Regulated commitment of TNF receptor signaling: a molecular switch for death or activation

Tumor necrosis factor receptor (TNFR) superfamily members can induce a context-dependent apoptosis or cell activation. However, the mechanisms by which these opposing programs are selected remain unclear. We show that in T cells, TNFR2 (TNFRSF1B) signaling is dramatically affected by the intracellular mediator RIP, a protein Ser/Thr kinase required for NF-kappaB activation by TNFR1 (TNFRSF1A). In the presence of RIP, TNFR2 triggers cell death, whereas in the absence of RIP, TNFR2 activates NF-kappaB. RIP is induced during IL2-driven T cell proliferation, and its inhibition reduces susceptibility to TNF-dependent apoptosis. Evidence that signaling outputs are shaped by intracellular constraints helps reconcile conflicting views of TNFR1 and TNFR2 as apoptotic mediators.     

Tolerability of Leukotriene Modifiers in Asthma

The so called leukotriene antagonists or, more accurately, the leukotriene modifiers are a rather heterogeneous set of drugs that work by several mechanisms. Such mechanisms include: (i) 5-lipoxygenase enzyme inhibition (e.g. zileuton); (ii) 5-lipoxygenase-activating-protein inhibition (e.g. quiflapon, BAYx 1005); (iii) LTD4-receptor antagonism (e.g. zafirlukast, montelukast, MK-571, pranlukast). The first leukotriene modifiers tested (L-649,923 and tomelukast) had adverse gastrointestinal effects. Since then, several leukotriene modifiers have been marketed, including zafirlukast, zileuton and montelukast. Zafirlukast has been associated with 8 cases of Churg-Strauss syndrome, although these were probably not caused by zafirlukast. It is more likely that this syndrome is related to the underlying illness, which was masked by corticosteroids, and revealed after zafirlukast-mediated asthma treatment allowed steroid withdrawal and unmasking of underlying vasculitis. The main adverse effects of zileuton include liver function test abnormalities, while montelukast, the most recently marketed, has so far shown minimal adverse effects. Zafirlukast causes a decrease in warfarin clearance and a clinically significant increase in prothrombin time, probably by cytochrome P450 isoenzyme interactions. Moreover, terfenadine decreases zafirlukast maximum serum concentrations. Calcium antagonists, cyclosporin, cisapride and astemizole are metabolised via the cytochrome P450 system, and interactions with leukotriene modifiers can be expected.     

Regulation of plasma insulin-like growth factor-I levels in brown trout (Salmo trutta)

In this study we report that the use of a heterologous radioimmunoassay (RIA) is valid for the detection of insulin-like growth factor-I (IGF-I) levels in plasma of a variety of fish species. Parallelism between standard curves and plasma dilutions were observed and the standard curve obtained with mammalian IGF-I presented the same characteristics as that obtained with coho salmon recombinant IGF-I.The RIA was biologically validated since total plasma IGF-I values were significantly modified by different experimental conditions. Hyperinsulinemia induced either by arginine or insulin injection was accompanied by increases in IGF-I plasma levels in brown trout (Salmo trutta). In contrast, parallel decreases in insulin and IGF-I circulating levels were observed after 45 days of fasting and 20 days after a single streptozotocin injection. Administration of arginine in fasted fish led to a relative increase in insulin and IGF-I plasma concentrations, while arginine injection in fish previously treated with streptozotocin increased IGF-I levels only. The above data suggest that insulin, together with other factors, may act to increase the levels of IGF-I in plasma.     

Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs

Macrophage Fcgamma receptors have an important role in host defense and the pathophysiology of immune mediated disorders. Alteration of splenic macrophage Fcgamma receptors expression predisposes to severe infection. Inhibition or blockade of splenic macrophage Fcgamma receptors is one of the mechanisms by which immune cytopenias improve. Dopaminergic drugs have clinically significant regulatory functions on the immune response. Using an experimental model in the guinea pig we assessed the effect of commonly used dopaminergic drugs on the expression of macrophage Fcgamma receptors. Three dopa-antagonists, bromocryptine, leuprolide, and pergolide, and seven dopa-antagonists, chlorpromazine, SCH 23390, metochlopramide, sulpiride, veralipride, alizapride, and cisapride, were studied. Following guinea pig treatment with dopaminergic drugs, the clearance of IgG-sensitized RBCs in vivo, the in vitro binding of IgG-sensitized RBCs by isolated splenic macrophages and flow cytometry with monoclonal antibodies were performed. Treatment with dopa-agonists enhanced the clearance of IgG-sensitized RBCs, the in vitro binding of IgG-sensitized RBCs by isolated splenic macrophages, and the cell surface expression of both macrophage Fcgamma receptors, and vice versa, dopa-antagonists impaired macrophage Fcgamma receptors expression. Macrophage FcgammaR1,2 was more sensitive than FcgammaR2 to such dopaminergic effect. These alterations of macrophage Fcgamma receptors expression are mediated by both D1 and D2 dopamine receptors, with a major participation of D2 receptors. Dopaminergic drugs alter the clearance of IgG-coated cells by an effect at the expression of splenic macrophage Fcgamma receptors.     

Effects of topical application of free and liposome-encapsulated lactoferrin and lactoperoxidase on oral microbiota and dental caries in rats

Four groups of rats were inoculated with Streptococcus sobrinus ATCC 33478 and fed a cariogenic diet for 42 days. Topical treatment with either distilled water, sodium fluoride (0.2%), a solution containing lactoferrin and lactoperoxidase, or a solution containing liposome-encapsulated lactoferrin and liposome-encapsulated lactoperoxidase was applied at intervals for 35 days. Caries incidence in groups treated with liposome-encapsulated lactoferrin and lactoperoxidase was significantly lower than in control groups. The number of viable Strep. sobrinus and the proportion of Strep. sobrinus in the total counts were significantly higher in liposome-treated groups. Free lactoferrin and lactoperoxidase did not cause a significant reduction in caries incidence.     

Isolation of Malassezia furfur from a cat

During a survey of the occurrence of Malassezia species in the external ear canals of cats without otitis externa, Malassezia furfur was isolated. This is the first report of the isolation of M. furfur from cats.     

Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease

Without adequate protection, the cells of the human body would be susceptible to destruction by the complement system. The main defense against complement lysis is a molecule called protectin (CD59) that is widely distributed in human tissues. Because the complement system has been suggested to be involved in the pathogenesis of inflammatory bowel diseases, we examined the expression of protectin in the colonic epithelium of patients with ulcerative colitis or Crohn's disease and controls. Colorectal specimens from 6 patients with ulcerative colitis, 8 patients with Crohn's disease, and 4 controls were obtained from surgical resections. Frozen sections of the specimens were immunostained for protectin using the Bric 229 monoclonal antibody. The expression of protectin was found to be decreased in the epithelium of patients with ulcerative colitis. In patients with Crohn's disease, the epithelial expression of protectin was decreased in diseased areas of gut while the expression did not significantly differ from that in controls in macroscopically normal areas. There was no difference in the expression of protectin on vascular endothelium, mononuclear cells, or smooth muscle. The reduction in epithelial expression of protectin in patients with ulcerative colitis or Crohn's disease may render epithelial cells vulnerable to complement lysis and lead to the destruction of gut epithelium as seen typically in these diseases.     

Macroemg in manifesting carriers of Duchenne muscular dystrophy

The aim of present study was to analyse possible myopathic changes in the muscles of manifesting carriers of Duchenne Muscular Dystrophy (DMD) using concentric needle emg and macroemg methods. Our material consisted of 10 manifesting carriers aged 9-52 (mean 30 years) and 20 healthy age-matched females. Concentric needle emg (CNEMG) and macroemg was performed in biceps brachii (BB) muscle in both groups: carriers and controls. Myopathic changes were observed in BB muscle in 5 of 10 manifesting carriers using CNEMG and in all cases (10 carriers) using macroemg method. Macro electrode, which reflects total motor unit activity, i.e., the total number and size of component muscle fibres, supplies information about early myogenic lesion of the muscle. Therefore the macroemg seems to be a sensitive and useful electrophysiological diagnostic method in carriers of DMD.     

Dental caries and periodontal disease (prevention and control methods)

There is a compelling need to apply preventive programs in both private and community practice of dentistry. This is to maintain improvements in oral health in developed and industrialized countries, and to stem increases in oral diseases in underserved and developing ones. At the outset, the terms prevention and control must be understood. The former is considered to mean a procedure or course of action that prevents the onset of disease, whereas the latter, implies reversing or stabilizing disease conditions. To be more precise, prevention will refer to the pre-pathologic or pre-clinical stage encompassing the promotive and specific protection levels--primary prevention stage. On the other hand, control will encompass early diagnosis and prompt treatment, disability limitation and rehabilitation levels-termed also collectively, as pathologic, clinical and final stages, or secondary and tertiary prevention. Community-based programs are usually structured to compliment therapeutic interventions of oral diseases, as well as prevention. In this era, and towards the next millennium, preventive and control programs are given high priorities in order to minimize the need for curative, restorative and therapeutic management of oral diseases. This review of the literature will give emphasis on established methods and programs for the prevention and control of the two most common oral diseases, dental caries and periodontal disease. The problems, background, and oral health objectives for the year 2000 as proposed by the World Health Organization (WHO) and the Federation Dentaire Internationale (FDI), as well as the recent advances in oral health relative to these diseases will be discussed. Finally, to better improve the efficacy of existing prevention and control methods, research needs and areas of concern relative to these diseases will be given consideration.