Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile.

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

Rabeprazole 10 mg q.d.s. decreases 24-h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype.

BACKGROUND: Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid-related diseases. AIM: To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring. METHODS: Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing. RESULTS: In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6-6.4), 5.7 (4.1-7.4), 6.6 (4.9-8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2-100.0%)], irrespective to CYP2C19 genotype. CONCLUSION: Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night-time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.

Neutron activation analysis of a particle returned from asteroid Itokawa.

A single grain (~3 micrograms) returned by the Hayabusa spacecraft was analyzed by neutron activation analysis. This grain is mainly composed of olivine with minor amounts of plagioclase, troilite, and metal. Our results establish that the Itokawa sample has similar chemical characteristics (iron/scandium and nickel/cobalt ratios) to chondrites, confirming that this grain is extraterrestrial in origin and has primitive chemical compositions. Estimated iridium/nickel and iridium/cobalt ratios for metal in the Itokawa samples are about five times lower than CI carbonaceous chondrite values. A similar depletion of iridium was observed in chondrule metals of ordinary chondrites. These metals must have condensed from the nebular where refractory siderophile elements already condensed and were segregated.

In vivo detection of amyloid ß deposition using ¹9F magnetic resonance imaging with a ¹9F-containing curcumin derivative in a mouse model of Alzheimer's disease.

Amyloid ß (Aß) deposition in the brain is considered the initiating event in the progression of Alzheimer's disease (AD). Amyloid imaging is widely studied in diagnosing AD and evaluating the disease stage, with considerable advances achieved in recent years. We have developed a novel ¹9F-containing curcumin derivative (named FMeC1) as a potential imaging agent. This compound can exist in equilibrium between keto and enol tautomers, with the enol form able to bind Aß aggregates while the keto form cannot. This study investigated whether FMeC1 is suitable as a ¹9F magnetic resonance imaging (MRI) probe to detect Aß deposition in the Tg2576 mouse, a model of AD. In ¹9F nuclear magnetic resonance (NMR) spectra obtained from the whole head, a delayed decreased rate of F ¹9F signal was observed in Tg2576 mice that were peripherally injected with FMeC1 in comparison to wild-type mice. Furthermore, ¹9F MRI displayed remarkable levels of ¹9F signal in the brain of Tg2576 mice after the injection of FMeC1. Histological analysis of FMeC1-injected mouse brain showed penetration of the compound across the blood-brain barrier and binding to Aß plaques in peripherally injected Tg2576 mice. Moreover, the distribution of Aß deposits in Tg2576 mice was in accordance with the region of the brain in which the ¹9F signal was imaged. FMeC1 also exhibited an affinity for senile plaques in human brain sections. These findings suggest the usefulness of FMeC1 as a ¹9F MRI probe for the detection of amyloid deposition in the brain. Furthermore, the properties of FMeC1 could form the basis for further novel amyloid imaging probes.

Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina.

BACKGROUND: Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. OBJECTIVE: The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. PATIENTS AND DESIGN: Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. RESULTS: Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7­73.7) ng/ml vs 20.5 (15.9­27.9) ng/ml, p<0.0001), but there was no significant difference between the two groups in patients with SAP. On multivariate analysis, raised plasma MPO levels and Braunwald class III were independent factors for angiographically-detected complex lesions (adjusted OR 12.49, 95% CI 3.24 to 48.17, p=0.0002). In the atherectomy specimens the number of MPO-positive cells in patients with UAP with complex lesions was significantly higher (p<0.0005) than in patients with simple lesions. Moreover, in this cohort, plasma MPO levels were positively correlated with the number of MPO-positive cells in atherectomy specimens (R=0.42, p=0.024). CONCLUSIONS: This study shows that increased expression and plasma MPO levels are closely related to the presence of angiographically-detected complex lesion morphology in patients with UAP.

Eosinophilic airway inflammation in a cynomolgus monkey.

The present article describes an occurrence of eosinophilic airway inflammation of a 4-year-old female cynomolgus monkey in a vehicle control group of a routine toxicology study. Histologically, the airway lesion was characterized by prominent eosinophilic infiltrates, accompanied by mast cells, lymphocytes, and plasmacytes. The eosinophilic infiltrates were distributed throughout the airway: from trachea through respiratory bronchioles in the lung. The morphological feature of the lesion was indicative of an allergic airway disorder that can occur in humans with asthma. The present case is remarkable in that there is a paucity of reports on naturally occurring allergic airway disorders in nonhuman primates.

Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori.

BACKGROUND: Polymorphism in MDR1 is associated with variation in the plasma level of a proton pump inhibitor. AIM: To investigate whether MDR1 polymorphism is associated with eradication rates of Helicobacter pylori by a triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP2C19 genotype status and bacterial susceptibility to clarithromycin. METHODS: A total of 313 patients infected with H. pylori completed the treatment with lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week. MDR1 C3435T polymorphism and CYP2C19 genotypes of patients and sensitivity of H. pylori to clarithromycin were determined. RESULTS: Logistic regression analysis revealed that the MDR1 polymorphism as well as CYP2C19 genotypes of patients and clarithromycin-resistance of H. pylori were significantly associated with successful eradication. Eradication rates for H. pylori were 82% (83/101: 95% CI = 73-89), 81% (112/139: CI = 73-87), and 67% (44/73: CI = 48-72) in patients with the MDR1 3435 C/C, C/T and T/T genotype, respectively (P = 0.001). CONCLUSIONS: Polymorphism of MDR1 is one of the determinants of successful eradication of H. pylori by the triple therapy with lansoprazole, amoxicillin and clarithromycin, together with CYP2C19 genotype and bacterial susceptibility to clarithromycin.

Neopterin is associated with plaque inflammation and destabilisation in human coronary atherosclerotic lesions.

BACKGROUND: Previous studies have shown that recent activation of the inflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilisation. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages. OBJECTIVE: To elucidate the role of neopterin in coronary plaque destabilisation by immunohistochemical study of the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). PATIENTS AND METHODS: All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n = 25) and UAP (n = 25). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils and neopterin. RESULTS: In 22/25 patients with UAP, abundant neopterin-positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from patients with SAP, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin-positive macrophage score was significantly higher (p<0.001) in patients with UAP than in patients with SAP. Moreover, the neopterin-positive macrophage score showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.55, p<0.001; T cells, r = 0.70, p<0.001). CONCLUSIONS: Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Its exact role in the process needs to be investigated further.

Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori.

Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined.

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s). AIM: To clarify the association between CYP2C19 polymorphisms and gastric cancer development in Japanese. Methods : We determined CYP2C19 genotypes (CYP2C19*1, *2 and *3) in 111 Helicobacter pylori-positive patients with gastric cancer and 315 H. pylori-positive controls without gastric cancer consisting of patients with gastritis only or peptic ulcer. Frequencies of CYP2C19 genotypes and serum pepsinogen I and II levels, a biomarker of gastric atrophy, in the gastric cancers and controls were compared. RESULTS: Frequencies of homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers were 31.5%, 42.3% and 26.2% in the gastric cancers and 38.1%, 47.0% and 14.9% in the controls, respectively (P = 0.046). Poor metabolizers were associated with an increased risk for developing gastric cancer with the age- and sex-adjusted odds ratio (OR) of 1.975 [95% confidence interval (CI): 1.068-3.649], especially for diffuse type (OR: 3.385, CI: 1.187-9.648). There is no significant association between CYP2C19 genotypes and serum pepsinogen I level or pepsinogen I/II ratios, although serum pepsinogen I level in gastric cancers were significantly decreased. CONCLUSIONS: In H. pylori-positive Japanese, poor metabolizers of CYP2C19 appear to be at an increased risk for developing gastric cancer, especially diffuse type, and may require an intensive follow-up for scrutinizing possible gastric cancer development.

Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status.

BACKGROUND: Famotidine increases Helicobacter pylori-eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. AIM: To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. METHODS: Twenty healthy volunteers with different CYP2C19 genotypes--consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers--underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. RESULTS: With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). CONCLUSION: Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine.

Efficacy of gemtuzumab ozogamicin on ATRA- and arsenic-resistant acute promyelocytic leukemia (APL) cells.

Acute promyelocytic leukemia (APL) cells express a considerable level of CD33, which is a target of gemtuzumab ozogamicin (GO), and a significantly lower level of P-glycoprotein (P-gp). In this study, we examined whether GO was effective on all-trans retinoic acid (ATRA)- or arsenic trioxide (ATO)-resistant APL cells. Cells used were an APL cell line in which P-gp was undetectable (NB4), ATRA-resistant NB4 (NB4/RA), NB4 and NB4/RA that had been transfected with MDR-1 cDNA (NB4/MDR and NB4/RA/MDR, respectively), ATO-resistant NB4 (NB4/As) and blast cells from eight patients with clinically ATRA-resistant APL including two patients with ATRA- and ATO-resistant APL. The efficacy of GO was analyzed by (3)H-thymidine incorporation, the dye exclusion test and cell cycle distribution. GO suppressed the growth of NB4, NB4/RA and NB4/As cells in a dose-dependent manner. GO increased the percentage of hypodiploid cells significantly in NB4, NB4/RA and NB4/As cells, and by a limited degree in NB4/MDR and NB4/RA/MDR cells. Similar results were obtained using blast cells from the patients with APL. GO is effective against ATRA- or ATO-resistant APL cells that do not express P-gp, and the mechanism of resistance to GO is not related to the mechanism of resistance to ATRA or ATO in APL cells. Leukemia (2005) 19, 1306-1311. doi:10.1038/sj.leu.2403807; published online 26 May 2005.

Concomitant dosing of famotidine with a triple therapy increases the cure rates of Helicobacter pylori infections in patients with the homozygous extensive metabolizer genotype of CYP2C19.

BACKGROUND: Proton-pump inhibitors, such as lansoprazole, are metabolized in the liver by CYP2C19 and cannot inhibit acid sufficiently in homozygous extensive metabolizers of CYP2C19. AIM: To examine whether famotidine would increase the cure rates of Helicobacter pylori infection by a standard triple therapy. METHODS: A total of 177 H. pylori-positive patients were randomly assigned to either lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week (LCA group; n = 89) or famotidine 20 mg b.d., lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week (FLCA group; n = 88). Famotidine was administered after lunch and before sleep, and the others were after breakfast and dinner. CYP2C19 genotypes were determined by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In the LCA group, the eradication rates for homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers were 63%, 87%, and 100%, respectively (P = 0.014). Those in the FLCA group were 85%, 85%, and 100%, respectively (N.S.). The cure rate for homozygous extensive metabolizers in the FLCA group was significantly higher than that in the LCA group (P = 0.035). CONCLUSION: Famotidine improves the cure rate of H. pylori infection by a triple therapy in CYP2C19 homozygous extensive metabolizers patients.

Acute improvement of atrial mechanical stunning after electrical cardioversion of persistent atrial fibrillation: comparison between biatrial and single atrial pacing.

OBJECTIVE: To evaluate the acute effects of atrial pacing at different pacing sites on mechanical stunning after cardioversion of atrial fibrillation (AF). SETTING: Tertiary referral centre. PATIENTS: 20 patients with persistent AF were studied. INTERVENTIONS: Spontaneous echo contrast (SEC), left atrial appendage emptying velocity (LAAEV), and left atrial appendage emptying fraction (LAAEF) were assessed by transoesophageal echocardiography (TOE) during AF, after conversion to sinus rhythm, and during atrial pacing from the right atrial appendage, left lateral atrium, and both atria simultaneously. Transmitral inflow velocity of the atrial wave (TMIF-A) by TOE and the maximum P wave duration in 12 lead ECG were also measured during sinus rhythm and atrial pacing. MAIN OUTCOME MEASURES: Comparison of atrial mechanical function and P wave duration in 12 lead ECG during atrial pacing from different sites after cardioversion of AF. RESULTS: Compared with sinus rhythm, atrial pacing at 80 beats/min increased LAAEV from mean (SD) 14.6 (10.1) to 33.4 (19.8) cm/s (p = 0.001), LAAEF from 13.8 (8.5) to 32.1 (11.2)% (p < 0.001), and TMIF-A from 24.6 (11.9) to 45.6 (21.0) cm/s (p < 0.001) and reduced SEC grade from 2.6 (1.0) to 1.6 (0.9) (p < 0.001). These effects had a positive force-frequency relation. Biatrial pacing produced the shortest P wave duration and resulted in the most significant improvement in atrial function (LAAEV, 33.2 (19.3) v 53.7 (23.9) cm/s, p = 0.0001; LAAEF, 31.9 (11.1) v 46.2 (12.6)%, p < 0.0001; TMIF-A, 37.7 (18.3) v 54.1 (21.2) cm/s, p < 0.001; SEC grade, 1.4 (1.1) v 0.8 (0.9), p = 0.001, right atrial appendage versus biatrial pacing). CONCLUSIONS: Atrial pacing at increased rates can improve atrial mechanical function after cardioversion of persistent AF. Biatrial pacing may be the most effective technique to reverse atrial mechanical stunning.

Differential expression of cornified cell envelope precursors in normal skin, intraorally transplanted skin and normal oral mucosa.

BACKGROUND: Skin flaps have routinely been used as substitutes for oral mucosa after extensive resection of oral tissues. However, it remains unknown how the transplanted skin flaps perform as a host defence in the new environment of the oral cavity. OBJECTIVES: To evaluate the expression of cornified cell envelope (CCE) precursors in pretransplanted (normal) skin, intraorally transplanted skin and normal oral mucosa, because CCEs are highly responsible for a protective barrier in each type of epithelium. METHODS: We used immunohistochemistry and immunoelectron microscopy to examine the expression of CCE precursors, small proline-rich protein (SPR) 2 and 3 and loricrin, in biopsy specimens of normal skin, transplanted skin and normal oral mucosa, including buccal and lingual (non-keratinized) mucosae, and palatal (keratinized) mucosa. RESULTS: Transplanted skin flaps were classified into two groups. About two-thirds of the transplanted skin flaps displayed a reddish appearance and were devoid of the stratum corneum (SC) together with a psoriasiform inflammatory tissue reaction. Others showed a native appearance, retaining the SC. While SPR2 expression was limited to the stratum granulosum (SG) in both normal and transplanted skin retaining the SC, it extended to the stratum spinosum (SS) of the transplanted skin lacking the SC and that of the normal oral mucosa. Although SPR3 expression was not found in normal skin or in the transplanted skin retaining the SC, it was strongly expressed in the SS of the transplanted skin lacking the SC and the non-keratinized oral mucosa, and in the SS and SG of the keratinized oral mucosa. Loricrin, which was expressed in the SG of normal skin, the transplanted skin retaining the SC and the keratinized oral mucosa, was not detected in the transplanted skin lacking the SC or in the non-keratinized oral mucosa. Immunoelectron microscopy confirmed the ultrastructural localization of SPR3 directly under the cytoplasmic membrane of keratinocytes of the transplanted skin lacking the SC and that of the oral mucosa. CONCLUSIONS: The altered expression of SPR2, SPR3 and loricrin reflects the possible adaptation of epidermal keratinocytes in the new environment of the oral cavity.

Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori.

Current regimens for the eradication of Helicobacter pylori consist of a proton pump inhibitor (PPI) plus one or two antibacterial agents, such as amoxicillin (AMPC), clarithromycin (CAM) or metronidazole (MNZ). PPIs are mainly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. The polymorphism of CYP2C19 is associated with the pharmacokinetics and pharmacodynamics of PPIs. Eradication rates by PPI-based therapies are also affected by this genotype, as well as bacterial resistance to antibiotics. An individualized treatment strategy based on CYP2C19-related pharmacogenetics or pharmacogenomics and bacterial resistance is expected to increase the cure rate of the initial treatment. It is also necessary to recognize that there is a possible drug-drug interaction between some of the drugs used in this treatment regimen.

Proliferative activity of canine mast cell tumours evaluated by bromodeoxyuridine incorporation and Ki-67 expression.

The proliferative activity of 91 canine mast cell tumours was assessed on the basis of the Ki-67 positive index (Ki-67 PI) and mitotic index (MI) and, in 15 cases, also by the labelling index of bromodeoxyuridine (BrdU; an analogue of tritiated thymidine) incorporated in vivo into S-phase cells. BrdU and Ki-67 were detected immunohistochemically. The tumours were graded histologically (I, II or III). The BrdU labelling index (BrdU LI) tended to increase as the grade became higher. In terms of the mean values of Ki-67 PI, significant differences were found between histological tumour grades I and II (P < 0.01) and between grades II and III (P < 0.01). In terms of mean MI, grades I and II were found to differ significantly (P < 0.05). With Spearman rank correlation coefficient and linear regression analysis, the BrdU LI and Ki-67 PI showed a highly significant correlation. This strong correlation indicated that Ki-67 was, like BrdU, a useful marker for proliferative potential in canine mast cell tumours; moreover, its use did not require the prior administration of any reagent to the live animal.

Effect of Helicobacter pylori infection and its eradication on nutrition.

AIMS: To investigate the effects of Helicobacter pylori infection and eradication on nutrition. METHODS: The body weight, height, blood pressure, gastric juice pH and fasting serum levels of glucose, total protein, albumin, total cholesterol and triglyceride were measured in H. pylori-positive and H. pylori-negative subjects, and the effect of eradication of H. pylori on these parameters was determined. The development of gastro-oesophageal reflux disease after treatment was also examined. Eight patients underwent a pancreatic function test before and after H. pylori eradication therapy. RESULTS: The incidence of hypoproteinaemia in H. pylori-positive subjects was significantly higher than that in H. pylori-negative subjects. After eradication of H. pylori, the gastric juice pH values were significantly decreased, and the body weight and serum levels of total cholesterol, total protein and albumin were significantly increased. The incidence of hyperlipidaemia significantly increased and that of hypoproteinaemia significantly decreased in the group with eradication. Pancreatic function improved significantly after eradication of H. pylori. No significant changes in these parameters were observed in the group without eradication. Obese patients had a higher risk of the development of gastro-oesophageal reflux disease after eradication of H. pylori infection. CONCLUSIONS: The eradication of H. pylori appears to improve some nutritional parameters.

Comparison of lansoprazole and famotidine for gastric acid inhibition during the daytime and night-time in different CYP2C19 genotype groups.

BACKGROUND: The acid inhibitory effect of lansoprazole depends on the S-mephenytoin 4'-hydroxylase (CYP2C19) genotype status. The effect of famotidine is independent of this genotype. AIM: To investigate the acid inhibitory effects of lansoprazole vs. famotidine during the daytime and night-time with reference to different CYP2C19 genotypes. METHODS: Fifteen healthy volunteers were given 20 mg famotidine twice a day or 30 mg lansoprazole once a day for 8 days. On post-dose day 8, 24-h intragastric pH monitoring was performed. RESULTS: During the daytime, the intragastric pH with lansoprazole was significantly higher than that with famotidine in the heterozygous extensive metabolizer group, whereas no significant difference was observed in the homozygous extensive metabolizer group. During the night-time, the intragastric pH with famotidine was quite similar to that with lansoprazole in the heterozygous extensive metabolizer and poor metabolizer groups. However, during the night-time, the intragastric pH with famotidine was significantly higher than that with lansoprazole in the homozygous extensive metabolizer group. CONCLUSIONS: An insufficient acid inhibition by lansoprazole during the night-time in the homozygous extensive metabolizer group could be compensated for by famotidine. CYP2C19 genotype testing appears to be useful for predicting the optimal acid inhibitory drug treatment collated with circadian intragastric pH change.