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1.
Pharm Res ; 41(5): 937-945, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698196

RESUMO

BACKGROUND: Phosphate buffer is often used as a replacement for the physiological bicarbonate buffer in pharmaceutical dissolution testing, although there are some discrepancies in their properties making it complicated to extrapolate dissolution results in phosphate to the in vivo situation. This study aims to characterize these discrepancies regarding solubility and dissolution behavior of ionizable compounds. METHODS: The dissolution of an ibuprofen powder with a known particle size distribution was simulated in silico and verified experimentally in vitro at two different doses and in two different buffers (5 mM pH 6.8 bicarbonate and phosphate). RESULTS: The results showed that there is a solubility vs. dissolution mismatch in the two buffers. This was accurately predicted by the in-house simulations based on the reversible non-equilibrium (RNE) and the Mooney models. CONCLUSIONS: The results can be explained by the existence of a relatively large gap between the initial surface pH of the drug and the bulk pH at saturation in bicarbonate but not in phosphate, which is caused by not all the interfacial reactions reaching equilibrium in bicarbonate prior to bulk saturation. This means that slurry pH measurements, while providing surface pH estimates for buffers like phosphate, are poor indicators of surface pH in the intestinal bicarbonate buffer. In addition, it showcases the importance of accounting for the H2CO3-CO2 interconversion kinetics to achieve good predictions of intestinal drug dissolution.


Assuntos
Bicarbonatos , Liberação Controlada de Fármacos , Ibuprofeno , Fosfatos , Solubilidade , Soluções Tampão , Bicarbonatos/química , Concentração de Íons de Hidrogênio , Ibuprofeno/química , Fosfatos/química , Tamanho da Partícula , Simulação por Computador , Pós/química , Cinética , Química Farmacêutica/métodos
2.
PeerJ ; 12: e17316, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699185

RESUMO

This review discusses the importance of homeostasis with a particular emphasis on the acid-base (AB) balance, a crucial aspect of pH regulation in living systems. Two primary organ systems correct deviations from the standard pH balance: the respiratory system via gas exchange and the kidneys via proton/bicarbonate secretion and reabsorption. Focusing on kidney functions, we describe the complexity of renal architecture and its challenges for experimental research. We address specific roles of different nephron segments (the proximal convoluted tubule, the loop of Henle and the distal convoluted tubule) in pH homeostasis, while explaining the physiological significance of ion exchange processes maintained by the kidneys, particularly the role of bicarbonate ions (HCO3-) as an essential buffer system of the body. The review will be of interest to researchers in the fields of physiology, biochemistry and molecular biology, which builds a strong foundation and critically evaluates existing studies. Our review helps identify the gaps of knowledge by thoroughly understanding the existing literature related to kidney acid-base homeostasis.


Assuntos
Equilíbrio Ácido-Base , Homeostase , Rim , Humanos , Equilíbrio Ácido-Base/fisiologia , Rim/metabolismo , Rim/fisiologia , Homeostase/fisiologia , Concentração de Íons de Hidrogênio , Animais , Bicarbonatos/metabolismo
3.
Pharm Res ; 41(5): 959-966, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38653942

RESUMO

PURPOSE: The purpose of this study was to clarify the extent to which the dissolution profiles of immediate release (IR) products of various drugs differ between biorelevant bicarbonate buffer (BCB) and compendial phosphate buffer (PPB). METHODS: The dissolution profiles of the IR products of fifteen poorly soluble ionizable drugs were measured in BCB and PPB. BCB was set to be relevant to the small intestine (pH 6.8, 10 mM). The pH was maintained using the floating lid method. The Japanese pharmacopeia second fluid (JP2, 25 mM phosphate buffer, nominal pH 6.8) was used as compendial PPB. The compendial paddle apparatus was used for the dissolution tests (500 mL, 50 rpm, 37°C). RESULTS: In 11/15 cases, a difference in dissolved% (< 0.8 or > 1.25-fold) was observed at a time point. In 4/15 cases, the ratio of the area under the dissolution curve was not equivalent (< 0.8 or > 1.25-fold). In the cases of free-form drugs, the dissolution rate tended to be slower in BCB than in JP2. In the case of salt-form drugs, a marked difference was observed for the cases that showed supersaturation. However, no trend was observed in the differences. CONCLUSIONS: Many IR products showed differences in the dissolution profiles between biorelevant BCB and compendial PPB. With the floating lid method, BCB is as simple and easy to use as PPB. Biorelevant BCB is recommended for dissolution testing.


Assuntos
Bicarbonatos , Fosfatos , Solubilidade , Soluções Tampão , Fosfatos/química , Concentração de Íons de Hidrogênio , Bicarbonatos/química , Preparações Farmacêuticas/química , Química Farmacêutica/métodos , Liberação Controlada de Fármacos
4.
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
5.
J Photochem Photobiol B ; 255: 112924, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38688041

RESUMO

Whether rapid oxygen isotopic exchange between bicarbonate and water occurs in photosynthesis is the key to determine the source of oxygen by classic 18O-labeled photosynthetic oxygen evolution experiments. Here we show that both Microcystis aeruginosa and Chlamydomonas reinhardtii utilize a significant proportion (>16%) of added bicarbonate as a carbon source for photosynthesis. However, oxygen isotopic signal in added bicarbonate cannot be traced in the oxygen in organic matter synthesized by these photosynthetic organisms. This contradicts the current photosynthesis theory, which states that photosynthetic oxygen evolution comes only from water, and oxygen in photosynthetic organic matter comes only from carbon dioxide. We conclude that the photosynthetic organisms undergo rapid exchange of oxygen isotope between bicarbonate and water during photosynthesis. At the same time, this study also provides isotopic evidence for a new mechanism that half of the oxygen in photosynthetic oxygen evolution comes from bicarbonate photolysis and half comes from water photolysis, which provides a new explanation for the bicarbonate effect, and suggests that the Kok-Joliot cycle of photosynthetic oxygen evolution, must be modified to include a molecule of bicarbonate in addition to one molecule of water which in turn must be incorporated into the cycle instead of two water molecules. Furthermore, this study provides a theoretical basis for constructing a newer artificial photosynthetic reactor coupling light reactions with the dark reactions.


Assuntos
Bicarbonatos , Chlamydomonas reinhardtii , Isótopos de Oxigênio , Fotossíntese , Água , Bicarbonatos/química , Bicarbonatos/metabolismo , Água/química , Água/metabolismo , Isótopos de Oxigênio/química , Chlamydomonas reinhardtii/metabolismo , Microcystis/metabolismo , Oxigênio/metabolismo , Oxigênio/química , Dióxido de Carbono/metabolismo , Dióxido de Carbono/química
6.
J Cardiothorac Surg ; 19(1): 266, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664851

RESUMO

BACKGROUND: St. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido's cardioplegic solution provides a prolonged duration of safe myocardial arrest, yet it was primarily intended for pediatric cardiac surgery. Recently, there has been an increasing interest in using Del Nido's in adults; this might be due to its ease of administration and extended re-dosing intervals. This study contrasted Del Nido's to modified St. Thomas cardioplegia in adults. METHODS: This study was conducted on 200 patients. Troponin-T was the primary outcome within the first 24 and 48 h post-surgery. Cardiopulmonary bypass time, cross-clamp time, intraoperative use of inotropic support, defibrillator and/or intra-aortic balloon were the secondary outcomes of the study. RESULTS: There was a significant reduction in post-operative Troponin-T levels in the first 24 and 48 h within Del Nido's group compared to the modified St. Thomas group. The cross-clamp and cardiopulmonary bypass times were also found to be lower within Del Nido's group. CONCLUSION: This study has demonstrated a significant reduction in early postoperative Troponin-T levels as well as operative times favoring Del Nido's in adults.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Soluções Cardioplégicas , Eletrólitos , Parada Cardíaca Induzida , Lidocaína , Sulfato de Magnésio , Manitol , Bicarbonato de Sódio , Soluções , Troponina T , Humanos , Parada Cardíaca Induzida/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Cardíacos/métodos , Troponina T/sangue , Adulto , Ponte Cardiopulmonar/métodos , Idoso , Cloreto de Potássio , Resultado do Tratamento , Bicarbonatos , Cloreto de Cálcio , Cloreto de Sódio , Magnésio
7.
FEMS Microbiol Ecol ; 100(5)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38632042

RESUMO

Dissolved inorganic carbon has been hypothesized to stimulate microbial chemoautotrophic activity as a biological sink in the carbon cycle of deep subsurface environments. Here, we tested this hypothesis using quantitative DNA stable isotope probing of metagenome-assembled genomes (MAGs) at multiple 13C-labeled bicarbonate concentrations in hydrothermal fluids from a 750-m deep subsurface aquifer in the Biga Peninsula (Turkey). The diversity of microbial populations assimilating 13C-labeled bicarbonate was significantly different at higher bicarbonate concentrations, and could be linked to four separate carbon-fixation pathways encoded within 13C-labeled MAGs. Microbial populations encoding the Calvin-Benson-Bassham cycle had the highest contribution to carbon fixation across all bicarbonate concentrations tested, spanning 1-10 mM. However, out of all the active carbon-fixation pathways detected, MAGs affiliated with the phylum Aquificae encoding the reverse tricarboxylic acid (rTCA) pathway were the only microbial populations that exhibited an increased 13C-bicarbonate assimilation under increasing bicarbonate concentrations. Our study provides the first experimental data supporting predictions that increased bicarbonate concentrations may promote chemoautotrophy via the rTCA cycle and its biological sink for deep subsurface inorganic carbon.


Assuntos
Bicarbonatos , Ciclo do Carbono , Isótopos de Carbono , Metagenoma , Microbiota , Bicarbonatos/metabolismo , Isótopos de Carbono/metabolismo , Bactérias/genética , Bactérias/metabolismo , Bactérias/classificação , Carbono/metabolismo , Fontes Hidrotermais/microbiologia , Água Subterrânea/microbiologia , Crescimento Quimioautotrófico , Archaea/genética , Archaea/metabolismo
8.
Pflugers Arch ; 476(4): 457-465, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581526

RESUMO

Soluble adenylyl cyclase (sAC) differs from transmembrane adenylyl cyclases (tmAC) in many aspects. In particular, the activity of sAC is not regulated by G-proteins but by the prevailing bicarbonate concentrations inside cells. Therefore, sAC serves as an exquisite intracellular pH sensor, with the capacity to translate pH changes into the regulation of localization and/or activity of cellular proteins involved in pH homeostasis. In this review, we provide an overview of literature describing the regulation of sAC activity by bicarbonate, pinpointing the importance of compartmentalization of intracellular cAMP signaling cascades. In addition, examples of processes involving proton and bicarbonate transport in different cell types, in which sAC plays an important regulatory role, were described in detail.


Assuntos
Adenilil Ciclases , AMP Cíclico , Adenilil Ciclases/metabolismo , AMP Cíclico/metabolismo , Bicarbonatos/metabolismo , Transdução de Sinais/fisiologia , Concentração de Íons de Hidrogênio
9.
BMC Anesthesiol ; 24(1): 152, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649834

RESUMO

The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg-1·h-1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3-, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg2+, Na+ and K+ also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.


Assuntos
Hepatectomia , Soluções Isotônicas , Laparoscopia , Lactato de Ringer , Humanos , Masculino , Feminino , Laparoscopia/métodos , Hepatectomia/métodos , Lactato de Ringer/administração & dosagem , Pessoa de Meia-Idade , Soluções Isotônicas/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Adulto , Solução de Ringer , Ácido Láctico/sangue , Bicarbonatos , Resultado do Tratamento
10.
Environ Sci Technol ; 58(15): 6595-6604, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38573735

RESUMO

Meaningful interpretation of U isotope measurements relies on unraveling the impact of reduction mechanisms on the isotopic fractionation. Here, the isotope fractionation of hexavalent U [U(VI)] was investigated during its reductive mineralization by magnetite to intermediate pentavalent U [U(V)] and ultimately tetravalent U [U(IV)]. As the reaction proceeded, the remaining aqueous phase U [containing U(VI) and U(V)] systematically carried light isotopes, whereas in the bicarbonate-extracted solution [containing U(VI) and U(V)], the δ238U values varied, especially when C/C0 approached 0. This variation was interpreted as reflecting the variable relative contribution of unreduced U(VI) (δ238U < 0‰) and bicarbonate-extractable U(V) (δ238U > 0‰). The solid remaining after bicarbonate extraction included unextractable U(V) and U(IV), for which the δ238U values consistently followed the same trend that started at 0.3-0.5‰ and decreased to ∼0‰. The impact of PIPES buffer on isotopic fractionation was attributed to the variable abundance of U(V) in the aqueous phase. A few extremely heavy bicarbonate-extracted δ238U values were due to mass-dependent fractionation resulting from several hypothesized mechanisms. The results suggest the preferential accumulation of the heavy isotope in the reduced species and the significant influence of U(V) on the overall isotopic fractionation, providing insight into the U isotope fractionation behavior during its abiotic reduction process.


Assuntos
Óxido Ferroso-Férrico , Urânio , Bicarbonatos , Isótopos , Fracionamento Químico
11.
J Vet Sci ; 25(2): e27, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38568828

RESUMO

BACKGROUND: A urethral obstruction (UO) is an emergency commonly observed in male cats, which can result in significant clinical and laboratory alterations, leading to complications and death. OBJECTIVES: This study aimed to correlate symmetric dimethylarginine (SDMA) with the urea, creatinine, potassium, and bicarbonate levels in cats with UO. In addition, the correlation between clinical score and time of obstruction was evaluated. METHODS: Thirty male cats were selected and allocated into a control group (CG, n = 13) and an obstruction group (OG, n = 17). The laboratory analyses were conducted before treatment (M0) and at different times after treatment (12 h [M12], 24 h [M24], and 48 h [M48]). Correlations were established between SDMA and creatinine, urea, bicarbonate, potassium, time of obstruction, and the clinical score. RESULTS: A strong correlation (r > 0.6) was observed between SDMA and creatinine, urea, and potassium in the OG. Furthermore, there was substantial agreement (kappa value) between SDMA and creatinine at M24. A higher clinical score was associated with a longer time of obstruction. In the OG, at M48, the SDMA and creatinine levels were 50% and 41.2% higher, respectively. CONCLUSIONS: A correlation was observed between SDMA and creatinine in obstructed cats, and significant agreement between these values was observed 24 h after the unblocking treatment. A correlation among SDMA, urea, and potassium was observed. Approximately 9% more cats continued to have elevated SDMA levels after 48 h of treatment compared to creatinine. This suggests a slightly lower sensitivity of the latter biomarker but does not exclude the possibility of congruent and normalized values after a longer evaluation period.


Assuntos
Arginina/análogos & derivados , Doenças do Gato , Insuficiência Renal Crônica , Gatos , Animais , Masculino , Insuficiência Renal Crônica/veterinária , Creatinina , Ureia , Potássio , Bicarbonatos , Biomarcadores , Doenças do Gato/diagnóstico
12.
Eur Rev Med Pharmacol Sci ; 28(6): 2305-2316, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38567593

RESUMO

OBJECTIVE: Residual kidney function (RKF) is an important prognostic indicator in peritoneal dialysis (PD) patients. So far, there are no prediction tools available for RKF, and the association between serum bicarbonate and RKF has received little attention in patients with PD. We aimed to develop a nomogram for the preservation of RKF based on the time-averaged serum bicarbonate (TA-Bic) levels. PATIENTS AND METHODS: A prediction model was established by conducting a retrospective cohort study of 151 PD patients who had been treated at the First Affiliated Hospital of Anhui Medical University. The nomogram was developed using a multivariate Cox regression model. The discrimination, calibration, and clinical utility of the model were evaluated by the C-index, receiver operating curve (ROC) curve, calibration curve, and decision curve analysis. RESULTS: In the elderly PD onset, higher baseline values of residual glomerular filtration rate, total Kt/V and higher TA-Bic levels were identified as protective predictors of RKF loss. The nomogram was conducted on the basis of the minimum value of the Akaike Information Criterion and Bayesian Information Criterion with a reasonable C-index of 0.766, showing great discrimination, proper calibration, and high potential for clinical practice. Through the total score of the nomogram, the patients were classified into the high-risk group and low-risk group, and a higher cumulative incidence of complete RRF loss was found in the high-risk group compared with the patients in the low-risk group. CONCLUSIONS: The novel predictive nomogram model can predict the probability of RKF preservation in long-term PD patients with high accuracy. Future studies are needed to externally validate the current nomogram before clinical application.


Assuntos
Bicarbonatos , Diálise Peritoneal , Humanos , Idoso , Estudos Retrospectivos , Nomogramas , Teorema de Bayes , Fatores de Risco , Rim
13.
Medicine (Baltimore) ; 103(17): e38000, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669370

RESUMO

This study aimed to assess the clinical utility of blood lactate-to-bicarbonate (L/B) ratio, as a prognostic factor for 28-day in-hospital mortality in children with dengue shock syndrome (DSS), admitted to the pediatric intensive care unit (PICU). This single-center retrospective study was conducted at a tertiary children hospital in southern Vietnam from 2013 to mid-2022. Prognostic models for DSS mortality were developed, using a predefined set of covariates in the first 24 hours of PICU admission. Area under the curves (AUCs), multivariable logistic and Least Absolute Shrinkage and Selection Operator (LASSO) regressions, bootstrapping and calibration slope were performed. A total of 492 children with DSS and complete clinical and biomarker data were included in the analysis, and 26 (5.3%) patients died. The predictive values for DSS mortality, regarding lactate showing AUC 0.876 (95% CI, 0.807-0.944), and that of L/B ratio 0.867 (95% CI, 0.80-0.934) (P values of both biomarkers < .001). The optimal cutoff point of the L/B ratio was 0.25, while that of lactate was 4.2 mmol/L. The multivariable model showed significant clinical predictors of DSS fatality including severe bleeding, cumulative amount of fluid infused and vasoactive-inotropic score (>30) in the first 24 hours of PICU admission. Combined with the identified clinical predictors, the L/B ratio yielded higher prognostic values (odds ratio [OR] = 8.66, 95% confidence interval [CI], 1.96-38.3; P < .01) than the lactate-based model (OR = 1.35, 95% CI, 1.15-1.58; P < .001). Both the L/B and lactate models showed similarly good performances. Considering that the L/B ratio has a better prognostic value than the lactate model, it may be considered a potential prognostic biomarker in clinical use for predicting 28-day mortality in PICU-admitted children with DSS.


Assuntos
Bicarbonatos , Biomarcadores , Mortalidade Hospitalar , Unidades de Terapia Intensiva Pediátrica , Ácido Láctico , Dengue Grave , Humanos , Masculino , Feminino , Estudos Retrospectivos , Prognóstico , Ácido Láctico/sangue , Dengue Grave/sangue , Dengue Grave/mortalidade , Dengue Grave/diagnóstico , Criança , Pré-Escolar , Biomarcadores/sangue , Bicarbonatos/sangue , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Vietnã/epidemiologia , Valor Preditivo dos Testes , Lactente , Área Sob a Curva
14.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674160

RESUMO

Slc4a genes encode various types of transporters, including Na+-HCO3- cotransporters, Cl-/HCO3- exchangers, or Na+-driven Cl-/HCO3- exchangers. Previous research has revealed that Slc4a9 (Ae4) functions as a Cl-/HCO3- exchanger, which can be driven by either Na+ or K+, prompting investigation into whether other Slc4a members facilitate cation-dependent anion transport. In the present study, we show that either Na+ or K+ drive Cl-/HCO3- exchanger activity in cells overexpressing Slc4a8 or Slc4a10. Further characterization of cation-driven Cl-/HCO3- exchange demonstrated that Slc4a8 and Slc4a10 also mediate Cl- and HCO3--dependent K+ transport. Full-atom molecular dynamics simulation on the recently solved structure of Slc4a8 supports the coordination of K+ at the Na+ binding site in S1. Sequence analysis shows that the critical residues coordinating monovalent cations are conserved among mouse Slc4a8 and Slc4a10 proteins. Together, our results suggest that Slc4a8 and Slc4a10 might transport K+ in the same direction as HCO3- ions in a similar fashion to that described for Na+ transport in the rat Slc4a8 structure.


Assuntos
Potássio , Simportadores de Sódio-Bicarbonato , Animais , Camundongos , Bicarbonatos/metabolismo , Sítios de Ligação , Antiportadores de Cloreto-Bicarbonato/metabolismo , Antiportadores de Cloreto-Bicarbonato/genética , Cloretos/metabolismo , Transporte de Íons , Simulação de Dinâmica Molecular , Potássio/metabolismo , Sódio/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismo , Simportadores de Sódio-Bicarbonato/genética
15.
Medicine (Baltimore) ; 103(10): e37475, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457574

RESUMO

BACKGROUND: Metabolic acidosis (MA) is frequently associated with chronic kidney disease (CKD) progression. Our aim was to compare the effect of oral sodium citrate (SC) with that of oral sodium bicarbonate (SB) on renal function and serum bicarbonate correction, as well as to evaluate their safety profile in patients with MA of CKD. METHODS: We conducted a prospective, single-center, randomized 1:1, parallel, controlled, unblinded clinical trial of 124 patients with MA and CKD stages 3b and 4. The primary outcome was the mean change in estimated glomerular filtration rate (eGFR). The secondary outcomes were mean change in serum bicarbonate level, eGFR decrease by 30%, eGFR decrease by 50%, dialysis, death or prolonged hospitalization, and a combined endpoint. RESULTS: No significant difference was found between the groups in terms of mean eGFR change [adjusted mean difference = -0.99 mL/min/1.73 m2 (95% CI: -2.51 to 0.93, P = .20)]. We observed a mean serum bicarbonate change of 6.15 mmol/L [(95% CI: 5.55-6.74), P < .001] in the SC group and of 6.19 mmol/L [(95% CI: 5.54-6.83), P < .001] in the SB group, but no significant difference between the 2 groups [adjusted mean difference = 0.31 mmol/L (-0.22 to 0.85), P = .25]. Cox proportional hazard analysis showed similar risks regarding eGFR decrease by 30% (P = .77), eGFR decrease by 50% (P = .50), dialysis (P = .85), death or prolonged hospitalization (P = .29), and combined endpoint (P = .57). Study drug discontinuation due to adverse events was significantly more common in the SB group (17.7% vs 4.8%, P = .02). CONCLUSIONS: SC and SB have a similar effect on kidney function decline, both improve serum bicarbonate level, but SB is associated with higher rates of medication discontinuation due to adverse events.


Assuntos
Acidose , Insuficiência Renal Crônica , Humanos , Bicarbonato de Sódio/uso terapêutico , Bicarbonatos , Citrato de Sódio/uso terapêutico , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Acidose/tratamento farmacológico , Acidose/etiologia
16.
J Chem Inf Model ; 64(8): 3375-3385, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38533570

RESUMO

Phosphoenolpyruvate carboxylase (PEPC) is used in plant metabolism for fruit maturation or seed development as well as in the C4 and crassulacean acid metabolism (CAM) mechanisms in photosynthesis, where it is used for the capture of hydrated CO2 (bicarbonate). To find the yet unknown binding site of bicarbonate in this enzyme, we have first identified putative binding sites with nonequilibrium molecular dynamics simulations and then ranked these sites with alchemical free energy calculations with corrections of computational artifacts. Fourteen pockets where bicarbonate could bind were identified, with three having realistic binding free energies with differences with the experimental value below 1 kcal/mol. One of these pockets is found far from the active site at 14 Å and predicted to be an allosteric binding site. In the two other binding sites, bicarbonate is in direct interaction with the magnesium ion; neither sequence alignment nor the study of mutant K606N allowed to discriminate between these two pockets, and both are good candidates as the binding site of bicarbonate in phosphoenolpyruvate carboxylase.


Assuntos
Bicarbonatos , Simulação de Dinâmica Molecular , Fosfoenolpiruvato Carboxilase , Fosfoenolpiruvato Carboxilase/metabolismo , Fosfoenolpiruvato Carboxilase/química , Bicarbonatos/metabolismo , Sítios de Ligação , Termodinâmica , Conformação Proteica
17.
Pflugers Arch ; 476(4): 479-503, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38536494

RESUMO

Cellular and organism survival depends upon the regulation of pH, which is regulated by highly specialized cell membrane transporters, the solute carriers (SLC) (For a comprehensive list of the solute carrier family members, see: https://www.bioparadigms.org/slc/ ). The SLC4 family of bicarbonate (HCO3-) transporters consists of ten members, sorted by their coupling to either sodium (NBCe1, NBCe2, NBCn1, NBCn2, NDCBE), chloride (AE1, AE2, AE3), or borate (BTR1). The ionic coupling of SLC4A9 (AE4) remains controversial. These SLC4 bicarbonate transporters may be controlled by cellular ionic gradients, cellular membrane voltage, and signaling molecules to maintain critical cellular and systemic pH (acid-base) balance. There are profound consequences when blood pH deviates even a small amount outside the normal range (7.35-7.45). Chiefly, Na+-coupled bicarbonate transporters (NCBT) control intracellular pH in nearly every living cell, maintaining the biological pH required for life. Additionally, NCBTs have important roles to regulate cell volume and maintain salt balance as well as absorption and secretion of acid-base equivalents. Due to their varied tissue expression, NCBTs have roles in pathophysiology, which become apparent in physiologic responses when their expression is reduced or genetically deleted. Variations in physiological pH are seen in a wide variety of conditions, from canonically acid-base related conditions to pathologies not necessarily associated with acid-base dysfunction such as cancer, glaucoma, or various neurological diseases. The membranous location of the SLC4 transporters as well as recent advances in discovering their structural biology makes them accessible and attractive as a druggable target in a disease context. The role of sodium-coupled bicarbonate transporters in such a large array of conditions illustrates the potential of treating a wide range of disease states by modifying function of these transporters, whether that be through inhibition or enhancement.


Assuntos
Bicarbonatos , Simportadores de Sódio-Bicarbonato , Simportadores de Sódio-Bicarbonato/genética , Simportadores de Sódio-Bicarbonato/metabolismo , Bicarbonatos/metabolismo , Bicarbonato de Sódio , Sódio/metabolismo , Proteínas de Membrana Transportadoras , Concentração de Íons de Hidrogênio
18.
Comp Med ; 74(2): 70-80, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508687

RESUMO

Whole blood analysis can evaluate numerous parameters, including pH, pCO2, pO2, HCO3 - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep (Ovis aries) is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO2, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female Ovis arie s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.


Assuntos
Técnica de Fontan , Animais , Feminino , Masculino , Ovinos , Creatinina/sangue , Concentração de Íons de Hidrogênio , Nitrogênio da Ureia Sanguínea , Bicarbonatos/sangue , Análise Química do Sangue/veterinária , Ácido Láctico/sangue , Dióxido de Carbono/sangue , Carneiro Doméstico/sangue
19.
Rev Paul Pediatr ; 42: e2023186, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38537035

RESUMO

OBJECTIVE: To develop a rapid method for analysing polyphenols, which are potentially active antioxidants against neonatal oxidative stress, from small human milk (HM) volumes. METHODS: Acid and alkaline extractions were compared using two dyes: Folin-Ciocalteu and Fast Blue BB. Linearity, sensitivity, recovery percentage, polyphenol content, precision, and stability were assessed in 14 HM samples and compared using the Kruskal-Wallis H test (p<0.05). The best technique was applied to 284 HM samples to determine their polyphenolic content and its association with maternal diet by multifactorial linear regression. RESULTS: Acidic extraction successfully recovered the gallic acid reference standard, whereas alkaline extraction overestimated it. Calibration curves for all methods were linear (R2>0.96) up to 500 mg/L. All bicarbonate-based Folin-Ciocalteu methods assayed were stable and repeatable, whereas Fast Blue BB-based variants were not. HM polyphenols (mean=94.68 mg/L) positively correlated to the dietary intake of hydroxycinnamic acids, the most consumed polyphenolic family in this population. CONCLUSIONS: A bicarbonate-based Folin-Ciocalteu micromethod allowed the accurate determination of polyphenols in HM, which might be useful for translational research settings and HM banks.


Assuntos
Compostos de Diazônio , Leite Humano , Polifenóis , Recém-Nascido , Humanos , Polifenóis/análise , Leite Humano/química , Bicarbonatos , Análise Custo-Benefício
20.
Bioresour Technol ; 399: 130592, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518878

RESUMO

Distillation is among the best techniques for management of ammoniacal nitrogen in anaerobic digestate; however, the suitability of the conventional system is neglected in favor of using more advanced setups. This investigation proves the reliability of the classical batch distillation apparatus for high throughput separation of solid crystals of ammonium bicarbonate from food waste digestate (FWD) liquor. Three replicates were carried out: 80 g of FWD liquor with a content of 50 g/L NH4HCO3 was processed for 7.5 h under minimum heating power (<60 °C) and 200 rpm to avoid excessive foam formation. After performing the reactive distillation, 81 % of NH4HCO3 was recovered as white solid crystals at the top of the distillation still. Although the distillation provided a solid material with the same structure and composition as those of the reagent-grade NH4HCO3, the stability of the isolated inorganic fertilizer was poorer, and it could lead to pollution swapping.


Assuntos
Bicarbonatos , Perda e Desperdício de Alimentos , Eliminação de Resíduos , Alimentos , Reprodutibilidade dos Testes , Nitrogênio/análise , Anaerobiose
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