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1.
Environ Geochem Health ; 46(5): 158, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592363

RESUMO

Groundwater, a predominant reservoir of freshwater, plays a critical role in providing a sustainable potable water and water for agricultural and industry uses in the In Salah desert region of Algeria. This research collected 82 underground water samples from Albian aquifers to assess water quality and identify hydrogeochemical processes influencing mineralization. To achieve this objective, various methods were employed to evaluate water quality based on its intended uses. The drinking water quality index utilized revealed the water potability status, while the indicators of irrigation potability were employed to evaluate its quality for agricultural purposes. Additionally, an assessment of groundwater susceptibility to corrosion and scaling in an industrial context was conducted using several indices, e.g., Langelier index, Larson-Skold index, Ryznar index, chloride-sulfate mass ratio, Puckorius index, aggressiveness index, and the Revelle index. The findings of this study revealed that the groundwater quality for consumption fell into four categories: good (2.44%), fair (29.27%), poor (65.85%), and non-potable (2.44%). Concerning agricultural irrigation, the indexical results indicated that 15.85% of the waters exhibited adequate quality, while 84.15% were questionable for irrigation. Calculations based on various corrosion and scaling evaluation indices showed that most wells were prone to corrosion, with a tendency for calcium bicarbonate deposit formation. Furthermore, the hydrochemical study identified three water types: Na-Cl (53.66%), Ca-Mg-Cl (37.80%), and Ca-Cl (8.54%) waters. Analyses of correlation matrices, R-type clustering, factor loadings, Gibbs diagrams, scatterplots, and chloro-alkaline indices highlighted that the chemistry of the Albian groundwater is fundamentally impacted by a number of processes such as silicate weathering, evaporite dissolution, ionic exchange, and anthropogenic inputs, that played impactful role in the aquifer's water chemistry.


Assuntos
Irrigação Agrícola , Água Subterrânea , África do Norte , Agricultura , Bicarbonatos , Cloretos
2.
Pan Afr Med J ; 47: 37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586073

RESUMO

Introduction: type 2 Diabetes mellitus is a chronic metabolic disease with devastating effects on patients and results in numerous healthcare challenges in terms of its management and the cost burden among the affected. Successful management involves maintaining optimal glycemic control to prevent complications, with adherence to antidiabetic medications playing a crucial role in achieving this objective. Additionally, maintaining a healthy electrolyte balance is key for overall well-being and physiological function. However, the correlation between glycated hemoglobin and electrolyte balance remains under investigated, particularly in patients with suboptimal adherence. The aim of this research was to study the relationship between glycated hemoglobin and electrolytes among diabetic patients with poor adherence to antidiabetic medications. Methods: this study was conducted at Samburu County Referral Hospital in Samburu County, Kenya. We employed a descriptive cross-sectional design focusing on adult diabetic patients aged 18 years and above who had visited the diabetic clinic over a three-month period. To evaluate their adherence levels, we employed a Morisky Medication Adherence Scale-8. Seventy-two diabetic patients who got adherence level scores of < 6 were categorized as having low adherence and their blood samples were collected for measuring glycated hemoglobin levels and electrolytes levels particularly potassium, sodium, calcium, magnesium, phosphorus and chloride. Relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics was determined using Karl Pearson correlation. Results: among the study participants, the lowest hemoglobin A1C (HbA1c) level recorded was 5.1% while the highest was 15.0% and the majority (41.7%) fell within the HbA1c range of 5-7%. A high proportion of individuals (58.3%) with poor adherence to antidiabetics had elevated HbA1c levels, indicating poor glycemic control. The correlations observed between glycated hemoglobin and electrolytes which included magnesium, sodium, chloride, calcium and phosphorus was r= -0.07, -0.32, -0.05 -0.24 and -0.04 respectively. Conclusion: this study concluded that there is a relationship between electrolytes and glycated hemoglobin among diabetic patients with poor adherence to antidiabetics. A statistically significant negative correlation was observed between glycated hemoglobin and calcium level (r=-0.2398 P ≤0.05) and also sodium (r=-0.31369 P≤0.05). A negative correlation (P≥0.05) was observed between phosphorus, magnesium, chloride and potassium with HbA1c levels though not statistically significant.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Hemoglobinas Glicadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos Transversais , Cálcio , Magnésio , Cloretos/uso terapêutico , Glicemia/metabolismo , Hipoglicemiantes/uso terapêutico , Eletrólitos , Sódio , Potássio , Fósforo
3.
Sci Rep ; 14(1): 7846, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570623

RESUMO

Previous studies have suggested that levels of sodium and chloride in the blood may be indicative of the prognosis of different medical conditions. Nevertheless, the assessment of the prognostic significance of the sodium-to-chloride (Na/Cl) ratio in relation to in-hospital mortality among individuals suffering from acute heart failure (AHF) remains unexplored. In this study, the participants were selected from the Medical Information Mart for Intensive Care IV database and divided into three groups based on the Na/Cl ratio level upon admission. The primary results were the mortality rate within the hospital. Cox regression, Kaplan-Meier curves, receiver operator characteristic (ROC) curve analysis and subgroup analyses were utilized to investigate the correlation between the admission Na/Cl ratio and outcomes in critically ill patients with AHF. A total of 7844 patients who met the selection criteria were included in this study. After adjusting for confounders, the multivariable Cox regression analysis revealed that the baseline Na/Cl ratio significantly elevated the risk of in-hospital mortality among critically ill patients with AHF (HR = 1.34, 95% CI 1.21-1.49). Furthermore, when the Na/Cl ratio was converted into a categorical factor and the initial tertile was taken as a point of comparison, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the second and third tertiles were 1.27 (1.05-1.54) and 1.53 (1.27-1.84), respectively. Additionally, a P value indicating a significant trend of < 0.001 was observed. ROC curve analysis showed that Na/Cl ratio had a more sensitive prognostic value in predicting in-hospital mortality of AHF than the sodium or chloride level alone (0.564 vs. 0.505, 0.544). Subgroup examinations indicated that the association between the Na/Cl ratio upon admission and the mortality rate of critically ill patients with AHF remained consistent in the subgroups of hyponatremia and hypochlorhydria (P for interaction > 0.05). The linear relationship between the Na/Cl ratio and in-hospital mortality in AHF patients indicates a positive association.


Assuntos
Insuficiência Cardíaca , Cloreto de Sódio , Humanos , Cloretos , Mortalidade Hospitalar , Estado Terminal , Prognóstico , Sódio , Estudos Retrospectivos
4.
Proc Natl Acad Sci U S A ; 121(15): e2322135121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38568964

RESUMO

Endothelial cells (ECs) line the wall of blood vessels and regulate arterial contractility to tune regional organ blood flow and systemic pressure. Chloride (Cl-) is the most abundant anion in ECs and the Cl- sensitive With-No-Lysine (WNK) kinase is expressed in this cell type. Whether intracellular Cl- signaling and WNK kinase regulate EC function to alter arterial contractility is unclear. Here, we tested the hypothesis that intracellular Cl- signaling in ECs regulates arterial contractility and examined the signaling mechanisms involved, including the participation of WNK kinase. Our data obtained using two-photon microscopy and cell-specific inducible knockout mice indicated that acetylcholine, a prototypical vasodilator, stimulated a rapid reduction in intracellular Cl- concentration ([Cl-]i) due to the activation of TMEM16A, a Cl- channel, in ECs of resistance-size arteries. TMEM16A channel-mediated Cl- signaling activated WNK kinase, which phosphorylated its substrate proteins SPAK and OSR1 in ECs. OSR1 potentiated transient receptor potential vanilloid 4 (TRPV4) currents in a kinase-dependent manner and required a conserved binding motif located in the channel C terminus. Intracellular Ca2+ signaling was measured in four dimensions in ECs using a high-speed lightsheet microscope. WNK kinase-dependent activation of TRPV4 channels increased local intracellular Ca2+ signaling in ECs and produced vasodilation. In summary, we show that TMEM16A channel activation reduces [Cl-]i, which activates WNK kinase in ECs. WNK kinase phosphorylates OSR1 which then stimulates TRPV4 channels to produce vasodilation. Thus, TMEM16A channels regulate intracellular Cl- signaling and WNK kinase activity in ECs to control arterial contractility.


Assuntos
Cloretos , Proteínas Serina-Treonina Quinases , Camundongos , Animais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Cloretos/metabolismo , Células Endoteliais/metabolismo , Canais de Cátion TRPV/metabolismo , Transdução de Sinais/fisiologia
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(3): 523-532, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38597444

RESUMO

OBJECTIVE: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism. METHODS: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release. RESULTS: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2-induced vascular contraction. CONCLUSION: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.


Assuntos
Aorta Torácica , Compostos de Bário , Cloretos , Triterpenos , Vasodilatação , Ratos , Animais , Pressão Sanguínea , Células Endoteliais , Cálcio , Cloreto de Cálcio/farmacologia , Nitroarginina/farmacologia , Ratos Sprague-Dawley , 4-Aminopiridina/farmacologia , Indometacina/farmacologia , Ésteres/farmacologia , Endotélio Vascular , Relação Dose-Resposta a Droga
6.
Appl Microbiol Biotechnol ; 108(1): 289, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587649

RESUMO

Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future. KEY POINTS: • Epiberberine is the most effective inhibitor of rumen urease from Rhizoma Coptidis. • Urease accessory protein UreG is an effective target for design of urease inhibitor. • Epiberberine may be used as natural feed additive to reducing NH3 release in ruminants.


Assuntos
Berberina , Berberina/análogos & derivados , Animais , Berberina/farmacologia , Urease , Amônia , Cloretos , Rúmen , Inibidores Enzimáticos/farmacologia , Nitrogênio , Ruminantes
7.
Int J Mol Sci ; 25(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38612883

RESUMO

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.


Assuntos
Ácido Cítrico , Osteoporose , Estrôncio , Tiofenos , Feminino , Animais , Camundongos , Densidade Óssea , Cloretos , Citratos , Osteoporose/tratamento farmacológico , Halogênios , Modelos Animais de Doenças
8.
Sci Rep ; 14(1): 8597, 2024 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615119

RESUMO

Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein-protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein-protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.


Assuntos
Acidose , Proteínas Culina , Humanos , Cloretos , Simulação de Acoplamento Molecular , Biomarcadores , Halogênios , Proteínas Quinases , Treonina , Serina
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 331-334, 2024 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-38448024

RESUMO

OBJECTIVE: To explore the genetic etiology of two patients with Gitelman syndrome (GS). METHODS: Two patients who had presented at the Linyi People's Hospital in January and June 2022 respectively were selected as the study subjects. Peripheral blood samples of them were collected and subjected to whole exome sequencing (WES). Electrolyte levels in their serum and urine were detected. Candidate variants were verified by Sanger sequencing. PyMOL software was used to predict the impact of the variants on the protein structure. RESULTS: Patient 1 was a 27-year-old female with decreased serum levels of sodium, potassium, chloride and magnesium, along with decreased urine chloride and calcium. WES revealed that she has harbored compound heterozygous variants of the SLC12A3 gene, namely c.1456G>A (p.D486N) and c.179C>T (p.T60M). The former was inherited from her mother and known to be pathogenic. Patient 2 was a 4-year-old male with lower serum sodium, chloride and magnesium levels, and his serum potassium level was found to be critically low. He was found to harbor compound heterozygous variants of c.602-16G>A and c.805_806insTTGGCGTGGTCTCGGTCA (p.V268_T269insIGVVSV) of the SLC12A3 gene, which were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2_Supporting+PP3; PVS1+PM2_Supporting+PM4). CONCLUSION: The above heterozygous variants of the SLC12A3 gene probably underlay the GS in these patients.


Assuntos
Síndrome de Gitelman , Humanos , Feminino , Masculino , Adulto , Pré-Escolar , Síndrome de Gitelman/genética , Cloretos , Magnésio , Potássio , Sódio , Membro 3 da Família 12 de Carreador de Soluto/genética
10.
J Toxicol Sci ; 49(3): 95-103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432956

RESUMO

This study was conducted as part of an investigation into the cause of vesnarinone-associated agranulocytosis. When HL-60 cells were exposed to vesnarinone for 48 hr, little cytotoxicity was observed, although reduced glutathione (GSH) content decreased in a concentration-dependent manner. Significant cytotoxicity and reactive oxygen species (ROS) production were observed when intracellular GSH content was reduced by treatment with L-buthionine-(S, R)-sulphoximine. The involvement of myeloperoxidase (MPO) metabolism was suggested, as when HL-60 cells were exposed to a reaction mixture of vesnarinone-MPO/H2O2/Cl-, cytotoxicity was also observed. In contrast, the presence of GSH (1 mM) protected against these cytotoxic effects. Liquid chromatography-mass spectrometry analysis of the MPO/H2O2/Cl- reaction mixture revealed that vesnarinone was converted into two metabolites, (4-(3,4-dimethoxybenzoyl)piperazine [Metabolite 1: M1] and 1-chloro-4-(3,4-dimethoxybenzoyl)piperazine [Metabolite 2: M2]). M2 was identified as the N-chloramine form, a reactive metabolite of M1. Interestingly, M2 was converted to M1, which was accompanied by the conversion of GSH to oxidized GSH (GSSG). Furthermore, when HL-60 cells were exposed to synthetic M1 and M2 for 24 hr, M2 caused dose-dependent cytotoxicity, whereas M1 did not. Cells were protected from M2-derived cytotoxicity by the presence of GSH. In conclusion, we present the first demonstration of the cytotoxic effects and ROS production resulting from the MPO/H2O2/Cl- metabolic reaction of vesnarinone and newly identified the causative metabolite, M2, as the N-chloramine metabolite of M1, which induces cytotoxicity in HL-60 cells. Moreover, a protective role of GSH against the cytotoxicity was revealed. These findings suggest a possible nonimmunological cause of vesnarinone agranulocytosis.


Assuntos
Agranulocitose , Antineoplásicos , Pirazinas , Quinolinas , Humanos , Cloraminas , Glutationa , Células HL-60 , Peróxido de Hidrogênio/toxicidade , Espécies Reativas de Oxigênio , Agranulocitose/induzido quimicamente , Cloretos , Piperazinas
11.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473702

RESUMO

The aim of this study was to investigate how introducing halophilic sulfur-oxidizing bacteria (SOB) Halothiobacillus halophilus to the growth substrate affects the physiological and biochemical responses of the halophyte Tripolium pannonicum (also known as sea aster or seashore aster) under salt and cadmium stress conditions. This study assessed the plant's response to these stressors and bacterial inoculation by analyzing various factors including the accumulation of elements such as sodium (Na), chloride (Cl), cadmium (Cd) and sulfur (S); growth parameters; levels of photosynthetic pigments, proline and phenolic compounds; the formation of malondialdehyde (MDA); and the plant's potential to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH). The results revealed that bacterial inoculation was effective in mitigating the deleterious effect of cadmium stress on some growth criteria. For instance, stem length was 2-hold higher, the growth tolerance index was 3-fold higher and there was a 20% increase in the content of photosynthetic pigments compared to non-inoculated plants. Furthermore, the SOB contributed to enhancing cadmium tolerance in Tripolium pannonicum by increasing the availability of sulfur in the plant's leaves, which led to the maintenance of an appropriate, about 2-fold-higher level of phenolic compounds (phenylpropanoids and flavonols), as well as chloride ions. The level of MDA decreased after bacterial application in all experimental variants except when both salt and cadmium stress were present. These findings provide novel insights into how halophytes respond to abiotic stress following inoculation of the growth medium with sulfur-oxidizing bacteria. The data suggest that inoculating the substrate with SOB has a beneficial effect on T. pannonicum's tolerance to cadmium stress.


Assuntos
Cádmio , Plantas Tolerantes a Sal , Cádmio/farmacologia , Cloretos/farmacologia , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta/farmacologia , Sódio/farmacologia , Oxirredução , Enxofre/farmacologia , Bactérias
12.
Sao Paulo Med J ; 142(4): e2022370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38477733

RESUMO

BACKGROUND: Hyperchloremia is often encountered due to the frequent administration of intravenous fluids in critically ill patients with conditions such as shock or hypotension in the pediatric intensive care unit, and high serum levels of chloride are associated with poor clinical outcomes. OBJECTIVES: This study aimed to determine the association between hyperchloremia and in-hospital mortality in pediatric patients with major trauma. DESIGN AND SETTING: This retrospective cohort study was conducted at a tertiary university hospital in Turkey. METHODS: Data were collected between March 2020 and April 2022. Patients aged 1 month to 18 years with major trauma who received intravenous fluids with a concentration > 0.9% sodium chloride were enrolled. Hyperchloremia was defined as a serum chloride level > 110 mmol/L. Clinical and laboratory data were compared between the survivors and nonsurvivors. RESULTS: The mortality rate was 23% (n = 20). The incidence of hyperchloremia was significantly higher in nonsurvivors than in survivors (P = 0.05). In multivariate logistic analysis, hyperchloremia at 48 h was found to be an independent risk factor for mortality in pediatric patients with major trauma. CONCLUSIONS: In pediatric patients with major trauma, hyperchloremia at 48-h postadmission was associated with 28-day mortality. This parameter might be a beneficial prognostic indicator.


Assuntos
Cloretos , Humanos , Criança , Estudos Retrospectivos , Mortalidade Hospitalar , Hospitais Universitários , Análise Multivariada
13.
Biosens Bioelectron ; 253: 116166, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428069

RESUMO

Eccrine sweat can serve as a source of biomarkers for assessing physiological health and nutritional balance, for tracking loss of essential species from the body and for evaluating exposure to hazardous substances. The growing interest in this relatively underexplored class of biofluid arises in part from its non-invasive ability for capture and analysis. The simplest devices, and the only ones that are commercially available, exploit soft microfluidic constructs and colorimetric assays with purely passive modes of operation. The most sophisticated platforms exploit batteries, electronic components and radio hardware for inducing sweat, for electrochemical evaluation of its content and for wireless transmission of this information. The work reported here introduces a technology that combines the advantages of these two different approaches, in the form of a cost-effective, easy-to-use device that supports on-demand evaluation of multiple biomarkers in sweat. This flexible, skin-interfaced, miniaturized system incorporates a hydrogel that contains an approved drug to activate eccrine sweat glands, electrodes and a simple circuit and battery to delivery this drug by iontophoresis through the surface of the skin, microfluidic channels and microreservoirs to capture the induced sweat, and multiple colorimetric assays to evaluate the concentrations of chloride, zinc, and iron. As demonstrated in healthy human participants monitored before and after a meal, such devices yield results that match those of traditional laboratory analysis techniques. Clinical studies that involve cystic fibrosis pediatric patients illustrate the use of this technology as a simple, painless, and reliable alternative to traditional hospital systems for measurements of sweat chloride.


Assuntos
Técnicas Biossensoriais , Suor , Humanos , Criança , Cloretos , Colorimetria , Biomarcadores
14.
ACS Appl Bio Mater ; 7(3): 1703-1712, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38433388

RESUMO

Cationic bolaamphiphiles have gained significant attention in various research fields, including materials science, drug delivery, and gene therapy, due to their unique properties and potential applications. The objective of the current research is to develop more effective cationic bolaamphiphiles. Thus, we have designed and synthesized two cationic bolaamphiphiles (-(CH2)12(2,3-dihydroxy-N,N-dimethyl-N-(3-ureidopropyl)propan-1-aminium chloride))2 (C12(DDUPPAC)2)) and (-(CH2)12(N-(3-(carbamoyloxy)propyl)-2,3-dihydroxy-N,N-dimethylpropan-1-aminium chloride)2 (C12(CPDDPAC)2) containing urea and urethane linkages, respectively. We have investigated their self-assembly properties in water using several techniques, including surface tension, electrical conductivity, fluorescence probe, calorimetry, dynamic light scattering, and atomic force microscopy. Their biological applications, e.g., in vitro gene transfection, antibacterial activity, and cytotoxicity, were studied. Both bolaamphiphiles were observed to produce aggregates larger than spherical micelles above a relatively low critical aggregation concentration (cac). The calorimetric experiments suggested the thermodynamically favorable spontaneous aggregation of both bolaforms in water. The results of interaction studies led to the conclusion that C12(CPDDPAC)2 binds DNA with a greater affinity than C12(DDUPPAC)2. Also, C12(CPDDPAC)2 is found to act as a more efficient gene transfection vector than C12(DDUPPAC)2 in 264.7 cell lines. The in vitro cytotoxicity assay using MTT, however, revealed that neither of the bolaamphiphiles was toxic, even at higher quantities. Additionally, both bolaforms show beneficial antibacterial activity.


Assuntos
Cloretos , Furanos , Piridonas , Água , Transfecção , Linhagem Celular
15.
Bioresour Technol ; 398: 130548, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458263

RESUMO

Anaerobic fermentation (AF) has been identified as a promising method of transforming waste activated sludge (WAS) into high-value products (e.g., short-chain fatty acids (SCFAs)). This study developed thiosulfate/FeCl3 pre-treatment and investigated the effects of different thiosulfate/FeCl3 ratios (S:Fe = 3:1, 3:2, 1:1, 3:4 and 3:5) on SCFA production and sulfur transformation during the AF of WAS. At a S:Fe ratio of 1:1, the maximal SCFA yield (933.3 mg COD/L) and efficient H2S removal (96.5 %) were obtained. S:Fe ratios ≤ 1:1 not only benefited hydrolysis and acidification but largely mitigated H2S generation. These results were supported by the enriched acidogens and reduced sulfur-reducing bacteria (SRB). Molecular ecological network analysis further revealed that the keystone taxon (g_Saccharimonadales) was found in S:Fe = 1:1, together with reductions in associations among methanogens, acidogens and SRB. This work provides a strategy for enhancing high-value product recovery from WAS and minimising H2S emissions.


Assuntos
Cloretos , Compostos Férricos , Microbiota , Esgotos , Fermentação , Esgotos/microbiologia , Anaerobiose , Tiossulfatos , Ácidos Graxos Voláteis , Concentração de Íons de Hidrogênio
16.
Environ Sci Technol ; 58(11): 5174-5185, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38451543

RESUMO

Nanofiltration (NF) has the potential to achieve precise ion-ion separation at the subnanometer scale, which is necessary for resource recovery and a circular water economy. Fabricating NF membranes for selective ion separation is highly desirable but represents a substantial technical challenge. Dipole-dipole interaction is a mechanism of intermolecular attractions between polar molecules with a dipole moment due to uneven charge distribution, but such an interaction has not been leveraged to tune membrane structure and selectivity. Herein, we propose a novel strategy to achieve tunable surface charge of polyamide membrane by introducing polar solvent with a large dipole moment during interfacial polymerization, in which the dipole-dipole interaction with acyl chloride groups of trimesoyl chloride (TMC) can successfully intervene in the amidation reaction to alter the density of surface carboxyl groups in the polyamide selective layer. As a result, the prepared positively charged (PEI-TMC)-NH2 and negatively charged (PEI-TMC)-COOH composite membranes, which show similarly high water permeance, demonstrate highly selective separations of cations and anions in engineering applications, respectively. Our findings, for the first time, confirm that solvent-induced dipole-dipole interactions are able to alter the charge type and density of polyamide membranes and achieve tunable surface charge for selective and efficient ion separation.


Assuntos
Cloretos , Nylons , Cloretos/química , Nylons/química , Membranas Artificiais , Solventes , Água
17.
Biointerphases ; 19(2)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38526056

RESUMO

Bletilla striata polysaccharide (BSP) and chitosan (CS) were chemically cross-linked using oxalyl chloride to prepare a composite hemostatic sponge (BSP-CS), and the process parameters were optimized using the Box-Behnken design (BBD) with response surface methodology. To optimize the performance of the hemostatic sponge, we adjusted the ratio of independent variables, the amount of oxalyl chloride added, and the freeze-dried volume. A series of evaluations were conducted on the hemostatic applicability of BSP-CS. The characterization results revealed that BSP-CS had a stable bacteriostatic effect on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa within 72 h, and the bacteriostatic rate was above 30%. The CCK-8 cytotoxicity test demonstrated that BSP-CS had a certain effect on promoting cell proliferation of L929 cells. In the mouse tail-cutting experiment, the hemostasis time of BSP-CS was 463.0±38.16 s, shortened by 91.3 s on average compared with 554.3±34.67 s of the gauze group. The blood loss of the BSP-CS group was 28.47±3.74 mg, which was 34.7% lower than that of the control gauze group (43.6±3.83 mg). In the in vitro coagulation experiment, the in vitro coagulation index of the BSP-CS group was 97.29%±1.8%, which was reduced to 8.6% of the control group. The CT value of the BSP-CS group was 240±15 s, which was 155 s lower than that of the gauze group (355±31.22 s). All characterization results indicate that BSP-CS is an excellent hemostatic material.


Assuntos
Quitosana , Cloretos , Hemostáticos , Orchidaceae , Oxalatos , Camundongos , Animais , Hemostáticos/farmacologia , Hemostáticos/química , Quitosana/farmacologia , Quitosana/química , Hemostasia , Polissacarídeos/farmacologia , Polissacarídeos/química , Orchidaceae/química
18.
Se Pu ; 42(3): 275-281, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38503704

RESUMO

A non-invasive condensation collection-ion chromatography method was established for the determination of organic acids and anions including lactic acid, formic acid, acetic acid, pyruvic acid, chloride, nitrate, nitrite, and sulfate in the exhaled breath of humans. The breath exhaled was condensed and collected using a home-made exhaled breath condensation equipment. This equipment included a disposable mouthpiece as a blow-off port, one-way valve and flow meter, cold trap, disposable condensate collection tube placed in the cold trap, and gas outlet. A standard sampling procedure was used. Before collection, the collection temperature and sampling volume were set on the instrument control panel, and sampling was started when the cold-trap temperature dropped to the set value, while maintaining the balance. Subjects were required to gargle with pure water before sampling. During the sampling process, the subjects were required to inhale deeply until the lungs were full of gas and then exhale evenly through the air outlet. When the set volume was collected, the instrument made a prompt sound; then, the collection was immediately ended, the expiration time was recorded, and the average collection flow was calculated according to the expiration time and sampling volume. After collection, the disposable condensation collection tube was immediately taken out, sealed, and stored in the refrigerator at -20 ℃ away from light, and immediately used for further testing. The organic acids and anions in exhaled breath condensation (EBC) were filtered through a 0.22 µm membrane filter before injection and detected by ion chromatography with conductivity detection. Factors such as collection temperature and collection flow rate during condensation collection were optimized. The optimal cooling temperature was set at -15 ℃, and the optimal exhaled breath flow rate was set at 15 L/min. The mobile phase consisted of a mixture of sodium carbonate (1.5 mmol/L) and sodium bicarbonate (3 mmol/L). The flow rate was 0.8 mL/min, and the injection volume was 100 µL. An IC-SA3 column (250 mm×4.0 mm) was used, and the temperature was set at 45 ℃. An ICDS-40A electrodialysis suppressor was used, and the current was set at 150 mA. The linear ranges of the eight organic acids and anions were 0.1-10.0 mg/L; their correlation coefficients (r) were ≥0.9993. The limits of detection (LODs) for the eight organic acids and anions were 0.0017-0.0150 mg/L based on a signal-to-noise ratio of 3, and the limits of quantification (LOQs) were 0.0057-0.0500 mg/L based on a signal-to-noise ratio of 10. The intra-day precisions were 5.06%-6.33% (n=5), and the inter-day precisions were 5.37%-7.50% (n=5). This method was used to detect organic acids and anions in the exhaled breath of five healthy subjects. The contents of organic acids and anions in the exhaled breath were calculated. The content of lactic acid was relatively high, at 1.13-42.3 ng/L, and the contents of other seven organic acids and anions were 0.18-11.0 ng/L. During a 10 km-long run, the majority of organic acids and anions in the exhaled breath of five subjects first increased and then decreased. However, due to abnormal metabolism, the content changes of lactic acid, acetic acid, pyruvic acid and chloride in one subject were obviously different from others during exercise, showing a continuous rise. This method has the advantages of involving a simple sampling process and exhibiting good precision, few side effects, and no obvious discomfort or risk to the subjects. This study provides experimental ideas and a theoretical basis for future research on human metabolites.


Assuntos
Cloretos , Ácido Pirúvico , Humanos , Ânions , Ácido Láctico/análise , Cromatografia , Acetatos/análise
19.
Sci Transl Med ; 16(739): eadk9109, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507469

RESUMO

Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the neuromuscular junction (NMJ) from motor neurons to skeletal muscle fibers. As a result, patients with MG have reduced skeletal muscle function and present with symptoms of severe muscle weakness and fatigue. ClC-1 is a skeletal muscle specific chloride (Cl-) ion channel that plays important roles in regulating neuromuscular transmission and muscle fiber excitability during intense exercise. Here, we show that partial inhibition of ClC-1 with an orally bioavailable small molecule (NMD670) can restore muscle function in rat models of MG and in patients with MG. In severely affected MG rats, ClC-1 inhibition enhanced neuromuscular transmission, restored muscle function, and improved mobility after both single and prolonged administrations of NMD670. On this basis, NMD670 was progressed through nonclinical safety pharmacology and toxicology studies, leading to approval for testing in clinical studies. After successfully completing phase 1 single ascending dose in healthy volunteers, NMD670 was tested in patients with MG in a randomized, placebo-controlled, single-dose, three-way crossover clinical trial. The clinical trial evaluated safety, pharmacokinetics, and pharmacodynamics of NMD670 in 12 patients with mild MG. NMD670 had a favorable safety profile and led to clinically relevant improvements in the quantitative myasthenia gravis (QMG) total score. This translational study spanning from single muscle fiber recordings to patients provides proof of mechanism for ClC-1 inhibition as a potential therapeutic approach in MG and supports further development of NMD670.


Assuntos
Cloretos , Miastenia Gravis , Humanos , Ratos , Animais , Cloretos/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Músculo Esquelético/fisiologia , Junção Neuromuscular , Canais de Cloreto
20.
Nutrients ; 16(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542744

RESUMO

Potassium is a monovalent cation widely present in nature, where it is not in metallic form, but always in combination with other substances, especially chloride [...].


Assuntos
Cloretos , Potássio , Humanos , Cloreto de Potássio
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