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Biomedical subjects

M A Rossi

Publications and source records attributed to M A Rossi.

At least 73 records · Page 4Linked to original sources
PubMed1991

Experimental studies on the mechanism of action of 4-hydroxy-2,3-trans-nonenal, a lipid peroxidation product displaying chemotactic activity toward rat neutrophils.

The effects of 4-hydroxy-2,3-trans-nonenal (HNE) and nonanal on the activity of phosphoinositide-specific phospholipase C of rat neutrophils have been studied in parallel with their action on neutrophil oriented migration. Concentrations of HNE ranging from 10(-7) to 10(-5) M significantly stimulated the oriented migration of rat polymorphonuclear leukocytes. HNE stimulated both the basal and GTP gamma S-induced phospholipase C activity when used at concentrations between 10(-8) and 10(-6) M. Nonanal was devoid both of chemotactic activity and of any action on phospholipase C activity. The effect of GTP gamma S on the stimulation of phospholipase C induced by HNE was higher when the lowest dose of the aldehyde was used; the finding of an additive effect between 10(-8) M HNE and 2 x 10(-5) M GTP gamma S suggests that the two compounds may share a final common pathway of action. These results suggest that the chemotactic activity of HNE might be mediated, like that of other more well-known chemoattractants, by the stimulation of phosphoinositide-specific phospholipase C.

Aldehydes↗
PubMed1991

Reversible rat mesenteric mast cell swelling caused by vagal stimulation or sham-feeding.

Fragments of rat mesentery were examined using acetylthiocholine to detect cholinergic nerve fibers and toluidine blue to identify mast cells. 59.2 +/- 2.6 percent of mast cells were at less than one-half mean cell diameter (4-5 microns), from the nerve fibers. Under the electron microscope, the membrane of mast cells was within less than 50 nm from axon membranes, suggesting a synaptic type of connection. Average mast cell area in fasted rats increased following feeding, stimulation of the left abdominal vagus nerve or exposure of the animal to the smell of food. It returned to control values within 60-80 min. Granule exocytosis was not observed. Mast cell swelling was prevented by atropine and induced by intravenously administered carbamylcholine. It appears that in rat mesentery, impulses travelling via cholinergic, parasympathetic fibers innervating mast cells, cause mast cell swelling. Compound 48/80 administered to rats at doses causing little degranulation and minimum release of histamine, caused extensive, reversible swelling of mesentery mast cells.

Animals↗
PubMed1991

The pattern of myocardial fibrosis in chronic Chagas' heart disease.

Observations are described on the fibrillar nature and structural features of the collagenous interstices of the human myocardium in chronic chagasic cardiomyopathy, comparing them with similar observations in normal hearts, using the picrosirius red technique and polarization microscopy. A total of 28 adult hearts obtained at autopsy were used: 5 control without evidence of cardiac disease, and 23 with chronic Chagas' heart disease. The findings in the myocardium of those without Chagas' disease were in keeping with those reported in the literature. In those with Chagas' disease diffuse interstitial fibrosis could be observed in all cases, albeit to varying degree. The pattern was that of a diffuse increase in the amount of thick collagen fibers surrounding bundles of muscle fibers (perimysial matrix), varying in intensity from one area to another, and around the intramyocardial coronary vessels, combined with a less pronounced increase in the matrix of endomysial collagen. The relationship between the observed myocardial fibrosis and cardiac function, and the potential mechanisms for its production, are discussed. Further research is needed into the patterns and pathogenesis of myocardial fibrosis in order to offer possibilities for prevention and development of corrective forms of therapy for the fibrotic process.

Adult↗
PubMed1991

Cardiac hypertrophy due to pressure and volume overload: distinctly different biological phenomena?

Myocardial hypertrophy is a morphological adaptive response to chronic work overload imposed on the heart. It has been categorized into two distinct basic types: concentric hypertrophy, occurring in response to a sustained pressure overload in which wall thickness increases without chamber enlargement, and eccentric hypertrophy, in response to a chronic volume overload in which chamber volume enlarges without a relative increase in its wall thickness. It should be emphasized, in this context, that these adjectives are somewhat confusing, since the hypertrophy observed is not eccentric in the fashion often seen in the left ventricle of patients with hypertrophic cardiomyopathy. In fact, the hypertrophy is concentric in both instances, but is associated with an increase in chamber volume when described as eccentric, yet occurring with a maintained volume when said to be concentric. In rats made anemic by iron deficiency, the volume overloaded heart achieves an adaptive increase in mass characterized as hypertrophy occurring in the setting of dilated ventricle. This so-called eccentric hypertrophy depends on catecholamines as possible signals for myocardial growth, and progresses with preserved ultrastructure and contractile performance of the cardiac muscle. A gradually imposed volume overload results in a harmonious growth of the heart (it retains a relative normal shape, becoming a magnified normal heart), probably mediated by release of catecholamines into the myocardium. This process resembles the normal cardiac growth in response to the obligatory volume load imposed by an increasing cardiac output (greater metabolic demands) and blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Long-term low-dose glucocorticoid therapy in hyperandrogenized women: utility and effects on bone mineral content and hypothalamic-pituitary-adrenocortical function.

The effect of chronic low-dose glucocorticoid administration on bone mineral content and corticotrope reserve was investigated in 12 hyperandrogenized women treated with 1-6 mg oral evening doses of 16 beta-methylprednisone for 12-58 months. The hypothalamic-pituitary-adrenal axis was evaluated in 9 patients by a standard metyrapone test after 45-75 days off steroid therapy. All the patients had a normal rise in serum 11-deoxycortisol after metyrapone. Bone densitometry was assessed at the end of therapy using dual photon absorptiometry. No significant differences between patients and age-matched hyperandrogenic controls were found either in spine (1.048 +/- 0.096 vs. 1.023 +/- 0.175 g/cm2) or femoral neck (0.863 +/- 0.115 vs. 0.899 +/- 0.216 g/cm2), respectively. In conclusion, absence of quantitative bone mass reduction and normal corticotrope reserve were observed even after 58 months of daily steroid administration.

Adolescent↗
PubMed1991

Influence of 4-hydroxynonenal on bombesin-induced stimulation of phospholipase C activity in rat liver.

The influence of 4-hydroxynonenal (HNE) on bombesin-induced PIP2-phospholipase C activity (PL-C) was studied in vitro on isolated liver membranes. Both bombesin and HNE stimulated the enzymatic activity at micromolar concentrations and their effect was enhanced by the nucleotide GTPgammaS. An additive synergism was observed with 1 microM bombesin and 0.1 microM HNE. When GTPgammaS was added to the reaction mixture, the degree of PL-C stimulation in the presence of both compounds was not different from the activity value induced by bombesin alone. Since such micromolar amounts of HNE can be actually found in normal liver cells, these results support the hypothesis of a physiological importance of lipid peroxidation in the regulation of phospholipase-C activity.

Aldehydes↗
PubMed1991

Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy.

OBJECTIVE: To study the fibrillar nature and structural features of the collagenous interstitium of the myocardium in normal and cardiomyopathic human hearts, employing the picrosirius red technique and polarization microscopy. DESIGN: A survey, case series study. SETTING: Referral autopsy service at a university medical centre (Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto). CASES AND METHODS: A total of 46 adult hearts obtained at autopsy were used: five control hearts without evidence of cardiac disease, nine hearts with dilated cardiomyopathy, five with hypertrophic cardiomyopathy, four with endomyocardial fibrosis affecting the left ventricle, and 23 with chronic Chagasic cardiopathy. Fragments of myocardial tissue were obtained from the equator of the left ventricular free wall, fixed in formalin, dehydrated, and embedded in paraffin. Sections were stained with a modification of the picrosirius red technique and examined using direct light and polarization microscopy. RESULTS: The findings in the control myocardium did not differ from those reported in the literature. The myocardium in both dilated and hypertrophic cardiomyopathies showed diffuse fibrosis varying in degree from one case to another, but present in all cases. The basic pattern was characterized by a diffuse increase in both endomysial and perimysial collagen thick fibres, particularly surrounding individual myocytes (endomysial sheath). The microscopic study of the cases of endomyocardial fibrosis showed a thickened fibrotic endocardium consisting predominantly of thick collagen fibres extending as a septum, corresponding to broad perimysial sheaths, into the myocardium. In the superficial muscle fibre bundles usually composed of atrophic fibres, there was an increase in thickness of collagen fibres in both the perimysial and endomysial connective tissue matrix. To a variable degree (but present in all cases) interstitial and diffuse fibrosis could be observed in the chronic myocarditis of Chagas's disease. This was manifested by a diffuse increase in the amount of thick collagen fibres surrounding muscle fibre bundles (perimysial matrix), varying in intensity from one area to another, and around intramural coronary vessels, combined with a less pronounced increase in the endomysial collagen matrix. CONCLUSIONS: These findings extend knowledge of the various expressions of interstitial myocardial fibrosis in the idiopathic cardiomyopathies and chronic Chagasic cardiopathy and perhaps provide insight into pathogenesis. Further research into the patterns and pathogenesis of myocardial fibrosis are needed in order to offer prevention and corrective forms of therapy of the fibrotic process.

Adult↗
PubMed1990

Effect of 4-hydroxylalkenals on hepatic phosphatidylinositol-4,5-bisphosphate-phospholipase C.

The effects of some 4-hydroxyalkenals, carbonylic products of lipid peroxidation, on hepatic phosphatidylinositol-4,5-bisphosphate (PIP2)-phospholipase C (PL-C) activity were investigated. The enzymatic activity was assayed in vitro by measuring the hydrolysis of [3H]PIP2 added as exogenous substrate to liver membranes. 4-Hydroxyhexenal (HEE), 4-hydroxyoctenal (HOE) and 4-hydroxynonenal (HNE) were able to stimulate both the basal and the GTPgammaS induced PL-C activity, whereas 4-hydroxyundecenal was inactive. HOE was the most active compound, being able to accelerate PIP2 breakdown at concentrations between 10(-12) and 10(-6) M, while in the case of HEE the effective doses ranged from 10(-11) to 10(-7) M and from 10(-9) to 10(-6) M in the case of HNE. 4-Hydroxynonenal was able to increase also bombesin stimulated PL-C activity. As these aldehydes accelerated PIP2 breakdown at doses which can be actually reached in tissues, the effects shown in vitro are likely to occur in vivo.

Aldehydes↗
PubMed1990

Endomyocardial fibrosis in dermatomyositis.

The case reported in this paper, besides illustrating many of the clinical and pathological aspects of chronic dermatomyositis, documents a yet undescribed feature of involvement of the heart in dermatomyositis, namely endomyocardial fibrosis. The pathogenetic mechanism of such a happening is discussed, and its possible relationship to tropical endomyocardial fibrosis is considered.

Adult↗
PubMed1990

Cell-mediated immunity to chemically xenogenized tumors. V. Failure of novel antigens to increase the frequency of tumor-specific cytotoxic T cells.

Xenogenized variant cells (L5178Y/DTIC) of a murine lymphoma line confer a high degree of specific protection against subsequent challenge of mice with parental L5178Y cells. In an attempt to better define the effect of DTIC-induced determinants on parental antigen recognition and the mechanisms involved in this protection, we evaluated the frequency of anti-parental tumor cytotoxic T lymphocyte precursors following priming of mice with xenogenized cells in vivo. In addition, we tested the effect of host sensitization with the immunogenic, retrovirus-related proteins that are precipitated from the surface of L5178Y/DTIC cells by means of specific antibody. Our results indicated that the novel determinants induced by DTIC treatment on L5178Y cells do not act as helper determinants for the generation of tumor-specific cytotoxic responses. Therefore, increased frequency of tumor-specific cytotoxic lymphocytes does not seem to be a major mechanism of anti-parental tumor immunity induced by xenogenized variant cells.

Animals↗
PubMed1990

Permeability alteration of the sarcolemmal membrane, particularly at the site of macrophage contact, in experimental chronic Trypanosoma cruzi myocarditis in mice.

Sarcolemmal membrane permeability characteristics have been investigated, particularly at the site of macrophage contact, in experimental chronic Trypanosoma cruzi myocarditis in BALB/c mice, employing ruthenium red (RR) as an electron tracer. The ultrastructural features of the myocardium from infected animals were similar to those previously described. Briefly, focal myocarditis was detected, with areas of myocytolytic necrosis, atrophic myofibres, an inflammatory response composed of mononuclear cells, predominantly macrophages and a few lymphocytes, and interstitial fibrosis. This study provided the following new information: (I) the cytoplasmic components of mononuclear cells have a very high affinity for RR. It is conceivable that mononuclear cell activation parallels a physiological change in plasma membrane permeability; (2) RR diffusely strains the sarcoplasm of cardiocytes with anomalous contraction bands, indicating leaky sarcolemmal membranes; (3) most non-degenerating cardiocytes from experimental animals appear darker with RR staining than controls. They also frequently show rows of RR-stained sub-plasmalemmal tiny vesicles. Both changes probably reflect increased membrane permeability; (4) RR intensely labels the cytoplasmic components of cardiocytes at the site of macrophage contact or close apposition, indicating areas of altered membrane with remarkably increased permeability. This observation provides insight into a role for the macrophages in myocardial cell damage in experimental chronic Trypanosoma cruzi myocarditis. An obvious consequence of increased membrane permeability is that it may cause impairment of the transmembrane ion gradients and cause loss of intracellular elements, thus contributing to cardiocyte death. Furthermore, the findings in the present study imply that one of the consequences of macrophage-mediated cytotoxicity may be alteration in the permeability of the plasma membranes of nearby target cells, possibly due to a change in the structural integrity of the membrane resulting from peroxidation of cell membrane lipids.

Animals↗
PubMed1990

Myocardial damage in Trypanosoma cruzi myocarditis: a role for macrophages.

Sarcolemmal membrane permeability characteristics, particularly at the site of macrophage contact, were investigated in experimental chronic Trypanosoma cruzi myocarditis in BALB/c mice, employing ruthenium red as an electron tracer. The ultrastructural features of the myocardium from infected animals were similar to those previously described. Briefly, focal myocarditis was detected, with areas of myocytolytic necrosis, atrophic myofibres, an inflammatory response composed of mononuclear cells, predominantly macrophages and a few lymphocytes, and interstitial fibrosis. The immunohistochemical study confirmed that the macrophages are in fact the majority of the inflammatory cells identified in the interstitium of the myocardium, which stained positively with both monoclonal antibodies to the class II histocompatibility (Ia and Ie) antigens (cytoplasmic and plasma membrane staining), and negatively with kappa and lambda immunoglobulin chains and S-100 protein. This study provided the following new information: the cytoplasmic components of mononuclear cells in the chronic myocarditis of T cruzi-infected mice have a very high affinity for ruthenium red. It is conceivable that mononuclear cell activation parallels some physiological change of their plasma membrane permeability. Ruthenium red diffusely stains the sarcoplasm of cardiocytes with anomalous contraction bands, indicating leaky sarcolemmal membranes. Most nondegenerating cardiocytes from experimental animals appear darker with ruthenium red staining when compared to controls. They also frequently show rows of ruthenium red-stained subplasmalemmal tiny vesicles (caveolae). Both changes probably reflect increased membrane permeability. Ruthenium red intensely labels the cytoplasmic components of cardiocytes at the site of macrophage contact or close apposition, indicating areas of altered membrane with remarkably increased permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Intensification of acute Trypanosoma cruzi myocarditis in BALB/c mice pretreated with low doses of cyclophosphamide or gamma irradiation.

This study was carried out to examine the development of acute myocarditis in Trypanosoma cruzi-infected BALB/c mice after they were treated with low doses of cylophosphamide or gamma irradiation. It has been claimed that, in mice, such treatments temporarily interfere with the host-immune suppressor network, but cause no immunodepression. A severe extensive and diffuse acute myocarditis developed in the treated mice infected with T. cruzi, whereas a slight to moderate focal or occasionally diffuse acute myocarditis developed in control mice infected with T. cruzi. It is very likely that the transient abolition of T-suppressor activity facilitates the anti-myocardium immune response in the acute phase of experimental Chagas' disease in mice.

Acute Disease↗
PubMed1990

Lipid extraction attenuates the calcific degeneration of bovine pericardium used in cardiac valve bioprostheses.

Bovine pericardial bioprostheses frequently fail due to dystrophic calcification. Since (a) recent studies indicate that membrane-associated complexed acidic phospholipids play an important role in the process of both physiologic and pathologic calcification, and (b) cytoplasmic organelles and plasma membrane of interstitial cells seem to serve as initial sites of calcific degeneration of bioprosthetic bovine pericardial tissue, this investigation was undertaken to evaluate whether, and if so, to what extent, the mineralization of valve tissue could be attenuated by previous lipid extraction. Pretreatment of glutaraldehyde-preserved bovine pericardium with acidified sulphuric ether (pH 3.0-4.0) attenuated calcification significantly: 28 days after subcutaneous implantation in young rats the degree of mineral deposition was approximately equal to typical 7 days implants in this model. The mechanism of this beneficial effect is suggested to be due to partial extraction of tissue phospholipids, as demonstrated by electron microscopy, thus reducing the number of available sites for deposition of hydroxyapatite crystals. In addition, and importantly, the present results indicate that any attempt to reduce cardiac valve bioprosthesis mineralization will have to take into account the role of lipids and, particularly, the membranous phospholipids in the calcification mechanism.

Animals↗
PubMed1989

[Influence of reduced glutathione on changes in the activity of phospholipase C induced by 4-hydroxynonenal].

4-Hydroxynonenal (HNE) is a major end-product of lipid peroxidation. 1 mM HNE inhibits the activity of liver phospholipase C (PL-C) and this effect is prevented by 1 mM GSH; on the contrary GSH is unable to counteract the stimulation of PL-C induced by a low concentration of HNE (100 nM). Other hydroxyalkenals are able to stimulate PL-C at low doses (micromolar or less), the most effective being 4-hydroxyoctenal which acts at picomolar doses. The lack of a correlation between the chain length of the aldehydes used and the degree of PL-C stimulation seems to exclude the possibility that their effect could be due to an aspecific solvent action toward the phosphatidylinositol-4,5-diphosphate used as substrate for the enzymatic assay.

Aldehydes↗