Sex-Differences in Solute Transport Along the Nephrons: Effects of Na+ Transport Inhibition.
Abstract
Each day approximately 1.7kg of NaCl and 180L of water are reabsorbed by nephron segments in humans, with urinary excretion fine-tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na+ transporters. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and how those effects may vary between males and females. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes a...
Source: American Journal of Physiology. Renal Physiology - August 2, 2020 Category: Physiology Authors: Hu R, McDonough AA, Layton AT Tags: Am J Physiol Renal Physiol Source Type: research
Role of NKCC1 Activity in Glioma K+ Homeostasis and Cell Growth: New Insights With the Bumetanide-Derivative STS66
Conclusion: The new BMT-derivative NKCC1 inhibitor STS66 is more effective than BMT in reducing glioma cell growth in part by inhibiting NKCC1-mediated K+ influx. TMZ + STS66 combination treatment reduces glioma cell growth via inhibiting cell cycle and AKT-ERK signaling. (Source: Frontiers in Physiology)
Source: Frontiers in Physiology - July 30, 2020 Category: Physiology Source Type: research
Bumetanide for Core Symptoms of Autism Spectrum Disorder (BAMBI): A Single Center, Double-Blinded, Participant-Randomized, Placebo-Controlled, Phase Two, Superiority Trial
Recent trials have indicated positive effects of bumetanide in autism spectrum disorder (ASD). We tested efficacy of bumetanide on core symptom domains using a mono-center, parallel-group, participant-randomized, double-blind, placebo-controlled phase-2 superiority trial in a tertiary Netherlands hospital. (Source: Journal of the American Academy of Child and Adolescent Psychiatry)
Source: Journal of the American Academy of Child and Adolescent Psychiatry - July 26, 2020 Category: Psychiatry Authors: Jan J. Sprengers, Dorinde M. van Andel, Nicolaas PA. Zuithoff, Mandy G. Keijzer-Veen, Annelien JA. Schulp, Floortje E. Scheepers, Marc R. Lilien, Bob Oranje, Hilgo Bruining Tags: New Research Source Type: research
Androgenic Modulation of the Chloride Transporter NKCC1 Contributes to Age-dependent Isoflurane Neurotoxicity in Male Rats
ConclusionsVulnerability to isoflurane neurotoxicity is abolished by blocking the androgen receptor, disrupting the function of NKCC1, or delaying the time of exposure to at least 2 weeks of age in male rats. These results support a dynamic role for androgens and chloride transporter proteins in perinatal anesthetic neurotoxicity.Editor ’s PerspectiveWhat We Already Know about This TopicExperimental data in laboratory animals suggest sex-dependent differences in neurocognitive and behavioral vulnerability to early life anesthesia exposureSteroid sex hormones play an important role in guiding sex-specific brain developmen...
Source: Anesthesiology - June 25, 2020 Category: Anesthesiology Source Type: research
Empagliflozin in Heart Failure: Diuretic and Cardio-Renal Effects.
Conclusions:Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in HF patients and may represent a mechanism contributing to the superior long-term HF outcomes observed with these agents. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03029760.
PMID: 32410463 [PubMed - as supplied by publish...
Source: Circulation - May 14, 2020 Category: Cardiology Authors: Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM Tags: Circulation Source Type: research
Photoluminescence and in vitro cytotoxicity analysis in a novel mononuclear Zn(II) coordination compound based on bumetanide
Publication date: 1 September 2020Source: Inorganica Chimica Acta, Volume 509Author(s): Amalia García-García, Estitxu Echenique-Errandonea, Javier Cepeda, Duane Choquesillo-Lazarte, José M. Seco, Alfonso Salinas-Castillo, Manuel Sánchez-Moreno, José M. Méndez-Arriaga, Antonio Rodríguez-Diéguez (Source: Inorganica Chimica Acta)
Source: Inorganica Chimica Acta - May 12, 2020 Category: Chemistry Source Type: research
Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study
ConclusionsBumetanide treatment is a potential treatment to alleviate the behavioral burden and quality of life associated with TSC. More elaborate trials are needed to determine the application and effect size of bumetanide for the TSC population.Trial registrationEU Clinical Trial Register, EudraCT 2016-002408-13 (www.clinicaltrialsregister.eu/ctr-search/trial/2016-002408-13/NL). Registered 25 July 2016. (Source: Molecular Autism)
Source: Molecular Autism - May 6, 2020 Category: Molecular Biology Source Type: research
Photoluminescence and in vitro cytotoxicity analysis in a novel mononuclear Zn (II) coordination compound based on bumetanide
Publication date: Available online 29 April 2020Source: Inorganica Chimica ActaAuthor(s): Amalia García-García, Estitxu Echenique-Errandonea, Javier Cepeda, Duane Choquesillo-Lazarte, José M. Seco, Alfonso Salinas-Castillo, Manuel Sánchez-Moreno, José M. Méndez-Arriaga, Antonio Rodríguez-Diéguez (Source: Inorganica Chimica Acta)
Source: Inorganica Chimica Acta - April 30, 2020 Category: Chemistry Source Type: research
Drugs for Hypertension
Date: May 18, 2020
Issue #:
1598Summary:
Drugs available for treatment of chronic hypertension
and their dosages, adverse effects, and costs are
listed in the tables. Treatment
of hypertensive urgencies and emergencies is not
discussed here. (Source: The Medical Letter)
Source: The Medical Letter - April 29, 2020 Category: Drugs & Pharmacology Authors: admin Tags: Accupril Accuretic ACE inhibitors Acebutolol Adalat Aldactone aliskiren Altace Amiloride Amlodipine ARBs Atacand Atenolol Avalide Avapro azilsartan benazapril Benicar Beta blockers Betaxolol Bisoprolol Bumetanide Source Type: research
Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on bumetanide scaffold.
Abstract
Herein, we describe the design and synthesis of new benzenesulfonamide derivatives as selective COX-2 inhibitors based on bumetanide scaffold. Benzenesulfonamides bearing both the pyrazole 6b and the triazoles 9a, 9c were good inhibitors of COX-2 with IC50 values of 0.32, 0.28 and 0.17 µM, respectively. These benzenesulfonamides 6b, 9a and 9c exhibited a higher selectivity index than the reference drug celecoxib. Molecular modeling study showed that incorporation of bumetanide led to a unique binding mode that is most likely the reason for the observed significant COX-2 selectivity. The anti-inf...
Source: Bioorganic Chemistry - April 25, 2020 Category: Chemistry Authors: Ibrahim TS, Salem IM, Mostafa SM, El-Sabbagh OI, ElKhamisi MKM, Hegazy L, Elgendy B Tags: Bioorg Chem Source Type: research
TRPV1 activation stimulates NKCC1 and increases hydrostatic pressure in mouse lens.
Abstract
The porcine lens response to a hyperosmotic stimulus involves an increase in the activity of NKCC1. Recent studies with agonists and antagonists pointed to a mechanism that appears to depend on activation of TRPV1. Here we compare responses in lenses and cultured lens epithelium obtained from TRPV1-/- and wild type (WT) mice. Hydrostatic pressure (HP) in lens surface cells was determined using a manometer-coupled microelectrode approach. The TRPV1 agonist capsaicin caused a transient HP increase in WT lenses that peaked after ~30 min then returned toward baseline. TRPV1-/- lenses did not respond t...
Source: Am J Physiol Cell Ph... - April 14, 2020 Category: Cytology Authors: Shahidullah M, Mandal A, Mathias RT, Gao J, Križaj D, Redmon S, Delamere NA Tags: Am J Physiol Cell Physiol Source Type: research
Interleukin-18 from neurons and microglia mediates depressive behaviors in mice with post-stroke depression.
In this study, we demonstrate that in IL-18 level in the ischemic brain significantly increased in mice with depression-like behaviors that caused by the combined use of chronic spatial restraint stress and middle cerebral artery occlusion. Interestingly, IL-18 expression was mainly found in neurons at early phase and in microglia in late phase. Injection of exogenous IL-18 in to the amygdala, but not the hippocampus or the striatum, caused severe depression-like behaviors. On the contrary, the blockage of endogenous IL-18 by IL-18 binding protein, a specific antagonist of IL-18, rescued depressive phenotypes in SIR mice. ...
Source: Brain, Behavior, and Immunity - April 5, 2020 Category: Neurology Authors: Wu D, Zhang G, Zhao C, Yang Y, Miao Z, Xu X Tags: Brain Behav Immun Source Type: research
Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease.
Abstract
The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for cellular metabolism and pH regulation. MCTs 1-4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. MCT1 has als...
Source: Pharmacological Reviews - March 8, 2020 Category: Drugs & Pharmacology Authors: Felmlee MA, Jones RS, Rodriguez-Cruz V, Follman KE, Morris ME Tags: Pharmacol Rev Source Type: research
Lubiprostone Protects Esophageal Mucosa from Acid Injury in Porcine Esophagus.
Abstract
Esophageal injury from acid exposure related to gastroesophageal reflux disease is a common problem and a risk factor for development of Barrett's esophagus and esophageal adenocarcinoma. Our previous work highlights the benefits of using porcine esophagus to study human esophageal disease because of the similarities between porcine and human esophagus. In particular, esophageal submucosal glands (ESMGs) are present in human esophagus and proximal porcine esophagus, but not in rodent esophagus. Although CFTR is expressed in the ducts of ESMGs, very little is known about CFTR and alternate anion ch...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - February 17, 2020 Category: Physiology Authors: Krüger L, Pridgen TA, Taylor ER, Garman KS, Blikslager AT Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios
Translational Psychiatry, Published online: 12 February 2020; doi:10.1038/s41398-020-0747-4Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios (Source: Translational Psychiatry)
Source: Translational Psychiatry - February 11, 2020 Category: Psychiatry Authors: Lingli Zhang Chu-Chung Huang Yuan Dai Qiang Luo Yiting Ji Kai Wang Shining Deng Juehua Yu Mingyu Xu Xiujuan Du Yun Tang Chun Shen Jianfeng Feng Barbara J Sahakian Ching-Po Lin Fei Li Source Type: research
