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Biomedical subjects

M Marra

Publications and source records attributed to M Marra.

125 records · Page 7Linked to original sources

Study of the effects of ozone in emphysematous rats.

The effects of short-term exposure to ozone on control and elastase-induced emphysematous rats were examined to investigate whether emphysema would change the pulmonary susceptibility to oxidant air pollution. Emphysema was induced in rats after a single intratracheal instillation of 0.2 IU elastase/g body weight. Histologically, panacinar emphysema was apparent at 2, 4, 8, and 16 wk, that is, the total duration of the experiment. The diagnosis was confirmed by morphometry: the mean linear intercepts (MLI) of elastase-treated rats were significantly increased at all observation times, whereas the internal surface areas (ISA) of the elastase-treated rats were significantly decreased. In addition, pulmonary function tests provided supportive evidence for the diagnosis of emphysema. Respiratory system compliance and functional residual capacity showed a significant increase in elastase-treated rats. No differences in inspiratory capacity or in forced vital capacity between control rats and elastase-treated rats were observed. The above data are indicative for a rat model for elastase-induced emphysema. Short-term exposure to ozone of elastase-treated rats revealed panacinar emphysema, including an inflammatory response in the centroacinar region. No differences in MLI as well as in ISA between ozone-exposed rats (with or without emphysema) and their respective controls were observed. Short-term exposure to ozone induced an identical, significant increase in protein content, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase activities in lungs of normal and emphysematous rats. Moreover, these results strongly suggest that emphysematous rats are not more susceptible to ozone than nonemphysematous rats.

Air Pollutants↗

Influence of exposure regimen on nitrogen dioxide-induced morphological changes in the rat lung.

Experiments were performed to study the influence of concentration, exposure pattern, and length of exposure on the degree and extent of morphological alterations in the NO2-exposed rat lung. Four weeks of continuous exposure to 20 mg NO2/m3 consecutively revealed damage and loss of cilia, replacement of desquamated type I pneumocytes by type II pneumocytes resulting in a cuboidal epithelial lining, an influx of alveolar macrophages, and hypertrophy and hyperplasia of the bronchiolar epithelium. The animals recovered almost completely from the induced lesions within 8 days. Continuous exposure to 1, 2.5, or 5 mg/m3 displayed minimal alterations in the 5 mg/m3 group. The effects increased with exposure time. Intermittent or continuous exposure to 20 mg NO2/m3 resulted in minor differences after 4 weeks. The onset of the lesions was delayed and the massive influx of alveolar macrophages in the continuously exposed animals failed to appear in the intermittently exposed animals. This work demonstrates that in subacute experiments: Concentration plays a more important role in inducing pulmonary lesions than exposure time when the product of concentration and time is kept constant. This effect is stronger during intermittent exposure than during continuous exposure. Continuous exposure seems to be a more important factor with regard to a macrophage response than intermittent exposure. The rat lung has a large capacity to repair almost completely from damage caused by short-term NO2 exposure.

Animals↗

Glutathione pathway enzyme activities and the ozone sensitivity of lung cell populations derived from ozone exposed rats.

Rats were exposed to 1.5 +/- 0.1 mg ozone/m3 for 4 days and the activities of glucose-6-P dehydrogenase (G6PDH), glutathione reductase (GR) and glutathione peroxidase (GSHPx) were measured in the cytosolic fraction of lungs from exposed and control rats. Enzyme activities were also measured in isolated alveolar macrophages and type II cells. After ozone exposure enzyme activities, expressed per gram of protein, showed the following changes. G6PDH activity was increased (P less than 0.001) in the whole rat lung and showed the same tendency in isolated alveolar macrophages and type II cells. GR activity did not change significantly neither in whole lungs, nor in isolated cell populations. GSHPx activity was increased (P less than 0.001) in whole lung homogenates, and was also markedly increased in both alveolar macrophages (P less than 0.05) and type II cells (P less than 0.01) isolated from ozone-exposed rats. From these results it was concluded that biochemical changes measured in whole lung homogenates might reflect biochemical changes that occur within specific cell types. Furthermore, it was demonstrated, using an in vitro ozone exposure system, that lung cell populations isolated from ozone-exposed rats, in spite of their marked increase in GSHPx activity, did not show a decreased ozone sensitivity compared to cells from unexposed rats, as determined by trypan blue exclusion or phagocytosis. So an increase in GSHPx activity might not be related to an increased cellular resistance to ozone.

Animals↗

[The use of doxapram chlorohydrate (t-doxapril) as an anti-shivering drug].

Following a brief review of the main causes of anaesthetic shock, reference is made to the results obtained with the use of a well-known analeptic: doxapram chlorohydrate, as an anti-shock drug. Using a continuous venous perfusion technique, practically no side-effects were encountered, while the effectiveness of the drug was of undoubted interest (75% of cases). The hypothesis of the anti-shock action remains open.

Body Temperature↗

[Cystic lymphangioma of the spleen associated with hypersplenism].

A rare case of cystic lymphangioma of the spleen accompanying hypersplenism syndrome is described. After stressing the importance of certain examinations such as arteriography and splenic scintigraphy in diagnosis the condition, the many ways in which cystic lymphangioma of the spleen may present clinically are reviewed; these go from asymptomatic to straightforward splenomegaly, with or without clinical signs, up to a clear-cut hypersplenism syndrome. The present case merits consideration for three reasons: 1) The absolutely exceptional nature of cystic lymphangioma of the spleen; 2) Exceptional association with hypersplenism syndrome; 3) Remission of the syndrome following splenectomy. It is concluded that, notwithstanding the condition's rarity, cystic lymphangioma of the spleen should be considered in the differential diagnosis of splenomegalic syndromes when these are also accompanied by hypersplenism.

Adult↗

Characteristics of Gross virus-induced leukemia cell clones. I. In vivo and in vitro properties.

Clones of four Gross virus-induced murine lymphoblast lines, established in culture from C3H mice, were selected for detailed study of the relationships among in vitro growth parameters, oncogenicity, and agglutination with concanavalin A. The four clones were intially divided into two groups on the basis of their in vitro growth properties. Two strains, N-811 and H-111, had low saturation densities, low cloning efficiencies, and slower doubling times; the other two strains, L-274 and L-258, had higher saturation densities, higher cloning efficiencies, and faster doubling times. The ability of the strains to produce tumors in mice correlated with their in vitro growth properties: L-274 and L-258, with their high saturation densities and high cloning efficiencies, were more tumorigenic in mice than were N-811 and H-111 cells with their lower saturation densities and lower cloning efficiencies. All strains were agglutinable with concanavalin A; however, the agglutination response did not correlate with saturation density or oncongenicity.

AKR murine leukemia virus↗

Characteristics of Gross virus-induced leukemia cell clones. II. Oncornavirus production.

Oncornavirus production differed quantitatively among four Gross virus-induced murine leukemia clones. To determine the proportion of cells in each clone that were producing virus particles, the cells were stained by indirect immunofluorescence with antiserum to Gross antigen. All four clones had the same percentage of cells positive for the presence of Gross antigens irrespective of their ability to produce virus particles. A direct correlation was observed between the amount of RNA tumor virus attached to the plasma membrane and agglutination by concanavalin A. The leukemia strain that produced the most virus also had the greatest degree of agglutination. Oncornavirus production was indirectly related to oncogenicity of the cells in vivo: The clones that produced the most virus were the least malignant. The interaction of the host and virus-producing cells was monitored during animal passage, and virus production decreased during animal passage whereas transplantability increased.

AKR murine leukemia virus↗

Effect of reduced glutathione on mitochondrial parameters of proliferating splenocytes from young and old rats.

The time-dependent changes of mitochondrial membrane potential and mass have been investigated on splenocytes from young, adult and old rats stimulated with Con A in the presence and absence of reduced glutathione (GSH). In addition, the basal level as well as the level of GSH during a 3-day culture period has been determined. No age-dependent changes of cellular GSH content were observed in freshly prepared splenocytes; however, in proliferating cells from old animals the expected increase in GSH levels was delayed. As regards the mitochondrial parameters, their membrane potential and mass were measured by means of the fluorescent probes rhodamine-123 (Rh-123) and nonyl acridine orange (NAO), respectively, and flow cytometry. During aging and with time of culture, an increased number of cells showed depolarization and loss of mitochondrial mass. This age-dependent impairment was completely prevented by addition of GSH to the culture medium, which resulted in a sharp increase in intracellular GSH. The present findings support the view that an impairment of the antioxidant defense system may be responsible for the damage observed in the mitochondria of proliferating splenocytes from old animals.

Journal Article↗

Melatonin is an efficient antioxidant.

We have compared the peroxyl radical scavenger ability of melatonin with that of vitamin E, ascorbic acid (As.A.), reduced glutathione (GSH) and mannitol. All the antioxidants, except mannitol, prevented the lysis of human erythrocytes exposed to an azo-initiator of peroxyl radicals (2,2'-azo-bis(2-amidinopropane)dihydrochloride) at 37 degrees C. The percentage of this inhibition of erythrocyte lysis varied with the concentration of antioxidants, but the efficiency was melatonin > vitamin E > As.A. > GSH. Based on the assumption that each molecule of vitamin E scavenges two peroxyl radicals, the scavenging capacity of melatonin was four peroxyl radicals/molecule.

Journal Article↗

Food restriction in female Wistar rats. VII. Mitochondrial parameters in resting and proliferating splenic lymphocytes.

The effect of food restriction on the mitochondria of resting and proliferating rat splenocytes was examined, measuring the membrane potential and mass of these organelles, by means of the specific fluorescent probes Rhodamine-123 and Nonyl Acridine Orange, respectively. Food restriction was applied on an every-other-day schedule (EOD) starting at the age of 3.5 months. The ad libitum fed (AL) animals were killed when they were 4, 11 and 24 months old, whereas the EOD rats were killed at 11 and 26 months. Resting lymphocytes from AL rats showed an age-dependent increase of both membrane potential and mass of their mitochondria. However, the mitochondrial mass increased to a larger extent when compared with the membrane potential resulting in a decrease of the respiratory quotient (RQ), i.e. of the respiratory activity per unit of mitochondrial mass. In EOD animals, the mitochondrial membrane potential was lower and the mitochondrial mass was higher in the corresponding age-matched controls, resulting in a further decrease of RQ. Following mitogenic stimulation, most of the cells from young and adult AL rat showed an increase of membrane potential and mass of their mitochondria. In contrast about 50% of cells from old AL rats had depolarized organelles after 72 h from the stimulation. Food restriction was able to prevent these alterations allowing the majority of cells, including those from old animals, to maintain the hyperpolarization of their mitochondria during the 3-day culture. In light of the well known sensitivity of mitochondrial membrane potential to peroxidative stress, present data suggest that the increase of respiration occurring during mitogenesis may increase free radical production, which is better tolerated by cells from EOD animals than by those from AL animals.

Journal Article↗

The modulation of intracellular glutathione level modulates the mitochondrial response in proliferating rat splenocytes.

We have investigated the effect of intracellular reduced glutathione (GSH) levels on the mitochondrial parameters of proliferating rat splenocytes. The intracellular GSH content of the cells was altered by continuous culture with buthionine-S, R-sulfoximine (BSO), a specific inhibitor of GSH synthesis. BSO decreased the GSH levels, inhibited DNA synthesis and caused depolarization of mitochondria in 52% of cells stimulated to proliferate for 72 h. These data support the proposition that GSH influences the lymphocyte proliferation at more than one site, one of which is the energy producing machinery.

Journal Article↗

Age-dependent changes of serum oxygen radical scavenger capacity and haemoglobin glycosylation in non-insulin-dependent diabetic patients.

BACKGROUND: Contradictory results have been reported in the literature concerning the correlation between glycosylated haemoglobin (HbA1c) and peroxidation level in serum of diabetic patients. OBJECTIVE: To evaluate this correlation in type 2 diabetic patients by comparing the level of HbA1c with the oxygen radical absorbance capacity (ORAC(OH)) of serum. METHODS: One hundred and five type 2 diabetic patients were enrolled for the study. After having obtained informed consent, venous blood samples were drawn after overnight fast at the time of routine diabetic check-ups. The blood was collected in plain and EDTA (1 mg/ml) tubes. Glycosylated haemoglobin (HbA1c) was determined by cation-exchange chromatography (HPLC), and spectrophotometric detection (Diamat Analyzer, BioRad). Serum was used for biochemical determinations performed by standard laboratory procedures and for ORAC(OH) analysis. This last parameter was determined measuring the loss of beta-phycoerytrin fluorescence due to oxidation by hydroxyl radicals generated by Cu(2+) and H(2)O(2), in the presence and absence of serum. Seventy-eight control age-matched subjects were obtained from the personnel staff of our Research Department and old healthy subjects, selected on the basis of Senieur Protocol, were relatives of the above mentioned personnel. RESULTS: When the population of diabetic patients was taken as a whole, a decrease of ORAC(OH) has been observed compared to the controls. Moreover, negative correlations were found comparing ORAC(OH) either with HbA1c (r = -0.213; p = 0.029) and with the age of patients (r = -0.27; p = 0.005). To better understand the effect of age, the data were re-examined dividing the diabetics into two populations, i.e. under and over 65 years of age. An age-dependent decrease of ORAC(OH) and an increase in HbA1c levels has been observed comparing these two populations; however, the correlation between the two parameters remained statistically significant only in the oldest group (r = -0.31; p = 0.026). CONCLUSIONS: Present data point to an involvement of oxidative stress in the glycation of haemoglobin especially in old diabetic patients, and provide support for the potential use of an antioxidant therapy in these patients, irrespective of their glycaemic control.

Adult↗

[Macromastia in adolescents: notes on clinical aspects and therapy].

The surgical correction of macromastia is justified on both physical and psychological grounds. Hypertrophy of the breast may alter the development of the body, causing severe damage to the spinal cord. It may also condition the psychological or mental development of the patient, even going so far as to bring about fully fledged psychoses. The definitive scars of the surgical correction are generally accepted by the patients.

Adolescent↗