Potassium citrate and metabolic acidosis in children with epilepsy on the ketogenic diet: a prospective controlled study.

AIM: To investigate if potassium citrate, a mild alkaline compound, can prevent metabolic acidosis in children with epilepsy treated with the ketogenic diet without reducing antiepileptic efficacy. METHOD: In this prospective controlled study, we investigated the frequency of initial uncompensated metabolic acidosis in 51 participants. There were 22 participants with and 29 without potassium citrate supplementation. The ketogenic diet was used as add-on treatment to children with drug resistant epilepsy. We also estimated the proportion of participants with a greater than 50% seizure reduction after 7 months. RESULTS: None of the 22 participants (15 males, seven females; median age 1y 7mo, interquartile range [IQR] 3y 3mo) with, and 10 of 29 (12 males, 17 females; median age 6y 1mo, IQR 4y 8mo) without potassium citrate developed metabolic acidosis (odds ratio=0.04, 95% CI 0.00-0.75 [p<0.01]); median pH 7.32 vs 7.24; [p<0.001]), and median bicarbonate 19.7mmol/L vs 14.0mmol/L (p<0.001). The number of seizures was reduced by more than 50% in 9 of 22 with potassium citrate and 8 of 29 participants without potassium citrate, 7 months after introducing a ketogenic diet (p=0.4). INTERPRETATION: In the ketogenic diet, potassium citrate supplementation can prevent metabolic acidosis, without reducing antiepileptic efficacy. WHAT THIS PAPER ADDS: Citrate supplementation prevents metabolic acidosis in children treated with a ketogenic diet. Efficacy of the ketogenic diet is not affected by supplementation with citrate. Citrate supplementation does not affect beta-hydroxybuturate concentration. Potassium citrate reduces the time needed to reach an optimal ketogenic ratio. This article is commented on by Schoeler on page 8 of this issue.

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats.

BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

Influence of electro-activated solutions of weak organic acid salts on microbial quality and overall appearance of blueberries during storage.

The aim of this work was to study the potential of diluted electro-activated solutions of weak organic acid salts (potassium acetate, potassium citrate and calcium lactate) to extend the shelf life of blueberries during post-harvest storage. The sanitizing capacity of these solutions was studied against pathogenic bacteria Listeria monocytogenes and E. coli O157:H7 as well as phytopathogenic fungi A. alternata, F. oxysporum and B. cinerea. The results showed that a 5-min treatment of inoculated blueberries with electro-activated solutions resulted in a 4 log CFU/g reduction in Listeria monocytogenes for all solutions. For E. coli O157:H7, the electro-activated potassium acetate and potassium citrate solutions achieved a decrease of 3.5 log CFU/g after 5 min of berry washing. The most important fungus reduction was found when blueberries were washed with an electro-activated solution of potassium acetate and a NaOCl solution. After 5 min of blueberry washing with an electro-activated potassium acetate solution, a very high reduction effect was observed for A. alternata, F. oxysporum and B. cinerea, which showed survival levels of only 2.2 ± 0.16, 0.34 ± 0.15 and 0.21 ± 0.16 log CFU/g, respectively. Regarding the effect of the washing on the organoleptic quality of blueberries, the obtained results showed no negative effect on the product color or textural profile. Finally, this work suggests that washing with electro-activated solutions of weak organic acid salts can be used to enhance the shelf-life of blueberries during post-harvest storage.

Effect of electro-activated aqueous solutions, nisin and moderate heat treatment on the inactivation of Clostridium sporogenes PA 3679 spores in green beans puree and whole green beans.

In this work, the synergistic effect of electro-activated solutions (EAS) of potassium acetate and potassium citrate, nisin and moderate heat treatment to inactivate C. sporogenes PA 3679 spores was evaluated in green beans puree and whole green beans. Electro-activated solutions (EAS) of potassium acetate and potassium citrate were generated under 400 mA during 60 min. They were characterized by an oxidation-reduction potential (ORP) and pH values ranged from +300 to +1090 mV and 2.8 to 3.67, respectively. Moreover, the EAS were combined with a bacteriocin nisin at concentrations of 250, 500, 750 and 1000 IU/mL and the targeted sporicidal effect was evaluated under moderate heat treatment. The inoculated mixtures were subjected to temperatures of 95, 105 and 115 °C for exposure times of 5, 15 and 30 min. After plate counting, the synergistic effect of the hurdle principle composed of electro-activated solutions, nisin and moderate temperatures was demonstrated. The obtained results showed that the synergistic effect of the used hurdle was able to achieve an inactivation efficacy of 5.9-6.1 log CFU/mL. Furthermore, experiments carried out with whole green beans showed that spore inactivation level was significantly higher and reach 6.5 log CFU/mL. Moreover, spore morphology was examined by transmission electron microscopy and the obtained micrographs showed important damages in all of the treated spores.

The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis.

UNLABELLED: The role of acid-base metabolism in bone health is controversial. In this meta-analysis, potassium bicarbonate and potassium citrate lowered urinary calcium and acid excretion and reduced the excretion of the bone resorption marker NTX. These salts may thus be beneficial to bone health by conserving bone mineral. INTRODUCTION: The role of acid-base homeostasis as a determinant of bone health and the contribution of supplemental alkali in promoting skeletal integrity remain a subject of debate. The objective of this study was, therefore, to conduct a meta-analysis to assess the effects of supplemental potassium bicarbonate (KHCO3) and potassium citrate (KCitr) on urinary calcium and acid excretion, markers of bone turnover and bone mineral density (BMD) and to compare their effects with that of potassium chloride (KCl). METHODS: A total of 14 studies of the effect of alkaline potassium salts on calcium metabolism and bone health, identified by a systematic literature search, were analysed with Review Manager (Version 5; The Cochrane Collaboration) using a random-effects model. Authors were contacted to provide missing data as required. Results are presented as the standardised (SMD) or unstandardized mean difference (MD) (95 % confidence intervals). RESULTS: Urinary calcium excretion was lowered by intervention with both KHCO3 (P = 0.04) and KCitr (P = 0.01), as was net acid excretion (NAE) (P = 0.002 for KHCO3 and P = 0.0008 for KCitr). Both salts significantly lowered the bone resorption marker NTX (P < 0.00001). There was no effect on bone formation markers or BMD. KHCO3 and KCitr lowered calcium excretion to a greater extent than did KCl. CONCLUSIONS: This meta-analysis confirms that supplementation with alkaline potassium salts leads to significant reduction in renal calcium excretion and acid excretion, compatible with the concept of increased buffering of hydrogen ions by raised circulating bicarbonate. The observed reduction in bone resorption indicates a potential benefit to bone health.

Kaliuresis and Intracellular Uptake of Potassium with Potassium Citrate and Potassium Chloride Supplements: A Randomized Controlled Trial.

BACKGROUND: A potassium replete diet is associated with lower cardiovascular risk but may increase the risk of hyperkalemia, particularly in people using renin-angiotensin-aldosterone system inhibitors. We investigated whether intracellular uptake and potassium excretion after an acute oral potassium load depend on the accompanying anion and/or aldosterone and whether this results in altered plasma potassium change. METHODS: In this placebo-controlled interventional cross-over trial including 18 healthy individuals, we studied the acute effects of one oral load of potassium citrate (40 mmol), potassium chloride (40 mmol), and placebo in random order after overnight fasting. Supplements were administered after a 6-week period with and without lisinopril pretreatment. Linear mixed effect models were used to compare blood and urine values before and after supplementation and between the interventions. Univariable linear regression was used to determine the association between baseline variables and change in blood and urine values after supplementation. RESULTS: During the 4-hour follow-up, the rise in plasma potassium was similar for all interventions. After potassium citrate, both red blood cell potassium-as measure of the intracellular potassium-and transtubular potassium gradient (TTKG)-reflecting potassium secretory capacity-were higher than after potassium chloride or potassium citrate with lisinopril pretreatment. Baseline aldosterone was significantly associated with TTKG after potassium citrate, but not after potassium chloride or potassium citrate with lisinopril pretreatment. The observed TTKG change after potassium citrate was significantly associated with urine pH change during this intervention ( R =0.60, P < 0.001). CONCLUSIONS: With similar plasma potassium increase, red blood cell potassium uptake and kaliuresis were higher after an acute load of potassium citrate as compared with potassium chloride alone or pretreatment with lisinopril. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Potassium supplementation in patients with chronic kidney disease and healthy subjects: effects on potassium and sodium balance, NL7618.

Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial.

BACKGROUND: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. METHODS: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. RESULTS: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. CONCLUSION: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR 1900023646.

Nerve-targeted desensitizing toothpastes occlude dentin tubules and induce mineral precipitation.

PURPOSE: To examine the laboratory dentin tubules occlusion and mineral precipitation capability of two potassium salts-containing desensitizing toothpastes. METHODS: 40 dentin disks were obtained and divided into four groups, including artificial saliva (AS), distilled water (DW), Sensodyne Freshmint (SF) and Colgate Sensitive (CS). Dentin permeability measurement was performed after EDTA etching, initial brush, 3-day brush, 7-day brush and citric acid challenge, respectively. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to monitor the variation of mineral content before and after treatments. The ultra-morphology of dentin surface was examined using scanning electron microscopy (SEM) to evaluate tubule occlusion. RESULTS: The two potassium salts-containing desensitizing toothpastes significantly reduced dentin permeability to less than 40% after 7-day treatment (P<0.05). The ATR-FTIR analysis showed increase of the intensity of the phosphate peak after a 7-day brushing period using both of the tested toothpastes. However, the dentin permeability significantly increased and the intensity of phosphate peak decreased after acid etching for all groups. The SEM examination revealed partially occluded dentin tubules after toothpaste treatments, but after the acid challenge the tubules were opened again.

Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial.

BACKGROUND: High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment. METHODS: This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance. RESULTS: A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (-9.19% in the ITT analysis, - 9.21% in the MITT analysis, and -9.73% in the PP analysis) was greater than the predefined non-inferiority margin of -10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P  < 0.001). Symptom improvement rates and patients' compliance were similar between the two groups. CONCLUSIONS: Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04678492.

Ethylene glycol induces calcium oxalate crystal deposition in Malpighian tubules: a Drosophila model for nephrolithiasis/urolithiasis.

Several animal species are used to study calcium oxalate urolithiasis; however, an ideal model has yet to be identified. We used Drosophila as a model organism and fed the flies lithogenic agents such as ethylene glycol, hydroxyl-L-proline, and sodium oxalate. At different times, the Malpighian tubules, the kidney equivalent of insects, were dissected and a polarized light microscope used to highlight the birefringent crystals. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed that the crystal composition was predominately calcium oxalate. Furthermore, administration of potassium citrate successfully reduced the quantity of and modulated the integrity of the ethylene glycol-induced crystals. Thus, the Drosophila model of bio-mineralization produces crystals in the urinary system through many lithogenic agents, permits observation of crystal formation, and is amenable to genetic manipulation. This model may mimic the etiology and clinical manifestations of calcium oxalate stone formation and aid in identification of the genetic basis of this disease.

Medullary sponge kidney: causes and treatments.

Medullary sponge kidney is a little known and little understood disease. A patient with a medullary sponge kidney may undergo decades of suffering in the form of infections and pain before any diagnosis is even made. When a diagnosis is made, it is more than likely to be an incidental finding from a test for another problem. However, on diagnosis there are a number of options available to treat this condition. These include non-invasive treatments such as drug therapy, diet or extracorporeal shock wave lithotripsy, to invasive therapies such as percutaneous nephrolithotomy, ureteroscopy and more advanced surgery. The aim of this article is to highlight this little known condition, outline the effects, and discuss the treatment options available to patients.

Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults.

A multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2-3 h and potassium bicarbonate up to 10-12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose-response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment.

Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

Long-term intake of a high-protein diet with or without potassium citrate modulates acid-base metabolism, but not bone status, in male rats.

High dietary protein intake generates endogenous acid production, which may adversely affect bone health. Alkaline potassium citrate (Kcit)(2) may contribute to the neutralization of the protein-induced metabolic acidosis. We investigated the impact of 2 levels of protein intake and Kcit supplementation on acid-base metabolism and bone status in rats. Two-month-old Wistar male rats were randomly assigned to 4 groups (n = 30 per group). Two groups received a normal-protein content (13%) (NP) or a high-protein (HP) content diet (26%) for 19 mo. The 2 other groups received identical diets supplemented with Kcit (3.60%) (NPKcit and HPKcit). Rats were pair-fed based on the ad libitum intake of the HP group. At 9, 16, and 21 mo of age, 10 rats of each group were killed. The HP diet induced a metabolic acidosis characterized by hypercalciuria, hypermagnesuria, and hypocitraturia at all ages. Kcit supplementation neutralized this effect, as evidenced by decreased urinary calcium and magnesium excretion by the HPKcit rats. Femoral bone mineral density, biomechanical properties, bone metabolism biomarkers (osteocalcin and deoxypyridinoline), and plasma insulin-like growth factor 1 levels were not affected by the different diets. Nevertheless, at 21 mo of age, calcium retention was reduced in the HP group. This study suggests that lifelong excess of dietary protein results in low-grade metabolic acidosis without affecting the skeleton, which may be protected by an adequate calcium supply.

Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs.

Although pH modification is one of the effective strategies for dissolving or preventing uroliths, little is known about its effects on the pharmacokinetics of phenobarbital in dogs. Five spayed, female Beagles were fed with a twice-daily diet that included potassium citrate and ammonium chloride for urine alkalinization and acidification, respectively. After a stabilizing period of 7 days, a single clinical dose of phenobarbital (3 mg/kg) was orally administered, and time-course changes in its serum and urine concentrations were determined by high-performance liquid chromatography. Total amounts of unchanged phenobarbital excreted into urine for 216 h were decreased by urine acidification and increased by urine alkalinization. The elimination half-life of serum phenobarbital in dogs with urine alkalinization was shortened and Cl(R) increased when compared with dogs with urine acidification. Other pharmacokinetic parameters, including C(max), T(max), AUC(0-216), Cl/F, and A(e0-216) were not changed by modification of the urine pH. These results suggest that the pH of urine is likely to be a determinant of the pharmacokinetics, especially urine excretion rate, of a clinical dose of oral phenobarbital. It is possible that the serum concentration of phenobarbital might be altered when a pH modifying-diet is administered for the purpose of dissolving or preventing uroliths.

The Impact of Thiazides and Potassium Citrate on Bone Mineral Density Evaluated by CT Scan in Stone Formers.

INTRODUCTION: Thiazides and citrate prevent kidney stones and improve bone mineral density (BMD). The objective of this study was to opportunistically utilize the noncontrast CT (NCCT) scan used for stone detection to identify those with low BMD and follow the impact of potassium citrate and thiazides on longitudinal BMD measurements. MATERIALS AND METHODS: A retrospective analysis was performed on 299 kidney stone patients treated with thiazides and/or potassium citrate for a minimum of 1 year. For each patient, BMD was estimated at L1 with CT attenuation measured in HU. A level of 160 HU was chosen to distinguish normal from low BMD. Pairwise t-test was used to compare the continuous outcomes before and after treatment for the whole cohort and the low BMD subgroup. Linear regression was performed to find if any association exists between the duration of follow-up and the changes in HU. A matched pair t-test was performed to compare among the medications used and the impact of their doses on the HU outcomes. RESULTS: Patients with low BMD (HU <160) comprised (n = 186, 62.2%) the cohort. A total of 16.1% normalized after 1 year of treatment and 68% had an increase in HU. The mean change in HU was 8.6 (p = 0.0001). Linear regression demonstrated no association between the duration of treatment and the HU changes (p = 0.64). Hydrochlorothiazide (HCTZ) 50 mg was more effective at improving BMD (HU +19.7, p = 0.04) compared with 25 mg (+2.9) or 12.5 mg (HU +6.4). Majority of the low BMD subgroup were either postmenopausal women (n = 88) or men with age older than 60 (n = 74) and both showed a significant increase in HU (3.125, 10.731), p-value (0.0453, 0.0007), respectively. CONCLUSION: Stone health and bone health are synergistic. The impact of thiazides and citrates on BMD can be monitored opportunistically with the NCCT scan.

Antiurolithiatic effect of the taraxasterol on ethylene glycol induced kidney calculi in male rats.

Taraxasterol is one of the important constituents of Taraxacum officinale L. (Compositae) with antioxidant potential. The present study was designed to evaluate and compare the antiurolithiatic effects of taraxasterol and potassium citrate in the ethylene glycol induced urolithiatic rat. Urolithiasis was induced by ammonium chloride and ethylene glycol in adult male rats. Taraxasterol (2, 4 and 8 mg/kg) and potassium citrate (2.5 g/kg) were treated for 33 days by gavage. Then, the animals were anesthetized and weighted and blood, urine, liver and kidney sampling were done. The kidney sections were prepared by hematoxylin & eosin staining. The liver and kidney coefficients, urine pH, calcium, magnesium, oxalate and citrate levels, serum albumin, calcium and magnesium levels, serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, superoxide dismutase and glutathione peroxidase activities in serum, kidney and liver, number of calcium oxalate crystal deposits, score of crystal deposits, score of histopathological damages and score of inflammation in kidney sections were evaluated. The results showed that taraxasterol decreased liver and kidney coefficients (p < 0.001), serum calcium (p < 0.01) level, serum alanine aminotransferase (p < 0.001), aspartate aminotransferase (p < 0.001), lactate dehydrogenase (p < 0.05) activities, urine magnesium (p < 0.05) and oxalate (p < 0.001) levels, number of crystal deposits (p < 0.001), score of crystal deposits (p < 0.01), score of histopathological damages (p < 0.001) and score of inflammation (p < 0.01) in kidney sections, while increased urine pH (p < 0.01), calcium (p < 0.001) and citrate (p < 0.05), serum magnesium (p < 0.001) and albumin (p < 0.01) levels, superoxide dismutase and glutathione peroxidase in serum (p < 0.01), kidney (p < 0.05 and p < 0.001, respectively) and liver (p < 0.01 and p < 0.001, respectively) tissue homogenates in treated urolithiatic rats in comparison to the control urolithiatic rats. The effect of potassium citrate is the same as taraxasterol in treated urolithiatic rats. In conclusion, the effect of taraxasterol could be by improving liver function, changing serum and urine parameters, maintaining the antioxidant environment, reducing crystal deposition, excretion of small deposits from kidney and reducing the chance of them being retained in the urinary tract.

Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

The extracellular acidic milieu in bones results in activation of osteoclasts (OC) and inhibition of osteoblasts (OB) causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate) has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4) versus acidic (pH 6.9) culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a) inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b) enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c) were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low-grade acidosis.

Effects of chemical additives on the fermentation quality and N distribution of alfalfa silage in south of China.

In order to better utilize the last cut alfalfa harvested before killing frost in a high moisture environment, the effects of chemical additives on the quality of alfalfa silage were studied in south of China. The alfalfa was freshly harvested at branching stage, and wilted by dry matter content of about 300 g/kg (fresh matter basis). Silage was prepared by using a small-scale silage fermentation system, where sucrose, potassium citrate, sodium carbonate, formic acid, acetic acid and propionic acid were used as silage additives, and no additives served as control. These silos were stored at ambient temperature (5-20°C), and the silage qualities were analyzed after 120 days of fermentation. All additive treatments affected the chemical composition and N distribution, increased the water-soluble content and crude protein contents, decreased non-protein nitrogen (NPN) content, and enhanced the in vitro ruminal dry matter digestibility (except for sodium carbonate). Silages treated with organic acids were preserved with significantly (P < 0.05) lower pH value, ethanol content and NPN content compared with control. When the fermentation quality, chemical composition and N distribution were considered, the treatment with sucrose or organic acids resulted in high quality of alfalfa silage ensiled before killing frost, with formic acid having the best effect.

Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet.

The amount of sodium chloride in the diet of industrialized nations far exceeds physiological requirements. The impact of abundant dietary salt on skeletal health has yet to be established, but is potentially detrimental through increased urinary calcium losses. We examined the effect of increased dietary sodium chloride on urine calcium excretion and bone turnover markers in postmenopausal women and, further, whether potassium citrate attenuates the effects of increased dietary salt. Postmenopausal women (n = 60) were adapted to a low-salt (87 mmol/d sodium) diet for 3 wk, then randomized to a high-salt (225 mmol/d sodium) diet plus potassium citrate (90 mmol/d) or a high-salt diet plus placebo for 4 wk. Urine calcium, urine N-telopeptide, urine cAMP, serum osteocalcin, and fasting serum PTH were measured at the end of the low- and high-salt diets. On the high salt plus placebo diet, urine calcium increased 42 +/- 12 mg/d (mean +/- SEM), but decreased 8 +/- 14 mg/d in the high salt plus potassium citrate group (P = 0.008, potassium citrate vs. placebo, unpaired t test). N-telopeptide increased 6.4 +/- 1.4 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus placebo group and 2.0 +/- 1.7 nanomoles bone collagen equivalents per millimole creatinine in the high salt plus potassium citrate group (P < 0.05, potassium citrate vs. placebo, unpaired t test). Osteocalcin, PTH, and cAMP were not significantly altered. The addition of oral potassium citrate to a high-salt diet prevented the increased excretion of urine calcium and the bone resorption marker caused by a high salt intake. Increased intake of dietary sources of potassium alkaline salts, namely fruit and vegetables, may be beneficial for postmenopausal women at risk for osteoporosis, particularly those consuming a diet generous in sodium chloride.