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1.
Parasitol Int ; 87: 102528, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34942361

RESUMO

The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes eosinophilic meningitis or meningoencephalitis. Heme oxygenase 1 (HO-1) has several cytoprotective properties such as anti-oxidative, anti-inflammatory, and anti-apoptotic effects. HO-1 in brain tissues was induced in A. cantonensis-infected group and showed positive modulation in cobalt protoporphyrin (CoPP)-treated groups. Assay methods for the therapeutic effect include western blot analysis, enzyme-linked immunosorbent assay, gelatin zymography, blood-brain barrier permeability evaluation and eosinophil count in cerebrospinal fluid. The combination of albendazole (ABZ) and CoPP significantly decreased pro-inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1ß, IL-5, and IL-33 but significantly increased anti-inflammatory cytokines IL-10 and transforming growth factor-ß. In addition, worm recovery, matrix metalloproteinase-9, BBB permeability, and eosinophil counts were decreased in the ABZ and CoPP co-treated groups. Induction of HO-1 with CoPP strongly inhibited the protein levels of caspase-3 and increased the induction of annexin-V and B-cell leukemia 2. Thus, co-treatment with ABZ and CoPP prevented A. cantonensis-induced eosinophilic meningoencephalitis and its anti-apoptotic effect by promoting HO-1 signaling prior to BBB dysfunction. HO-1 induction might be a therapeutic modality for eosinophilic meningoencephalitis.


Assuntos
Angiostrongylus cantonensis/fisiologia , Heme Oxigenase-1/uso terapêutico , Infecções por Strongylida/tratamento farmacológico , Albendazol/uso terapêutico , Angiostrongylus cantonensis/patogenicidade , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Encefalite/tratamento farmacológico , Encefalite/parasitologia , Heme Oxigenase-1/análise , Heme Oxigenase-1/metabolismo , Masculino , Meningoencefalite/tratamento farmacológico , Meningoencefalite/parasitologia , Camundongos , Camundongos Endogâmicos BALB C
2.
Hawaii J Health Soc Welf ; 79(8): 246-248, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32789295

RESUMO

Human infection with Angiostrongyloides cantonensis, or rat lungworm disease, manifests most commonly with neurologic symptoms that often include severe diffuse pain. While pain is reported by the majority of patients with rat lungworm disease, there are presently no published guidelines on the approach to pain management for these patients. Here we report a case of rat lungworm disease where severe refractory pain was the most prominent symptom and an intravenous lidocaine infusion was used as a successful treatment modality. Intravenous lidocaine has been shown to be safe and effective in neuropathic pain, refractory cancer pain, and peri-operative pain management. To our knowledge, this is the first case report on the use of lidocaine infusion for the management of refractory pain from rat lungworm disease, and among the first reports of any approach, to pain management for rat lungworm disease. We suggest that a lidocaine infusion protocol be considered when pain from rat lungworm disease fails to respond to first-line analgesics.


Assuntos
Infusões Intravenosas/normas , Lidocaína/administração & dosagem , Dor Intratável/tratamento farmacológico , Infecções por Strongylida/complicações , Adulto , Analgesia/métodos , Analgesia/normas , Analgesia/estatística & dados numéricos , Angiostrongylus cantonensis/efeitos dos fármacos , Angiostrongylus cantonensis/patogenicidade , Animais , Havaí , Humanos , Infusões Intravenosas/métodos , Infusões Intravenosas/estatística & dados numéricos , Masculino , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Infecções por Strongylida/tratamento farmacológico
3.
Rheumatol Int ; 40(7): 1171-1176, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32424614

RESUMO

Pulmonary angiitis is a small vessel vasculitis commonly reported in granulomatosis with polyangiitis (GPA) but is rarely attributed to angiostrongyliasis. We report a case of a patient with well-controlled rheumatoid arthritis, who was treated for GPA based on lung biopsy results with glucocorticoids (GC). Upon re-review of the initial pathology, along with peripheral eosinophilia and history of recent travel, the patient was eventually diagnosed with angiostrongylus-like nematode infection. GCs were subsequently discontinued and instead, the patient was treated with anthelmintics with complete resolution of symptoms. Commonly associated with eosinophilic meningitis or abdominal angiostrongyliasis in humans, clinical pulmonary manifestations of this parasite species are rare. With parasitic infiltration of the pulmonary vessels mimicking clinical GPA, diagnosis and treatment can be difficult in these patients. We discuss the third-reported case and first-reported survivor of Angiostrongylus-induced pulmonary angiitis followed by a focused review of the literature.


Assuntos
Erros de Diagnóstico , Granulomatose com Poliangiite/diagnóstico , Pulmão/patologia , Artéria Pulmonar/patologia , Infecções por Strongylida/diagnóstico , Vasculite/diagnóstico , Anti-Helmínticos/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Artrite Reumatoide , Biópsia , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Infecções por Strongylida/complicações , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/patologia , Tomografia Computadorizada por Raios X , Vasculite/etiologia , Vasculite/patologia
4.
Int J Biol Sci ; 15(10): 2211-2223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592236

RESUMO

BACKGROUND: Angiostrongylus cantonensis infection can cause demyelination in the central nervous system, and there is no effective treatment. METHODS: We used dexamethasone, Tanshinone IIA (TSIIA) and Cryptotanshinone(Two traditional Chinese medicine monomers) in combination with albendazole (AB, a standard anti-helminthic compound) to observe their therapeutic effect on demyelination in A. cantonensis-infected mice. Luxol fast blue staining and electron microscope of myelin sheath, Oligodendrocyte (OL) number and myelin basic protein (MBP) expression in brain was detected in above groups. RESULTS: TSIIA+AB facilitated OL proliferation and significantly increased both myelin sheath thickness and the population of small-diameter axons. In addition, TSIIA treatment inhibited the expression of inflammation-related factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, inducible nitric oxide synthase [iNOS]) rather than inhibiting eosinophil infiltration in brain. TSIIA also decreased microglial activation and shifted their phenotype from M1 to M2. CONCLUSIONS: Taken together, these results provide evidence that TSIIA combined with AB may be an effective treatment for demyelination caused by A. cantonensis infection and other demyelinating diseases.


Assuntos
Abietanos/uso terapêutico , Angiostrongylus cantonensis/efeitos dos fármacos , Angiostrongylus cantonensis/patogenicidade , Infecções por Strongylida/tratamento farmacológico , Albendazol/farmacologia , Animais , Western Blotting , Doenças Desmielinizantes/tratamento farmacológico , Imunofluorescência , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Bainha de Mielina/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Remielinização/efeitos dos fármacos , Infecções por Strongylida/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Parasit Vectors ; 12(1): 97, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30867041

RESUMO

BACKGROUND: Troglostrongylus brevior, a lungworm usually affecting wild felids, has been recently recorded in a number of cases in domestic cats, mainly in Mediterranean areas. Although feline troglostrongylosis is a severe and life-threatening disease, especially in young cats, treatment options are very limited. The present study evaluated the efficacy and safety of a spot-on formulation containing emodepside 2.1% and praziquantel 8.6% (Profender®, Bayer), which is licensed for treatment of the more common cat lungworm Aelurostrongylus abstrusus, for the treatment of natural troglostrongylosis. METHODS: Sixteen cats enrolled in the study were 1:1 allocated to two groups, i.e. Group T, treated with Profender® spot-on on days 0 and 14 (± 2) at the recommended clinical dose, and Group C which remained untreated. After study completion, the control cats received two rescue treatments with Profender® on days 28 (± 2) and 42 (± 2). The primary efficacy criterion was the absence of T. brevior L1 following treatment. Other efficacy parameters were the quantitative comparison of L1 presence before (baseline) and after treatment in both groups, and the comparison of clinical signs pre- and post-treatment. RESULTS: In terms of stopping larval shedding, Profender® showed an efficacy of 97% and 97.5% (arithmetic and geometric means, respectively) for group T, 97.1% and 98.5% for group C after one administration, and 100% for both groups after two doses. Overall, 12 cats showed clinical signs related to T. brevior. Specifically, 9 were clinically affected before treatment while clinical signs appeared after the first treatment in 3 cats. At the end of the study, all symptomatic cats fully recovered with the exception of 3 cats that showed clinical signs similar to those observed at the pre-treatment examination at the end of the study. CONCLUSIONS: This study shows that Profender® is effective against T. brevior.


Assuntos
Antiparasitários/farmacologia , Doenças do Gato/tratamento farmacológico , Depsipeptídeos/farmacologia , Praziquantel/farmacologia , Infecções por Strongylida/tratamento farmacológico , Estrongilídios/efeitos dos fármacos , Animais , Doenças do Gato/parasitologia , Gatos , Felidae , Feminino , Larva , Projetos Piloto , Infecções por Strongylida/parasitologia
6.
Vet Immunol Immunopathol ; 199: 1-7, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29678224

RESUMO

Members of Cyathostominae are pervasive parasites of equids that can cause larval cyathostominosis, a potentially life-threatening disease that occurs when a multitude of encysted larvae synchronously excyst from the wall of the large intestine. Moxidectin and fenbendazole are the two current labeled drugs that target the encysted larval stages; however, there is limited knowledge of the local inflammatory response to the larvae and to the two treatments in clinically healthy horses. This study is the first to evaluate the local inflammatory response to cyathostomin larvae and to larvicidal treatment at 2 and 5 weeks post treatment. Thirty-six ponies with naturally acquired cyathostomin infections were randomly allocated into 3 groups: Group 1, fenbendazole at 10 mg/kg for 5 days, Group 2, a single dose of moxidectin at 0.4 mg/kg, and Group 3, untreated controls. Tissue samples from the cecum and dorsal and ventral colons were used for histopathological and immunohistochemical evaluation. Tissues were stained with routine hematoxylin and eosin (H&E) for light microscopy and immunohistochemically for MAC387, CD20, and CD3 for differentiation of activated macrophages, B cells, and T cells, respectively. Semiquantitative scores were assigned for all inflammatory cell types and fibrous connective tissue. Larvae observed by light microscopy were enumerated and classified by stage. Mucosal ulcerations and submucosal granulomas were also enumerated. Mean macrophage scores were higher in the moxidectin group than the fenbendazole group (p = 0.0185) and the control group had a higher activated macrophage score than both treatment groups (p = 0.0104, p = 0.0004). T lymphocyte scores were higher in the moxidectin group when compared to the control group (p = 0.0069). Goblet cell hyperplasia scores were elevated at 5 weeks post treatment compared to 2 weeks post treatment (p = 0.0047) and were elevated in the ventral colon compared to the dorsal colon (p = 0.0301). Eosinophil scores were elevated surrounding degenerative larvae when compared to intact larvae (p = 0.0001). Mucosal ulcerations were found only in the control group at 2 weeks post treatment. This study found subtle inflammatory differences between treatment groups but provided new information about goblet cells and eosinophils in relation to encysted cyathostomin larvae.


Assuntos
Anti-Helmínticos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Inflamação/veterinária , Mucosa Intestinal/efeitos dos fármacos , Infecções por Strongylida/veterinária , Strongyloidea , Animais , Eosinófilos/fisiologia , Fenbendazol/uso terapêutico , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/parasitologia , Doenças dos Cavalos/parasitologia , Cavalos , Inflamação/parasitologia , Inflamação/fisiopatologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/fisiopatologia , Larva/efeitos dos fármacos , Macrolídeos/uso terapêutico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/fisiopatologia , Strongyloidea/efeitos dos fármacos , Linfócitos T/fisiologia
7.
Acta Trop ; 173: 76-84, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28545897

RESUMO

Resveratrol, a natural herbal compound found in high levels in grapes and red wine, is frequently used as activator of sirtuin-1. This study investigated the potential function of sirtuin-1 in regulating angiostrongyliasis meningoencephalitis in resveratrol-treated mice. Mice were subjected to meningoencephalitis to study the protective effect of resveratrol against meningoencephalitis and investigate the effects of sirtuin-1 activation on brain. Results demonstrated that sirtuin-1 level decreased in mice with meningoencephalitis and significantly increased in resveratrol-treated mice. Moreover, resveratrol treatment significantly reduced eosinophil counts, p65, Interferon-γ, interleukin (IL)-5, IL-33, and tumor necrosis factor-α levels, matrix metalloproteinase-9 activity, claudin-5 degradation, and blood-brain barrier permeability. By contrast, the anti-inflammatory factor IL-10 was significantly increased in resveratrol-treated mice. Resveratrol treatment was partially beneficial in controlling the pathological processes of angiostrongyliasis meningoencephalitis. The results demonstrate the neuroprotective and anti-inflammatory effects of resveratrol against Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis in mice. Treatment with sirtuin-1 agonist was given within a therapeutic window after A. cantonensis infection.


Assuntos
Angiostrongylus cantonensis , Regulação da Expressão Gênica/efeitos dos fármacos , Meningoencefalite/parasitologia , Sirtuína 1/metabolismo , Estilbenos/farmacologia , Infecções por Strongylida/tratamento farmacológico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Masculino , Meningoencefalite/tratamento farmacológico , Camundongos , Resveratrol
8.
Mucosal Immunol ; 10(1): 205-214, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27049059

RESUMO

Infections with helminth parasites are endemic in the developing world and are a target for intervention with new therapies. Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic effects in inflammation and immune responses. We investigated the role of MIF in a naturally cleared model of helminth infection in rodents, Nippostrongylus brasiliensis. At day 7 postinfection, MIF-deficient (MIF-/-) mice had reduced parasite burden and mounted an enhanced type 2 immune response (Th2), including increased Gata3 expression and interleukin-13 (IL-13) production in the mesenteric lymph nodes (MLNs). Bone marrow reconstitution demonstrated that MIF produced from hematopoietic cells was crucial and Rag1-/- reconstitution provided direct evidence that MIF-/- CD4+ T cells were responsible for the augmented parasite clearance. MIF-/- CD4+ T cells produced less IL-6 postinfection, which correlated with enhanced Th2 responses. MIF-/- CD4+ T cells exhibited lower nuclear factor-κB activation, potentially explaining the reduction in IL-6. Finally, we demonstrated enhanced clearance of the parasite and Th2 response in wild-type mice treated with the MIF tautomerase inhibitor, sulforaphane, a compound found naturally found in cruciferous vegetables. These results are the first to describe the importance of the tautomerase enzyme activity in MIF function in N. brasiliensis infection.


Assuntos
Fator de Transcrição GATA3/metabolismo , Interleucina-13/metabolismo , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Macrófagos/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Células Th2/imunologia , Animais , Antígenos de Helmintos/imunologia , Células Cultivadas , Feminino , Fator de Transcrição GATA3/genética , Imunidade , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/genética , Isotiocianatos/uso terapêutico , Fatores Inibidores da Migração de Macrófagos/genética , Macrófagos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Carga Parasitária , Infecções por Strongylida/tratamento farmacológico , Sulfóxidos , Células Th2/efeitos dos fármacos , Células Th2/parasitologia
9.
J Feline Med Surg ; 19(10): 1017-1029, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27694367

RESUMO

Objectives The aim of this study was to retrospectively describe clinical, radiographic and therapeutic features of feline lungworm infection. Methods Medical records of cats with lungworm diagnosis, thoracic radiography and without concurrent diseases between 2013 and 2015 were reviewed. Collection of data included physical examination, haematology, serum biochemistry, therapy with a variety of anthelmintics and outcomes. Results Thirty-seven records were recovered and 26 were included in the study. Single infections by Aelurostrongylus abstrusus (n = 15), Troglostrongylus brevior (n = 3) and Capillaria aerophila (n = 1) and coinfections by T brevior/ A abstrusus (n = 6) and T brevior/ C aerophila (n = 1) were diagnosed. The most common respiratory signs were coughing (n = 12), increased vesicular sounds (n = 10), dyspnoea (n = 9), such as laboured breathing, orthopnoea or open-mouth breathing, and tachypnoea (n = 6). Two cats were subclinically infected. The most common laboratory abnormality was anaemia (n = 7). Radiographic patterns recorded were interstitial (n = 24), bronchial (n = 21), alveolar (n = 10) and vascular (n = 2). Twenty-five cats had a complete recovery within 2-6 weeks of therapy. One kitten died 7 days after the diagnosis. Conclusions and relevance Lungworms should always be included in the differential diagnosis in cats living in endemic areas and presenting with respiratory signs and radiographic abnormalities. A copromicroscopic examination should be considered as the first diagnostic step for all cats at risk of lungworm infections. In most cases, timely therapy with a variety of anthelmintics guarantees recovery.


Assuntos
Doenças do Gato/parasitologia , Pneumopatias Parasitárias/veterinária , Infecções por Strongylida/veterinária , Animais , Anti-Helmínticos/uso terapêutico , Doenças do Gato/diagnóstico , Doenças do Gato/tratamento farmacológico , Gatos , Coinfecção/veterinária , Pneumopatias Parasitárias/diagnóstico , Pneumopatias Parasitárias/tratamento farmacológico , Pneumopatias Parasitárias/parasitologia , Metastrongyloidea/isolamento & purificação , Estudos Retrospectivos , Infecções por Strongylida/diagnóstico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia
10.
Vet Parasitol ; 228: 23-29, 2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-27692327

RESUMO

The control of equid gastrointestinal nematodes in developed countries, in particular the cyathostomins, is threatened by high levels of anthelmintic resistance. In recent years, there has been increasing interest in the evaluation of traditional 'ethnoveterinary' medicines as alternatives to chemical anthelmintics. The cysteine proteinases (CPs), a group of enzymes derived from fruits such as papaya (Carica papaya), pineapple (Ananas comosus) and figs (Ficus spp.), have shown good efficacy against adult stages of a range of parasitic nematodes, in vitro and in vivo. The efficacy of CPs against cyathostomins remains to be explored. In this study, the efficacy of a crude preparation of CPs, papaya latex supernatant (PLS), against the free-living stages of cyathostomins was evaluated using two in vitro tests, the egg hatch test (EHT) and the larval migration inhibition test (LMIT). It was demonstrated that PLS had a potent effect in the EHT, with EC-50 values in the range of 0.12-0.22µM. At concentrations above 6.25µM the eggs did not develop, below this concentration the L1 developed but they lost integrity of the cuticle upon hatching. These effects were inhibited by pre-incubation of PLS with the CP inhibitor L-trans-epoxysuccinyl-l-leucylamido-(4-guanidino butane) (E64), indicating that CPs were responsible for the anti-parasitic activity. A dose-dependent inhibition of migration of third stage larvae (L3) in the LMIT was demonstrated at higher concentrations of PLS, with EC-50 values in the range of 67.35-106.31µM. Incubation of PLS with E64 prior to use in the LMIT did not reverse the anti-migratory effect, suggesting that CPs were not responsible for the reduced migration of cyathostomin L3 and that PLS also contains an additional active compound. This is the first report of PLS and/or CPs showing activity against the free-living stages of a parasitic helminth. In addition, it suggests that cyathostomins are highly sensitive to the effects of CPs and further evaluation of their efficacy against parasitic stages and in vivo are strongly indicated.


Assuntos
Anti-Helmínticos/farmacologia , Carica/química , Inibidores de Cisteína Proteinase/farmacologia , Látex/farmacologia , Extratos Vegetais/farmacologia , Estrongilídios/efeitos dos fármacos , Animais , Cisteína Proteases/metabolismo , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Estrongilídios/crescimento & desenvolvimento , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia , Infecções por Strongylida/veterinária
11.
Mucosal Immunol ; 9(2): 428-43, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26286232

RESUMO

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.


Assuntos
Imunidade nas Mucosas/efeitos dos fármacos , Macrófagos/imunologia , Nematospiroides dubius/imunologia , Infecções por Strongylida/imunologia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Neutralizantes/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Granulócitos/parasitologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-2/farmacologia , Subunidade alfa de Receptor de Interleucina-2/antagonistas & inibidores , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Nematospiroides dubius/efeitos dos fármacos , Carga Parasitária , Transdução de Sinais , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/parasitologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/parasitologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/parasitologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia
12.
J Biol Chem ; 291(6): 2787-98, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26644468

RESUMO

The plasticity of macrophages is evident in helminthic parasite infections, providing protection from inflammation. Previously we demonstrated that the micronutrient selenium induces a phenotypic switch in macrophage activation from a classically activated (pro-inflammatory; M1/CAM) toward an alternatively activated (anti-inflammatory; M2/AAM) phenotype, where cyclooxygenase (COX)-dependent cyclopentenone prostaglandin J2 (15d-PGJ2) plays a key role. Here, we hypothesize that dietary selenium modulates macrophage polarization toward an AAM phenotype to assist in the increasing clearance of adult Nippostrongylus brasiliensis, a gastrointestinal nematode parasite. Mice on a selenium-adequate (0.08 ppm) diet significantly augmented intestinal AAM presence while decreasing adult worms and fecal egg production when compared with infection of mice on selenium-deficient (<0.01 ppm) diet. Further increase in dietary selenium to supraphysiological levels (0.4 ppm) had very little or no impact on worm expulsion. Normal adult worm clearance and enhanced AAM marker expression were observed in the selenium-supplemented Trsp(fl/fl)Cre(WT) mice that express selenoproteins driven by tRNA(Sec) (Trsp), whereas N. brasiliensis-infected Trsp(fl/fl)Cre(LysM) selenium-supplemented mice showed a decreased clearance, with lowered intestinal expression of several AAM markers. Inhibition of the COX pathway with indomethacin resulted in delayed worm expulsion in selenium-adequate mice. This was rescued with 15d-PGJ2, which partially recapitulated the effect of selenium supplementation on fecal egg output in addition to increasing markers of AAMs in the small intestine. Antagonism of PPARγ blocked the effect of selenium. These results suggest that optimal expression of selenoproteins and selenium-dependent production of COX-derived endogenous prostanoids, such as Δ(12)-PGJ2 and 15d-PGJ2, may regulate AAM activation to enhance anti-helminthic parasite responses.


Assuntos
Regulação da Expressão Gênica/imunologia , Ativação de Macrófagos , Macrófagos/imunologia , Nippostrongylus/imunologia , Selenoproteínas/imunologia , Infecções por Strongylida/imunologia , Animais , Suplementos Nutricionais , Macrófagos/parasitologia , Macrófagos/patologia , Masculino , Camundongos , Prostaglandina D2/análogos & derivados , Prostaglandina D2/imunologia , Selênio/farmacologia , Infecções por Strongylida/tratamento farmacológico
13.
Vet Dermatol ; 26(4): 293-e65, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25963239

RESUMO

BACKGROUND: Angiostrongylus vasorum is a nematode that primarily infects Canidae. The adult parasites are found in the pulmonary arterial circulation and the right side of the heart. The most common clinical sign is respiratory dysfunction. Bleeding, neurological, ocular, cardiovascular and gastrointestinal disorders are also reported. Skin lesions are very unusual. HYPOTHESIS/OBJECTIVES: This report describes a nematode dermatitis due to A. vasorum infection. To the best of the authors' knowledge, this is the first case of a dog infected with this parasite that initially presented with skin lesions only. ANIMAL: A 3-year-old female Weimaraner dog presented with a crusted papular dermatitis on the bridge of the nose and on the pinnae, and an erythematous pododermatitis with erosions and perionyxis of one digit of 1 week's duration. Two weeks later the dog developed respiratory distress. METHODS AND RESULTS: Skin scrapings and fungal culture were negative for parasites and dermatophytes. Histopathological examination showed dermal granulomas and pyogranulomas with eosinophils centred around parasitic elements compatible with nematode larvae. Angiostrongylus vasorum DNA was demonstrated in skin biopsies. Chest radiographs were compatible with verminous pneumonia and a Baermann test revealed A. vasorum larvae. The dog was treated orally with fenbendazole, with rapid improvement and complete cure after 3 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Angiostrongylus vasorum should be considered in dogs presented with skin lesions and respiratory signs. Skin biopsy, chest radiographs and Baermann test should be included in the diagnostic investigation.


Assuntos
Angiostrongylus , Doenças do Cão/parasitologia , Infecções por Strongylida/veterinária , Animais , Antinematódeos/uso terapêutico , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Feminino , Fenbendazol/uso terapêutico , Pele/patologia , Infecções por Strongylida/diagnóstico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/patologia
14.
Parasitol Res ; 114(7): 2535-41, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25855350

RESUMO

The development of plant-derived cysteine proteinases, such as those in papaya latex, as novel anthelmintics requires that the variables affecting efficacy be fully evaluated. Here, we conducted two experiments, the first to test for any effect of host sex and the second to determine whether the intensity of the worm burden carried by mice would influence efficacy. In both experiments, we used the standard C3H mouse reference strain in which papaya latex supernatant (PLS) consistently shows >80 % reduction in Heligmosomoides bakeri worm burdens, but to broaden the perspective, we also included for comparison mice of other strains that are known to respond more poorly to treatment with papaya latex. Our results confirmed that there is a strong genetic influence affecting efficacy of PLS in removing adult worm burdens. However, there was no effect of host sex on efficacy (C3H and NIH) and no effect of infection intensity (C3H and BALB/c). These results offer optimism that plant-derived cysteine proteinases (CPs), such as these from papaya latex, can function as effective anthelmintics, with neither host sex nor infection intensity presenting further hurdles to impede their development for future medicinal and veterinary usage.


Assuntos
Anti-Helmínticos/administração & dosagem , Carica/química , Cisteína Proteases/administração & dosagem , Látex/administração & dosagem , Nematospiroides/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Proteínas de Plantas/administração & dosagem , Infecções por Strongylida/tratamento farmacológico , Animais , Anti-Helmínticos/química , Cisteína Proteases/química , Feminino , Látex/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Nematospiroides/fisiologia , Extratos Vegetais/química , Proteínas de Plantas/química , Infecções por Strongylida/parasitologia , Resultado do Tratamento
15.
Vet Parasitol ; 209(3-4): 273-7, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25819917

RESUMO

The increasing reports of Aelurostrongylus abstrusus infection and the new information on Troglostrongylus brevior have spurred the interest of the scientific community towards the research of pharmaceutical compounds effective against both pathogens. A novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel (Broadline®, Merial) has been released for the treatment of a variety of feline parasitic infections. The present study reports the efficacy of this spot-on in treating cats naturally infected by feline lungworms. Client owned cats (n=191) were enrolled from three geographical areas of Italy and faecal samples were examined by floatation and Baermann techniques. Twenty-three individuals were positive for L1 of A. abstrusus (n=18) or T. brevior (n=3) or for both species (n=2) and they were topically treated with Broadline®. Seventeen of them were also concomitantly infected by other parasites. Four weeks after treatment, faecal samples were collected and examined to assess the efficacy of a single administration of the product. Based on lungworm larvae counts, the efficacy of the treatment was 90.5% or 100% for A. abstrusus or T. brevior, respectively. Cats released significantly lower amounts of lungworm larvae after treatment compared to pre-treatment (p<0.0001). All but three cats were negative for other nematodes after treatment and all cats recovered from respiratory signs. Results of this study indicate that a single administration of the topical combination fipronil, (S)-methoprene, eprinomectin and praziquantel is effective and safe for the treatment of A. abstrusus and/or T. brevior infections in cats living under field conditions.


Assuntos
Doenças do Gato/parasitologia , Ivermectina/análogos & derivados , Metoprene/uso terapêutico , Praziquantel/uso terapêutico , Pirazóis/uso terapêutico , Infecções por Strongylida/veterinária , Administração Tópica , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/farmacologia , Antiparasitários/administração & dosagem , Antiparasitários/farmacologia , Doenças do Gato/tratamento farmacológico , Doenças do Gato/epidemiologia , Gatos , Combinação de Medicamentos , Feminino , Itália/epidemiologia , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Masculino , Metastrongyloidea , Metoprene/administração & dosagem , Praziquantel/administração & dosagem , Pirazóis/administração & dosagem , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/epidemiologia , Resultado do Tratamento
16.
Parasitology ; 142(7): 989-98, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25736575

RESUMO

Eight strains of mice, of contrasting genotypes, infected with Heligmosomoides bakeri were studied to determine whether the anthelmintic efficacy of papaya latex varied between inbred mouse strains and therefore whether there is an underlying genetic influence on the effectiveness of removing the intestinal nematode. Infected mice were treated with 330 nmol of crude papaya latex or with 240 nmol of papaya latex supernatant (PLS). Wide variation of response between different mouse strains was detected. Treatment was most effective in C3H (90·5-99·3% reduction in worm counts) and least effective in CD1 and BALB/c strains (36·0 and 40·5%, respectively). Cimetidine treatment did not improve anthelmintic efficacy of PLS in a poor drug responder mouse strain. Trypsin activity, pH and PLS activity did not differ significantly along the length of the gastro-intestinal (GI) tract between poor (BALB/c) and high (C3H) drug responder mouse strains. Our data indicate that there is a genetic component explaining between-mouse variation in the efficacy of a standard dose of PLS in removing worms, and therefore warrant some caution in developing this therapy for wider scale use in the livestock industry, and even in human medicine.


Assuntos
Anti-Helmínticos/farmacologia , Carica/química , Cisteína Proteases/farmacologia , Látex/farmacologia , Proteínas de Plantas/farmacologia , Doenças dos Roedores/genética , Infecções por Strongylida/genética , Animais , Anti-Helmínticos/metabolismo , Carica/enzimologia , Cimetidina/farmacologia , Cisteína Proteases/metabolismo , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/parasitologia , Genótipo , Especificidade de Hospedeiro , Concentração de Íons de Hidrogênio , Látex/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Nematospiroides/efeitos dos fármacos , Nematospiroides/fisiologia , Proteínas de Plantas/metabolismo , Doenças dos Roedores/tratamento farmacológico , Doenças dos Roedores/parasitologia , Especificidade da Espécie , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia
17.
BMC Vet Res ; 10: 236, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25262002

RESUMO

BACKGROUND: Canine angiostrongylosis is a nematode infection in domestic dogs and wild carnivores. The present report focuses on epidemiological, clinical and histopathological findings in a case of fatal disseminated angiostrongylosis in a dog living in southern Italy and provides data on the extent of the spread of Angiostrongylus vasorum in the same area. CASE PRESENTATION: A 4-year-old female English Setter from the Campania region of southern Italy was referred with a 2-week history of cough and severe respiratory distress that did not respond to antimicrobial therapy. Based on clinical, radiological, echographical and cytological findings (including the presence of larvae), a suspect diagnosis of lungworm infection was performed. After few days the dog died due to progressive clinical aggravation. Complete postmortem examination was conducted within 24 hours from death and samples from lungs, heart, liver, kidney, spleen, stomach and small intestine were fixed in 10% buffered formalin. Grossly, several hemorrhagic foci were observed mostly in the lungs, liver, kidney. Microscopically, the lungs contained numerous, multifocal to coalescing granulomas composed of epitheliod macrophages, multinucleated giant cells and some neutrophils, frequently associated with parasite eggs and larvae. The lungs contained many firm nodules, many adult nematodes approximately 1.5 to 2 cm in length were observed in cut sections and identified as A. vasorum. A subsequent parasitological survey performed with FLOTAC on stray dogs living in the same area showed the presence of A. vasorum larvae in 17 of 1639 stray dogs examined (1.04%). CONCLUSION: This survey provides new data on distribution of A. vasorum and underlines that canine angiostrongylosis should be considered as differential diagnosis in dogs.


Assuntos
Angiostrongylus/classificação , Doenças do Cão/parasitologia , Infecções por Strongylida/veterinária , Animais , Anti-Helmínticos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Evolução Fatal , Feminino , Macrolídeos/uso terapêutico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia , Infecções por Strongylida/patologia
18.
Mem. Inst. Oswaldo Cruz ; 109(4): 399-407, 03/07/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-716315

RESUMO

Eosinophilic meningitis (EoM) is an acute disease that affects the central nervous system. It is primarily caused by infection with the nematode Angiostrongylus cantonensis. This infection was previously restricted to certain Asian countries and the Pacific Islands, but it was first reported in Brazil in 2007. Since then, intermediate and definitive hosts infected with A. cantonensis have been identified within the urban areas of many states in Brazil, including those in the northern, northeastern, southeastern and southern regions. The goals of this review are to draw the attention of the medical community and health centres to the emergence of EoM in Brazil, to compile information about several aspects of the human infection and mode of transmission and to provide a short protocol of procedures for the diagnosis of this disease.


Assuntos
Animais , Humanos , Infecções Parasitárias do Sistema Nervoso Central , Eosinofilia , Meningite , Infecções por Strongylida , Angiostrongylus cantonensis , Brasil/epidemiologia , Doenças Transmissíveis Emergentes , Infecções Parasitárias do Sistema Nervoso Central/diagnóstico , Infecções Parasitárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Parasitárias do Sistema Nervoso Central/epidemiologia , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Eosinofilia/epidemiologia , Eosinofilia/parasitologia , Meningite/diagnóstico , Meningite/tratamento farmacológico , Meningite/epidemiologia , Meningite/parasitologia , Caramujos/parasitologia , Infecções por Strongylida/diagnóstico , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/epidemiologia
19.
J Feline Med Surg ; 16(10): 864-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24710593

RESUMO

A 7-month-old, female, domestic shorthair, indoor/outdoor cat on the island of St Kitts was presented to the Veterinary Teaching Hospital at Ross University School of Veterinary Medicine as part of a student training spay-neuter program. Observation of diarrhea prompted a double centrifugation fecal analysis. Ova of Mammomonogamus species, in addition to Ancylostoma species, Trichuris species and Platynosomum species, were found. Mammomonogamus ierei is a parasitic nematode found on many Caribbean islands for which treatment is not well documented. Five days of fenbendazole (50 mg/kg bodyweight) was administered, and fecal analyses gave negative results for Mammomonogamus species eggs 1 week after the last fenbendazole treatment.


Assuntos
Antinematódeos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Fenbendazol/uso terapêutico , Infecções por Strongylida/veterinária , Animais , Doenças do Gato/parasitologia , Gatos , Fezes/parasitologia , Feminino , Hospitais Veterinários , Estrongilídios/isolamento & purificação , Infecções por Strongylida/tratamento farmacológico , Infecções por Strongylida/parasitologia , Índias Ocidentais
20.
Vet Parasitol ; 202(1-2): 64-8, 2014 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-24703080

RESUMO

The efficacy of a novel topical combination of fipronil 8.3% w/v, (S)-methoprene 10% w/v, eprinomectin 0.4% w/v, and praziquantel 8.3% w/v (BROADLINE(®),(1) Merial) against larval and adult Aelurostrongylus abstrusus lungworms in cats was assessed in a controlled laboratory study. The study included 48 purpose-bred, short-haired cats which were each inoculated with 225 infective A. abstrusus larvae. The cats were formed into eight blocks based on pre-treatment bodyweight and were then, within each block, randomly allocated to one of six treatment groups: untreated control; treated once when A. abstrusus were expected to be third-stage larvae (4 days post inoculation [dpi]), fourth-stage larvae (7 dpi), immature adults (14 dpi) or adult nematodes (32 dpi), or treated twice, once when A. abstrusus were expected to be third-stage larval and once again when A. abstrusus were expected to be adult nematodes (4 dpi+32 dpi). Cats weighing ≥ 0.8-2.5 kg received one 0.3 mL applicator and cats weighing >2.5-7.5 kg received one 0.9 mL applicator. For determination of the efficacy of treatments, lungworm larval counts were established on faecal samples collected from all cats 32, 39, 46, 53 and 60 dpi. At each occasion from 46 dpi on, cats treated with fipronil, (S)-methoprene, eprinomectin and praziquantel had significantly lower A. abstrusus larval counts than the untreated controls with percentage reductions of 91.6% (cats treated 14dpi; P=0.012), ≥ 98.9% (cats treated either 4 dpi, 7 dpi or 32 dpi; P<0.001) or >99.9% (cats treated 4 dpi+32 dpi; P<0.001) at 60 dpi. Thus, the novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel was highly effective in the prevention and treatment of A. abstrusus lungworm infection in cats.


Assuntos
Antiparasitários/administração & dosagem , Doenças do Gato/tratamento farmacológico , Infecções por Strongylida/veterinária , Animais , Antiparasitários/farmacologia , Gatos , Combinação de Medicamentos , Feminino , Ivermectina/administração & dosagem , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Metastrongyloidea/efeitos dos fármacos , Metoprene/administração & dosagem , Metoprene/farmacologia , Praziquantel/administração & dosagem , Praziquantel/farmacologia , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Distribuição Aleatória , Infecções por Strongylida/tratamento farmacológico , Resultado do Tratamento
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