The unique allosteric property of crocodilian haemoglobin elucidated by cryo-EM.

The principal effect controlling the oxygen affinity of vertebrate haemoglobins (Hbs) is the allosteric switch between R and T forms with relatively high and low oxygen affinity respectively. Uniquely among jawed vertebrates, crocodilians possess Hb that shows a profound drop in oxygen affinity in the presence of bicarbonate ions. This allows them to stay underwater for extended periods by consuming almost all the oxygen present in the blood-stream, as metabolism releases carbon dioxide, whose conversion to bicarbonate and hydrogen ions is catalysed by carbonic anhydrase. Despite the apparent universal utility of bicarbonate as an allosteric regulator of Hb, this property evolved only in crocodilians. We report here the molecular structures of both human and a crocodilian Hb in the deoxy and liganded states, solved by cryo-electron microscopy. We reveal the precise interactions between two bicarbonate ions and the crocodilian protein at symmetry-related sites found only in the T state. No other known effector of vertebrate Hbs binds anywhere near these sites.

In search of the pH limit of growth in halo-alkaliphilic cyanobacteria.

Cyanobacteria have many biotechnological applications. Increasing their cultivation pH can assist in capturing carbon dioxide and avoiding invasion by other organisms. However, alkaline media may have adverse effects on cyanobacteria, such as reducing the Carbon-Concentrating Mechanism's efficiency. Here, we cultivated two halo-alkaliphilic cyanobacteria consortia in chemostats at pH 10.2-11.4. One consortium was dominated by Ca. Sodalinema alkaliphilum, the other by a species of Nodosilinea. These two cyanobacteria dominate natural communities in Canadian and Asian alkaline soda lakes. We show that increasing the pH decreased biomass yield. This decrease was caused, in part, by a dramatic increase in carbon transfer to heterotrophs. At pH 11.4, cyanobacterial growth became limited by bicarbonate uptake, which was mainly ATP dependent. In parallel, the higher the pH, the more sensitive cyanobacteria became to light, resulting in photoinhibition and upregulation of DNA repair systems.

Metabolic alkalosis in cystic fibrosis: from vascular volume depletion to impaired bicarbonate excretion.

Cystic fibrosis (CF) is the most common life-threatening genetic disease in the United States and among people of European descent. Despite the widespread distribution of the cystic fibrosis transmembrane conductance regulator (CFTR) along kidney tubules, specific renal phenotypes attributable to CF have not been well documented. Recent studies have demonstrated the downregulation of the apical Cl-/HCO3 - exchanger pendrin (Slc26a4) in kidney B-intercalated cells of CF mouse models. These studies have shown that kidneys of both mice and humans with CF have an impaired ability to excrete excess HCO3 -, thus developing metabolic alkalosis when subjected to excess HCO3 - intake. The purpose of this minireview is to discuss the latest advances on the role of pendrin as a molecule with dual critical roles in acid base regulation and systemic vascular volume homeostasis, specifically in CF. Given the immense prevalence of vascular volume depletion, which is primarily precipitated via enhanced chloride loss through perspiration, we suggest that the dominant presentation of metabolic alkalosis in CF is due to the impaired function of pendrin, which plays a critical role in systemic vascular volume and acid base homeostasis.

Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.

The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it is responsible for catalyzing the exchange of bicarbonate and chloride anions across the plasma membrane. To elucidate the structural mechanism of the band 3 transporter, detergent solubilized human ghost membrane reconstituted in nanodiscs was applied to a cryo-EM holey carbon grid to define its composition. With this approach, we identified and determined structural information of the human band 3 transporter. Here, we present 5 different cryo-EM structures of the transmembrane domain of dimeric band 3, either alone or bound with chloride or bicarbonate. Interestingly, we observed that human band 3 can form both symmetric and asymmetric dimers with a different combination of outward-facing (OF) and inward-facing (IF) states. These structures also allow us to obtain the first model of a human band 3 molecule at the IF conformation. Based on the structural data of these dimers, we propose a model of ion transport that is in favor of the elevator-type mechanism.

The effect of serum biochemical parameters on clinical prognosis in children presenting with diabetic ketoacidosis.

OBJECTIVE: The aim of this study was to determine whether diabetes mellitus has a high risk of diabetic ketoacidosis-related complications. Biochemical parameters affect the resolution time of diabetic ketoacidosis. METHODS: The present study is based on a retrospective evaluation of the records of patients who presented to the Pediatrics Clinic of Adiyaman University Hospital between January 1, 2017, and October 1, 2022, with a diagnosis ofdiabetic ketoacidosis. The demographic characteristics, serum biochemical parameters, blood gas results, and time to transition to subcutaneous insulin therapy were all recorded. RESULTS: This study included 49 (49%) female and 51 (51%) male patients aged 1-17 years (mean age: 9.05±4.33 years). The average time to clinical improvement of the sample, that is, transition to subcutaneous insulin therapy, was 21.04±7.8 h. An evaluation of the presence of acute kidney injury based on serum urea and creatinine levels and eGFR values revealed no significant effect on the rate of clinical recovery (respective p-values: p=0.076, p=0.494, and p=0.884). A univariate analysis identified blood glucose (p=0.025), blood gas pH (p<0.001), and blood bicarbonate (p=0.004) values as prognostic factors, while a multivariate analysis revealed pH values had an independent and significant effect on the resolution time of diabetic ketoacidosis. CONCLUSION: Serum glucose, pH, and bicarbonate levels are the most important determinants of clinical prognosis in patients with diabetic ketoacidosis. These findings can serve as a guide for clinicians in the follow-up and treatment of such patients.

Activation of H2O2-HCO3- by Ca2Co2O5 for pollutant degradation.

The bicarbonate-activated hydrogen peroxide (BAP) system is widely studied for organic pollutant degradation in wastewater treatment. Ca2Co2O5, a heterogeneous catalyst containing multivalent cobalt including Co(II) and Co(III), was herein investigated as a BAP activator, and Acid Orange 7 (AO7) was used as a model pollutant. Ca2Co2O5 exhibited good activation performance. The degradation rate and the initial rate constant of the Ca2Co2O5-activated BAP system were 5.4 and 11.2 times as high as the BAP system, respectively. The removal rate of AO7 reached 90.9% in 30 min under optimal conditions (AO7 20 mg/L, Ca2Co2O5 0.2 g/L, H2O2 1 mM, NaHCO3 5 mM, pH 8.5, 25℃). The Ca2Co2O5 catalyst exhibited good stability and recyclability, retaining 85% of AO7 removal rate in the fifth run. Compared to the BAP system, a lower dosage of H2O2 was required and a higher initial concentration of pollutants allowed for effective degradation in the Ca2Co2O5-BAP system. X-ray photoelectron spectroscopy was used to analyze the catalytic mechanism. The analysis showed that the good catalytic performance of Ca2Co2O5 attributes to its high proportion of oxygen vacancies and Co(III) species, and the presence of Ca. The active species O2•-, •OH, and 1O2 are responsible for the degradation, as indicated by the quenching experiments. The degradation mechanism of AO7 was speculated based on UV-Vis spectral analysis and the identification of degradation intermediates. The azo form, naphthalene and benzoic rings in the AO7 structure are destroyed in the decomposition. This research provides a feasible approach to designing effective and reusable BAP activators for pollutant degradation in wastewater treatment.

Ammonium bicarbonate buffers combined with hybrid surface technology columns improve the peak shape of strongly tailing lipids.

BACKGROUND: Lipids such as phosphatidic acids (PAs) and cardiolipins (CLs) present strongly tailing peaks in reversed phase liquid chromatography, which entails low detectability. They are usually analyzed by hydrophilic interaction liquid chromatography (HILIC), which hampers high-throughput lipidomics. Thus, there is a great need for improved analytical methods in order to obtain a broader coverage of the lipidome in a single chromatographic method. We investigated the effect of ammonium bicarbonate (ABC) on peak asymmetry and detectability, in comparison with ammonium formate (AFO) on both a conventional BEH C18 column and an HST-CSH C18 column. RESULTS: The combination of 2.5 mM ABC buffer pH 8 with an HST-CSH C18 column produced significantly improved results, reducing the asymmetry factor at 10 % peak height of PA 16:0/18:1 from 8.4 to 1.6. Furthermore, on average, there was up to a 54-fold enhancement in the peak height of its [M - H]- ion compared to AFO and the BEH C18 column. We confirmed this beneficial effect on other strongly tailing lipids, with accessible phosphate moieties e.g., cardiolipins, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate, phosphorylated ceramide and phosphorylated sphingosine. Furthermore, we found an increased detectability of phospho- and sphingolipids up to 28 times in negative mode when using an HST-CSH C18 column. The method was successfully applied to mouse liver samples, where previously undetected endogenous phospholipids could be analyzed with improved chromatographic separation. SIGNIFICANCE: In conclusion, the use of 2.5 mM ABC substantially improved the peak shape of PAs and enhanced the detectability of the lipidome in negative mode on an RPLC-ESI-Q-TOF-MS system on both BEH C18 and HST-CSH C18 columns. This method provides a wider coverage of the lipidome with one single injection for future lipidomic applications in negative mode.

Exploring the Influence of Acid-Base Status on Athletic Performance during Simulated Three-Day 400 m Race.

This study aimed to investigate the ability of highly trained athletes to consistently perform at their highest level during a simulated three-day 400 m race and to examine the impact of an alkaline diet associated with chronic consumption of bicarbonate-rich water or placebo on their blood metabolic responses before and after the three races. Twenty-two highly trained athletes, divided into two groups-one with an alkalizing diet and placebo water (PLA) and the other with an alkalizing diet and bicarbonate-rich water (BIC)-performed a 400 m race for three consecutive days. Performance metrics, urine and blood samples assessing acid-base balance, and indirect markers of neuro-muscular fatigue were measured before and after each 400 m race. The evolution of the Potential Renal Acid Load (PRAL) index and urinary pH highlights the combination of an alkalizing diet and bicarbonate-rich hydration, modifying the acid-base state (p < 0.05). Athletes in the PLA group replicated the same level of performance during three consecutive daily races without an increase in fatigue-associated markers. Athletes experienced similar levels of metabolic perturbations during the three 400 m races, with improved lactate clearance 20 min after the third race compared to the first two (p < 0.05). This optimization of the buffering capacity through ecological alkaline nutrition and hydration allowed athletes in the BIC group to improve their performance during the third 400 m race (p < 0.01). This study highlights athletes' ability to replicate high-level performances over three consecutive days with the same extreme level of metabolic disturbances, and an alkaline diet combined with bicarbonate-rich water consumption appears to enhance performance in a 400 m race.

Factors associated with carbon dioxide transfer in an experimental model of severe acute kidney injury and hypoventilation during high bicarbonate continuous renal replacement therapy and oxygenation membrane support.

OBJECTIVE: To investigate the factors influencing carbon dioxide transfer in a system that integrates an oxygenation membrane in series with high-bicarbonate continuous veno-venous hemodialysis in hypercapnic animals. METHODS: In an experimental setting, we induced severe acute kidney injury and hypercapnia in five female Landrace pigs. Subsequently, we initiated high (40mEq/L) bicarbonate continuous veno-venous hemodialysis with an oxygenation membrane in series to maintain a pH above 7.25. At intervals of 1 hour, 6 hours, and 12 hours following the initiation of continuous veno-venous hemodialysis, we performed standardized sweep gas flow titration to quantify carbon dioxide transfer. We evaluated factors associated with carbon dioxide transfer through the membrane lung with a mixed linear model. RESULTS: A total of 20 sweep gas flow titration procedures were conducted, yielding 84 measurements of carbon dioxide transfer. Multivariate analysis revealed associations among the following (coefficients ± standard errors): core temperature (+7.8 ± 1.6 °C, p < 0.001), premembrane partial pressure of carbon dioxide (+0.2 ± 0.1/mmHg, p < 0.001), hemoglobin level (+3.5 ± 0.6/g/dL, p < 0.001), sweep gas flow (+6.2 ± 0.2/L/minute, p < 0.001), and arterial oxygen saturation (-0.5 ± 0.2%, p = 0.019). Among these variables, and within the physiological ranges evaluated, sweep gas flow was the primary modifiable factor influencing the efficacy of low-blood-flow carbon dioxide removal. CONCLUSION: Sweep gas flow is the main carbon dioxide removal-related variable during continuous veno-venous hemodialysis with a high bicarbonate level coupled with an oxygenator. Other carbon dioxide transfer modulating variables included the hemoglobin level, arterial oxygen saturation, partial pressure of carbon dioxide and core temperature. These results should be interpreted as exploratory to inform other well-designed experimental or clinical studies.

Independent variables of pH: Ten Knights of the Hydrogen Ion Kingdom-Part I. A prospective observational study.

CO2, HCO3, SID, and total weak acids have been defined as pH's independent variables. However, according to Gamble, HCO3 should be equal to the difference between the sum of cations and the sum of anions besides HCO3. Therefore, if this mathematical expression is substituted for HCO3 in the Henderson-Hasselbalch equation, all independent variables of pH can be demonstrated. Our aim is to test this theory in this study. This prospective observational study was conducted between 2019 and 2020. All admitted patients to the intensive care unit who were >18 years old were included. Demographic data, blood gas parameters, albumin, magnesium, and inorganic phosphorus levels, and outcomes were recorded twice (at admission and at the 24th hour). The multivariate linear regression model was used to determine pH's independent variables. In the multivariate linear regression model, pH was significantly increased by each unit increase in Na, K, Ca, and Mg (mmol L-1). In contrast, pH was significantly decreased by each unit increase in CO2, Cl, lactate, albumin (g dL-1), inorganic phosphorus (mg dL-1), and the strong ion gap. Ten independent variables can accurately predict the changes in pH. For this reason, all ten independent variables should be separately evaluated when interpreting the acid-base status. With this understanding, all algorithms regarding acid-base evaluation may become unnecessary.

Bicarbonate and Serum Lab Markers as Predictors of Mortality in the Trauma Patient.

Introduction: Severe trauma-induced blood loss can lead to metabolic acidosis, shock, and death. Identification of abnormalities in the bicarbonate and serum markers may be seen before frank changes in vital signs in the hemorrhaging trauma patient, allowing for earlier lifesaving interventions. In this study the author aimed to evaluate the usefulness of serum bicarbonate and other lab markers as predictors of mortality in trauma patients within 30 days after injury. Methods: This retrospective, propensity-matched cohort study used the TriNetX database, covering approximately 92 million patients from 55 healthcare organizations in the United States, including 3.8 million trauma patients in the last two decades. Trauma patients were included if they had lab measurements available the day of the event. The analysis focused on mortality within 30 days post-trauma in comparison to measured lab markers. Cohorts were formed based on ranges of bicarbonate, lactate, and base excess levels. Results: Before propensity score matching, a total of 1,275,363 trauma patients with same-day bicarbonate, lactate, or base excess labs were identified. A significant difference in mortality was found across various serum bicarbonate lab ranges compared to the standard range of 21-27 milliequivalents per liter (mEq/L), post-propensity score matching. The relative risk of death was 6.806 for bicarbonate ≤5 mEq/L; 8.651 for 6-10; 6.746 for 11-15; 2.822 for 16-20; and 1.015 for bicarbonate ≥28. Serum lactate also displayed significant mortality outcomes when compared to a normal level of ≤2 millimoles per liter. Base excess showed similar significant correlation at different values compared to a normal base excess of -2 to 2 mEq/L. Conclusion: This study, approximately 100 times larger than prior studies, associated lower bicarbonate levels with increased mortality in the trauma patient. While lactate and base excess offer prognostic value, lower bicarbonate values have a higher relative risk of death. The greater predictive value of bicarbonate and accessibility during resuscitations suggests that it may be the superior prognostic marker in trauma.

Effect of bicarbonate on hydrogen generation by Zero-Valent iron and its impact on generation of acetic acid by seven different inocula.

This study demonstrates the substantial role of bicarbonate within a zero-valent iron (ZVI) system in hydrogen evolution, demonstrating that heightened concentration levels notably enhance hydrogen output. The acetic acid performance production of seven different inocula was examined when exposed to ZVI and CO2 as the sole carbon source, separately. Along the seven inocula, river and constructed wetland sludges show the highest production rates at 300 mg/L day-1 and 269 mg/L day-1, respectively. Acetobacterium levels significantly rose in CO2-enriched environments, particularly in river and wetland sludges. Moreover, bacteria attached to ZVI showed accelerated hydrogen consumption and acetic acid production compared to their freely suspended or ZVI-detached counterparts when hydrogen was primarily added externally. This study highlighted the positive effect of high concentrations of soluble CO2, which acted both as a reactant with ZVI for hydrogen production and as a substrate for homoacetogens, leading to high acetic acid generation.

Production of Peroxymonocarbonate by Steady-State Micromolar H2O2 and Activated Macrophages in the Presence of CO2/HCO3- Evidenced by Boronate Probes.

Peroxymonocarbonate (HCO4-/HOOCO2-) is produced by the reversible reaction of CO2/HCO3- with H2O2 (K = 0.33 M-1, pH 7.0). Although produced in low yields at physiological pHs and H2O2 and CO2/HCO3- concentrations, HCO4- oxidizes most nucleophiles with rate constants 10 to 100 times higher than those of H2O2. Boronate probes are known examples because HCO4- reacts with coumarin-7-boronic acid pinacolate ester (CBE) with a rate constant that is approximately 100 times higher than that of H2O2 and the same holds for fluorescein-boronate (Fl-B) as reported here. Therefore, we tested whether boronate probes could provide evidence for HCO4- formation under biologically relevant conditions. Glucose/glucose oxidase/catalase were adjusted to produce low steady-state H2O2 concentrations (2-18 µM) in Pi buffer at pH 7.4 and 37 °C. Then, CBE (100 µM) was added and fluorescence increase was monitored with time. The results showed that each steady-state H2O2 concentration reacted more rapidly (∼30%) in the presence of CO2/HCO3- (25 mM) than in its absence, and the data permitted the calculation of consistent rate constants. Also, RAW 264.7 macrophages were activated with phorbol 12-myristate 13-acetate (PMA) (1 µg/mL) at pH 7.4 and 37 °C to produce a time-dependent H2O2 concentration (8.0 ± 2.5 µM after 60 min). The media contained 0, 21.6, or 42.2 mM HCO3- equilibrated with 0, 5, or 10% CO2, respectively. In the presence of CBE or Fl-B (30 µM), a time-dependent increase in the fluorescence of the bulk solution was observed, which was higher in the presence of CO2/HCO3- in a concentration-dependent manner. The Fl-B samples were also examined by fluorescence microscopy. Our results demonstrated that mammalian cells produce HCO4- and boronate probes can evidence and distinguish it from H2O2 under biologically relevant concentrations of H2O2 and CO2/HCO3-.

Optimizing wheat productivity through integrated management of irrigation, nutrition, and organic amendments.

Enhancing wheat productivity by implementing a comprehensive approach that combines irrigation, nutrition, and organic amendments shows potential for collectively enhancing crop performance. This study examined the individual and combined effects of using irrigation systems (IS), foliar potassium bicarbonate (PBR) application, and compost application methods (CM) on nine traits related to the growth, physiology, and yield of the Giza-171 wheat cultivar. Analysis of variance revealed significant (P ≤ 0.05) main effects of IS, PBR, and CM on wheat growth, physiology, and yield traits over the two growing seasons of the study. Drip irrigation resulted in a 16% increase in plant height, leaf area index, crop growth rate, yield components, and grain yield compared to spray irrigation. Additionally, the application of foliar PBR at a concentration of 0.08 g/L boosted these parameters by up to 22% compared to the control. Furthermore, the application of compost using the role method resulted in enhanced wheat performance compared to the treatment including mix application. Importantly, the combined analysis revealed that the three-way interaction between the three factors had a significant effect (P ≤ 0.05) on all the studied traits, with drip irrigation at 0.08 g PBR rate and role compost application method (referred as Drip_0.08g_Role) resulting in the best performance across all traits, while sprinkle irrigation without PBR and conventional mixed compost method (referred as sprinkle_CK_Mix) produced the poorest results. This highlights the potential to synergistically improve wheat performance through optimized agronomic inputs.

Hypocapnia in women with fibromyalgia.

OBJECTIVES: The purpose of this study was to investigate whether people with fibromyalgia (FM) have dysfunctional breathing by examining acid-base balance and comparing it with healthy controls. METHODS: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate acid-base balance, arterial blood was sampled from the radial artery. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for between-group differences. Blood gas analyses were performed stepwise on each individual to detect acid-base disturbance, which was categorized as primary respiratory and possible compensation indicating chronicity. A three-step approach was employed to evaluate pH, carbon dioxide and bicarbonate in this order. RESULTS: Women with FM had significantly lower carbon dioxide pressure (p = 0.013) and higher lactate (p = 0.038) compared to healthy controls at the group level. There were no significant differences in oxygen pressure, bicarbonate, pH and base excess. Employing a three-step acid-base analysis, 11 individuals in the FM group had a possible renally compensated mild chronic hyperventilation, compared to only 4 among the healthy controls (p = 0.042). CONCLUSIONS: In this study, we could identify a subgroup of individuals with FM who may be characterized as mild chronic hyperventilators. The results might point to a plausible dysfunctional breathing in some women with FM.

Artificial neural network modeling for the oxidation kinetics of divalent manganese ions during chlorination and the role of arsenite ions in the binary/ternary systems.

This study investigated the coexistence and contamination of manganese (Mn(II)) and arsenite (As(III)) in groundwater and examined their oxidation behavior under different equilibrating parameters, including varying pH, bicarbonate (HCO3-) concentrations, and sodium hypochlorite (NaClO) oxidant concentrations. Results showed that if the molar ratio of NaClO: As(III) was >1, the oxidation of As(III) could be achieved within a minute with an extremely high oxidation rate of 99.7 %. In the binary system, the removal of As(III) prevailed over Mn(II). The As(III) oxidation efficiency increased from 59.8 ± 0.6 % to 70.8 ± 1.9 % when pH rose from 5.7 to 8.0. The oxidation reaction between As(III) and NaClO releases H+ ions, decreasing the pH from 6.77 to 6.19 and reducing the removal efficiency of Mn(II). The presence of HCO3- reduced the oxidation rate of Mn(II) from 63.2 % to 13.9 % within four hours. Instead, the final oxidation rate of Mn(II) increased from 68.1 % to 87.7 %. This increase can be attributed to HCO3- ions competing with the free Mn(II) for the adsorption sites on the sediments, inhibiting the formation of H+. Moreover, kinetic studies revealed that the oxidation reaction between Mn(II) and NaClO followed first-order kinetics based on their R2 values. The significant factors affecting the Mn(II) oxidation efficiency were the initial concentration of NaClO and pH. Applying an artificial neural network (ANN) model for data analysis proved to be an effective tool for predicting Mn(II) oxidation rates under different experimental conditions. The actual Mn(II) oxidation data and the predicted values obtained from the ANN model showed significant consistency. The training and validation data sets yielded R2 values of 0.995 and 0.992, respectively. Moreover, the ANN model highlights the importance of pH and NaClO concentrations in influencing the oxidation rate of Mn(II).

Evaluation of agreement between a noninvasive method for real-time measurement of critical blood values with a standard point-of-care device.

The purpose of this work was to investigate the degree of agreement between two distinct approaches for measuring a set of blood values and to compare comfort levels reported by participants when utilizing these two disparate measurement methods. Radial arterial blood was collected for the comparator analysis using the Abbott i-STAT® POCT device. In contrast, the non-invasive proprietary DBC methodology is used to calculate sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation using four input parameters (temperature, hemoglobin, pO2, and pCO2). Agreement between the measurement for a set of blood values obtained using i-STAT and DBC methodology was compared using intraclass correlation coefficients, Passing and Bablok regression analyses, and Bland Altman plots. A p-value of <0.05 was considered statistically significant. A total of 37 participants were included in this study. The mean age of the participants was 42.4 ± 13 years, most were male (65%), predominantly Caucasian/White (75%), and of Hispanic ethnicity (40%). The Intraclass Correlation Coefficients (ICC) analyses indicated agreement levels ranging from poor to moderate between i-STAT and the DBC's algorithm for Hb, pCO2, HCO3, TCO2, and Na, and weak agreement for pO2, HSO2, pH, K, Ca, and Cl. The Passing and Bablok regression analyses demonstrated that values for Hb, pO2, pCO2, TCO2, Cl, and Na obtained from the i-STAT did not differ significantly from that of the DBC's algorithm suggesting good agreement. The values for Hb, K, and Na measured by the DBC algorithm were slightly higher than those obtained by the i-STAT, indicating some systematic differences between these two methods on Bland Altman Plots. The non-invasive DBC methodology was found to be reliable and robust for most of the measured blood values compared to invasive POCT i-STAT device in healthy participants. These findings need further validation in larger samples and among individuals afflicted with various medical conditions.

Impact of AKI on metabolic compensation for respiratory acidosis in ICU patients with AECOPD.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can result in severe respiratory acidosis. Metabolic compensation is primarily achieved by renal retention of bicarbonate. The extent to which acute kidney injury (AKI) impairs the kidney's capacity to compensate for respiratory acidosis remains unclear. MATERIALS AND METHODS: This retrospective analysis covers clinical data between January 2009 and December 2021 for 498 ICU patients with AECOPD and need for respiratory support. RESULTS: 278 patients (55.8%) presented with or developed AKI. Patients with AKI exhibited higher 30-day-mortality rates (14.5% vs. 4.5% p = 0.001), longer duration of mechanical ventilation (median 90 h vs. 14 h; p = 0.001) and more severe hypercapnic acidosis (pH 7.23 vs. 7.28; pCO2 68.5 mmHg vs. 61.8 mmHg). Patients with higher AKI stages exhibited lower HCO3-/pCO2 ratios and did not reach expected HCO3- levels. In a mixed model analysis with random intercept per patient we analyzed the association of pCO2 (independent) and HCO3- (dependent variable). Lower estimates for averaged change in HCO3- were observed in patients with more severe AKI. CONCLUSION: AKI leads to poor outcomes and compromises metabolic compensation of respiratory acidosis in ICU patients with AECOPD. While buffering agents may aid compensation for severe AKI, their use should be approached with caution.

DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function.

Duodenal bicarbonate secretion is critical to epithelial protection, as well as nutrient digestion and absorption, and is impaired in cystic fibrosis (CF). We examined if linaclotide, typically used to treat constipation, may also stimulate duodenal bicarbonate secretion. Bicarbonate secretion was measured in vivo and in vitro using mouse and human duodenum (biopsies and enteroids). Ion transporter localization was identified with confocal microscopy, and de novo analysis of human duodenal single-cell RNA sequencing (scRNA-Seq) data sets was performed. Linaclotide increased bicarbonate secretion in mouse and human duodenum in the absence of cystic fibrosis transmembrane conductance regulator (CFTR) expression (Cftr-knockout mice) or function (CFTRinh-172). Na+/H+ exchanger 3 inhibition contributed to a portion of this response. Linaclotide-stimulated bicarbonate secretion was eliminated by down-regulated in adenoma (DRA, SLC26A3) inhibition during loss of CFTR activity. ScRNA-Seq identified that 70% of villus cells expressed SLC26A3, but not CFTR, mRNA. Loss of CFTR activity and linaclotide increased apical brush border expression of DRA in non-CF and CF differentiated enteroids. These data provide further insights into the action of linaclotide and how DRA may compensate for loss of CFTR in regulating luminal pH. Linaclotide may be a useful therapy for CF individuals with impaired bicarbonate secretion.

Mechanisms and physiological relevance of acid-base exchange in functional units of the kidney.

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.