Role of Citrus Fruit Juices in Prevention of Kidney Stone Disease (KSD): A Narrative Review.

To explore the relationship between citrus fruit juices (oranges, grapefruits, and lemonades) and kidney stone disease (KSD). METHODS: A systematic review was performed using the Medline, EMBASE, and Scopus databases, in concordance with the PRISMA checklist for all English, French, and Spanish language studies regarding the consumption of citrus fruit juices and the relationship to urinary stone disease. The main outcome of interest was the association of citrus fruit juices with KSD. RESULTS: Thirteen articles met the criteria for inclusion in the final review. Three large epidemiological studies found that grapefruit juice was a risk factor for stone formation, while orange juice did not increase the risk for KSD. Ten small prospective clinical studies found that orange, grapefruit, and lemon juices all increased urinary citrate levels. Only orange and grapefruit juices had an alkalinizing effect and while lemon juice has a protective effect by raising urinary citrate levels, it lacked a significant alkalinizing effect on urine pH. Orange juice and grapefruit juices significantly increased urinary oxalate levels, while orange juice also had a high carbohydrate content. CONCLUSION: While orange juice seems to play a protective role against stone formation, grapefruit was found to raise the risk of KSD in epidemiological studies but had a protective role in smaller clinical studies. Lemon juice had a smaller protective role than orange juice. Larger amounts of, as well as more accurate, data is needed before recommendations can be made and a high carbohydrate content in these juices needs to be taken into consideration.

Sonochemical effects on the structure and antioxidant activity of egg white protein-tea polyphenol conjugates.

The antioxidant properties of proteins could be enhanced by forming covalent conjugates with polyphenols. In this study, the antioxidant activity of egg white protein (EWP) was improved by conjugating with tea polyphenols (TP) using traditional and ultrasound-assisted alkaline/free radical methods. In addition, the influences of TP conjugation on the antioxidant activities and structural and digestive properties of EWP were comprehensively studied. Compared with the traditional methods, the sonochemistry (40 kHz) approaches significantly increased the efficiency of TP grafting to the EWP (P < 0.05) from 24 h to 1 h. Amino acid analysis showed that in the ultrasound-assisted alkaline method, TP was successfully conjugated to the EWP through proline, glutamic acid, cysteine, and tryptophan residues, whereas proline, cysteine, and tryptophan were involved in the free radical method. However, the number of cross-linking sites was increased significantly after ultrasound-assisted treatments. Moreover, the antioxidant activities of the EWP were significantly improved after covalent conjugation with TP using traditional and ultrasound-assisted alkaline/free radical methods, particularly the ultrasound-assisted approaches. Furthermore, circular dichroism revealed that the ultrasound-assisted approaches had the greatest impact with regard to decreasing the α-helix content and increasing the random coil content, which loosened the protein structure, thereby improving its reactivity and digestibility. Therefore, ultrasound-assisted alkaline/free radical methods were efficient and safe means for the production of EWP-TP conjugates.

Effects of Food and Antacids on Pharmacokinetics and Pharmacodynamics of Lesinurad, a Selective Urate Reabsorption Inhibitor.

Two clinical studies were performed in healthy volunteers to investigate food and antacid effects on lesinurad, a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. Study 1 evaluated a high-fat, high-calorie meal or high doses of antacids (3000 mg calcium carbonate or 1600 mg magnesium hydroxide/1600 mg aluminum hydroxide) on the pharmacokinetics (PK) and pharmacodynamics (PD) of 400 mg oral lesinurad. Study 2 evaluated low doses of antacids (1250 mg calcium carbonate or 800 mg magnesium hydroxide/800 mg aluminum hydroxide) on the PK and PD of 400 mg lesinurad. Food did not alter the plasma AUC of lesinurad and only reduced its Cmax by 18%. In the fasted conditions, high-dose calcium carbonate reduced the Cmax and AUC of lesinurad by 54% and 38%, respectively, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced Cmax and AUC by 36% and 31%, respectively. Food enhanced the maximum serum urate (sUA)-lowering effect of lesinurad by approximately 20% despite reducing the Cmax of lesinurad. High-dose calcium carbonate decreased the urate-lowering effect approximately 20% in the first 6 hours, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced the effect by 26%. Low-dose calcium carbonate or magnesium hydroxide/aluminum hydroxide in the presence of food did not significantly affect plasma lesinurad Cmax and AUC or the sUA lowering and renal handling of uric acid. In summary, study results suggest food did not meaningfully alter lesinurad PK and PD. High doses of antacids reduced lesinurad AUC up to 40% and reduced the lesinurad uric acid-lowering effect.

Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells.

BACKGROUND: Over a century of advancements in the field of additive solutions for red blood cell (RBC) storage has made transfusion therapy a safe and effective practice for millions of recipients worldwide. Still, storage in the blood bank results in the progressive accumulation of metabolic alterations, a phenomenon that is mitigated by storage in novel storage additives, such as alkaline additive solutions. While novel alkaline additive formulations have been proposed, no metabolomics characterization has been performed to date. STUDY DESIGN AND METHODS: We performed UHPLC-MS metabolomics analyses of red blood cells stored in SAGM (standard additive in Europe), (PAGGSM), or alkaline additives SOLX, E-SOL 5 and PAG3M for either 1, 21, 35 (end of shelf-life in the Netherlands), or 56 days. RESULTS: Alkaline additives (especially PAG3M) better preserved 2,3-diphosphoglycerate and adenosine triphosphate (ATP). Deaminated purines such as hypoxanthine were predictive of hemolysis and morphological alterations. Guanosine supplementation in PAGGSM and PAG3M fueled ATP generation by feeding into the nonoxidative pentose phosphate pathway via phosphoribolysis. Decreased urate to hypoxanthine ratios were observed in alkaline additives, suggestive of decreased generation of urate and hydrogen peroxide. Despite the many benefits observed in purine and redox metabolism, alkaline additives did not prevent accumulation of free fatty acids and oxidized byproducts, opening a window for future alkaline formulations including (lipophilic) antioxidants. CONCLUSION: Alkalinization via different strategies (replacement of chloride anions with either high bicarbonate, high citrate/phosphate, or membrane impermeant gluconate) results in different metabolic outcomes, which are superior to current canonical additives in all cases.

Controlled-release of antacids from biopolymer microgels under simulated gastric conditions: Impact of bead dimensions, pore size, and alginate/pectin ratio.

The highly acidic nature of the gastric fluids inside the human stomach can cause have health problems in certain individuals e.g., acid reflux and ulcers. Antacid-loaded biopolymer microgels can be used to control the acidity of the gastric fluids, which may be useful for developing functional foods to treat these problems. In this study, the impact of biopolymer microgel dimensions and composition on the dissolution rate of encapsulated antacid was determined under simulated gastric conditions. The microgels were formed by injecting antacid (magnesium hydroxide) and biopolymers (alginate or alginate/pectin) into a calcium chloride solution to promote cross-linking. Microgels of varying dimensions were formed using either a hand-held syringe or a vibrating nozzle encapsulation device with different nozzle sizes. The rate of antacid dissolution was measured using an automatic titration device (pH stat) that added HCl solution into the simulated gastric fluids to maintain a constant pH of 2.5. The antacid dissolution rate decreased with increasing microgel diameter (300 to 1660 µm) and decreasing pore size (0.8 to 2.0% alginate). The slowest dissolution rate was observed in microgels containing 80% alginate and 20% pectin, which may have been due to the impact of biopolymer composition on bead dimensions and pore size. The results of this study may be useful for the design of biopolymer microgels that can control the release of antacids in the stomach, thereby leading to better control over the pH of the gastric fluids.

A comparative study of the antacid effect of some commonly consumed foods for hyperacidity in an artificial stomach model.

OBJECTIVES: The incorporation of certain alkalinizing vegetables, fruits, milk and its products in the diet has been known to alleviate hyperacidity. These foods help to restore the natural gastric balance and function, curb acid reflux, aid digestion, reduce the burning sensation due to hyperacidity and soothe the inflamed mucosa of the stomach. The present study evaluates and compares the antacid effect of broccoli, kale, radish, cucumber, lemon juice, cold milk and curd in an artificial stomach model. DESIGN: The pH of the test samples and their neutralizing effect on artificial gastric acid was determined and compared with that of water, the active control sodium bicarbonate and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid by the test samples. The neutralizing capacity of the test samples was determined in vitro using the classical titration method of Fordtran. RESULTS: All test samples except lemon showed significantly higher (p<0.05 for cucumber and p<0.001 for the rest) acid neutralizing effect than water. All test samples also exhibited a significantly (p<0.001) higher duration of consistent neutralization and higher antacid capacity than water. Highest antacid activity was demonstrated by cold milk and broccoli which was comparable with ENO and sodium bicarbonate. CONCLUSION: It may be concluded that the natural food ingredients used in this study exhibited significant antacid activity, justifying their use as essential dietary components to counter hyperacidity.

A comparative study of the antacid effect of raw spinach juice and spinach extract in an artificial stomach model.

BackgroundSpinacia oleracea known as spinach is a green-leafy vegetable consumed by people across the globe. It is reported to possess potent medicinal properties by virtue of its numerous antioxidant phytoconstituents, together termed as the natural antioxidant mixture (NAO). The present study compares the antacid effect of raw spinach juice with an antioxidant-rich methanolic extract of spinach (NAOE) in an artificial stomach model. MethodsThe pH of NAOE at various concentrations (50, 100 and 200 mg/mL) and its neutralizing effect on artificial gastric acid was determined and compared with that of raw spinach juice, water, the active control sodium bicarbonate (SB) and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid for the test compounds. The neutralizing capacity of test compounds was determined in vitro using the classical titration method of Fordtran. Results NAOE (50, 100 and 200 mg/mL), spinach juice, SB and ENO showed significantly better acid-neutralizing effect, consistent duration of neutralization and higher antacid capacity when compared with water. Highest antacid activity was demonstrated by ENO and SB followed by spinach juice and NAOE200. Spinach juice exhibited an effect comparable to NAOE (200 mg/mL). ConclusionsThus, it may be concluded that spinach displays significant antacid activity be it in the raw juice form or as an extract in methanol.

Influence of calcium carbonate on extraction yield and quality of extra virgin oil from olive (Olea europaea L. cv. Coratina).

The aim of the research was to evaluate the effect of calcium carbonate (1%, 2%, and 4% of addition) at two different particle sizes (2.7µm and 5.7µm), added at the beginning of the malaxation phase, on both the extraction yield and the quality of oil obtained from Coratina olives at different ripening index. The results showed that calcium carbonate significantly increased the extraction yield of olive oil, more than affecting chemical indices. In particular, for less ripened olives, 1-2% of larger particle size calcium carbonate addiction determined a significant increase of the extraction effectiveness, ranging from 4.0 to 4.9%, while more ripened olives required higher amounts of coadjuvant (2-4% when using the larger particle size and 4% when using the smaller one), with a significant increase of the extraction yield up to 5%. Moreover, an increase of pungent perception was observed in some cases when adding calcium carbonate to more ripened olives.

Evaluation of antisecretory, gastroprotective and in-vitro antacid capacity of Fumaria indica in rats.

Fumaria indica is used for its anthelmintic, antidyspeptic, cholagogue, diaphoretic, diuretic, laxative, stomachic, tonic properties and claimed to possess various properties for the ailments of blood, skin, gastrointestinal systems and central nervous system. The present study was undertaken to evaluate antisecretory, gastroprotective and in-vitro antacid capacity of ethanol extract from F. indica in rats. Evaluation of F. indica extract as antisecretory was carried out by pyloric ligation induced ulcer model. The gastroprotective effect was carried out by absolute ethanol induced ulcer model. Integrity of gastric mucosa was evaluated by estimation of GSH and gastric mucus level. The in-vitro antacid capacity was evaluated by titration method. Ethanol extract of F. indica at 200 mg kg(-1), orally showed inhibition of secretion in pyloric ligation model. GSH level (1.67 µg mg(-1) protein), gastricwall mucus (240.76 µg g(-1) wet glandular tissue) and percentage protection (77.59%) of ulcer were significantly (P < 0.05) increased in absolute ethanol induced ulcer model. The in-vitro antacid capacity of ethanol extract of F. indica was compared with the standard. Conclusively, it appears that F. indica possess antisecretory (inhibition of acid secretion), gastroprotective (potentiation of defensive factors) and in-vitro antacid activity.

Colloidal bismuth subcitrate impedes proton entry into Helicobacter pylori and increases the efficacy of growth-dependent antibiotics.

BACKGROUND: Successful eradication of Helicobacter pylori is becoming more difficult, mainly due to emerging antibiotic resistance. Treatment regimens containing bismuth have increased efficacy, but the mechanism is unknown. Helicobacter pylori is a neutralophile adapted to survive the acidic gastric environment via acid acclimation, but demonstrates more robust growth at neutral pH. Many antibiotics used to treat H. pylori rely on bacterial growth. AIM: To investigate the mechanism of increased efficacy of bismuth-containing H. pylori treatment regimens. METHODS: RNAseq and qPCR, urease activity in permeabilised and intact bacteria, internal pH and membrane potential were measured with and without colloidal bismuth subcitrate (CBS). Bacterial survival was assessed with CBS and/or ampicillin. RESULTS: Genes involved with metabolism and growth were upregulated in the presence of CBS at acidic pH. Urease activity of permeabilised H. pylori at pH 7.4 and 4.5 decreased in the presence of CBS, but intact urease activity decreased only at acidic pH. The fall in cytoplasmic pH with external acidification was diminished by CBS. The increase in membrane potential in response to urea addition at acidic medium pH was unaffected by CBS. The impact of CBS and ampicillin on H. pylori survival was greater than either agent alone. CONCLUSIONS: Bismuth is not acting directly on urease or the urea channel. Colloidal bismuth subcitrate impedes proton entry into the bacteria, leading to a decrease in the expected fall in cytoplasmic pH. With cytoplasmic pH remaining within range for increased metabolic activity of a neutralophile, the efficacy of growth-dependent antibiotics is augmented.

In vitro and in vivo evaluation of the inhibitory effect of Limnophila indica (Linn.) Druce on shigellosis.

OBJECTIVE: The research aimed to evaluate the anti-Shigella and antacid activities of the methanolic extract of Limnophila indica. METHODS: The whole plant of L. indica was extracted using methanol and then subjected to preliminary chemical screening. The in vitro antibacterial screening on two Gram-positive and two Gram-negative bacteria as well as three Shigella species of which two bacteria were antibiotic-resistant were evaluated by disc diffusion method. Castor oil-induced diarrhoea on Wistar albino rats was performed by using loperamide as a standard control. The in vitro antacid activity was tested by artificial stomach model. The neutralization efficiency, capacity, volume and hydrogen ions consumed were also evaluated. RESULTS: The preliminary chemical screening on methanolic extract of L.indica showed the presence of phenolic compounds, flavonoids, alkaloids, fats and oils. It was proved to be a potent antibacterial agent against the four bacterial strains. Screening against Shigella species revealed that it was a powerful antibacterial agent towards antibiotic-resistant Shigella species. In the case of in vivo antidiarrheal activity, the plant has shown a dose-dependent activity and the lowest dose at 100 mg/kg gave a much better result than loperamide (P<0.01). The in vitro antacid study showed a mild activity. CONCLUSION: As the plant L. indica has been proved to be a competent antibacterial as well as a compelling antidiarrheal agent with mild antacid activity, this plant can be very well suggested to be an eminent substitute for the various synthetic anti-dysentery and antidiarrheal agents available in the market.

Antiulcer activity of methanolic extract and fractions of Picralima nitida seeds(Apocynacaea) in rats.

OBJECTIVE: To investigated the antisecrectory activities of the methanol extract, chloroform fraction and methanol fraction of Picralima nitida seeds. METHODS: The methanol extract of Picralima nitida seeds was fractionated into chloroform fraction and methanol fraction. They were evaluated for antiulcer activity and gastric emptying time in rats using aspirin-pylorus-ligation model. RESULTS: Oral administration of the methanol extract, chloroform fraction and methanol fraction at 1 000 mg/kg reduced gastric ulcer by 56.4%, 40.0% and 56.3%, respectively; and the fractions of the extract significantly (P<0.05) reduced gastric emptying time when compared to the control. Gastric acidity was significantly decreased when compared with saline group, 40.25 mEq/L in methanol extract, 50.0 mEq/L in chloroform fraction 51.25 mEq/L in methanol fraction but had no significant effect on the gastric secretion volume. CONCLUSIONS: These findings showed that methanol extract, chloroform fraction and methanol fraction of the seeds of Picralima possessed potent antiulcer properties and some antisecretory properties.

Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: analysis of underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC. (Asteraceae) is a species native to South America used in Brazilian folk medicine to treat gastrointestinal and liver diseases, kidney disorders and diabetes. Previous studies from this laboratory confirmed the antacid and antiulcer activities of the plant aqueous extract (AE) in rat and mouse models. AIM OF THE STUDY: To investigate the mechanisms involved in the antacid action of AE and isolated compounds from Baccharis trimera. MATERIALS AND METHODS: AE was assayed in vivo in cold-restraint stress gastric ulcers and in pylorus-ligated mice. Nine fractions (F2-F10) previously isolated from AE were assayed in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands, and on gastric microsomal H(+), K(+)-ATPase preparations. Chlorogenic acids (F2, F3, F6, F7), flavonoids (F9), an ent-clerodane diterpene (F8) and a dilactonic neo-clerodane diterpene (F10) have been identified in these fractions. RESULTS: Intraduodenal injection of AE (1.0 and 2.0 g/kg) in 4h pylorus-ligated mice decreased the volume (20 and 50%) and total acidity (34 and 50%) of acid secretion compared to control values. Administered orally at the same doses AE protected against gastric mucosal lesions induced in mice by restraint at 4°C. Exposure of isolated rabbit gastric glands to fractions F8 (10-100 µM) and F9 (10-300 µg/ml) decreased the basal [(14)C]-AP uptake by 50 and 60% of control (Ratio=6.2±1.1), whereas the remaining fractions were inactive. In the presence of the secretagogues F2 and F4 (30-300 µg/ml) decreased the [(14)C]-AP uptake induced by histamine (His) with a 100-fold lower potency than that of ranitidine. F5 and F6 reduced the [(14)C]-AP uptake stimulated by carbachol (CCh), but they were 10 to 20-fold less potent than atropine. F8 (diterpene 2) and F9 (flavonoids) decreased both the His- and CCh-induced [(14)C]-AP uptake, whereas F10 (diterpene 1) was inactive against the [(14)C]-AP uptake stimulated by secretagogues. Diterpene 2 was the most active of all tested compounds being 7-fold less potent than ranitidine and equipotent to atropine in reducing acid secretion in vitro. This compound also reduced the gastric H(+), K(+)-ATPase activity by 20% of control, while the remaining fractions were inactive on the proton pump in vitro. CONCLUSIONS: The results indicate that Baccharis trimera presents constituents that inhibit gastric acid secretion by acting mainly on the cholinergic regulatory pathway. The plant extract also contains compounds that exert moderate inhibition of the histaminergic regulatory pathway of acid secretion and the gastric proton pump. Altogether these active constituents appear to provide effective inhibition of acid secretion in vivo, which may explain the reputed antiulcer activity of the plant extract.

Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers.

Raltegravir's divalent metal ion chelating motif may predispose the drug to interactions with divalent cations. We determined whether a divalent cation-containing antacid interacted with raltegravir. Twelve HIV-1-seronegative subjects were enrolled in this randomized, prospective, crossover study of single-dose raltegravir (400 mg) with and without an antacid. Subjects underwent two intensive pharmacokinetic visits in the fasted state separated by a 5- to 12-day washout period. With simultaneous antacid administration, time to peak raltegravir concentration occurred 2 h sooner (P = 0.002) and there was a 67% lower raltegravir concentration at 12 h postdose (P < 0.0001) than with administration of raltegravir alone. The raltegravir area under the-concentration-time curve from 0 to 12 h and maximum concentration were unchanged with the addition of an antacid. Studies are needed to determine the clinical relevance of this interaction, whether it remains after multiple dosing to steady state, whether it is mitigated by temporal separation, and whether raltegravir interacts with divalent cation-containing vitamins, supplements, or foods.

Antacid effects of Chinese herbal prescriptions assessed by a modified artificial stomach model.

AIM: To assess the antacid effects of the tonic Chinese herbal prescriptions, si-jun-zi-tang (SJZT) and shen-ling-bai-zhu-san (SLBZS). METHODS: Decoctions of the tonic Chinese herbal prescriptions, SJZT and SLBZS, were prepared according to Chinese original documents. The pH of the prescription decoctions and their neutralizing effects on artificial gastric acids were determined and compared with water and the active controls, sodium bicarbonate and colloidal aluminum phosphate. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization effect on artificial gastric acids. The neutralization capacity in vitro was determined with the titration method of Fordtran's model. RESULTS: The results showed that both SJZT and SLBZS have antacid effects in vitro. Compared with the water group, SJZT and SLBZS were found to possess significant gastric acid neutralizing effects. The duration for consistent neutralization of SLBZS was significantly longer than that of water. Also, SLBZS and SJZT exhibited significant antacid capacities compared to water. CONCLUSION: SJZT and SLBZS were consistently active in the artificial stomach model and are suggested to have antacid effects similar to the active control drugs.

Effect of oral aluminium hydroxide on iron absorption from iron(III)-hydroxide polymaltose complex in patients with iron deficiency anemia / a single-centre randomized controlled isotope study.

The study was carried out as an open-label, laboratory-blind, single-dose, randomized, two-period crossover, isotope efficacy study. Twenty-two patients with iron-deficiency anemia were enrolled in the study. The study consisted of two treatment phases of 15 days each, including blood sample measurements for Fe-59 activity. The 2 treatments were given orally. Treatment A was Fe-59 labeled iron(III)-hydroxide polymaltose complex (IPC, Maltofer), equivalent to 100 mg elemental iron given orally, and Treatment B consisted of Treatment A combined with 600 mg aluminium hydroxide (CAS 21645-51-2) (10 ml). No differences between the two treatment groups with regard to the erythrocyte uptake were found, and thus IPC can be used with aluminium hydroxide, if necessary.

Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antiacid secretion and antidepressant-like activities.

This study reports the extraction process and standardization of the aqueous extract (AE) of a Cecropia species aiming its pharmacological characterization as a phytomedicine to be used in primary health care. The plant was originally collected in its environment, and was thereafter specially cultivated for the present work. To standardize the plant AE, several 2.0% tea of the dried leaves were prepared under controlled conditions and freeze dried. The AE (20% yield) was partitioned with n-butanol yielding the butanolic fraction (BuF; 1% yield). The activity of AE on vital organ functions (cardiovascular, respiratory, gastrointestinal and central nervous system) was determined in vivo. The effects of AE were compared to those of BuF in the same models and the relative potency determined. BuF was further evaluated in representative in vitro models to assess possible mechanisms of action. Chemical constituents of BuF were isolated in preparative HPLC columns yielding 10 highly purified compounds chemically identified as catechins (2), procyanidins (4), flavonoids (2), mixed sugars (1) and chlorogenic acid. All the compounds were identified by chemical analytic instrumentation (13C-NMR, 1H-NMR, LC-MS). Their relative concentrations in AE were ca 12% catechins, 19% procyanidins and 19% flavonoids. The pharmacological activity of the standardized AE is reported in accompanying papers.

Effects of Nidus Vespae extract and chemical fractions on the growth and acidogenicity of oral microorganisms.

Nidus Vespae is the honeycomb of Polistes Olivaceous (De Geer), P. Japonicus Saussure, and Parapolybiavaria Fabricius. It is known to have a number of pharmacological effects, including antimicrobial, anti-inflammatory, anti-virus, anti-tumor and anesthetic properties. The present study evaluated the antimicrobial activity and acid inhibition properties of extracts and chemical fractions of Nidus Vespae. The raw material was first extracted using 95% ethanol/water. Subsequent fractions were prepared from this extract using cyclohexane/ethyl acetate, petroleum ether/ethyl acetate, and chloroform/methanol. For the antimicrobial activity assays, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined using the microdilution method. The chloroform/methanol (Chl/MeOH) fraction showed the highest antibacterial activities with a MIC of 8-16mg/ml and an MBC of 16-32mg/ml. In addition, the extract and chemical fractions of Nidus Vespae showed a remarkable capacity for inhibiting the acid production of common oral bacteria at sub-MIC concentrations. Sub-MIC levels of the petroleum ether/ethyl acetate fraction significantly inhibited acid production by Streptococcus mutans ATCC 25175. The significant antiacidogenic activity demonstrated by Nidus Vespae shows it to be a promising source of novel anticariogenic agents.

Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice.

Bromelain is a mixture of proteinases derived from pineapple stem that is marketed by health food stores as a "digestive aid". A number of studies suggest that bromelain may also have anti-inflammatory activity in vivo, including an anecdotal report describing potential efficacy in inflammatory bowel disease. We and others have previously shown that proteolytically active bromelain removes certain cell surface molecules and affects leukocyte migration, activation, and production of cytokines and inflammatory mediators in vitro. The purpose of this study was to determine whether ingested bromelain retains proteolytic activity within the murine gastrointestinal tract in vivo. The proteolytic activity of bromelain was determined in vitro using model substrates or immunofluorescence assays after administration of various doses and formulations orally to mice. Immune responses against bromelain were detected by enzyme immunoassays. When formulated in antacid, oral bromelain retained substantial proteolytic activity throughout the gastrointestinal tract. Bromelain concentrations within the colon were dependent on both dose and formulation and were sufficient to remove bromelain-sensitive molecules from both leukocytes and colon epithelial cells. Peak activity in the stool was observed 4 h after oral dosing. Although anti-bromelain IgG was detected in both serum and stool after long-term oral therapy, these antibodies did not prevent bromelain proteolytic activity within the gastrointestinal tract. These studies demonstrate that bromelain enzymes can remain intact and proteolytically active within the murine gastrointestinal tract. They provide further support for the hypothesis that oral bromelain may potentially modify inflammation within the gastrointestinal tract via local proteolytic activity within the colonic microenvironment.

The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats.

The control of serum phosphorus (P) and calcium-phosphate (Ca x P) product is critical to the prevention of ectopic calcification in chronic renal failure (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders, markedly increase serum Ca and positive Ca balance, the new calcium- and aluminum-free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without altering serum Ca in hemodialysis patients. Using an experimental model of CRF, these studies compare sevelamer and calcium carbonate (CaCO(3)) in the control of serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6 nephrectomized rats underwent one of the following treatments for 3 mo: uremic + high-P diet (U-HP); UHP + 3% CaCO(3) (U-HP+C); UHP + 3% sevelamer (U-HP+S). Sevelamer treatment controlled serum P independent of increases in serum Ca, thus reducing serum Ca x P product and further deterioration of renal function, as indicated by the highest creatinine clearances. Sevelamer was as effective as CaCO(3) in the control of high-P-induced SH, as shown by similar serum PTH levels, parathyroid (PT) gland weight, and markers of PT hyperplasia. Also, both P binders elicited similar efficacy in reducing the myocardial and hepatic calcifications induced by uremia. However, sevelamer caused a dramatic reduction of renal Ca deposition (29.8 +/- 8.6 micro g/g wet tissue) compared with both U-HP (175.5 +/- 45.7 micro g/g wet tissue, P < 0.01) and the U-HP+C (58.9 +/- 13.7 micro g/g wet tissue, P < 0.04). Histochemical analyses using Von Kossa and Alizarin red S staining of kidney sections confirmed these findings. The high number of foci of calcification in the kidney of uremic controls (108 +/- 25) was reduced to 33.0 +/- 11.3 by CaCO(3) and decreased even further with sevelamer (16.4 +/- 8.9, P < 0.02 versus CaCO(3)). Importantly, the degree of tubulointerstitial fibrosis was also markedly lower in U-HP+S (5%) compared with either U-HP+C (30%) or U-HP (50%). It is concluded that in experimental CRF in rats, despite a similar control of serum P and SH, sevelamer is more effective than CaCO(3) in preventing renal Ca deposition and tubulointerstitial fibrosis, including better preservation of renal function. These findings cannot be extrapolated to human disease, and further studies in patients are necessary to determine the benefits of either P binder.