[Immunological and morphological studies in experimental Chagas' disease in mice].
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Biomedical subjects
Publications and source records attributed to D Alonso.
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Efforts to improve myocardial preservation during aortocoronary bypass procedures have led to the perfusion of saphenous vein segments with potassium cardioplegic (KCP) solutions after completion of the distal anastomosis. Recent reports show that the procurement of veins leads to varying degrees of damage, particularly to the endothelial surface, as a result of the dissection itself, the hydrostatic pressure required to distend the veins in obtaining hemostasis and the composition of the solutions used to irrigate the harvested segments. The biologic activity of arterialized vein segments is largely unknown. We tested the hypothesis that the degree of venous injury inherent in vein harvesting may be compounded by perfusion with a potassium-rich solution, a known vascular irritant. The external jugular vein was removed from 18 dogs. Half of the vein was perfused with 300 ml of a KCP solution at 4 degrees C (40 mEq/l KCl, 10 ml sodium bicarbonate, pH 7.6, osmolarity 340 mosmol) and the other half with lactated Ringer's solution (LR). The treated vein was reversed and interposed into the excluded internal carotid circulation. A sham dissection was done on the opposite jugular vein. The veins were harvested after 6 weeks and assayed for spontaneous and arachidonate-stimulated (AS) prostacyclin activity as well as light microscopic analysis of morphologic changes. Spontaneous and AS production of prostacyclin did not differ significantly in the sham, LR and KCP groups: 1539 +/- 709 and 4166 +/- 1802, 1569 +/- 763 and 3767 +/- 2706, 1860 +/- 1233 and 3947 +/- 3347 pg/ml). Light microscopic analysis revealed an intense adventitial fibrotic reaction in the KCP group and the appearance of fibroblast-like cells in the outer layer of the vein wall. The intima was intact in all three groups. We conclude that intimal damage sustained during harvesting is repaired within 6 weeks, and there is no impairment to surface production of prostacyclin. The intense adventitial fibrotic reaction observed in the KCP-treated group has not been previously reported, and its significance remains unexplained.
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In the absence of thiamine deficiency, the specific effects of protein-calorie malnutrition on left ventricular (L.V.) function are unknown. Mature beagle dogs of both sexes were subjected to a hypocaloric, nitrogen-poor diet which resulted in a weight loss of approximately 40% after seven weeks. Following preparation of this nutritional model, myocardial contractility was assessed acutely by obtaining isovolumetric L.V. contractions on cardiopulmonary bypass at constant heart rate, mean aortic pressure, and at a wide range of end-diastolic volumes. These changes were compared to a matched group of animals which were normally fed. There were consistent decreases in L.V. compliance in malnourished animals compared with normals; indices of ventricular contractility per se (L.V. dp/dt, force-velocity relations, peak developed L.V. pressure) were also diminished in the experimental animals. Myocardial concentration of glycogen was diminished in malnourished compared to control animals. Light and electron microscopic examination confirmed the presence of myofibrillar atrophy in the presence of interstitial edema. These results suggest that protein-calorie malnutrition seriously interferes with normal L.V. function in the experimental animal by reducing compliance as a result of "starvation edema," and by reducing myocardial contractility associated with atrophy of the myofibers.
An attempt to increase the permeability of gastric mucosa to exogenous Krebs cycle intermediates seemed advisable for a better understanding their relationship with acid secretion. At pH 7.4, citrate, oxoglutarate, fumarate, and malate had no significant effect on oxygen uptake (QO2) nor on acid secretion (QH+) by toad gastric mucosa; succinate increased QO2 slightly and had no effect on QH+; but at pH 5.0, oxoglutarate and succinate increased QO2 by 18 and 21%, respectively. 14CO2 evolved by gastric mucosa incubated with [14C]oxoglutarate, succinate, malate, or citrate was 155, 92, 128, and 353%, respectively, greater at pH 5. Citrate, oxoglutarate, succinate, fumarate, and malate increased QH+ by theophylline-stimulated mucosa at pH 5.0 by 25, 39, 35, 17 and 28%, respectively. Oxoglutarate-dependent respiration was shown to correlate with oxoglutarate oxidation. Malonate and arsenite inhibited QO2 and QH+; malonate inhibition was reversed by washout or by succinate. Arsenite was reversed by washout and accelerated by addition of lipoate immediately after washout. The results suggest that the Krebs cycle has concomitant roles in the regulation of QH+ and oxidative metabolism in the toad gastric mucosa.
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Mycocarditis is an uncommon manifestation and, very rarely, a lethal complication of infectious mononucleosis. A 14-year-old girl initially had exudative pharyngitis and splenomegaly and developed refractory ventricular fibrillation. The diagnosis of infectious mononucleosis was confirmed by both a strongly positive heterophil antibody test and a high titer of Epstein-Barr virus. Pathologic studies demonstrated extensive histiocytic and lypmhocytic infiltration of the myocardium.
The mechanism of action of lipoate on frog gastric mucosa was investigated. Oxalacetate (OAA) reversed lipoate-inhibited QO2 and QH+ of chambered mucosas by 70 and 40%, respectively. Pyruvate or glucose produced similar effects. Neither activity was affected by OAA when added after glucose, pyruvate, decanoate, butyrate, or lipoate-propionate-inhibited mucosa. Lipoate-treated or lipoate-propionate-treated mucosa did not respond to histamine; OAA addition prior to histamine restored responsiveness. Tracer and chromatographic techniques showed that lipoate reduced and pyruvate increased OAA formation. Preincubation of mitochondrial extracts of gastric mucosa with 2 mM lipoate increased pyruvic dehydrogenase activity 110%. Pyruvic carboxylase (PC) activity was primarily in the mitochondrial fraction of the gastric mucosa. The PC preparation was shown to have an absolute requirement for CoASAc, contained biotin, was not inhibited by lipoate, and had an apparent Km approximately equal to 3.6 X 10(-4) M for pyruvate. The results suggest that OAA concentration is regulated by PC activity and is one of the factors controlling QO2 and QH+ in the frog gastric mucosa.
Acid secretion (QH+) and oxygen consumption (Qo2) by frog gastric mucosae in vitro were sharply stimulated by lipoate. A rapid decline followed stimulation, subsequently falling below control values. Addition of only glucose or lactate had no effect on Qo2 or QH+. Pyruvate caused slight significant stimulation of Qo2. Any one of these compounds added to lipoate-treated mucosae increased the stimulatory effect of lipoate and markedly slowed the rate of decline subsequent to maximum stimulation. Various fatty acids had a moderate-to-high stimulatory effect on Qo2 and QH+. Lipoate added prior to the addition of fatty acids decreased the stimulatory effect of buryrate (minus 56%), decanoate (minus 87%), and palmitate (minus 60%). Propionate became an inhibitor in the presence of lipoate. Lipoate increased (plus 100%) the amount of glycogen oxidized and decreased (minus 69%) the amount of triglycerides oxidized. Lipoate-treated mucosae did not respond to histamine. Addition of glucose restored responsiveness. The results indicate that beta-oxidation of fatty acids plays a major role in the acid secretory process and is centrally involved in cyclic AMP and histamine stimulation of QH+.
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We postulated that methyl xanthines stimulate hydrochloric acid production in the isolated frog gastric mucosa by inhibiting the phosphodiesterase that destroys adenosine-3',5'-monophosphate (cyclic AMP). In support of this theory, several criteria were satisfied. Exogenously supplied cyclic AMP stimulated hydrogen and chloride transport in the spontaneously secreting mucosa and in the non-acid secreting mucosa in a similar fashion as did the methyl xanthines. Methyl xanthines increased the mucosal content of cyclic AMP, and the increase preceded the secretory response; thereafter, the magnitude of these two quantities paralleled each other. A correspondence was found between the concentration of methyl xanthines that affected acid secretion and the concentration of methyl xanthines that affected the tissue content of cyclic AMP. Theophylline was more effective than caffeine in increasing cyclic AMP content, which is in accord with the previously reported differences in their effect on acid secretion and phosphodiesterase activity.
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eSS rats exhibit a non-insulin-dependent diabetic syndrome, significantly influenced by diet. Long-term effects of intermittent dietary restriction were studied in male eSS rats. Experimental animals were fed ad libitum during 48 h and food-deprived the next 24 h (R) while controls (L) of the same strain were freely fed every day. This schedule was maintained from 21 days of age until all rats were sacrificed. R animals were leaner than L rats at 5, 8 and 13 months of age. Moreover, an improved metabolic profile (i.e., lower levels in blood triglycerides, total blood cholesterol, basal blood glucose and blood glucose after an oral glucose load) was found. Histological examination of nuchal skin specimens showed a significant increase of dermal thickness and epidermal hypotrophy in free-fed animals. Collagenous fibers closely packed were found just beneath the dermo-epidermal junction in L rats. This finding was less pronounced in R rats. The above mentioned results suggest that eSS rats would draw advantage from living in environments where food availability is uncertain. The importance of early dietary restrictions in predisposed genotypes appears to be a valuable preventive measure against diabetic evolution and complications.
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