Plasmid stability of potential probiotic Lactobacillus plantarum strains in artificial gastric juice, at elevated temperature, and in the presence of novobiocin and acriflavine.

In this study, the presence of plasmids responsible for carbohydrate fermentation and antibiotic resistance and the stability of these plasmids in artificial gastric juice were investigated in 20 Lactobacillus plantarum strains with probiotic properties. Plasmid curing was performed with novobiocin, acriflavine and elevated incubation temperature to identify plasmids encoded with carbohydrate fermentation and antibiotic resistance genes and to compare them with artificial gastric juice. Plasmid profiling of the strains revealed that 100% of the strains were harbouring plasmids in varying sizes and numbers. The plasmid number of the potential probiotic strains ranged between 1 and 4, and the plasmid size ranged between 5.779 and 16.138 kb. The potential probiotic strains could not survive in the artificial gastric juice at pH 2.0. Although the strains maintained their viability in an artificial gastric juice at pH 2.5 and 3.0, and their derivatives lost their plasmids at a high rate (100%). Similarly, high levels of cured derivatives were obtained with 8 µg/mL novobiocin and 100 µg/mL acriflavine applications, and 24 h incubation at 43 °C. All the experiments were also performed to compare with two L. plantarum-type strains containing plasmids responsible for tetracycline and tetracycline + erythromycin resistances. Artificial gastric juice and other plasmid curing treatments caused a high-frequency loss in the antibiotic resistances of type strains. Determining plasmid stability in artificial gastric juice is a novel approach. Plasmid stability in the gastrointestinal tract is important for maintaining the plasmid-encoded probiotic properties.

Copper alloys' metal migration and bioaccessibility in saliva and gastric fluid.

The oral bioaccessibility of copper alloys and pure metals was assessed using in vitro methods with synthetic saliva and gastric fluid. The metal-specific migration rates from polished alloy surfaces are higher in gastric (pH 1.5) than in saliva fluid (pH 7.2). In both media, migrations are higher for lead than for other metals. The bioaccessible metal concentrations in massive copper alloys, after 2 h in gastric fluid, was only <0.01%-0.18%, consistent with the low surface reactivity of copper alloys (defined as 1 mm spheres). The average metal-specific migrations of cobalt, copper, nickel and lead from most of the tested copper alloys in gastric media are comparable to the ones from their pure metals. The data further show that the bioaccessibility of metals in massive copper alloys primarily depends on the bioelution medium, the exposed surface area and the composition of the alloy. The tested copper alloys show only limited evidence for influence of alloy surface microstructure. This is contrary to findings for other alloys such as stainless steel. Additional investigations on other copper alloys could allow to further refine these conclusions. These findings are useful for establishing the hazard and risk profile of copper alloys following oral exposure.

Gastroprotective Effects of Inulae Flos on HCl/Ethanol-Induced Gastric Ulcers in Rats.

Inulae Flos, the flower of Inula britannica L., is used as a dietary supplement, beverage, and medicine in East Asia. In this study, we evaluated the gastroprotective effects of Inulae Flos extract (IFE) against gastric mucosal lesions induced by hydrochloric acid (HCl)/ethanol in rats and explored its potential mechanisms by measuring antioxidant enzyme activity, mucus secretion, and prostaglandin E2 (PGE2) levels. Pretreatment with IFE at doses of 100 and 300 mg/kg significantly inhibited gastric lesions in HCl/ethanol-treated rats. IFE increased the activities of superoxide dismutase and catalase and the levels of glutathione and PGE2 in gastric tissues. The administration of IFE also significantly increased the gastric wall mucus contents in HCl/ethanol-induced gastric lesions. These findings suggest that IFE has gastroprotective effects against HCl/ethanol-induced gastric lesions and exerts these effects through increased antioxidant levels and gastric mucus secretion. Inulae Flos may be a promising agent for the prevention and treatment of gastritis and gastric ulcers.

A rapid and sensitive reversed phase-HPLC method for simultaneous determination of ibuprofen and paracetamol in drug samples and their behaviors in simulated gastric conditions.

Paracetamol is a widely used drug for fever and pain relief. Ibuprofen is a common nonsteroidal anti-inflammatory drug. In this study, a sensitive and accurate reversed phase high performance liquid chromatography method was developed for the simultaneous determination of ibuprofen and paracetamol. The chromatographic separation was achieved on a Phenomenex C18 (250 mm, 4.6 mm, 5 µm) column. Fifty milli molar phosphate buffer (pH 7.5) and methanol were used as mobile phase in a gradient elution mode. The retention times of paracetamol and ibuprofen were 5.7 and 10.4 min, respectively. The linearity of the developed method was established in the range of 0.25 - 250 mg/L with a correlation coefficient of 0.9998 for both analytes. The limit of detection/quantification values were found to be 0.06/0.19 and 0.08/0.26 mg/L for ibuprofen and paracetamol, respectively. The method was successfully applied in drug samples in the form of tablets and suspensions. The calculated concentrations matched with the claimed values on their prospectuses. The drug samples were studied under simulated gastric conditions to determine the behaviors of the analytes in the human body. The obtained results showed no change in the retention time of the analyte peak shapes throughout the 210 minutes.

The Phylogeny and Biological Function of Gastric Juice-Microbiological Consequences of Removing Gastric Acid.

Gastric juice is a unique combination of hydrochloric acid (HCl), lipase, and pepsin. Acidic gastric juice is found in all vertebrates, and its main function is to inactivate microorganisms. The phylogenetic preservation of this energy-consuming and, at times, hazardous function (acid-related diseases) reflects its biological importance. Proton pump inhibitors (PPIs) are one of the most widely used drugs in the world. Due to the reduced prevalence of Helicobacter pylori infection as well as the increased use of inhibitors of gastric acid secretion, the latter has become the most important cause of gastric hypoacidity. In the present manuscript, we review the microbiological consequences of removing gastric acidity. The resulting susceptibility to infections has not been studied extensively, and focus has mainly been restricted to bacterial and parasitic agents only. The strongest evidence concerning the relationship between hypochlorhydria and predisposition to infections relates to bacterial infections affecting the gastrointestinal tract. However, several other clinical settings with increased susceptibility to infections due to inhibited gastric acidity are discussed. We also discuss the impact of hypochlorhydria on the gut microbiome.

Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility.

Tegoprazan [(S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide], a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H+/K+-ATPase. Tegoprazan inhibited porcine, canine, and human H+/K+-ATPases in vitro with IC50 values ranging from 0.29 to 0.52 µM, while that for canine kidney Na+/K+-ATPase was more than 100 µM. A kinetic analysis revealed that tegoprazan inhibited H+/K+-ATPase in a potassium-competitive manner and the binding was reversible. Oral single administrations of tegoprazan ranging from 0.3 to 30 mg/kg in dogs were well absorbed into the blood stream and distributed in gastric tissue/fluid higher than in plasma. Tegoprazan potently inhibited histamine-induced gastric acid secretion in dogs, and a complete inhibition was observed at 1.0 mg/kg starting from 1 hour after administration. Moreover, an oral administration of tegoprazan at 1 and 3 mg/kg reversed the pentagastrin-induced acidified gastric pH to the neutral range. Interestingly, 3 mg/kg tegoprazan immediately evoked a gastric phase III contraction of the migrating motor complex in pentagastrin-treated dogs and similar effects was observed with the other P-CAB, vonoprazan. Tegoprazan is the novel P-CAB that may provide a new option for the therapy of gastric acid-related and motility-impaired diseases.

The Prebiotic Activity of Simulated Gastric and Intestinal Digesta of Polysaccharides from the Hericium erinaceus.

Hericium erinaceus (HE) is a well-known edible and medicinal fungus widely grown in Asian countries. Polysaccharides from the Hericium erinaceus (HEP) are major biological macromolecules. It has been reported that HEP has multiple biological activities, such as antioxidant activity, immunomodulatory effects, anti-inflammatory effect, anti-chronic gastritis activity, and so on. In the current study, we investigated the biological property of HEP during gastrointestinal digestion. The results indicated that both simulated gastric and small intestinal digesta of HEP has better stimulation of probiotics growth than HEP alone, especially for Lactobacillus plantarum BG112. The prebiotic activity was the strongest when HEP was treated by simulated gastric juice for 2 h and by simulated small intestinal juice for 4 h. The molecular weight (Mw) of HEP decreased from 1.68 × 106 Da and 2.32 × 104 Da to 529.3 ± 7.2 Da, as digestion time increased. Meanwhile, the reducing sugar content was significantly increased from 0.610 ± 0.007 to 22.698 ± 0.752 mg/ml, suggesting that the decrease of Mw was likely due to the breakdown of glycosidic bonds. Considerable mannose and galactopyranose were released throughout the gastrointestinal digestion period, indicating that the gastrointestinal digestion resulted in production of free monosaccharides. After fermentation of L. plantarum BG112, the Mw of HEP was decreased and short chain fatty acids (SCFAs) including acetic acid, isovaleric acid, lactic acid, and butyric acid were produced. We speculated that the release of free monosaccharides during gastrointestinal digestion and utilization of HEP, by the probiotics, contributed to the prebiotic activity of HEP's gastric and intestinal digesta. These results unveiled some mechanisms on the close relationship between the structure and bioactivity of polysaccharides, during digestion.

In vitro physiological and antibacterial characterization of ZnO nanoparticle composites in simulated porcine gastric and enteric fluids.

BACKGROUND: Diarrhea in piglets is one of the main causes of animal death after weaning; zinc oxide (ZnO) has been used in high doses for the control of this sickness. The aim of this study was to determine the physicochemical properties of ZnO nanoparticles synthesized and immobilized on a chitosan/alginate (CH/SA) complex and investigate the antimicrobial activity and in vitro release profile of zinc (Zn2+) from these new compounds. The ZnO nanoparticles composites were prepared and combined with CH/SA or CH/SA and sodium tripolyphosphate (TPP). The structure and morphology of the composites were analyzed by characterization methods such as X-ray diffraction, FTIR spectroscopy, thermogravimetric analysis, atomic absorption spectrophotometry and scanning electron microscopy. RESULTS: The crystallite size of ZnO nano was 17 nm and the novel ZnO composites were effective in protecting ZnO in simulated gastric fluid, where Zn2+ reached a concentration six-fold higher than the levels obtained with the unprotected commercial-zinc oxide. In addition, the novel composites suggest effective antimicrobial activity against Escherichia coli and Staphylococcus aureus. CONCLUSIONS: The results described herein suggest that the novel nano composites may work as an alternative product for pig feeding as verified by the in vitro assays, and may also contribute to lower the zinc released in the environment by fecal excretion in animals waste.

Volume, distribution and acidity of gastric secretion on and off proton pump inhibitor treatment: a randomized double-blind controlled study in patients with gastro-esophageal reflux disease (GERD) and healthy subjects.

BACKGROUND: Postprandial accumulation of gastric secretions in the proximal stomach above the meal adjacent to the esophagogastric junction (EGJ), referred to as the 'acid pocket', has been proposed as a pathophysiological factor in gastro-esophageal reflux disease (GERD) and as a target for GERD treatment. This study assessed the effect of proton pump inhibitor (PPI) therapy on the volume, distribution and acidity of gastric secretions in GERD and healthy subjects (HS). METHODS: A randomized, double blind, cross-over study in 12 HS and 12 GERD patients pre-treated with 40 mg pantoprazole (PPI) or placebo b.i.d. was performed. Postprandial secretion volume (SV), formation of a secretion layer and contact between the layer and the EGJ were quantified by Magnetic Resonance Imaging (MRI). Multi-channel pH-monitoring assessed intragastric pH. RESULTS: A distinct layer of undiluted acid secretion was present on top of gastric contents in almost all participants on and off high-dose acid suppression. PPI reduced SV (193 ml to 100 ml, in HS, 227 ml to 94 ml in GERD; p < 0.01) and thickness of the acid layer (26 mm to 7 mm, 36 mm to 9 mm respectively, p < 0.01). No differences in secretion volume or layer thickness were observed between groups; however, off treatment, contact time between the secretion layer and EGJ was 2.6 times longer in GERD compared to HS (p = 0.012). This was not the case on PPI. CONCLUSIONS: MRI can visualize and quantify the volume and distribution dynamics of gastric secretions that form a layer in the proximal stomach after ingestion of a liquid meal. The secretion volume and the secretion layer on top of gastric contents is similar in GERD patients and HS; however contact between the layer of undiluted secretion and the EGJ is prolonged in patients. High dose PPI reduced secretion volume by about 50% and reduced contact time between secretion and EGJ towards normal levels. TRIAL REGISTRATION: NCT01212614.

Effects of Cichorium Intybus L. Root Extract on Secretory Activity of the Stomach in Health and Ulcer Disease.

Gastroprotective effect of Cichorium intybus L. root extract is demonstrated on H. Shay's model of experimental ulcer in rats. The effect is attributed to the antisecretory activity of the plant and stimulation of defense barrier function of the gastric mucosa. The regulatory effect of the phytocomplex on seasonal characteristics of the gastric secretory and defense functions in dogs with Basov's fistula is detected.

Correlation between chronic treatment with proton pump inhibitors and bacterial overgrowth in the stomach: any possible beneficial role for selected lactobacilli?

BACKGROUND: The inhibition of physiological gastric acid secretion induced by proton pump inhibitors (PPIs), the most widely used drugs in the world, may cause a significant bacterial overgrowth in the gastrointestinal tract as a side effect. This study was undertaken firstly to correlate PPI intake with concentration of specific bacterial groups in the stomach as well as possible Helicobacter pylori infection, and secondly to assess the efficacy of the 4 lactobacilli L. rhamnosus LR06 (DSM 21981), L. pentosus LPS01 (DSM 21980), L. plantarum LP01 (LMG P-21021), and L. delbrueckii subsp. delbrueckii LDD01 (DSM 22106) in the restoration of a physiological gastric barrier. METHODS: Total bacteria, sulphite-reducing bacteria (SRB), total coliforms, and total lactobacilli were quantified in samples of gastric juice from 29 subjects taking PPIs for at least 3 months compared with 36 control subjects. The presence of H. pylori was also assessed.The subjects treated with PPIs with a concentration of total bacteria in the gastric juice higher than 10(5) cells/mL were selected for an intervention study with the 4 lactobacilli L. rhamnosus LR06, L. pentosus LPS01, L. plantarum LP01, and L. delbrueckii subsp. delbrueckii LDD01. After 15 days of supplementation, the same bacterial groups were quantified to compare these values with the baseline. RESULTS: No significant correlation was found between the presence of H. pylori and PPI intake. The baseline quantification of bacterial groups (log10 CFU/mL of gastric juice, PPI group vs. control) showed: total bacteria 8.35 versus 3.95 (P<0.001); total coliforms 4.98 versus 2.35 (P<0.001); SRB 5.71 versus 2.28 (P=0.065); and total lactobacilli 3.85 versus 2.20 (P=0.005). After 15 days of treatment with the 4 lactobacilli, the quantification of bacterial groups gave the following results: total bacteria 7.91 versus 8.35 at time zero (P=0.002); total coliforms 4.21 versus 4.98 at time zero (P<0.001); SRB 4.94 versus 5.71 at baseline (P=0.060); and total lactobacilli 7.20 versus 3.85 at baseline (P=0.040). CONCLUSIONS: A significant impairment of intragastric acidity is sufficient to induce a relevant bacterial overgrowth, with particular reference to SRB and total coliforms. This fact can contribute to an increase in the risk of infections and intestinal diseases. It could be crucial to restore the physiological "gastric barrier." The 2-week supplementation with the 4 lactobacilli tested proved to be effective in significantly reducing total bacteria and coliforms in the gastric milieu in subjects chronically treated with PPIs. It is therefore possible to hopothesise a beneficial role for such lactobacilli in clinical practice.

The effect of induction of endogenous CO by heme-oxygenase inducer, hemin versus heme-oxygenase blocker, zinc mesoporphyrin on gastric secretion and ulceration under different conditions in adult male albino rats.

Although its role and importance is less well studied, carbon monoxide (CO) has been identified as the second gasotransmitter in the GI tract. This study was performed to investigate the effect of modifying the endogenous CO production by altering heme oxygenase (HO) activity either by induction through hemin administration or inhibition by zinc mesoporphyrin administration on gastric secretion and ulceration induced by either cold restraint stress (CRS) or indomethacin (IND) treatment in adult male albino rats. Our results revealed that hemin significantly increased HO-1 levels with an increase in carboxyhemoglobin (COHb) level while zinc mesoporphyrin significantly decreased HO-1 levels with a decrease in COHb level in all groups. Hemin pretreatment significantly attenuated the gastric mucosal lesions induced by CRS and IND administration, which was accompanied by significant reduction in free and total acidity of gastric secretion, decreased proteolytic activity and marked attenuation of lipid peroxidation inspite of decreased NO and PGE2 levels. On the other hand, Inhibition of HO-1 activity by zinc mesoporphyrin prevented most of the effects caused by hemin administration except for its similar reduction in gastric mucosal NO and PGE2 levels. On conclusion, Hemin exerts a protective effect against CRS and IND-induced gastric ulcers possibly via inducing HO-1 and increasing endogenous production of CO (Tab. 2, Fig. 4, Ref. 75).

[The ways of prophylaxis of the gastro-intestinal hemorrhage recurrence].

Through three-years period 57 patients, suffering gastro-intestinal hemorrhage (GIH) of the ulcer genesis, were treated in the clinic. Among them were 37 (64.9%) men and 20 (35.1%) women. The patients have had (56.3 +/- 4.7) yrs old at average. The treatment programm for the patients have included a local arrest of GIH, medicinal therapy, directed on restoration of the circulating blood volume, gastric secretion inhibition, rising of the blood coagulation property. In cases of a middle and severe blood loss the blood preparations were transfused--the erythrocytic mass and freshly frozen plasm. Three patients were operated in the high period of GIH. The GIH recurrence was absent. In 7 - 8 days, if a persistent hemostasis was achieved, the patients were transferred to therapeutic department for the conservative therapy prolongation.

Anti-Helicobacter pylori and antiulcerogenic activities of the root cortex of Paeonia suffruticosa.

In this study, we evaluated the gastric protective activities of mokdanpi in vitro. Further, we used experimental ulcer models to identify the active ingredients of mokdanpi. As a preliminary evaluation of mokdanpi ethanolic extract and its ingredients, we assessed its radical scavenging activities. In addition, its antimicrobial activity against Helicobacter pylori (H. pylori) was investigated. The antiulcerogenic activity of the active ingredients was evaluated in pylorus-ligated rats, an HCl/ethanol-induced and an absolute ethanol-induced ulcer model. We confirmed the scavenging effect of the ethanolic extract of mokdanpi and its ingredients against 2,2-diphenyl-1-picrylhydrazyl, nitric oxide and superoxide radicals, and we demonstrated that mokdanpi could inhibit the colonization of H. pylori. In an HCl-ethanol-induced ulcer model, gallic acid and catechin (100 mg/kg) inhibited 40.6% and 41.7% of gastric lesions, respectively. Catechin (100 mg/kg) significantly reduced (p<0.05) the gastric secretion induced by pylorus ligature in rats in comparison to the control group. Gallic acid (100 mg/kg) significantly increased (p<0.05) the mucus contents in an ethanol-induced ulcer model. The antioxidant ingredients (catechin and gallic acid) present in mokdanpi play a major role in antiulcerogenic activity, and demonstrate novel activity against H. pylori.

Changes in gastric pH and in pharmacokinetics of ulipristal acetate - a drug-drug interaction study using the proton pump inhibitor esomeprazole.

OBJECTIVE: Ulipristal acetate is a novel selective progesterone receptor modulator for the treatment of benign gynecological conditions such as uterine myoma. As a Biopharmaceutical Classification System (BCS) II compound, it is highly soluble at low pH but has low solubility at neutral conditions. Esomeprazole, a proton pump inhibitor used widely for treatment of gastric and duodenal ulcers, efficiently increases gastric pH. Thus, the aim of this study was to determine the effects of esomeprazole on the pharmacokinetics of ulipristal acetate. MATERIALS AND METHODS: This was a nonrandomized, single sequence, 2 period, open, study in 18 healthy female subjects. Subjects received oral ulipristal acetate tablets (10 mg) once on Days 1 and 13 and daily esomeprazole administrations (20 mg) from Days 9 through 14. RESULTS: Co-administration of esomeprazole decreased geometric mean Cmax of ulipristal acetate by 65% (geometric mean ratio point estimate (90% CI): 0.35 (0.28 - 0.42)), and delayed median tmax from 0.75 to 1.00 h (Hodges-Lehmann estimate of difference (90% CI): tmax 0.63 (0.25 - 1.25)) but had minor effects on AUCs of +15% and +11% (geometric mean ratio point estimates (90% CI): AUC0-t 1.15 (1.02 - 1.31) and AUC0-∞ (1.11 (0.98 - 1.27)), respectively. A total of 6 adverse events were reported by 4 subjects, none of them being serious. CONCLUSIONS: Concomitant use of ulipristal acetate with esomeprazole at therapeutic concentrations led to a modified absorption rate while exposure in terms of AUC remained close to bioequivalence limits. In the context of chronic administration of ulipristal acetate, no clinically significant effects are expected from co-administration with drugs increasing gastric pH.

Histamine: an undercover agent in multiple rare diseases?

Histamine is a biogenic amine performing pleiotropic effects in humans, involving tasks within the immune and neuroendocrine systems, neurotransmission, gastric secretion, cell life and death, and development. It is the product of the histidine decarboxylase activity, and its effects are mainly mediated through four different G-protein coupled receptors. Thus, histamine-related effects are the results of highly interconnected and tissue-specific signalling networks. Consequently, alterations in histamine-related factors could be an important part in the cause of multiple rare/orphan diseases. Bearing this hypothesis in mind, more than 25 rare diseases related to histamine physiopathology have been identified using a computationally assisted text mining approach. These newly integrated data will provide insight to elucidate the molecular causes of these rare diseases. The data can also help in devising new intervention strategies for personalized medicine for multiple rare diseases.

Protective effects of nebivolol against cold restraint stress-induced gastric ulcer in rats: role of NO, HO-1, and COX-1,2.

Nebivolol, a ß(1)-adrenoceptor antagonist, exhibits vasodilatory and anti-oxidative properties that rendering it attractive candidate for protecting against gastric ulcer. The aim of this study therefore is to evaluate the protective effects of nebivolol against cold restraint stress (CRS)-induced gastric ulcer in rats. Rats were restrained, and maintained at 4°C for 3 h. Nebivolol (5 mg/kg, p.o.) was suspended in 0.5% aqueous solution of carboxymethyl cellulose and was administered 30 min before CRS. Nebivolol exhibited gastroprotective effects as evidenced by significant decreases in ulcer index as well as free and total acid output, and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, with concomitant increases in gastric juice pH and mucin concentration along with gastric mucosal reduced glutathione and nitric oxide (NO) concentrations compared with CRS rats. Moreover, immunohistochemical analysis demonstrated that nebivolol treatment markedly enhanced heme oxygenase-1 as well as cyclooxygenase-1 and cyclooxygenase-2 expressions. The protective effects of nebivolol were confirmed by gastric histopathological examination. Pretreatment with N(ω)-nitro-L-arginine, a NO synthase inhibitor, partly altered the protection afforded by nebivolol. In conclusion, nebivolol protected rats' gastric mucosa against CRS-induced gastric ulceration possibly through anti-oxidant activity, enhancement of gastric mucosal barrier and reduction in acid secretory parameters.

Twice-daily proton pump inhibitor therapy does not decrease the frequency of reflux episodes during nocturnal recumbency in patients with refractory GERD: analysis of 200 patients using multichannel intraluminal impedance-pH testing.

Over half of patients with gastroesophageal reflux disease (GERD) report nocturnal symptoms. Proton pump inhibitors (PPIs) are the main medications used to treat GERD. Multichannel intraluminal impedance with pH (MII-pH) monitoring is the most sensitive method for detection and characterization of GERD. The aim of this study was to assess and compare reflux frequency in patients with refractory GERD symptoms on and off PPI therapy during the nocturnal recumbent period, as assessed by MII-pH testing. We analyzed 24-hour MII-pH studies performed in 200 patients monitored either on twice-daily (n = 100) or off (n = 100) PPI therapy. Demographic analysis of the on-therapy group revealed a mean age of 52 years (24-78 years) with 37% males, and the off-therapy group revealed a mean age of 49 years (18-84 years) with 40% males. All studies were interpreted to assess and characterize the number of acid and nonacid reflux episodes in the nocturnal recumbent period identified by each patient on an overnight recorder (Zephyr, Sandhill Scientific, Inc., Highlands Ranch, CO, USA). The nocturnal recumbent period was the period documented by patients during which they lie in the recumbent period at night to sleep with average periods lasting 456 and 453 minutes for patients on and off PPI therapy. There were more mean recumbent reflux episodes in the on-therapy group in comparison with the off-therapy group (3.76 mean reflux episodes [mre] per patient in the recumbent vs. 2.82 mre); the difference was not statistically significant (P = 0.187). When the reflux events are classified into acid and non-acid reflux episodes, the relative occurrence of acid reflux events is less in the on-therapy group (P = 0.047), while the off-therapy group have fewer nonacid reflux episodes (P = 0.003). PPIs decrease the acidity of esophageal refluxate but do not decrease the relative frequency of reflux episodes in the recumbent position in patients with refractory GERD despite twice-a-day treatment with PPI therapy. The explanation for the finding of numerically increased, although not statistically significant, amount of reflux episodes in the PPI treatment group in this study, and previous studies is unclear and warrants further evaluation.

Effect of Flabellaria paniculata Cav. extracts on gastric ulcer in rats.

BACKGROUND: The leaves and root of Flabellaria paniculata (Malpighiaceae) are frequently used in the treatment of wounds and ulcers in Nigerian folk medicine. The purpose of this study was to compare the effect of ethanolic extracts from the leaves (FPL) and root (FPR) of F. paniculata on gastric ulcers in rats. METHODS: The effect of FPL and FPR (100, 200 and 400 mg/kg) was evaluated in ethanol and indomethacin gastric ulcer models. Control groups for FPL and FPR were orally treated with 3% Tween 20 and distilled water respectively. FPL was further investigated in pylorus ligation model. Misoprostol and cimetidine were used as reference. RESULTS: FPL significantly (P < 0.05) reduced gastric lesions by 82.22% and 67.32% in ethanol and indomethacin induced ulcer models at 100 mg/kg respectively while FPR (100, 200 and 400 mg/kg) did not exert significant effect in the two models. In pylorus ligation model, FPL exerted a significant preventive antiulcer effect as indicated by reduction in gastric volume at 200 and 400 mg/kg doses. Only 400 mg/kg of the extract exerted a significant reduction in ulcer index when compared with the control group. The oral route LD50 of FPL was estimated to be 4570 mg/kg while that of FPR was 2754 mg/kg. The LD50 in intraperitoneal injection was estimated to be 1202.26 and 1380.38 mg/kg for FPL and FPR respectively. The phytochemical investigation showed that both extracts possess triterpenoids and saponin, while the presence of flavonoid was detected only in FPL. CONCLUSIONS: The results of this study indicated that FPL and not FPR is effective against experimentally induced gastric ulcers. The presence of varied phytochemical constituents probably influenced the pharmacological differences between the two extracts.

Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored therapeutic regimen".

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs.Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.