[Effects of cholestasis on hepatotoxicity of acetaminophen in rats]. / Efectos de la colestasis sobre la toxicidad hepatica del acetaminofen en ratas.

Acetaminophen high doses toxicity has been reported in clinical and experimental studies in relation with cytochrome P-450. (Acetaminophen metabolite). Thinking that biliary tract obstructions hould increases drugs toxicity because interferes toxic substances excretion or it modify the activity of P-450 we decided to study acetaminophen toxicity in rats with biliary tract obstruction. Male sprague Dawley rats were used (body weight 250-400 gr) in two groups: Group I control (6 rats) with choledoco bile duct ligated; two doses of saline solution 0.9% Intraperitoneal, 0.2 ml/100 gr. were administrated. Group II (Same surgical intervention) received two doses of acetaminophen (intraperitoneal) solution (400 mg/Kg). This group was divided in two (6 rats each), one of this was sacrificed at 48 h. and the other one at 120 h. after acetaminophen injection. Total, direct and indirect bilirubin, alkaline phosphatase, ALT and AST transaminases, hematology study, liver weight, histological studies of liver and kidney were performed in all rats. High incidence of liver necrosis ans significative transaminases increases were found in group II. Our results were discussed taking account that recent biliary tract obstruction increase acetaminophen toxicity, at a half doses reported in other studies. It is possible that mixed oxidation system activity of cytochrome P-450 was increased in our research.

[Reflux esophagitis]. / Esofagitis de reflujo.

Chronic Esophageal reflux induces reflux esophagitis, which is a common finding in gastroenterological practice. Reflux esophagitis produce symptoms like pirosis, regurgitation and in some cases respiratory complains resembling asthma or angina-like chest pain. The pathophysiology of this disease is based on a multifactorial origin, which usually results in the chronic evolution of the disease. In recent years, there have appeared new evidences pointing out to alterations in the relaxing mechanisms of the lower esophageal sphincter; however, some patients having reflux esophagitis show normal shincteric pressure. The sweep action of esophageal smooth muscle is a key point for sending back to stomach the eventually refluxed material; it has been demonstrated that this sweeping action is impaired in many patients having reflux esophagitis. Incompetence of lower esophageal sphincter seems to be related a local to neural alteration rather than to smooth muscle functional disturbance. Recent findings stablis a link between local nitric oxide release and relaxation of the lower esophageal sphincter. Esophageal mucosaldisplay an intrinsic resistance to HCL, pepsin, bilis and enzymes deleterious action by a blockade of back-defusion of hydrogen ions contained in the refluxed material. Nevertheless, some other luminal and non-luminal factors are involved in this mucosalprotection. When these intrinsic resistance factors are abated, tisular lesions like ersion, ulcer and Barret's mucosal changes can occur; is of particular interest because its potential malignant evolution. Esophageal reflux usually resolves with medical treatmen, but in some particular cases surgical correction is indicated for improving the antireflux barrier.

[Physiopathological basis for the treatment of peptic ulcer]. / Fundamentos fisiopatológicos para el tratamiento de la úlcera péptica.

Peptic ulcer pathophysiology has advanced in several ways during the last years; the following facts has been put forward: a) There has been recognized specific receptors controlling oxyntic cell secretion for histamine, acetylcholine, gastrin and prostaglandins. Agonists and antagonists for the above mentioned receptors has been synthesized. The physiology of the proton-pump located at the luminal side of the mucous membrane has been clarified. This pump is responsible for HCl secretion and can be blocked with omeprazole and trimeprazole. b) There is a comprehensive view of the gastric mucosal barrier, which is important for gastric self-protection, against inner or outer noxious stimuli. The mucosal barrier rupture can be the initial step of some gastroduodenal diseases, so the understanding of its functioning is very important to explain the pathophysiology of peptic ulcer. Finally, some etiopathogenic factors has been proved in the development of peptic ulcer, as Helicobacter pylori, which adheres to gastric cells mucus, damaging the cells after colonization, and producing the rupture of the mucosal barrier; which in turn favours peptic ulcer disease. The use of non-steroidal antiinflammatory drugs (NSAID) can act at several levels; the most important one seems to be the alteration of prostaglandins synthesis and consequent decrease of mucus and bicarbonate secretion. At the same time NSAID can cause antro-pyloric motor disturbances which contributes to peptic ulcer development. The understanding of all those pathophysiological factors has promoted the designs of new pharmacological approaches to the medical treatment of peptic ulcer, so new antiulcer drugs can act at different stages of peptic-acid secretion, like H2-antagonists, proton-pump blockers, cytoprotector drugs and antimicrobial agents for Helicobacter pylori eradication.

Potassium transport across the distal colon in man.

1. The mechanism of potassium transport across human distal colon was investigated in twenty-two individuals without evidence of bowel disease, by using a dialysis method in conjunction with measurements of the transepithelial potential difference (p.d.). 2. Whether potassium was absorbed or secreted depended on its initial concentration in the lumen. The potassium net flux was approximately zero when the luminal potassium concentration was between 30 and 50 mmol/l. 3. Potassium secretion rate was little affected by sodium absorption rate, or by the luminal sodium concentration or by the osmolality of the luminal solution. 4. Potassium secretion rate was increased by partial substitution of other cations for sodium, in the descending order Li greater than NH4 greater than Rb greater than Na. Potassium concentration increased on average to over 80 mmol/l when lithium was in the lumen. 5. The observed transepithelial p.d. was inadequate to account for the intraluminal potassium concentrations attained, the discrepancy being most marked when ammonium or lithium was in the lumen. It is suggested that some potassium is secreted by the epithelial cells and this component of the total potassium flux into the lumen is increased when rubidium, ammonium or lithium is substituted for sodium.

Effect of aldosterone on lithium permeability of rat colon mucosa.

The effect of aldosterone on the ionic composition of colonic epithelial cells and on lithium absorption rate was studied by experiments on rats in vivo. Aldosterone considerably increased the rate of sodium absorption without measurably altering the sodium and potassium content of the epithelium. Aldosterone did not alter the electrical resistance of the tissue. With lithium in the lumen, the net sodium fluxes in the colon were similar in normal and aldosterone-stimulated rats but the rate of diffusion of lithium across the epithelium was greater in the aldosterone-stimulated group. The amount of lithium accumulating in the epithelial layer was also considerably increased by aldosterone stimulation. Aldosterone appears to increase the permeability of the mucosal (luminal) barrier allowing increased entry of lithium into the colonic epithelial cells.

Electrical potential difference and absorption of water, sodium, and potassium by the terminal ileum of ileostomy patients.

Measurements of electrical potential difference (pd) and of absorption by a dialysis method were carried out in the terminal ileum of patients with an ileostomy. The pd measured with saline in the lumen and at a few centimetres within the stoma averaged 9.2 mV, lumen negatively charged. The pd values were similar whether the ileostomy had been recently or long established. The pd rose considerably when glucose was added to the luminal solution, the maximum effect being attained with a concentration of 40 mmol/1. With a saline bicarbonate solution (Na 145 or 140 m-equiv/1, K 5, or 10 m-equiv/1) in the dialysis tube, considerable absorption of fluid and sodium was demonstrable with little change in sodium concentration. Potassium secretion occurred with the lower, and absorption with the higher, concentration. The final luminal potassium concentration reached was consistent with a passive distribution between blood and lumen.