Challenging management dogma where evidence is non-existent, weak, or outdated: part II.

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal.

Efficacy of anti-hyperkalemic agents during cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

Aim: We assessed the efficacy of anti-hyperkalemic agents for alleviating hyperkalemia and improving clinical outcomes in patients with out-of-hospital cardiac arrest (OHCA). Methods: This was a single-center, retrospective observational study of OHCA patients treated at tertiary hospitals between 2010 and 2020. Adult patients aged 18 or older who were in cardiac arrest at the time of arrival and had records of potassium levels measured during cardiac arrest were included. A linear regression model was used to evaluate the relationship between changes in potassium levels and use of anti-hyperkalemic medications. Cox proportional hazards regression analysis was performed to analyze the relationship between the use of anti-hyperkalemic agents and the achievement of return of spontaneous circulation (ROSC). Results: Among 839 episodes, 465 patients received anti-hyperkalemic medication before ROSC. The rate of ROSC was higher in the no anti-hyperkalemic group than in the anti-hyperkalemic group (55.9 % vs 47.7 %, P = 0.019). The decrease in potassium level in the anti-hyperkalemic group from pre-ROSC to post-ROSC was significantly greater than that in the no anti-hyperkalemic group (coefficient 0.38, 95 % confidence interval [CI], 0.13-0.64, P = 0.003). In Cox proportional hazards regression analysis, the use of anti-hyperkalemic medication was related to a decreased ROSC rate in the overall group (adjusted hazard ratio [aHR] 0.66, 95 % CI, 0.54-0.81, P < 0.001), but there were no differences among subgroups classified according to initial potassium levels. Conclusions: Anti-hyperkalemic agents were associated with substantial decreases in potassium levels in OHCA patients. However, administration of anti-hyperkalemic agents did not affect the achievement of ROSC.

Efficacy and safety of oral sodium bicarbonate in kidney-transplant recipients and non-transplant patients with chronic kidney disease: a systematic review and meta-analysis.

Introduction: We investigated the efficacy and safety of oral sodium bicarbonate in kidney-transplant recipients and non-transplant patients with chronic kidney disease (CKD), which are currently unclear. Methods: PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials investigating the efficacy and safety of sodium bicarbonate versus placebo or standard treatment in kidney-transplant and non-transplant patients with CKD. Results: Sixteen studies of kidney-transplant recipients (two studies, 280 patients) and non-transplant patients with CKD (14 studies, 1,380 patients) were included. With non-transplant patients, sodium bicarbonate slowed kidney-function declines (standardized mean difference [SMD]: 0.49, 95% confidence interval [CI]: 0.14-0.85, p = 0.006) within ≥12 months (SMD: 0.75 [95% CI: 0.12-1.38], p = 0.02), baseline-serum bicarbonate <22 mmol/L (SMD: 0.41 [95% CI: 0.19-0.64], p = 0.0004) and increased serum-bicarbonate levels (mean difference [MD]: 2.35 [95% CI: 1.40-3.30], p < 0.00001). In kidney-transplant recipients, sodium bicarbonate did not preserve graft function (SMD: -0.07 [95% CI: -0.30-0.16], p = 0.56) but increased blood pH levels (MD: 0.02 [95% CI: 0.00-0.04], p = 0.02). No significant adverse events occurred in the kidney-transplant or non-transplant patients (risk ratio [RR]: 0.89, [95% CI: 0.47-1.67], p = 0.72; and RR 1.30 [95% CI: 0.84-2.00], p = 0.24, respectively). However, oral sodium bicarbonate correlated with increased diastolic pressure and worsened hypertension and edema (MD: 2.21 [95% CI: 0.67-3.75], p = 0.005; RR: 1.44 [95% CI: 1.11-1.88], p = 0.007; and RR: 1.28 [95% CI: 1.00-1.63], p = 0.05, respectively). Discussion: Oral sodium bicarbonate may slow kidney-function decline in non-transplant patients with CKD taking sodium bicarbonate supplementation for ≥12 months or a baseline serum bicarbonate level of <22 mmol/L, without preserving graft function in kidney-transplant recipients. Sodium bicarbonate may increase diastolic pressure, and elevate a higher incidence of worsening hypertension and edema. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023413929.

Lauric acid improved the quality of fresh noodles with/without sodium bicarbonate by altering physical properties and structure of wheat starch.

To know the influence of lauric acid (LA) on wheat flour fresh noodles (WFN) quality and the latent mechanism, the effect of LA on cooking properties, digestibility and structure of WFN with/without sodium bicarbonate (SB) and the properties of wheat flour (WF) with/without SB were studied. The results indicated that LA reduced cooking loss and digestibility of WFN with SB and slightly decreased water adsorption and increased the free water binding ability and hardness of WFN without SB. Furthermore, LA increased the degree of short- and long-range order and molecular weight of starch in cooked WFN with/without SB and it had greater effect on the degree of short- and long-range order and molecular weight of starch in cooked WFN with SB than that without SB. Differential scanning calorimeter (DSC) and rapid viscosity analysis (RVA) displayed that WFN with LA and SB formed more starch-LA or/and starch-LA-protein complexes than WFN with LA. Additionally, the impact of LA on WFN quality and WF properties was influenced by SB concentration. This study will provide theoretical basis and new thoughts for the design of high-quality fresh noodles with low digestibility, low cooking loss and high hardness.

An assessment on the effects of buffers on the productive, behavioral and metabolic parameters of Holstein dairy cows.

This study aimed to evaluate the impact of supplementing sodium bicarbonate or a commercial blend of buffering agents (BBA) comprising calcareous calcitic, magnesium oxide, calcareous algae, and sodium bicarbonate on the productive, behavioral and metabolic parameters of Holstein cows fed starchy diets. Over a 60-day trial period, thirty-six multiparous cows with an average milk yield of 38.84 ± 9.24 kg/day and 63.74 ± 18.63 days in milk (DIM), were randomly divided into two groups. The control group (n = 18) received a supplementation of 1.1% dry matter (DM) of sodium bicarbonate (Raudi®, Totalmix, Brazil), while the BBA group (n = 18) was administered with 0.5% DM of a blend of buffering agents (Equalizer®, Nutron/Cargill, Brazil). The mean values of ruminal pH (control 6.80 ± 0.06 and BBA 6.77 ± 0.06; P > 0.05) and volatile fatty acid (VFA) production (control: acetate 62.63 ± 1.29%, propionate 22.99 ± 1.07%, butyrate 14.30 ± 0.52%; BBA: acetate 63.07 ± 1.32%, propionate 23.47 ± 1.10%, butyrate 13.70 ± 0.57%), were similar (P > 0,05) between the two groups. The value of faecal pH was higher (P < 0.05) in the BBA group (6.25 ± 0.02) than the control group (6.12 ± 0.02). Animals treated with BBA exhibited lower (P < 0,05) dry matter intake (DMI) (24.75 ± 0.64 kg/day), higher feed efficiency (FE) (1.64 ± 0.03), and reduced feeding frequency (52.89 ± 3.73 n°/day) than the control group (DMI, 26.75 ± 0.62 kg/day; FE, 1.50 ± 0.03; feeding frequency, 66.07 ± 3.64 n°/day). Milk production remained similar across both groups (control, 39.11 ± 0.92 kg/day and BBA, 39.87 ± 0.92 kg/day; P > 0.05). Notably, the control group displayed a higher (P < 0,05) concentration of milk protein (1.21 ± 0.05 kg/day) than the BBA (1.18 ± 0.05 kg/day) group. The study concluded that both treatments effectively buffered the rumen and mitigated the risk of ruminal acidosis. Moreover, the higher faecal pH in the BBA-treated group suggests potential intestinal action attributable to the synergistic effects of diverse additives with buffering properties. Despite a reduced DMI, BBA-treated animals exhibited improved FE.

Effect of ultrasound-assisted treatment on meat tenderization for elderly individuals.

This study evaluated the effect of ultrasound using papain and sodium bicarbonate (SC) on meat tenderness to achieve the desired texture for elderly individuals. Meats were immersed in distilled water (DW) or papain (PI), ultrasonically treated with papain (UPI), or ultrasonically treated with papain and SC (UPIS). Response surface methodology was used to optimize the processing conditions with the lowest hardness, and the optimal conditions were determined as follows: 400 U/mL papain, ultrasonic for 30 min, and 4% SC. Hardness, color, and myofibrillar fragmentation index (MFI) were investigated. The hardness followed the order of DW (22.50 N), PI (18.62 N), UPI (12.08 N), and UPIS (7.16 N), and UPIS showed the highest MFI. Papain and SC affected the color of the meat. Overall, ultrasound-assisted treatment using papain and SC resulted in hardness levels of less than 7.8 N, which can be easily compressed by low tongue pressure.

Pre-Exercise Caffeine and Sodium Bicarbonate: Their Effects on Isometric Mid-Thigh Pull Performance in a Crossover, Double-Blind, Placebo-Controlled Study.

Caffeine and sodium bicarbonate are extensively researched ergogenic aids known for their potential to enhance exercise performance. The stimulant properties of caffeine on the central nervous system, coupled with the buffering capacity of sodium bicarbonate, have been associated with improved athletic performance. This has led to investigations of their combined effects on strength. The aim of the present study is to investigate the effect of isolated and combined caffeine and sodium bicarbonate consumption on strength using the isometric mid-thigh pull test (IMTP). Nineteen male college students (age 23.6 ± 1.6 years) participated in this crossover, double-blind, placebo-controlled study. They were exposed to the following conditions: control (no supplement), placebo (20 g maltodextrin), caffeine (6 mg/kg), sodium bicarbonate (0.3 g/kg), and a combination of caffeine and sodium bicarbonate. Supplements and placebo were diluted in water and consumed 60 min prior to the IMTP tests. Two 5 s IMTP trials were performed at 40-60% and 60-80% of One Repetition of Maximum (1RM) with a 60 s rest between. Consumption of caffeine or Caf + NaHCO3 did not significantly change peak IMTP strength values at any intensity (p = 0.110). The peak IMTP values did not show significant differences between conditions or from control condition values (1091 ± 100 N) to Caf (1224 ± 92 N), NaHCO3 (1222 ± 74 N), and Caf ± NaHCO3 (1152 ± 109 N). However, the test of the results of the ANOVA analysis of repeated measures of effect within the caffeine condition was significant for the increase in IMTP relative strength compared to control (p < 0.05). Thus, the IMTP force values increased significantly from control to Caf (p = 0.016) and from Pla to Caf (p = 0.008), but not for other comparisons (p > 0.05). In summary, caffeine supplementation alone, taken 60 min before exercise, positively affects submaximal strength performance. In contrast, sodium bicarbonate, whether taken alone or in combination with caffeine, does not enhance submaximal strength in the IMTP tests.

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.

Preservatives for postmortem brain tissue in biomechanical testing: A pilot study.

Postmortem human subject (PMHS) studies are essential to brain injury research in motor vehicle safety. However, postmortem deterioration reduces the similarity between postmortem test results and in vivo response in material testing of brain tissue and in biomechanical testing of the whole head. This pilot study explores the effect of potential preservatives on brain tissue breakdown to identify promising preservatives that warrant further investigation. To identify preservatives with potential to slow postmortem degradation, samples from an initial PMHS were refrigerated at 10°C to qualitatively compare tissue breakdown from 58 to 152 h postmortem after storage in candidate solutions. On brain tissue samples from a second PMHS, compressive stiffness was measured on six samples immediately after harvest for comparison to the stiffness of 23 samples that were stored at 10°C in candidate solutions for 24 h after harvest. The candidate solutions were artificial cerebrospinal fluid (ACSF) without preservatives; ACSF with a combination of antibiotics and antifungal agents; ACSF with added sodium bicarbonate; and ACSF with both the antibiotic/antifungal combination and sodium bicarbonate. Results were analyzed using multiple linear regression of specimen stiffness on harvest lobe and storage solution to investigate potential differences in tissue stiffness. Qualitative evaluation suggested that samples stored in a solution that contained both the antibiotic/antifungal combination and sodium bicarbonate exhibited less evidence of tissue breakdown than the samples stored without preservatives or with only one of those preservatives. In compression testing, samples tested immediately after harvest were significantly stiffer than samples tested after 24 h of storage at 10°C in ACSF (difference: -0.27 N/mm, 95% confidence interval (CI): -0.50, -0.05) or ACSF with antibiotics/antifungal agents (difference: -0.32 N/mm, 95% CI: -0.59, -0.04), controlling for harvest lobe. In contrast, the stiffness of samples tested after storage in either solution containing sodium bicarbonate was not significantly different from the stiffness of samples tested at harvest. There was no significant overall difference in the mean tissue stiffness between samples from the frontal and parietal lobes, controlling for storage solution. Given the importance of PMHS studies to brain injury research, any strategy that shows promise for helping to maintain in vivo brain material properties has the potential to improve understanding of brain injury mechanisms and tolerance to head injury and warrants further investigation. These pilot study results suggest that sodium bicarbonate has the potential to reduce the deterioration of brain tissue in biomechanical testing. The results motivate further evaluation of sodium bicarbonate as a preservative for biomechanical testing using additional test subjects, more comprehensive material testing, and evaluation under a broader set of test conditions including in whole-head testing. The effect of antibiotics and antifungal agents on brain tissue stiffness was minimal but may have been limited by the cold storage conditions in this study. Further exploration of the potential for microbial agents to preserve tissue postmortem would benefit from evaluation of the effects of storage temperature.

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Treating Diphenhydramine Overdose: A Literature Review of Currently Available Treatment Methods.

From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.

Genomic investigation and clinical correlates of the in vitro ß-lactam: NaHCO3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to ß-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with ß-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal ß-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a ß-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a ß-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro ß-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a ß-lactam.

Effects of sodium bicarbonate solution on hypergravity-induced Fos expression in neurons of the amygdala in rats: Implication of sodium bicarbonate therapy for vertigo.

OBJECTIVE: In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO3) had been originally developed to inhibit motion sickness and then have long been used to treat vertigo. Previously, we reported that Fos-positive neurons appear in the amygdala after hypergravity stimulation in rats. In the present study, we examined whether injection of 7 % NaHCO3 inhibits hypergravity-induced Fos expression in the neurons in the central nucleus of the amygdala in rats. METHODS: Rats were exposed to 2 G hypergravity in an animal centrifuge device for 3 h. A solution of 7 % NaHCO3 at a dose of 4 mM/kg was injected intraperitoneally before 2 G hypergraviy. Fos-positive neurons in the amygdala were stained immunohistochemically. RESULTS: The number of Fos-positive neurons in the central nucleus of the amygdala was significantly increased after 2 G hypergravity in rats that received no drugs or saline, compared to that in rats exposed only to the noise of the centrifuge and received 7 % NaHCO3 solution. The number of Fos-positive neurons in the central nucleus of the amygdala after 2 G hypergravity was significantly decreased in rats that received 7 % NaHCO3 solution, compared to that in rats that received no drugs or saline. CONCLUSION: Since Fos expression is a marker of activated neurons, the present findings suggest that hypergravity activates the amygdala and that administration of 7 % NaHCO3 suppresses hypergravity-induced activation of the amygdala. Hypergravity disturbs spatial orientation to produce motion sickness and the amygdala is involved in fear response. Recently, Ziemann et al. suggested that fear-evoking stimuli reduce the pH in the amygdala to activate it, leading to induction of fear behavior and that administering HCO3- attenuates fear behavior [Cell 2009; 139: 1012-1021]. Therefore, it is possible that hypergravity reduces the pH in the amygdala to activate it, thereby inducing the fear associated with motion sickness and that administration of 7 % NaHCO3 increases the brain pH thereby suppressing hypergravity-induced activation of the amygdala and inhibiting the fear associated with motion sickness. In patients with vertigo, 7 % NaHCO3 therapy may increase the brain pH thereby suppressing the activation of the amygdala and inhibiting the fear associated with vertigo to elicit a beneficial clinical effect.

Alkalinization Using Sodium Bicarbonate for COVID-19 Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: A systematic review and meta-analysis have been conducted to evaluate the efficacy of alkalinization for COVID-19 patients based on current evidence to determine the impact of alkalinization on COVID-19 outcomes. METHODS: We searched MEDLINE (Pubmed), Web of Science, Cochrane Library, and Clinicaltrials.gov for studies evaluating the efficacy of alkalinization up to 30 April 2023. Based on the PRISMA 2020 statement criteria a systematic review and meta-analysis of studies were performed. RESULTS: The results of our meta-analysis showed a significant reduction in mortality rate in the alkalinization group compared to controls (RR 0.73, 95% CI: 0.56-0.95; I2 = 0%). However, our subgroup analysis showed no significant improvement in RCT-only studies (RR 0.78, 95% CI: 0.59-1.05; I2 = 0%), the recovery rate was significantly higher in the alkalinization group (RR 2.13, 95% CI: 1.39-3.26; I2 = 0%), duration of recovery also has improved in alkalinization group (SMD 0.76, 95% CI: 0.33-1.18; I2 = 0%). The results of our meta-analysis showed a significant reduction in the duration of hospitalization in the alkalinization group compared to controls with very low certainty of evidence (SMD -0.66, 95% CI: -0.97 to -0.35; I2 = 36%). CONCLUSION: With low certainty of evidence, alkalinization (by sodium bicarbonate) can be an efficient and safe adjuvant treatment for COVID-19 patients. Future randomized controlled trials are needed to strengthen the available evidence.

Lyophilized rumen fluid as a ruminal fermentation modifier in high grain-fed acidotic goats.

Rumen cud transfaunation re-establishes rumen micro environment and improves fermentation in recipient animals affected with digestive disorders. Preserving rumen cud or fluid will increase its availability for the treatment of rumen fermentation disorders, without having to maintain donor animals. Rumen fluid collected from healthy goats, fed standard ration having roughage 70% and concentrate 30%, was lyophilized (prefreezing -80 °C, 48 h; lyophilization -45 °C, 32 h) using 5% glycerol as cryoprotectant. The 16 S metagenome analysis of the lyophilized rumen fluid (LRF) revealed an abundance of Prevotella (33.2%). Selenomonas ruminantium (1.87%) and Megasphaera elsdenii (0.23%) were also present. Twenty-four goats having history of high grain feeding and exhibiting clinical symptoms of rumen fermentation disorders were randomly distributed into either one of the two treatment groups viz., T1 = oral administration of LRF 31 g/animal/day and T2 = oral administration of sodium bicarbonate (SB) 15 g/animal/day. Post intervention LRF and SB, improved animal body condition, feed intake, fecal consistency, elevated the ruminal pH at 48 h, reduced propionate and lactate at 48 h, reduced total volatile fatty acids (TVFA) and ammonia nitrogen at 24 h. Significant reduction in serum blood urea nitrogen (BUN) and urea levels were observed even from 24 h post intervention irrespective of the treatments. LRF significantly improved acetate and decreased propionate production compared to SB. LRF at 7.5% (v/v) can thus be used to counteract ruminal fermentation disorders in goats sequel to high grain ration.

Sodium Bicarbonate Decreases Alcohol Consumption in Mice.

We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.

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.

Temporal Transcriptomic Profiling Reveals Dynamic Changes in Gene Expression of Giant Freshwater Prawn upon Acute Saline-Alkaline Stresses.

Bicarbonate and sulfate are among two primary ion constituents of saline-alkaline water, with excessive levels potentially causing metabolic disorders in crustaceans, affecting their molting and interrupting development. As an economically important crustacean species, the molecular adaptive mechanism of giant freshwater prawn Macrobrachium rosenbergii in response to the stress of bicarbonate and sulfate remains unexplored. To investigate the mechanism underlying NaHCO3, Na2SO4, and mixed NaHCO3, Na2SO4 stresses, M. rosenbergii larvae were exposed to the above three stress conditions, followed by total RNA extraction and high-throughput sequencing at eight distinct time points (0, 4, 8, 12, 24, 48, 72, and 96 h). Subsequent analysis revealed 13, 16, and 13 consistently identified differentially expressed genes (DEGs) across eight time points under three stress conditions. These consistently identified DEGs were significantly involved in the Gene Ontology (GO) terms of chitin-based cuticle development, protein-carbohydrate complex, structural constituent of cuticle, carnitine biosynthetic process, extracellular matrix, and polysaccharide catabolic process, indicating that alkaline stresses might potentially impact the energy metabolism, growth, and molting of M. rosenbergii larvae. Particularly, the transcriptome data revealed that DEGs associated with energy metabolism, immunity, and amino acid metabolism were enriched across multiple time points under three stress conditions. These DEGs are linked to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including glycolysis/glucogenesis, amino sugar and nucleotide sugar metabolism, and lysine degradation. Consistent enrichment findings across the three stress conditions support conclusions above. Together, these insights are instrumental in enhancing our understanding of the molecular mechanisms underlying the alkaline response in M. rosenbergii larvae. Additionally, they offer valuable perspectives on the regulatory mechanisms of freshwater crustaceans amid saline-alkaline water development.

pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain.

Strict homeostatic control of pH in both intra- and extracellular compartments of the brain is fundamentally important, primarily due to the profound impact of free protons ([H+]) on neuronal activity and overall brain function. Astrocytes, crucial players in the homeostasis of various ions in the brain, actively regulate their intracellular [H+] (pHi) through multiple membrane transporters and carbonic anhydrases. The activation of astroglial pHi regulating mechanisms also leads to corresponding alterations in the acid-base status of the extracellular fluid. Notably, astrocyte pH regulators are modulated by various neuronal signals, suggesting their pivotal role in regulating brain acid-base balance in both health and disease. This review presents the mechanisms involved in pH regulation in astrocytes and discusses their potential impact on extracellular pH under physiological conditions and in brain disorders. Targeting astrocytic pH regulatory mechanisms represents a promising therapeutic approach for modulating brain acid-base balance in diseases, offering a potential critical contribution to neuroprotection.