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Background: Metabolic acidosis accelerates the progression of chronic kidney disease (CKD) and increases the mortality rate. Whether oral alkali drug therapy benefits pre-dialysis CKD patients is controversial. We performed a meta-analysis of the effects of oral alkali drug therapy on major clinical outcomes in pre-dialysis CKD patients., Methods: We systematically searched MEDLINE using the Ovid, EMBASE, and Cochrane Library databases without language restriction. We included all eligible clinical studies that involved pre-dialysis CKD adults and compared those who received oral alkali drug therapy with controls., Results: A total of 18 eligible studies, including 14 randomized controlled trials and 4 cohort studies reported in 19 publications with 3695 participants, were included. Oral alkali drug therapy led to a 55% reduction in renal failure events (relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.25-0.82), a rate of decline in the estimated glomerular filtration rate (eGFR) of 2.59 mL/min/1.73 m 2 per year (95% CI, 0.88-4.31). There was no significant effect on decline in eGFR events (RR: 0.34; 95% CI: 0.09-1.23), proteinuria (standardized mean difference: -0.32; 95% CI: -1.08 to 0.43), all-cause mortality events (RR: 0.90; 95% CI: 0.40-2.02) and cardiovascular (CV) events (RR: 1.03; 95% CI: 0.32-3.37) compared with the control groups., Conclusion: Based on the available and low-to-moderate certainty evidence, oral alkali drug therapy might potentially reduce the risk of kidney failure events, but no benefit in reducing all-cause mortality events, CV events, decline in eGFR and porteninuria.

Low urine pH is a metabolic risk factor for stone formation. While medical therapy is typically prescribed (as urinary alkalinization), patients typically prefer dietary modifications. We aimed to assess capacity to alter urine pH with dietary management alone. We analyzed a retrospective cohort of stone formers seen between 2000 and 2015 with multiple 24-h urine collections (24hUC). Patients ≥ 18 years old with low urine pH (< 6.0) were included; those prescribed alkalinizing agents or thiazides were excluded. Demographic data, 24hUC parameters, and medications were abstracted. 24hUC was utilized to calculate gastrointestinal alkali absorption (GIAA). The primary outcome was urine pH ≥ 6.0 on second 24hUC. Predictors were selected utilizing multivariable logistic regression. The database consisted of 2197 stone formers; 224 of these met inclusion criteria. On second 24hUC, 124 (55.4%) achieved a favorable pH ≥ 6.0. On univariable analysis, a second pH ≥ 6.0 was associated with high initial pH, low initial sulfate, younger age, increase in citrate/GIAA/urine volume, and decrease in ammonium (P < 0.02). On multivariable analysis, high initial pH (OR = 23.64, P < 0.001), high initial GIAA (OR = 1.03, P = 0.001), lower initial sulfate (OR = 0.95, P < 0.001), increase in urine volume (OR = 2.19, P = 0.001), increase in GIAA (OR = 8.6, P < 0.001), increase in citrate (OR = 2.7, P = 0.014), decrease in ammonium (OR = 0.18, P < 0.001), and younger age (OR = 0.97, P = 0.025) were associated with a second pH ≥ 6.0. The analysis demonstrated a corrected AUC of 0.853. These data suggest that certain dietary recommendations (increases in urine volume, citrate, GIAA, and decreased acid load) may normalize urine pH in a select group of patients. This may allow urologists to counsel patients with low urine pH on possibility of success with dietary modification alone.

Background and Objectives: Metabolic acidosis is associated with progression of CKD and has significant adverse effects on muscle and bone. A systematic review and meta-analysis was conducted to evaluate the benefits and risks of metabolic acidosis treatment with oral alkali supplementation or a reduction of dietary acid intake in those with CKD., Design, Setting, Participants, & Measurements: MEDLINE, Embase, and Cochrane CENTRAL were searched for relevant trials in patients with stage 3-5 CKD and metabolic acidosis (<22 mEq/L) or low-normal serum bicarbonate (22-24 mEq/L). Data were pooled in a meta-analysis with results expressed as weighted mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs), using a random effects model. Study quality and strength of evidence were assessed using Cochrane risk of bias and the Grading of Recommendations Assessment, Development and Evaluation criteria., Results: Fourteen clinical trials were included ( n =1394 participants). Treatment of metabolic acidosis with oral alkali supplementation or a reduction of dietary acid intake increased serum bicarbonate levels (14 studies, 1378 patients, mean difference 3.33 mEq/L, 95% CI, 2.37 to 4.29) and resulted in a slower decline in eGFR (13 studies, 1329 patients, mean difference -3.28 ml/min per 1.73 m 2 , 95% CI, -4.42 to -2.14; moderate certainty) and a reduction in urinary albumin excretion (very-low certainty), along with a reduction in the risk of progression to ESKD (relative risk, 0.32; 95% CI, 0.18 to 0.56; low certainty). Oral alkali supplementation was associated with worsening hypertension or the requirement for increased antihypertensive therapy (very-low certainty)., Conclusions: Low-to-moderate certainty evidence suggest that oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline and potentially reduce the risk of ESKD in patients with CKD and metabolic acidosis., (Copyright © 2019 by the American Society of Nephrology.)

Hydration is one of the most significant issues for combat sports as athletes often use water restriction for quick weight loss before competition. It appears that alkaline water can be an effective alternative to sodium bicarbonate in preventing the effects of exercise-induced metabolic acidosis. Therefore, the main aim of the present study was to investigate, in a double blind, placebo controlled randomized study, the impact of mineral-based highly alkaline water on acid-base balance, hydration status, and anaerobic capacity. Sixteen well trained combat sport athletes (n = 16), were randomly divided into two groups; the experimental group (EG; n = 8), which ingested highly alkaline water for three weeks, and the control group (CG; n = 8), which received regular table water. Anaerobic performance was evaluated by two double 30 s Wingate tests for lower and upper limbs, respectively, with a passive rest interval of 3 minutes between the bouts of exercise. Fingertip capillary blood samples for the assessment of lactate concentration were drawn at rest and during the 3rd min of recovery. In addition, acid-base equilibrium and electrolyte status were evaluated. Urine samples were evaluated for specific gravity and pH. The results indicate that drinking alkalized water enhances hydration, improves acid-base balance and anaerobic exercise performance., Competing Interests: The authors have declared that no competing interests exist.

Vesicoureteric reflux (VUR) is the most common congenital anomaly of the urinary tract that occurs in 30%-50% of children presenting with recurrent urinary tract infections. Long-standing untreated VUR results in renal scarring and hydronephrotic changes ultimately leading to chronic renal failure and arterial hypertension. However, it may also result in diffuse tubulopathy compromising the concentrating capacity of tubules and urinary acidification defects. Renal tubular dysfunction should be considered in all children with VUR presenting with failure to thrive, rickets, bony deformity/pain, hypokalemia, and metabolic acidosis. We report such a case of a 16-year-old male adolescent who presented with rickets, failure to gain weight and height, bony pains, and muscle weakness with a history of VUR. On investigation, he was found to have normal anion gap metabolic acidosis with hypokalemia suggestive of distal renal tubular acidosis. He responded well to oral alkali and potassium replacement therapy., Competing Interests: None declared.

Background: Tricyclic antidepressants (TCAs) are a major cause of fatal drug poisoning due to their cardiotoxicity. Alkalinization by sodium bicarbonate (NaHCO3) administration, the first-line therapy for TCA-induced cardiotoxicity, can occasionally yield insufficient efficacy in severe cases. Because most TCAs are highly lipophilic, lipid emulsion may be more effective than alkalinization. However, it remains to be determined whether lipid emulsion is more beneficial than alkalinization in reversing amitriptyline-induced cardiotoxicity., Methods: Hemodynamic variables were recorded from in vivo guinea pig models and Langendorff-perfused hearts. Whole-cell patch-clamp experiments were conducted on enzymatically isolated ventricular cardiomyocytes to record fast sodium currents (INa). Lipid solutions were prepared using 20% Intralipid. The pH of the alkaline solution was set at 7.55. We assessed the effect of lipid emulsion on reversing amitriptyline-induced cardiotoxicity, in vivo and in vitro, compared to alkalinization. The data were evaluated by Student t test, 1-way repeated-measures analysis of variance, or analysis of covariance (covariate = amitriptyline concentration); we considered data statistically significant when P < .05., Results: In the in vivo model, intervention with lipids significantly reversed the amitriptyline-induced depression of mean arterial pressure and prolongation of QRS duration on electrocardiogram more than alkalinization (mean arterial pressure, mean difference [95% confidence interval]: 19.0 mm Hg [8.5-29.4]; QRS duration, mean difference [95% confidence interval] -12.0 milliseconds [-16.1 to -7.8]). In the Langendorff experiments, perfusion with 1% and 2% lipid solutions demonstrated significant recovery in left ventricular developed pressure (LVdevP), maximum change rate of increase of LVdevP (dP/dtmax) and rate-pressure product compared with alkaline solution (LVdevP [mm Hg], alkaline 57 ± 35, 1% lipid 94 ± 12, 2% lipid 110 ± 14; dP/dtmax [mm Hg/s], alkaline 748 ± 441, 1% lipid 1502 ± 334, 2% lipid 1753 ± 389; rate-pressure product [mm Hg·beats·minute], alkaline 11,214 ± 8272, 1% lipid 19,025 ± 8427, 2% lipid 25,261 ± 4803 with analysis of covariance). Furthermore, lipid solutions (0.5%-4%) resulted in greater recovery of hemodynamic parameters at 3 μM amitriptyline. Amitriptyline inhibited INa in a dose-dependent manner: the half-maximal inhibitory concentration (IC50) was 0.39 μM. The IC50 increased to 0.75 μM in the alkaline solution, 3.2 μM in 1% lipid solution, and 6.1 μM in 2% lipid solution. Furthermore, the lipid solution attenuated the use-dependent block of sodium channels by amitriptyline more than alkaline solution. On 30 consecutive pulses at 1 Hz, the current decreased to 50.1 ± 2.1, 60.3 ± 1.9, and 90.4% ± 1.8% in standard, alkaline, and 1% lipid solution, respectively. Even 0.5% lipid solution showed greater effects than the alkaline solution in all experiments., Conclusions: Lipid emulsion significantly suppressed amitriptyline-induced INa, inhibition, which was likely related to the marked improvement in hemodynamic status observed in vivo and in isolated perfused hearts. These results suggest the superiority of lipid emulsion as the first-line therapy for TCA-induced cardiotoxicity compared to alkalinization therapy.

Western diet, high in protein-rich foods and poor in vegetables, is likely to be responsible for the development of a moderate acid excess leading to metabolism deregulation and the onset or worsening of chronic disturbances. Available findings seem to suggest that diets with high protein/vegetables ratio are likely to induce the development of calcium lithiasis, especially in predisposed subjects. Moreover, some evidence supports the hypothesis of bone metabolism worsening and enhanced bone loss following acid-genic diet consumption although available literature seems to lack direct and conclusive evidence demonstrating pathological bone loss. According to other evidences, diet-induced acidosis is likely to induce or accelerate muscle wasting or sarcopenia, especially among elderlies. Furthermore, recent epidemiological findings highlight a specific role of dietary acid load in glucose metabolism deregulation and insulin resistance. The aim of this review is to investigate the role of acid-genic diets in the development of the mentioned metabolic disorders focusing on the possible clinical improvements exerted by alkali supplementation.

Objective: To analyse the length and area of corneal surface occupied by vessels, and their location in an experimental model of alkali burn-induced corneal neovascularization., Methods: An injury to the central cornea of the right eye in 91 Sprague-Dawley rats was induced using a silver nitrate pencil. The rats were divided in 7 groups that were sacrificed 2, 4, 6, 8, 10, 12 and 14 days post-injury, and then perfused with a mixture of Chinese ink in PBS -phosphate buffer saline-. Corneas were flat-mounted processed and divided in 4 quadrants. Corneal neovascular growth parameters (length and area) and the location of these vessels were performed blind. The results were statistically analysed., Results: Neovascular growth was observed from day 2, reaching its maximum peak in length and area on the 12th day post-injury. A slight reduction in corneal neovascularization was observed after this day. The vessels were initially located in the middle third of the stroma and tended to be observed in the anterior third during the course of the experiment., Conclusions: Neovascularisation was observed on day 2 post-injury in all sectors of corneal surface. Neovascular growth was uniform during the experiment. Neovessels were located in the middle and anterior third of the cornea., (Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.)

Unlabelled: Conservation of muscle mass is important for fall and fracture prevention but further understanding of the causes of age-related muscle loss is required. This study found a more alkaline diet was positively associated with muscle mass in women suggesting a role for dietary acid-base load in muscle loss., Introduction: Conservation of skeletal muscle is important for preventing falls and fractures but age-related loss of muscle mass occurs even in healthy individuals. However, the mild metabolic acidosis associated with an acidogenic dietary acid-base load could influence loss of muscle mass., Methods: We investigated the association between fat-free mass (FFM), percentage FFM (FFM%) and fat-free mass index (FFMI, weight/height²), measured using dual-energy X-ray absorptiometry in 2,689 women aged 18-79 years from the TwinsUK Study, and dietary acid-base load. Body composition was calculated according to quartile of potential renal acid load and adjusted for age, physical activity, misreporting and smoking habit (FFM, FFMI also for fat mass) and additionally with percentage protein., Results: Fat-free mass was positively associated with a more alkalinogenic dietary load (comparing quartile 1 vs 4: FFM 0.79 kg P < 0.001, FFM% 1.06 % <0.001, FFMI 0.24 kg/m² P = 0.002), and with the ratio of fruits and vegetables to potential acidogenic foods., Conclusions: We observed a small but significant positive association between a more alkaline diet and muscle mass indexes in healthy women that was independent of age, physical activity and protein intake equating to a scale of effect between a fifth and one half of the observed relationship with 10 years of age. Although protein is important for maintenance of muscle mass, eating fruits and vegetables that supply adequate amounts of potassium and magnesium are also relevant. The results suggest a potential role for diet in the prevention of muscle loss.

High sodium chloride (NaCl) intake can induce low-grade metabolic acidosis (LGMA) and may thus influence bone and protein metabolism. We hypothesized that oral potassium bicarbonate (KHCO(3)) supplementation may compensate for NaCl-induced, LGMA-associated bone resorption and protein losses. Eight healthy male subjects participated in a randomized trial with a crossover design. Each of two study campaigns consisted of 5 d of dietary and environmental adaptation followed by 10 d of intervention and 1.5 d of recovery. In one study campaign, 90 mmol KHCO(3)/d were supplemented to counteract NaCl-induced LGMA, whereas the other campaign served as a control with only high NaCl intake. When KHCO(3) was ingested during high NaCl intake, postprandial buffer capacity ([HCO(3)(-)]) increased (P = 0.002). Concomitantly, urinary excretion of free potentially bioactive glucocorticoids [urinary free cortisol (UFF) and urinary free cortisone (UFE)] was reduced by 14% [∑(UFF,UFE); P = 0.024]. Urinary excretion of calcium and bone resorption marker N-terminal telopeptide of type I collagen was reduced by 12 and 8%, respectively (calcium, P = 0.047; N-terminal bone collagen telopeptide, P = 0.044). There was a trend of declining net protein catabolism when high NaCl was combined with KHCO(3) (P = 0.052). We conclude that during high salt intake, the KHCO(3)-induced postprandial shift to a more alkaline state reduces metabolic stress. This leads to decreased bone resorption and protein degradation, which in turn might initiate an anticatabolic state for the musculoskeletal system in the long run.

Previous studies have shown anti-inflammatory potential of alkaline extract of the leaves of Sasa senanensis Rehder (SE). The aim of the present study was to clarity the molecular entity of SE, using various fractionation methods. SE inhibited the production of nitric oxide (NO), but not tumour necrosis factor-α by lipopolysaccharide (LPS)-stimulated mouse macrophage-like cells. Lignin carbohydrate complex prepared from SE inhibited the NO production to a comparable extent with SE, whereas chlorophyllin was more active. On successive extraction with organic solvents, nearly 90% of SE components, including chlorophyllin, were recovered from the aqueous layer. Anti-HIV activity of SE was comparable with that of lignin-carbohydrate complex, and much higher than that of chlorophyllin and n-butanol extract fractions. The CYP3A inhibitory activity of SE was significantly lower than that of grapefruit juice and chlorophyllin. Oral administration of SE slightly reduced the number of oral bacteria. When SE was applied to HPLC, nearly 70% of SE components were eluted as a single peak. These data suggest that multiple components of SE may be associated with each other in the native state or after extraction with alkaline solution.

Purpose: Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis., Materials and Methods: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient., Results: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist Orange, Diet 7Up, Sprite Zero, Diet Canada Dry Ginger Ale, Sierra Mist Free, Diet Orange Crush, Fresca and Diet Mountain Dew. Colas, including Caffeine Free Diet Coke, Coke Zero, Caffeine Free Diet Pepsi and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content., Conclusions: Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH., (Copyright 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A technology for the deposition of a persistent hydrophobicity to alkaline-color-treated weathered hair surfaces using 18-MEA (18-methyleicosanoic acid) is presented. Two approaches were examined in order to make 18-MEA bind tightly to the alkaline-color-treated weathered hair surface. One was to apply 18-MEA as an acid form and the other was to apply 18-MEA as a salt or complex. It was found that the combination of 18-MEA with specific cationic surfactants [stearoxypropyldimethylamine (SPDA) and docosyldimethylamine (DSDA)] makes the alkaline-color-treated weathered hair surface hydrophobic and that its hydrophobicity is maintained even after shampooing. Characterization of adsorbed layers of 18-MEA/SPDA on a mica surface, as a possible hydrophilic surface model, was performed using atomic force microscopy (AFM) and angle-resolved X-ray photoelectron spectroscopy (AR-XPS). The results revealed that 18-MEA/SPDA formed a layer with high wear resistance, with an alkyl chain, the hydrophobic moiety, oriented at an angle of around 25 degrees to the air interface.

This study aims to determine the effects of a high protein diet and alkaline supplementation on bone metabolic turnover in rats. Eight-week-old male Sprague-Dawley rats were investigated by bone status, including bone mineral density (BMD) and biomechanical markers from blood and urine. Thirty rats were randomly divided into three groups and treated for 8 weeks as follows: baseline control group (n. 10, C), high-protein supplemented diet group (n. 10, chronic acidosis, CA group) and supplemented chronic acidosis (n.10, SCA). Diet-treated rats were fed an acidic high-protein diet and the supplementation consisted in a modified alkaline formula (Basenpulver, NaMed, Italy). At the end of the experimental period, the rats were sacrificed, blood samples were drawn and femur and tibia were removed for analysis of bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA). In the CA group, 24-hour urinary calcium (Ca) and phosphorus (P) excretion were increased 2.1-fold (p<0.05 vs normal diet controls) as well as kidney weight. However, serum Ca and P concentration, as well as urinary Dpd excretion were not significantly changed. Femural and tibial BMD was significantly decreased in the CA group (p<0.05), but alkaline supplementation prevented such phenomenon (p<0.05 vs CA). These results suggest that blood Ca and P concentrations in chronic acidosis condition during the 12-week supplementation might be maintained by hypercalciuria and hyperphosphaturia at the expenses of bone structure. However, modified alkaline supplementation is able to prevent such derangements.

Background: The authors provide an overview of chewing gum as a delivery vehicle for dental-protective agents, highlighting xylitol and its potential application in caries-prevention programs for children., Types of Studies Reviewed: The authors reviewed selected clinical investigations and previous reviews associated with chewing gum containing substances such as calcium, bicarbonate, carbamide, chlorhexidine, fluoride and xylitol and their effects on reducing caries. They searched the MEDLINE database by using the key words "dental caries," "oral health," "calcium," "bicarbonate," "carbamide," "chlorhexidine," "fluoride" and "xylitol.", Results: Chewing gum is being used as a delivery vehicle for substances such as calcium, bicarbonate, carbamide, chlorhexidine, fluoride and xylitol to improve oral health and reduce caries. These substances exhibit properties that are protective of the oral environment and mediate common oral diseases. The debate for advocating xylitol use in caries prevention is advancing; however, chewing gum use by young schoolchildren in the United States is hindered by choking hazard concerns and lack of specific xylitol dosing recommendations., Clinical Implications: The use of chewing gum containing dental-protective substances, particularly xylitol, in caries-prevention programs can reduce the tooth decay epidemic. Chewing gum use by children in the school setting should be reconsidered.

Medical treatment of cystinuria is often disappointing. Patients undergo frequent surgery, which is often followed by early relapse. The aim of our study was to evaluate the efficacy of medical treatment of cystinuria, to prevent formation or to reduce the numbers and dimensions of renal stones. Twenty cystinuric patients were treated with a combined approach, including cystine-binding drugs. Free and bound urine cystine levels were measured every 4 months. Drug dosage was adjusted to maintain free urine cystine level below 100 micromol/mmol creatinine. Eighteen patients completed the study; detection of new stones was reduced from 0.28 per year to 0.03 per year, and, in six patients, the numbers and dimensions of pre-existing renal stones were reduced. Surgery was required in one subject, and no relapse was observed 12 months afterwards. The dosage required to achieve target levels was closely correlated with patient body weight: older children required a lower dose. Medical management of cystinuria is feasible. The treatment must be personalised in children, as the amount of drug required is strictly dependent on body size.

Focal necrotizing encephalitis due to Toxoplasma gondii infection represents one of the most common opportunistic infection in patients with the acquired inmunodeficiency syndrome (AIDS), and the treatment is commonly with a combination sulphadiazine, and pyrimethamine. A major side effect of sulfadiazine therapy is the occurrence of crystallization in the urinary collecting system. We report a patient with AIDS and Toxoplasmic encephalitis treated with sulfadiazine who developed acute renal failure. Renal ultrasound demonstrated echogenic areas within the renal parenchyma, presumed to be sulfa crystals. Renal failure and ultrasound findings resolved rapidly with hydratation and administration of alkali. Patients infected with AIDS frequently have characteristic that increase intratubular crystal precipitation and they require treatment with one or more of the drugs that are associated with crystal-induced renal failure. Controlled alkalinization of the urine and high fluid intake are recommended for prophylaxis of crystalluria. The literature concerning crystalluria and renal failure due to sulfadiazine is reviewed.

Previous studies have shown that the anionic alkali mineral complex BARODON has an immunoenhancing effect on pigs as an adjuvant and as a nonspecific immunostimulant. Likewise, the equine immune system has been defined with various monoclonal antibodies specific to equine leukocyte differentiation antigens to determine the possibility of enhancing equine resistance to respiratory diseases and promoting other immunostimulatory effects with the application of BARODON. Compared with the control group, after 3 weeks of treatment, BARODON-treated groups showed higher proportions of cells (P < 0.05) expressing major histocompatibility complex class II and CD2, CD4(+), CD4(+) CD25(+), CD8(+), and CD8(+) CD25(+) T lymphocytes, dendritic cells, and surface immunoglobulin M(+) B lymphocytes in peripheral blood, as well as enhanced cell proliferative responses with phytohemagglutinin and increased phagocytic activity against Streptococcus equi and Staphylococcus aureus strains with high antibiotic resistance, the bacteria frequently identified as etiologic agents of equine respiratory diseases at the Seoul Race Park in Seoul, Korea. This study shows that BARODON may act as an immunostimulator and can be an effective alternative to antimicrobial feed additives for nonspecific improvements in equine immune responses, particularly against respiratory diseases.

Intrinsic defects in tubular transport mechanisms of the kidney may cause impairment of urinary acidification or a loss of base equivalents, thereby inducing systemic metabolic acidosis. Different types of this disorder termed renal tubular acidosis (RTA) can be distinguished based on the localization of the disturbance along the nephron (proximal vs. distal) and their association with potassium transport (hypo-/hyperkalemic). Except for the proximal type RTA results in positive acid balance and negatively impacts on bone metabolism and the formation of kidney stones. The diagnosis is based on analysis of acid/base status, urinary pH and determination of ammonium excretion after an oral acid load. Both functional defects of specific tubular transport mechanisms and global impairment of renal tubular function can be causative of RTA. Their therapy is based on treatment of the primary disease process and correction of acidosis by alkali supplementation.

Potassium and sodium containing nanoapatite cements were produced by the reaction of mechanically activated CaNaPO(4) (CSP), CaKPO(4) (CPP) and Ca(2)KNa(PO(4))(2) (CPCP) with a 2.5% Na(2)HPO(4) solution. The cements exhibited clinically acceptable setting times of approximately 5 min and compressive strengths of 5-10 MPa. The antimicrobial properties of the cements were tested with the agar diffusion test using Streptococcus salvarius, Staphylococcus epidermis and Candida albicans. All types of alkali ion containing cements showed a significantly higher antimicrobial potency with inhibition zones of approx. 4-11 mm than a commercial calcium hydroxide cement which resulted in small inhibition zones around the cement samples of a maximum of 1.5 mm. The antimicrobial properties of all the cements were not found to diminish even after longer incubation times. This behaviour was attributed to the formation of soluble alkaline metal phosphates during setting which increased the pH value in the agar gel around the alkali containing calcium phosphate cement to 8.5-10.7 compared to 6.5-8.0 for the Ca(OH)(2) product. The high antimicrobial potency of alkali-calcium phosphate cements may find an application in dentistry as pulp capping agents, root fillers or cavity liners.

In 2 women with distal renal tubular acidosis and osteomalacia, alkali treatment cured the bone disease and was accompanied by marked increases in the serum 1,25 dihydroxyvitamin D concentration, without a significant change in the 25-hydroxyvitamin D concentration., (Copyright 2005 S. Karger AG, Basel.)

Background: Ingestion of caustic substances often leads to severe morbidity and, frequently, death. This study compared complications and survival for patients who ingested an acidic substance, mainly glacial acetic acid, or an alkaline agent., Methods: Records for 179 patients hospitalized for ingestion of a caustic agent (85 acid [75 glacial acetic acid], 94 alkali) were reviewed. Mucosal injury, systemic and GI complications, and survival were scored., Results: Outcome was less favorable for patients who ingested acid compared with those who ingested alkali with respect to mucosal injury (median: grade 2 vs. grade 1; p=0.013), hospital stay (mean: 9.9 vs. 7.2 days; p=0.01), admittance to the intensive care unit (44% vs. 22%; p=0.002), systemic complications (24% vs. 3%; p < 0.001), perforation (6% vs. 0%; p=0.017), and mortality (14% vs. 2%; p=0.003). There was no difference in the development of strictures (acid, 15% vs. alkali, 17%). The grade of mucosal injury at endoscopy was the strongest predictive factor for the occurrence of systemic and GI complications and mortality (relative risk 9: 95% CI[3, 30]). Ten of 29 (34%) patients with strictures were treated by endoscopic dilation alone, whereas the others primarily (n=7) or secondarily (n=11) underwent surgery. One patient with an esophageal stricture died from systemic complications., Conclusions: Acid ingestion, particularly glacial acetic acid, is associated with a higher frequency of complications and mortality rate than alkali ingestion. Early endoscopy probably is safe and provides important prognostic information. Endoscopic treatment of caustic-induced strictures is only moderately successful.

Because of its officinal value, strychnos is widely used by clinic and individual. Since toxic dose and therapeutic dose are very close, strychnos poisoning cases are frequently reported. In this paper the chemical component, toxic dose, mechanisms of toxicity, poisoning symptom and pathological changes after strychnos poisoning are reviewed.

Our objective was to describe the process of alkali disposal in rats. Balance studies were performed while incremental loads of alkali were given to rats fed a low-alkali diet or their usual alkaline ash diet. Control groups received equimolar NaCl or KCl. Virtually all of the alkali was eliminated within 24 h when the dose exceeded 750 micromol. The most sensitive response to alkali input was a decline in the excretion of NH(4)(+). The next level of response was to increase the excretion of unmeasured anions; this rise was quantitatively the most important process in eliminating alkali. The maximum excretion of citrate was approximately 70% of its filtered load. An even higher alkali load augmented the excretion of 2-oxoglutarate to >400% of its filtered load. Only with the largest alkali load did bicarbonaturia become quantitatively important. We conclude that renal mechanisms eliminate alkali while minimizing bicarbonaturia. This provides a way of limiting changes in urine pH without sacrificing acid-base balance, a process that might lessen the risk of kidney stone formation.

The urine-acidifying properties of food constituents depend on their content of non-oxidizable acids or precursors. Acidifying constituents such as animal proteins may negatively affect calcium metabolism and accelerate bone resorption, thus representing an aggravating factor for osteoporosis. This four-period, double-crossover study investigated whether a diet intervention specifically focused on acid load could modify calcium metabolism in humans. Eight healthy volunteers underwent a four-day metabolic preparation with two types of diets, one rich in acid ash-forming nutrients, and one providing base-forming nutrients (including bicarbonate-rich mineral water), both having similar contents of calcium, phosphate, sodium, proteins and calories. On the fourth day, a single oral dose of 1 g calcium was given, either as carbonate or as gluconolactate. Serial blood and urine samples revealed that the diet affected blood pH (average difference 0.014, p=0.002) and urine pH (average difference 1.02, p<0.0001) in the expected direction, but had no influence on the absorption of the calcium supplement. The acid-forming diet increased urinary calcium excretion by 74% when compared with the base-forming diet (p<0.0001), both at baseline and after the oral calcium load, and C-telopeptide excretion by 19% (p=0.01), suggesting a skeletal origin for the excess calcium output. This observation confirms that renally excreted acids derived from food influence calcium metabolism, and that alkalizing nutrients inhibit bone resorption. Further studies are needed to determine the clinical impact of dietary counseling for avoiding diet acids as a preventive measure against osteoporosis.

Alkalinizing action on root dentin was investigated by treating the enlarged root canals of a total of 120 extracted teeth for 24 h, 3 days, or 7 days with either gutta-percha points (size 40) containing calcium hydroxide or an equivalent quantity of aqueous calcium hydroxide suspension. After splitting the teeth longitudinally the pH of the dentin was determined using a pH microelectrode in small cavities at each of four set measuring points. The gutta-percha points were unable to alkalinize the root dentin over a period of 7 days. Clear, rapid, and prolonged alkalinization of the dentin extending through to the root surface was achieved, however, with the aqueous calcium hydroxide suspension.

The doses of lidocaine used for lipoplasty often exceed what is commonly recommended for other surgical procedures. When using these high volumes of lidocaine and wetting solutions, a variety of safety issues must be considered. The author knows of no other plastic surgery operation in which the safety of the procedure is so influenced by the medications administered. Each component of the wetting solution--the alkalized fluid, the epinephrine, and the lidocaine--has an individual and interrelated role. The absorption of lidocaine with epinephrine after subcutaneous installation for lipoplasty probably represents a unique situation, and the concepts presented should not necessarily be extrapolated to other types of procedures.

Five strains of lithotrophic, nitrite-oxidizing bacteria (AN1-AN5) were isolated from sediments of three soda lakes (Kunkur Steppe, Siberia; Crater Lake and Lake Nakuru, Kenya) and from a soda soil (Kunkur Steppe, Siberia) after enrichment at pH 10 with nitrite as sole electron source. Morphologically, the isolates resembled representatives of the genus Nitrobacter. However, they differed from recognized species of this genus by the presence of an additional S-layer in their cell wall and by their unique capacity to grow and oxidize nitrite under highly alkaline conditions. The influence of pH on growth of one of the strains (AN1) was investigated in detail by using nitrite-limited continuous cultivation. Under such conditions, strain AN1 was able to grow at a broad pH range from 6.5 to 10.2, with an optimum at 9.5. Cells grown at pH higher than 9 exhibited a clear shift in the optimal operation of the nitrite-oxidizing system towards the alkaline pH region with respect to both reaction rates and the affinity. Cells grown at neutral pH values behaved more like neutrophilic Nitrobacter species. These data demonstrated the remarkable potential of the new nitrite-oxidizing bacteria for adaptation to varying alkaline conditions. The 16S rRNA gene sequences of isolates AN1, AN2, and AN4 showed high similarity (> or = 99.8%) to each other, and to sequences of Nitrobacter strain R6 and of Nitrobacter winogradskyi. However, the DNA-DNA homology in hybridization studies was too low to consider these isolates as new strains. Therefore, the new isolates from the alkaline habitats are described as a new species of the genus Nitrobacter, N. alkalicus, on the basis of their substantial morphological, physiological, and genetic differences from the recognized neutrophilic representatives of this genus.

The reperfusion of a limb which has been submitted to a severe and prolonged period of ischemia may be followed by dramatic local and systemic complications. The results of several experimental studies have given insights on the biochemical and physiopathological alterations occurring in the ischemic and reperfused skeletal muscle. Therefore the technique of the controlled limb reperfusion has been developed. we present the results obtained in two patients with this technique. Two patients were admitted for a limb-threatening ischemia consecutive to embolism. After removal of the thrombi with a Fogarty's catheter and before reperfusion with the normal blood, a controlled limb reperfusion was performed by mixing the systemic blood with a crystalloid solution in order to obtain a hyperosmolar, hypocalcemic, alcalotic and substrate-enriched (aspartate and glutamate) reperfusate. This reperfusate was infused during 30 min with a roller pump into the deep and superficial femoral arteries. The delivery conditions (temperature, flow and reinjection pressure) were closely monitored. In both cases, no post-operative complication was observed and the pedal pulses were restored after the operation. Complete recovery of the motor and sensitive functions were observed and the patient were discharged at the 10th post-operative day.

Background: Pulmonary hypertension is responsible for a substantial part of perioperative and postoperative mortality and morbidity after cardiac transplantation. Treatment of right ventricular failure after increased pulmonary vascular resistance is difficult especially in infants and children. Therefore we started a preventive therapy of pulmonary hypertension after cardiac transplantation to avoid right ventricular failure and compared the results with a group of patients with conventional therapy., Methods: Group 1 (n = 13), with transplantation from 1988 to 1991, was treated with vasodilators when symptoms of right ventricular failure developed. Group 2 (n = 19) had preventive treatment with prostaglandin E1 (PGE1), the phosphodiesterase-III inhibitor enoximone, and alkalinazation starting during weaning from cardiopulmonary bypass., Results: Six patients in group 1 died; four of them as the result of right ventricular failure in the immediate postoperative course despite aggressive treatment. In group 2 there were three deaths as the results of rejection (2) and infection (1). None of these patients developed right ventricular failure (p = 0.02). Cold ischemic time, extracorporeal circulation time, and waiting time before transplantation were significantly longer in group 2. Side effects of this preventive therapy were not observed., Conclusions: We conclude that prophylactic therapy of pulmonary hypertension with vasodilators in infants and children after heart transplantation is safe and effective in preventing right ventricular failure in the postoperative course.

Background: Previous reports have suggested that sequential applications of sodium fluorescein (NaF) to the ocular surface cause loss of epithelial cells. In those experiments the solutions were free of preservatives, but delivered a hypertonic and alkaline load. It is possible that either the hyperosmolarity, NaF, and/or alkalinity may have contributed to the epithelial cell loss. Our study explored the possible impact of these three factors on epithelial integrity., Methods: We used a paradigm in which we designed four test solutions to isolate the cytotoxic effects of the three factors. Fifteen subjects were exposed to one of the solutions on separate visits. One solution was instilled in both eyes, every 3 min, for a total of seven applications, and a slitlamp examination was performed. Staining was graded on a scale of 0 to 3 for each of five corneal sectors., Results: Application of solution 1 (NaF, hyperosmotic, and alkaline) resulted in staining for all subjects. For the other three solutions (without NaF), insignificant staining occurred., Conclusions: The epithelium tolerates changes in pH and osmolarity between 7.2 to 7.8 and 290 to 350, respectively. However, NaF when applied in multiple doses may be cytotoxic.

The purpose of this study was to evaluate the plasma potassium (K+) response after administration of tromethamine (THAM) or sodium bicarbonate (NaHCO3) in an acidotic rabbit model. Eighteen healthy, adult female New Zealand White rabbits were subjected to severe hypoxia until a base deficit of -10 mEq/L resulted. Rabbits were then randomized to receive THAM solution, NaHCO3, or no drug (control). The drug was administered over 2 min in quantities calculated to correct a base deficit of 10 or greater. Plasma K+ and sodium (Na+) were measured for 45 min after drug administration. No difference in K+ response was noted after THAM, NaHCO3, or no drug. In contrast, THAM resulted in significantly lower Na+ concentrations when compared to the NaHCO3 or the control group (P < 0.05). In this rabbit model, alkalinization after THAM administration results in K+ changes similar to those after NaHCO3. THAM should be considered when treating acidosis in patients where hypernatremia is a concern.

The objective of this experimental work was to identify and compare the histopathological changes induced in the respiratory tract of Swiss mice exposed to repeated inhalation (4, 9 or 14 days) at typical concentrations of RD50, 0.3 x RD50 and 3 x RD50 of airborne chemicals. These substances were selected from ten chemical families: aldehydes, organic acids, alcohols, ketones, ethers, aromatic hydrocarbons, halogenated aromatic hydrocarbons, inorganic bases, amines and isocyanates. These experiments showed that the lesion intensity observed in the nasal passages varied with exposure duration and type of airborne chemical, but did not depend on the concentration of the substance. Results did not allow us to establish a relationship between the histopathological changes and the type of chemical family. No injuries were observed in trachea and lungs.

1. The effect of hexamethonium on the exocrine pancreatic response to intraduodenal acidification and alkalinization, and the secretin and VIP release after these stimuli, was studied. 2. The hydroelectrolyte secretion after hydrochloric acid and sodium carbonate perfusion was reduced by hexamethonium treated (322 +/- 44% of maximum response in flow rate to sodium carbonate perfusion in untreated animals vs 140 +/- 12% in pretreated animals, and 252 +/- 19% of maximum response in flow rate to HCl in untreated animals vs 166 +/- 11% in pretreated animals). 3. However, hexamethonium has no effect on secretin plasma levels after either intraduodenal acidification or alkalinization. 4. On the contrary, the ganglion blocker significantly (P < 0.01) reduced plasma VIP levels in response to intraduodenal HCl (maximum response 320 +/- 74% in untreated vs 184 +/- 44% in hexamethonium-treated animals). 5. Plasma VIP levels showed a similar increase in both untreated (maximum response: 151 +/- 12%) and ganglion blocked animals (170 +/- 26%) in response to sodium carbonate. 6. These data suggest the existence of complex neural mechanisms in the exocrine pancreatic response to intraduodenal stimuli, these mechanisms being different depending on the intraduodenal stimulus.

Exocrine pancreatic response to duodenal perfusion with alkaline solutions (pH 11.4) was studied in the anaesthetized rabbit; secretin and vasoactive intestinal polypeptide (VIP) levels in portal plasma were measured and the contribution of cholinergic mechanisms was also evaluated. Intraduodenal perfusion of sodium carbonate stimulated flow rate and bicarbonate output to a maximum of 322 +/- 44 and 609 +/- 105% respectively compared with basal levels. Significant increases of plasma secretin levels, with a maximum of 267 +/- 38% as compared with basal, were also observed. A lower increase in VIP levels (maximum of 151 +/- 12%) was seen. All these effects, except the VIP response, were substantially inhibited by atropine. Our results show that exocrine pancreatic response to intraduodenal sodium carbonate is specifically focused on hydroelectrolytic secretion. Keeping in mind what occurs after intraduodenal alkaline phosphate buffer administration (at the same pH as sodium carbonate: 11.4) it seems that about 50% of the pancreatic response to sodium carbonate may be ascribed to pH and the remaining 50% to the carbonate anion. Moreover, this response would mainly be mediated by secretin, whose release can be facilitated by a cholinergic reflex.

The process of oleandomycin inactivation in aqueous alkaline solutions with their heating was studied by using the microbiological method of the antibiotic content assay. The initial specific rate of inactivation of crystalline oleandomycin in buffer solutions and oleandomycin in the fermentation broth filtrate was evaluated. It was shown that the inactivation was retarded by the reaction products and the components of the fermentation broth filtrate. The production rate of oleandomycin anhydro derivatives amounting to 3-40 per cent of the total mass of the inactivation product was estimated by UV spectrophotometry.

The effect of treatment and supplementary value of corn (C) or crayfish (CR) on the protein quality of breadfruit (Treculia Africana) flours were studied in eighteen young rats. The 70:30 or 70:15:15 (Protein basis) combinations of breadfruit flours and corn or crayfish or both provided 1.6 g N/100 g diet for the 35 day study. The addition of 'akanwu' to the cooking water reduced cooking time and crude protein and saved fuel. The addition of 'akanwu' and replacement of CR with C was not beneficial as judged by the parameters tested except for the wt. gain and PER. On the other hand, when crayfish was the only source of supplementary protein (30%) to breadfruit cooked without 'akanwu' there were increases in all parameters tested over those with added 'akanwu' except for the N intake, wt. gain, and PER. These results appear to suggest that addition of 'akanwu' to TA was detrimental to its protein utilization and that TA appears to be an economic source of N in areas where it is a staple. Based on the results of this study, one would suggest that the use of 'akanwu' as a tenderizer should be seriously looked into before further use.

Our data demonstrate that correction of acidosis is sustained in children with type 1 RTA when alkali therapy is given in doses of 5 to 14 mEq/kg/day. The large doses are required as a result of renal bicarbonate-wasting. Children with type 1 RTA and acidosis who have significant growth impairment experience catch-up growth and attain normal stature for their age when correction of acidosis is sustained. Whether chronic acidosis impairs growth in any clinical condition except type 1 RTA is not settled. Whether sustained correction of acidosis with alkali therapy will allow attainment of normal stature in children with nonuremic diffuse renal disease is not yet determined. With the increasing availability of microchemistry and microgasometry and the new standards for growth based on mean-parent height [40], it can be anticipated that answers to these clinically important questions will be forthcoming.

Because accurate diagnosis of the alkaline reflux gastritis syndrome has been elusive, surgical treatment has had a high failure rate, particularly with respect to relief of pain. We have used intragastric infusion of alkali as a provocative test in 147 patients with symptoms and endoscopic findings suggestive of bile gastritis and in 19 asymptomatic control subjects. Subjects received saline solution, 0.1 normal hydrochloric acid, and 0.1 normal sodium hydroxide solutions, as well as their own gastric aspirates in random blinded fashion by a nasogastric tube. There were no complications. A positive test result was defined as pain with sodium hydroxide but not with saline solution or hydrochloric acid infusion. All of the control subjects had negative test results. A total of 87 percent of the symptomatic patients have been followed (mean 4.3 years, minimum 1 year); 47 of those 128 had a Roux-Y gastrojejunal reconstruction to divert duodenal contents from the stomach. Correlation of the test results and the subsequent clinical status showed 87 percent of those with negative test results improved spontaneously or with other treatment versus 15 percent if the test results were positive (p less than 0.001), and 78 percent of those with positive test results had lasting relief of pain after surgical diversion versus a 30 percent success rate if the test results were negative (p less than 0.01). We conclude that positive alkali infusion test results predict that symptoms will likely respond best to surgical diversion of duodenal contents, and that negative test results should be a strong deterrent to surgical diversion. The test is safe, simple, and deserves further trial.

Clinical and pathophysiologic studies were performed in five unrelated children with primary distal renal tubular acidosis who were diagnosed during infancy and followed for 3 to 9 1/2 years. All patients had permanent defects in hydrogen ion secretion, sodium reabsorption, and concentrating capacity. A transient, age-related, proximal tubular defect in sodium and bicarbonate reabsorption was also present. Renal bicarbonate wasting was mainly observed during the first years of life and progressively decreased with advancing age. Glomerular filtration rate remained within normal limits. Following sustained therapy with sodium and potassium bicarbonate, the patients had optimal growth, arrest of progression of nephrocalcinosis, and lack of other characteristic features of the disease with the exception of polyuria. Dosage of alkali was mainly determined by the magnitude of the renal bicarbonate loss and decreased progressively from a maximum of 3.9 to 10.0 mEq/kg/day during the first year of life to about 3 mEq/kg/day at or beyond 6 years of age. The total dosage of alkali required could be derived by the sum of the urinary excretion of bicarbonate plus 2 mEq/kg/day, which represents mean endogenous acid production. Although calciuria was normal when metabolic acidosis was corrected, patients with higher urinary sodium excretion had higher urinary excretion of calcium and thus were at greater risk of developing nephrocalcinosis if therapy was not carefully controlled.

Phenobarbitone levels in the blood do not always provide a reliable guide in the management of the poisoned patient. They may rise in response to active treatment though the patient may be improving clinically. Some reasons for this are considered, with illustrations from three cases. It is concluded that the poor correlation of phenobarbitone levels with a patient's condition is due not to inadequate analytical techniques but to the poor representation of the "whole body" situation by a single blood specimen. The usefulness of analysing such specimens is questioned.

Clinical study of the efficacy of four types of fluid treatment in mild and moderately severe burn shock in 134 patients showed that the prescription of oral alkaline solutions is sufficient in mild burn shock whereas in moderately severe shock fluids must be given by infusion. Intravenous infusion of glucose-electrolyte solutions is sufficiently effective in such cases.

Graffi et al. have proposed the use of exogenous enzymes for selective cleavage of inactive transport forms of cancerostatic substances in tumor tissue. Enzymes appropriate for this purpose should, if possible, show also a certain enrichment in the tumor tissue. In studies on the pH-labile alpha-L-arabinofuranosidase from G. myabena in tumor-bearing mice, under defined conditions in the tumors there could be demonstrated a higher concentration of the active form of the enzyme than in most of the normal tissues. However, the enzyme activity is eliminated from the organism in a relatively short time through excretion and inactivation. The application of glucose led to a strong increase of activity of the enzyme injected, both in the tumors and in the normal tissues. It has been shown in the present investigations that this increase in the enzyme activity can be curtailed more strongly in normal tissue by alkali application than in the tumors. In this way, a distribution of the enzyme activity favorable for therapy experiments is obtained. Only in the kidney and urine has a higher activity of the applied enzyme been measured than in the tumors. In the second part of this work it has been attempted to achieve accumulation of activity of the pH-stable alpha-L-arabinofuranosidase from A. niger through application of angiotensin, but no positive results have been reached under the various experimental conditions used.

A radiotelemetric technique was used to document the pH level within the intact small intestine of the dog. It was found that the pH in the area of the upper part of the jejunum ranged in a neutral zone between 6 to 7 in the fasting dog. Stimulation of the Thiry-Vella loop in these dogs, with either acid or alkaline solution, always resulted in the pH rising toward a higher level, the highest pH level being recorded as 8.2. All dogs demonstrated a lowering of this pH level toward a neutral range of 6 to 7 within three hours after Thiry-Vella loop challenge.

Experiments on white rats studied percutaneous resorption of 137Cs and 89Sr during their skin application in the form of 10 per cent and 40 per cent solutions of NaOH. The study also involved deactivation of the contaminated skin by means of traditional means of first aid recommended for alkali burn and the application of 5 per cent solution of boric acid with the addition of some detergent or 10 per cent solution of sodium hexametaphosphate. The dependence of deactivation efficacy on the time of beginning sanitary treatment, decontamination procedure and alkali concentration was established.