[Mediastinal paraganglia lesions in chronic chagasic heart disease: cause of sudden death?].
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Chagas Cardiomyopathy↗
Biomedical subjects
M A Rossi
Publications and source records attributed to M A Rossi.
Evidences of 4-hydroxynonenal involvement in modulation of phagocyte activities.
The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of various carbonylic compounds: among these, 4-hydroxynonenal (HNE) displays many biological properties related to neutrophil functions. It stimulates rat and human polymorphonuclear (PMN) cell migration and has been detected during inflammation. The aim of this study was to elucidate and well characterize the mechanism of action of HNE. We observed that micromolar HNE concentrations that influence migration do not stimulate differently from many other chemoattractants the human PMN chemiluminescence (CL) induced by opsonized zymosan or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-arginine (L-arg), the substrate of nitric oxide synthase, into the incubation medium had the effect of modifying human CL. In fact, HNE at 10-6 M, a concentration which is ineffective in absence of L-Arg, at 10-5 M reduces CL emission of PMA-stimulated human PMN. These observations have been confirmed by electron-spin resonance (ESR) analysis. HNE, according to other stimuli, induced PMN phosphoinositide-specific phospholipase C (PL-C). All these results considered together suggest the conclusion that HNE represents an interesting endogenous molecule that plays a role as an inflammatory mediator involved a) in the recruitment of phagocytic cells at the inflamed area, and b) in the modulation of respiratory burst and of nitric oxide (NO) production.
Aldehydes↗
Activation of phosphoinositide-specific phospholipase C of rat neutrophils by the chemotactic aldehydes 4-hydroxy-2,3-trans-nonenal and 4-hydroxy-2,3-trans-octenal.
A comparison has been made between the effects of 4-hydroxy-2,3-trans-nonenal (HNE) and 4-hydroxy-2,3-trans-octenal (HOE), two lipid peroxidation products, on the basal and GTPgammaS-stimulated activities of phosphoinositide-specific phospholipase C (PL-C) of rat polymorphonuclear leukocytes. PL-C activity was determined in vitro by measuring the hydrolysis of [3H] phosphatidylinositol-4,5-bis- phosphate (PtdIns-P2) added as exogenous substrate to neutrophil plasma membranes. PL-C was activated by concentrations of HNE ranging from 10(-8) to 10(-6) M both in the presence and in the absence of 2 x 10(-5) M GTPgammaS; HOE stimulated the enzymatic activity between 10(-11) and 10(-8) M; maximal stimulation was given by 10(-11) M HOE plus GTPgammaS. The aldehyde concentrations able to accelerate PtdIns-P2 breakdown displayed a good correspondence with those which have been reported to stimulate the oriented migration of rat neutrophils. Pretreatment of neutrophils with pertussis toxin prevented the stimulation of PL-C by 10(-11) M HOE and by HOE plus GTPgammaS. Our results suggest that the chemotactic action of HNE and HOE might depend on the activation of PL-C; furthermore a regulatory G protein appears to be involved in the acceleration of PtdIns-P2 turnover by HOE.
Aldehydes↗
Focal cerebral ischemia and patent cardiac foramen ovale.
By means of transthoracic contrast echocardiography, the prevalence of a patent foramen ovale (PFO) was studied, in a continuous series of 48 patients aged less than 50 years with a recent episode of acute cerebral ischemia. A PFO was found in 11 subjects (23%). In the subgroup of younger patients (aged less than 30 years), the prevalence was much higher than in those aged 30 or more (58% against 11%, p = 0.0022). In the 19 patients with clear evidence of extracardiac causal factors of cerebral ischemia, there was no PFO; of the remaining 29 subjects, a PFO was present in 11 (38%) (p = 0.0015). In conclusion, the possible presence of a PFO must be carefully investigated in subjects with cerebral ischemia aged less than 30, as well as in subjects aged between 30 and 50 in whom there is no acceptable explanation for their cerebral ischemic episode.
Adult↗
Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum-induced rat liver fibrosis.
The effect of captopril on the development of hepatic septal fibrosis in a specific experimental model produced by repeated injections of whole pig serum into the peritoneal cavity of rats was studied. The results afforded four basic conclusions. First, the experimental model used seems to be a pure form of septal fibrosis, which depends on active tissue fibroplasia, without hepatocyte necrosis. The fibrotic septa, located between limiting plates of adjacent classic hepatic lobules, and delimiting the classic liver lobule, consisted of collagen fibers infiltrated by eosinophils, mast cells, fat-storing cells (Ito cells), transitional cells and interstitial fibroblasts. Second, the angiotensin-converting enzyme inhibitor captopril attenuated the hepatic fibrosis induced by pig serum administration, as proven by a decrease in hepatic hydroxyproline concentration and histological examination of the liver. Third, this attenuation of hepatic fibrosis might be related, at least in part, to diminished mast cell and eosinophil accumulation in the hepatic tissue. Finally, these data may indicate a novel action of angiotensin-converting enzyme inhibitor in general, and for captopril in particular, as drugs potentially capable of reducing eosinophils in fibrotic processes.
Animals↗
[Failure of the treatment with penicillin in a case of Neisseria meningitidis meningitis].
Most Neisseria meningitidis are susceptible to penicillin with a minimal inhibitory concentration (MIC) < or = 0.6 mg/L and mortality related to meningococcal meningitis has been low. In recent years, however, N. meningitidis moderately susceptible to penicillin (MIC 0.12-1 mg/L) has been isolated in South Africa, England, USA, and mainly Spain. We report a case of a 16-year old male patient, who was admitted with a diagnosis of meningitis. Because group C N. meningitidis was isolated from cerebrospinal fluid, the patient received 300,000 Ul/Kg penicillin G. Seventy-two hours later, a new lumbar puncture was performed, and N. meningitidis was again isolated from culture. Beta-lactamase activity of the isolate was negative and MIC measurement showed that it was moderately susceptible to penicillin, probably due to modification of a penicillin binding protein. Penicillin G was then discontinued, and the patient was given 50 mg/Kg ceftriaxone. A third lumbar puncture performed on the eighth day after admission showed a negative bacteriological culture. The patient was discharged without neurological sequelae after 14 days of treatment. This case report shows that small changes in N. meningitidis sensitivity may be of clinical relevance.
Adolescent↗
Pathologic findings in 74 dysfunctional Braile-Biomédica bovine pericardial heart valves recovered at reoperation, 1978 to 1990.
This report describes the morphological data obtained from 74 Braile-Biomédica bovine pericardial valves (previously named IMC bovine pericardial valve) recovered at reoperation in our institution between 1978 and 1990. This retrospective analysis allowed for a thorough evaluation of the pathologic findings after long-term implantation of the Braile-Biomédica pericardial xenograft. The major cause of valve failure was pericardial tissue calcification, causing cuspal stiffening or structural defect responsible for clinical symptoms of stenosis and/or regurgitation. Our results demonstrated calcification in 65% of the explanted bioprostheses. Calcific deposits were most extensive in the tunica fibrosa of the pericardium, more prevalent in patients less than 30 years old at the time of implantation, and in valves implanted in the mitral position. Mild to moderate degenerative changes of the native pericardium were observed. No differences between men and women could be detected. Endocarditis was the second most frequent cause of xenograft failure (16%). Cuspal tears, contrasting with previous reports on the pathological features in clinically failed pericardial valves, were relatively infrequent (6.8%). Two valves explanted (2.7%) because clinical manifestation of valvular incompetence showed marked degenerative changes of the pericardial native tissue as the only findings. These observations, very similar to those reported for porcine aortic valves, complement and give support to previously published data on the satisfactory clinical performance of the Braile-Biomédica pericardial bioprosthesis. The discrepancy between the present observations and those reported by other authors on different types of pericardial valves, reinforces the opinion that these pericardial bioprostheses should not be studied as an unified group, the results and conclusions must be specific for each one of them.
Adolescent↗
An age-related gamma delta T cell suppressor activity correlates with the outcome of autoimmunity in experimental Trypanosoma cruzi infection.
In this work the suppressive activity of splenic T cells from young and aged BALB/c mice infected with Trypanosoma cruzi were compared and correlated with the development of autoimmune myocarditis. The T cells from young adult BALB/c mice with acute T. cruzi infection exhibit suppressor activity when added to full allogeneic or Mls-disparate mixed lymphocyte cultures. This suppression could not be reverted by exogenous interleukin (IL)-2 and was not directly dependent on the presence of IL-4, IL-10 or transforming growth factor-beta. Further characterization of the T cell lineage responsible for the suppressor activity by in vitro and/or in vivo depletion with monoclonal antibody to alpha beta or gamma delta T cell receptor revealed that splenic gamma delta T cells function as suppressor lymphocytes in young T. cruzi-infected mice. In addition, these young adult BALB/c mice do not develop autoimmune myocarditis and showed a low incidence of syngeneic heart graft rejection in the early chronic phase of the infection. In contrast, T cells from acutely infected aged BALB/c mice lacked demonstrable T suppressor activity. Furthermore, these mice developed a severe autoimmune myocarditis as early as 2 months after the onset of the infection, when the majority of them reject syngeneic heart grafts. These findings suggest that a gamma delta T cell-mediated suppressor mechanism may operate in the avoidance of the breaking of tissue-specific tolerance during the acute infection. Moreover, such a mechanism is likely related to the immune system chronobiology.
Aging↗
Occlusive thrombosis in myocardial bridging.
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Adult↗
Action of lipid peroxidation products on phosphoinositide specific phospholipase C.
4-Hydroxynonenal (HNE), a major lipid peroxidation product, displays several biological actions. Among them, the differentiation of human HL-60 cells and the stimulation of neutrophil oriented migration occur at concentrations which can be actually found in normal tissues and in body fluids. In spite of its chemotactic activity, HNE fails to increase neutrophil oxidative metabolism. The action of the aldehyde on cell migration appears to be mediated by a phosphoinositide specific phospholipase C. The acceleration of phosphatidylinositol turnover induced by 10 pM 4-hydroxyoctenal, another lipid peroxidation product, is prevented by the pretreatment of neutrophils with pertussis toxin. The mechanism of action of these 4-hydroxyalkenals appears to follow pathways common to other chemoattractants, but some differences can be found too. In particular HNE seems unable to stimulate phospholipase D activity. The action of 4-hydroxyalkenals and other lipid peroxidation products on transmembrane signalling systems and on phospholipid metabolism might regulate several cell functions, such as motility, proliferation and differentiation.
Aldehydes↗
Effect of 4-hydroxy-2,3-trans-nonenal and related aldehydes on phospholipase C activity of rat neutrophils.
Our work has evaluated the effects of certain lipid peroxidation products, i.e. 4-hydroxy-2,3-trans-nonenal (HNE), 4-hydroxy-2,3-trans-octenal (HOE), 2-trans-nonenal and nonanal, on phosphoinositide-specific phospholipase C (PL-C). The enzymatic activity has been determined in vitro by measuring the hydrolysis of labelled phosphatidylinositol-4,5-bisphosphate added to plasma membranes isolated from rat neutrophils. Concentrations of HNE between 10(-8) and 10(-6) M, and concentrations of HOE ranging from 10(-11) to 10(-8) M, were able to activate PL-C. Neither 2-trans-nonenal nor nonanal induced any change of PL-C activity. HNE, HOE and 2-nonenal, but not nonanal, have been shown to possess chemotactic properties towards rat neutrophils. The good correlation between the concentrations of HNE and HOE active on PL-C and those able to stimulate cell migration suggests that their chemotactic activity might be mediated by the activation of PL-C, as in the case of most chemoattractants. On the contrary, this mechanism of action cannot be applied to 2-nonenal, an aldehyde much more hydrophobic than HNE or HOE; its chemotactic activity might be the consequence of some perturbation of the lipidic environment of the cell membrane where it dissolves easily.
Aldehydes↗
Cystic fibroelastoma of the mitral valve: report of a case.
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Adolescent↗
Selective inhibition by 4-hydroxynonenal of sphingosine-stimulated phospholipase D in NIH 3T3 cells.
In fibroblasts, the mitogenic effects of sphingosine involves a rapid rise in the cellular content of phosphatidic acid (PtdOH) which may be due to the stimulation of phospholipase D, or inhibition of PtdOH phosphohydrolase, or both. Here, we demonstrate that in fibroblasts, 4-hydroxynonenal is a selective inhibitor of sphingosine-stimulated phospholipid hydrolysis, and it also inhibits sphingosine-induced formation of PtdOH.
3T3 Cells↗
Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi.
The contribution of autoimmunity in the genesis of chronic Chagas' heart pathology is not clear. In the present study, we show that: (a) BALB/c mice chronically infected with Trypanosoma cruzi reject syngeneic newborn hearts; (b) in vivo treatment with anti-CD4 but not anti-CD8 monoclonal antibodies (mAbs) abrogates rejection; (c) CD4+ T cells from chronically infected mice proliferate in vitro to syngeneic myocardium antigens and induce heart graft destruction when injected in situ; (d) anti-CD4 treatment of chronically infected mice establishes long-term tolerance to syngeneic heart grafts; and (e) the state of tolerance is related to in vitro and in vivo unresponsiveness of the CD4+ T cells. These findings allow us to suggest that autoimmunity is the major mechanism implicated in the rejection of syngeneic heart tissues grafted into the pinna of the ear of mice chronically infected with T. cruzi. The similarity of the lesions to those found in humans suggests that autoimmunity is involved in the pathogenesis of chagasic cardiomyopathy in humans. Moreover, this could imply therapeutic strategies by reestablishing long-term tissue-specific tolerance with anti-CD4 mAb treatment, mediating anergy, or deleting the responder CD4+ T cells to heart tissue antigens.
Animals↗
Effect of captopril on the prevention and regression of myocardial cell hypertrophy and interstitial fibrosis in pressure overload cardiac hypertrophy.
This article reports on the effects of captopril on both the prevention and the regression of myocardial cell hypertrophy and interstitial fibrosis in experimental animals (rats) with pressure overloaded hearts. Constriction of the abdominal aorta just below the diaphragm during periods of 20 days (prevention experiment) and 40 days (regression experiment) resulted in hypertension and cardiac hypertrophy. In the prevention experiment, captopril was able to inhibit the development of high blood pressure levels and cardiac hypertrophy in aortic-constricted rats. Similarly, the treatment of sham-operated rats with captopril led to a reduction in the weight of the heart and in the myocyte diameter compared with controls. The myocyte volume fraction of the left ventricles of both aortic-constricted and sham-operated animals that were treated with captopril was significantly diminished compared with that of the control group. The interstitial collagen volume fraction of all experimental groups was elevated as compared with the control group. As a consequence, the ratios of myocytes to interstitial collagen in groups of aortic-constricted rats, aortic-constricted rats that were treated with captopril, and sham-operated rats that were treated with captopril were reduced compared with the control group; that is, although captopril was able to prevent myocardial cell hypertrophy after aortic constriction, it could not prevent the maintenance of a normal ratio of myocytes to interstitial collagen, which was due to increased collagen volume fraction. In the regression experiment, captopril lowered high blood pressure levels and augmented heart weights to control values. The mean myocyte transverse diameter in aortic-constricted rats that were treated with captopril was significantly smaller than that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chronic chagasic myocarditis pathogenesis: dependence on autoimmune and microvascular factors.
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Animals↗
Parasympathetically-mediated swelling of mast cell granules during feeding.
Mesentery mast cells have been observed to swell and to spontaneously return to their original size following feeding of 12-h fasted rats. This effect may be controlled by parasympathetic efferent nerve impulses, since it is inhibited by atropine. It was reproduced in vitro in isolated rat peritoneal fluid mast cells exposed for 30s to 10(-8)-10(-11) M acetylcholine. When examined under the electron microscope, mast cell average granule diameters had increased by 29% (p less than 0.001) following treatment. Swollen granules did not leave (exocytose) acetylcholine-treated mast cells. They gradually and spontaneously returned to their original size. This recovery only differed from that occurring in the fed rat by its greater speed.
Acetylcholine↗
Chronic hemodynamic unloading regulates the morphologic development of newborn mouse hearts transplanted into the ear of isogeneic adult mice.
The morphologic development of newborn mouse hearts transplanted into the pinna of the ears of isogeneic adult mice was assessed in comparison to in situ ventricular myocardium of recipients. The grafted hearts became vascularized from the auricular artery at the base of the ear, and although these preparations appeared not to be intrinsically innervated, most of them showed grossly visible pulsatile activity. Since they were not subjected to hemodynamic load due to working against a pressure gradient, this technique provided an interesting experimental model for studies on the growth of chronically unloaded tissue. The ultrastructure of the myocardium from neonatal mouse hearts, which were fixed immediately after dissection, revealed no differences in comparison to previously published observations. By 2 months, there was virtually no change in the myocardial cell size as compared with newborn mouse cardiac tissue. The heterotopic hearts showed a mature ultrastructural appearance, with parallel bands of myofibrils alternating with rows of mitochondria and differentiated intercalated discs comparable to in situ myocardium. The interstitial space was widened due to fibrous tissue, with activated fibroblasts and a few mononuclear cells. In contrast, by 6 months after transplantation, the heterotopic myocardium showed a dispersion of the measured cell diameter of myocytes, with atrophy of a certain population of cells and hypertrophy in others; nevertheless, the mean cell diameter was similar to that observed in 2-month grafts. The myocytes showed significant dissociation from each other in fibrous tissue and a cellular infiltrate composed predominantly of mononuclear cells, and greater variability of the parallel arrangement of cells. They often contained myofibrils coursing in different directions rather than in parallel. Normal-sized or predominantly atrophic degenerated myocytes, characterized by a wide variety of ultrastructural alterations, were present. By 12 months after transplantation, the myocytes of heterotopic hearts were smaller in size in comparison to those after 2 or 6 months. The graft cells were separated from each other by fibrous tissue and mononuclear cells and were not aligned in parallel within the tissue; often, they appeared to have lost their connections with adjacent cells. The myofibrils within cells were strikingly disorganized, coursing in different directions. Severely degenerated myocytes were commonly seen. These results, without precluding the possible role of neural and hormonal stimuli, clearly indicate that hemodynamic work load regulates the developmental growth of newborn mouse heart transplanted into the pinna of the ear of isogeneic adult recipient mice. In other words, the mass of cardiac tissue would be adjusted to meet the prevailing hemodynamic demands.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗