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bumetanide

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https://www.readbyqxmd.com/read/29319897/application-of-a-physiologically-based-pharmacokinetic-model-for-the-prediction-of-bumetanide-plasma-and-brain-concentrations-in-the-neonate
#1
Maria D Donovan, Khaled Abduljalil, John F Cryan, Geraldine B Boylan, Brendan T Griffin
Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on disorders of the central nervous system, including neonatal seizures. Therefore, prediction of unbound bumetanide concentrations in brain is relevant from a pharmacological prospective. A physiologically-based pharmacokinetic (PBPK) model was developed for the prediction of bumetanide disposition in plasma and brain in adult and pediatric populations. A compound file was built for bumetanide integrating physicochemical data and in vitro data...
January 10, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29235092/bumetanide-blocks-the-acquisition-of-conditioned-fear-in-adult-rats
#2
Meng-Chang Ko, Ming-Chung Lee, Tso-Hao Tang, Tamara G Amstislavskaya, Maria A Tikhonova, Yi-Ling Yang, Kwok-Tung Lu
BACKGROUND AND PURPOSE: Administration of bumetanide has anxiolytic effects in rat models of conditioned fear. As a loop diuretic, bumetanide may act as an anxiolytic by modulating GABAergic synaptic transmission through the antagonism of cation-chloride cotransporters (CCCs). Its clinical potential for the treatment of anxiety disorders deserves further investigation. In this study, we evaluated the possible role of the basolateral nucleus of amygdala (BLA) in the anxiolytic effect of bumetanide...
December 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29218440/biochemical-properties-of-the-sensitivity-to-gabaaergic-ligands-cl-hco3-atpase-isolated-from-fish-cyprinus-carpio-olfactory-mucosa-and-brain
#3
Sergey Menzikov
This paper presents a comparative study of the roles of Cl- and HCO3- in the functioning of the GABAAR-associated Cl-/HCO3--ATPase of the plasma membranes of the olfactory sensory neurons (OSNs) and mature brain neurons (MBNs) of fish. The ATPase activity of OSNs and its dephosphorylation were increased twofold by Cl-(15-30 mmol l-1), whereas the enzyme from MBNs was not significantly affected by Cl-. By contrast, HCO3-(15-30 mmol l-1) significantly activated the MBN enzyme and its dephosphorylation, but had no effect on the OSN ATPase...
December 7, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29209227/the-role-of-na-k-2cl-cotransporter-1-nkcc1-slc12a2-in-dental-epithelium-during-enamel-formation-in-mice
#4
Rozita Jalali, Johannes C Lodder, Behrouz Zandieh-Doulabi, Dimitra Micha, James E Melvin, Marcelo A Catalan, Huibert D Mansvelder, Pamela DenBesten, Antonius Bronckers
Na+:K+:2Cl- cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl- transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1-null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29204056/effects-of-hemp-seed-soft-capsule-on-colonic-ion-transport-in-rats
#5
Xiao-Fang Lu, Meng-Di Jia, Sheng-Sheng Zhang, Lu-Qing Zhao
AIM: To investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion transport and its related mechanisms in constipation rats. METHODS: Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d...
November 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29179179/naringenin-regulates-cftr-activation-and-expression-in-airway-epithelial-cells
#6
Rui Shi, Zi-Ting Xiao, Yi-Jun Zheng, Yi-Lin Zhang, Jia-Wen Xu, Jie-Hong Huang, Wen-Liang Zhou, Pei-Bo Li, Wei-Wei Su
BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29176723/potassium-regulation-in-medaka-oryzias-latipes-larvae-acclimated-to-fresh-water-passive-uptake-and-active-secretion-by-the-skin-cells
#7
Jiun-Lin Horng, Li-Lu Yu, Sian-Tai Liu, Po-Yen Chen, Li-Yih Lin
Molecular mechanisms of Na+, Cl-, and Ca2+ regulation in ionocytes of fish have been well investigated. However, the regulatory mechanism of K+ in fishes has been largely unknown. In this study, we investigated the mechanism of K+ regulation in medaka larvae acclimated to fresh water. Using a scanning ion-selective electrode technique (SIET) to measure the K+ fluxes at skin cells, significant K+ effluxes were found at ionocytes; in contrast, significant K+ influxes were found at the boundaries between keratinocytes...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29159314/vasoconstriction-triggered-by-hydrogen-sulfide-evidence-for-na-k-2cl-cotransport-and-l-type-ca-2-channel-mediated-pathway
#8
Sergei N Orlov, Svetlana V Gusakova, Liudmila V Smaglii, Svetlana V Koltsova, Svetalana V Sidorenko
Objectives: This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC). Methods: Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na(+)/K(+)-pump and Na(+),K(+),2Cl(-)cotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the (86)Rb influx, respectively...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29146941/developmental-excitatory-to-inhibitory-gaba-polarity-switch-is-disrupted-in-22q11-2-deletion-syndrome-a-potential-target-for-clinical-therapeutics
#9
Hayder Amin, Federica Marinaro, Davide De Pietri Tonelli, Luca Berdondini
Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel (+/-)), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29029515/discovery-of-nkcc1-as-a-potential-therapeutic-target-to-inhibit-hepatocellular-carcinoma-cell-growth-and-metastasis
#10
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29024278/why-do-sglt2-inhibitors-reduce-heart-failure-hospitalization-a-differential-volume-regulation-hypothesis
#11
REVIEW
Karen M 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 that of 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/28982596/subsequent-maternal-separation-exacerbates-neurobehavioral-abnormalities-in-rats-neonatally-exposed-to-sevoflurane-anesthesia
#12
Jiaojiao Yang, Lingsha Ju, Min Jia, Hui Zhang, Xiaoru Sun, Muhuo Ji, Jianjun Yang, Anatoly E Martynyuk
Several recent studies suggest that in the human population, a routine, short anesthetic in otherwise healthy infants is void of neurodevelopmental insult. On the other hand, many human retrospective epidemiological studies report evidence of cognitive abnormalities in children after testing those who had different anesthesia-requiring procedures in early childhood. We tested in a rat model whether post-anesthesia stressful environmental factors can contribute to developmental abnormalities that were initiated by a relatively short exposure to sevoflurane, the most widely used anesthetic in pediatric anesthesia, whose polyvalent actions include enhancement of gamma-aminobutyric acid type A receptor (GABAAR) activity...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28964752/inhibition-of-nkcc1-promotes-axonal-growth-and-motor-recovery-in-ischemic-rats
#13
X P Mu, H B Wang, X Cheng, L Yang, X Y Sun, H L Qu, S S Zhao, Z K Zhou, T T Liu, T Xiao, B Song, J Jolkkonen, C S Zhao
Bumetanide is a selective inhibitor of the Na(+)-K(+)-Cl(-)-co-transporter 1(NKCC1). We studied whether bumetanide could affect axonal growth and behavioral outcome in stroke rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats treated with vehicle or bumetanide, and ischemic rats treated with vehicle or bumetanide. Endothelin-1 was used to induce focal cerebral ischemia. Bumetanide administration (i.c.v.) started on postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine (BDA) was injected into the right imotor cortex on postoperative day 14 to trace corticospinal tract (CST) fibers sprouting into the denervated cervical spinal cord...
December 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28956955/a-resurging-boom-in-new-drugs-for-epilepsy-and-brain-disorders
#14
Iyan Younus, Doodipala Samba Reddy
Epilepsy is one of the most common neurological diseases affecting approximately 50 million people worldwide. Despite many advances in epilepsy research, nearly a third of patients with epilepsy have refractory or pharmacoresistant epilepsy. Despite the approval of a dozen antiepileptic drugs (AEDs) over the past decade, there are no agents that halt the development of epilepsy. Thus, newer and better AEDs that can prevent refractory seizures and modify the disease are needed for curing epilepsy. Areas covered: In this article, we highlight the recent advances and emerging trends in new and innovative drugs for epilepsy and seizure disorders...
October 23, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28943860/bumetanide-as-a-candidate-treatment-for-behavioral-problems-in-tuberous-sclerosis-complex
#15
Chantal Vlaskamp, Simon-Shlomo Poil, Floor Jansen, Klaus Linkenkaer-Hansen, Sarah Durston, Bob Oranje, Hilgo Bruining
BACKGROUND: Recent studies indicate excitatory GABA action in and around tubers in patients with tuberous sclerosis complex (TSC). This may contribute to recurrent seizures and behavioral problems that may be treated by agents that enhance GABAergic transmission by influencing chloride regulation. CASE PRESENTATION: Here, we used the chloride transporter antagonist bumetanide to treat a female adolescent TSC patient with refractory seizures, sensory hyper-reactivity, and a variety of repetitive and compulsive behaviors...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28928398/bumetanide-treatment-during-early-development-rescues-maternal-separation-induced-susceptibility-to-stress
#16
Die Hu, Zhou-Long Yu, Yan Zhang, Ying Han, Wen Zhang, Lin Lu, Jie Shi
Stress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the present study, we found that maternal separation increased the susceptibility to stress in adolescent rats, increased the expression of Na(+)/K(+)/2Cl(-) cotransporter 1 (NKCC1) on postnatal day 14, and increased the expression of K(+)/2Cl(-) cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABAA) receptor subunits on postnatal day 40 in the hippocampus...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889825/enhancement-of-diuresis-with-metolazone-in-infant-paediatric-cardiac-intensive-care-patients
#17
Russell T Wise, Brady S Moffett, Ayse Akcan-Arikan, Marianne Galati, Natasha Afonso, Paul A Checchia
BACKGROUND: Few data are available regarding the use of metolazone in infants in cardiac intensive care. Researchers need to carry out further evaluation to characterise the effects of this treatment in this population. METHODS: This is a descriptive, retrospective study carried out in patients less than a year old. These infants had received metolazone over a 2-year period in the paediatric cardiac intensive care unit at our institution. The primary goal was to measure the change in urine output from 24 hours before the start of metolazone therapy to 24 hours after...
January 2018: Cardiology in the Young
https://www.readbyqxmd.com/read/28877883/versatility-of-nacl-transport-mechanisms-in-the-cortical-collecting-duct
#18
REVIEW
Aurélie Edwards, Gilles Crambert
The cortical collecting duct (CCD) forms part of the aldosterone-sensitive distal nephron and plays an essential role in maintaining the NaCl balance and acid-base status. The CCD epithelium comprises principal cells as well as different types of intercalated cells. Until recently, transcellular Na+ transport was thought to be restricted to principal cells, whereas (acid-secreting) type A and (bicarbonate-secreting) type B intercalated cells were associated with the regulation of acid-base homeostasis. This review describes how this traditional view has been upended by several discoveries in the past decade...
December 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28862222/efficiency-of-combined-blocking-of-aerobic-and-glycolytic-metabolism-pathways-in-treatment-of-n1-s1-hepatocellular-carcinoma-in-a-rat-model
#19
Hooman Yarmohammadi, Luke R Wilkins, Joseph P Erinjeri, Ronald D Novak, Agata A Exner, Hanping Wu, Elena N Petre, Edward Boas, Etay Ziv, John R Haaga
BACKGROUND/AIM: The aim of this study was to determine whether the addition of bumetanide (BU), a glycolytic metabolism pathway inhibitor, to arterial embolization improves tumor necrosis of N1-S1 hepatocellular carcinoma in a rat model. MATERIALS AND METHODS: N1-S1 tumors were surgically implanted in the liver of 14 Sprague-Dawley rats. The rats were divided into three groups: In control group (n = 5), 1 ml of normal saline was injected intra-arterially. The tumor in the transarterial embolization group (TAE, n = 4) was embolized using 10 mg of 50-150 μ polyvinyl alcohol (PVA) particles and embolization plus BU group (TAE + BU, n = 5) were embolized with 10 mg of PVA plus 0...
July 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28860458/intracellular-chloride-regulation-in-avp-and-vip-neurons-of-the-suprachiasmatic-nucleus
#20
Nathan J Klett, Charles N Allen
Several reports have described excitatory GABA transmission in the suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. However, there is disagreement regarding the prevalence, timing, and neuronal location of excitatory GABA transmission in the SCN. Whether GABA is inhibitory or excitatory depends, in part, on the intracellular concentration of chloride ([Cl(-)]i). Here, using ratiometric Cl(-) imaging, we have investigated intracellular chloride regulation in AVP and VIP-expressing SCN neurons and found evidence suggesting that [Cl(-)]i is higher during the day than during the night in both AVP+ and VIP+ neurons...
August 31, 2017: Scientific Reports
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