-
1.
Intracellular Cl- Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy.
Yasuda, M, Inui, TA, Hirano, S, Asano, S, Okazaki, T, Inui, T, Marunaka, Y, Nakahari, T
International journal of molecular sciences. 2020;(11)
Abstract
Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl-), and is enhanced by a decreased concentration of intracellular Cl- ([Cl-]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD, an index of ciliary beat amplitude) in cHNECs has been developed using high-speed video microscopy, which revealed that a decrease in [Cl-]i increased CBD, but not CBF, and an increase in [Cl-]i decreased both CBD and CBF. Thus, [Cl-]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl- sensors and be regulated by [Cl-]i. These observations indicate that the activation of Cl- secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl-]i in cHNECs. Thus, [Cl-]i is critical for controlling ciliary beating in cHNECs. This review introduces the concept of Cl- regulation of ciliary beating in cHNECs.
-
2.
Synthetic (E)-3-Phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium Chloride Derivatives as Promising Chemotherapy Agents on Cell Lines Infected with HTLV-1.
Sousa-Pereira, D, Oliveira, TS, Paiva, RO, Chaves, OA, Netto-Ferreira, JC, Echevarria-Lima, J, Echevarria, A
Molecules (Basel, Switzerland). 2020;(11)
Abstract
Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a-d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51-7.70 M in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a-d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a-d is spontaneous and moderate (Ka ~ 104 M-1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.
-
3.
Emergence of Chloride as an Overlooked Cardiorenal Connector in Heart Failure.
Kazory, A, Ronco, C
Blood purification. 2020;(1-2):219-221
Abstract
Several studies have recently challenged the sodium-centric view that has been dominating the field of heart failure (HF) and cardiorenal syndrome. The previously observed benefits of severe dietary restriction of salt do not seem to be consistently reproduced by contemporary studies. Moreover, there is evidence that too low intake may paradoxically lead to adverse outcomes in more advanced stages of HF. Facing the escalating controversy, investigators have shifted their focus from sodium to its often overlooked counter ion in salt, the chloride. Emerging data suggest that serum chloride levels could portend robust independent prognostic value in a wide range of HF syndromes possibly stronger than that of sodium. The untoward impact of hypochloremia on the outcomes could be mechanistically linked to renal tubular regulatory pathways, neurohormonal activation, and diuretic resistance. As such, it can be a potential target of therapy in this setting. In this article, the authors provide a brief overview of the role of serum chloride as a cardiorenal connector and explore the context in which the contemporary data should be interpreted. Implementation of predictive and therapeutic strategies incorporating the emerging evidence would be refined through discussion of nuances of such findings as well as their biological and clinical relevance.
-
4.
Females with Cystic Fibrosis Demonstrate a Differential Response Profile to Ivacaftor Compared with Males.
Secunda, KE, Guimbellot, JS, Jovanovic, B, Heltshe, SL, Sagel, SD, Rowe, SM, Jain, M
American journal of respiratory and critical care medicine. 2020;(8):996-998
-
5.
Urinary chloride concentration as a prognostic marker in critically ill patients.
Komaru, Y, Doi, K, Matsuura, R, Yoshida, T, Miyamoto, Y, Yoshimoto, K, Nangaku, M
Nephrology (Carlton, Vic.). 2020;(5):384-389
Abstract
AIM: Associations have been reported among serum chloride concentration, mortality and incidence of acute kidney injury (AKI) in intensive care units (ICU). This study aimed to examine associations among urinary chloride, mortality, and AKI incidence in ICU patients. METHODS A retrospective observational study was conducted among medical-surgical ICU in a tertiary hospital wherein 170 consecutive ICU patients were evaluated from October 2015 to March 2016 and 116 patients were enrolled. Serial data of serum and urine electrolytes from day 1 to day 4 of ICU admission were examined. The primary and secondary outcomes were ICU mortality and incidence of AKI in the ICU, respectively. RESULTS Among the 116 enrolled patients, 15 (13%) died during their ICU stay. Although serum and urinary sodium and potassium on day 1 did not significantly differ between ICU survivors and non-survivors, urinary chloride concentration on day 1 was significantly lower in non-survivors. Receiver operating characteristic analysis showed that the cutoff value of day 1 urinary chloride concentration for prediction of ICU mortality was 53 mEq/L. The lower urinary chloride concentration group on day 1 showed a significantly lower survival rate, even in long-term follow-up, compared with the higher urinary chloride group. Addition of day 1 urinary chloride concentration improved prediction of AKI incidence in the ICU by Sequential Organ Failure Assessment score alone. CONCLUSION Lower urinary chloride concentration was associated with increased mortality and incidence of AKI in the ICU. Further investigation is necessary to clarify the mechanism of urinary chloride regulation.
-
6.
What biologists want from their chloride reporters - a conversation between chemists and biologists.
Zajac, M, Chakraborty, K, Saha, S, Mahadevan, V, Infield, DT, Accardi, A, Qiu, Z, Krishnan, Y
Journal of cell science. 2020;(2)
Abstract
Impaired chloride transport affects diverse processes ranging from neuron excitability to water secretion, which underlie epilepsy and cystic fibrosis, respectively. The ability to image chloride fluxes with fluorescent probes has been essential for the investigation of the roles of chloride channels and transporters in health and disease. Therefore, developing effective fluorescent chloride reporters is critical to characterizing chloride transporters and discovering new ones. However, each chloride channel or transporter has a unique functional context that demands a suite of chloride probes with appropriate sensing characteristics. This Review seeks to juxtapose the biology of chloride transport with the chemistries underlying chloride sensors by exploring the various biological roles of chloride and highlighting the insights delivered by studies using chloride reporters. We then delineate the evolution of small-molecule sensors and genetically encoded chloride reporters. Finally, we analyze discussions with chloride biologists to identify the advantages and limitations of sensors in each biological context, as well as to recognize the key design challenges that must be overcome for developing the next generation of chloride sensors.
-
7.
The association between serum chloride levels and chronic kidney disease progression: a cohort study.
Khatri, M, Zitovsky, J, Lee, D, Nayyar, K, Fazzari, M, Grant, C
BMC nephrology. 2020;(1):165
Abstract
BACKGROUND Limited data suggest serum chloride levels associate with mortality in heart failure, chronic kidney disease (CKD), and pulmonary arterial hypertension. Randomized trials have also shown that administration of crystalloid intravenous fluids with lower chloride concentration may have better renal outcomes. However, chloride has not been studied longitudinally for CKD progression. METHODS We used a prospective cohort of subjects with stage 3 and 4 CKD recruited from a nephrology clinic at a single medical center. Linear regression, linear regression with generalized estimating equations, and Cox proportional hazards models were created for outcomes of overall change in estimated glomerular filtration rate (eGFR), longitudinal changes in eGFR, and time to > 30% decline in eGFR, respectively. Baseline chloride was modeled continuously and categorically, and models were adjusted for potential confounders. RESULTS Median follow-up was 1.7 years. Baseline median age was 72 years and median eGFR was 35.7 mL/min/1.73m2. In multivariable analysis, higher serum chloride associated with worsened eGFR decline. Every 1 mEq/L increase in chloride associated with an overall eGFR decline of 0.32 mL/min/1.73m2 (p = 0.003), while the difference in eGFR decline in the highest quartile of chloride was 3.4 mL/min/1.73m2 compared to the lowest quartile (p = 0.004). No association between serum chloride and time to 30% decline in eGFR was observed in multivariable analysis (hazard ratio 1.05 per 1 mEq/L increase in serum chloride, p = 0.103). CONCLUSIONS In CKD patients, higher serum chloride associated with a modestly steeper rate of eGFR decline, and may be a useful biomarker to predict CKD progression. Further studies are needed to determine causality.
-
8.
Prospective, randomized, controlled, open-label study to compare efficacy of a mineral-rich solution vs normal saline after complete ethmoidectomy.
de Gabory, L, Escabasse, V, Boudard, P, de Bonnecaze, G, Rumeau, C, Jankowski, R, Debry, C, Morinière, S, Merino, B, Mortuaire, G, et al
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2019;(2):447-457
-
-
Free full text
-
Abstract
PURPOSES The purpose of this study was to compare the efficacy of a mineral-rich solution vs normal saline solution (0.9% NaCl) following endoscopic complete bilateral ethmoidectomy. METHODS This was a prospective, multicenter, randomized, controlled, open-label trial in subjects suffering from steroid-resistant sinonasal polyposis. Adults performed 4 nasal irrigations of mineral or saline solutions daily for 28 days. Evaluations included subject-reported RHINO quality of life (QoL) and NOSE scores, tolerability, and satisfaction, the Lund-Kennedy endoscopic score and assessments of crusting, secretions and mucociliary clearance (rhinoscintigraphy). RESULTS A total of 189 subjects were randomized. Clinically relevant improvements (> 20 points) in RhinoQOL and NOSE scores were measured in both groups without any significant inter-group difference. Among the subjects with impaired RhinoQOL at pre-inclusion, the change in Impact-RhinoQOL score was significantly superior in mineral-rich vs saline solution at day 21 (p = 0.028) and day 28 (p = 0.027). The Lund-Kennedy score continuously improved in both groups earlier with the mineral-rich solution. Crusts were significantly fewer in number and less severe/obstructive in patients receiving mineral-rich vs saline solution at day 7 (p = 0.026) and day 14 (p = 0.016). Furthermore, secretions disappeared significantly more quickly and were less thick/purulent with mineral-rich solution at day 14 (p = 0.002) and day 21 (p = 0.043). Less epistaxis was reported in the mineral vs saline solution (p = 0.008 at day 21). CONCLUSIONS Our findings indicate that the composition of a nasal irrigation solution influences endoscopic scores and QoL after sinus surgery for patients over 60, those with an initially poor QoL and higher symptom score, and smokers.
-
9.
Perioperative Hyperchloremia and its Association With Postoperative Acute Kidney Injury After Craniotomy for Primary Brain Tumor Resection: A Retrospective, Observational Study.
Oh, TK, Kim, CY, Jeon, YT, Hwang, JW, Do, SH
Journal of neurosurgical anesthesiology. 2019;(3):311-317
Abstract
BACKGROUND Hyperchloremia is known to influence postoperative outcomes and may result in postoperative acute kidney injury (AKI). This study sought to investigate whether hyperchloremia was associated with postoperative AKI in patients who underwent surgery for primary brain tumor resection. MATERIALS AND METHODS This is a retrospective, observational study of patients who underwent craniotomy for primary brain tumor resection at a single tertiary care hospital between January 2005 and October 2017. Maximum levels of serum chloride (mmol/L) measured on postoperative days (PODs) 0 to 3 and increase in serum chloride (mmol/L), (maximum serum chloride-baseline serum chloride before surgery) were measured. We examined whether perioperative hyperchloremia was associated with postoperative AKI during PODs 0 to 3. Univariate and multivariate logistic regression analyses were used in this study. RESULTS A total of 726 patients were included in the analysis; of these, 39 (5.4%) were diagnosed with postoperative AKI during PODs 0 to 3. The risk of postoperative AKI was associated with maximum chloride levels (odds ratio, 1.10; 95% confidence interval, 1.02-1.19; P=0.015) and with an increase in serum chloride levels during PODs 0 to 3 (odds ratio, 1.11; 95% confidence interval, 1.04-1.19; P=0.004). CONCLUSIONS Our study shows that perioperative hyperchloremia during PODs 0 to 3 was associated with an increased risk of postoperative AKI during this period after craniotomy for primary brain tumor resection.
-
10.
Hyperchloremic normal gap metabolic acidosis.
Palmer, BF, Clegg, DJ
Minerva endocrinologica. 2019;(4):363-377
Abstract
Metabolic acidosis is defined as a pathologic process that, when unopposed, increases the concentration of hydrogen ions (H+) in the body and reduces the bicarbonate (HCO3-) concentration. Metabolic acidosis can be of a kidney origin or an extrarenal cause. Assessment of urinary ammonium excretion by calculating the urine anion gap or osmolal gap is a useful method to distinguish between these two causes. Extrarenal processes include increased endogenous acid production and accelerated loss of bicarbonate from the body. Metabolic acidosis of renal origin is due to a primary defect in renal acidification with no increase in extrarenal hydrogen ion production. This situation can occur because either the renal input of new bicarbonate is insufficient to regenerate the bicarbonate lost in buffering endogenous acid as with distal renal tubular acidosis (RTA) or the RTA of renal insufficiency, or the filtered bicarbonate is lost by kidney wasting as in proximal RTA. In either condition, because of loss of either NaHCO3 (proximal RTA) or NaA (distal RTA), effective extracellular volume is reduced and as a result the avidity for chloride reabsorption derived from the diet is increased and results in a hyperchloremic normal gap metabolic acidosis. The RTA of renal insufficiency is also characterized by a normal gap acidosis, however, with severe reductions in the glomerular filtration rate an anion gap metabolic acidosis eventually develops.