Immune response against Trypanosoma cruzi antigens in Cebus apella monkeys.

The american primate Cebus apella has been used as an experimental model for the study of acute and chronic Chagas' disease. The antibody response elicited by 4 x 10(6) blood trypnomastigotes injected into four monkeys was analysed. Peak titres of IgM and IgG of anti-Trypanosoma cruzi antibodies were found at day 22, and between days 20 and 40 post-infection (p.i.), respectively. The ability of a Mr 37kDa (T37K) glycoprotein purified from T. cruzi epimastigotes to generate IgG anti-T. cruzi antibodies in monkeys, and protect them against a challenge with trypomastigotes, was also studied. Monkeys non-immunized with T37K reached peak values of parasitaemia between days 18 and 21 post-infection, whereas immunized monkeys had lower parasitaemias without important variation. Anti-T37K antibodies in immunized monkeys decreased from day 2 with the lowest titres between days 14 to 22 p.i., coincident with the peak of parasitaemia in control non-immunized monkeys. These results suggest that anti-T37K antibodies could be responsible for the low parasitaemia detected in immunized monkeys.

Gastric acid secretion response in the Cebus apella. A monkey model of chronic Chagas' disease.

The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg) or pentagastrin (64 micrograms/kg) in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n = 10; Colombian, n = 4 and Tulahuen, n = 4) and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead) and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (p < 0.01 and p < 0.05 respectively; "t" test) in comparison to the controls. Barium contrast studies showed enlargement and dilatation of the colon in three infected animals. Histopathological lesions were seen in 75% of the autopsied animals either in colon alone (33%) or both, in colon and esophagus (42%). The normal secretion observed in the CA1 infected group could be due to a lower virulence of the strain, a lower esophageal tropism or the necessity of a longer post-infection time to cause lesions.

Electrocardiographic changes in chronic Trypanosoma cruzi infected Cebus apella monkeys.

PURPOSE: To evaluate electrocardiographic data of Cebus apella monkeys with Chagas' disease. MATERIAL AND METHODS: 53 Cebus apella monkeys (juvenile and adult of both sexes) were used: 35 as a control group and 18 inoculated four-five years ago with 3 different Trypanosoma cruzi strains (CA1, n = 10; Colombian, n = 4; Tulahuen, n = 4). RESULTS: The normal electrocardiogram (ECG) showed differences with that of man, a) high cardiac rate; b) presence of "pulmonary p" wave without pulmonary pathology. The ECT alterations found between 11 and 58 months after last inoculation were: right bundle branch block; intermittent right bundle branch block; left ventricle overload; repolarization disturbances; left anterior hemiblock; extra systole. These alterations resemble those found in humans, as well as clinical parasitological and immunological alterations. Their incidence and the time at which they appeared, seem to vary according to the route, strain, inoculum and frequency of the inoculation. Three of the monkeys died spontaneously 46, 48 and 52 months after the infections due to the natural evolution of the disease, and six were sacrificed during the follow-up. In both cases histopathological lesions were found, and their intensity was directly related to the time and resembled the human disease. CONCLUSION: The Cebus apella, as it reproduces human electrocardiographic and histopathological alterations, a short time after experimental infection, is a suitable model for the study of the different aspects of the physiopathology, immunopathology and therapeutics of the indeterminate and chronic phases of Chagas' disease.

Chronic myocardial damage in experimental T. cruzi infection of a New World primate, Cebus sp. monkey.

Eighteen Cebus apella monkeys, (juvenile and adult of both sexes) were inoculated five years ago, with three Trypanosoma cruzi strains (CA1, n = 10; Colombian, n = 4 and Tulahuen, n = 4), either by conjunctival or intraperitoneal route, once or repeatedly. Parasitological, hematological, serological, enzymatic, radiographic, electro and echocardiographic findings have been previously published and they are similar to those observed in human pathology. The most frequent electrocardiographic alteration was right branch bundle block. Six animals, chosen at random, were sacrificed. Those sacrificed 20 to 25 months post-first inoculation showed focal accumuli of leukocytes with myocytolysis. Foci of diffuse interstitial fibrosis with mild infiltrate of leukocytes among fibers were observed in the animals sacrificed 36 to 47 months post-inoculation. No parasites were seen. The lesions were more prominent in the ventricular walls and the septum. The fact that the infiltrates were predominant in the animals sacrificed at a shorter time after first inoculation and that fibrosis was more severe in those sacrificed at a longer time suggests that there is a progression of the infiltrative lesions to fibrosis, with a leukocytic activity indicative of a chronic phase. These lesions are similar to those described in human chronic Chagas' disease. This would demonstrate that this model is useful in evaluating a progress in the knowledge of the pathogenesis which is still a controversial issue, immunology, immunogenesis and chemotherapeutic agents of the chronic and indeterminate phases of this disease.

Influence of jejunal hypertonic glucose infusion on sham-feeding-stimulated gastric acid secretion: evidence of a defective mechanism in duodenal ulcer patients.

The aims of the present study were to determine in 14 healthy subjects and 14 duodenal ulcer patients the reproducibility of the acid secretory response to a modified sham-feeding test and the effect on this response of intrajejunal hypertonic glucose instillation, in order to evaluate the possibility of the existence of a defective inhibition of the cephalic phase of gastric acid secretion in duodenal ulcer disease. The reproducibility of the acid secretory response to a modified sham-feeding test was demonstrated in both groups in two consecutive tests. The hypertonic glucose instillation produced a significant inhibition of the acid secretory response to modified sham feeding only in the healthy subjects, suggesting that duodenal ulcer patients may have a defective mechanism of acid inhibition during vagal stimulation by modified sham feeding. Non-significant changes were observed in plasma gastrin and pancreatic glucagon levels.

Humoral and cellular parameters of the immune system of Cebus apella monkeys. Cross reactivity between monkey and human immunoglobulins.

The humoral and cellular immunological parameters of the New World non-human primate Cebus apella were analysed. The study included: serum protein immunoelectrophoretic analysis; cross reactivity between monkey and human immunoglobulins by immunoprecipitation, ELISA and indirect immunofluorescence tests; immunoglobulin quantitation by radial immunodiffusion; and assays with peripheral blood lymphocytes involving tests for E and EAC rosettes and detection of surface markers (surface immunoglobulins and CD4-CD8 antigens). The results obtained showed that (a) at least three immunoglobulins with electrophoretic mobility corresponding to IgG, IgA and IgM which showed cross reactivity with the human ones were present in serum; (b) it was possible to evaluate the relative monkey immunoglobulin concentration using specific antibodies against human immunoglobulins and to obtain absolute values using adequate conversion factors; (c) lymphocytes forming E and EAC rosettes were found in peripheral blood in a similar proportion to that reported in man; (d) lymphocyte surface immunoglobulins were detected using anti-human immunoglobulin serum; (e) it was not possible to demonstrate the presence of T helper and T suppressor/cytotoxic lymphocytes using OK T4 and OK T8 monoclonal antibodies.

Determinations of serum and muscle magnesium in Cebus monkeys infected with different T. Cruzi strains

Se midió magnesio (Mg++) sérico y musuclar en monos Cebus apella infectados con diferentes cepas de T. cruzi (CA1, Colombiana y Tulahuén). Los animales se dividieron en cuatro grupos: 1) control (n = 6); 2) CAI (n = 7); 3) Colombiana (n = 2), y 4) Tulahuén (n = 3), según el diseño experimental que se observa en la Tabla 1. En todos los grupos se realizó una biopsia del tensor faciae latae para determinar el Mg++ muscular mediante espectrofotometría de absorción atómica y simultáneamente se tomaron muestras de sangre de la vena femoral para medir magnesemia por complejación, durante la etapa crónica d ela enfermedad. No se observaron diferencias estadísticas, por análisis de varianza, entre los diferentes grupos (Tabla 2). Por lo tanto, podemos inferir que la enfermedad de Chagas no modifica per se los valores de Mg++ sérico y muscular

Determinations of serum and muscle magnesium in Cebus monkeys infected with different T. Cruzi strains

Se midió magnesio (Mg++) sérico y musuclar en monos Cebus apella infectados con diferentes cepas de T. cruzi (CA1, Colombiana y Tulahuén). Los animales se dividieron en cuatro grupos: 1) control (n = 6); 2) CAI (n = 7); 3) Colombiana (n = 2), y 4) Tulahuén (n = 3), según el diseño experimental que se observa en la Tabla 1. En todos los grupos se realizó una biopsia del tensor faciae latae para determinar el Mg++ muscular mediante espectrofotometría de absorción atómica y simultáneamente se tomaron muestras de sangre de la vena femoral para medir magnesemia por complejación, durante la etapa crónica d ela enfermedad. No se observaron diferencias estadísticas, por análisis de varianza, entre los diferentes grupos (Tabla 2). Por lo tanto, podemos inferir que la enfermedad de Chagas no modifica per se los valores de Mg++ sérico y muscular (AU)

Delayed gastric emptying of liquids and solids following Roux-en-Y biliary diversion.

Recent reports cite an increased incidence in delayed gastric emptying following Roux-en-Y biliary diversion for alkaline reflux gastritis. The effect of Roux-en-Y diversion on the gastric emptying of liquids and solids was evaluated following vagotomy and antrectomy and vagotomy and subtotal gastrectomy. Twenty dogs underwent placements of large Thomas cannula in the stomach. Four dogs with intact stomachs served a controls. Eight dogs each with vagotomy and antrectomy were subdivided into Roux-en-Y gastrojejunostomy (RYA) and a Billroth II (B-IIA) group. Eight dogs each with vagotomy and subtotal gastrectomy were subdivided into similar groups. Four dogs - Roux-en-Y (RSTG) and four dogs - Billroth II (B-IISTG). Gastric emptying of solid food, normal saline and 25% dextrose was evaluated. RYA dogs demonstrated a significant delay in gastric emptying of solids compared with corresponding B-IIA animals. RYA dogs had 76, 61 and 42% of solid food retained at three, five and eight hours while B-II animals retained 56, 41 and 20%, respectively. The results are highly significant at all time intervals (p less than 0.001 at five and eight hours). Control animals retained 34, 17 and 3% of solid food at three, five and eight hours. RSTG animals had 73, 52 and 28% retained solids at three, five and eight hours, while B-IISTG animals had 55, 42 and 13% retention, respectively (p less than 0.05 at eight hours). Normal saline was significantly delayed in both Roux-en-Y subgroups compared with B-II dogs (p less than 0.02 in V/A, p less than 0.05 in V/STG). There was a trend toward delayed emptying of 25% dextrose in the Roux-en-Y groups, but significance was achieved only in the RYA compared with B-IIA groups (p less than 0.02 at 30 minutes). Delayed gastric emptying following Roux-en-Y gastrojejunostomy is documented in the experimental animals which underwent vagotomy and appears greater in magnitude than that observed following vagotomy and B-II gastrectomy. These data corroborate the clinical observations of severe delayed gastric emptying in patients undergoing Roux-en-Y diversions for alkaline gastritis.

Effect of intraduodenal acid on the pre- and postvagotomy basal gastric secretion and gastrin.

Acid instillation into the duodenum inhibits basal and stimulated gastric secretion. In man vagotomy suppresses this secretory inhibition. It is postulated that such inhibition responds to a dual mechanism: an hormonal one (enterogastrone) and a nervous one (vagus nerve). This study showed that preoperative duodenal acidification of duodenal ulcer patients results in a decrease in basal gastric secretion and in gastrin levels. On the contrary, in patients submitted to vagal denervation--either through truncal division or highly selective vagotomy--duodenal acidification does not inhibit gastric secretion; however, a drop occurs in basal gastrin levels. An intact gastric vagal innervation therefore, seems necessary for the preservation of the sensitivity of the parietal cell to the effect of hormonal inhibitors, it being immaterial whether duodenal innervation is present or not, as that duodenal acidification provokes a significant fall in serum gastrin levels as determined by radioimmunoassay. This hormonal decrease produced by duodenal acidification can be explained by the inhibition of gastrin release from the antrum. Agreement is expressed with the opinion of other authors that highly selective vagotomy does not appear to carry any advantage over truncal section of the vagus nerves from the standpoint of the inhibitory mechanism of gastric secretion from the duodenum.