Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

Abstract:

BACKGROUND:The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/-)) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY:Rhesus monkeys and C57BL/6 and Nos2(-/-) mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+) cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue. RESULTS:Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+) cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/-) mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. CONCLUSION:T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC severity, mainly disturbing of the molecular pathway involved in electrical synchrony. These findings open a new avenue for therapeutic tools in Chagas' heart disease.

journal_name

PLoS Negl Trop Dis

authors

Carvalho CM,Silverio JC,da Silva AA,Pereira IR,Coelho JM,Britto CC,Moreira OC,Marchevsky RS,Xavier SS,Gazzinelli RT,da Glória Bonecini-Almeida M,Lannes-Vieira J

doi

10.1371/journal.pntd.0001644

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

e1644

issue

5

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-11-01063

journal_volume

6

pub_type

杂志文章
  • Correlative and dynamic imaging of the hatching biology of Schistosoma japonicum from eggs prepared by high pressure freezing.

    abstract:BACKGROUND:Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle. Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000334

    authors: Jones MK,Bong SH,Green KM,Holmes P,Duke M,Loukas A,McManus DP

    更新日期:2008-01-01 00:00:00

  • Potential for sylvatic and urban Aedes mosquitoes from Senegal to transmit the new emerging dengue serotypes 1, 3 and 4 in West Africa.

    abstract::Dengue fever (DEN) is the most common arboviral disease in the world and dengue virus (DENV) causes 390 million annual infections around the world, of which 240 million are inapparent and 96 million are symptomatic. During the past decade a changing epidemiological pattern has been observed in Africa, with DEN outbrea...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0007043

    authors: Gaye A,Wang E,Vasilakis N,Guzman H,Diallo D,Talla C,Ba Y,Dia I,Weaver SC,Diallo M

    更新日期:2019-02-13 00:00:00

  • Impact of age-specific immunity on the timing and burden of the next Zika virus outbreak.

    abstract::The 2015-2017 epidemics of Zika virus (ZIKV) in the Americas caused widespread infection, followed by protective immunity. The timing and burden of the next Zika virus outbreak remains unclear. We used an agent-based model to simulate the dynamics of age-specific immunity to ZIKV, and predict the future age-specific r...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0007978

    authors: Counotte MJ,Althaus CL,Low N,Riou J

    更新日期:2019-12-26 00:00:00

  • Advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta.

    abstract::Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta. Traditionally, the human treponematoses have been differentiated based upon their clinical manif...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pntd.0002283

    authors: Mitjà O,Šmajs D,Bassat Q

    更新日期:2013-10-24 00:00:00

  • Contrasting spatial distribution and risk factors for past infection with scrub typhus and murine typhus in Vientiane City, Lao PDR.

    abstract:BACKGROUND:The aetiological diagnostic of fevers in Laos remains difficult due to limited laboratory diagnostic facilities. However, it has recently become apparent that both scrub and murine typhus are common causes of previous undiagnosed fever. Epidemiological data suggests that scrub typhus would be more common in ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000909

    authors: Vallée J,Thaojaikong T,Moore CE,Phetsouvanh R,Richards AL,Souris M,Fournet F,Salem G,Gonzalez JP,Newton PN

    更新日期:2010-12-07 00:00:00

  • A dual drug sensitive L. major induces protection without lesion in C57BL/6 mice.

    abstract::Leishmaniasis is a major health problem in some endemic areas and yet, no vaccine is available against any form of the disease. Historically, leishmanization (LZ) which is an inoculation of individual with live Leishmania, is the most effective control measure at least against cutaneous leishmaniasis (CL). Due to vari...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002785

    authors: Davoudi N,Khamesipour A,Mahboudi F,McMaster WR

    更新日期:2014-05-29 00:00:00

  • Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic Vibrio cholerae.

    abstract::The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence factors to thrive in the human small intestine and environmental reservoirs. Among this pathogen's arsenal of virulence factors is the tightly regulated type VI secretion system (T6SS). This system acts as an inverted bacteriophage to inj...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0004031

    authors: Bachmann V,Kostiuk B,Unterweger D,Diaz-Satizabal L,Ogg S,Pukatzki S

    更新日期:2015-08-28 00:00:00

  • Exploratory space-time analyses of Rift Valley Fever in South Africa in 2008-2011.

    abstract:BACKGROUND:Rift Valley fever (RVF) is a zoonotic arbovirosis for which the primary hosts are domestic livestock (cattle, sheep and goats). RVF was first described in South Africa in 1950-1951. Mechanisms for short and long distance transmission have been hypothesised, but there is little supporting evidence. Here we de...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0001808

    authors: Métras R,Porphyre T,Pfeiffer DU,Kemp A,Thompson PN,Collins LM,White RG

    更新日期:2012-01-01 00:00:00

  • Evaluation of the loop mediated isothermal DNA amplification (LAMP) kit for malaria diagnosis in P. vivax endemic settings of Colombia.

    abstract:BACKGROUND:Most commonly used malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections which are frequent in low transmission settings. Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too laborious for field...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0003453

    authors: Vallejo AF,Martínez NL,González IJ,Arévalo-Herrera M,Herrera S

    更新日期:2015-01-08 00:00:00

  • The roles of stakeholder experience and organizational learning in declining mass drug administration coverage for lymphatic filariasis in Port-au-Prince, Haiti: A case study.

    abstract::The World Health Organization (WHO) defines an effective round of mass drug administration (MDA) for lymphatic filariasis (LF) as one that reaches at least 65% of the target population. In its first round of MDA in 2011-2012, the National Program to Eliminate LF in Haiti achieved a 79% epidemiological coverage in urba...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0008318

    authors: Wodnik BK,Louis DH,Joseph M,Wilkers LT,Landskroener SD,Desir L,Lemoine JF,Lavery JV

    更新日期:2020-05-29 00:00:00

  • Footprint of positive selection in Treponema pallidum subsp. pallidum genome sequences suggests adaptive microevolution of the syphilis pathogen.

    abstract::In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0001698

    authors: Giacani L,Chattopadhyay S,Centurion-Lara A,Jeffrey BM,Le HT,Molini BJ,Lukehart SA,Sokurenko EV,Rockey DD

    更新日期:2012-01-01 00:00:00

  • T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

    abstract::The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody producti...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0001938

    authors: de Melo AB,Nascimento EJ,Braga-Neto U,Dhalia R,Silva AM,Oelke M,Schneck JP,Sidney J,Sette A,Montenegro SM,Marques ET

    更新日期:2013-01-01 00:00:00

  • Targeting trachoma control through risk mapping: the example of Southern Sudan.

    abstract:BACKGROUND:Trachoma is a major cause of blindness in Southern Sudan. Its distribution has only been partially established and many communities in need of intervention have therefore not been identified or targeted. The present study aimed to develop a tool to improve targeting of survey and control activities. METHODS...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000799

    authors: Clements AC,Kur LW,Gatpan G,Ngondi JM,Emerson PM,Lado M,Sabasio A,Kolaczinski JH

    更新日期:2010-08-17 00:00:00

  • A research agenda for helminth diseases of humans: basic research and enabling technologies to support control and elimination of helminthiases.

    abstract::Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vecto...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pntd.0001445

    authors: Lustigman S,Geldhof P,Grant WN,Osei-Atweneboana MY,Sripa B,Basáñez MG

    更新日期:2012-01-01 00:00:00

  • wMel limits zika and chikungunya virus infection in a Singapore Wolbachia-introgressed Ae. aegypti strain, wMel-Sg.

    abstract:BACKGROUND:Zika (ZIKV) and Chikungunya (CHIKV) viruses are emerging Aedes-borne viruses that are spreading outside their known geographic range and causing wide-scale epidemics. It has been reported that these viruses can be transmitted efficiently by Ae. aegypti. Recent studies have shown that Ae. aegypti when transin...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005496

    authors: Tan CH,Wong PJ,Li MI,Yang H,Ng LC,O'Neill SL

    更新日期:2017-05-19 00:00:00

  • Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases.

    abstract:BACKGROUND:Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using n...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0005598

    authors: Stefani MMA,Avanzi C,Bührer-Sékula S,Benjak A,Loiseau C,Singh P,Pontes MAA,Gonçalves HS,Hungria EM,Busso P,Piton J,Silveira MIS,Cruz R,Schetinni A,Costa MB,Virmond MCL,Diorio SM,Dias-Baptista IMF,Rosa PS,Matsuoka M

    更新日期:2017-06-15 00:00:00

  • Favipiravir (T-705) inhibits Junín virus infection and reduces mortality in a guinea pig model of Argentine hemorrhagic fever.

    abstract:BACKGROUND:Junín virus (JUNV), the etiologic agent of Argentine hemorrhagic fever (AHF), is classified by the NIAID and CDC as a Category A priority pathogen. Presently, antiviral therapy for AHF is limited to immune plasma, which is readily available only in the endemic regions of Argentina. T-705 (favipiravir) is a b...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0002614

    authors: Gowen BB,Juelich TL,Sefing EJ,Brasel T,Smith JK,Zhang L,Tigabu B,Hill TE,Yun T,Pietzsch C,Furuta Y,Freiberg AN

    更新日期:2013-12-26 00:00:00

  • Dextran fractional clearance studies in acute dengue infection.

    abstract:BACKGROUND:Although increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear. Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0001282

    authors: Nguyen-Pouplin J,Pouplin T,Van TP,The TD,Thi DN,Farrar J,Tinh HT,Wills B

    更新日期:2011-08-01 00:00:00

  • Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods.

    abstract::All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0006280

    authors: Mulindwa J,Leiss K,Ibberson D,Kamanyi Marucha K,Helbig C,Melo do Nascimento L,Silvester E,Matthews K,Matovu E,Enyaru J,Clayton C

    更新日期:2018-02-23 00:00:00

  • An investig-ation into the epidemiology of chikungunya virus across neglected regions of Indonesia.

    abstract:BACKGROUND:Chikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited. METHODOLOGY/PRINCIPAL FINDINGS:Four hundred and seventy nine acutely febrile...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0008934

    authors: Stubbs SCB,Johar E,Yudhaputri FA,Yohan B,Santoso MS,Hayati RF,Denis D,Blacklaws BA,Powers AM,Sasmono RT,Myint KSA,Frost SDW

    更新日期:2020-12-21 00:00:00

  • Viral aetiology of central nervous system infections in adults admitted to a tertiary referral hospital in southern Vietnam over 12 years.

    abstract:BACKGROUND:Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0003127

    authors: Tan le V,Thai le H,Phu NH,Nghia HD,Chuong LV,Sinh DX,Phong ND,Mai NT,Man DN,Hien VM,Vinh NT,Day J,Chau NV,Hien TT,Farrar J,de Jong MD,Thwaites G,van Doorn HR,Chau TT

    更新日期:2014-08-28 00:00:00

  • Safety of azithromycin in infants under six months of age in Niger: A community randomized trial.

    abstract:BACKGROUND:Mass azithromycin distribution reduces under-5 child mortality. Trachoma control programs currently treat infants aged 6 months and older. Here, we report findings from an infant adverse event survey in 1-5 month olds who received azithromycin as part of a large community-randomized trial in Niger. METHODS ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章,随机对照试验

    doi:10.1371/journal.pntd.0006950

    authors: Oldenburg CE,Arzika AM,Maliki R,Kane MS,Lebas E,Ray KJ,Cook C,Cotter SY,Zhou Z,West SK,Bailey R,Porco TC,Keenan JD,Lietman TM,MORDOR Study Group.

    更新日期:2018-11-12 00:00:00

  • The role of imported cases and favorable meteorological conditions in the onset of dengue epidemics.

    abstract:BACKGROUND:Travelers who acquire dengue infection are often routes for virus transmission to other regions. Nevertheless, the interplay between infected travelers, climate, vectors, and indigenous dengue incidence remains unclear. The role of foreign-origin cases on local dengue epidemics thus has been largely neglecte...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000775

    authors: Shang CS,Fang CT,Liu CM,Wen TH,Tsai KH,King CC

    更新日期:2010-08-03 00:00:00

  • A schistosome cAMP-dependent protein kinase catalytic subunit is essential for parasite viability.

    abstract::Eukaryotes, protozoan, and helminth parasites make extensive use of protein kinases to control cellular functions, suggesting that protein kinases may represent novel targets for the development of anti-parasitic drugs. Because of their central role in intracellular signaling pathways, cyclic nucleotide-dependent kina...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000505

    authors: Swierczewski BE,Davies SJ

    更新日期:2009-08-25 00:00:00

  • Molecular investigations of a locally acquired case of melioidosis in Southern AZ, USA.

    abstract::Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus, primarily found in soils in Southeast Asia and northern Australia. A recent case of melioidosis in non-endemic Arizona was determined to be the result of locally acquired infection, as the patient had no travel history to endemic regions and...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0001347

    authors: Engelthaler DM,Bowers J,Schupp JA,Pearson T,Ginther J,Hornstra HM,Dale J,Stewart T,Sunenshine R,Waddell V,Levy C,Gillece J,Price LB,Contente T,Beckstrom-Sternberg SM,Blaney DD,Wagner DM,Mayo M,Currie BJ,Keim P,Tua

    更新日期:2011-10-01 00:00:00

  • Diagnosis of Persistent Fever in the Tropics: Set of Standard Operating Procedures Used in the NIDIAG Febrile Syndrome Study.

    abstract::In resource-limited settings, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers complex [1-5]. Febrile illnesses are diagnosed clinically in most rural centers, and both Rapid Diagnostic Tests (RDTs) and clinical algorithms can be valuable aids to health wo...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0004749

    authors: Alirol E,Horie NS,Barbé B,Lejon V,Verdonck K,Gillet P,Jacobs J,Büscher P,Kanal B,Bhattarai NR,El Safi S,Phe T,Lim K,Leng L,Lutumba P,Mukendi D,Bottieau E,Boelaert M,Rijal S,Chappuis F

    更新日期:2016-11-03 00:00:00

  • An Outbreak of Lymphocutaneous Sporotrichosis among Mine-Workers in South Africa.

    abstract:BACKGROUND:The largest outbreak of sporotrichosis occurred between 1938 and 1947 in the gold mines of Witwatersrand in South Africa. Here, we describe an outbreak of lymphocutaneous sporotrichosis that was investigated in a South African gold mine in 2011. METHODOLOGY:Employees working at a reopened section of the min...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0004096

    authors: Govender NP,Maphanga TG,Zulu TG,Patel J,Walaza S,Jacobs C,Ebonwu JI,Ntuli S,Naicker SD,Thomas J

    更新日期:2015-09-25 00:00:00

  • Estimated incidence and Prevalence of noma in north central Nigeria, 2010-2018: A retrospective study.

    abstract:BACKGROUND:Noma is a spreading and fulminant disease believed to be native to Sub-Saharan Africa over the last decade and associated with low socioeconomic status of citizens of the region. Within this noma belt, most epidemiological reports regarding the disease have emanated from the north western region of Nigeria. ...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0007574

    authors: Bello SA,Adeoye JA,Oketade I,Akadiri OA

    更新日期:2019-07-22 00:00:00

  • Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells.

    abstract::Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytome...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0003414

    authors: Katawa G,Layland LE,Debrah AY,von Horn C,Batsa L,Kwarteng A,Arriens S,W Taylor D,Specht S,Hoerauf A,Adjobimey T

    更新日期:2015-01-08 00:00:00

  • Allergies and diabetes as risk factors for dengue hemorrhagic fever: results of a case control study.

    abstract:BACKGROUND:The physiopathology of dengue hemorrhagic fever (DHF), a severe form of Dengue Fever, is poorly understood. We are unable to identify patients likely to progress to DHF for closer monitoring and early intervention during epidemics, so most cases are sent home. This study explored whether patients with select...

    journal_title:PLoS neglected tropical diseases

    pub_type: 杂志文章

    doi:10.1371/journal.pntd.0000699

    authors: Figueiredo MA,Rodrigues LC,Barreto ML,Lima JW,Costa MC,Morato V,Blanton R,Vasconcelos PF,Nunes MR,Teixeira MG

    更新日期:2010-06-01 00:00:00