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\"The pH scale measures how acidic or basic a substance is, ranging from 0 to 14. Readers will learn how certain substances rank on the pH scale, what happens when acids and bases are mixed, and how water can make a substance either acidic or basic. These significant science concepts are discussed in clear and approachable text and supported by motivating fact boxes, charts, and images and photographs.\"-- Provided by publisher.

Abstract Context Elevated urine net acid excretion (NAE), indicative of subclinical metabolic acidosis, has been associated with higher bone turnover. Urine citrate, which is a common clinical measure, changes in response to acid-base status but its association with bone turnover is uncertain. Objective We evaluated the association between change in urine citrate and change in bone turnover and calcium excretion. Design, Intervention, and Participants A total of 233 healthy men and women ≥60 years old were randomly assigned to 1.0 mmol/kg/d potassium bicarbonate (KHCO3), 1.5 mmol/kg/d KHCO3, or placebo for 84 days. Outcome Measures Urine citrate, NAE, N-telopeptide of collagen type-I (NTX), calcium excretion, and serum amino-terminal propeptide of type 1 procollagen (P1NP) were measured before and after intervention. Results Urine citrate increased dose dependently after KHCO3 supplementation (P trend < 0.001). The urine citrate change was significantly inversely associated with P1NP change (P = 0.021) but not with change in NTX (P = 0.051) or calcium excretion (P = 0.652). The NAE change was positively associated with change in NTX and calcium excretion (P ≤ 0.003) but not with change in P1NP (P = 0.051). When the urine citrate change and NAE change were included in the same model, the urine citrate change was not associated with change in NTX, calcium excretion, or serum P1NP (P ≥ 0.086), whereas change in NAE remained associated with change in NTX and calcium excretion (P ≤ 0.003). Conclusion Urine citrate may not be a suitable alternative to NAE when assessing acid-base status in relation to bone turnover in older adults. In older adults, urine citrate excretion increased in response to alkali supplementation, but the change in urine citrate was not a robust indicator of change in bone resorption or calcium excretion.

Purpose. Coconut water has long been touted for its medicinal qualities including natural hydration. We sought to determine whether its consumption would induce changes to urinary lithogenic factors beyond changes in urine volume. Materials and Methods. After Institutional Review Board approval, volunteers with no prior history of nephrolithiasis were recruited. Each participant was randomized initially to either the coconut water or the water phase of the study. Participants kept meticulous food and fluid intake logs during the first phase of the study and were asked to replicate that diet for the second phase. For each phase the participant consumed 2L of either Taste of Nirvana® pure coconut water or tap water daily for four days. Participants were not restricted to consume additional fluid of their choice during their assigned study phase. During days 3 and 4 of each phase the participant collected a 24-hour urine specimen. Coconut water citrate and malate content were measured and were used along with the beverage pH to calculate the total alkali content of the coconut water. Supersaturation levels were calculated using Equil2. Nonparametric paired analysis using the Wilcoxon test was performed for statistical analysis. Results. There were 4 adult male and 4 adult female participants. Each individual’s 24-hour urine collection had a creatinine excretion within 20% of the mean for each subject’s four samples corroborating that all samples were collected properly. The two samples from each phase for each individual were averaged. The coconut water itself was also analyzed and it was calculated to have a total alkali content of 13.8 mEq/L. Consumption of coconut water significantly increased urinary citrate (29%, p=0.02), urinary potassium (130%, p=0.01), and urinary chloride (37%, p=0.03), without affecting urine pH (p=0.16) or volume beyond that of tap water (p=1.00). Conclusions. Coconut water consumption increases urinary potassium, chloride, and citrate in nonstone forming individuals.

Key Points The regulation of pH in tumours involves the interplay of several proteins, including: the carbonic anhydrases (EC 4.2.1.1) CA2, CA9 and CA12; the vacuolar ATPase (V-ATPase); anion exchangers AE1, AE2 and AE3; Na + /HCO 3 − co-transporters (NBCs); electroneutral Na + -driven Cl − /HCO 3 − exchanger (NDCBE); the monocarboxylate transporters MCT1, MCT2, MCT3 and MCT4; and Na + /H + exchanger 1, among others. The concerted action of these proteins maintains a slightly alkaline intracellular pH (pH i ) and an acidic extracellular pH (pH e ) within the tumours, which favours the growth and spread of the primary tumour, leading to the formation of metastases. The inhibition of one or more of these pH regulators with specific inhibitors causes both pH i and pH e values to return to normal, with the consequent impairment of tumour growth. This property represents an antitumour mechanism that is not exploited by the classical anticancer drugs. The inhibition of CA9 and/or CA12 with sulphonamide- or coumarin-based small-molecule inhibitors reverses the effects of tumour acidification, leading to inhibition of cancer cell growth in both primary tumours and metastases. Some of these compounds are in preclinical development. This effect can also be exploited for the imaging and treatment of tumours that overexpress CA9 or CA12. The same effect has been observed with antibodies targeting CA9 (and, more recently, also CA12). Some of these antibodies (for example, cG250) are in Phase III clinical development as antitumour and diagnostic agents. Some sulphonamides also inhibit anion exchangers, whereas proton pump inhibitors of the omeprazole type show antitumour effects by inhibiting V-ATPase, thus interfering with other tumour pH regulators. Potent, specific and non-toxic compounds as well as antibodies that interfere with these proteins may represent valuable new antitumour drugs. Changes in pH i towards basic values lead to the production of splice isoforms of extracellular matrix components at the tumour site, which are ideal targets for antibody-based pharmacodelivery strategies. The ability of tumour cells to maintain a slightly alkaline intracellular pH and an acidic extracellular pH aids the growth of primary tumours and the formation of metastases. Inhibiting pH-regulating proteins in tumours represents a novel therapeutic strategy that is not exploited by the classical anticancer drugs. The high metabolic rate of tumours often leads to acidosis and hypoxia in poorly perfused regions. Tumour cells have thus evolved the ability to function in a more acidic environment than normal cells. Key pH regulators in tumour cells include: isoforms 2, 9 and 12 of carbonic anhydrase, isoforms of anion exchangers, Na + /HCO 3 − co-transporters, Na + /H + exchangers, monocarboxylate transporters and the vacuolar ATPase. Both small molecules and antibodies targeting these pH regulators are currently at various stages of clinical development. These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy.

SummaryPotassium bicarbonate was administrated to an already alkaline diet in seven male subjects during a 21-day bed rest study and was able to decrease bed rest induced increased calcium excretion but failed to prevent bed rest-induced bone resorption.IntroductionSupplementation with alkali salts appears to positively influence calcium and bone metabolism and, thus, could be a countermeasure for population groups with an increased risk for bone loss. However, the extent to which alkalization counteracts acid-induced bone resorption or whether it merely has a calcium and bone maintenance effect is still not completely understood. In the present study, we hypothesized that additional alkalization to an already alkaline diet can further counteract bed rest-induced bone loss.MethodsSeven healthy male subjects completed two parts of a crossover designed 21-day bed rest study: bed rest only (control) and bed rest supplemented with 90 mmol potassium bicarbonate (KHCO3) daily.ResultsKHCO3supplementation during bed rest resulted in a more alkaline status compared to the control intervention, demonstrated by the increase in pH and buffer capacity level (pH p = 0.023, HCO3p = 0.02, ABE p = 0.03). Urinary calcium excretion was decreased during KHCO3 supplementation (control 6.05 ± 2.74 mmol/24 h; KHCO3 4.87 ± 2.21 mmol/24 h, p = 0.03); whereas, bone formation was not affected by additional alkalization (bAP p = 0.58; PINP p = 0.60). Bone resorption marker UCTX tended to be lower during alkaline supplementation (UCTX p = 0.16).ConclusionsThe more alkaline acid-base status, achieved by KHCO3 supplementation, reduced renal calcium excretion during bed rest, but was not able to prevent immobilization-induced bone resorption. However, advantages of alkaline salts on bone metabolism may occur under acidic metabolic conditions or with respect to the positive effect of reduced calcium excretion within a longer time frame.Trial registrationTrial number: NCT01509456

In a porcine cystic fibrosis model, lack of cystic fibrosis transmembrane conductance regulator (CFTR) is shown to result in acidification of airway surface liquid (ASL), and this decrease in pH reduces the ability of ASL to kill bacteria; the findings directly link loss of the CFTR anion channel to impaired defence against bacterial infection. Lung susceptibility to bacterial infection in cystic fibrosis The discovery of a link between cystic fibrosis and mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene has stimulated two decades of extensive research. As a result, the genetic, functional and cellular aspects of CFTR are well known. But despite these advances, it has proved impossible to relate the pathogenesis of bacterial lung infection, the major cause of morbidity and mortality in the disease, to the basic physiological abnormality — the loss of CFTR anion channels. The experiments reported here show that without CFTR, when airway epithelial HCO 3 secretion is defective, the pH of the airway surface liquid falls and inhibits antimicrobial function. This impairs the killing of bacteria that enter the lungs. Reducing the pH of the airway surface layer diminished bactericidal activity in wild-type pigs, whereas increasing the pH restored antimicrobial activity in pigs lacking CFTR . These findings link CFTR mutations to defective bacterial eradication, and suggest that increasing the pH of the airway surface liquid might prevent the initial infection in patients with cystic fibrosis. Cystic fibrosis (CF) is a life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene 1 . Although bacterial lung infection and the resulting inflammation cause most of the morbidity and mortality, how the loss of CFTR function first disrupts airway host defence has remained uncertain 2 , 3 , 4 , 5 , 6 . To investigate the abnormalities that impair elimination when a bacterium lands on the pristine surface of a newborn CF airway, we interrogated the viability of individual bacteria immobilized on solid grids and placed onto the airway surface. As a model, we studied CF pigs, which spontaneously develop hallmark features of CF lung disease 7 , 8 . At birth, their lungs lack infection and inflammation, but have a reduced ability to eradicate bacteria 8 . Here we show that in newborn wild-type pigs, the thin layer of airway surface liquid (ASL) rapidly kills bacteria in vivo , when removed from the lung and in primary epithelial cultures. Lack of CFTR reduces bacterial killing. We found that the ASL pH was more acidic in CF pigs, and reducing pH inhibited the antimicrobial activity of ASL. Reducing ASL pH diminished bacterial killing in wild-type pigs, and, conversely, increasing ASL pH rescued killing in CF pigs. These results directly link the initial host defence defect to the loss of CFTR, an anion channel that facilitates HCO 3 − transport 9 , 10 , 11 , 12 , 13 . Without CFTR, airway epithelial HCO 3 − secretion is defective, the ASL pH falls and inhibits antimicrobial function, and thereby impairs the killing of bacteria that enter the newborn lung. These findings suggest that increasing ASL pH might prevent the initial infection in patients with CF, and that assaying bacterial killing could report on the benefit of therapeutic interventions.

Background and Objective Dabigatran etexilate (DE) is an anticoagulant with proven efficacy and tolerability for stroke prevention in patients with non-valvular atrial fibrillation. For the commercial capsule, a complex formulation is used to maintain the acidic microenvironment required for maximal absorption. Consequently, its efficacy and safety are similar with or without concomitant intake of proton-pump inhibitors (PPIs). A simplified DE tablet formulation was developed and tested in two studies. One investigated bioequivalence (BE) of the novel DE tablet versus the commercial DE capsule. The other investigated DE bioavailability (BA) under pretreatment with the PPI rabeprazole and assessed the effect of elevated pH on exposure to dabigatran. Methods BE of the novel DE tablet versus the DE capsule was assessed in a randomized two-treatment, four-period, two-sequence crossover study (NCT03070171). The effect of rabeprazole on the BA of the DE tablet was assessed in an open-label, single-arm study (NCT03143166). Both studies were conducted at sites in Japan. Participants were healthy male volunteers, aged ≥ 20–40 years. In the BE study, participants received the DE tablet or capsule (single oral dose, 110 mg); primary endpoints were area under the concentration–time curve from baseline to the last quantifiable data point (AUC 0–tz ) and maximum plasma concentration ( C max ) of unconjugated dabigatran. In the relative BA study, participants received the DE tablet (single oral dose, 110 mg) with or without rabeprazole pretreatment (once daily for 5 days, 20 mg); primary endpoints were AUC 0–tz and C max of total dabigatran. Results In total, 160 participants were randomized in the BE study; 36 participants were enrolled in the BA study. The 90% confidence intervals of geometric mean (gMean) ratios for AUC 0–tz (101.4–116.0%) and C max (101.8–116.6%) of unconjugated dabigatran were within pre-defined acceptance criteria for BE. In the relative BA study, the gMeans of AUC 0–tz (667 to 192 ng h/mL) and C max (83.1 to 21.8 ng/mL) were decreased by approximately 70% when the tablet was administered under rabeprazole pretreatment. The reduction in BA was observed at a mean gastric pH of 5.3. Treatment was well tolerated; no deaths, serious adverse events (AEs) or significant AEs were reported in either study. Conclusion The DE tablet demonstrated BE to the capsule; however, at high gastric pH, BA of the tablet was reduced by approximately 70%, which may lead to reduced efficacy. Data indicate the importance of examining not only BE under standard conditions, but relative BA at elevated gastric pH. Such investigations may avoid the reduced BA at elevated pH that is quite common in the target population (the elderly and/or patients treated with gastric-acid modifying co-medications), and therefore reduce treatment failure with DE. Registration: ClinicalTrials.gov identifier numbers: NCT03070171, and NCT03143166

Aim: The aim of the study is to compare the anticariogenic effectiveness of Casein phosphopeptide- Amorphous Calcium phosphate (CPP-ACP) and xylitol chewing gums based on salivary pH, buffer capacity, and Streptococcus mutans levels. Materials and Methods: A group of twenty individuals in the age group of 18-25 years were randomly divided into two Groups A and B. Test arm A received xylitol gums and test arm B received CPP-ACP gums and they were instructed to use the gums thrice daily for 2 weeks. Unstimulated salivary samples were collected before they began the use of the gums for baseline values, 24 h after beginning the usage of chewing gums and at the end of 14 days. The samples were analyzed for pH, buffer capacity, and S. mutans levels. Results: A statistically significant reduction of salivary S. mutans levels, improvement in salivary pH, and buffer capacity were displayed in both groups 24 h and 14 days after the intervention when compared with baseline. Group B showed more statistically significant improvement in pH than group A after 24 h (P = 0.028) and at the end of 2 weeks (P = 0.041). Conclusion: CPP-ACP has better ability than xylitol in improving the pH of saliva. Both CPP-ACP and xylitol gums individually have remarkable ability in bringing down S. mutans levels while simultaneously improving the pH and buffer of saliva.

Previous evidence showed that use of phenylephrine was associated with higher umbilical artery pH (UA pH) than ephedrine after elective cesarean delivery (CD). However, the best choice of vasopressor and its effect on funic gases in cases of acute fetal compromise require additional studies. Ninety parturients showing acute fetal compromise during intrapartum period and taken up for CD (category II) under spinal anesthesia were randomized to receive prophylactic infusion of ephedrine 2.5mg/min or phenylephrine 30μg/min. Systolic blood pressure was targeted between 90% and 110% of baseline. Incidence of fetal acidosis (UA pH <7.2 and/or base deficit >12mmol/L) was recorded. Other parameters of cord gases, Apgar score, need for immediate resuscitation, maternal hemodynamics, and adverse events were also compared. Number of neonates showing acidosis with ephedrine or phenylephrine was comparable (P=.22). Of these, newborns with base deficit >12mmol had low 1-minute Apgar scores (n=15/23). The ephedrine group had higher oxygen content in UA (P=.03). There was no adverse neonatal outcome during the period of observation. Incidence of maternal nausea and vomiting was higher with ephedrine than with phenylephrine (22.2% vs 4.4%; P=.02). Maternal bradycardia was observed with phenylephrine (P=.02). Our data report similar fetal acidosis with either phenylephrine or ephedrine administered during spinal anesthesia for treating maternal hypotension in cases of emergency CD. •Fetal acidosis has been reported after spinal anesthesia.•Maintaining baseline blood pressure results in best neonatal outcome in elective CD.•Only retrospective data are available for CD indicated for acute fetal compromise.•We report fetal acidosis using vasopressor during CD for acute fetal compromise.

Background: Dental caries is a multifactorial disease in which microorganisms play an important role. Recently, herbs have been tried as mouthrinses to combat the side effects of chemical mouthrinses. The anticaries efficacy of Sodium fluoride, Tulsi leaf, and Black myrobalans fruit extracts on Streptococcus mutans (S. mutans) have been reported in the literature, but no comparative study has been done yet. Aim: This study aims to observe the change in the pH of saliva and to assess the efficacy of the herbal rinses-Tulsi and Black myrobalans on S. mutans count while comparing it with Sodium fluoride mouthrinse. Methods: Herbal ethanolic extracts of Tulsi (4%) and Black myrobalans (2.5%) were prepared as mouthrinses and compared with sodium fluoride mouthrinse (0.05%). Sixty high caries risk patients were selected and allocated randomly into three groups [n = 20], categorized as Group A-Sodium fluoride mouthrinse, Group B-Tulsi mouthrinse, and Group C-Black myrobalans mouthrinse. They were instructed to rinse their mouth with their assigned mouthrinses for 7 days. Salivary samples were collected and sent to the laboratory at baseline, 1 h postrinsing and after 7th day of rinsing for determining the salivary pH and S. mutans count. The increase in pH and reduction of S. mutans were determined. The values obtained were tabulated and statistically analyzed. Results: There was a significant increase in the salivary pH and reduction in S. mutans count after rinsing in all the three groups. Increase in salivary pH was more in the Sodium fluoride mouthrinse when compared to the experimental herbal groups (Group B and Group C). While S. mutans counts reduced more with Tulsi mouthrinse at 1 h postrinsing and after the 7th day of rinsing more reduction was seen in Black myrobalans mouthrinse group. Conclusion: The results of the study suggest that herbal mouthrinses could be tried as an adjunctive anticaries agent against dental caries causing microorganisms.