Recent ultrastructural investigations revealed early epithelial lesions in Crohn's disease, while a specific morphological pattern was not identifiable. An increase in plasma cells, lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic granulocytes, as well as focal edema and inflammation of tissue structures was seen in the lamina propria, submucosa and deeper layers. The results are consistent with the frequent discussion about a pathogenetically significant defect of the mucosal 'barrier function', which consists of mechanical, cellular, humoral, immunological and nonimmunological mechanisms, including different histotopographically defined lines of defense of the epithelium and lamina propria. An intact epithelial layer plays an important role as the first line of defense. It is evident that components of the epithelial barrier (absorptive cells, goblet cells, Paneth cells, M cells) show ultrastructural signs of alteration or injury, while the primary agent or event remains unknown. Another pathomechanism would be a preexisting defect in intestinal 'barrier function'. Such a defect would result in an increased uptake of, or an inadequate immune reaction to, ubiquitously occurring antigens/agents (with genetic predisposition). However, no primary defect of epithelial or inflammatory cells has been definitely identified so far. Direct toxic damage of tissue secondarily introducing the inflammatory changes is also possible. Although the morphological alterations in Crohn's disease are not yet clearly understood and exactly interpreted, transmission electron microscopy has been helpful in defining early lesions and has led to further knowledge about the pathogenesis of this disease.

Crohn Disease↗

PubMed1993

[Animal experiment studies of ultrastructural changes in the lamina propria of the ileum caused by dietary fats and comparison with cytopathology in Crohn disease].

Experimental investigations have shown alterations of the ileal mucosal surface after specific fat diets resembling early changes in Crohn's disease. An animal experiment in pigs has been conducted. After creation of an anisoperistaltic segment these were fed either a specific fat diet containing chemically processed, partially hydrogenated fats or a low fat control diet over a period of 3 months. Defined areas of the ileal lamina propria were examined by transmission electron microscopy with the underlying question to what extent ultrastructural alterations could be compared to Crohn's disease. In comparison to the control group these areas were characterized by a dense infiltration of "inflammatory" cells like lymphocytes, histiocytes, macrophages and plasma cells indicating a hyperplasia and activation of lympho-plasmocytotic cells. Additionally, a focal prominent infiltration of mast cells with degranulation was observed as well as a dilatation of axons with depletion of axonal organelles in half of the animals after fat-feeding. Compared to patients with Crohn's disease the results show obvious similarities. It is concluded, that chemically processed fats could cause direct stimulation of immunologically-specific and non-specific cells in the lamina propria mucosae or directly injure the intestinal mucosa with secondary infiltration of inflammatory cells into the lamina propria.

Animals↗

PubMed1992

Effects of sodium salts on pressor reactivity in salt-sensitive men.

Blood pressure in patients with essential hypertension is raised by sodium chloride but not by nonchloride sodium salts. Although a high sodium chloride diet is known to augment the pressor response to norepinephrine and angiotensin II, the effect of nonchloride sodium salts on pressor responsiveness has not been studied so far. To examine whether sodium chloride and nonchloride sodium salts evoke different pressor responses to these agonists, we performed graded norepinephrine and angiotensin II infusions in salt-sensitive (n = 7) and salt-resistant (n = 8) normotensive subjects. The subjects were given a low salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo was added for 1 week each. We found that, although sodium chloride raised mean arterial blood pressure in the salt-sensitive subjects (p less than 0.005), sodium citrate did not. However, under both sodium salts pressor response to norepinephrine and angiotensin II was significantly greater than under placebo (p less than 0.02). Furthermore, with both sodium salts, pressor response in the salt-sensitive subjects was greater than in the salt-resistant subjects (p less than 0.01). This study thus demonstrates that, although blood pressure in salt-sensitive individuals is raised by sodium chloride only, both sodium chloride and sodium citrate evoke similar increases in pressor response to norepinephrine and angiotensin II. Since pressor response increased with both sodium salts but resting blood pressure increased only with sodium chloride, enhanced pressor responsiveness alone cannot account for the sodium chloride-induced rise in resting blood pressure.

Adult↗

PubMed1992

[Experimental damage of the epithelial layer of the ileum by dietary fats: transmission electron microscopy findings and their comparison with cell pathology in Crohn disease].

Regarding the unknown pathogenesis of Crohn's disease repeatedly the importance of diet has been accentuated. Epidemiological, biochemical and animal experimental results have focused on a possible relationship between the consumption of chemically processed, partial hydrogenated fats and the development of regional enteritis. In this context an experimental animal model in pigs was designed to analyze, whether transmission electron microscopic alterations of ileal mucosa could be induced by forage of chemically processed fats. By creation of a retroperistaltic ileal segment the contact time between chyme and intestinal mucosa was prolonged. Our underlying question was to what extent disorders of the intestinal barrier function could be compared to Crohn's disease. Present study concentrates on the epithelial-cell-layer. It was shown that in comparison to the control animals the lamina epithelialis mucosae of all animals after fat-feeding was characterized by: sublethal lesion of the enterocytes/crypt-epithelial cells (shortening and alteration of the microvilli, degeneration of mitochondria, formation of autophagocytic vacuoles); goblet cell hyperplasia and increased production of mucus; focal appearance of intraepithelial lymphocytes as well as presence of polymorphonuclear granulocytes in the epithelium; widening of the intercellular-space locally up to total loss of the functional structure of the epithelial-cell-layer. In total the picture can be evaluated as an inflammatory process of the ileal mucosa. It can be concluded, that chemically processed fats as used in the described experimental conditions could induce this process. The feature of mucosal damage shows obvious similarities to ultrastructural findings in Crohn's disease if compared.

Animals↗

PubMed1990

Dietary sodium restriction: adverse effect on plasma lipids.

In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study. Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P less than 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P less than 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion.

Adult↗

PubMed1990

Salt sensitivity in humans is associated with abnormal acid-base regulation.

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.

Acid-Base Equilibrium↗

PubMed1989

Reliability of salt-sensitivity testing in normotensive subjects.

We examined the reliability of dietary salt-sensitivity testing by repeatedly studying the effects of a high (220 mmol/day) and low (20 mmol/day) salt diet in 15 normotensive subjects. Reliability of classification of salt-sensitivity as described by the kappa statistic was 0.87 implying an almost perfect strength of agreement between the two parts of the study. Whereas only 20% of the subjects with negative familial histories of hypertension were salt-sensitive, this was the case with 68% of the subjects with positive familial histories. Our results show that salt-sensitivity can be reliably tested in normotensive subjects and that it is related to a familial history of hypertension.

Adult↗

PubMed1988

[Pathogenesis of Crohn's disease. Evaluation criteria for an animal model].

The origin of Crohn's disease is controverted. Experimental animal studies have not thus far supported a specific pathogenetic factor, a situation ascribed to the fact that the standard requirements of an "ideal" animal model are unsuited to diseases with a multifactorial pathogenesis such as Crohn's disease. In a new experimental animal model the hypothesis of a causal relationship between chemically processed dietary fats and the development of Crohn's disease was studied in 32 pigs. One finding was that experimental animals showed early morphologic lesions of the mucosa as specific to regional enteritis. The primary changes in the mucosa are thought to play a fundamental role in the pathogenesis of the disease. The model opens up new perspectives for planning, management and evaluation of experimental animal models in studying further aspects of etiology in Crohn's disease.

Animals↗