Mast cell changes in experimental diabetes: focus on attenuation of allergic events

The prevalence of atopic diseases and diabetes is increasing worldwide though the concurrence of these pathologies in individual patients is found less frequent than it would be predicted. Moreover, co-existence of diabetes and allergy is generally marked by attenuation of their respective symptoms, and effective treatment of one disease exacerbates the other. This review gives an update of the state-of-the-art concerning the intercurrence of allergy and diabetes, particularly focusing on the consequences to the allergen-evoked vascular and cellular changes. It is proposed that the reduction in mast cell numbers and reactivity may be a pivotal mechanism behind the mutual exclusion phenomenon.

Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases

Phosphodiesterases (PDEs) are responsible for the breakdown of intracellular cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing isoenzymes found in inflammatory and immune cells. This generated greatest interest on PDE4 as a potential target to treat lung inflammatory diseases. For example, cigarette smoke-induced neutrophilia in BAL was dose and time dependently reduced by cilomilast. Beside the undesired side effects associated with the first generation of PDE4 inhibitors, the second generation of selective inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma and chronic obstrutive pulmonary diseases trials, thus re-enhancing the interest on these classes of compounds. However, the ability of PDE4 inhibitors to prevent or modulate the airway remodelling remains relatively unexplored. We demonstrated that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP)-9 activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI-1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the bronchial airways are associated with destruction of normal tissue structure, our data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling associated with chronic lung diseases.

Local anaesthetic medication for the treatment of asthma

It is presumed that drugs able to prevent bronchial spasm and/or inflammation may have therapeutic potential to control asthma symptoms. The local anaesthetic lidocaine has recently received increased attention as an alternative form of treatment for asthmatic patients. This paper reviews the major findings on the topic and summarizes the putative mechanisms underlying the airway effects of local anaesthetic agents. We think that lidocaine extends the spectrum of options in asthma therapy, probably by counteracting both spasmogenic and inflammatory stimuli in the bronchial airways. The possibility of development of new anti-asthma compounds based on the synthesis of lidocaine derivatives is also on the horizon.

The role of the external mycelial network of arbuscular mycorrhizal fungi: III.A study of nitrogen tranfer between plants interconnected by a commom mycelium

An experiment under greenhouse conditions was carried out to evaluate the relative contribution of arbuscular mycorrhizal fungi (AMF) in the process of nitrogen transfer from cowpea to maize plants, using the isotope 15

Modulatory role of eosinophils in allergic inflammation: new evidence for a rather outdated concept

The eosinophilic response has been identified as a key alteration in the pathogenesis of asthma and other allergic diseases. A close-correlation between disease severity and eosinophilia, and the eosinophil ability to provide toxic and pro-inflammatory agents are the major elements supporting the interpretation that there is indeed a causal relationship between these phenomena. Nevertheless, controversy still persists since some studies have clearly demonstrated that eosinophil infiltration is not necessarily accompanied by tissue damage or hyperresponsiveness. In addition, there are some examples in the literature in which such alterations are not modified following abrogation of eosinophil influx. In this review it will be argued, based on a model of IgE-dependent pleuristy, that eosinophil infiltration can be associated with down-regulation of allergic inflammatory response. The potential mechanism by which eosinophils could be acting as a immunomodulatory cells in this particular system will also be assessed.

Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE) type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF) and leukotriene B4 (LTB4) in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP) and N2-2'-O-dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP) has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95 per cent purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4 in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor) nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppresive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

Antigen-induced pleural eosinophilia is suppressed in diabetic rats: role of corticosteroid hormones

Previous studies have evidenced for the existence of interactive regulatory mechanisms between insulin and steroid hormones in different systems. In this study, we have investigated whether endogenous corticosteroids could be implicated in the hyporeactivity to antigen challenge observed in sensitized diabetic rats. Alloxinated rats showed a long-lasting increase in the blood glucose levels and a reduction in the number of pleural mast cells at 48 and 72 hr, but not at 24 hr after alloxan administration. In parallel, they also showed a significant elevation in the plasma levels of corticosterone together with an increase in the adrenal/body weight ratio. Antigen-evoked eosinophil accumulation appeared significantly reduced in rats pretreated with dexamethasone as weel as in those rendered diabetic 72 hr after alloxan. In the same way, naive animals treated with dexamethasone also responded with a significant decrease in the number of pleural mast cells. Interestingly, when sensitized diabetic rats were pretreated with the steroid antagonist RU 38486 a reversion of the reduction in the allergen-induced eosinophil accumulation was noted. We conclude that the down-regulation of the allergic inflammatory response in diabetic rats is close-related to reduction in mast cell numbers and over expression of endogenous corticosteroids.

The role of external mycellial network of arbuscular mycorrhizal (am) fungi. II. S study of phosphorus transfer between plants interconnected by a common mycellium

A transferência de 32 p entre Lolium pereme (planta doadora) e plantago lanceolata (planta receptora), mediada por fungos micorrízicos arbusculares (FMA), foi avaliada quando as espécimes cresceram juntas ou separadas. Os resultados demonstraram que a infecçäo micorrízica arbusculares proporcionou aumento significativo na quantidade de 32 P transferida das plantas doadoras para as receptoras näo somente quando as mesmas foram cutivadas com os sistemas radiculares juntos, mas também quando tiveram seus sistemas radiculares separados por uma distância de 2,33 cm. A maior quantidade de 32p transferido entre as duas espécies de plantas ocorreu através da transferência direta via micélio fúngico que as interligou

PAF-acether and the acute inflammatory reaction

PAF-aceter é um fosfolipídio que exerce um papel importante na reaçäo inflamatória aguda. No modelo experimental do edema da para de rato e pleurisia, a reaçäo induzida pelo PAF era acompanhada de hemoconcentraçäo, embora esses processos pareçam ser mediados por mecanismos distintos. Antagonistas específicos do PAF, como BN 52021 e WEB 2086, inibem 60% do edema induzido pelo PAF. Leucotrienos e mecanismos histaminérgicos envolvendo receptores H2 parecem participar no processo. A participaçäo do sistema adrenérgico e de metabólitos da ciclooxigenase é controversa. Infiltraçäo de leucócitos, observada após a injeçäo de PAF, e plaquetas näo säo necessárias para a formaçäo de edema. Auto-dessensibilizaçäo induzida pelo PAF pôde ser observada, sendo seletiva e dependente a interaçäo do PAF com receptores específicos em um processo de regulaçäo depressiva ("dow-regulation"). Nenhuma participaçäo deo PAF foi observada na reaçäo inflamatória induzida pela carregenina, contrariamente áquela provocada pelo zimosan, que é principalmente dependente do PAF-aceter