Development and evaluation of a biorelevant medium simulating porcine gastrointestinal fluids.

Simulated human intestinal media, have proved to be a useful biopharmaceutics tool as a dissolution media for predicting in vivo dissolution and pharmacokinetic profile in humans. During drug product development preclinical animal models are also required to assess drug product performance, and there is a need to develop species specific intestinal media to similarly predict in vivo pharmacokinetic profiles in each preclinical model. Pigs, are increasingly being used in preclinical drug development, however to date there is a lack of quantitative information about the composition of porcine gastrointestinal (GI) fluids. As a result, a porcine biorelevant medium has not yet been developed, which is essential to improve interpretation and forecast of preclinical results using biorelevant in vitro dissolution studies. GI fluid samples, were collected from landrace pigs, and characterized. Fasted State Simulated Intestinal Fluid of pigs (FaSSIFp) was developed based on the physiological composition of the GI fluids in terms of pH, buffer capacity, osmolality, surface tension, as well as the bile salt, phospholipid and free fatty acid content. This study demonstrated that FaSSIFp was superior at predicting the solubility of the six model drugs in porcine intestinal fluids (PIF). A markedly high correlation (r2 0.98) was observed between the solubility obtained in PIF and FaSSIFp, whereas poor correlation (r2 0.12) was found for the solubility of the model drugs between human FaSSIF and PIF. This confirms that species specific biorelevant intestinal media are crucial to provide more accurate predictions of pharmacokinetic studies in preclinical models. Additionally, the availability of a species specific intestinal medium offers the potential to improve in vitro-in silico approaches to predict in vivo absorption and to reduce the overall number of animals needed in oral drug product development testing.

Cellular antioxidant activity and in vitro inhibition of α-glucosidase, α-amylase and pancreatic lipase of oregano polyphenols under simulated gastrointestinal digestion.

Different oregano species have been traditionally used as infusions in folk medicine. Oregano medicinal properties, such as antioxidant and anti-inflammatory, have been partially attributed to its polyphenolic content. However, information regarding bioaccessibility of oregano polyphenols is limited. Cell-based antioxidant activity, and in vitro hypoglycemic, and hypolipidemic properties of polyphenolic extracts from three species of oregano species, namely, Hedeoma patens (HP), Lippia graveolens (LG) and Lippia palmeri (LP), subjected to simulated gastrointestinal digestion were evaluated. LC-TOF-MS analysis of HP, LG and LP allowed the identification of 9 flavonoids and 6 hydroxycinnamic acid derivatives with nutraceutical significance. Oregano polyphenolic extracts and digests from HP, LG, and LP exhibited cellular antioxidant capacity, hypoglycemic and hypolipidemic properties. Altogether, our results suggest that HP, LG and LP polyphenols exhibit potential for use as hypoglycemic, hypolipidemic, and antioxidant agents.

Systematic evaluation of bioactive components and antioxidant capacity of some new and common bayberry cultivars using an in vitro gastrointestinal digestion method.

This study was aimed to investigate the impact of in vitro gastrointestinal digestion on some common and new bayberry cultivars. The contents of total phenolics (246-669mg gallic acid equivalents/kg FW (fresh weight)), flavonoids (116-689mg quercetin-3-O-rutinoside equivalents/kg FW), procyanidins (28-133mg catechin equivalents/kg FW) and anthocyanins (1-7mg cyaniding-3-O-glucoside equivalents/kg FW) were detected in digested cultivars. HPLC-TOF-MS analysis identified 17 phenolic compounds in digested sample. Among all digested cultivars, the new cultivars Anhaizaomei (ABTS, IC50=2.95mg/mL; FRAP, 401.32mg vitamin C equivalents (VCE)/kg FW) and Yingsi (ABTS, IC50=3.28mg/mL; FRAP, 400.81mg VCE/kg FW) showed better in vitro antioxidant capacity. Further cellular assay indicated that the common cultivar Dongkui (2mg/mL) possessed the strongest ROS scavenging activity. The comprehensive evaluation of bioactive components and antioxidant properties using principal component analysis suggests that common cultivar Dongkui, new cultivars Yingsi and Anhaizaomei could be considered as dietary supplements.

Consequences of Hypoacidity Induced by Proton Pump Inhibitors - a Practical Approach.

BACKGROUND:   Proton pump inhibitors (PPIs) are often a part of drug regimens for many patients, including cancer patients. These drugs are very effective suppressors of gastric acid secretion; a significant increase in the gastric pH is seen with chronic use. This affects absorption of drugs, vitamins, and minerals. PURPOSE: PPIs are associated with many adverse drug reactions; nevertheless, these adverse effects are often neglected in clinical practice. The main aim of this article is to emphasize some of the adverse effects and theoretical mechanisms underlying these adverse reactions, the expected length of therapy before their clinical manifestation, and potential ways of dealing with these adverse reactions. We will focus on hypergastrinemia and rebound hyper-acidity, which occur in patients on long-term therapy with high dose PPIs. Next, we will focus on osteoporosis and hypomagnesemia, adverse effects for which the assumed mechanism is decreased absorption of particular ions from the gastrointestinal tract. Furthermore, clinically significant pharmacokinetic drug interactions at the level of absorption will be analyzed. Tyrosine kinase inhibitors (TKIs) are drugs with limited solubility; this solubility is pH-dependent. Some recommendations seek to ensure optimal absorption with minimal inter-day variability. Tables sum-marizing the optimal relationship between food and TKIs, and (sometimes) the optimal regimen of concomitant PPIs, are included. Key words: proton pump inhibitors - drug-related side effects and adverse reactions- drug interactions - tyrosine kinase inhibitors - hypochlorhydria The author declares she has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 24. 8. 2018 Accepted: 17. 10. 2018.

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.

Impact of diet on 24-hour intragastric pH profile in healthy horses.

An electrode incorporated into a polyethylene hose was introduced under endoscopic control into the stomach of six fasting adult horses for long-lasting pH measurements. The intragastric pH was recorded every four seconds for a period of 24 hours. The Warmblood horses were assigned randomly to receive hay ad libitum (H group); 1.5 kg hay/100 kg BW/day and 1 kg concentrate/100 kg BW/ day (C group) or protocol C plus 75 g pectin-lecithin supplement/100 kg BW/day (P group). The horses were adapted to each diet for 14 days. The 24-hour median pH value for protocol H (2.69) was significantly lower compared to protocol C (3.35) and P (3.44) (p < 0.05). The horses in protocol P had a significant higher percentage (40.1 %) of 24-hour intragastric pH values ≥ 4 than in protocol C (36.2 %) or in protocol H (25.3 %) (p < 0.05).

Antacid activity of Laportea aestuans (L.) Chew.

ETHNOPHARMACOLOGICAL RELEVANCE: Laportea aestuans (L.) Chew (Urticaceae) was historically ingested together with chalk by pregnant women in Ghana when suffering from heartburn. The aim of this study was to evaluate the antacid activity of the aerial parts of L. aestuans. MATERIALS AND METHODS: Aerial parts of L. aestuans were collected in the Accra region of Ghana. The antacid activity was measured according to Fordtran׳s titration model. 90 mL tap water and test material in a 500 mL beaker were warmed to 37°C on a magnetic stirrer and was continuously stirred at approximately 30 rpm in order to mimic the movements of the stomach. A titration was carried out with an artificial gastric acid to the end point of pH 3. The acid secretion rate was approximately 3 mL and pH was monitored with a pH meter. Concentrations of 666 and 1332 mg dried plant material were tested, both with and without addition of calcium carbonate (CaCO3). RESULTS: Both CaCO3 and L. aestuans had a significant better ability than water to neutralise an artificial stomach acid. 666 mg plant material together with CaCO3 compared to CaCO3 alone showed approximately the same neutralisation time. When mixing 1332 mg plant material with CaCO3 the neutralisation time was significantly higher than for CaCO3 alone and exhibited an antacid profile that was able to maintain the neutralising activity one pH-unit higher for an extended period of time. CONCLUSION: The results indicate that L. aestuans showed an antacid activity when combined with CaCO3. With further investigations of the active compound, mechanism of action and possible toxicity, the plant could form the basis of a novel antacid.

Role of gastric acid inhibition, prostaglandins and endogenous-free thiol groups on the gastroprotective effect of a proteolytic fraction from Vasconcellea cundinamarcensis latex.

OBJECTIVES: The aim of this study was to extend our knowledge about the mechanism involved in the gastroprotective effect of P1G10, a proteolytic fraction rich in cysteine proteinases from Vasconcellea cundinamarcensis (syn. Carica candamarcensis) latex, which demonstrated gastric healing and protection activities in rats. METHODS: Wistar rats were submitted to gastric lesions by indomethacin and treated with P1G10 (10 mg/kg). Free thiol groups and prostaglandin E2 content were measured in gastric mucosal and gastrin levels in blood samples. To evaluate the participation of nitric oxide (NO) or proteolytic activity of P1G10 on its gastroprotective effect, animals were treated with an inhibitor of NO production (L-NAME) or the fraction inhibited by iodoacetamide, respectively. Gastric secretion study (acidity and pepsin activity) was also performed. KEY FINDINGS: P1G10 (10 mg/kg) inhibited the occurrence of gastric lesions by indomethacin, restored the free thiol groups content on gastric mucosa and increased moderately prostaglandin E2 levels (34%). Furthermore, the treatment decreased the gastrin levels (95%), suggesting a possible modulation of secretory activity. This effect was accordant with attenuation of gastric acidity (42%) and pepsin activity (69%) seen in animals subjected to pyloric ligation. The inhibition of NO production or the proteolytic activity of P1G10 does not affect the gastroprotective effect. CONCLUSIONS: These results can explain the gastroprotective activity of P1G10 and serve a basis for further studies of this active principle.

Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress.

BACKGROUND: The incidence of upper gastrointestinal bleeding from stress ulcers has decreased within the last 30 years. Improvements in intensive care medicine including advanced equipment for artificial ventilation, better sedoanalgesic therapies, and the use of stress ulcer prophylaxis are credited for the decline. OBJECTIVES: To determine the effectiveness of proton pump inhibitors (PPIs) on gastric pH in patients exposed to a defined severe stress situation during a specified time period. METHODS: Prospective open study in a tertiary community hospital. A high dose (80 mg bolus followed by 8 mg/h) of either pantoprazol or omeprazol was infused in 17 patients with opiate dependence who were undergoing ultra-rapid opiate withdrawal by barbiturate anesthesia. MEAN OUTCOME MEASURE: Gastric pH. RESULTS: Gastric pH did not change significantly in the majority of patients (mean pH 1.2 ± 0.9 immediately before, 1.5 ± 1.6 at 60 min after, and 1.3 ± 1.5 at 120 min after PPI infusion began). Gastric pH increased temporarily in two of the nine patients receiving omeprazol. In two of the eight patients, pantoprazol led to a late but sustained increase in gastric pH (pH 3.9 and 6.0 at 120 min post infusion). CONCLUSION: High doses of PPIs are ineffective in elevating gastric pH in patients exposed to severe stress such as ultra-rapid opiate detoxification. Therefore, adequate sedoanalgesia might be the main factor responsible for preventing stress-related bleeding in critically ill patients.

Alkaloids from Mahonia bealei posses anti-H⁺/K⁺-ATPase and anti-gastrin effects on pyloric ligation-induced gastric ulcer in rats.

The purpose of this study was to investigate the underlying mechanism(s) of the total alkaloids (TA) from Mahonia bealei in treating pyloric ligation-induced gastric ulcers in rats. Animals were sacrificed after 19 h of the ligation. Gastric acid, peptic activities, mucin levels, H(+)/K(+)-ATPase activities and the gastrin level were analyzed. To improve the accuracy of the observations, IPP 6.0 software was introduced to measure the area of ulcer. TA (18.56 mg/kg/day, i.g.) showed an antiulcer effect by significantly decreasing the gastric ulcer areas (11.28 mm(2)) compared with model group (26.36 mm(2)). The TA ulcer inhibition ratio was 57.2%, compared with the effect of the positive control, omeprazole (62.96%). The results also showed that TA had a significant effect in inhibiting the release of H(+)/K(+)-ATPase, reducing the content of gastrin and decreasing gastric acidity on experimental animals. However, the TA had no significant effects on gastric mucus secretion and pepsin activity. Data indicated that TA had gastric ulcer protective effects by modulating the H(+)/K(+)-ATPase activity and gastrin level. TA has a potential to be developed as a pharmacological agent for the treatment of gastric ulcers.

Pollen grains for oral vaccination.

Oral vaccination can offer a painless and convenient method of vaccination. Furthermore, in addition to systemic immunity it has potential to stimulate mucosal immunity through antigen-processing by the gut-associated lymphoid tissues. In this study we propose the concept that pollen grains can be engineered for use as a simple modular system for oral vaccination. We demonstrate feasibility of this concept by using spores of Lycopodium clavatum (clubmoss) (LSs). We show that LSs can be chemically cleaned to remove native proteins to create intact clean hollow LS shells. Empty pollen shells were successfully filled with molecules of different sizes demonstrating their potential to be broadly applicable as a vaccination system. Using ovalbumin (OVA) as a model antigen, LSs formulated with OVA were orally fed to mice. LSs stimulated significantly higher anti-OVA serum IgG and fecal IgA antibodies compared to those induced by use of cholera toxin as a positive-control adjuvant. The antibody response was not affected by pre-neutralization of the stomach acid, and persisted for up to 7 months. Confocal microscopy revealed that LSs can translocate into mouse intestinal wall. Overall, this study lays the foundation of using LSs as a novel approach for oral vaccination.

Role of Blepharis maderaspatensis and Ammannia baccifera plant extracts on in vitro oxygen radical scavenging, secretion of gastric fluid and gastroprotection on ulcer induced rats.

CONTEXT: Blepharis maderaspatensis L. Roth (BM) (Acanthaceae) and Ammannia baccifera L. (AB) (Lythraceae) are used in folk medicine for various stomach disorders. OBJECTIVE: The chloroform and ethanol extracts of both plants were evaluated for antioxidant, gastric antisecretory, and gastroprotective properties. METHODS: Antioxidant properties of the extracts were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and nitric oxide (NO) scavenging assay. The gastric antisecretory properties of the extracts were assessed, at a dose of 100 and 200 mg/kg, using aspirin-pylorus ligation induced gastric ulcer models and the gastroprotective activity of the extracts was assessed, at a dose of 100 and 200 mg/kg, using HCl-ethanol induced ulcer models in rats. RESULTS AND DISCUSSION: Ethanol extract of BM (EBM) possessed good antioxidant property with IC50 values of 37.4 and 44.1 µg/mL in DPPH and NO scavenging assays respectively, where 25-250 µg/mL concentration in DPPH assay and 30-300 µg/mL concentration in NO scavenging assay were used. Ethanol extract of AB (EAB) at a dose of 200 mg/kg reduced the free acidity to 142.66 mEq/L and total acidity to 451.22 mEq/L. It reduced the gastric secretion with increase in pH from 2.2 to 3.15. Possessing good antisecretory activity, it also reduced the ulcer by 92.2% in aspirin and pylorus ligation induced gastric ulcer models. EAB increased the mucus secretion and adherent mucus in the tissues with a 71.43% reduction of ulcerin HCl-ethanol induced ulcer models, at a dose of 200 mg/kg. This activity can be attributed to the various flavonoids like rutin and kaempferol-3-O-ß-glucopyranoside, and the phytosterol, ß-sitosterol-3-O-ß-glucopyranoside, and phenolics present in the extracts. CONCLUSION: EBM possessed significant antioxidant property while EAB possessed good antisecretory and gastroprotective activity.

Psidium guajava Linn confers gastro protective effects on rats.

BACKGROUND AND OBJECTIVES: The best alternatives to synthetic medicines, available, for the treatment of gastric ulcer disorders, are the natural products found in plants. They are known to exhibit a variety of activities. The present study is aimed at the screening of Psidium (P.) guajava Linn for its gastro protective effect. MATERIAL AND METHODS: The methanol extracts of the leaves of P. guajava were tested in three different ulcer models viz. aspirin (ASP), pyloric ligation (PL) and ethanol (EtoH) induced ulcer models in rats. RESULTS AND DISCUSSION: The treatment of P. guajava at varying doses (100 mg/kg and 200 mg/kg) significantly (p < 0.001) inhibited the gastric lesions induced by ASP (70.5%), PL (65.07%) and EtoH (70.4%) respectively and the potency was found to be equivalent as compared to the standard drug, omeprazole. Reduction in the gastric secretory volume, acid secretion and increased gastric pH were the factors observed in treated rats. The presence of volatile oil, flavonoids and saponins present in the extracts of P. guajava may be responsible for the anti-ulcer property exhibited. CONCLUSIONS: The results further suggest that P. guajava possess gastro protective as well as ulcer healing properties which might also be due to its anti-secretory properties.

Anti-ulcer and antioxidant activity of GutGard.

The present study was undertaken to determine the anti-ulcer and antioxidant potential of GutGard, a standardized extract of Glycyrrhiza glabra commonly known as licorice. Effect of various doses (12.5, 25, and 50 mg/kg, po) of GutGard was studied on gastric ulcers in pylorus ligation-, cold-restraint stress- and indomethacin induced gastric mucosal injury in rats. Anti-ulcer activity was evaluated by measuring the ulcer index, gastric content, total acidity, and pH of gastric fluid. GutGard dose dependently decreased gastric content, total acidity, ulcer index and increased pH of gastric fluid in pylorus ligation ulcer model. In cold-restraint stress- and indomethacin induced ulcer models all the doses of GutGard decreased the ulcer index and increased the pH of gastric fluid. The antioxidant activity was evaluated by the oxygen radical absorbance capacity (ORAC) assay. GutGardT exhibited potent antioxidant activity with high hydrophilic and lipophilic ORAC value. GutGard possessed anti-ulcerogenic properties that might be afforded via cytoprotective mechanism by virtue of its antioxidant properties. These results supported the ethnomedical uses of licorice in the treatment of gastric ulcer.

Development of an in vitro system combining aqueous and lipid phases as a tool to understand gastric nitrosation.

Nitrite has long been considered a potential pre-carcinogen for gastric cancer. Acidification of salivary nitrite, derived from dietary nitrate, produces nitrosative species such as NOSCN, NO(+) and N(2)O(3), which can form potentially carcinogenic N-nitroso compounds. Ascorbic acid inhibits nitrosation by converting the nitrosative species into nitric oxide (NO). However, NO diffuses rapidly to adjacent lipids, where it reacts with oxygen to reform nitrosative species. Nitrosation has been studied in vitro in aqueous systems and less frequently in organic systems; however, there is a need to investigate acid-catalysed nitrosation in a system combining aqueous and lipid environments, hence providing a physiologically relevant model. Here, we describe a two-phase system, which can be used as a tool to understand acid-catalysed nitrosation. Using gas chromatography/ion trap tandem mass spectrometry, we investigated the nitrosation of secondary amines as a function of the lipid phase composition and reaction mixing. An increased interface surface area was a driver for nitrosation, while incorporation of unsaturated fatty acids affected morpholine and piperidine nitrosation differently. Linoleic acid methyl esters did not affect morpholine nitrosation and only had a limited effect on N-nitrosopiperidine formation, while incorporation of free linoleic acid to the lipid phase significantly reduced N-nitrosopiperidine formation, but increased N-nitrosomorpholine formation at low levels. The mechanisms driving these effects are thought to involve amine partitioning, polarity and unsaturated fatty acids acting as scavengers of nitrosating species, findings relevant to the nitrosative chemistry occurring in the stomach, where the gastric acid meets a range of dietary fats which are emulsified during digestion.

[Preparation and prescription of enteric coated pellets of Panax notoginseng saponins pellets].

OBJECTIVE: To prepare enteric coated pellets containing panax notoginseng saponins. METHOD: Panax notoginseng saponins loaded pellets were prepared by Extrusion-Spheronization method, and coated by Eudragit L30D-55 using Glatt fluid bed with the bottom spray process, central composite design was used to optimize the coating prescription. RESULT: The drug release of enteric coated pellets of panax notoginseng saponins pellets would be lower than 5% in 2 h in simulated gastric fluid, but reach above 85% in 3 h in simulated human gastroenteric environment. CONCLUSION: The enteric coated pellets of panax notoginseng saponins have good acid residence to avoid panax notoginseng saponins from degrading in gastric acid.

Statistical optimization of ranitidine HCl floating pulsatile delivery system for chronotherapy of nocturnal acid breakthrough.

Present work conceptualizes a specific technology, based on combining floating and pulsatile principles to develop drug delivery system, intended for chronotherapy in nocturnal acid breakthrough. This approach will be achieved by using a programmed delivery of ranitidine hydrochloride from a floating tablet with time-lagged coating. In this study, investigation of the functionality of the outer polymer coating to predict lag time and drug release was statistically analyzed using the response surface methodology (RSM). RSM was employed for designing of the experiment, generation of mathematical models and optimization study. The chosen independent variables, i.e. percentage weight ratios of ethyl cellulose to hydroxypropyl methyl cellulose in the coating formulation and coating level (% weight gain) were optimized with a 3(2) full factorial design. Lag time prior to drug release and cumulative percentage drug release in 7h were selected as responses. Results revealed that both, the coating composition and coating level, are significant factors affecting drug release profile. A second-order polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimized formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. The proposed mathematical model is found to be robust and accurate for optimization of time-lagged coating formulations for programmable pulsatile release of ranitidine hydrochloride, consistent with the demands of nocturnal acid breakthrough.

On the potential of Tephrosia purpurea as anti-Helicobacter pylori agent.

AIM OF THE STUDY: Since Tephrosia purpurea (Linn.) Pers. (Fabaceae) has traditional use in curing different types of wounds including gastroduodenal ulcers, it was of interest to evaluate the in vitro anti-Helicobacter pylori activity profile of the plant extract and its fractions with a view to examining its therapeutic potential, if any. MATERIALS AND METHODS: Employing clinical isolates and standard strains of Helicobacter pylori, the extract and fractions were bioevaluated in terms of MIC and MBC values, acid stability, time-kill kinetics, drug resistance, and synergistic potential. RESULTS: The methanolic extract showed promising activity against clinical isolates and standard strains of Helicobacter pylori, including metronidazole-resistant strains. Fractionation of the extract revealed the n-hexane and chloroform fractions to possess marked activity. The extract and the less polar fractions remained functionally active in acidic condition similar to stomach environment, exhibited consistent bacteriostatic activity during repeated exposure, and demonstrated synergism, complete or partial, even with antibiotic-resistant strains. CONCLUSION: Apolar fractions of Tephrosia purpurea may have therapeutic potential in combating Helicobacter pylori mediated gastroduodenal disorders.

Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants.

UNLABELLED: In 17 adults on a fixed metabolic diet, an 11-day course of cinacalcet increased serum gastrin and basal gastric acid output, but not maximal gastric acid output, compared with a placebo. These findings indicate that the calcium sensor receptor plays a role in the regulation of gastric acid. INTRODUCTION: Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cinacalcet, a CaR allosteric agonist, increases serum gastrin and gastric acid secretion. METHODS: Seventeen healthy adults with normal gastric acid output were placed on an 18-day metabolic diet. On day 8 (baseline), participants were given cinacalcet (15 then 30 mg/day) or placebo for 11 days. Changes in gastric acid output, serum gastrin, and other measures were compared in the two groups. RESULTS: Changes in serum gastrin and basal acid output (adjusted for baseline body weight) were significantly more positive in the cinacalcet group compared with placebo (P = 0.004 and P = 0.039 respectively). Change in maximal acid output was similar in the two groups (P = 0.995). As expected, cinacalcet produced significant decreases in serum PTH (P < 0.001) and ionized calcium levels (P = 0.032), and increases in serum phosphorus levels (P = 0.001) and urinary calcium (P = 0.023). CONCLUSIONS: This study provides in vivo evidence that activation of the CaR increases serum gastrin levels and basal gastric acid secretion in healthy adults.