Dynamics of local defensive reactions in the lungs in acute experimental inflammatory process induced by respiratory syncytial virus

Study has been made of broncho-associated lymphoid tissue (BALT), the number and functional activity of lung phagocytes, with 42 mice BALB/c, induced by respiratory-syncytial virus. With virus inflammation a decreased number of lung macrophages, their stronger attraction and increased lung chemotaxis have been observed. The addition of bacterial infection was accompanied by an increase in lung neutrophil, lymphocyte and macrophage, a decrease in lung neutrophil chemotaxis, an increase in macrophage phagocytosis and BALT hyperplasia.     

Antimycotic therapy of experimental infections caused by dematiaceous fungi

Experimental infections of mice with Wangiella dermatitidis and Fonsecaea pedrosoi provided a model for evaluating new antifungal agents or new combination therapy. In our models flucytosine exerted a dose-related therapeutic effect on the acute and on the more chronic infection. In the acute Wangiella infection amphotericin B also showed therapeutic activity whereas in the Fonsecaea model the effect was weak. The azole derivative ICI 153066 was the most efficacious drug in the Wangiella model whereas ketoconazole was inactive. The effect on colony-forming units of fungi in the brain was stronger with all drugs tested than the effect on survival time. Combination therapy with flucytosine + amphotericin B showed reproducible potentiating effects whereas the combination of flucytosine + ketoconazole was only additive and amphotericin B + ketoconazole showed no synergistic effect.     

Circadian and circannual variation of the carrageenin inflammatory effect in rat

The circadian variation of edema produced by carrageenin (carr.) administration into plantar tissue was studied in rats kept under a 12 light - 12 dark regimen. Three doses were used (125, 250 and 500 micrograms per rat) injected at different time (02.00, 08,00, 14.00 and 20.00 h). With the high doses, the level of edema for the four hour period after carr. administration was similar whatever the hour of injection. In contrast, with the lower dose (125 micrograms) a circadian rhythm in the intensity of the edema produced was observed, showing a maximum of susceptibility during the light span. Repetitive experiments performed at different periods of the year validated this finding. Comparing mean mesors, analysis of this data showed two distinct levels of inflammation, with the lower level observed in autumn and winter indicating evidence for a circannual variability.     

Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis

Background

Adrenomedullin (AM), a 52-amino acid ringed-structure peptide with C-terminal amidation, was originally isolated from human pheochromocytoma. AM are widely distributed in various tissues and acts as a local vasoactive hormone in various conditions.

Methods

In the present study, we investigated the efficacy of AM on the animal model of bleomycin (BLM)-induced lung injury. Mice were subjected to intratracheal administration of BLM and were assigned to receive AM daily by an intraperitoneal injection of 200 ngr/kg.

Results and Discussion

Myeloperoxidase activity, lung histology, immunohistochemical analyses for cytokines and adhesion molecules expression, inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly (ADP-ribose) polymerase (PARP) were performed one week after fibrosis induction. Lung histology and transforming growth factor beta (TGF-β) were performed 14 and 21 days after treatments. After bleomycin administration, AM-treated mice exhibited a reduced degree of lung damage and inflammation compared with BLM-treated mice, as shown by the reduction of (1) myeloperoxidase activity (MPO), (2) cytokines and adhesion molecules expression, (3) nitric oxide synthase expression, (4) the nitration of tyrosine residues, (5) poly (ADP-ribose) (PAR) formation, a product of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (6) transforming growth factor beta (TGF-β) (7)and the degree of lung injury.

Conclusions

Our results indicate that AM administration is able to prevent bleomycin induced lung injury through the down regulation of proinflammatory factors.     

Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease

Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease.     

Dynamics of arachidonic acid mobilization by inflammatory cells

The development of mass spectrometry-based techniques is opening new insights into the understanding of arachidonic acid (AA) metabolism. AA incorporation, remodeling and release are collectively controlled by acyltransferases, phospholipases and transacylases that exquisitely regulate the distribution of AA between the different glycerophospholipid species and its mobilization during cellular stimulation. Traditionally, studies involving phospholipid AA metabolism were conducted by using radioactive precursors and scintillation counting from thin layer chromatography separations that provided only information about lipid classes. Today, the input of lipidomic approaches offers the possibility of characterizing and quantifying specific molecular species with great accuracy and within a biological context associated to protein and/or gene expression in a temporal frame. This review summarizes recent results applying mass spectrometry-based lipidomic approaches to the identification of AA-containing glycerophospholipids, phospholipid AA remodeling and synthesis of oxygenated metabolites.     

Dynamics of arachidonic acid mobilization by inflammatory cells

The development of mass spectrometry-based techniques is opening new insights into the understanding of arachidonic acid (AA) metabolism. AA incorporation, remodeling and release are collectively controlled by acyltransferases, phospholipases and transacylases that exquisitely regulate the distribution of AA between the different glycerophospholipid species and its mobilization during cellular stimulation. Traditionally, studies involving phospholipid AA metabolism were conducted by using radioactive precursors and scintillation counting from thin layer chromatography separations that provided only information about lipid classes. Today, the input of lipidomic approaches offers the possibility of characterizing and quantifying specific molecular species with great accuracy and within a biological context associated to protein and/or gene expression in a temporal frame. This review summarizes recent results applying mass spectrometry-based lipidomic approaches to the identification of AA-containing glycerophospholipids, phospholipid AA remodeling and synthesis of oxygenated metabolites.     

Dynamics of the avian inflammatory response to Salmonella following administration of the Toll-like receptor 5 agonist flagellin

Previous work has shown that flagellin (FGN) is a potent stimulator in vitro of phagocytic cell functions of chickens. The purpose of this study was to define the effects of FGN on the inflammatory response to Salmonella enteritidis (SE) in chickens. Intra-abdominal (IA) FGN administration caused significant increases in peripheral blood leukocytes (PBL) compared with SE-injected controls at 4 and 8 h postinjection (P相似文献   

Hormonal responsiveness of liver cells during the liver regeneration process induced by carbon tetrachloride administration

In control rats most of the ureagenic effect of adrenaline is mediated through alpha1-adrenoceptors with little participation of beta-adrenoceptors. Administration of carbon tetrachloride to rats induces significant changes in the adrenergic responsiveness of their hepatocytes. In rats intoxicated 3-5 days before the experiments were performed there is a marked increase in the beta-adrenergic and a decrease in the alpha-adrenergic responsiveness of the hepatocytes. The alpha1-adrenergic responsiveness increased with time reaching its basal level 15 days after the administration of carbon tetrachloride; simultaneously, the betal-adrenergic responsiveness was decreased. No change in the responsiveness to vasopressin and angiotensin II was observed in intoxicated animals as compared to the controls. In contrast, the responsiveness to glucagon was increased. Increased ability of local anesthetics to decrease urea production was observed in cells from intoxicated animals. It is suggested that changes at the plasma membrane level (lipids, receptors and transducing proteins) might participate in producing these effects.     

In vivo experimental modelling of the infectious process caused by stable L forms of the causative agent of typhoid

To simulate the infectious process and to study the persistence of L-forms, rabbits and guinea pigs were infected with S. typhi stable L-forms. The materials presented in this work indicate that both subconjunctival and intraperitoneal infection led to the development of the clinically indistinct, but morphologically pronounced pathological process with characteristic localization and typical changes in the gastrointestinal tract. The typical features of the process were the generalized immunomorphological reaction of the lymphoid apparatus with the appearance of light-colored reticulomacrophagal elements, the signs of the activation of humoral and cell-mediated immunity and the formation of small epitheloidocellular granulomas. The results of the investigation indicate that the stable cultures of S. typhi L-forms are highly pathogenic and capable of inducing the infectious process in experimental animals.     

Formation of nitric oxide in animal tissues during inflammatory process

EPR evidence was obtained that more intensive formation of mononitrosyl non-heme iron complexes with diethyl-dithiocarbamate (DETC) took place in mouse liver when inflammation process was initiated in mice by the lipopolysaccharide isolated from Salmonella typhimurium bacterium wall DETC intraperitoneally injected bound with endogenous non-heme iron resulted with DETC-Fe complex formation. These complexes were as a traps of nitric oxide appeared in animal tissues, and NO-Fe-DETC complexes were observed. Phenazone known as a free radical process inhibitor lowered NO production in animal organism. The free radical processes were suggested to intensify under inflammation reactions and to cause the various amino groups oxidation to nitroso groups which were capable to release free nitric oxide.     

Stimulation of DNA synthesis and mitoses in the rat liver in experimental galactosemia caused by the prolonged administration of galactose]

Feeding of rats with galactose-rich ration results in the activation of galactoso-1-phosphate-uridililtransferase in the liver after 2--4 days. By days 5--13, the activity of the enzyme decreased to the control level in spite of continued feeding of rats with galactose-rich ration. The activation of galactoso-1-phosphate-uridililtransferase occurred on the first 5 days of the experiment, whereas all proliferative activity in the liver increased from days 12--60, and the maximum mitotic was attained by the 20th and 50th days of feeding with galactose-rich diet. DNA synthesis also increased considerably, and this evidenced the increased H3-thymidine incorporation in hepatocyte nuclei. If one accept that the induction of enzyme transforming galactose to glucose is an adaptive response of cells (organism) to galactose in the diet, then the subsequent stage of adaptation would be hepatocyte proliferation.