Bioactive extracellular compounds produced by the dinoflagellate Alexandrium minutum are highly detrimental for oysters.

Blooms of the dinoflagellate Alexandrium spp., known as producers of paralytic shellfish toxins (PSTs), are regularly detected on the French coastline. PSTs accumulate into harvested shellfish species, such as the Pacific oyster Crassostrea gigas, and can cause strong disorders to consumers at high doses. The impacts of Alexandrium minutum on C. gigas have often been attributed to its production of PSTs without testing separately the effects of the bioactive extracellular compounds (BECs) with allelopathic, hemolytic, cytotoxic or ichthyotoxic properties, which can also be produced by these algae. The BECs, still uncharacterized, are excreted within the environment thereby impacting not only phytoplankton, zooplankton but also marine invertebrates and fishes, without implicating any PST. The aim of this work was to compare the effects of three strains of A. minutum producing either only PSTs, only BECs, or both PSTs and BECs, on the oyster C. gigas. Behavioral and physiological responses of oysters exposed during 4 days were monitored and showed contrasted behavioral and physiological responses in oysters supposedly depending on produced bioactive substances. The non-PST extracellular-compound-producing strain primarily strongly modified valve-activity behavior of C. gigas and induced hemocyte mobilization within the gills, whereas the PST-producing strain caused inflammatory responses within the digestive gland and disrupted the daily biological rhythm of valve activity behavior. BECs may therefore have a significant harmful effect on the gills, which is one of the first organ in contact with the extracellular substances released in the water by A. minutum. Conversely, the PSTs impact the digestive gland, where they are released and mainly accumulated, after degradation of algal cells during digestion process of bivalves. This study provides a better understanding of the toxicity of A. minutum on oyster and highlights the significant role of BECs in this toxicity calling for further chemical characterization of these substances.

Prucalopride induces high-amplitude propagating contractions in the colon of patients with chronic constipation: a randomized study.

BACKGROUND: This study compared prucalopride, a selective, prokinetic, 5-HT4 receptor agonist, with polyethylene glycol 3350 + electrolytes (PEG3350), an osmotic laxative, on colonic motility parameters, primarily high-amplitude propagating contractions (HAPCs) in patients with chronic constipation. METHODS: This randomized, cross-over, reader-blinded study was conducted at a single site in the USA. The study was open to men and women aged 18-75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 × 13.8 g PEG3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude ≥100 mmHg, propagation ≥20 cm [HAPC1 ]) in the 12 h after treatment administration. Analyses were also conducted at two co-primary thresholds: mean amplitude ≥75 mmHg, propagation ≥20 cm (HAPC2 ); and mean amplitude ≥75 mmHg, propagation ≥10 cm (HAPC3 ). Secondary endpoints included HAPC area under the curve (AUC), contraction force, amplitude, duration, and propagation velocity. KEY RESULTS: Thirteen women were enrolled, with 12 completing the study. Significantly more HAPC1 (8.7 ± 2.06 vs 2.9 ± 2.06; p = 0.012) and HAPC2 (9.0 ± 2.11 vs 3.3 ± 2.11; p = 0.017) were observed in the 12-h periods with prucalopride than with PEG3350. Prucalopride significantly increased mean propagation distance and velocity (HAPC2 ) and mean AUC, force, and amplitude (HAPC3 ) compared with PEG3350. Adverse events were mild or moderate. CONCLUSIONS & INFERENCES: Prucalopride was superior to PEG3350 in inducing HAPCs in patients with chronic constipation. ClinicalTrials.gov number NCT01707667.

Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.

BACKGROUND: A substantial proportion of patients with gastro-oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying. AIM: To evaluate the effect of revexepride, a novel prokinetic 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs. METHODS: A phase 2b, double-blind, parallel-group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e-diary data captured patients' symptoms over an 8-week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation-free days in the second half of the study (weeks 5-8). RESULTS: In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation-free days increased from baseline (range, 15.0-18.8%) to week 8 (62.3-70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose-dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment-emergent adverse events (TEAEs) was revexepride dose-dependent. Only one serious TEAE occurred and none resulted in death. CONCLUSIONS: Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.

Intragastric acidity and omeprazole exposure during dosing with either PA32540 (enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg) or enteric-coated aspirin 325 mg + enteric-coated omeprazole 40 mg - a randomised, phase 1, crossover study.

BACKGROUND: Aspirin therapy is associated with adverse upper gastrointestinal effects. PA32540 is a coordinated-delivery tablet containing enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg. Immediate-release omeprazole (located in outer layer of tablet) is available for instantaneous dissolution rapidly after ingestion, while dissolution of the EC-ASA core is delayed until pH >5.5. AIM: To compare the pharmacodynamic and pharmacokinetic effects of PA32540 (EC-ASA 325 mg + IR-omeprazole 40 mg) vs. enteric-coated (EC)-omeprazole 40 mg. METHODS: This single-centre, open-label, randomised, two-way crossover study in healthy volunteers compared 7 days of once-daily dosing with PA32540 with 7 days of once-daily EC-ASA 325 mg + EC-omeprazole 40 mg dosed concomitantly. The primary endpoint was per cent time intragastric pH >4 over 24 h on Day 7. A key secondary endpoint was determination of the pharmacokinetics of omeprazole and salicylic acid. RESULTS: Twenty-six subjects (mean age 29 years) were enrolled into the study. On Day 7, mean per cent time intragastric pH >4 was 50.6% for PA32540 and 57.6% for EC-omeprazole 40 mg (P = 0.004) and geometric least squares mean AUC0-24 for omeprazole was 1446 h*ng/mL for PA32540 and 2558 h*ng/mL for EC-omeprazole 40 mg. Day 7 median Tmax of omeprazole was 0.5 h for PA32540 and 1.25 h for EC-omeprazole 40 mg. CONCLUSION: Total exposure to omeprazole from PA32540 was 57% of that from EC-omeprazole for the same dose amount (40 mg), while absolute difference in 24-h acid control was 7%. Omeprazole exposure and pH control with PA32540 appear similar to EC-omeprazole 20 mg.

Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome - a double-blind, placebo-controlled study.

BACKGROUND: There is a need for safe and effective treatment options for irritable bowel syndrome (IBS). AST-120 (spherical carbon adsorbent) is a non-absorbed, carbon-based adsorbent with extensive adsorbing capability for histamine, serotonin and other substances implicated in IBS pathogenesis. AIM: To evaluate the efficacy and safety of AST-120 in non-constipating forms of IBS. METHODS: This randomised, double-blind, placebo-controlled trial conducted in the US and Belgium enrolled 115 male and female patients fulfilling Rome III criteria for IBS; individuals with predominantly constipation symptoms were excluded. Subjects were randomised to AST-120 2 g tds or placebo for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo washout and 8-week single-blind active treatment. The primary efficacy endpoint was the proportion of subjects achieving at least a 50% reduction in the number of days with abdominal pain compared with baseline. RESULTS: At Week 4, 26.8% of subjects treated with AST-120 responded on the primary endpoint vs. 10.2% in the placebo arm (P=0.029); at Week 8 response rates were 32.1 and 25.4% respectively (NS). More AST-120 treated subjects experienced improvement in bloating and stool consistency. These benefits abated when AST-120 was replaced by placebo, and resumed once AST-120 was restarted. The frequency of adverse events with AST-120 were less than or equal to placebo. CONCLUSIONS: AST-120 is safe and well-tolerated and reduces pain and bloating in non-constipating IBS, although beneficial effects may be limited in duration. AST-120 represents a locally acting, non-absorbed, novel treatment for IBS and warrants further studies.

Clinical trial: evaluation of gastric acid suppression with three doses of immediate-release esomeprazole in the fixed-dose combination of PN 400 (naproxen/esomeprazole magnesium) compared with naproxen 500 mg and enteric-coated esomeprazole 20 mg: a randomized, open-label, Phase I study in healthy volunteers.

BACKGROUND: PN 400 is a fixed-dose combination formulated to provide sequential delivery of immediate-release (IR) esomeprazole and enteric-coated (EC) naproxen. AIM: To evaluate gastric acid suppression with three doses of esomeprazole in PN 400 compared with EC esomeprazole 20 mg. METHODS: In this Phase I, randomized, open-label study, 28 healthy adults received PN 400 b.d. (naproxen 500 mg plus esomeprazole 10, 20 and 30 mg) and non-EC naproxen 500 mg b.d. plus EC esomeprazole 20 mg o.d., each for 9 days in a crossover fashion. The primary endpoint was percentage of time on day 9 that intragastric pH was >4.0; secondary endpoints included pharmacokinetics and safety. RESULTS: Day 9 percentage of time where intragastric pH was >4.0 was 76.5%, 71.4%, 40.9% and 56.9% [corrected] for PN 400 containing 30, 20 and 10 mg esomeprazole, and naproxen plus esomeprazole 20 mg respectively. This was significantly greater for PN 400 containing 30 and 20 mg esomeprazole vs. naproxen plus esomeprazole 20 mg (95% CI: 13.0-26.0 and 7.8-20.7 respectively). The pharmacokinetics of PN 400 were consistent with its formulation. No serious adverse events occurred. CONCLUSION: PN 400 containing 20 mg esomeprazole was the lowest dose to achieve gastric acid suppression comparable to EC esomeprazole 20 mg and was selected for further evaluation.

Effects of a single dose of rabeprazole 20 mg and pantoprazole 40 mg on 24-h intragastric acidity and oesophageal acid exposure: a randomized study in gastro-oesophageal reflux disease patients with a history of nocturnal heartburn.

BACKGROUND: Nocturnal heartburn is common in patients with gastro-oesophageal reflux disease (GERD). AIM: To compare the effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg on 24-h intragastric acidity and oesophageal acid exposure (OAE). METHODS: A total of 52 subjects with GERD and a >or=6-month history of heartburn were randomized into a blinded, 2 x 2 crossover trial. Subjects' intragastric pH was monitored in two 48-h study periods with 6- to 13-day washout between periods. Patients received placebo on day 1, a single dose of rabeprazole 20 mg or pantoprazole 40 mg on day 2, and standardized meals throughout. RESULTS: The mean percentage time with intragastric pH >4 was significantly greater with rabeprazole vs. pantoprazole for the 24-h postdose interval (44.0% vs. 32.8%; P < 0.001). Significant differences were observed in the daytime (51.0% vs. 42.2%; P < 0.001) and nighttime (32.0% vs. 16.9%; P < 0.001). Rabeprazole was also significantly superior in other intragastric pH parameters. There was no statistical difference for OAE between treatments. CONCLUSIONS: In GERD patients with nocturnal heartburn, rabeprazole 20 mg was significantly more effective than pantoprazole 40 mg in percentage time with intragastric pH >4 during the nighttime, daytime, and 24-h periods. Differences between treatments in OAE were not demonstrated. This trial is registered with http://clinicaltrials.gov, number NCT00237367.

Omeprazole-Mg 20.6 mg is superior to lansoprazole 15 mg for control of gastric acid: a comparison of over-the-counter doses of proton pump inhibitors.

BACKGROUND: Over-the-counter (OTC) proton pump inhibitors (PPIs) relieve heartburn by decreasing the production of gastric acid, but may not do so with equal effectiveness. It is important for healthcare professionals to compare the ability of OTC PPIs to control gastric acid when recommending them for patients with frequent heartburn. AIM: To compare the effects of omeprazole-Mg 20.6 mg and lansoprazole 15 mg (OTC doses in the US) on 24-h steady state gastric acid suppression. METHODS: This single-centre, randomized, double-blind clinical study compared the steady-state gastric acid control of omeprazole-Mg 20.6 mg vs. lansoprazole 15 mg, dosed before breakfast. Volunteers were enrolled in a 3-period, cross-over design (ABB, BAA) with 24-h gastric pH monitoring on dosing day 5. The primary efficacy variable was the percentage time intragastric pH was >4.0 over 24 h on day 5 of dosing. RESULTS: Forty subjects were enrolled; all completed the study. The mean (SE) percentage time pH was >4.0 was 45.7% (3.45%) for omeprazole-Mg 20.6 mg and 36.8% (3.45%) for lansoprazole 15 mg, an absolute difference of 8.9% (P < 0.0001), and a relative difference of 24.2%. Both drugs were well tolerated. CONCLUSION: Omeprazole-Mg 20.6 mg provided a statistically significantly (P < 0.0001) greater acid control than lansoprazole 15 mg.

Intravenous esomeprazole 40 mg vs. intravenous lansoprazole 30 mg for controlling intragastric acidity in healthy adults.

BACKGROUND: Intravenous (IV) formulations of proton pump inhibitors are effective for patients in whom oral therapy is not appropriate. AIM: To compare IV esomeprazole and IV lansoprazole for the control of intragastric pH. METHODS: In this open-label crossover study, healthy, Helicobacter pylori-negative adults were randomized to one of two treatment sequences, each consisting of two 5-day dosing periods of IV esomeprazole 40 mg or IV lansoprazole 30 mg. Twenty-four-hour intragastric pH monitoring was conducted on days 1 and 5 of each dosing period. RESULTS: On days 1 and 5, intragastric pH was >4.0 significantly longer with esomeprazole than lansoprazole (least-squares means: day 1, 40.0% vs. 33.6%; day 5, 61.9% vs. 45.4%; both P < 0.0001). During the first 4 h of pH monitoring, intragastric pH was >4.0 significantly longer on days 1 and 5 with esomeprazole than lansoprazole (P < 0.0001). Kaplan-Meier estimates of median hours to stable pH >4.0 were 4.92 for esomeprazole and 5.75 for lansoprazole (P = 0.0014 for test on Gehan scores). CONCLUSION: In healthy adults, IV esomeprazole 40 mg controlled intragastric acidity faster and more effectively than IV lansoprazole 30 mg.

Comparison of gastric pH with omeprazole magnesium 20.6 mg (Prilosec OTC) o.m. famotidine 10 mg (Pepcid AC) b.d. and famotidine 20 mg b.d. over 14 days of treatment.

BACKGROUND: The onset of acid inhibition for proton pump inhibitors is slower than with H2RAs and generally considered to be at a steady-state after 5 days. Thus, little direct comparison data exists between H2RAs and proton pump inhibitors for gastric acid suppression on day 1 of therapy. Furthermore, the durability of their acid suppression has not been systematically compared. AIM: To compare the effects of 20.6 mg omeprazole magnesium o.m. (Ome-Mg 20), famotidine 10 mg b.d. (Fam 10) and famotidine 20 mg b.d. (Fam 20) on intragastric pH on day 1 and throughout 14 days of dosing. METHODS: The study was a randomized, double-blind, three-dosing regimens, three-period crossover. Healthy adults with frequent heartburn (> or =2 days/week) underwent 24-h gastric pH monitoring on days 0 (baseline), 1, 3, 7 and 14. RESULTS: Thirty-one subjects were included in the per-protocol analyses. On day 1, the mean percentage time pH > 4 (pH4%) was higher for Ome-Mg 20, 44.6%, than for Fam 10, 36.7% (P = 0.032), and not different from Fam 20, 46.9% (P = 0.541). The pH4% was higher for Ome-Mg 20 than either famotidine regimen on all subsequent monitoring days (P < 0.001). The 24-h area under the mean intragastric pH curve showed a similar pattern. Furthermore, after day 1, Ome-Mg 20 demonstrated an increasing and sustained effect in contrast to a decreasing effect for famotidine, consistent with H2RA tolerance. CONCLUSION: Gastric acid suppression on Ome-Mg 20 mg o.m. over 14 days was comparable with Fam 10 mg b.d. or Fam 20 mg b.d. on day 1, and superior thereafter.

Effect of naproxen on gastric acid secretion and gastric pH.

BACKGROUND: The mechanisms for the non-steroidal anti-inflammatory drug-induced inflammation in the stomach are unclear. AIMS: To determine if naproxen (Naprosyn, Roche, Nutley, NJ, USA) alters basal acid output, pentagastrin-stimulated maximal acid output, or fasting gastrin. METHODS: Basal acid output and maximal acid output gastric aspirations were performed pre-naproxen and 7 days post-naproxen 500 mg b.d. in 24 healthy subjects. Volume, pH and acid mEq were determined. Fasting gastrin was obtained. Comparisons were made using paired t-tests (alpha = 0.05). RESULTS: Dosing with naproxen did not statistically decrease mean pH of the basal acid output gastric fluid (3.3 vs. 3.1; N.S.) or the pentagastrin-stimulated maximal acid output gastric fluid (2.7 vs. 2.6; N.S.). Basal acid output total volume was significantly decreased post-naproxen (84 vs. 61 mL/h; P = 0.01), with no change in maximal acid output total volume (196 vs. 188 mL/h; N.S.). Basal acid output mean gastric acidity was significantly increased post-naproxen (0.04 vs. 0.05 mEq/mL; P = 0.03), with no change in maximal acid output mean gastric acidity after naproxen (0.10 vs. 0.10; N.S.). Gastrin was not altered by dosing with naproxen. CONCLUSIONS: Naproxen does not influence total acid secreted but does decrease basal gastric fluid volume, thereby increasing basal gastric acid concentration. These observations define one mechanism by which non-steroidal anti-inflammatory drugs may induce gastric injury.

Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial.

BACKGROUND: Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis. AIM: To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis. METHOD: A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points. RESULTS: No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine. CONCLUSIONS: Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.

A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis.

BACKGROUND: Alicaforsen is an antisense oligonucleotide designed to inhibit expression of human intercellular adhesion molecule 1. Previous clinical studies have demonstrated activity of alicaforsen enema in ulcerative colitis and pouchitis. AIM: To determine the minimally effective dosing regimen of alicaforsen enema in subjects with mild to moderate left-sided ulcerative colitis. METHODS: Randomized, placebo-controlled, double-blind, two-dose ranging multicentre study. One hundred and twelve subjects were equally randomized to receive one of four alicaforsen enema regimens or placebo daily for 6 weeks. Primary end point was Disease Activity Index at week 6. Secondary end points included evaluation of clinical improvement, relapse rates and durability of response. Analysis of data were performed on the intent-to-treat population. RESULTS: No significant difference was observed between treatment arms and placebo in the primary end point. A prolonged reduction in mean% Disease Activity Index relative to baseline was observed in the daily 240 mg alicaforsen enema treatment arm in comparison with placebo from week 18 (51% vs. 18%, P=0.04) to week 30 (50% vs. 11%, P=0.03). CONCLUSIONS: Alicaforsen enema was safe and well tolerated at all doses studied. The durability of the response to alicaforsen enema treatment may suggests a disease-modifying effect.

Bioavailability and therapeutic activity of alicaforsen (ISIS 2302) administered as a rectal retention enema to subjects with active ulcerative colitis.

BACKGROUND: Alicaforsen is a phosphorothioate-modified antisense oligodeoxynucleotide designed to sequence-specifically reduce intercellular adhesion molecule 1 messenger RNA levels. AIMS: To determine the systemic and local bioavailability of alicaforsen, and its activity when administered as a once daily enema in subjects with active ulcerative colitis. METHODS An open-label study was conducted to assess the relative absorption (local and systemic pharmacokinetics) and pharmacologic activity of alicaforsen enema in subjects with active ulcerative colitis. Fifteen subjects received nightly enemas of alicaforsen (240 mg) for a treatment period of 6 weeks. Alicaforsen concentrations in plasma and colonic tissue biopsies were determined. Disease activity index and multiple measurements including endoscopy were used to assess alicaforsen activity in these subjects. RESULTS: Plasma concentrations of parent alicaforsen represented < 0.6% mean bioavailability when compared with historical intravenous area under the plasma concentration-time curves. Concentrations of the intact oligonucleotide in mucosal colonic tissue biopsies were orders of magnitude higher than those observed in plasma. A 46% reduction in mean Disease Activity Index and 33% rate of remission as defined by complete mucosal healing were observed at the end of treatment. Conclusion These data confirm that alicaforsen enema provides local treatment for a local disease with little meaningful systemic exposure.

Intragastric acid control in non-steroidal anti-inflammatory drug users: comparison of esomeprazole, lansoprazole and pantoprazole.

BACKGROUND: Studies to date have not directly compared the pharmacodynamic efficacies of different proton pump inhibitors in controlling intragastric acidity in patients treated with non-steroidal anti-inflammatory drugs. AIM: To compare acid suppression with once-daily esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drug therapy. METHODS: In this multicentre, open-label, comparative, three-way crossover study, adult patients (n = 90) receiving non-steroidal anti-inflammatory drugs were randomized to one of six treatment sequences. At the study site, patients were administered esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg for 5 days each, with a washout period of > or =10 days between each treatment. Twenty-four-hour pH testing was performed on day 5 of each dosing period. RESULTS: The mean percentage of time during the 24-h pH monitoring period that gastric pH was >4.0 was significantly greater with esomeprazole (74.2%) compared with lansoprazole (66.5%; P < 0.001) and pantoprazole (60.8%; P < 0.001), and significantly greater with esomeprazole (P < 0.05) than with the comparators regardless of whether using non-selective vs. cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs. CONCLUSIONS: At the doses studied, esomeprazole treatment provides significantly greater gastric acid suppression than lansoprazole or pantoprazole in patients receiving non-selective or cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs.

The effects of changing temperature correction factors on measures of acidity calculated from gastric and oesophageal pH recordings.

BACKGROUND: Recently, Medtronic notified customers that new correction factors should be used for their Slimline and Zinetics24 single-use, internal-standard pH catheters. AIM AND METHODS: We selected 24-h recordings of oesophageal and gastric pH with the Zinetics24 from our archives for five healthy subjects and for five gastro-oesophageal reflux disease subjects who were studied at baseline and again after 8 days of treatment with a proton-pump inhibitor. All pH values obtained with the old correction factors were rescaled using the new correction factors. Values for median pH, integrated acidity and time pH < or = 4 were then calculated from pH values with old and new correction factors. RESULTS: The new correction factors changed values for median pH, integrated acidity and time pH < or = 4. Values for median pH and integrated acidity changed in a predictable, proportionate way, whereas values for time pH < or = 4 did not. CONCLUSIONS: The new correction factors will not change the interpretation of previously published results with median pH or integrated acidity. In contrast, values for time < or =4 cannot be converted in an obvious way with the new correction factors. Instead, the raw pH data will need to be rescaled and values for time pH < or = 4 recalculated using the rescaled pH data.

Review article: physiologic and clinical effects of proton pump inhibitors on non-acidic and acidic gastro-oesophageal reflux.

The control of oesophageal acid exposure through gastric acid inhibition, as the basis for gastro-oesophageal reflux disease (GERD) treatment, arose from the apparent pH dependency of erosive oesophagitis and relationship to GERD symptoms. The current perception is that reflux disease is an entirely acid-mediated condition, and antisecretory therapies, particularly proton pump inhibitors, are the treatment of choice for patients with erosive and non-erosive reflux disease. A positive patient response to an empiric trial of proton pump inhibitor (PPI) therapy, or the 'PPI test', is commonly suggested as a method of GERD diagnosis. Recent studies have modified our understanding of the relationship between oesophageal acid exposure and GERD pathology, manifestations and symptoms. Whereas the use of PPIs to reduce oesophageal acid exposure in patients with erosions is associated with increased healing rates, non-erosive reflux disease patients are less likely to have an abnormal oesophageal pH profile. Patterns of oesophageal acid exposure, particularly nocturnal oesophageal acid exposure, have been linked to increased disease severity. Non-acidic reflux and the effect of PPIs on this parameter, including bile reflux and the toxicity of bile acids, may also be an important factor in GERD. This article explores some of these assumptions, practices and relationships, including: the association between oesophageal acid exposure and erosive and non-erosive gastro-oesophageal reflux disease; the effect of PPIs on oesophageal acid exposure in erosive oesophagitis patients; the influence of nocturnal acid secretion in GERD and the use of PPIs to control this parameter; the relevance of the PPI test for reflux disease diagnosis; and PPI influence on non-acidic reflux.

Techniques for delivery of arachidonic acid to Pacific oyster, Crassostrea gigas, spat.

The present study tested two techniques for dietary supplementation of Crassostrea gigas spat with PUFA, such as arachidonic acid (AA). The first technique consisted of a preliminary enrichment and growth of an algal concentrate (T-ISO, Isochrysis sp.) with AA dissolved in an ethanol solution, the whole culture then being fed to the spat. This enrichment increased the AA weight percentage in T-ISO neutral and polar lipids from 0.6 to 22.4% and from 0.4 to 6.8%, respectively. The second delivery technique was direct addition separately of free AA dissolved in ethanol solution and algal concentrate (T-ISO + AA) to the spat-rearing tank. To test the efficiency of these delivery techniques, oyster spat were supplemented with AA-enriched T-ISO, T-ISO + AA, and T-ISO alone. The possible biological impacts of these dietary treatments were assessed by measuring growth, condition index, and TAG content of oyster spat. Dry weight and condition index of spat fed AA-enriched T-ISO decreased by 24 and 49%, respectively, after 26 d of feeding; basically, TAG content declined 88% after 34 d of conditioning. When AA was added directly to seawater, spat growth and condition index were comparable with those of oysters fed T-ISO alone. AA incorporation in oyster tissues was assessed by analysis of the FA compositions in both neutral and polar lipid fractions. After 34 d, AA content in neutral lipids reached 7 and 11.7% in the spat fed, respectively, AA-enriched T-ISO and T-ISO + AA, as compared with 1.1% in spat fed only T-ISO. AA incorporation was greater in polar lipids than in neutral lipids, reaching 7.8 and 12.5% in spat fed AA-enriched T-ISO and T-ISO + AA, respectively. A direct addition of PUFA along with the food supply represents an effective and promising means to supplement PUFA to oyster spat.

Comparison of the effects of intravenously and orally administered esomeprazole on acid output in patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Intravenous esomeprazole may be beneficial for patients who cannot take oral medications. AIM: To compare intravenous esomeprazole with oral esomeprazole for effects on maximal acid output during pentagastrin stimulation in patients with gastro-oesophageal reflux disease symptoms. METHODS: In four separate open-label, randomized, two-way crossover studies, adult patients were administered esomeprazole 20 or 40 mg once daily either orally or intravenously (by 15-min infusion or 3-min injection) for 10 days and switched to the other formulation with no washout period. Basal acid output and maximal acid output were measured on days 11, 13 and 21. RESULTS: In the four studies (total of 183 patients), least-squares mean maximal acid output ranged from 3.0 to 4.1 mmol/h after intravenous esomeprazole 40 or 20 mg and from 2.2 to 3.3 mmol/h after oral esomeprazole 20 or 40 mg. Differences between formulations were small and not statistically significant but did not meet the prospectively defined criterion for non-inferiority of the intravenous formulation. Median basal acid output values ranged from 0.04 to 0.27 mmol/h after intravenous administration and from 0.05 to 0.25 mmol/h after oral esomeprazole. CONCLUSIONS: Intravenous esomeprazole is an acceptable alternative to the oral formulation for treatment of up to 10 days of duration.

The fractal nature of human gastro-oesophageal reflux.

BACKGROUND: We are unaware of the analyses of time series data resulting from 24 h recordings of human gastric or oesophageal pH. As a result, we have no understanding of the quantitative changes in gastric or oesophageal acidity over time, the patterns that might characterize these changes, or the physiological significance of gastro-oesophageal reflux. AIM: To examine the time series for gastric and oesophageal pH. METHODS: Detrended fluctuation analysis and lag analysis were used to analyse data from 24 h recordings of oesophageal and gastric pH in five normal subjects and five subjects with gastro-oesophageal reflux disease. RESULTS: Analyses of the patterns of gastric and oesophageal pH over time in normal subjects and subjects with gastro-oesophageal reflux disease indicate that the fluctuations in pH are self-similar across different time scales and are consistent with an underlying fractal process. Furthermore, there is a significant statistical association between sequential pH values separated by as much as 2.2 h. CONCLUSIONS: We hypothesize that the self-similar, fractal pattern encodes information about gastric acidity and that the oesophagus decodes this information and, when appropriate, may signal the stomach to reduce gastric acidity. Subjects with gastro-oesophageal reflux disease might have an impaired oesophageal-gastric feedback mechanism that results in increased gastric acid, which reflux from the stomach into the oesophagus.