The effect of oral dissolution therapy for pancreatic stones was evaluated in patients with chronic calcific pancreatitis. The anti-epileptic agent trimethadione was given orally to 30 outpatients at a dose of 0.9-1.5 g daily. On plain X-ray films and CT scans of the abdomen, pancreatic stones began to be dissolved around 8 months of treatment, and diminished in size and number or disappeared in 21 patients (70%) during the mean follow-up period of 32 months. The effect of trimethadione treatment on dissolution of stones was not closely related to the aetiology of the disease, distribution and size of stones, previous history of surgical interventions, or the degree of pancreatic dysfunctions. In three patients who stopped this medication of their own accord, pancreatic stones re-increased or reappeared about 6 months later. During trimethadione treatment, impaired exocrine pancreatic function returned to normal in four of nine patients examined, and diabetes mellitus was well controlled by either diet therapy alone or oral hypoglycaemic agents in eight of 10 patients who did not need insulin before trimethadione treatment. Complete relief of pain was noted in 73% of patients during the treatment. Overall gains and no change in bodyweight were observed in 83% of patients. Mild photophobia was the most common side effect, but could be easily overcome by wearing sunglasses. No severe side effects were observed in the liver, kidney, blood or the eyeground. Pancreatic stones in 30 patients not treated with trimethadione neither disappeared nor diminished spontaneously. Trimethadione treatment may be a useful tool for chemical dissolution of pancreatic stones.

Administration, Oral↗

PubMedDate not supplied

Effect of dimethadione administered intravenously on pancreatic secretion in dogs.

In order to detect both pancreatic excretion of dimethadione (DMO), a weak organic acid, and the effect of pancreatic DMO on secretin-stimulated pancreatic secretion, DMO was given intravenously to dogs with pancreatic fistulae at a dose of 50, 100 and 200 mg/kg. DMO was promptly excreted into pancreatic juice; the concentration decreased exponentially as it did in plasma at the highest dose of the compound. At equilibrium of DMO between pancreatic juice and plasma, the DMO concentration in the juice depended directly on that in plasma; the juice/plasma concentration ratios for DMO exceeded 1.0, ranging from 1.7 to 2.1. Pancreatic DMO caused a small but significant decrease in the water, bicarbonate and sodium secretion at non-equilibrium, and in the bicarbonate secretion at equilibrium. A decrease in the bicarbonate secretion may result largely from the buffer action of bicarbonate on protons provided by the undissociated form of DMO. The sum of both bicarbonate and chloride concentrations in pancreatic juice decreased with the increased DMO concentration in the juice, implying that DMO may compete with the secretion of bicarbonate and/or chloride across the apical membrane of the duct cell. Pancreatic DMO can act as a non-specific inhibitor of pancreatic water and electrolyte secretions.

Animals↗

PubMedDate not supplied

[Importance of Helicobacter pylori in the pathogenesis of gastric cancer. Experimental models in rodents].

UNLABELLED: We found that the seroprevalence in Cancer Institute of H. pylori infection was significantly more frequent in gastric cancer than in age- and gender-matched controls. This study suggested an epidemiological link between H. pylori infection and gastric cancer. H. pylori exhibits a complex system of enzymes which serve a range of functions. Toxic effects are produced by urease (UR), phospholipase (PL) and alcohol dehydrogenase (ADH). We embarked on an exploration of the enzyme activities of H. pylori infected patients using a TLC-autoradioluminography. This method has a wide dynamic range and could offer an analytical technique for studying a radioactive compound and its enzymes in H. pylori infected mucosa. Biopsies samples taken from 21 gastric cancer patients and 95 controls were studied. Although high activity of UR indicates well the presence of H. pylori impairment, activities of ADH and PL reflects more the chronicity of mucosal damage in both groups. Clearly, the enzyme profile showed in our study reflects the "physiological" adaptations behind chronic injured mucosal changes but its relation to gastric cancer and H. pylori needs further study. There is an urgent need to understand the carcinogenesis process using animal models. We performed previous study for to explore the effect of H. pylori infection on N- methyl-N-nitrosourea-induced (MNU) gastric carcinogenesis in mice C57BL/6 mice were administered broth culture of H. pylori and given MNU in drinking water. In terms of the incidence of neoplasms development was increase in the MNU group pre-infected with H. pylori. That findings showed that C57BL/6 mice-infected model is well suited for investigating the bacteria promoter effect in the gastric carcinogenesis. Finally another rodent model study (still in process) showed rapid development of hyperplastic gastritis with gastric erosions in H. pylori-infected MTH1 knockout mice. We sought to further evaluate MTH1 knockout mice as potential test animal for carcinogenesis. CONCLUSION: It is suggested that H. pylori infection is an important risk factor for the development of gastric cancer. The possibility that this organism acts etiologically, exerting its effect over long period of time, is biologically plausible. However, the role of H. pylori per se in that process is still a matter of discussion. The various enzymes of H. pylori discussed in this paper support colonization, and are perhaps important for epithelial damage, they could contribute to the stimulation and modulation of the chronic inflammatory response, but its relation to gastric cancer and H. pylori needs further study. Finally H. pylori in C57BL/6 and knockout mice showed excellent colonization at two months and six months after infection there was adenomatous, hyperplastic and ulcerative changes. Those findings showed that both mice-infected models are well suited for investigating the bacteria promoter effect in the gastric carcinogenesis.

Adenocarcinoma↗