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Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis  [PDF]
Maria Fátima Horta,Bárbara Pinheiro Mendes,Eric Henrique Roma,Fátima Soares Motta Noronha,Juan Pereira Macêdo,Luciana Souza Oliveira,Myrian Morato Duarte,Leda Quercia Vieira
Journal of Parasitology Research , 2012, DOI: 10.1155/2012/203818
Abstract: Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO?) in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response. 1. Introduction More than 20 Leishmania species cause leishmaniasis in people with different genetic backgrounds and general states of health. Further, the diversity of clinical manifestations, epidemiology, and immunopathology makes leishmaniasis a complex disease to study. Clinical manifestations include ulcerative skin lesions, destructive mucosal inflammation, and disseminated visceral infection (kala azar). Morbidity includes disfigurement and disability. However, some features are shared by all forms of infection by these protozoan parasites: parasitism is persistent, tissue macrophages are the main parasitized cell, and the host immune response defines the outcome of the disease [1]. Cutaneous leishmaniasis is caused by several species of the genus Leishmania, including L. major, L. tropica, L. aethiopica, L. mexicana, L. braziliensis, L. guyanensis, L. panamensis, L. peruviana, and L. amazonensis. The Leishmania genus is divided in two subgenera, Leishmania and Viannia. In the subgenus Leishmania, L. amazonensis, L. mexicana (complex L. mexicana), and L. major (complex L. major) are by far the most studied species that cause cutaneous leishmaniasis. The subgenus Viannia comprises two important species that cause cutaneous leishmaniasis, L. guyanensis (complex L. guyanensis) and L. braziliensis (complex L. braziliensis) [2, 3]. The promastigote stage of the parasite lives in the gut of sandflies (Phlebotomus in the Old World and Lutzomyia in the New World) [4]. In the insect gut, Leishmania promastigotes develop into metacyclic (infective) forms and enter the vertebrate host when female sandflies take a blood meal. In the vertebrate host, phagocytic cells ingest the metacyclic promastigotes that, inside the phagolysosome, differentiate into the amastigote form and replicate. The
Investigation on nitric oxide and C-reactive protein involvement in anti-leishmanial effects of artemisinin and glucantim on cutaneous leishmaniasis
S. Nemati,H. Nahrevanian,A. Haniloo,M. Farahmand
Advanced Studies in Biology , 2013,
Abstract: Cutaneous leishmaniasis (CL), a dermatological parasitic infection caused byLeishmania major and L .tropica. This disease is still one of the health problemsin the tropical and sub tropical parts of world, region and Iran. Although,artemisinin (qinghaosu) is widely used as anti-malarial agent, it is alsodemonstrated its anti-promastigote effects on some leishmania species.Inflammatory responses against leishmania consist of chemokines, immune cellsand mediators. This study investigates two immunological pathways includingnitric oxide (NO) and C-reactive protein (CRP) in L. major infected Balb/c micefollowing treatment with artemisinin and glucantim. Plasma was investigated forNO and CRP alterations using Griess Micro Assay (GMA) and Latex Agglutinations Test (LAT) respectively. The results indicated a significant declinein NO levels due to atemisinin treatment (P≤0.05) and in untreated group(P≤0.05). No changes in CRP were observed in experimental groups. It isindicated that L. major infection naturally decreased NO induction in Balb/c miceas a result of amastigote action; therefore artemisinin was not able to increase NOto combat parasite. It is concluded that artemisinin/glucantim action in CL wasnot associated with NO and CRP pathways; however more studies are needed toclarify other immunological parameters.
Analysis of regulation role of sRNA (istR) in Salmonella resistant to reactive nitrogen and oxygen intermediates

CAO Xue-Song,JIANG Hui-Yuan,CAO Ming-Hui,GU Hong-Wei,ZENG Ke,

微生物学通报 , 2011,
Abstract: Salmonella is a facultative intracellular pathogen that is associated with gastroenteritis,sep-ticemia,and typhoid fever.It survives and replicates in macrophages during the course of infection and can be exposed to a number of stressful environments during its life cycle.Among the major antimicro-bial products of macrophages are reactive intermediates of the oxidation of nitrogen(RNI) and the re-duction of oxygen(ROI) which belong to oxygen-dependent antimicrobial systems of phagocytic cells.Resistance to ...
Cutaneous leishmaniasis with unusual presentation  [cached]
Khatri M,Shafi M,Banghazil M
Indian Journal of Dermatology, Venereology and Leprology , 1999,
Abstract: Three cases of cutaneous leishmaniasis with unusual presentation seen at Central Hospital Tripoli, Libya are described. Case No. 1 and 2 had 102 and 109 noduloulcerative lesions with generalized almost bilaterally symmetrical distribution, suggestive of dissemination. Case No. 3 had large verrucous carcinoma but histopathology suggested lupoid (chronic cutaneous) leishmaniasis. Patient No. 2 developed hypersensitivity reaction to sodium stibogluconate after 10 days but responded well to the treatment. Case No. 2 did not tolerate the above treatment and was treated successfully with combination of rifampicin and INH. Case No. 3 was treated successfully with liquid nitrogen cryotherapy by Cryosurg-Frigitonics, using special open probes.
Flow Cytometric Analysis of Leishmania Reactive CD4+/CD8+ Lymphocyte Proliferation in Cutaneous Leishmaniasis
M Nateghi Rostami,A Khamesipour,SE Eskandari,A Miramin Mohammadi
Iranian Journal of Parasitology , 2008,
Abstract: Background: Determination of the division history of T cells in vitro is helpful in the study of effector mechanisms against infections. Technique described here uses the intracellular fluorescent label carboxyfluorescein diacetate succinimidyl ester (CFSE) to monitor the proliferation. Methods: In a cross sectional study, blood samples were collected from 7 volunteers with history of cutaneous leishmania-sis (CL) and one healthy control from endemic areas in Isfahan province who referred to the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), then CD4+/CD8+ lymphocytes and CD14+ monocytes were isolated from peri-pheral blood mononuclear cells (PBMC) using mAbs and magnetic nanoparticles. CFSE labeled CD4+ or CD8+ lympho-cytes cultured with autologous monocytes in the presence of PHA, SLA, live Leishmania major or as control with-out sti-mulation. Cells were harvested after 7 days and were analyzed using flow cytometry. Results: Five consecutive divisions were monitored separately. Stimulation of CD4+ or CD8+ lymphocytes from CL sub-jects with SLA showed a significant difference in proliferation comparing with unstimulated cells (P< 0.05). The signifi-cant difference in the percentages of CD4+ cells stimulated with SLA was revealed at different divisions for each subject. In CD8+ lymphocyte, significant stronger stimulation of SLA was evident later in the proliferation process. The mean number of divisions in both CD4+/CD8+ lymphocytes stimulated with SLA was significantly greater than when stimulated with live L. major (P=0.007 / P=0.012, respectively) Conclusion: The percentage of divided cells might be calculated separately in each division. The cells remained active following CFSE staining and there is possibility of functional analysis simultaneously.
Cutaneous Leishmaniasis of the Eyelid: A Case Report  [PDF]
Jamshid Ayatollahi,Ali Ayatollahi,Seyed Hossein Shahcheraghi
Case Reports in Infectious Diseases , 2013, DOI: 10.1155/2013/214297
Abstract: Cutaneous leishmaniasis is endemic in certain areas of Iran, and in recent years, there has been an increase in the number of reports for rare and new forms of cutaneous leishmaniasis. We describe one unusual clinical form of cutaneous leishmaniasis. In a 27-year-old man, who noted a pimple on the upper eyelid 4 months before. The lesion was nodular and measured 1?cm?× 1?cm in diameter. A diagnosis of eyelid cutaneous leishmaniasis was made, and treatment was started with intramuscular meglumine antimonate. He showed a dramatic response, and the lesion almost completely disappeared. 1. Introduction Cutaneous leishmaniasis is a common protozoal disease and an important public health problem in Iran [1]. Cutaneous Leishmaniasis is a zoonotic disease caused by the Leishmania spp., and transmission occurs through the bite of a female sandfly infected with Leishmania parasites [2]. The Leishmania spp. may produce several clinical syndromes. Cutaneous leishmaniasis is the most common form, and the initial lesion is a nodule at the bite site by an infected sandfly. Fever or pain is not a feature of ulcer. We describe an unusual site of infection, eyelid cutaneous leishmaniasis. The patient was from the Yazd province, which is in the center of Iran. 2. Case Report A 27-year-old man from center of Iran noted a small pimple on eyelid 4 months before presentation. The eyelid lesion enlarged slowly. It was as a well-defined, firm, nontender, and subcutaneous skin-colored nodule. The lesion measured 1?cm × 1?cm in diameter (Figure 1). Figure 1: The lesion of eyelid on right eye. The lesion had been enlarging slowly and had slightly erythematous, raised borders and was crusty and painless. CBC (complete blood cell count), ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), and blood chemistries gave results within normal limits. Sample culture of the lesion grew Staphylococcus aureus. Various treatments with cephalexin, cloxacillin, amoxicillin-claulanate, and steroids failed to heal the lesion. These treatments were performed for 10 days Although there was cutaneous leishmaniasis in the patient’s residence, and also because lack of response to treatment, cutaneous leishmaniasis or basal cell carcinoma was proposed as a differential diagnosis for him. A slit-skin smear was taken from the edge of the nodule before a biopsy could be taken. Giemsa stain of the sample showed numerous leishman bodies within the macrophages (Figure 2), and the diagnosis of cutaneous leishmaniasis was confirmed. The patient was treated with meglumine antimonate (glucantime) in a
Histopathological spectrum in cutaneous leishmaniasis: A study in Oman  [cached]
Venkataram Mysore,Moosa Mohammed,Devi Leena
Indian Journal of Dermatology, Venereology and Leprology , 2001,
Abstract: Cutaneous leishmaniasis presents a spectrum of manifestations both clinically and histologically. Several previous studies have established the value of histological examination in the diagnosis of cutaneous leishmaniasis. Different reaction patterns have been reported. Forty caes of cutaneous leishmaniasis were studied in the Sultanate of Oman, with particular reference to the different histological features. Clinical features were correlated with the histological patterns. Four histological patterns were identified-1) diffuse macrophage infiltration without necrosis, 2) macrophage infiltration with necrosis. 3) early reactive granuloma and 4) established epitheloid granuloma. LD bodies were identified in 65% of cases. Epidermal features were nonspecific. Though the patterns could be correlated with the duration and the clinical type of lesion in a few cases, the correlation was not consistent.
Role of Reactive Oxygen Intermediates and Nitric Oxide in Resistance to Plant Diseases

WANG Li-Guo,LI Ling,

植物学报 , 2003,
Abstract: 植物与病原菌互作时,活性氧中间体(reactive oxygen intermediates,ROI)和一氧化氮(NO)参与了植物抗病性的建立。寄主与病原菌非亲合性互作产生二次氧爆发高峰,体内NO增加。许多氧化酶可以催化氧爆发产生ROI。ROI和NO通过氧化还原信号启动寄主细胞局部的过敏性坏死反应和全株系统获得性抗病性。
Leishmania?braziliensis-Reactive T Cells Are Down-Regulated in Long-Term Cured Cutaneous Leishmaniasis, but the Renewal Capacity of T Effector Memory Compartments Is Preserved  [PDF]
Regina Pereira-Carvalho, Carolina O. Mendes-Aguiar, Manoel P. Oliveira-Neto, Cláudia J. F. Covas, álvaro L. Bertho, Alda M. Da-Cruz, Adriano Gomes-Silva
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081529
Abstract: Leishmania?(Viannia)?braziliensis control and tissue damage relate to the effector immune response, which in turn affects clinical outcome. Leishmania reactive CD4+ and CD8+ T cells are expanded in long-term healed cutaneous leishmaniasis (hCL) patients but their functional characteristics remain to be determined. This study investigates antigen-specific recall in long-term healed CL caused by L.?braziliensis infection. Healed CL subjects were grouped according to the time elapsed since the end of therapy: less than two years and two to five years. Activation phenotype (CD69+ or CD25+) and subpopulations of memory T cell phenotypes [central memory (Tcm): CD45RO+ CCR7+ or effector memory (Tem): CD45RO+ CCR7-] were quantified in ex vivo blood mononuclear cells and after Leishmania antigens stimuli. A reduction in the percentage of activated Leishmania-responder CD4+ and CD8+ T cells in hCL was associated with the time elapsed since clinical cure. Percentage of CD69+ in TCD4+ and TCD8+ cells were negatively correlated with IL-10 levels. Ex vivo analyses showed contracted Tem CD4+ and Tem CD8+ compartments from hCL with long time elapsed since clinical cure, although renewal of these compartments was observed following in vitro exposure to leishmanial stimuli. Our results show that healed L.?braziliensis infected patients exhibit a recall response to Leishmania antigens with evident expansion of effector memory T cells. Regulated leishmanial-specific response seems to emerge only about two years after initial contact with the parasite antigens.
Production of reactive oxygen (H2O2) and nitrogen (NO) intermediates and TNF-α in mice genetically selected for high (H) and low (L) antibody response and experimentally infected with Leptospira serovar pomona
Haanwinckel, Maria Cristina Santos;Oliveira, Silvio Luis de;
Brazilian Journal of Microbiology , 2011, DOI: 10.1590/S1517-83822011000200041
Abstract: the aim of the present study was to evaluate the activity of macrophages, and the production of tnf-α and antibodies against experimental infection by leptospira serovar pomona in mice genetically selected for high (h) or low (l) humoral immune response. to evaluate macrophagic activity, peritoneal and splenic lavages were performed for determination of oxygen (h2o2) and nitrogen (no) intermediates. the production of the tumor necrosis factor (tnf-α) was investigated through bioassays in serum and homogenates of splenic and hepatic cells of control and infected animals, as was as specific antibodies production. the immune response against serovar pomona in those lines, was characterized by high antibody production, especially in later periods of the infectious process, whereas values of bacterial recovery in culture medium were lower. the production of reactives oxygen and nitrogen intermediate, also helped to eliminate leptospira pomona in both lines; h2o2 production an important factor in hiv-a, as well as no production in liv-a, especially in later post-inoculation periods. the same was detected for tnf-α. results suggest that such lines could be an important model to investigate the pathogenesis and the immune response of animals against the several leptospira serovars.
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