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1.
Rev Bras Parasitol Vet ; 26(1): 54-59, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28327881

RESUMEN

Platynosomiasis is a common feline hepatic disease caused by Platynosomum fastosum (Trematoda - Dicrocoelidae), which is also known as 'lizard poisoning'. Most reports of feline platynosomiasis show that this disease is sporadic and manifests with uncommon lesions; its pathogenicity is still not well understood. This study aimed to describe liver injuries and enzymatic changes associated with natural P. fastosum infection in 47 stray cats in an endemic area. Overall, 38.3% (18/47) of cats were parasitized, and 2,358 flukes (P. fastosum) were collected (131 - mean intensity of parasitism; 50.2 - mean abundance). The alanine transaminase (ALT) measure was significantly higher in parasitized animals, while alkaline phosphatase (ALP) showed no statistical difference between parasitized and non-parasitized animals. In infected animals, gross pathological lesions and microscopic liver injuries ranged from mild to severe, and were similar to those in previous descriptions of feline platynosomiasis. Nonetheless, the intensity of parasitism was not related to the severity of macroscopic or microscopic hepatic injuries. However, feline platynosomiasis should be considered in the differential diagnosis of feline liver disorders, as well as, in any program of helminth control, even if no clinical abnormalities are present.


Asunto(s)
Enfermedades de los Gatos/patología , Enfermedades de los Gatos/parasitología , Dicrocoeliidae/aislamiento & purificación , Parasitosis Hepáticas/veterinaria , Infecciones por Trematodos/veterinaria , Alanina Transaminasa , Animales , Enfermedades de los Gatos/enzimología , Gatos , Parasitosis Hepáticas/enzimología , Parasitosis Hepáticas/parasitología , Parasitosis Hepáticas/patología , Trematodos , Infecciones por Trematodos/enzimología , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/patología
2.
Rev. bras. parasitol. vet ; 26(1): 54-59, Jan.-Mar. 2017. tab, graf
Artículo en Inglés | LILACS | ID: biblio-844128

RESUMEN

Abstract Platynosomiasis is a common feline hepatic disease caused by Platynosomum fastosum (Trematoda - Dicrocoelidae), which is also known as ‘lizard poisoning’. Most reports of feline platynosomiasis show that this disease is sporadic and manifests with uncommon lesions; its pathogenicity is still not well understood. This study aimed to describe liver injuries and enzymatic changes associated with natural P. fastosum infection in 47 stray cats in an endemic area. Overall, 38.3% (18/47) of cats were parasitized, and 2,358 flukes (P. fastosum) were collected (131 – mean intensity of parasitism; 50.2 – mean abundance). The alanine transaminase (ALT) measure was significantly higher in parasitized animals, while alkaline phosphatase (ALP) showed no statistical difference between parasitized and non-parasitized animals. In infected animals, gross pathological lesions and microscopic liver injuries ranged from mild to severe, and were similar to those in previous descriptions of feline platynosomiasis. Nonetheless, the intensity of parasitism was not related to the severity of macroscopic or microscopic hepatic injuries. However, feline platynosomiasis should be considered in the differential diagnosis of feline liver disorders, as well as, in any program of helminth control, even if no clinical abnormalities are present.


Resumo Platinossomiase é uma doença hepática felina comum causada por Platynosomum fastosum (Trematoda - Dicrocoelidae), também é conhecida como “envenenamento por lagartixa”. A maioria dos relatos de platinossomiase felina mostra que esta doença é esporádica e se manifesta com lesões incomuns; sua patogenicidade ainda não é bem compreendida. Este estudo objetivou descrever as lesões no fígado e alterações enzimáticas associadas à infecção natural por P. fastosum em 47 gatos errantes em uma área endêmica. No total, 38,3% (18/47) dos gatos estavam parasitados, e 2.358 trematódeos (P. fastosum) foram coletados (131 – intensidade média de parasitismo; 50,2 – abundância média). A quantidade de alanina transaminase (ALT) foi significativamente maior nos animais parasitados, enquanto a fosfatase alcalina (ALP) não apresentou diferença estatística entre os animais parasitados e não parasitados. Nos animais infectados, lesões patológicas macroscópicas e microscópicas hepáticas variaram de leve a grave, e foram semelhantes a descrições anteriores de platinossomiase felina. No entanto, a intensidade do parasitismo não foi relacionada à gravidade das lesões hepáticas macroscópicas ou microscópicas. Contudo, a platinossomiase felina deve ser considerada no diagnóstico diferencial de distúrbios hepáticos em felinos, assim como, em qualquer programa de controle de helmintos, mesmo que nenhuma anormalidade clínica esteja presente.


Asunto(s)
Animales , Gatos , Infecciones por Trematodos/veterinaria , Enfermedades de los Gatos/parasitología , Enfermedades de los Gatos/patología , Dicrocoeliidae/aislamiento & purificación , Parasitosis Hepáticas/veterinaria , Trematodos , Infecciones por Trematodos/enzimología , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/patología , Enfermedades de los Gatos/enzimología , Alanina Transaminasa , Parasitosis Hepáticas/enzimología , Parasitosis Hepáticas/parasitología , Parasitosis Hepáticas/patología
3.
Res Vet Sci ; 110: 79-84, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28159241

RESUMEN

The enzyme adenosine deaminase (ADA) is critical for modulating the immune system, and in the presence of zinc, its activity is catalyzed. The aim of this study was to evaluate the ADA activity in pancreas of cattle naturally infected by Eurytrema coelomaticum in relation to the results of zinc levels, pathological findings and parasite load. For this study 51 slaughtered cattle were used. The animals were divided into two groups: Group A consisting of animals naturally infected by E. coelomaticum (n=33) and Group B of uninfected animals (n=18). Blood and pancreas were collected of each animal for analysis of zinc and ADA, respectively. Infected cattle showed a reduction on seric levels of zinc, and decreased ADA activity in the pancreas (P>0.05). A positive correlation between zinc levels and ADA activity was observed. Thus, high parasite load and severity of histopathologic lesions affect the ADA activity in pancreas, as well as the zinc levels in serum of infected animals (negative correlation between these variables). Therefore, we can conclude that cattle infected by E. coelomaticum have low ADA activity in pancreas, which can be directly related to zinc reduction, responsible for ADA activation and catalyzes.


Asunto(s)
Adenosina Desaminasa/metabolismo , Enfermedades de los Bovinos/metabolismo , Dicrocoeliidae/fisiología , Páncreas/parasitología , Carga de Parásitos/veterinaria , Infecciones por Trematodos/veterinaria , Zinc/sangre , Animales , Bovinos , Enfermedades de los Bovinos/enzimología , Enfermedades de los Bovinos/parasitología , Páncreas/metabolismo , Espectrofotometría/veterinaria , Infecciones por Trematodos/enzimología , Infecciones por Trematodos/metabolismo , Infecciones por Trematodos/parasitología
4.
Trends Parasitol ; 33(5): 400-413, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28089171

RESUMEN

Protease inhibitors play crucial roles in parasite development and survival, counteracting the potentially damaging immune responses of their vertebrate hosts. However, limited information is currently available on protease inhibitors from schistosomes and food-borne trematodes. Future characterization of these molecules is important not only to expand knowledge on parasitic fluke biology but also to determine whether they represent novel vaccine and/or drug targets. Moreover, protease inhibitors from flukes may represent lead compounds for the development of a new range of therapeutic agents against inflammatory disorders and cancer. This review discusses already identified protease inhibitors of fluke origin, emphasizing their biological function and their possible future development as new intervention targets.


Asunto(s)
Interacciones Huésped-Parásitos/inmunología , Inhibidores de Proteasas/inmunología , Trematodos/fisiología , Infecciones por Trematodos/enzimología , Infecciones por Trematodos/parasitología , Animales , Descubrimiento de Drogas , Humanos , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Inhibidores de Proteasas/uso terapéutico , Trematodos/enzimología , Trematodos/inmunología , Infecciones por Trematodos/inmunología
5.
Artículo en Inglés | MEDLINE | ID: mdl-27638119

RESUMEN

The aim of this study was to evaluate seric NTPDase and 5'nucleotidase activities of cattle naturally infected by Eurytrema coelomanticum, as well as to correlate them to histopathological lesions in the pancreas and the degree of parasitism. Blood samples and pancreas of 51 bovines were collected on a slaughterhouse in Southern Brazil: 33 from cattle naturally infected by E. coelomanticum (the Group A), and 18 from uninfected animals (the Group B). Infected animals showed an average of 532 parasites per pancreas. In the pancreatic histology, ducts displayed hyperplasia, stenosis, proliferation of fibrous tissue, and interstitial inflammatory infiltration of lymphocytes. The serum from infected animals showed an increase in NTPDase activity when ATP was used as substrate (P<0.001). For the ADP substrate, there was no difference between groups regarding NTPDase activity (P=0.37), as well as 5'-nucleotidase activity (P=0.27). Correlating NTPDase activity (ATP substrate) with the degree of histopathological lesions (rho=0.66, P<0.001) and the parasitic load on the pancreas (rho=0.65, P<0.001), a positive correlation was observed. Similar results were found between the degree of histopathological lesions and NTPDase activity (ADP substrate; rho=0.29, P=0.03), and 5'nucleotidase activity (rho=0.35, P=0.01). Based on the results of NTPDase and 5'nucleotidase enzymes in cattle naturally infected by E. coleomanticum, it is possible to suggest that these enzymes are involved in the modulation of inflammation, and they can act as markers of inflammatory response.


Asunto(s)
5'-Nucleotidasa/sangre , Apirasa/sangre , Enfermedades de los Bovinos/patología , Dicrocoeliidae , Inflamación/veterinaria , Páncreas/parasitología , Infecciones por Trematodos/veterinaria , Mataderos , Animales , Antígenos CD , Biomarcadores/sangre , Brasil , Bovinos , Enfermedades de los Bovinos/enzimología , Enfermedades de los Bovinos/parasitología , Inflamación/enzimología , Inflamación/patología , Linfocitos , Páncreas/patología , Carga de Parásitos , Infecciones por Trematodos/enzimología , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/patología
6.
Zh Evol Biokhim Fiziol ; 46(1): 24-9, 2010.
Artículo en Ruso | MEDLINE | ID: mdl-20297666

RESUMEN

A comparative analysis of changes of activities of detoxifying and antioxidant enzymes was carried out in the body homogenate of the pond snail Lymnaea stagnalis. Juvenile snails with the shell size of 4-6 mm were infested with cercariae of one (Echinoparyphium aconiatum or E. recurvatum or Moliniella anceps) or two (E. aconiatum +M. anceps or E. aconiatum + E. recurvatum or E. recurvatum + M. anceps) trematode species. It has been revealed that activities of detoxifying and antioxidant enzymes in the body of the snail L. stagnalis change at invasion with trematodes and that the character of the changes depends on the stage of development of the trematodes in the host body, the variant of infestation (monoinvasion or mixed infestation), and the species of the parasite. The first 2 h after penetration of the trematode cercariae into the molluse tissues is accompanied by an increase of activities of the detoxifying and antioxidant enzymes. A long coexistence of metacercariae in the host body (no less than for 13 days) is accompanied by a decrease of activities of non-specific esterases and glutathione-S-transferase and by an increase of superoxide dismutase.


Asunto(s)
Antioxidantes/metabolismo , Glutatión Transferasa/metabolismo , Lymnaea , Superóxido Dismutasa/metabolismo , Trematodos , Infecciones por Trematodos/enzimología , Animales , Esterasas/metabolismo , Lymnaea/enzimología , Lymnaea/parasitología , Factores de Tiempo
7.
Fish Shellfish Immunol ; 23(4): 793-807, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17467294

RESUMEN

Analysis of differential gene expression in salmon (Salmo salar) blood following infection with the monogenean parasite Gyrodactylus salaris, resulted in the isolation of a thymidylate kinase gene not previously described from fish and which showed similarity to an LPS-inducible thymidylate kinase gene isolated from mouse macrophages. This salmon TYKi-like gene may play a role in an innate generalised response to pathogen infection as it was upregulated in salmon following infection with the parasite, and also in response to injection with the immunostimulants LPS and Poly I:C, used to emulate bacterial and viral infections, respectively. The possible role of this gene in the biosynthesis of mitochondrial DNA in activated macrophages, in response to G. salaris infection is discussed.


Asunto(s)
Enfermedades de los Peces/enzimología , Nucleósido-Fosfato Quinasa/genética , Salmo salar/genética , Salmo salar/parasitología , Trematodos/fisiología , Infecciones por Trematodos/veterinaria , Regulación hacia Arriba , Adyuvantes Inmunológicos/farmacología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario/química , Enfermedades de los Peces/parasitología , Lipopolisacáridos/farmacología , Datos de Secuencia Molecular , Nucleósido-Fosfato Quinasa/química , Filogenia , Poli I-C/farmacología , Alineación de Secuencia/veterinaria , Factores de Tiempo , Infecciones por Trematodos/enzimología
8.
Wiad Parazytol ; 50(4): 657-64, 2004.
Artículo en Polaco | MEDLINE | ID: mdl-16862800

RESUMEN

Proteases (peptide hydrolases) aside from known catabolic functions and protein processing play numerous roles in many tasks imposed by a parasitic life cycle; this includes parasite immunoevasion, excystment/encystment, tissue penetration and digestion of host tissue for nutrition. They have been identified in biological systems from viruses to vertebrates. Proteases are divided into four major groups on the basis of the catalytic mechanism used during the hydrolytic process - serine, aspartic, cysteine and metalloproteinases; other 'undefined' or cryptic proteases may also exist. There are a number of excellent reviews covering general parasite proteinases but by far the largest number of papers in the literature report on enzymes belonging to the papain superfamily of cysteine proteinases. It turns out, however, that although many different proteases have been characterized in parasitic helminths many of them have yet to be discovered.


Asunto(s)
Cisteína Endopeptidasas/metabolismo , Elastasa Pancreática/metabolismo , Trematodos/enzimología , Infecciones por Trematodos/enzimología , Secuencia de Aminoácidos , Animales , Cisteína Endopeptidasas/química , Cisteína Endopeptidasas/clasificación , Interacciones Huésped-Parásitos/fisiología , Elastasa Pancreática/química , Inhibidores de Proteasas/clasificación , Alineación de Secuencia , Especificidad por Sustrato/fisiología , Infecciones por Trematodos/veterinaria
10.
Korean J Parasitol ; 33(1): 37-43, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7735784

RESUMEN

Neodiplostomum seoulensis, one of the human intestinal trematodes, was reinfected to albino rats, and worm recovery rates, histopathology and activity changes of the intestinal brush border membrane bound enzymes were observed. The experimental groups were three; uninfected, primary infection and reinfection. The worm recovery rate in the reinfection group was much lower than in the primary infection group 14 days after infection. The duodenal histopathology showed villous atrophy during the first and second week in the primary infection group. In the reinfection group, however, villous changes occurred as early as 3 days after the infection, and the lesion was found healed 7 days after infection. The activities of alkaline phosphatase and sucrase in the duodenum of primary infection rats decreased nearly half of the controls 2 weeks after infection, whereas the activities were unchanged in the reinfection group. However, no changes in the activities were observed in the proximal jejunum between the experimental groups. These findings suggested that a secondary infection of N. seoulensis in rats should make less damage on the intestinal mucosa than a primary infection.


Asunto(s)
Parasitosis Intestinales/patología , Intestino Delgado/enzimología , Intestino Delgado/patología , Infecciones por Trematodos/patología , Fosfatasa Alcalina/metabolismo , Animales , Humanos , Parasitosis Intestinales/enzimología , Microvellosidades/enzimología , Ratas , Ratas Sprague-Dawley , Sacarasa/metabolismo , Trematodos/aislamiento & purificación , Infecciones por Trematodos/enzimología
11.
Parasitol Res ; 79(8): 675-82, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8295905

RESUMEN

The ultrastructural study of adult Lymnaea truncatula hemocytes reveals a preponderance of spreading cells at different stages of differentiation. A few round cells may represent a distinct population of hemocytes. As in L. stagnalis, spreading cells are remarkable in that they synthesize peroxidase that is stored in secretory granules, but in L. truncatula hemocytes, endogenous peroxidase activity is also localized in multivesicular bodies. The ultrastructure and peroxidase content of hemocytes do not seem to be affected in snails with established parasites. Evidence that parasites interfere with normal hemocyte functions is that in the few capsules that occurred in parasitized snails the hemocytes did not spread normally and their peroxidase granules were resorbed into multivesicular bodies.


Asunto(s)
Hemocitos/parasitología , Hemocitos/ultraestructura , Lymnaea/parasitología , Infecciones por Trematodos/enzimología , Fosfatasa Ácida/aislamiento & purificación , Animales , Hemocitos/enzimología , Histocitoquímica , Peroxidasa/aislamiento & purificación , Infecciones por Trematodos/patología
12.
Kisaengchunghak Chapchi ; 29(1): 9-20, 1991 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1911629

RESUMEN

The present study intended to evaluate the influences of Metagonimus yokogawai on the activities of brush border membrane bound enzymes of the small intestine. Mice were infected with 500 metacercariae respectively, and the worm recovery, morphological changes and enzyme activities were observed chronologically. A part of them were followed after the treatment. Recovered worms decreased in number continuously after the infection, and they were less than 10% after 2 weeks and almost zero after 28 weeks. Villous atrophy and stromal inflammation were found at two locations of the proximal jejunum from 2 weeks to 4 weeks after the infection. The enzymes, alkaline phosphatase, leucine aminopeptidase and disaccharidases (sucrase, lactase, maltase, and trehalase), showed lowered activities in the duodenum and proximal jejunum of the infected mice but they increased in the distal jejunum for the first two weeks. From three weeks after the infection, the activities were gradually recovered. In one week treated mice, they recovered the activities at 2 weeks from the treatment, but there found no differences of the activities between the 3 week treated group and infected controls. The present data reveal that M. yokogawai infection induces degenerative changes of the host's intestinal mucosa not only morphologically but functionally during the initial phase of infection. The lowered enzyme activities in acute metagonimiasis should be associated with malabsorption and diarrhea.


Asunto(s)
Heterophyidae , Intestino Delgado/enzimología , Microvellosidades/enzimología , Infecciones por Trematodos/enzimología , Fosfatasa Alcalina/metabolismo , Animales , Disacaridasas/metabolismo , Intestino Delgado/patología , Leucil Aminopeptidasa/metabolismo , Ratones , Microvellosidades/patología , Infecciones por Trematodos/patología
13.
Int J Parasitol ; 20(8): 1113-5, 1990 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2074142

RESUMEN

Polyacrylamide gel electrophoresis of the two digenetic trematodes, Gigantocotyle explanatum from the liver and Gastrothylax crumenifer from the rumen of the water buffalo, Bubalus bubalis revealed the presence of at least six and seven isoenzymes of lactate dehydrogenase (LDH), respectively in a partially purified enzyme preparation. The respective host tissues showed five isoenzymes of LDH, which are characteristic to the vertebrates. Both parachloromercuribenzoate and iodoacetate affected the LDH activity of the parasites and host tissues differently. Spectrophotometric analysis also showed different specific activity and susceptibility to the action of thiol inhibitors. The host LDH was quite stable at 57 degrees C for 30 min, but that of the parasites was less stable.


Asunto(s)
Búfalos/parasitología , L-Lactato Deshidrogenasa/análisis , Trematodos/enzimología , Infecciones por Trematodos/veterinaria , Animales , Isoenzimas , Hígado/enzimología , Rumen/enzimología , Infecciones por Trematodos/enzimología
14.
Comp Biochem Physiol B ; 94(4): 753-7, 1989.
Artículo en Inglés | MEDLINE | ID: mdl-2605914

RESUMEN

Esterases of the digestive gland-gonad (DGG) complex of individual snails from a wild population of Helisoma trivolvis infected with the trematode Echinostoma revolutum were analyzed by vertical slab PAGE and compared to similar DGG homogenates of uninfected conspecifics from the same population. Our analysis indicated that: 1. Four classes of esterases, some atypical, could be resolved using diagnostic inhibitors. 2. Uninfected snails demonstrated polymorphism for two of these four esterase groups, including cholinesterases (CHE), in the 34 individual DGGs analyzed. 3. The rarer of the two ChE phenotypes in the uninfected sample (29.4%) was present in 100% of the 17 infected snails examined. However, no changes in esterase zymograms of infected DGGs due to the parasite were noted. 4. The possibility that the 'rare' ChE phenotype is somehow related to host susceptibility to Echinostoma revolutum is discussed in view of similar apparent linkages in other snail-trematode systems.


Asunto(s)
Equinostomiasis/enzimología , Esterasas/metabolismo , Caracoles/enzimología , Infecciones por Trematodos/enzimología , Animales , Vectores de Enfermedades , Echinostoma/enzimología , Echinostoma/genética , Esterasas/genética , Interacciones Huésped-Parásitos/genética , Interacciones Huésped-Parásitos/fisiología , Fenotipo , Polimorfismo Genético , Caracoles/genética , Caracoles/parasitología
15.
Parazitologiia ; 22(5): 394-7, 1988.
Artículo en Ruso | MEDLINE | ID: mdl-2852346

RESUMEN

The infection of Planorbarius banaticus with sporocysts of Cotylurus cornutus is accompanied by an increase in aldolase activity of molluscs' haemolymph of 1.2 fold. In solutions of nitroammofoska (0.1, 1 and 10 mg/1) the activity of this ferment in infected individuals increases much higher than in non-infected ones. This results in fast carbohydrate expenditures by molluscs, intermediate hosts of trematodes, and their death from exhaustion.


Asunto(s)
Fertilizantes/toxicidad , Fructosa-Bifosfato Aldolasa/metabolismo , Hemolinfa/efectos de los fármacos , Caracoles/efectos de los fármacos , Caracoles/parasitología , Infecciones por Trematodos/veterinaria , Animales , Hemolinfa/enzimología , Compuestos de Nitrógeno , Caracoles/enzimología , Soluciones , Infecciones por Trematodos/enzimología
16.
Comp Biochem Physiol B ; 85(4): 847-50, 1986.
Artículo en Inglés | MEDLINE | ID: mdl-2949928

RESUMEN

Day old Leghorn chickens were infected with the digenetic trematode Amphimerus elongatus. After different periods of growth, birds were sacrificed and liver enzyme activity determined for six enzymes. Specific activities of adenylate kinase, lactate dehydrogenase, malate dehydrogenase and phosphoglucomutase were significantly lower in infected chickens than in controls. Creatine kinase and glucosephosphate isomerase activities were unaffected by the parasite.


Asunto(s)
Hígado/enzimología , Infecciones por Trematodos/enzimología , Adenilato Quinasa/metabolismo , Animales , Pollos , Creatina Quinasa/metabolismo , Glucosa-6-Fosfato Isomerasa/metabolismo , Cinética , L-Lactato Deshidrogenasa/metabolismo , Malato Deshidrogenasa/metabolismo , Perciformes , Fosfoglucomutasa/metabolismo , Trematodos/aislamiento & purificación
18.
Parazitologiia ; 18(3): 228-32, 1984.
Artículo en Ruso | MEDLINE | ID: mdl-6739124

RESUMEN

Studies were conducted of the content of ferments with which metacercariae of trematodes of the genus Diplostomum affect the tissues of the host's crystalline lens. The following ferments were found in exudates of metacercariae: pepsin, cathepsin, hyaluronidase and lipase. Their activity depends to a great extent on temperature. Considerable changes in the biochemical content of crystalline lens infected with the parasites were found. The character and force of pathogenic effect of diplostomatids on fishes depend on the factors associated with activation and inhibition of ferments of metacercariae, temperature and the presence of ions-inhibitors in particular.


Asunto(s)
Trematodos/enzimología , Animales , Enfermedades de los Peces/enzimología , Enfermedades de los Peces/parasitología , Peces , Cristalino/enzimología , Cristalino/parasitología , Temperatura , Trematodos/patogenicidad , Infecciones por Trematodos/enzimología , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/veterinaria
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