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 (l0.0 and 20.0 mg/kg) and long-term (10.0 mg kg(-1) day(-l), 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 carrageenininduced 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.

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 per cent), CD8+ (about 1-3 per cent), macrophages (about 21-22 per cent), lymphocyte B (about 0-1 per cent) and NK (about 1-2 per cent) 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.

Influência da baixa temperatura ambiental sobre a atividade fagocítica de trombócitos de rä touro gigante (Rana catesbeiana) / Influence of low environmental temperature on the phagocytic activity of bullfrog (Rana catesbeiana) thrombocytes

O objetivo do presente trabalho foi o de investigar a influência da baixa temperatura ambiental sobre a atividade fagocitária de trombócitos de rä touro gigante (Rana catesbeiana). O modelo indutor de fagocitose utilizado foi a injeçäo de carväo coloidal no saco linfático dorsal. Os resultados alcançados mostraram que o frio foi capaz de modular significativamente a capacidade fagocítica dos trombócitos. Animais tratados e mantidos a 6§C exibiram uma lenta atividade inicial à 1h (16,3 mais ou menos 4,3; resultados expressos com média desvio padräo de trombócitos positivos em 400 células analisadas/animal; n=6), que aumentou discretamente às 6h e 12h (45,8 mais ou menos 12,2; 55,5 mais ou menos 9,6), alcançando o máximo de reaçäo aos 3d e 7d (80,3 mais ou menos 27,5; 78,3 mais ou menos 29,5). Por outro lado, räs mantidas a 24§C apresentaram uma forte resposta inicial à 1h (90,0 mais ou menos 16,7), aumentando marcadamente até 1d (196,0 mais ou menos 49,8), e entäo diminuindo até 7d (56,0 mais ou menos 10,6). Os resultados obtidos suportam estudos prévios que demonstram a importância da temperatura ambiental sobre múltiplos processos relativos aos mecanismos de defesa desses animais

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

The relationship between social isolation and Ehrlicha 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 µl of a cell tumor suspension at a concentration of 1 to 5 x 10**7 tumor cells/ml was incolulated into the footpad and footpad size was measured for 10 days. Isolated mice presented a 30 percent reduction in tumor growth. Sciatic and saphenous neurectomy in one leg of 5 isolated mic (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 apw. 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 comapared 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

Chronically inflamed tissue activates plasma mediators of vascular permeability

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 + or - 1.11 to 8.70 + or - 1.18 (nistatin, 4 and 21 days) and 7.30 + or - 0.66 to 7.54 + or - 0.80 (BCG, 4 and 21 days). Steroidal (acetyltriamcinolone, 25 mg/kg) and non-steroidal (indomethacin, 2 mg/kg) anti-inflammatory drugs markedly decreased this effect on 14-day old lesions induced by nistatin plus "non-activated" plasma (2.37 + or - 0.10 for acetyltriamcinolone treatment vs 8.15 + or - 1.22 for untreated animals; 3.34 + or - 0.41 for indomethacin treatment vs 8.15 + or - 1.22 for untreated animals) and BCG plus "non-activated" plasma (1.67 + or - 0.11 for acetyltriamcinolne treatment vs 10.27 + or - 0.52 for untreated animals; 5.87 + or - 0.35 for indomethacin treatment vs 9.14 + or - 0.23 for untreated animals). 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

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

Do connective tissue components induce plasma activation in vivo?

1. this oaoer describes the effect if homologous plasma in contact with connective tissue on vascular perveability, edema and cell migration. 2. The contact of "non-activated"plasma with connective tissue structures does not tesults in generation of mediators responsible for increase in vascular premeability 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

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

The effect of administration of hyperosmotic NaCl (2ml, 7.8% NaCl, iv) on carregeenan induced pleurism was determined in adrenalectomized and intact rats. tThe 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 cells for adrenalectomized animlas and 28.90 x 10**6 ñ 11.43 x 10**6 cells for intact animals compared to 63.67 x 10**6 cells for their untreated controls. Tretament 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