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Biomedical subjects

B E Malucelli

Publications and source records attributed to B E Malucelli.

14 recordsLinked to original sources

Reduction of acute inflammation in rats by diazepam: role of peripheral benzodiazepine receptors and corticosterone.

Carrageenin causes a reproducible inflammatory reaction and remains the standard irritant for examining acute inflammation and anti-inflammatory drugs. High doses of diazepam (10.0-20.0 mg/Kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenin administration. The present experiment was undertaken to investigate the possible roles of peripheral-type benzodiazepine receptors (PBRs) and corticosterone on the anti-inflammatory effects of diazepam. Five experiments were conducted to assess the effects of a single dose (10.0 mg/Kg) of diazepam on carrageenin-induced paw edema (CIPE), pleurisy and increase in vascular permeability in rats. Results showed that: 1. diazepam or Ro5-4864 (a PBR agonist) treatment reduced CIPE values; 2. prior treatment with PK11195 (a non-benzodiazepine PBR antagonist) suppressed the effects of either diazepam or Ro5-4864 on CIPE; 3. diazepam reduced the volume of the pleural exudate in carrageenin-injected rats, as well as its leukocyte count; 4. diazepam treatment reduced the magnitude of the increase in vascular permeability caused by carrageenin; 5. adrenalectomy suppressed the effects of diazepam on CIPE; and 6. diazepam treatment increased the serum concentration of corticosterone. These results suggest a relevant role of PBR and corticosterone on diazepam-induced changes in inflammation. They are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE.

Acute Disease↗

Effects of social isolation on ehrlich tumor growth and tumor leukocyte infiltration in mice: evidence of participation of the submaxillary salivary gland.

OBJECTIVE: Considering previous studies on stress and Ehrlich tumor growth from our laboratory and also known cell growth and behavior-related properties of submaxillary salivary gland products, we studied the effects of stress by social isolation, in combination or not with sialectomy (submaxillary gland ablation), on growth and leukocyte infiltration into Ehrlich adenocarcinomas. METHODS: 5 x 10(7) tumor cells/ml were inoculated into the footpads of mice and tumor growth was evaluated by measuring paw thickness on alternate days. Ten days after inoculation, tumors were harvested and processed for immunocytochemical analysis of tumor-infiltrating leukocytes (TIL) and nerve-like growth factor (NGF)/epidermal growth factor (EGF)-positive tumor cells. T and B lymphocyte, NK cell and macrophage percentages were calculated. RESULTS: Sialectomy slightly reduced tumor growth and caused a significant increase in NK cell infiltration of tumors (p < 0.05). Social isolation caused a highly significant enhancement of both tumor growth (p < or = 0.05) and percentage of macrophages infiltrating tumors (p < 0.05). Sialectomized isolated animals showed few significant changes in tumor growth rate (p < or = 0.05), but presented increased percentages of NK cells, macrophages and B lymphocytes (p < 0.05). A reduction in the percentage of NGF+ tumor cells was also observed (p < 0.05). All of these effects were seen only in 8-month-old mice, but not in younger animals. CONCLUSION: A possible link between salivary gland factors, tumor growth and TIL patterns was considered, suggesting that growth factors may modulate tumor leukocyte infiltration as well as tumor growth rate.

Animals↗

Substance P does not modify mononuclear cell migration into Ehrlich tumor mass.

In the present study, seven adult male mice were inoculated with Ehrlich tumor into the footpad after local substance P release was blocked by neurectomy of the sciatic and saphenous nerves. The contralateral footpad was also inoculated but sham-operated, and used as control. This procedure did not modify the percent of CD4+ (about 1-2%), CD8+ (about 1-3%), macrophages (about 21-22%), lymphocyte B (about 0-1%) and NK (about 1-2%) mononuclear cells present among tumor cells. These data suggest that chemotactic activity of substance P may not be relevant in this situation because the lack of this neurotransmitter (checked by immunohistochemistry) secondary to neurectomy did not change the cell migration profile into tumor mass.

Animals↗

Effects of high doses of diazepam on carrageenin-induced paw edema in rats.

Benzodiazepine (BDZ) receptor sites play a relevant role in immune/inflammatory reactions. Acute BDZ treatments were shown not only to suppress cell proliferation in rat thymus but also to decrease TNF-alpha, IL-1 and IL-6 release from adult mouse macrophages. In the present investigation the effects of acute (10.0 and 20.0 mg/kg) and long-term (10.0 mg kg-1 day-1, for 21 days) diazepam treatment on carrageenin-induced paw edema were studied in rats. The results showed that acute treatment with high doses of diazepam decreased paw edema volume in a dose-dependent manner, and this effect was observed as early as 1 h after the administration of the 20.0 mg/kg dose and continued until the last measurement was performed (8 h). In contrast, long-term diazepam administration did not modify the phlogistic-induced edema. Taken together, these data show that 1) acute diazepam treatment with high doses decreases the volume of the acute inflammatory paw edema developed by the organism as a response to carrageenin-induced injury, and 2) long-term diazepam treatment induces tolerance to this effect. These results are discussed in the light of a possible effect of diazepam on the components of the rat cellular and humoral immune/inflammatory reaction such as T lymphocytes and/or interleukins.

Animals↗

The influence of social isolation and peripheral innervation on Ehrlich tumor growth in mice.

The relationship between social isolation and Ehrlich tumor growth was investigated in seven male NIH mice about 2 months old living separately in small cages for 28 days. Fifteen control animals were kept grouped in conventional cages (10 animals in one and 5 in another) for the same period. After this period, 40 to 50 microliters of a cell tumor suspension at a concentration of 1 to 5 x 10(7) tumor cells/ml was inoculated into the footpad and footpad size was measured for 10 days. Isolated mice presented a 30% reduction in tumor growth. Sciatic and saphenous neurectomy in one leg of 5 isolated mice (experimental) and 5 grouped mice (control) performed 7 days before tumor inoculation abolished this difference, and more tumor growth was observed in the neurectomized paw compared to the non-neurectomized paw. The subordinate x dominant social relationship established between mice living in groups of two per cage (seven cages) did not modify the growth of tumor inoculated under the same conditions compared to the first experiment. We conclude that social isolation and an intact peripheral innervation are associated with reduced tumor growth, but dominance behavior has no effect.

Analysis of Variance↗

Chronically inflamed tissue activates plasma mediators of vascular permeability.

1. After inflammation was induced in the foot-pad of rats with nistatin or BCG, injection of "non-activated" homologous plasma at the inflamed site caused a significant increase in the vascular permeability of the lesions (Evans blue test), which was more intense in older lesions, increasing from 7.83 +/- 1.11 to 8.70 +/- 1.18 (nistatin, 4 and 21 days) and 7.30 +/- 0.66 to 7.54 +/- 0.80 (BCG, 4 and 21 days). 2. Steroidal (acetyltriamcinolone, 2 mg/kg) and non-steroidal (indomethacin, 25 mg/kg) [corrected] anti-inflammatory drugs markedly decreased this effect on 14-day old lesions induced by nistatin plus "non-activated" plasma (2.37 +/- 0.10 for acetyltriamcinolone treatment vs 8.15 +/- 1.22 for untreated animals; 3.34 +/- 0.41 for indomethacin treatment vs 8.15 +/- 1.22 for untreated animals) and BCG plus "non-activated" plasma (1.67 +/- 0.11 for acetyltriamcinolone treatment vs 10.27 +/- 0.52 for untreated animals; 5.87 +/- 0.35 for indomethacin treatment vs 9.14 +/- 0.23 for untreated animals). 3. These data suggest that an increase in exudation in chronic lesions might result in "reactivation" of the process as observed clinically, for example, in rheumatoid arthritis in man.

Animals↗

Hyperosmotic sodium chloride partially blocks the effects induced by Bothrops jararaca venom on vascular permeability and hemorrhage in the rat.

The effect of the administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on hemorrhage and vascular permeability changes induced by Bothrops jararaca venom in rats was determined 30 min after venom injection. This treatment given immediately after subcutaneous venom injection significantly reduced the hemorrhagic manifestations by 33%. The increase in vascular permeability was significantly reduced when the animals were pretreated with hyperosmotic saline or mannitol 15 min before receiving the venom (26% and 20%, respectively). However, when animals were treated immediately after venom injection, only the hyperosmotic NaCl solution significantly reduced vascular permeability (32%). Isotonic NaCl treatment had no effect on hemorrhagic lesions or vascular permeability.

Animals↗

Do connective tissue components induce plasma activation in vivo?

1. This paper describes the effect of homologous plasma in contact with connective tissue on vascular permeability, edema and cell migration. 2. The contact of "non-activated" plasma with connective tissue structures does not result in generation of mediators responsible for increase in vascular permeability or in edema. 3. "Activated" plasma is able to induce vascular permeability and edema when in contact with connective tissue components. 4. Injection of "non-activated" or "activated" plasma induced a mild inflammatory cell migration.

Animals↗

Effect of i.v. administered hyperosmotic sodium chloride on carrageenan-induced pleurisy in adrenalectomized and intact rats.

The effect of administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on carrageenan-induced pleurisy was determined in adrenalectomized and intact rats. The volume of the pleural exudate was significantly reduced 4 h after induction by treatment with hyperosmotic NaCl for both adrenalectomized (0.08 +/- 0.16 ml) and intact (0.03 +/- 0.08 ml) animals compared to their untreated controls (0.56 +/- 0.44 ml and 0.26 +/- 0.15 ml, respectively). Similarly, hyperosmotic NaCl treatment significantly reduced the total number of inflammatory cells in the pleural cavity: 29.60 x 10(6) +/- 7.80 x 10(6) cells for adrenalectomized animals and 28.90 x 10(6) +/- 11.43 x 10(6) cells for intact animals compared to 63.67 x 10(6) +/- 19.92 x 10(6) and 45.26 x 10(6) +/- 12.71 x 10(6) cells for their untreated controls. Treatment with isotonic saline did not affect carrageenan-induced pleurisy. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.

Adrenalectomy↗

Effect of hyperosmotic sodium chloride solution on vascular permeability and inflammatory edema in rats.

This study analyzes the effects of treatment with a hyperosmotic NaCl solution on carrageenan-induced inflammatory edema and vascular permeability in rats. Given 15 min before carrageenan, this treatment reduced paw edema measured for up to 6 h by 27 to 44%. Similarly, when the rats were treated 30 min after injection of the irritant, paw volume was significantly reduced (35 to 53%) between 1 and 6 h when compared to that of untreated animals. Increases in vascular permeability were significantly reduced at 30 min (73%) and 1 h (54%) in rats treated 15 min before, and at 1 h (49%) in animals treated 30 min after carrageenan. Treatment with hyperosmotic mannitol or isotonic NaCl solutions did not show any changes in inflammatory response to carrageenan. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.

Acute-Phase Reaction↗

Defective phagocytic ability of epithelioid cells reversed by levamisole.

Both E-macrophages and E-macrophage polykaryons (epithelioid cells) obtained from subcutaneous glass coverslips fail to express IgG (Fe) surface receptors as assessed by phagocytosis of SRBC coated with specific IgG(E(IgG)). When, however, these cells were incubated with E(IgG) in the presence of levamisole, their capacity to ingest these particles returned. It is concluded that loss of FC receptor activity during epithelioid transportation is a reversible phenomenon possibly associated with changes in cyclic AMP.

Animals↗

The haemorrhagic exudate and its possible relationship to neurogenic inflammation.

The morphological effects of an aqueous solution of Nistatin, of Clostridium septicum and Tityus serrulatus toxins, of Bothrops jararaca and Agkistrodon piscivorus venoms on the vessels of the tendinous portion of the diaphragm were investigated in guinea-pigs. It was demonstrated that all these substances, when injected intrapleurally induced not only an increase in the permeability of venules but also haemorrhages originating at this segment of the microcirculation. Red cells were shown to escape from venules either by diapedesis or from restricted areas of these vessels which showed intense ultrastructural disorganisation of the vessel wall. Previous treatment of the animals with steroidal or non-steroidal anti-inflammatory drugs or with anticoagulants and chemotherapeutic drugs did not abolish the effect of these irritants. Electrical or chemical stimulation of the phrenic nerve had effects on the microcirculation of the diaphragm similar to those of Nistatin, toxins and venoms. Because of these findings and because Nistatin when injected intrapleurally induces an intense perineuritis of the phrenic nerve, a tentative hypothesis is proposed linking haemorrhagic exudation to the antidromic stimulation of sensitive nerves.

Animals↗

Phagocytic potential of macrophages from within delayed hypersensitivity-mediated granulomata.

The phagocytic potential of macrophages from within granulomas associated with delayed hypersensitivity was studied in guinea-pigs sensitised with FCA and challenged either with PPD or live M. tuberculosis. The results show that FCA treatment induces a 30 percent increase in phagocytosis of IgG coated erythrocytes by macrophages which migrate into a foreign body granuloma. PPD treatment enhances this index to about 70 per cent. When live M. tuberculosis was used as antigen the phagocytic index of macrophages from lesions induced in sensitised animals was about 50 per cent. higher than in controls. The increase in phagocytosis by macrophages was maximal at 4 days and decreased 8 and 16 days after challenge, in both sensitised and non-sensitised animals. The results show that in granulomas associated with delayed hypersensitivity, macrophages have a transitory increase in their phagocytic activity. Later the older cells in the centre of the granuloma lose this property, thereby facilitating antigen persistence and chronicity.

Animals↗

Immunological and non-immunological phagocytosis by inflammatory macrophages, epithelioid cells and macrophage polykaryons from foreign body granulomata.

Inflammatory macrophages, epithelioid cells and macrophage polykaryons were obtained on the surface of round glass coverslips inserted into the subcutaneous tissue of mice and removed at different intervals. About 90 per cent of the macrophages and polykaryons express IgG, C and non-specific surface receptors, involved in phagocytosis, up to 15 days after coverslip implantation. In 21-day-old lesions, about 50 per cent of these cells lose the IgG resed with IgM and complement but do not incorporate these particles and are poorly phagocytic for glutaraldehyde-treated horse red blood cells. The ultrastructural study of these cells demonstrates that they are macrophages which have undergone epithelioid transformation. Whole-body irradiation of mice bearing implanted coverslips of 7 days duration reveals that 6 days after irradiation, the great majority of macrophages and multinucleate cells have acquired epithelioid characteristics. It is suggested that the loss of immunological receptors during epithelioid transformation in granulomas may protect bacteria and be disadvantageous to the host.

Age Factors↗