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      Neoplasias do trato alimentar superior de bovinos associadas ao consumo espontâneo de samambaia (Pteridium aquilinum) Translated title: Neoplasms of the upper digestive tract of cattle associated with spontaneous ingestion of bracken fern (Pteridium aquilinum)

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          Abstract

          Foram estudados 30 bovinos com neoplasias no trato alimentar superior (TAS) associadas ao consumo espontâneo de samambaia (Pteridium aquilinum) provenientes de 27 propriedades rurais, sendo 23 no município de Jaguari e quatro em Nova Esperança do Sul, Rio Grande do Sul. A população bovina total das 27 propriedades em que ocorreram os casos era de 1.090 bovinos e havia quantidade abundante de samambaia nas áreas de pastoreio dos animais. Vinte e seis bovinos eram vacas e 4 eram machos castrados. A idade variou de 3 a 13 anos, sendo o maior número de casos entre 7 e 8 anos (46,6%). Os sinais clínicos observados incluíram emagrecimento progressivo, atonia ruminal, tosse, disfagia, regurgitação, halitose, diarréia e timpanismo. Outros sinais clínicos menos freqüentes foram apetite seletivo, dispnéia e salivação. Dois bovinos tiveram morte espontânea e 28 foram submetidos à eutanásia em estágios avançados da doença e necropsiados. Os principais achados macroscópicos e histológicos observados nos 30 bovinos localizavam-se nos mesmos locais do TAS e consistiram de papilomas, papilomas em transformação para carcinomas de células escamosas (CCEs) e CCEs. Metástases de CCEs para linfonodos regionais e outros órgãos (como fígado e pulmões) foram também observadas (18/30). Vinte e nove bovinos tinham papilomas de diversos tamanhos, sendo a quantidade variável entre leve (45%), moderada (38%) e acentuada (17%). Nos papilomas examinados microscopicamente, foram observadas três fases de desenvolvimento: a) fase de inicial de crescimento, b) fase de desenvolvimento, e c) fase de regressão. Em 16 bovinos, observou-se a transformação maligna de papilomas em CCEs. Os CCEs eram únicos (12/30) ou múltiplos (18/30) e variaram quanto ao grau de diferenciação celular entre bem, moderadamente ou pouco diferenciados. Quando a distribuição dos CCEs de maior extensão foi agrupada em regiões cranial (base da língua, faringe/orofaringe, epiglote), média (terços cranial, médio e caudal do esôfago) e caudal (entrada do rúmen e rúmen) do TAS, observou-se que a localização era cranial em 39% dos casos, média em 16%, e caudal em 45%. Utilizando-se esse mesmo critério de agrupamento, porém considerando o número total de vezes em que CCEs (de tamanhos variados) foram diagnosticados nas regiões cranial, média e caudal, os números alteraram-se para 34, 26 e 40%, respectivamente. As evidências epidemiológicas e histomorfológicas relatadas neste estudo reforçam as observações de uma estreita correlação entre a infecção pelo papiloma-vírus bovino tipo 4, causador da papilomatose digestiva, e a co-carcinogênese química dos princípios tóxicos da samambaia na patogênese dos CCEs do TAS de bovinos. Entretanto, a presença de alterações pré-neoplásicas (áreas de displasia), áreas de CCE in situ ou CCEs em estágios iniciais de desenvolvimento, independentemente da presença de papilomas no local, mostram claramente ser possível o desenvolvimento de CCEs diretamente do epitélio normal, possivelmente por uma ação direta dos carcinó-genos químicos da samambaia.

          Translated abstract

          Thirty bovine with neoplasms of the upper digestive tract (UDT) associated with spontaneous ingestion of bracken fern (Pteridium aquilinum) were studied. They were from 27 farms, located in the municipalities of Jaguari (23) and Nova Esperança do Sul (4), Rio Grande do Sul, Brazil. The total cattle population in those farms was 1,090 and large amounts of bracken fern were found in the pastures. Twenty-six of the affected cattle were cows and four were castrated males, 3-13 years of age; most of them were 7-8 years old (46,6%). Clinical signs observed in the affected animals were progressive weight loss, absence of ruminal movements, cough, dysphagia, regurgitation, halitosis, diarrhea, and bloat. Less frequent signs were selective appetite, dyspnea, and salivation. Two bovine died and 28 were submitted to euthanasia in advanced stage of disease and necropsied. The main gross and microscopic alterations were found in identical areas of the UDT. They consisted of papillomas, transforming papillomas, and squamous cell carcinomas (SCCs). Metastases of SCCs to regional lymph nodes and other organs, such as liver and lungs, were also observed (18/30). Twenty-nine bovine had papillomas of various sizes in several areas of the UDT. The digestive papillomatosis ranged from mild (45%), to moderate (38%), to severe (17%). Three developing phases were observed microscopically in the examined papillomas: an early growing phase, a developing phase, and a regressing phase. In 16 cases, there was malignant transformation of papillomas into SCCs. The SCCs were solitary (12/30) or multiple (18/30) and were histologically well, moderately, or poorly differentiated. Grouping the distribution of SCCs of larger extension in the UDT into cranial region (base of the tongue, pharynx/oropharynx, and epiglottis), medial region (esophagus), and caudal region (cardia and rumen), the distribution was cranial in 39%, middle in 16%, and caudal in 45% of the cases. By the same grouping criteria, but considering the total number of times SCCs of varied extensions were diagnosed in the cranial, middle, and caudal regions, the percentages changed to 34%, 26%, and 40%, respectively. The epidemiological and histomorphological evidences found in this study are in agreement with the observations that point out the co-carcinogenesis between bovine papillomavirus type 4 infection and chemicals of bracken fern in the pathogenesis of the SCCs in the UDT of cattle. However, the presence of pre-neoplastic changes and SCCs in situ or in early stages of development, independently of the presence of papillomas, clearly indicates the possibility of development of SCCs from normal epithelium, probably due to the direct action of the chemical carcinogens contained in bracken fern.

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          Most cited references34

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          Plantas daninhas do Brasil: terrestres, aquáticas, parasitas, tóxicas e medicinais

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            Animal models of papillomavirus pathogenesis.

            Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less problematic and understandably research efforts have shifted in focus from animal to human PVs. However, there are still areas in which studies on animal PVs will continue to provide answers to questions pertaining to virus biology. One of these questions is the involvement of HPV in oesophageal and bladder cancer in humans as is the case for BPV in cattle. Another is the site of viral latency. Lymphocytes have been proposed as a site of latency for both BPV and HPV but only experiments performed in animals could clarify this point. Animal PVs have been instrumental in the development of vaccines as cattle, rabbit and more recently dog all provide the opportunity to study vaccination in the natural host. Several anti-HPV vaccines, both prophylactic and therapeutic, based on those developed in animals, are now in clinical trials with encouraging results. In vitro studies with two animal PV early proteins, the transcriptional regulator E2 and the oncoprotein E5, among others, have contributed to the elucidation of viral gene control and cell transformation. BPV E2 was the first viral product to be identified as a transcriptional regulator; more recently, its association with mitotic chromosomes has been suggested as a mechanism for the partition of viral genomes between daughter cells, and its L2-mediated localisation in the sub-nuclear compartments PODs is believed to favour viral DNA encapsidation. E5 is the major transforming protein of several BPVs. Many of the function of E5 proteins have been first established for BPV E5 and later validated for HPV E5. E5 interacts with 16k ductin/subunit c and this interaction is deemed responsible for the down-regulation of gap junction intercellular communication and the inhibition of acidification of endomembranes. E5 activates growth factor receptors and numerous kinases, including cdks, and down-regulates expression of MHC class I. Thus E5 would help the establishment of viral infection by promoting both cell proliferation and immune evasion. Despite the extensive studies on vaccination in animals, E5 has not been tried inE5 has not been tried in animal models as a possible anti-papillomavirus vaccine. A recent study has reported that vaccination of mice with HPV-16 E5 in a recombinant adenovirus reduced the growth of tumours induced by E5-expressing cells. Perhaps this is an instance in which work on animal PVs should follow HPV and the potential for E5 vaccination should be validated in naturally occurring animal models.
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              High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus.

              Cattle in upland areas of Scotland and northern England are substantially more prone to alimentary cancer than those of the immediately neighbouring lowlands, and epidemiological evidence implicates a combination of papilloma virus and bracken in the aetiology of the disease. Here Professor Jarrett outlines the circumstantial case against these agents and discusses its implications.
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                Author and article information

                Journal
                pvb
                Pesquisa Veterinária Brasileira
                Pesq. Vet. Bras.
                Colégio Brasileiro de Patologia Animal - CBPA (Rio de Janeiro, RJ, Brazil )
                0100-736X
                1678-5150
                June 2006
                : 26
                : 2
                : 112-122
                Affiliations
                [02] Santa Maria Rio Grande do Sul orgnameUFSM orgdiv1Departamento de Patologia orgdiv2Laboratório de Patologia Veterinária
                [05] orgnameUniversidade Federal de Pelotas orgdiv1Faculdade de Veterinária orgdiv2Laboratório Regional de Diagnóstico
                [03] Rio Grande do Sul orgnameInspetoria Veterinária de Jaguari
                [04] Patos Paraíba orgnameUniversidade Federal de Campina Grande
                [01] orgnameUniversidade Federal de Santa Maria
                Article
                S0100-736X2006000200009 S0100-736X(06)02600209
                6505ec06-fe9c-40b8-b55e-f9c47a26964b

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 04 January 2006
                : 19 December 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 42, Pages: 11
                Product

                SciELO Brazil


                intoxicação por planta,Poisonous plants,Pteridium aquilinum,plant poisoning,bovine papillomavirus type 4,squamous cell carcinoma,diseases of cattle,pathology,Plantas tóxicas,patologia,doenças de bovinos,carcinoma de células escamosas,papilomavírus bovino tipo 4

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