Treatment of Herpes Zoster

Resolution of acute pain related to herpes zoster is accelerated with any of the following: oral acyclovir (Zovirax) 800 mg five times daily for seven days; valacyclovir (Valtrex) 1,000 mg three times daily for seven days; or famciclovir (Famvir) 750 mg once daily, 500 mg twice daily, or 250 mg three times daily for seven days. (Strength of recommendation: A) Oral corticosteroids given during the acute phase of the illness have not been shown to reduce the incidence or severity of postherpetic neuralgia. (Strength of recommendation: B) There is no evidence to support the use of tricyclic antidepressants or anticonvulsants for the management of herpes zoster. (Strength of recommendation: B

Do human neutrophils make hydroxyl radical? Detection of free radicals by human neutrophils activated with a soluble or particulate stimulus using electron paramagnetic resonance spectrometry

Using electron paramagnetic resonance spectrometry and the spin trap 5,5-dimethyl-1-oxide (DMPO), neutrophil free radical production in response to phorbol myristate acetate and opsonized zymosan was investigated. Using phorbol myristate acetate and zymosan (3 mg/ml), the superoxide spin-trapped adduct 2-2-dimethyl-5-hydroperoxy-1-pyrrolidinyloxyl (DMPO-OOH) and the hydroxyl spin-trapped adduct 2-2-dimethyl-5-hydroxy-1-pyrrolidinyloxyl (DMPO-OH) were detected. Only DMPO-OH was observed with zymosan (0.5 mg/ml). Hydroxyl radical production in the presence of dimethylsulfoxide (Me2SO) and DMPO yields 2,2,5-trimethyl-1-pyrrolidinyloxyl. The only 2,2-trimethyl-1-pyrrolidinyloxyl detected following neutrophil stimulation was that expected from DMPO-OOH degradation. Superoxide dismutase but not catalase inhibited generation of all three spin-trapped adducts. These data indicate that DMPO-OH arose from DMPO-OOH degradation and does not represent hydroxyl radical production. Under certain conditions DMPO-OH is the predominant spin-trapped adduct resulting from neutrophil superoxide production, perhaps due to cellular bioreduction of DMPO-OOH to DMPO-OH. Cytochalasin B, which prevents phagosome closure, inhibited zymosan-stimulated neutrophil oxygen consumption and electron paramagnetic resonance superoxide detection. No hydroxyl radical was detected. Spin trapping with DMPO appears to detect intraphagosomal free-radical formation

Phagocyte-derived lactate stimulates oxygen consumption by Neisseria gonorrhoeae. An unrecognized aspect of the oxygen metabolism of phagocytosis.

L'acide lactique extra-cellulaire, libéré par suite de la glycolyse des neutrophiles, augmente le transfert des électrons et la consommation d'O2par les gonocoques. On discute les implications possibles de cette observation pour la pathogénie bactérienne

Role of extracellular iron in the action of the quinone antibiotic streptonigrin: mechanisms of killing and resistance of Neisseria gonorrhoeae.

The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococcal mutants. Streptonigrin (0.025 microgram/ml) efficiently killed gonococcal strain FA1090, and this effect depended on iron. Streptonigrin-resistant mutant FA6271 had normal iron uptake but was moderately deficient in total iron. Resistance most likely resulted from failure of FA6271 to divert electrons to streptonigrin, as demonstrated by a reduction in KCN-insensitive respiration (a hallmark of the action of quinones) and superoxide formation. Other mutants selected for inability to use human iron-binding proteins (strains FA6273 and FA6275) had no increase in streptonigrin MIC and no decrease in KCN-insensitive respiration. Mutants did not demonstrate an increase in superoxide dismutase or catalase. Streptonigrin killing of gonococci depended on a reaction(s) in which extracellular iron was important, presumably because iron was required for catalysis of hydroxyl radical. The results suggest that a membrane component may be a target for the actions of streptonigrin

Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques

<p>Abstract</p> <p>Background</p> <p>Myeloperoxidase (MPO) -containing macrophages and neutrophils have been described at sites of plaque rupture. The presence of these cells in precursor lesions to acute rupture (thin cap atheroma, or vulnerable plaque) and within thrombi adjacent to ruptures has not been described, nor an association with iron-containing macrophages within unstable plaques.</p> <p>Methods</p> <p>We studied 61 acute ruptures, 15 organizing ruptures, 31 thin cap fibroatheromas, and 28 fibroatheromas from 72 sudden coronary death victims by immunohistochemical and histochemical techniques. Inflammatory cells were typed with anti-CD68 (macrophages), anti-BP-30 (neutrophil bactericidal glycoprotein), and anti-MPO. Iron was localized by Mallory's Prussian blue stain. In selected plaques alpha smooth muscle actin (DAKO, Carpinteria, CA, clone M0851) was performed.</p> <p>Results</p> <p>MPO positive cells were present in 79% of ruptured caps, 28% of thin cap fibroatheroma, and no fibroatheromas; neutrophils were present in 72% of ruptures, 8% of thin cap fibroatheromas, and no fibroatheromas. Iron containing foam cells were present in the caps of 93% of acute ruptures, of 85% of organizing ruptures, 20% of thin cap atheromas, and 10% of fibroatheromas. MPO positive cells were more frequent in occlusive than non-occlusive thrombi adjacent to ruptures (p = .006) and were more numerous in diabetics compared to non-diabetics (p = .002)</p> <p>Conclusion</p> <p>Unstable fibrous caps are more likely to contain MPO-positive cells, neutrophils, and iron-containing macrophages than fibrous caps of stable fibroatheromas. MPO-positive cells in thrombi adjacent to disrupted plaques are associated with occlusive thrombi and are more numerous in diabetic patients.</p

Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

Glycobiology of cell death: when glycans and lectins govern cell fate

Although one typically thinks of carbohydrates as associated with cell growth and viability, glycosylation also has an integral role in many processes leading to cell death. Glycans, either alone or complexed with glycan-binding proteins, can deliver intracellular signals or control extracellular processes that promote initiation, execution and resolution of cell death programs. Herein, we review the role of glycans and glycan-binding proteins as essential components of the cell death machinery during physiologic and pathologic settings.Fil: Lichtenstein, Rachel. Ben-Gurion University of the Negev. Faculty of Engineering. Department of Biotechnology Engineering; IsraelFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica; Argentin

Protease-cleaved iron-transferrin augments oxidant-mediated endothelial cell injury via hydroxyl radical formation.

Previous work has shown that the Pseudomonas-derived protease, pseudomonas elastase (PAE), can modify transferrin to form iron complexes capable of catalyzing the formation of hydroxyl radical (.OH) from neutrophil (PMN)-derived superoxide (.O2-) and hydrogen peroxide (H2O2). As the lung is a major site of Pseudomonas infection, the ability of these iron chelates to augment oxidant-mediated pulmonary artery endothelial cell injury via release of 51Cr from prelabeled cells was examined. Diferrictransferrin previously cleaved with PAE significantly enhanced porcine pulmonary artery endothelial cell monolayer injury from 2.3-6.3 to 15.8-17.0% of maximum, resulting from exposure to H2O2, products of the xanthine/xanthine oxidase reaction, or PMA-stimulated PMNs. Iron associated with transferrin appeared to be responsible for cell injury. Spin trapping and the formation of thiobarbituric acid-reactive 2-deoxyribose oxidation products demonstrated the production of .OH in this system. The addition of catalase, dimethyl thiourea, and the hydrophobic spin trap, alpha-phenyl-n-terbutyl-nitrone, offered significant protection from injury (27.8-58.2%). Since sites of Pseudomonas infection contain other proteases, the ability of porcine pancreatic elastase and trypsin to substitute for PAE was examined. Results were similar to those observed with PAE. We conclude .OH formation resulting from protease alteration of transferrin may serve as a mechanism of tissue injury at sites of bacterial infection and other processes characterized by increased proteolytic activity