keyword
https://read.qxmd.com/read/38511069/comparison-of-different-medical-treatments-for-primary-hyperaldosteronism-a-systematic-review-and-network-meta-analysis
#1
JOURNAL ARTICLE
Wen-Yu Ho, Ching-Chung Hsiao, Ping-Hsun Wu, Jui-Yi Chen, Yu-Kang Tu, Vin-Cent Wu, Jia-Jin Chen
BACKGROUND: The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied. OBJECTIVE: To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events. DESIGN: Systematic review and NMA. DATA SOURCES AND METHODS: The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines...
2024: Therapeutic Advances in Chronic Disease
https://read.qxmd.com/read/38479593/evaluation-of-the-translation-of-multiple-cardiovascular-regulatory-mechanisms-in-the-anesthetized-dog
#2
JOURNAL ARTICLE
Olivera Antic, Yevgeniya E Koshman, Brandan M Bird, Geena Jasiek, Amanda S Wilsey, Scott W Mittelstadt, C Michael Foley
The strategic and targeted use of an anesthetized canine cardiovascular model early in drug discovery enables a comprehensive cardiovascular and electrophysiological assessment of potential safety liabilities and guides compound selection prior to initiation of chronic toxicological studies. An ideal model would enable exposure-response relationships to guide safety margin calculations, have a low threshold to initiate, and have quick delivery of decision quality data. We have aimed to profile compounds with diverse mechanism of actions (MoAs) of "non-QT" cardiovascular drug effects and evaluate the ability of nonclinical in vivo cardiovascular models to detect clinically reported effects...
March 11, 2024: Journal of Pharmacological and Toxicological Methods
https://read.qxmd.com/read/38460290/-heterotopic-abdominal-wall-ossification-a-case-report-information
#3
Mohadeseh Karimi, Seyed Abdollah Mousavi
INTRODUCTION AND IMPORTANCE: Heterotopic ossification is forming a new bone in tissues that do not normally ossify. HO was first reported in 1901 by Askanazy and Lubarsh in a case report study. The range of HO is wide from minute foci to large clinically significant ossification. The incidence of HO in abdominal scars is extremely low. CASE PRESENTATION: We present an 84-year-old man referred to our hospital after an unsuccessful elective colostomy reversal in a local hospital...
March 7, 2024: International Journal of Surgery Case Reports
https://read.qxmd.com/read/38405735/proteolytic-cleavage-of-the-enac-%C3%AE-subunit-impact-upon-na-and-k-handling
#4
Evan C Ray, Andrew Nickerson, Shaohu Sheng, Rolando Carrisoza-Gaytan, Tracey Lam, Allison Marciszyn, Lei Zhang, Alexa Jordahl, Chunming Bi, Aaliyah Winfrey, Zhaohui Kou, Sebastien Gingras, Annet Kirabo, Lisa M Satlin, Thomas R Kleyman
The ENaC gamma subunit is essential for homeostasis of Na + , K + , and body fluid. Dual subunit cleavage before and after a short inhibitory tract allows dissociation of this tract, increasing channel open probability (P O ), in vitro . Cleavage proximal to the tract occurs at a furin recognition sequence ( 143 RKRR 146 in mouse). Loss of furin-mediated cleavage prevents in vitro activation of the channel by proteolysis at distal sites. We hypothesized that 143 RKRR 146 mutation to 143 QQQQ 146 ( Q4 ) in 129/Sv mice would reduce ENaC P O , impair flow-stimulated flux of Na + (J Na ) and K + (J K ) in perfused collecting ducts, reduce colonic amiloride-sensitive short circuit current (I SC ), and impair Na + , K + , and body fluid homeostasis...
February 14, 2024: bioRxiv
https://read.qxmd.com/read/38367901/house-dust-mite-allergens-induce-ca-2-signalling-and-alarmin-responses-in-asthma-airway-epithelial-cells
#5
JOURNAL ARTICLE
Xuan Ouyang, James A Reihill, Lisa E J Douglas, Orla M Dunne, Gerard P Sergeant, S Lorraine Martin
Type 2 inflammation in asthma develops with exposure to stimuli to include inhaled allergens from house dust mites (HDM). Features include mucus hypersecretion and the formation of pro-secretory ion transport characterised by elevated basal Cl- current. Studies using human sinonasal epithelial cells treated with HDM extract report a higher protease activated receptor-2 (PAR-2) agonist-induced calcium mobilisation that may be related to airway sensitisation by allergen-associated proteases. Herein, this study aimed to investigate the effect of HDM on Ca2+ signalling and inflammatory responses in asthmatic airway epithelial cells...
February 15, 2024: Biochimica et Biophysica Acta. Molecular Basis of Disease
https://read.qxmd.com/read/38366201/flagellar-ph-homeostasis-mediated-by-na-h-exchangers-regulates-human-sperm-functions-through-coupling-with-catsper-and-ksper-activation
#6
JOURNAL ARTICLE
Min Liang, Nanxi Ji, Jian Song, Hang Kang, Xuhui Zeng
STUDY QUESTION: Whether and how do Na+/H+ exchangers (NHEs) regulate the physiological functions of human sperm? SUMMARY ANSWER: NHE-mediated flagellar intracellular pH (pHi) homeostasis facilitates the activation of the pH-sensitive, sperm-specific Ca2+ channel (CatSper) and the sperm-specific K+ channel (KSper), which subsequently modulate sperm motility, hyperactivation, flagellar tyrosine phosphorylation, and the progesterone (P4)-induced acrosome reaction. WHAT IS KNOWN ALREADY: Sperm pHi alkalization is an essential prerequisite for the acquisition of sperm-fertilizing capacity...
February 14, 2024: Human Reproduction
https://read.qxmd.com/read/38360119/personalised-oral-dosage-forms-using-an-ultra-compact-tablet-press-at-the-point-of-care
#7
JOURNAL ARTICLE
Ingo Krause, Rene Manigk, Elena Arribas Lopez, Dennis Douroumis
Over the last 10 years there is an increasing need for the design of personalised medicines at the point of care (PoC) that meet the specific needs of individual patients. A plethora of technologies has been introduced for making affordable personalised pharmaceutical products, which however, do not address manufacturing and regulatory challenges. Here we introduce a novel ultra-compact tablet press which was used for the design and compression of rosuvastatin-aspirin and amiloride-lysonipril bilayer tablets respectively...
February 13, 2024: European Journal of Pharmaceutics and Biopharmaceutics
https://read.qxmd.com/read/38345534/role-of-paraoxonase-3-in-regulating-enac-mediated-na-transport-in-the-distal-nephron
#8
JOURNAL ARTICLE
Stephanie M Mutchler, Sarah Christine M Whelan, Allison Marciszyn, Jingxin Chen, Thomas R Kleyman, Shujie Shi
Paraoxonase 3 (PON3) is expressed in the aldosterone-sensitive distal nephron, where filtered Na+ is reabsorbed mainly via the epithelial Na+ channel (ENaC) and Na+ -coupled co-transporters. We previously showed that PON3 negatively regulates ENaC through a chaperone mechanism. The present study aimed to determine the physiological role of PON3 in renal Na+ and K+ homeostasis. Pon3 knockout (KO) mice had higher amiloride-induced natriuresis and lower plasma [K+ ] at baseline. Single channel recordings in split-open tubules showed that the number of active channels per patch was significantly higher in KO mice, resulting in a higher channel activity in the absence of PON3...
February 12, 2024: Journal of Physiology
https://read.qxmd.com/read/38341030/collecting-duct-ncor1-controls-blood-pressure-by-regulating-mineralocorticoid-receptor
#9
JOURNAL ARTICLE
Ke Sun, Yong-Li Wang, Chen-Chen Hou, Da Shang, Lin-Juan Du, Lan Bai, Xing-Yu Zhang, Chuan-Ming Hao, Sheng-Zhong Duan
INTRODUCTION: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. OBJECTIVE: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. METHODS AND RESULTS: Collecting duct NCOR1 knockout (KO) mice manifested increased BP and aggravated vascular and renal injury in an angiotensin II (Ang II)-induced hypertensive model...
February 8, 2024: Journal of Advanced Research
https://read.qxmd.com/read/38338690/opioid-analgesic-as-a-positive-allosteric-modulator-of-acid-sensing-ion-channels
#10
JOURNAL ARTICLE
Dmitry I Osmakov, Lyudmila V Onoprienko, Aleksandr P Kalinovskii, Sergey G Koshelev, Vasiliy N Stepanenko, Yaroslav A Andreev, Sergey A Kozlov
Tafalgin (Taf) is a tetrapeptide opioid used in clinical practice in Russia as an analgesic drug for subcutaneous administration as a solution (4 mg/mL; concentration of 9 mM). We found that the acid-sensing ion channels (ASICs) are another molecular target for this molecule. ASICs are proton-gated sodium channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Using electrophysiological methods, we demonstrated that Taf could increase the integral current through heterologically expressed ASIC with half-maximal effective concentration values of 0...
January 24, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38329295/neuromodulation-of-acid-sensitive-ion-channels-asics-and-anti-inflammatory-potential-by-lichenxanthone-in-adult-zebrafish-danio-rerio-experimental-and-docking-studies
#11
JOURNAL ARTICLE
Hortência Ribeiro Liberato, Jéssica Bezerra Maciel, Antônio Wlisses Da Silva, Maria Eduarda Uchoa Bezerra, Luana San De Oliveira Brito, Jacilene Silva, Maria Kuerislene Amâncio Ferreira, Marcia Machado Marinho, Gabrielle S Marinho, Otília Deusdênia Loiola Pessoa, Maria Izabel F Guedes, Paulo Goberlânio De Barros Silva, Andreia Ferreira de Castro Gomes, Jane Eire Silva Alencar De Menezes, Helcio Silva Dos Santos
The xanthone Lichenxanthone did not show toxic effects (LC50 > 1.0 mg/mL). Lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5 mg/mL of Lichenxanthone reduced the edema induced by k-carrageenan 3.5%, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control)...
February 8, 2024: Chemistry & Biodiversity
https://read.qxmd.com/read/38318572/abiraterone-associated-mineralocorticoid-excess-a-case-report
#12
Saeed K Shaffi, Raja Ravender, Chandra Kumar Mallick Kodavanti, Brent Wagner, Manoocher Soleimani
Abiraterone acetate causes an adrenocorticotropic hormone (ACTH)-mediated mineralocorticoid excess. We present a 77-year-old man with prostate adenocarcinoma who developed signs and symptoms of mineralocorticoid excess while on abiraterone and discuss its pathophysiology and treatment options. The patient developed hypokalemia, metabolic alkalosis, and hypertension, indicative of increased mineralocorticoid activity, confirmed by elevated ACTH, corticosterone, and deoxycorticosterone levels. Abiraterone inhibits cytochrome P450c17 (CYP17A1), thus inhibiting testosterone and cortisol synthesis...
January 2024: Curēus
https://read.qxmd.com/read/38280499/dual-fluorescence-images-transport-pathway-and-blood-brain-barrier-penetration-of-b-met-w-o-w-se
#13
JOURNAL ARTICLE
Liang Fang, Junying Li, Hongyan Cheng, Huanhuan Liu, Caiyun Zhang
Borneol is an aromatic traditional Chinese medicine that can improve the permeability of the blood-brain barrier (BBB), enter the brain, and promotes the brain tissue distribution of many other drugs. In our previous study, borneol-metformin hydrochloride water/oil/water composite submicron emulsion (B-Met-W/O/W SE) was prepared using borneol and SE to promote BBB penetration, which significantly increased the brain distribution of Met. However, the dynamic images, transport pathway (uptake and efflux), promotion of BBB permeability, and mechanisms of B-Met-W/O/W SE before and after entering cells have not been clarified...
January 25, 2024: International Journal of Pharmaceutics
https://read.qxmd.com/read/38277795/acidosis-defense-mechanisms-in-the-preimplantation-stages-of-embryos-in-balb-c-strain-mice
#14
JOURNAL ARTICLE
Senay Dagilgan, Ebru Dundar-Yenilmez, Abdullah Tuli, Ibrahim Ferhat Urunsak, Seref Erdogan
Regulation of intracellular pH (pHi ) is an important homeostatic function of cells. There are three major pHi regulatory mechanisms: the HCO3 - /Cl- exchanger (AE), which alleviates alkalosis, and the Na+ /H+ exchanger (NHE) and Na+ ,HCO3 - /Cl- exchanger (NDBCE), both of which counteract acidosis. NHE activity, which is high at the germinal vesicle stage of oocyte, is inhibited during meiotic maturation, while this inhibition is abolished when the oocyte reaches the pronuclear (PN) stage of the zygote. On the other hand, we have previously found that NDBCE performs complementary regulation against acidosis during meiotic maturation...
January 19, 2024: Theriogenology
https://read.qxmd.com/read/38266583/silica-nanoparticles-inhibit-cadmium-uptake-by-the-protozoan-tetrahymena-thermophila-without-the-need-for-adsorption
#15
JOURNAL ARTICLE
Chao Wu, Chaofan Deng, Jia-Xin Zhang, Wei Pan, Liuyan Yang, Ke Pan, Qiao-Guo Tan, Tongtao Yue, Ai-Jun Miao
The simultaneous presence of nanoparticles (NPs) and heavy metals in the environment may affect their mutual biological uptake. Although previous studies showed that NPs could alter the cellular uptake of heavy metals by their adsorption of heavy metals, whether they could affect metal uptake without the need for adsorption is unknown. This study examined the effects of silica (SiO2 ) NPs on the uptake of Cd ion by the protozoan Tetrahymena thermophila. We found that, even with negligible levels of adsorption, SiO2 NPs at concentrations of 3 to 100 mg/L inhibited Cd uptake...
January 20, 2024: Journal of Hazardous Materials
https://read.qxmd.com/read/38254266/amiloride-reduces-urokinase-plasminogen-driven-intratubular-complement-activation-in-glomerular-proteinuria
#16
JOURNAL ARTICLE
Gustaf L Isaksson, Gitte R Hinrichs, Henrik Andersen, Marie L Bach, Kathrin Weyer, Rikke Zachar, Jan Erik Henriksen, Kirsten Madsen, Ida K Lund, Géraldine Mollet, Claus Bistrup, Henrik Birn, Boye L Jensen, Yaseelan Palarasah
BACKGROUND: Persistent proteinuria is associated with tubular interstitial inflammation and predicts progressive kidney injury. In proteinuria, plasminogen is aberrantly filtered and activated by urokinase-type plasminogen activator (uPA) which promotes kidney fibrosis. We hypothesized that plasmin activates filtered complement factors C3 and C5 directly in tubular fluid, generating anaphylatoxins and that this is attenuated by amiloride, an off-target uPA inhibitor. METHODS: Purified C3, C5, plasminogen, urokinase and urine from healthy humans were used for in vitro/ex vivo studies...
January 23, 2024: Journal of the American Society of Nephrology: JASN
https://read.qxmd.com/read/38246115/development-of-utx-143-a-selective-sodium-hydrogen-exchange-subtype-5-inhibitor-using-amiloride-as-a-lead-compound
#17
JOURNAL ARTICLE
Yusei Shinohara, Yuki Komiya, Kashin Morimoto, Yoshio Endo, Minoru Terashima, Takeshi Suzuki, Takahisa Takino, Itasu Ninomiya, Hisatsugu Yamada, Yoshihiro Uto
NHE5, an isoform of the Na+ /H+ exchanger (NHE) protein, is an ion-transporting membrane protein that regulates intracellular pH and is highly expressed in colorectal adenocarcinoma. Therefore, we hypothesized that NHE5 inhibitors can be used as anticancer drugs. However, because NHE1 is ubiquitously expressed in all cells, it is extremely important to demonstrate its selective inhibitory activity against NHE5. We used amiloride, an NHE non-selective inhibitor, as a lead compound and created UTX-143, which has NHE5-selective inhibitory activity, using a structure-activity relationship approach...
January 14, 2024: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/38207121/characterization-of-commercially-available-human-primary-alveolar-epithelial-cells
#18
JOURNAL ARTICLE
Christopher J Herbst, Elena Lopez-Rodriguez, Vladimir Gluhovic, Sabrina Schulz, Raphael Brandt, Sara Timm, Jubilant Abledu, Juliana Falivene, Peter Pennitz, Holger Kirsten, Geraldine Nouailles, Martin Witzenrath, Matthias Ochs, Wolfgang M Kuebler
In vitro lung research requires appropriate cell culture models that adequately mimic in vivo structure and function. Previously, researchers have extensively utilized commercially available and easily expandable A549 and NCI-H441 cells which replicate some yet not all features of alveolar epithelial cells. Specifically, these cells are often restricted by terminally altered expression while lacking important alveolar epithelial characteristics. Of late, human primary alveolar epithelial cells (hPAEpC) have become commercially available, but are so far poorly specified...
January 11, 2024: American Journal of Respiratory Cell and Molecular Biology
https://read.qxmd.com/read/38205254/hexamethylene-amiloride-synergizes-with-venetoclax-to-induce-lysosome-dependent-cell-death-in-acute-myeloid-leukemia
#19
JOURNAL ARTICLE
Xinya Jiang, Kexiu Huang, Xiaofan Sun, Yue Li, Lei Hua, Fangshu Liu, Rui Huang, Juan Du, Hui Zeng
Tumors maintain an alkaline intracellular environment to enable rapid growth. The proton exporter NHE1 participates in maintenance of this pH gradient. However, whether targeting NHE1 could inhibit the growth of tumor cells remains unknown. Here, we report that the NHE1 inhibitor Hexamethylene amiloride (HA) efficiently suppresses the growth of AML cell lines. Moreover, HA combined with venetoclax synergized to efficiently inhibit the growth of AML cells. Interestingly, lysosomes are the main contributors to the synergism of HA and venetoclax in inhibiting AML cells...
January 19, 2024: IScience
https://read.qxmd.com/read/38185879/ion-transport-and-inhibitor-binding-by-human-nhe1-insights-from-molecular-dynamics-simulations-and-free-energy-calculations
#20
JOURNAL ARTICLE
Nehad S El Salamouni, Benjamin J Buckley, Richmond Lee, Marie Ranson, Michael J Kelso, Haibo Yu
The human Na+ /H+ exchanger (NHE1) plays a crucial role in maintaining intracellular pH by regulating the electroneutral exchange of a single intracellular H+ for one extracellular Na+ across the plasma membrane. Understanding the molecular mechanisms governing ion transport and the binding of inhibitors is of importance in the development of anticancer therapeutics targeting NHE1. In this context, we performed molecular dynamics (MD) simulations based on the recent cryo-electron microscopy (cryo-EM) structures of outward- and inward-facing conformations of NHE1...
January 7, 2024: Journal of Physical Chemistry. B
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