on-central-axons
#13
Meneka Kanagaratnam, Christopher Pendleton, Danilo Almeida Souza, Joseph Pettit, James Howells, Mark D Baker
KEY POINTS: Optic nerve axons get less excitable with warming. F-fibre latency does not shorten at temperatures above 30°C. Action potential amplitude falls when the Na(+) -pump is blocked, an effect speeded by warming. Diuretics reduce the rate of action potential fall in the presence of ouabain. Our data are consistent with electroneutral entry of Na(+) occurring in axons and contributing to setting the resting potential. ABSTRACT: 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...
June 1, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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