André Mendes Ribeiro Corrêa

Intoxicação experimental por Trema micrantha (Ulmaceae) em caprinos

Green leaves of Trema micrantha were ground and mixed with water in a domestic blender and then administered by stomach tube to seven goats. One additional goat was fed ad libidum with the green leaves of T. micrantha. Clinical signs were observed in six goats that became ill 2 days after having been dosed with or fed the plant. There were five deaths, which occurred until 4 days after ingestion. Affected goats remained static during long periods and kept their heads low. Incoordination, rhythmical movements of the head, apathy, anorexia, and tenesmus were also noticed. Paddling movements and coma were seen in one goat. T. micrantha was toxic at dosages of 30 g/kg or higher. The most significant gross lesions were observed in the livers, which were yellowish, friable, and with pronounced lobular pattern. Their cut surfaces were reddened and depressed areas alternated with whitish ones. The liver of one goat was slightly but homogeneously reddened but did not show accentuated lobulation. Petechial haemorrhages in the region between the chest and scapula, in the epicardium, mediastinum and serosal membranes of the abdominal organs were also observed. The most important histologic finding was hepatic centrilobular coagulative necrosis, which was associated with congestion, haemorrhages and degenerative changes in the circumjacent hepatocytes. Additional microscopic lesions were found in the nervous system and included perineuronal and perivascular edema and swollen neurones, especially those of the frontal cortex.

Intoxicação espontânea por Baccharis coridifolia (Compositae) em ovinos

An outbreak of Baccharis coridifolia (Compositae) poisoning in sheep is reported, which occurred in November 2004 in the county of Caxias do Sul, Rio Grande do Sul (RS), southern Brazil. From a herd of 212 sheep, coming from a Baccharis coridifolia free area, in the county of Jaguarao, RS, 35 sheep died until 5 days after the arrival in the new area where the plant was found with abundance. The clinical signs began 8 hours after introduction of the animals into the new pasture and included apathy, anorexia, abdominal retraction or mild distension, weakness of hind limbs, dry feces, sternal ou lateral decumbency, struggling movements, coma and death. Clinical evolution was from 5 to 48 hours. Other sheep that were already before on the pasture were not affected. Main necropsy findings were in the gastrointestinal tube, with wall and serosal oedema, mainly in the reticulo-ruminal fold and of the abomasum, reddening and detachment of the mucosa of forestomachs, and intense hemorrhage in the submucosa. Histopathological findings were degeneration and necrosis of the epithelium of the forestomachs with polymorphonuclear infiltration associated with bacterial colonies, congestion, hemorrhage and oedema, and lymphoid tissue necrosis.

Toxicity and genotoxicity evaluation of Passiflora alata Curtis (Passifloraceae)

UNLABELLED Passiflora alata is an official species of Brazilian Pharmacopoeia and its aerial parts are used as medicinal plant by local population as well as constitutes many phytomedicines commercialized in Brazil as sedative. AIMS OF STUDY To evaluate the acute and sub-acute toxicity and genotoxicity of an aqueous spray-dried extract (PA) of Passiflora alata (2.6% flavonoids). MATERIALS AND METHODS The acute and the sub-acute toxicity was evaluated in mice and rats, respectively. Behavioural, biochemical, hematological, histological and urine parameters were considered. Genotoxicity was assessed by using micronucleus test performed in peripheral blood and bone marrow cells and comet assay in peripheral blood leukocytes. RESULTS Mice deaths were not observed up to 4800 mg/kg, p.o., single dose. Rats treated with aqueous extract at dose of 300 mg/kg, p.o., for 14 days did not present biochemical, hematological or histopathological significant alterations when compared to control group. However, these rats showed signs of irritability and did not show weight gain. In addition, mice acutely treated with extract 150, 300 and 600 mg/kg, p.o., presented DNA damage determined by comet assay in peripheral blood cells 3h after treatment. The effect of lower doses (12.5, 25 and 50mg/kg, p.o.) was evaluated at 3, 6 and 24h after treating. Only PA 50mg/kg (p.o.) induced significant damage at 3 and 6h. The maximum damage induction was observed at 6h. When the animals received PA 12.5, 25 or 50mg/kg/day during 3 days (i.e., 72h treatment) DNA damage (comet and micronucleus tests) increased significantly in a dose-dependent manner. CONCLUSION In conclusion Passiflora alata presented genotoxic effect and deserves further toxicity evaluation in order to guarantee its safety for human use.

Long-term cyclosporine treatment: Evaluation of serum biochemical parameters and histopathological alterations in Wistar rats

The immunosuppressant agent cyclosporine (CsA) is currently used in transplanted patients and in the therapy of autoimmune disorders. CsA treatment has significant acute and chronic side effects on the liver and kidney. However, in the clinical setting, it is difficult to distinguish a direct effect of CsA treatment from other confounding variables, such as allograft rejection and effects due to other drug therapies. In the present study, we assessed for direct associations between CsA immunosuppressive therapy and cytokines levels, kidney and liver functionality, as well as lung histopathological status in rats submitted to chronic CsA treatment without undergoing any transplantation. Male Wistar rats were divided into three groups. The control group received vehicle (corn oil), and treated groups received CsA 5 or 15 mg/kg, by daily gastric gavage during 8 weeks. The results demonstrated that CsA treatment decreases blood levels of interleukins 1α (IL-1α), 1β (IL-1β) and interleukin 2 (IL-2), but does not alter interleukin 6 (IL-6) and IFN-γ levels. Serum biochemical markers of renal (creatinine) and hepatic (SGPT and SGOT) injury/dysfunction did not vary with CsA treatment, despite the presence of small histological alterations, suggesting that the function of these metabolic organs were preserved. Pulmonary histopathological lesions were observed in the CsA groups, and they were attributed to the activation of the local immunoresponse mechanisms by the normal microbiota in immunosuppressive CsA cases. These results suggest that the CsA concentrations administered in our experimental protocol were able to induce immunosuppression in rats without causing nephro and hepatotoxicity.

Trema micrantha toxicity in horses in Brazil

After ingesting green leaves of T. micrantha, 2 horses showed apathy, locomotor deficit, blindness, recumbency, paddling, coma and death. The main gross findings were scattered haemorrhages, enhanced lobular pattern of the liver, and cerebral oedema. Histological changes included disseminated haemorrhages, massive hepatocellular necrosis, neuronal degeneration, Alzheimer type II astrocytes and cerebral perivascular oedema. Clinicopathological findings which were comparable with those observed in Trema micrantha poisoned ruminants, associated with epidemiological evidence suggested the diagnosis.Trema micrantha poisoning should be evaluated as a possible cause in the diagnosis of equine hepatopathy and occasional secondary encephalopathy.

Aspectos clínico-patológicos associados à circovirose suína no Rio Grande do Sul

No periodo de janeiro a julho de 2004, foram realizadas 97 necropsias de suinos que apresentaram subdesenvolvimento, aumento generalizado de linfonodos, palidez ou ictericia de mucosas e, ocasionalmente, problemas respiratorios. As principais lesoes macroscopicas encontradas incluiram aumento generalizado de linfonodos, pulmoes nao colapsados com bordos arredondados e areas de consolidacao, especialmente crânio-ventrais, alem de edema de septos interlobulares. Os rins estavam palidos, aumentados de volume e com pontos brancos que, difusamente distribuidos na superficie, infiltravam em forma de estrias ate a zona cortical. Alguns apresentavam pequenos pontos vermelhos, semelhantes a petequias, difusamente distribuidos no cortex renal. O achado histologico comum foi a presenca, em graus variaveis, de infiltrados linfo-histiocitarios em linfonodos, pulmoes e rins. O teste imuno-histoquimico utilizando anticorpo policlonal anti-circovirus suino tipo 2 foi positivo em amostras provenientes de 50 (89,2%) entre 56 suinos examinados.

Intestinal lesions in pigs affected with postweaning multisystemic wasting syndrome.

Samples of mesenteric lymph nodes and intestines from 79 unthrifty 3- to 5-month-old postweaning pigs, confirmed as naturally affected with postweaning multisystemic wasting syndrome (PMWS), were studied. Pigs originated from 12 farms in southern Brazil and were selected on the basis of clinical signs and/or gross lesions suggestive of enteric disorder. Lymphohistiocytic infiltrates of varying intensity were associated with anti-porcine circovirus type 2 (anti-PCV2) immunostaining (IS) in samples of intestines and mesenteric lymph nodes from all pigs. Although most findings were similar to those described in PCV2-associated enteritis, anti-PCV2 IS in association with depletion of the goblet cell mucin stores (24 pigs), diffuse ileal villous atrophy and fusion (18 pigs), and dilatation of the lymphatic vessels (11 pigs) combined or not with lymphangitis were also observed. PCV2 antigen was immunohistochemically demonstrated in the cytoplasm and nuclei from intralesional epithelial cells, histiocytes, and endothelial-like cells in intestinal tissues. Together these findings imply an association with PCV2. The presence of co-infections by Lawsonia intracellularis, Brachyspira spp., Mycobacterium spp., Salmonella spp., rotavirus, parvovirus, coronavirus and enteric calicivirus with PCV2 in the intestinal lesions was investigated.

Senecio brasiliensis (Asteraceae) poisoning in Murrah buffaloes in Rio Grande do Sul 1

Descreve-se a ocorrencia de um surto de intoxicacao espontânea por Senecio brasiliensis em bufalos Murrah (Bubalus bubalis) em uma propriedade localizada no municipio de Nova Prata, Estado do Rio Grande do Sul, no periodo de junho a agosto de 2006. De um total de 90 bufalos, 13 adoeceram e 11 morreram. Os animais eram mantidos em areas de pastoreio altamente infestadas por S. brasiliensis. Os principais sinais clinicos relatados foram letargia, apatia, emagrecimento progressivo, diarreia e decubito permanente. Necropsia foi feita em dois dos 11 animais mortos. As lesoes foram caracteristicas de intoxicacoes por alcaloides pirrolizidinicos. A grande quantidade da planta, forte estiagem e desnutricao consequente foram os principais achados epidemiologicos associados com a mortalidade.

Porcine circovirus 2 (PCV2) induces a procoagulant state in naturally infected swine and in cultured endothelial cells.

Porcine circovirus 2 (PCV2) is the primary causative agent of porcine circovirus disease (PCVD). PCVD is an emerging disease that has been reported worldwide, associated with wasting, lymphoid depletion, enteritis, pneumonia, vasculitis, ischemic lesions, and necrotizing dermatitis. Although PCVD causes considerable economic losses, the pathogenesis of PCV2 has not been fully understood. The aim of the present work was to study the participation of hemostatic system and of vascular endothelium in PCV2 infection, as well as their possible role in PCVD pathogenesis. Our results showed that naturally PCV2-infected swine displayed a prothrombotic state in vivo, since a diminished coagulation time (recalcification time, activated partial thromboplastin time and prothrombin time), a higher platelet aggregation ability (despite a diminished platelet blood count), and an increased thrombin plasma activity (associated with a reduced fibrinogen level) were observed. The PCV2-infected animals showed vasculitis and positive staining for PCV2 antigen in capillary vessels. Furthermore, PCV2-infected endothelial cells displayed an activated phenotype, characterized by an increase in cell surface procoagulant activity. Moreover, the PCV2-infected endothelial cells pre-treated with exogenous thrombin displayed an increased viral load. This work reports, for the first time, the role of the hemostatic system and of endothelium in the pathogenesis and infectivity of PCV2. The study reinforces the importance of the phenomena which occur during PCV2 infection, and affords a better knowledge of the mechanisms behind the pathophysiology of PCVD.

Surto de aflatoxicose em suínos no Estado do Rio Grande do Sul

An outbreak of aflatoxicosis in a swine herd, which occurred in fall 2004 in the county of Sentinela do Sul, RS, is described. The corn, which contained the micotoxin and has been used to feed the animals, was produced and processed on the farm. Seven sows and 8 growing pigs died, and 2 cases of abortion were reported. The clinical signs observed were apathy, anorexia, icterus, yellowish urine stained with blood, and photosensitization. Gamma glutamyltransferase and total bilirubin were elevated in the 4 pigs on which post-mortem examination was done. The main macroscopic findings were generalized icterus, an orange-yellow liver, edema of the gall bladder wall and yellowish effusion in the abdominal and pericardial cavities. The most important microscopic changes were found in the liver and included tumefaction, degeneration and individual necrosis of the parenchyme, with ductal proliferation and cholestasis. The diagnosis was based on the clinical signs, macroscopic and histological findings and on the high levels of B1 aflatoxin found in the corn and ration.