Combination of enprostil and cimetidine is more effective than cimetidine alone in treating gastric ulcer: prospective multicenter randomized controlled trial.

BACKGROUND/AIMS: Little is known about the clinical efficacy of co-therapy of enprostil, a prostaglandin E2 analogue, with a histamine H2-receptor antagonist. We aimed to assess the additive benefit of enprostil in combination with cimetidine for treating gastric ulcer in a prospective multicenter randomized controlled trial. METHODOLOGY: In 43 hospitals 171 intention-to-treat (ITT) patients, diagnosed as having gastric ulcer by endoscopy, were randomly allocated to receive either enprostil 25microg b.i.d. and cimetidine 400mg b.i.d. (Group E=85), or cimetidine 400mg b.i.d. alone (Group C=86) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks. RESULTS: Per protocol (PP) analysis comprised 166 patients (E=82, C=84). Despite no significant advantage at 4 weeks (E=55.3%, C=42.2%), the combination yielded higher healing rates at 8 weeks by ITT (E=89.4%, C=68.6%; p<0.001) and PP analysis (E=92.7%, C=70.2%; p<0.001). Symptom relief rates [E, C] at 2, 4, and 8 weeks were [80.2%, 68.3%] (not significant), [97.4%, 88.3%] (p<0.05), and [95.6%, 87.0%] (p<0.05), respectively. Significant advantage was observed in the patients aged 40 or older, with solitary ulcer (>5mm in diameter), and without smoking or drinking habits. No adverse effects were critical. CONCLUSIONS: Enprostil safely and significantly augmented gastric ulcer healing and symptom relief by cimetidine.

The effects of rabeprazole on parietal cells and enterochromaffin-like cells in rats: a comparison with omeprazole.

BACKGROUND: We investigated the effects of rabeprazole compared with those of omeprazole on enterochromaffin-like cells and parietal cells in rats. METHODS: Rabeprazole or omeprazole was administered for 7 days by intraperitoneal injection (100 mg/kg or 20mg/kg once a day) and the serum gastrin concentration, the antral density of G cells and D cells, fundic histamine content, fundic H+, K+-ATPase mRNA level, and parietal cell morphology were determined. RESULTS: Both rabeprazole and omeprazole inhibited gastric acid secretion and increased the intragastric pH to over 6.5, as well as causing a marked increase in the serum gastrin concentration. The serum gastrin level was lower with rabeprazole treatment than with omeprazole treatment at both doses. Also, the antral G-cell density was higher with omeprazole than with rabeprazole, while the increase in both the histamine content and the H+, K-ATPase mRNA level in the fundic mucosa was higher with omeprazole treatment at both doses, with the difference being significant at 100 mg/kg. Ultrastructural examination indicated that the stimulation of parietal cells by omeprazole was stronger than that by rabeprazole. CONCLUSIONS: Rabeprazole treatment does not drive enterochromaffin-like cells and parietal cells as strongly as omeprazole treatment despite its potent acid suppressive effect, suggesting that it represents a new generation of proton pump inhibitors.

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism.

BACKGROUND: The D allele of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. METHODS: We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7+/-13.3 years) undergoing coronary angiography. RESULTS: The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. CONCLUSION: We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism.

Diagnostic evaluation of acute pancreatitis in two patients with hypertriglyceridemia.

We present two diagnostically challenging cases of acute pancreatitis with hypertriglyceridemia accompanied with chylomicronemia caused with a deficiency of lipoprotein lipase and with the presence of type V hyperlipidemia. Both cases suffered from acute abdomen following the ingestion of fatty food and revealed the increase in parameters of inflammation without significant elevation of serum amylase levels. The imaging examination of ultrasonography could not detect significant findings of acute pancreatitis and a computer tomography scan eventually confirmed the findings of acute pancreatitis. Both cases responded to a low fat diet and administration of a cholecystokinin receptor antagonist, exhibiting a relief of abdominal symptoms. As in the present cases with acute abdomen following the ingestion of fatty food, the identification of serum hypertriglyceridemia and an abdominal computer tomography scan might be useful in establishing the diagnosis of acute pancreatitis and in developing the therapeutic regimen, when hypertriglyceridemia interferes with the evaluation of pancreatic enzyme activities and ultrasound examination provides poor pancreatic visualization.

Expression of fibroblast growth factor receptor genes in human hepatoma-derived cell lines.

The fibroblast growth factor (FGF) function has been considered to contribute to various human tumors and malignant growth of neoplasm. Hepatocellular carcinoma (HCC) is a typical hypervascular tumor, and it is suggested that FGF may be involved in hepatocarcinogenesis. Therefore, the relationship between the progression of HCC and expression of FGFs and FGF receptors (FGFRs) was evaluated in this study. We investigated the expression of messenger ribonucleic acids (mRNAs) of FGFs and FGFRs by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in eight human hepatoma-derived cell lines (Hep3B, HLE, HLF, HUH6, HUH7, KIM1, Li7, and PLC/PRF/5), one hepatoblastoma-derived cell line (HepG2), and human primary hepatocytes. In addition, effects of FGF-1, FGF-2, and FGF-7 on the growth of hepatoma-derived cell lines were studied in serum-free defined culture conditions. An RT-PCR analysis revealed that all cell lines except PLC/PRF/5 expressed all FGFR mRNAs: FGF-R1 (IIIc), -R2 (IIIb), -R2 (IIIc), -R3 (IIIb), -R3 (IIIc), and -R4 mRNAs. In contrast, human primary hepatocytes expressed FGF-R1 (IIIc), -R3 (IIIc), and -R4 mRNAs but not mRNAs of FGF-R2 (IIIb), -R2 (IIIc), and -R3 (IIIb). All cell lines except HUH6 and HUH7 expressed FGF-1 and FGF-2 mRNAs. Addition of exogenous FGF-1 or FGF-2 (or both) to culture stimulated cell proliferation in several cell lines, but FGF-7 exhibited no growth stimulation in all cells. Hepatoma cells may possess a proliferation mechanism regulated by an autocrine mechanism, a paracrine mechanism, or both, which are mediated by FGF-1/FGFR or FGF-2/FGFR (or both). In addition, a gain of FGF-R2 (IIIb), -R2 (IIIc), and -R3 (IIIb) may be associated with malignant transformation of liver tumor and may eventually serve as useful diagnostic and prognostic indicators.

Effects of aged garlic extract (AGE) on colorectal adenomas: a double-blinded study.

Aged garlic extract (AGE) is a material that has the possibility of a cancer-preventive effect according to epidemiologic and animal studies. In order to confirm the effects of AGE on colorectal adenomas, we conducted a double-blinded randomized study using high-AGE (AGE 2.4 ml/day) and low-AGE (AGE 0.16 ml/day) doses 1 groups. Fifty-one patients who were diagnosed as having colorectal adenomas by colonoscopy were randomly assigned to the high-AGE and low-AGE groups. The number and size of adenomas before intake (0 month) and 6 and 12 months after intake were measured using colonoscopy. In 37 patients chosen as efficacy evaluated subjects, 47.4% (9/19) in the high-AGE and 66.7% (12/18) in the low-AGE group had at least one new adenoma for the first and second interval (0 to 12 months after intake), and its relative risk was 0.71. The decrease rate of at least one adenoma was 50.0% (7/14) in the high-AGE group for the second interval (6 to 12 months after intake), whereas there was no decrease in subjects in the low-AGE group (p=0.02). The difference from the base-line for total size of adenomas increased in the low-AGE group, whereas an increase in the high-AGE group was suppressed for the second interval (p=0.04). The difference from the base-line for the total size of adenomas in subjects who had adenomas on the base-line increased in the low-AGE group and decreased in the high-AGE group for the second interval (p=0.03). The results of this study suggest the possibility of preventive and therapeutic effects of AGE on colorectal adenomas, though it is necessary to investigate these in larger-scale and longer-term trials.

[Gemcitabine in elderly patients with unresectable pancreas cancer].

The efficacy and safety of gemcitabine at a starting dose of 1,000 mg/m2 administrated once a week for 3 weeks with 1 week's rest was investigated in elderly 11 patients with unresectable pancreatic cancer. Objective response was not documented. However, pain intensity, analgesic consumption and Karnofsky Performance Status (KPS) were frequently improved. In total, a clinical benefit was observed in 8 out of 11 (73%) patients. Toxicity was mild and well tolerated. These results suggest that gemcitabine had a superior clinical benefit and a mild toxicity profile. Gemcitabine should be the standard treatment in elderly patients with unresectable pancreatic cancer.

Aged garlic extract has potential suppressive effect on colorectal adenomas in humans.

Epidemiological and animal studies suggest AGE and its organosulfur constituents, such as S-allylcysteine and S-allylmercaptocysteine have anticarcinogenic effects. To confirm these effects in humans, a preliminary double-blind, randomized clinical trial using high-dose AGE (AGE 2.4 mL/d) as an active treatment and low-dose AGE (AGE 0.16 mL/d) as a control was performed on patients with colorectal adenomas-precancerous lesions of the large bowel. The study enrolled 51 patients who were diagnosed as carrying colorectal adenomas. The patients were randomly assigned to the two groups after adenomas larger than 5 mm in diameter were removed by polypectomy. The number and size of adenomas right before intake (0 mo) and at 6 and 12 mo after intake were measured using colonoscopy. Thirty-seven patients (19 in the active group, 18 in the control group) completed the study and were evaluated for the efficacy of AGE. The number of adenomas increased linearly in the control group from the beginning (the baseline), but AGE significantly suppressed both the size and number of colon adenomas in patients after 12 mo of high-dose treatment (P=0.04). The results suggest AGE suppresses progression of colorectal adenomas in humans. It appears that AGE has multiple pathways to reduce cancer incidence and suppress its growth and proliferation.

Is apoptosis in antral mucosa correlated with serum nitrite concentration in Japanese Helicobacter pylori-infected patients?

BACKGROUND AND AIM: Helicobacter pylori infection in gastric mucosa is a form of chronic active gastritis that leads to expression of inducible nitric oxide synthase in host macrophages and polymorphonuclear leukocytes. Nitric oxide produced by these cells infiltrating the gastric mucosa could damage DNA. We correlated apoptosis in H. pylori-infected antral tissue from peptic ulcer patients with serum nitrate-plus-nitrite. METHODS: Biopsy specimens were obtained endoscopically from antrum and fundus in 17 peptic ulcer patients before and after H. pylori eradication. Tissue samples were subjected to rapid urease testing and histopathological scoring (updated Sydney system), as well as immunohistochemical detection of single-stranded DNA indicating apoptotic cells. Fasting serum samples were analyzed for combined nitrate and nitrite content. RESULTS: In all cases atrophy was absent to mild in antral mucosa and H. pylori was eradicated successfully. A strong positive correlation was present between apoptosis and both inflammation and activity scores in infected antral mucosa. A significant positive correlation also was noted between apoptosis and H. pylori density. Serum nitrite concentrations were decreased significantly by successful eradication of H. pylori, and showed a strong positive correlation with H. pylori density. Serum nitrite concentrations showed a significant positive correlation with numbers of single-stranded DNA-positive cells. CONCLUSIONS: High H. pylori density was associated with elevated serum nitrate-plus-nitrite (a marker of nitric oxide production in gastric mucosa). Increased apoptosis and abnormal gastric cell turnover are likely results.

Does serum nitrite concentration reflect gastric carcinogenesis in Japanese Helicobacter pylori-infected patients?

This study investigated whether the serum nitrite concentration reflects Helicobacter pylori-induced inflammation and atrophic changes of gastric mucosa. Ninety-seven patients underwent biopsy of both antrum and fundus. Samples were analyzed by the rapid urease test and histopathological examination according to the updated Sydney system. Fasting serum samples from each subject were analyzed for specific IgG Helicobacter pylori antibodies, pepsinogen I and II concentrations, and NO2-/NO3- content. Eleven patients had H. pylori eradicated with proton pump-based triple therapy. There was a strong positive correlation between the Helicobacter pylori density in the gastric mucosa and the serum nitrite concentration, but a negative correlation existed between the atrophic grade of the gastric mucosa and both serum nitrite concentration and Helicobacter pylori density in the gastric mucosa. Serum nitrite concentrations decreased significantly after successful eradication of Helicobacter pylori. Therefore, serum nitrite concentration may be a useful marker for oxidative DNA damage and apoptosis associated with Helicobacter pylori infection.

Comparative report on endoscopic and surgical treatment for early gastric cancer in elderly patients

Dois casos de pacientes idosos com câncer gástrico precoce similares, foram submetidos a tratamento endoscópico e cirúrgico e säo apresentados como exemplos. Considerando os pacientes idosos como um grupo distinto no processo da decisäo terapêutica, discute-se os prós e contras de cada abordagem, tendo em vista a eficácia, efeitos colaterais e qualidade de vida