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Activation of transepithelial ion transport by secretin in human intestinal Caco-2 cells.

Secretin stimulates bicarbonate secretion from pancreatic duct cells, but what influence secretin exerts on intestinal tissues remains to be clarified. The aim of this study is to examine effects of secretin on ion transport in intestinal epithelial Caco-2 cells. We mounted monolayers of Caco-2 cells grown on permeable supports for 21-28 d in a Ussing chamber and measured short-circuit currents (I(sc)). Addition of secretin (5-100 nM) to the basolateral solution dose-dependently induced biphasic increases of I(sc) (transient and sustained phase). Dibutyryl cyclic AMP (200 microM), forskolin (1

The Na+/H+ exchanger in immature and mature granulocytic HL-60 cells. Property changes induced by intracellular acidification and cell maturation.

We have compared the properties of the Na+/H+ exchanger in two cell populations: growing promyelocytic HL-60 cells (immature) and HL-60 cell … mature cells. Intracellular pH also influenced the pattern of inhibition of 22Na uptake by dimethylamiloride, a specific inhibitor of the exchanger. At intracellular pH 7.0 dimethylamiloride inhibition was mostly competitive in immature and competitive in mature cells. At lower intracellular pH, 5.9, the inhibition was mixed in both types of cells. Thus, t …

Ventricular dysrhythmias in middle-aged hypertensive men treated either with a diuretic agent or a beta-blocker.

The purpose of this study was to identify the frequency of cardiac dysrhythmias in two similar groups of hypertensive middle-aged males (age 45-66). They had previously been randomized either to a diuretic treatment (n = 42), or a beta-blocking agent (n = 41). A 24-hour ambulatory Holter monitoring, and serum potassium, was obtained in all patients, serum magnesium was measured in 35 patients. The mean number of ventricular premature beats (VPBs) and the frequency of complex arrhythmias (19 vs. 5) was significantly higher in the diuretic group (p less than 0.01). The serum potassium was signif

Chloride transport in glands of frog skin.

The effects of beta-adrenergic stimulation on the bidirectional fluxes of Na+ and Cl- across the frog skin glands were determined. Isoproterenol elicited net serosal-to-mucosal fluxes of both Na+ (JNanet) and Cl- (JClnet) equal to 0.19 +/- 0.05 (SE) and 0.57 +/- 0.05 mueq X cm-2 X h-1, respectively. The residual current (JClnet - JNanet) of 0.38 +/- 0.05 mueq X cm-2 X h-1 closely approximates the isoproterenol-induced short-circuit current of 0.30 +/- 0.04 mueq X cm-2 X h-1. Furosemide added to the serosal side prior to isoproterenol inhibited the isoproterenol-induced net fluxes of both Na+ a

Repurposing Cimetidine as a Therapeutic Candidate for Irritable Bowel Syndrome in a Rat Model.

BACKGROUND: Visceral hypersensitivity and impaired intestinal barrier function are hallmark features of irritable bowel syndrome (IBS), link … CRF-induced changes. In contrast, famotidine, another H2 blocker, did not replicate these effects. Amiloride, an NHE inhibitor, mimicked cimetidine's effects, both of which were abolished by intracisternal SB-334867, an orexin 1 receptor antagonist. Furthermore, atropine, sulpiride, and NG-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibi …

Механизм поглощения и токсичности антителного препарата BCMA в сочетании с полезной нагрузкой MMAF неантигенными функционирующими элементами.

Belantamab mafodotin, антитело-наркомания (ADC), продемонстрировал высокую эффективность в множестве миеломы. Он состоит из гуманизированного антиклектового антигена (BCMA) IgG1 моноклонального антитела, смешанного с монометил-ауристатином F (MMAF) с помощью манимидокапроилового связующего устройства. С помощью неизвестных механизмов поступили сообщения о связанных с окультизмом неблагоприятных явлениях, в частности о роговицах, в которых содержится АКЦ, в том числе белантамб мафодотин. В ходе этого исследования изучался механизм поглощения и цитотоксичности белантамбом мафодотином, содержащим

Совпадение в аннотации оригинала
Belantamab mafodotin, an antibody-drug conjugate (ADC), has shown strong efficacy in multiple myeloma. It comprises a humanized anti-B-cell … ntly reduced (~ 23%) following treatment with the macropinocytosis inhibitor 5-(N-Ethyl-N-isopropyl)amiloride. Co-treatment with endocytic pathway inhibitors nystatin or chlorpromazine also reduced ADC uptake, while siRNA depletion of specific endocytic pathways showed no consistent effects on uptake in HCEC. These in vitro data indicate BCMA-independent ma …

Nasal potential difference in young children is feasible - Report from a national referral center.

BACKGROUND: -Nasal Potential Difference (NPD) is an established diagnostic tool for CF. However, standardized values for very young patients … rmal, and 2 abnormal. In the normal group, the basal potential difference (PD) averaged -17 ± 6 mV, amiloride response was 7 ± 3 mV, and chloride-free + isoproterenol response was -9 ± 5 mV. The two abnormal results were observed in a 12-month-old with failure to thrive and a 6-day-old with meconium plug, presenting with basal PD of -30 mV and -28 mV respec …

Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.

Humans exposed to chlorine (Cl2) due to industrial accidents or acts of terrorism may develop lung injury culminating to Acute Respiratory D … ve increased airway resistance, alveolar injury and acute pulmonary edema due to loss of epithelial amiloride-sensitive sodium channels. Mice not succumbing acutely displayed a delayed syndrome of progressive increase in airway resistance and emphysematous-like changes in lung morphology. Global proteomics of lungs harvested 24 h post Cl2 exposure revealed …

Inhibition of early EHDV2-Ibaraki infection steps in bovine cells by endosome alkalinization or ikarugamycin, but not by blockage of individual endocytic pathways.

The Epizootic hemorrhagic disease virus (EHDV), an orbivirus, is the etiological factor of a fatal hemorrhagic disease of wild ruminants. A … ndow (i.e., before endosomal processing) with inhibitors of actin polymerization, macropinocytosis (amiloride), or dynamin GTPase activity (dynasore or dynole), or with the cholesterol-depleting agent methyl-β-cyclodextrin, failed to reduce EHDV2-Ibaraki infection. In contrast, in this same treatment time frame, ikarugamycin potently inhibited infection. Mo …

An electrolyte flip flop - a patient with chronic hyperkalemic acidosis presenting with severe hypokalemic alkalosis.

A 76-year-old man was evaluated in our emergency department (ED) for right toe swelling and pain. His initial ED workup revealed volume over … routes. He was treated for his volume overload and hypertension with furosemide. Spironolactone and amiloride, potassium sparing diuretics, were cautiously given only during his hypokalemic phase. His plasma sodium and potassium levels, blood pressure and volume status gradually improved. "Kayexalate" effect should be suspected in a patient presenting with …

Antinociceptive effect of triterpene acetyl aleuritolic acid isolated from Croton zehntneri in adult zebrafish (Danio rerio).

Croton zehntneri is a plant known as canelinha de cunhã, prevalent in the northeast region of Brazil. Many constituents of the vegetable hav … he antinociceptive effect of AAA was inhibited by methylene blue, ketamine, camphor, ruthenium red, amiloride, and mefenamic acid. The antinociceptive effect of AAA on the cornea of animals was inhibited by capsazepine. Therefore, AAA showed pharmacological potential for the treatment of acute pain, and this effect is modulated by cGMP, NMDA receptors, tran …

Tolvaptan therapy to treat severe hyponatremia in pediatric nephrotic syndrome.

BACKGROUND: Tolvaptan is a selective oral vasopressin V2-receptor antagonist. Some data have implicated stimulation of arginine vasopressin … Thus, in addition to immunosuppressive therapy, she received diuretics, furosemide 5 mg/kg/day, and amiloride 1 mg/kg/day, and required water restriction. She was hypertensive and was treated with a full dose of calcium inhibitor (amlodipine 0.5 mg/kg/day). After2 months of treatment, serum sodium reached 116 mmol/L and urinary osmolarity 547 mosmol/L, sugg …

Hypomagnesemia with Hypercalciuria Leading to Nephrocalcinosis, Amelogenesis Imperfecta, and Short Stature in a Child Carrying a Homozygous Deletion in the CLDN16 Gene.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disease caused by mutations in the CL … iferol, magnesium oxide and potassium citrate. Later, the combination with hydrochlorothiazide plus amiloride was prescribed, with a good response during follow-up. Our report broadens the phenotype of FHHNC, including severe early-onset amelogenesis and short stature, and reinforces the phenotype-genotype correlation of the large deletion found in CLDN16.

Cerebellar gangliocytoma as a cause of fluctuating hearing loss.

Cerebellar lesions could be a cause of fluctuating hearing loss, due to the increase of intracranial pressure by partially or complete block … rrupted. The patient was given two intratympanic steroids cycles combined with hydrochlorothiazide/ amiloride hydrochloride. The cerebral MRI described a left cerebellar focal lesion diagnosed as a cerebellar gangliocytoma. After receiving the second intratympanic steroids, cycle combined with systemic ameride showed a significant improvement of audition. B …

Health-related quality of life in blood pressure control and blood lipid-lowering therapies: results from the CHIEF randomized controlled trial.

Our study aimed to explore changes in health-related quality of life (HRQoL) during blood pressure control and blood lipid-lowering therapies. We conducted a 2 × 2 factorial-designed randomized controlled trial in 180 clinical centers in China. At baseline, participants were randomly assigned to an amlodipine + amiloride/hydrochlorothiazide group or an amlodipine + telmisartan group for the blood pressure control treatment and to a statin group or a routine intervention group for the blood lipid-lowering treatment. The allocation ratio was 1:1 for both treatments. Follow-up lasted for 4 years.…

Interpreting stimulated plasma renin and aldosterone to select physiologically individualized therapy for resistant hypertension: importance of the class of stimulating drugs.

In the treatment of resistant hypertension, physiologically individualized therapy based on phenotyping with plasma renin activity (PRA) and plasma aldosterone significantly improves blood pressure control. Patients with a low-renin/low aldosterone (Liddle) phenotype respond best to amiloride, while those with low-renin/high aldosterone respond best to aldosterone antagonists, and those with high renin/high aldosterone (renal phenotype) respond best to angiotensin receptor blockers (ARB). However, it is important to measure PRA in a stimulated condition to distinguish between low levels due to…

Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome.

The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients wi … th ENaC subunits and αENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na+ /K+ -ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process αENaC. Renal expression le …

Distribution of Fos-immunoreactive neurons in the gustatory cortex elicited by intra-oral infusion of taste solutions in conscious rats.

The location of neurons in the gustatory cortex (GC) activated by intra-oral infusion of solutions in conscious rats was mapped using Fos immunohistochemistry. Groups of adult male Wistar rats (N's = 5) received an infusion of one of the following: dH2O, 0.1 or 1.0 M NaCl, 0.1 or 1.0 M sucrose, 0.32 M MSG (with 100 µM amiloride and 2.5 M inosine 5'-monophosphate), 0.03 M HCl, or 0.003 M QHCl delivered via an intra-oral cannula (0.233 ml/min for 5 min). Unstimulated control rats received no infusion. Taste reactivity (TR) behaviors were videotaped and scored. The number of Fos-immunoreactive (F…

l-Serine-modified polyamidoamine dendrimer as a highly potent renal targeting drug carrier.

Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in th … tudy of Ser-PAMAM in LLC-PK1 cells in the presence of inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, and lysozyme] revealed that caveolae-mediated endocytosis, micropinocytosis, and megalin were associated with the renal accumulation of Ser-PAMAM. The efficient renal distribution and angiotensin-converting enzyme (ACE) inhibition effect of captopr …