scholarly journals Identification and Biological Characterization ofLeishmania (Viannia) guyanensisIsolated from a Patient with Tegumentary Leishmaniasis in Goiás, a Nonendemic Area for This Species in Brazil

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Alause da Silva Pires ◽  
Arissa Felipe Borges ◽  
Adriano Cappellazzo Coelho ◽  
Miriam Leandro Dorta ◽  
Ruy de Souza Lino Junior ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Murine Models ◽  
Biological Characterization ◽  
Field Isolates ◽  
Tegumentary Leishmaniasis ◽  
American Tegumentary Leishmaniasis ◽  
Growth Profiles

The aim of this study was to characterize clinical field isolates ofLeishmaniaspp. obtained from patients with American Tegumentary Leishmaniasis (ATL) who live in Goiás state, Brazil. The presumed areas of infection were in Goiás, Tocantins, and Pará states. Three isolates of parasites were identified asL. (Viannia) braziliensisand one asL. (V.) guyanensis. Thein vitrogrowth profiles were found to be similar for all parasites. Nevertheless, in C57BL/6 mice,L. (V.) guyanensisinfection was better controlled thanL. (V.) braziliensis. Yet in C57BL/6 mice deficient in interferon gamma,L. (V.) guyanensislesions developed faster than those caused byL. (V.) braziliensisisolates. In BALB/c mice, the development of lesions was similar for isolates from both species; however, on the 11th week of infection, amastigotes could not be observed in macrophages fromL. (V.) guyanensis-infected mice. Thus,L. (V.) guyanensiscan be circulating in Goiás, a state where autochthonous cases of this species had not yet been reported. Considering the difficulties to differentiateL. (V.) guyanensisfromL. (V.) braziliensisat the molecular, morphological, and clinical (human and murine models) levels, the presence ofL. (V.) guyanensisinfections is possibly underestimated in several regions of Brazil.

Morita-Baylis-Hillman adduct shows in vitro activity against Leishmania (Viannia) braziliensis associated with a reduction in IL-6 and IL-10 but independent of nitric oxide

Parasitology ◽  
2012 ◽  
Vol 140 (1) ◽  
pp. 29-38 ◽  
Author(s):  
F. M. AMORIM ◽  
Y. K. S. RODRIGUES ◽  
T. P. BARBOSA ◽  
P. L. N. NÉRIS ◽  
J. P. A. CALDAS ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cutaneous Leishmaniasis ◽  
Clinical Manifestations ◽  
Failure Rates ◽  
In Vitro Activity ◽  
Clinical Forms ◽  
Tegumentary Leishmaniasis ◽  
American Tegumentary Leishmaniasis ◽  
Human Infections

SUMMARYCurrent treatments for different clinical forms of leishmaniasis are unsatisfactory, highly toxic and associated with increasing failure rates resulting from the emergence of resistant parasites. Leishmania (Viannia) braziliensis is the main aetiological agent of different clinical forms of American tegumentary leishmaniasis, including the mucosal form for which treatment has high failure rates. The aim of this work was to investigate the activity of the Morita-Baylis-Hillman adduct, methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate in vitro against isolates of L. (V.) braziliensis obtained from patients with different clinical manifestations of tegumentary leishmaniasis: localized cutaneous leishmaniasis, mucosal leishmaniasis and disseminated cutaneous leishmaniasis. The adduct effectively inhibited the growth of promastigotes of the different isolates of L. (V.) braziliensis (IC50 ⩽ 7·77 μg/ml), as well as reduced the infection rate of macrophages infected with these parasites (EC50 ⩽ 1·37 μg/ml). It is remarkable to state that the adduct was more effective against intracellular amastigotes (P ⩽ 0·0045). The anti-amastigote activity correlated with an immunomodulatory effect, since the adduct was able to decrease the production of IL-6 and IL-10 by the infected macrophages. However, its effect was independent of nitric oxide production. This work demonstrates the anti-leishmanial activity of methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate and suggests its potential in the treatment of human infections caused by L. (V.) braziliensis.

scholarly journals APPLICABILITY OF kDNA-PCR FOR ROUTINE DIAGNOSIS OF AMERICAN TEGUMENTARY LEISHMANIASIS IN A TERTIARY REFERENCE HOSPITAL

2013 ◽  
Vol 55 (6) ◽  
pp. 393-399 ◽  
Author(s):  
Marcela M. Satow ◽  
Edite H. Yamashiro-Kanashiro ◽  
Mussya C. Rocha ◽  
Luiza K. Oyafuso ◽  
Rita C. Soler ◽  
...  
Keyword(s):  
Pcr Amplification ◽  
Molecular Method ◽  
Laboratory Methods ◽  
Tegumentary Leishmaniasis ◽  
Routine Diagnosis ◽  
Reference Hospital ◽  
American Tegumentary Leishmaniasis ◽  
Diagnosis Method ◽  
Pcr Method

SUMMARY This study evaluated the applicability of kDNA-PCR as a prospective routine diagnosis method for American tegumentary leishmaniasis (ATL) in patients from the Instituto de Infectologia Emílio Ribas (IIER), a reference center for infectious diseases in São Paulo - SP, Brazil. The kDNA-PCR method detected Leishmania DNA in 87.5% (112/128) of the clinically suspected ATL patients, while the traditional methods demonstrated the following percentages of positivity: 62.8% (49/78) for the Montenegro skin test, 61.8% (47/76) for direct investigation, and 19.3% (22/114) for in vitro culture. The molecular method was able to confirm the disease in samples considered negative or inconclusive by traditional laboratory methods, contributing to the final clinical diagnosis and therapy of ATL in this hospital. Thus, we strongly recommend the inclusion of kDNA-PCR amplification as an alternative diagnostic method for ATL, suggesting a new algorithm routine to be followed to help the diagnosis and treatment of ATL in IIER.

scholarly journals In vitro insights of Leishmania (Viannia) species related to their outcomes and virulence in American tegumentary leishmaniasis

2021 ◽  
Vol 1 (1) ◽  
pp. 1-15
Author(s):  
Daniele Stéfanie Sara Lopes Lera-Nonose ◽  
Áquila Carolina Fernandes Herculano Ramos-Milaré ◽  
Jully Oyama ◽  
Thaís Gomes Verzignassi Silveira ◽  
Izabel Galhardo Demarchi ◽  
...  
Keyword(s):  
Tegumentary Leishmaniasis ◽  
American Tegumentary Leishmaniasis

Tuberkulose - Screening

2011 ◽  
Vol 68 (7) ◽  
pp. 381-387
Author(s):  
Otto Schoch
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Interferon Gamma ◽  
Wird Eine ◽  
Interferon Gamma Release Assays

Das primäre Ziel der Aktivitäten zur bevölkerungsbezogenen Tuberkulosekontrolle ist die Identifizierung von Patienten mit sputummikroskopisch positiver Lungentuberkulose. Wenn diese Patienten umgehend therapiert werden, haben sie nicht nur eine optimale Heilungschance, sondern übertragen auch den Krankheitserreger nicht weiter auf andere Personen. Das Screening, die systematische Suche nach Tuberkulose, erfolgt in der Regel radiologisch bei der Suche nach Erkrankten, während immunologische Teste bei der Suche nach einer Infektion mit Mycobacterium tuberculosis zur Anwendung kommen. Diese Infektion, die ein erhöhtes Risiko für die Entwicklung einer Tuberkulose-Erkrankung mit sich bringt, wird im Rahmen der Umgebungsuntersuchungen oder bei Hochrisikogruppen gesucht. Neben dem traditionellen in vivo Mantoux Hauttest stehen heute die neueren in vitro Blutteste, die sogenannten Interferon Gamma Release Assays (IGRA) zur Verfügung, die unter anderem den Vorteil einer höheren Spezifität mit sich bringen, weil die verwendeten Antigene der Mykobakterien-Wand beim Impfstamm Bacille Calmitte Guerin (BCG) und bei den meisten atypischen Mykobakterien nicht vorhanden sind. Zudem kann bei Immunsupprimierten dank einer mitgeführten Positivkontrolle eine Aussage über die Wahrscheinlichkeit eines falsch negativen Testresultates gemacht werden. Bei neu diagnostizierter Infektion mit Mycobacterium tuberculosis wird eine präventive Chemotherapie mit Isoniazid während 9 Monaten durchgeführt.

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

scholarly journals Kenyan Plasmodium falciparum Field Isolates: Correlation between Pyrimethamine and Chlorcycloguanil Activity In Vitro and Point Mutations in the Dihydrofolate Reductase Domain

1998 ◽  
Vol 42 (1) ◽  
pp. 164-169 ◽  
Author(s):  
A. Nzila-Mounda ◽  
E. K. Mberu ◽  
C. H. Sibley ◽  
C. V. Plowe ◽  
P. A. Winstanley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Drug Response ◽  
Point Mutations ◽  
Distinct Group ◽  
Wild Type ◽  
Field Isolates ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT Sixty-nine Kenyan Plasmodium falciparum field isolates were tested in vitro against pyrimethamine (PM), chlorcycloguanil (CCG), sulfadoxine (SD), and dapsone (DDS), and their dihydrofolate reductase (DHFR) genotypes were determined. The in vitro data show that CCG is more potent than PM and that DDS is more potent than SD. DHFR genotype is correlated with PM and CCG drug response. Isolates can be classified into three distinct groups based on their 50% inhibitory concentrations (IC50s) for PM and CCG (P< 0.01) and their DHFR genotypes. The first group consists of wild-type isolates with mean PM and CCG IC50s of 3.71 ± 6.94 and 0.24 ± 0.21 nM, respectively. The second group includes parasites which all have mutations at codon 108 alone or also at codons 51 or 59 and represents one homogeneous group for which 25- and 6-fold increases in PM and CCG IC50s, respectively, are observed. Parasites with mutations at codons 108, 51, and 59 (triple mutants) form a third distinct group for which nine- and eightfold increases in IC50s, respectively, of PM and CCG compared to the second group are observed. Surprisingly, there is a significant decrease (P < 0.01) of SD and DDS susceptibility in these triple mutants. Our data show that more than 92% of Kenyan field isolates have undergone at least one point mutation associated with a decrease in PM activity. These findings are of great concern because they may indicate imminent PM-SD failure, and there is no affordable antimalarial drug to replace PM-SD (Fansidar).

Clinical features and therapeutic response in adult and pediatric patients with American tegumentary leishmaniasis in Rio de Janeiro

2019 ◽  
Author(s):  
Tatiana C R Senna ◽  
Maria Inês F Pimentel ◽  
Liliane F A Oliveira ◽  
Marcelo R Lyra ◽  
Mauricio N Saheki ◽  
...  
Keyword(s):  
Clinical Features ◽  
Rio De Janeiro ◽  
Pediatric Patients ◽  
Therapeutic Response ◽  
Age Groups ◽  
Healing Time ◽  
The Body ◽  
Reference Centre ◽  
Tegumentary Leishmaniasis ◽  
American Tegumentary Leishmaniasis

Abstract Background American tegumentary leishmaniasis (ATL) is a neglected disease with wide territorial distribution. Knowledge is scarce in children and adolescents. This study aims to compare the clinical features and response to antimony treatment in pediatric and adult patients with cutaneous leishmaniasis. Methods A retrospective cohort study was performed with 659 patients who attended a reference centre in Rio de Janeiro, Brazil, from 2000 to 2015. The pediatric cohort consisted of 131 (20%) patients and the adult cohort consisted of 528 (80%) patients. Results The epidemiological profile, antimony therapeutic response and incidence of adverse events (AE) were different in the pediatric cohort compared with the adult cohort. Mucosal form was less frequent in the pediatric cohort (RR:0.49, p=0.011). Lesions in the head, neck and trunk were more frequent in the pediatric cohort (RR:1.49, p=0.043). The effectiveness of antimony treatment was superior in the pediatric cohort (88.3% vs 76.6%) with a shorter healing time (RR:0.49, p=0.009). Pediatric patients had lower proportions of moderate to severe AE compared with adults (RR:0.45, p=0.027). Clinical AE predominated in the adult cohort (RR:0.40, p=0.000) and laboratory AE in the pediatric cohort (RR:1.50, p=0.023). Conclusions This study adds to the body of knowledge on differences that exist between different age groups in ATL.

scholarly journals Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.

1994 ◽  
Vol 179 (4) ◽  
pp. 1273-1283 ◽  
Author(s):  
R Manetti ◽  
F Gerosa ◽  
M G Giudizi ◽  
R Biagiotti ◽  
P Parronchi ◽  
...  
Keyword(s):  
T Cells ◽  
Interferon Gamma ◽  
Specific Antigen ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
T Helper ◽  
Ifn Gamma ◽  
Selection Of

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

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