An investigator blind trial was performed comparing bismuth salicylate, erythromycin ethylsuccinate, and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration. Fifty patients fulfilled the study criteria. There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis. Clearance of organisms led to improvement of the gastritis. C pyloridis was cleared from 15 patients; ofthese, 13 had gastritis initially, which resolved in 12. Conversely, gastritis resolved in only four of 32 patients not cleared of organisms (p<0-0001). There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted (p<0-001). In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate, only one of 15 patients receiving erythromycin ethylsuccinate, and none of 17 patients taking placebo.These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active, stable at low pH, and should penetrate gastric mucus. The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition.
Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given.
Constituent serum folates have been shown to be altered and in some cases raised in diseases in which total folate levels are known to be frequently decreased. Absorption experiments showed that orally administered folate analogues affect the folate pool in different ways. The stability of the 10-formyltetrahydrofolate level in normal subjects is demonstrated.
SUMMARY In an aseptic microbiological assay of folate compounds and their breakdown compounds, using Lactobacillus casei, Streptococcus faecalis, and Pediococcus cerevisiae, 4a-hydroxy-5-methyl-4,5,6,7-tetrahydrofolate and 5-methyl-5,8-dihydrofolate were inactive under all conditions to all three organisms and 5-methyl-5,6-dihydrofolate was inactive unless ascorbate was present in the incubation medium, and then only to L. casei. 5-Methyltetrahydrofolate was active only for L. casei, and activity in purified samples to S. faecalis was due to trace amounts of folic acid. Analysis of S. faecalis values in the serum in normal subjects and in patients with various disorders showed that levels of 10-formyltetrahydrofolate are raised in coeliac disease, leukaemia, rheumatoid arthritis, and schizophrenia.5-Methyltetrahydrofolate is readily absorbed by normal human subjects and by patients with pernicious anaemia but poorly absorbed by patients with coeliac disease or leukaemia. 5-Methyl-5,6-dihydrofolate was quickly absorbed by normal human subjects, being reflected by a considerably raised level of 5-methyltetrahydrofolate in serum when sodium bicarbonate was given by mouth before the 5-methyl-5,6-dihydrofolate. These higher levels were comparable to those in patients with pernicious anaemia after oral administration of 5-methyl-5,6-dihydrofolate. Oral 5-methyl-5,8-dihydrofolate and 4a-hydroxy-5-methyl-tetrahydrofolate did not appear as microbiologically active folates in the serum.The findings of this study suggest that the availability for biological utilisation of the major dietary folate compounds will depend on the amount of gastric acidity and of ascorbate in the intestinal chyme. Many may be unavailable for metabolic utilization in the body.
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