Therapeutic Success with the Suppression of Helicobacter pylori of Intractable Gastric Ulcers

Abstract: Three patients with a long history of gastric ulcers refractory to treatment first with an H₂-receptor antagonist, then with a prostaglandin E_t analogue plus an antagonist, and next with a proton-pump inhibitor, lansoprazole, were given amoxicillin together with an H₂-receptor antagonist, and the ulcers finally healed. The patients were men aged about 60, and two were smokers. Reduction of gastric acidity by lansoprazole may have been satisfactory in these patients because one dose of the drug raised the gastric pH to more than 3.0 for about 97% of the next 24h in all three of the patients, as by the continuous measurement of intraluminal pH. The gastric mucosa of these patients was found to be infected with Helicobacter pylori when tested at the end of treatment with this inhibitor. Their medication was changed from the proton-pump inhibitor to amoxicillin plus an H₂-receptor antagonist, and all of the ulcers healed within 6 weeks. H. pylori was not detected at the end of this treatment. These results indicate that reduction of gastric acidity alone was insufficient to cure the ulcers in these patients. H. pylori may be related to some ulcers being refractory to many antiulcer agents, even proton-pump inhibitors.     

Immunophenotyping of peripheral blood mononuclear cells collected by cytotoxic and cytotoxic/G-CSF mobilization

We investigated surface immunophenotypes of peripheral blood mononuclear cells (PBMC) collected by cytotoxic and cytotoxic/G-CSF mobilization of peripheral blood stem cells (PBSC) from 38 patients with haematological malignancies in complete remission who underwent consolidation chemotherapy. PBMC were collected by leucapheresis during the haemato poietic recovery phase after intensive chemotherapy. G-CSF was used for mobilization of PBSC in 19 cases. Surface immunophenotyping of frozen-thawed PBMC was performed by flow cytometry. Our findings showed that monocytes and T cells were the two major cell components of PBMC. There were very few B cells in PBMC. Expression of CD45RO and HLA-DR was elevated in lymphocytes, suggesting that T cells in PBMC were activated. The percentage of CD34 positive cells were significantly increased in PBMC collected by cytotoxic/G-CSF mobilization (group 1) compared with PBMC collected by cytotoxic mobil ization (group 2). There were significantly higher percentages of CD14 and CD33 positive cells in group 1 than in group 2. The percentage of CD4 positive lymphocytes positive for HLA-DR was significantly higher in group 1 compared with group 2. These observations indicated that PBMC contained a large number of monocytes and activated T cells, especially in cytotoxic/G-CSF mobilization.     

Effects of mineralocorticoid and angiotensin II receptor blockers on proteinuria and glomerular podocyte protein expression in a model of minimal change nephrotic syndrome

Aim: Several proteins constituting the slit diaphragm are considered important for maintaining capillary wall permselectivity. Early intervention with blockers of angiotensin II receptors (AR) and mineralocorticoid receptors (MR) is effective against proteinuria in models of chronic hypertensive and protein‐induced renal damage. However, the effects of AR and/or MR blockers in a model of acute nephrotic syndrome remain unknown. The effects of AR and MR blockers were examined in puromycin aminonucleoside (PAN)‐treated rats. Methods: Six week old male Sprague–Dawley (SD) rats were injected with PAN or vehicle and assigned to groups as follows: vehicle (group C); PAN (group P); PAN followed 3 days later by administration of the MR blocker, eplerenone (group MR), and by the AR blocker, losartan (group AR). Blood pressure and urinary protein excretion were measured and all rats were killed for immunohistochemical investigation on day 14 after PAN administration. Results: Blood pressure did not change throughout the study period. Proteinuria was decreased in groups MR and AR compared with group P (on day 14 after PAN administration, respectively; group P vs AR, P < 0.01; group P vs MR, P < 0.05). Nephrin, podocin and podocalyxin staining was preserved in the glomeruli of groups MR and AR compared with group P. Conclusion: The MR and AR blockers decreased proteinuria in the acute model of nephrotic syndrome with preserved expression of glomerular podocyte protein independently of blood pressure.     

Naive and memory T cell infiltrates in chronic hepatitis C: phenotypic changes with interferon treatment

The phenotypes of infiltrating lymphocytes in liver with chronic hepatitis C, including changes associated with interferon (IFN) treatment, were characterized. Specimens obtained from 22 patients treated with IFN were examined using avidin-biotin-peroxidase immunohistochemistry. In areas of lobular and periportal inflammation, most lymphocytes were CD8⁺ T cells of the CD45RO⁺ (memory) subset. The centres of lymphoid follicles were occupied by CD20⁺ B cells and a few CD4⁺ T cells which were CD45RA⁺ (naive subset). Follicular centres were surrounded mainly with CD4⁺ T cells. CD8⁺ T cells, mostly CD45RO⁺, were scattered through the mantle zones of follicles and extended around them. No significant changes in CD45RA⁺ lobular infiltrates accompanied IFN treatment. On the other hand, the number of CD45RO⁺ lobular infiltrates decreased after IFN treatment in complete responders (P <0.01). Moreover, there were significant correlations between CD45RO⁺ cell counts and serum alanine aminotransferase concentrations, CD45RO⁺ cell counts and the liver histologic grade and CD45RO⁺ cell counts and CD8⁺ cell counts. These results suggest that CD8⁺ memory T cells participate in hepatocyte injury in chronic hepatitis C, and that a decrease of CD8⁺ memory T cells correlates with the decreased liver inflammation with IFN treatment.     

Moment analysis of hepatic local disposition of allopurinol and oxipurinol: metabolism kinetics from allopurinol to oxipurinol in the rat isolated perfused liver

Abstract— Drug metabolism in the liver was examined by the rat isolated perfused liver using the single-pass bolus-input technique. The test compounds, allopurinol and its metabolite oxipurinol, were independently introduced into the liver from the portal vein, and the concentration profiles in the venous outflow were monitored and kinetically analysed by moment theory. The recovery ratios of allopurinol and oxipurinol after the individual administration of each drug were estimated to be 0·17 (±0·08 s.d.) and 1·03 (± 0·02 s.d.), respectively. The outflow recovery ratio of oxipurinol as the metabolite after allopurinol administration was estimated to be 0·80 (±0·07 s.d.). These results indicate that the combined outflow recovery of the precursor and the metabolite after allopurinol administration is almost 100% in the rat liver.