The electroneutral Na+-HCO3- cotransporter NBCn1 (SLC4A7) modulates colonic enterocyte pHi, proliferation, and migration.

NBCn1 (SLC4A7) is one of the two major Na+-HCO3- cotransporters in the human colonic epithelium, expressed predominantly in the highly proliferating colonocytes at the cryptal base. Increased NBCn1 expression levels are reported in tumors, including colorectal cancer. The study explores its importance for maintenance of the intracellular pH (pHi), as well as the proliferative, adhesive, and migratory behavior of the self-differentiating Caco2BBe colonic tumor cell line. In the self-differentiating Caco2BBe cells, NBCn1 mRNA was highly expressed from the proliferative stage until full differentiation. The downregulation of NBCn1 expression by RNA interference affected proliferation and differentiation and decreased intracellular pH (pHi) of the cells in correlation with the degree of knockdown. In addition, a disturbed cell adhesion and reduced migratory speed were associated with NBCn1 knockdown. Murine colonic Nbcn1-/- enteroids also displayed reduced proliferative activity. In the migrating Caco2BBe cells, NBCn1 was found at the leading edge and in colocalization with the focal adhesion markers vinculin and paxillin, which suggests that NBCn1 is involved in the establishment of cell-matrix adhesion. Our data highlight the physiological significance of NBCn1 in modulating epithelial pH homeostasis and cell-matrix interactions in the proliferative region of the colonic epithelium and unravel the molecular mechanism behind pathological overexpression of this transporter in human colorectal cancers.NEW & NOTEWORTHY The transporter NBCn1 plays a central role in maintaining homeostasis within Caco2BBe colonic epithelial cells through its regulation of intracellular pH, matrix adhesion, migration, and proliferation. These observations yield valuable insights into the molecular mechanism of the aberrant upregulation of this transporter in human colorectal cancers.

The influence of substituting dietary peptide-bound with free amino acids on nitrogen metabolism and acid-base balance of broiler chickens depends on asparagine and glutamine supply.

Reducing dietary crude protein (CP) concentration while maintaining adequate amino acid (AA) supply by free AA inclusion can contribute to attenuate the negative environmental effects of animal farming. This study investigated upper limits of dietary free AA inclusions without undesirable effects including the dependence on asparagine (Asn) and glutamine (Gln) supply. Ten broilers were allocated to sixty-three metabolism units each and offered nine experimental diets from day (d) 7-21 (n 7). One diet (167 g CP/kg) contained 80 g soya protein isolate (SPI)/kg. In the other diets, 25, 50, 75 and 100 % of the digestible AA from SPI were substituted with free AA. Digestible Asn+aspartic acid (Asp) and Gln+glutamic acid (Glu) were substituted with Asp/Glu or 50/50 mixes of Asp/Asn and Glu/Gln, respectively. Total excreta were collected from d 11-14 and from d 18-21. Growth and nitrogen accretion were unaffected by 25 and 50 % substitution without and with free Asn/Gln, respectively, but decreased at higher substitution (P ≤ 0·024). Circulating concentrations of Asp, Glu and Gln were unaffected by treatment, while Asn decreased at substitution higher than 50 % when Asn/Gln were not provided (P ≤ 0·005). Blood gas analysis on d 21 indicated a compensated metabolic acidosis at substitution higher than 50 and 75 % without and with free Asn/Gln, respectively (P ≤ 0·017). Results suggest that adding Asn/Gln increased an upper limit for proportion of dietary free AA from 10 to 19 % of dietary CP and enabled higher free AA inclusion without affecting the acid-base balance.

The effects of sodium hydrogen carbonate ingestion during the recovery period between two 200-m front-crawl time trials.

PURPOSE: The aim of this study was to determine how sodium hydrogen carbonate (NaHCO3) ingestion during a 1-h recovery period after a 200-m front-crawl swim affects blood-gas levels, acid-base balance, and performance during a successive trial. METHODS: Fourteen national-level male swimmers (age: 21 ± 3 years, body mass (BM):77 ± 10 kg, stature: 181 ± 7 cm) performed four maximal 200-m front-crawl tests. On one of the two days, the swimmers swam two 200-m tests with a 1-h recovery break, during which they drank water (WATER); on the other day, they performed the same protocol but consumed 0.3 g min-1 NaHCO3 solution during the recovery break (NaHCO3). RESULTS: The ingestion of NaHCO3 before the second test had no effect on swim time despite a greater [ HCO 3 - ] (19.2 ± 2.3 mmol L-1) than that measured during the first test (NaHCO3) (14.5 ± 1.1 mmol L-1) and the other two tests (WATER) (12.7 ± 2.4 and 14.8 ± 1.5 mmol L-1; F = 18.554; p = 0.000) and a higher blood pH (7.46 ± 0.03) than that measured during the first test (NaHCO3) (7.39 ± 0.02) and the other two tests (WATER) (7.16 ± 0.04 and 7.20 ± 0.05); (F = 5.255; p = 0.004). An increase in blood pCO2 (0.2 ± 0.3 kPa) between both tests (NaHCO3) compared to unchanged pCO2 values (- 0.1 ± 0.3 kPa) between the other two tests (WATER) (t = - 2.984; p = 0.011; power = 0.741) was confirmed. CONCLUSIONS: NaHCO3 ingestion during the recovery period between two 200-m front-crawl time trials had a strong buffering effect that did not positively affect performance. An increase in pCO2 may have counterbalanced this impact.

Enhancing exercise performance and recovery through sodium bicarbonate supplementation: introducing the ingestion recovery framework.

Sodium bicarbonate (SB) supplementation is an ergogenic strategy for athletes competing in high-intensity exercise, but the efficacy of SB for accelerating recovery from exercise and thus improving performance during repeated bouts of exercise is not fully understood. In a similar fashion to using SB as a pre-exercise buffer, it is possible accelerated restoration of blood pH and bicarbonate following an exercise bout mechanistically underpins the use of SB as a recovery aid. Physiological mechanisms contributing to beneficial effects for SB during repeated bout exercise could be more far-reaching however, as alterations in strong ion difference (SID) and attenuated cellular stress response might also contribute to accelerated recovery from exercise. From inspection of existing literature, ingestion of 0.3 g kg-1 body mass SB ~60-90 min pre-exercise seems to be the most common dosage strategy, but there is evidence emerging for the potential application of post-exercise supplementation timing, gradual SB doses throughout a competition day, or even ingestion during exercise. Based on this review of literature, an SB ingestion recovery framework is proposed to guide athletes and practitioners on the use of SB to enhance performance for multiple bouts of exercise.

Water, mineral, and blood acid-base balance in calves with naturally occurring diarrhea receiving two alternative oral rehydration solutions or a placebo.

Quantifying the water and mineral losses in feces is essential to determine the optimal composition of oral rehydration solutions (ORS) for diarrheic animals. In a randomized complete block design, this study evaluated water, mineral, and blood acid-base balance of calves with naturally occurring diarrhea receiving ORS or a placebo. On d 0, 45 calves (age: 18 ± 3.2 d; mean ± SD) were selected based on the presence of visual signs of diarrhea, such as dirty tail or wet feces, along with clinical symptoms evaluated by measuring the skin turgor and the degree of enophthalmos. On d 1, calves were divided into blocks of 3 animals based on blood base excess (BE) measured at 0900 h, and within each block, calves were randomly assigned to 1 of 3 treatments (15 calves per treatment) including (1) a hypertonic ORS (HYPER; Na+ = 110 mmol/L; 370 mOsm/kg; strong ion difference [SID] = 60 mEq/L), (2) a hypotonic ORS with low Na+ (HYPO; Na+ = 77 mmol/L; 278 mOsm/kg; SID = 71 mEq/L), and (3) a placebo consisting of lukewarm water with 5 g/L of whey powder (CON). Milk replacer (MR) was fed through teat buckets twice daily at 0630 h and 1700 h in 2 equally sized meals of 2.5 L from d 1 to 3 and of 3.0 L on d 4 and 5. Treatments consisting of 2.0 L lukewarm solutions were administered between milk meals from d 1 to 3 at 1200 h and 2030 h through teat buckets. Refusals of MR and treatments were recorded daily, and blood samples were collected from the jugular vein once daily at arrival in the afternoon of d 0 and at 0900 h from d 1 to 5 after arrival. Urine and feces were collected quantitatively over a 48-h period from 1200 h on d 1 to 1200 h on d 3, and a representative sample of each 24-h period was stored. In addition, the volume of extracellular fluid was evaluated on d 2 by postprandial sampling over a 4-h period relative to the injection of sodium thiosulfate at 1300 h. Total daily fluid intake (MR, treatment, and water) from d 1 to 3 was greater in HYPER (LSM ± SEM; 8.9 ± 0.36 L/d) and HYPO (7.8 ± 0.34 L/d) than in CON (6.6 ± 0.34 L/d). This resulted in a greater water balance (water intake - fluid output in urine and feces) in calves receiving ORS (59.6 ± 6.28 g/kg BW per 24 h vs. 39.6 ± 6.08 g/kg BW per 24 h). Fecal Na+ losses were greater in HYPER than in the other treatments (81 ± 12.0 mg/kg BW per 24 h vs. 24 ± 11.8 mg/kg BW per 24 h). Blood pH was higher in HYPO (7.41 ± 0.016) than CON (7.35 ± 0.016) over the 5 monitoring days, whereas HYPER (7.37 ± 0.017) did not differ with other treatments. In this experimental model, diarrheic calves were likely unable to absorb the high Na+ load from HYPER, resulting in greater Na+ losses in feces, which might have impaired the alkalinizing capacity of HYPER. In contrast, HYPO significantly sustained blood acid-base balance compared with CON, whereas HYPER did not. This suggests that low tonicity ORS with a high SID are more suitable for diarrheic calves.

Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects.

Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.

Effects of low protein diets on acid-base balance, electrolyte balance, intestinal structure, and amino acid transport in piglets.

Reducing the dietary crude protein (CP) could effectively reduce pressure on protein ingredient supplies. However, few data have been reported about the extent to which CP can be reduced and whether limiting the use of soybean meal leads to electrolyte imbalance. In this experiment, using the low protein (LP) diet [2% lower than NRC (2012)], seventy-two piglets (35 days old) were randomly divided into 2 groups with 6 replicates of 6 piglets each: CON group (CP = 18.5%) and LP group (CP = 16.5%), to investigate the effect of the LP diet on electrolyte balance, acid-base balance, intestinal structure and amino acid transport in piglets. The results revealed that the LP diet decreased the average daily gain and dietary CP digestibility, and damaged the villi structure of the small intestine. Compared with the CON diet, the potassium content decreased and the chlorine content increased in the LP diet, and similar trends were shown in piglet serum. The arterial pH, pCO2, HCO3 -, and base excess of piglets in the LP group were lower than those in the CON group, while pO2 was higher than those in the CON group. Interestingly, the LP diet significantly increased the lysine content in piglet serum and significantly decreased the levels of arginine, leucine, and glutamic acid. Furthermore, the LP diet significantly affected the expression of some amino acid transport vectors (B0AT1, EAAC1, and y+LAT1). In summary, these findings suggested that the LP diet leads to acid-base imbalance, amino acid transport disorder and amino acids imbalance in piglets, and the dietary electrolyte may be a key factor in the impact of the LP diet on piglet growth performance and intestinal health.

A Comparative Kidney Transcriptome Analysis of Bicarbonate-Loaded insrr-Null Mice.

The maintenance of plasma pH is critical for life in all organisms. The kidney plays a critical role in acid-base regulation in vertebrates by controlling the plasma concentration of bicarbonate. The receptor tyrosine kinase IRR (insulin receptor-related receptor) is expressed in renal ß-intercalated cells and is involved in alkali sensing due to its ability to autophosphorylate under alkalization of extracellular medium (pH > 7.9). In mice with a knockout of the insrr gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. The specific regulatory mechanisms in the kidney that are under the control of IRR remain unknown. To address this issue, we analyzed and compared the kidney transcriptomes of wild-type and insrr knockout mice under basal or bicarbonate-loaded conditions. Transcriptomic analyses revealed a differential regulation of a number of genes in the kidney. Using TaqMan real-time PCR, we confirmed different expressions of the slc26a4, rps7, slc5a2, aqp6, plcd1, gapdh, rny3, kcnk5, slc6a6 and atp6v1g3 genes in IRR knockout mice. Also, we found that the expression of the kcnk5 gene is increased in wild-type mice after bicarbonate loading but not in knockout mice. Gene set enrichment analysis between the IRR knockout and wild-type samples identified that insrr knockout causes alterations in expression of genes related mostly to the ATP metabolic and electron transport chain processes.

The mechanisms of alkali therapy in targeting renal diseases.

Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function and treatments aiming at stabilizing or slowing its progression may avoid or delay the necessity of kidney replacement therapy and the increased mortality associated with reduced kidney function. Metabolic acidosis, and less severe stages of the acid stress continuum, are common consequences of CKD and some interventional studies support that its correction slows the progression to end-stage kidney disease. This correction can be achieved with mineral alkali in the form of bicarbonate or citrate salts, ingestion of diets with fewer acid-producing food components or more base-producing food components, or a pharmacological approach. In this mini-review article, we summarize the potential mechanisms involved in the beneficial effects of alkali therapy. We also discuss the perspectives in the field and challenges that must be overcome to advance our understanding of such mechanisms.

The reduction in arterial pH with increased temperature is not affected by hyperoxia in toads (Rhinella marina) and pythons (Python molurus).

It is well established that arterial pH decreases with increased temperature in amphibians and reptiles through an elevation of arterial PCO2, but the underlying regulation remains controversial. The alphastat hypothesis ascribes the pH fall to a ventilatory regulation of protein ionisation, but the pH reduction with temperature is lower than predicted by the pKa change of the imidazole group on histidine. We hypothesised that arterial pH decreases at high, but not at low, temperatures when toads (Rhinella marina) and snakes (Python molurus) are exposed to hyperoxia. In toads, hyperoxia caused similar elevations of arterial PCO2 at 20 and 30°C, indicative of a temperature-independent oxygen-mediated drive to breathing, whereas PCO2 was unaffected by hyperoxia in snakes at 25 and 35°C. These findings do not support our hypothesis of an increased oxygen-mediated drive to breathing as body temperature increases.

Comment: Balanced Salt Solutions for Critically Ill Patients: Nonplused and Back to Basics.

The analysis of trial results of the intravenous fluids pharmacodynamics revealed problems common to all studies, such as varying study designs, clinical discretion for treatments, and heterogeneous patients. We believe that in the methodology of future research it is also necessary to pay due attention to the actual rather than theoretical physicochemical parameters of the solutions used, such as osmolality, pH, and potential excess of bases. Paying attention to these parameters of intravenous fluids will be useful for assessing their role in producing pharmacodynamic effects in critically ill patients.

Intravenous or Oral Acetazolamide for Treatment of Diuretic-Induced Alkalosis in Patients With Heart Failure.

BACKGROUND: Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown. OBJECTIVE: The purpose of this study was to characterize dosing strategies and determine the effectiveness of intravenous (IV) and oral (PO) acetazolamide for patients with heart failure (HF) with diuretic-induced metabolic alkalosis. METHODS: This was a multicenter, retrospective cohort study comparing the use of IV versus PO acetazolamide in patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis (serum bicarbonate CO2 ≥32). The primary outcome was the change in CO2 on the first basic metabolic panel (BMP) within 24 hours of the first dose of acetazolamide. Secondary outcomes included laboratory outcomes, such as change in bicarbonate, chloride, and incidence of hyponatremia and hypokalemia. This study was approved by the local institutional review board. RESULTS: IV acetazolamide was given in 35 patients and PO acetazolamide was given in 35 patients. Patients in both groups were given a median of 500 mg of acetazolamide in the first 24 hours. For the primary outcome, there was a significant decrease in CO2 on the first BMP within 24 hours after patients received the IV acetazolamide (-2 [interquartile range, IQR: -2, 0] vs 0 [IQR: -3, 1], P = 0.047). There were no differences in secondary outcomes. CONCLUSION AND RELEVANCE: IV acetazolamide resulted in significantly decreased bicarbonate within 24 hours of administration. IV acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with HF.

The effects of enteric-coated sodium bicarbonate supplementation on 2 km rowing performance in female CrossFit® athletes.

PURPOSE: Sodium bicarbonate (SB) supplementation can improve exercise performance, but few studies consider how effective it is in female athletes. The aim of the study was to establish the effect of individually timed pre-exercise SB ingestion on 2 km rowing time trial (TT) performance in female athletes. METHODS: Eleven female CrossFit® athletes (mean ± SD age, 29 y ± 4 y, body mass, 64.5 kg ± 7.1 kg, height, 1.7 m ± 0.09 m, peak oxygen uptake [VO2peak], 53.8 ± 5.7 mL·kg-1∙min-1). An initial trial identified individual time-to-peak [HCO3-] following enteric-coated 0.3 g·kg-1 BM SB ingestion. Participants then completed a 2 km TT familiarisation followed by a placebo (PLA) or SB trial, using a randomised cross-over design. RESULTS: The ingestion of SB improved rowing performance (514.3 ± 44.6 s) compared to the PLA (529.9 ± 45.4 s) and FAM trials (522.2 ± 43.1 s) (p = 0.001, pη2 = 0.53) which represents a 2.24% improvement compared to the PLA. Individual time-to-peak alkalosis occurred 102.3 ± 22.1 min after ingestion (range 75-150 min) and resulted in increased blood [HCO3-] of 5.5 ± 1.5 mmol⋅L-1 (range = 3.8-7.9 mmol⋅L-1). The change in blood [HCO3-] was significantly correlated with the performance improvement between PLA and SB trials (r = 0.68, p = 0.020). CONCLUSIONS: Ingesting a 0.3 g·kg-1 BM dose of enteric-coated SB improves 2 km rowing performance in female athletes. The improvement is directly related to the extracellular buffering capacity even when blood [HCO3-] does not change ≥ 5.0 mmol⋅L-1.

Sodium bicarbonate induces alkalosis, but improves high-intensity cycling performance only when participants expect a beneficial effect: a placebo and nocebo study.

The study aimed to investigate the effects of sodium bicarbonate (NaHCO3) intake with divergent verbal and visual information on constant load cycling time-to-task failure, conducted within the severe intensity domain. Fifteen recreational cyclists participated in a randomized double-blind, crossover study, ingesting NaHCO3 or placebo (i.e., dextrose), but with divergent information about its likely influence (i.e., likely to induce ergogenic, inert, or harmful effects). Performance was evaluated using constant load cycling time to task failure trial at 115% of peak power output estimated during a ramp incremental exercise test. Data on blood lactate, blood acid-base balance, muscle electrical activity (EMG) through electromyography signal, and the twitch interpolation technique to assess neuromuscular indices were collected. Despite reduced peak force in the isometric maximal voluntary contraction and post-effort peripheral fatigue in all conditions (P < 0.001), neither time to task failure, EMG nor, blood acid-base balance differed between conditions (P > 0.05). Evaluation of effect sizes of all conditions suggested that informing participants that the supplement would be likely to have a positive effect (NaHCO3/Ergogenic: 0.46; 0.15-0.74; Dextrose/Ergogenic: 0.45; 0.04-0.88) resulted in improved performance compared to control. Thus, NaHCO3 ingestion consistently induced alkalosis, indicating that the physiological conditions to improve performance were present. Despite this, NaHCO3 ingestion did not influence performance or indicators of neuromuscular fatigue. In contrast, effect size estimates indicate that participants performed better when informed that they were ingesting an ergogenic supplement. These findings suggest that the apparently ergogenic effect of NaHCO3 may be due, at least in part, to a placebo effect.

Functional divergence of teleost carbonic anhydrase 4.

The functional role of membrane-bound carbonic anhydrases (CAs) has been of keen interest in the past decade, and in particular, studies have linked CA in red muscle, heart, and eye to enhanced tissue oxygen extraction in bony fishes (teleosts). However, the number of purported membrane-bound CA isoforms in teleosts, combined with the imperfect system of CA isoform nomenclature, present roadblocks for ascribing physiological functions to particular CA isoforms across different teleost lineages. Here we developed an organizational framework for membrane-bound CAs in teleosts, providing the latest phylogenetic analysis of extant CA4 and CA4-like isoforms. Our data confirm that there are three distinct isoforms of CA4 (a, b, and c) that are conserved across major teleost lineages, with the exception of CA4c gene being lost in salmonids. Tissue distribution analyses suggest CA4a functions in oxygen delivery across teleost lineages, while CA4b may be specialized for renal acid-base balance and ion regulation. This work provides an important foundation for researchers to elucidate the functional significance of CA4 isoforms in fishes.

Production, physiological response, and calcium and magnesium balance of lactating Holstein cows fed different sources of supplemental magnesium with or without ruminal buffer.

The objective of this study was to evaluate the effects of dietary replacement of magnesium oxide (MgO) with calcium-magnesium hydroxide [CaMg(OH)2] and its interaction with ruminal buffer (sodium sesquicarbonate) supplementation on production, Ca and Mg balance, and overall physiological response of mid-lactation Holstein dairy cows. Sixty cows averaging 40.5 ± 7.0 kg of milk/d were used. Treatments were assigned following a 2 × 2 factorial arrangement: (1) MgO, (2) MgO + buffer, (3) CaMg(OH)2, or (4) CaMg(OH)2 + buffer. Diets were formulated to have 16.5% of crude protein, 1.82 Mcal/kg of net energy for lactation, 0.67% Ca, 0.39% P, and 0.25% Mg, all on a dry matter (DM) basis. Treatments were individually top dressed. Milk production, composition, and DM intake were evaluated. A subsample of 20 cows were randomly selected for the evaluation of Ca and Mg balance, blood gases, and electrolytes. Ruminal fluid was also collected for evaluation of pH and Ca and Mg solubility. Effects of Mg source, buffer, and the interaction Mg source × buffer were analyzed through orthogonal contrasts. An interaction of Mg source × buffer was found for DM intake and feed efficiency, in which cows fed CaMg(OH)2 had a similar feed efficiency regardless of ruminal buffer inclusion; however, when cows were fed MgO, the inclusion of buffer reduced feed efficiency. No effects on body weight and milk yield were observed. Buffer addition tended to increase the concentrations of fat, protein, and solids-not-fat, without affecting the yields of these milk components. Magnesium source and buffer did not affect ruminal fluid, blood, urine, or fecal pH; however, buffer supplementation increased urinary pH. Treatment with CaMg(OH)2 increased blood concentration of HCO3-, total CO2, and base excess compared with cows fed MgO. No differences were observed in the ruminal solubility of Ca and Mg or on milk or urinary Ca and Mg excretion. Greater plasma Mg concentration was observed for animals fed MgO compared with cows fed CaMg(OH)2; however, both sources were above the threshold recommended in the literature for dairy cows. Also, a reduction in fecal Mg excretion was observed in animals fed CaMg(OH)2. In summary, we provide evidence that CaMg(OH)2 could replace MgO without affecting performance, overall physiological response, or Ca and Mg balance of mid-lactating dairy Holstein cows.

Acute Ketone Monoester Supplementation Impairs 20-min Time-Trial Performance in Trained Cyclists: A Randomized, Crossover Trial.

Acute ketone monoester (KE) supplementation can alter exercise responses, but the performance effect is unclear. The limited and equivocal data to date are likely related to factors including the KE dose, test conditions, and caliber of athletes studied. We tested the hypothesis that mean power output during a 20-min cycling time trial (TT) would be different after KE ingestion compared to a placebo (PL). A sample size of 22 was estimated to provide 80% power to detect an effect size dz of 0.63 at an alpha level of .05 with a two-tailed paired t test. This determination considered 2.0% as the minimal important difference in performance. Twenty-three trained cyclists (N = 23; peak oxygen uptake: 65 ± 12 ml·kg-1 min-1; M ± SD), who were regularly cycling >5 hr/week, completed a familiarization trial followed by two experimental trials. Participants self-selected and replicated their diet and exercise for ∼24 hr before each trial. Participants ingested either 0.35 g/kg body mass of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate KE or a flavor-matched PL 30 min before exercise in a randomized, triple-blind, crossover manner. Exercise involved a 15-min warm-up followed by the 20-min TT on a cycle ergometer. The only feedback provided was time elapsed. Preexercise venous [ß-hydroxybutyrate] was higher after KE versus PL (2.0 ± 0.6 vs. 0.2 ± 0.1 mM, p < .0001). Mean TT power output was 2.4% (0.6% to 4.1%; mean [95% confidence interval]) lower after KE versus PL (255 ± 54 vs. 261 ± 54 W, p < .01; dz = 0.60). The mechanistic basis for the impaired TT performance after KE ingestion under the present study conditions remains to be determined.

Many foods are more acid-forming than acid-alkaline formulas indicate.

Foods contain substances impacting the acid-base balance. The Western diet is often viewed as being overly acid due to its high-level of animal-based protein and low-level of vegetable intake. Meanwhile, with ageing the ability to excrete acid compounds is reduced as kidney function declines and so there is a risk of acid retention and subsequent interstitial acidosis. Two systems used for calculating the Dietary Acid Load (DAL): the potential acid load of foods (PRAL) and the net endogenous acid production (NEAP). This report outlines weaknesses in these formulas and concludes that dietitians and nutritionists lack the necessary tools to research the acid-base hypothesis. Additionally, the report emphasizes the importance of food selection in the ageing population. Background: Foods contain substances impacting the acid-base balance. The Western diet is often viewed as being overly acid due to its high-level of animal-based protein and low-level of vegetable intake. There are concerns that the disproportionate acid intake promotes low-grade metabolic acidosis in the interstitial fluid, interstitial acidosis, and may lead to chronic disease. Two formulas are used for calculating the DAL: the PRAL and the NEAP. Both PRAL and NEAP are based on levels of protein and minerals. Aim: To identify additional food constituents that impact DAL. Methods: Review of the literature concerning the acid-forming and alkaline-forming constituents of foods. Results: Five additional food constituents were identified as potentially having a meaningful impact on DAL. The oxidation of taurine and the metabolism of fructose and purines increase acidity, whereas organic acids increase alkalinity. Additionally, polyphenols affect the microbiota which break down uric acid excreted in the intestinal tract. Conclusions: Neither PRAL nor NEAP provides complete assessments of the impact of foods on DAL. These formulas could be improved by the inclusion of dietary amino acids rather than protein, taurine, purines, fructose, organic acids and polyphenols. Currently, dietitians and nutritionists lack the necessary tools both to research the acid-base hypothesis and recommend managed diets. Managed diets are of particular importance for the elderly because of their reduced kidney function which increases the risk of acid retention and subsequent interstitial acidosis.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats. / ä¸åŒç¼ºæ°§å¹²é¢„å¯¹ä½ŽåŽ‹ä½Žæ°§æ¨¡åž‹é¼ è¡€æ°”åŠçº¢ç»†èƒžç›¸å ³æŒ‡æ ‡çš„å½±å“.

OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS: Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

Amino acid transporters revisited: New views in health and disease.

Amino acid transporters (AATs) are membrane-bound transport proteins that mediate transfer of amino acids into and out of cells or cellular organelles. AATs have diverse functional roles ranging from neurotransmission to acid-base balance, intracellular energy metabolism, and anabolic and catabolic reactions. In cancer cells and diabetes, dysregulation of AATs leads to metabolic reprogramming, which changes intracellular amino acid levels, contributing to the pathogenesis of cancer, obesity and diabetes. Indeed, the neutral amino acid transporters (NATs) SLC7A5/LAT1 and SLC1A5/ASCT2 are likely involved in several human malignancies. However, a clinical therapy that directly targets AATs has not yet been developed. The purpose of this review is to highlight the structural and functional diversity of AATs, their diverse physiological roles in different tissues and organs, their wide-ranging implications in human diseases and the emerging strategies and tools that will be necessary to target AATs therapeutically.