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pathogenesis of brain damage produced in sheep by clostridium perfringens type d epsilon toxin: a review.microvascular endothelial damage by the epsilon toxin of clostridium perfringens type d appears to be the fundamental cause of cerebral parenchymal injury and lesions occur in a seemingly dose- and time-dependent manner. large doses of circulating toxin produce a severe, generalised, vasogenic cerebral oedema and an acute or peracute clinical course to death. with lower doses of toxin, or in partially immune sheep, focal necrosis, often bilaterally symmetrical, occurs in certain selectively vuln ...200315080445
pcr detection of clostridium perfringens type d in formalin-fixed, paraffin-embedded tissues of goats and sheep.a polymerase chain reaction (pcr) was used to identify the genes encoding the alpha, epsilon and beta toxins of clostridium perfringens in formalin-fixed, paraffin-embedded intestinal tissues of goats and sheep. when pure cultures of cl. perfringens types b and d were used as control templates in the pcr, products of the following sizes were observed on the agarose gel: 247 bp (alpha primers), 1025 bp (beta primers) and 403 bp (epsilon primers). when used to identify cl. perfringens type d in fo ...199910432627
comparison of the effects of clostridium perfringens type d culture supernates in ligated intestinal loops of goats and sheep.the effects of clostridium perfringens type d culture supernates were compared in ligated loops of the small intestine (ileum) and colon of four goat kids and four lambs, the loops being examined histopathologically and electron microscopically 7 h after inoculation. no lesions were observed in the small intestine of any animal, or in control colonic loops. in the caprine and ovine colonic loops treated with culture supernates, most goblet cells were empty and the lumina contained a layer of muc ...199910405305
detection of alpha- and epsilon-toxigenic clostridium perfringens type d in sheep and goats using a dna amplification technique (pcr).clostridium perfringens isolated from sheep and goat with enterotoxaemia at necropsy and from healthy animals at slaughter were typed using specific pcr assays for the detection of the alpha-, beta- and epsilon-toxin genes. clostridium perfringens isolated from all 52 animals with pathological signs of enterotoxaemia showed the presence of the alpha- and epsilon-toxin genes but were devoid of the beta-toxin gene. these strains could therefore be identified as type d, characteristic for clostridi ...19989674169
effects of the intravenous administration of clostridium perfringens type d epsilon toxin on young goats and lambs.young goats (n = 18) and lambs (n = 10) were compared in respect of the effects of clostridium perfringens type d epsilon toxin. toxin produced neurological signs within 0.5-3 h of intravenous injection in (1) all of six kids given doses of 250, 185 or 120 mouse lethal doses 50% (mld50)/kg body weight, (2) two of the three kids given 60 mld50/kg, and (3) all of five lambs given 250 or 120 mld50/kg. six kids and three lambs given 45, 30 or 15 mld50/kg, one lamb given 60 mld50/kg, and three kids a ...19979076601
detection of clostridium perfringens epsilon toxin by elisa.an enzyme-linked immunosorbent assay (elisa) has been developed as an alternative to neutralisation tests in mice to detect clostridium perfringens type d epsilon toxin in the intestinal contents of animals which have died from suspected enterotoxaemia. the test was sensitive and quantitative and gave excellent agreement with the mouse protection test.19872884704
clinical signs, treatment, and postmortem lesions in dairy goats with enterotoxemia: 13 cases (1979-1982).enterotoxemia attributable to clostridium perfringens type d in goats is difficult to diagnose because of a lack of specific clinical signs or postmortem lesions, on which to base the diagnosis. this report describes the clinical signs, postmortem lesions, and clinical responses to treatment and vaccination in 4 goat herds, in which a diagnosis of enterotoxemia was confirmed. four clinical cases had the diagnosis confirmed on the basis of signs of diarrhea or sudden death and the isolation of c ...19921559880
evaluation of enzyme-linked immunosorbent assay for diagnosis of clostridium perfringens enterotoxemias.two double sandwich enzyme-linked immunosorbent assays (elisa) for clostridium perfringens beta and epsilon toxins were assessed for routine diagnosis of enterotoxemias on intestinal contents of 151 sheep that died suddenly. conventional tests (mouse assay and culture of organism) showed that 21 specimens were positive for clostridium perfringens type c (beta toxin) and 39 were positive for clostridium perfringens type d (epsilon toxin) enterotoxemias. comparison of the elisa results with conven ...19921496812
reverse phase passive haemagglutination and single radial immunodiffusion to detect epsilon antigen of clostridium perfringens type d.two in vitro immunological assays were developed for detection of the epsilon (epsilon) antigen of cl. perfringens type d. it was found that the reverse phase passive haemagglutination assay (rpha) was able to detect concentrations of epsilon-antigen as low as 6 x 10-7 mg/ml whereas the single radial immunodiffusion techniques (srid) was capable of detecting concentrations of epsilon-antigen above 0.01 mg/ml. when applied to gut contents from freshly dead infected sheep the rpha test was found t ...1978223537
the effect of passive immunization on active immunity against clostridium perfringens type d in lambs.lambs in different stages of development of active immunity against clostridium perfringens type d were treated with partially purified immunoglobulin in an attempt to superimpose a passive immunity on an existing or developing active immunity. three different studies were undertaken to determine the impact of partial purified immunoglobulins on these vaccinated animals. in 2 of the 3 studies, active immunity was induced by administering the normal routine enterotoxaemia vaccinations and allowin ...19892560536
vitamin e-enhanced humoral antibody response to clostridium perfringens type d in sheep. 19836301619
clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery.epsilon-toxin, the primary virulence factor of clostridium perfringens type d, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. it is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endothelial damage and edema. here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properti ...200516041001
evaluation of different fluids for detection of clostridium perfringens type d epsilon toxin in sheep with experimental enterotoxemia.enterotoxemia caused by clostridium perfringens type d is a highly lethal disease of sheep, goats and other ruminants. the diagnosis of this condition is usually confirmed by detection of epsilon toxin, a major exotoxin produced by c. perfringens types b and d, in the intestinal content of affected animals. it has been suggested that other body fluids can also be used for detection of epsilon toxin. this study was performed to evaluate the usefulness of intestinal content versus other body fluid ...200616857397
immune regulatory factors in sheep fetuses.after an antigenic stimulus in vitro, a fraction was found in the supernatant fluids of spleen (s-1) and thymus (t-1) cell cultures of 70 to 80-day-old sheep fetuses infected with ovine adenovirus in utero. the fraction agreed with alpha-1-fetoprotein in mobility and its molecular weight was 67 000. injected into adult sheep, s-1 and t-1 had a suppressive effect on the humoral immune response to both adenovirus and clostridium perfringens d vaccine. tests with peripheral lymphocytes suggested th ...19826283803
differences in signs and lesions in sheep and goats with enterotoxemia induced by intraduodenal infusion of clostridium perfringens type d.enterotoxemia was induced in 4 lambs and 4 goat kids by continuous intraduodenal infusion of a whole culture of clostridium perfringens type d. clinical signs, hematologic values, biochemical alterations, and postmortem lesions in the lambs and goat kids were compared. the 4 lambs and 4 goat kids died within 25 hours of beginning the infusions. lesions were not observed in the gastrointestinal tract of the 4 lambs; however, severe hemorrhagic enterocolitis was found in the 4 goat kids. this diff ...19911892271
neurological disorders produced by clostridium perfringens type d epsilon toxin.although the epsilon toxin of clostridium perfringens type d produces disease in many species of domestic livestock, neurological disturbance is more common and better studied in sheep. high levels of circulating toxin, especially in lambs, cause cerebral microvascular endothelial damage with disruption of the blood-brain barrier leading to a severe, diffuse vasogenic oedema and an acute or peracute clinical course to death. with lower toxin levels, or in partially immune sheep, a focal, bilater ...200416701511
resistance of ovine, caprine and bovine endothelial cells to clostridium perfringens type d epsilon toxin in vitro.ovine, caprine and bovine endothelial cells were grown in vitro and challenged with clostridium perfringens type d epsilon toxin to compare their susceptibility to this toxin. madin darby canine kidney (mdck) cells, which are known to be susceptible to epsilon toxin, were used as a positive control. no morphological alterations were observed in any of the endothelial cell cultures tested, even after challenging with doses as high as 1200 mld50/ml of epsilon toxin. mdck cells showed contour round ...199910493114
aquaporin-4 in acute cerebral edema produced by clostridium perfringens type d epsilon toxin.sheep, particularly lambs, with high circulating levels of clostridium perfringens type d epsilon toxin develop severe neurologic signs and often die suddenly. on microscopic examination, in the brain, there is microvascular endothelial injury and diffuse vasogenic edema. the aquaporin (aqp) family of membrane water-channel proteins, especially aqp-4, is important in the regulation of water balance in the brain and facilitates reabsorption of excess fluid. in rats given epsilon toxin, generalize ...200818487486
focal symmetrical encephalomalacia in a goat.focal symmetrical encephalomalacia (fse) is the most prominent lesion seen in the chronic form of enterotoxemia caused by clostridium perfringens type d in sheep. however, this lesion has not been reported in goats. the current paper reports a case of fse in a goat from the state of paraíba in the brazilian semiarid region. as reported by the farmer, 30, 4-48-month-old animals from a flock of 150 goats died after showing nervous signs, including blindness and recumbence, for periods varying betw ...201020807946
the pathology of peracute experimental clostridium perfringens type d enterotoxemia in sheep.the pathological findings in sheep with peracute experimental clostridium perfringens type d enterotoxemia are described. of 16 animals inoculated intraduodenally with a whole culture of this microorganism and a starch solution in the abomasum, 12 developed clinical signs including increased respiratory efforts, recumbency, paddling, bleating, convulsions, blindness, and opisthotonus. diarrhea was not observed in any of the animals. the time lapse between the beginning of intraduodenal infusion ...200415460322
the early effects of clostridium perfringens type d epsilon toxin in ligated intestinal loops of goats and sheep.clostridium perfringens type d produces enterotoxaemia in goats, sheep and other animals. the disease is caused by c. perfringens epsilon toxin and, while enterotoxaemia in goats is usually characterized by enterocolitis, the disease in sheep is characterized by systemic lesions (such as lung and brain oedema) with minor and inconsistent changes observed in the intestine. a possible explanation for these differences is that epsilon toxin is more promptly absorbed by the ovine than by the caprine ...200312777097
effects of intravenous injection of clostridium perfringens type d epsilon toxin in calves.in cattle, a neurological lesion similar to that produced in sheep and goats by clostridium perfringens type d enterotoxaemia has been reported. however, no causal relationship has been established between this disease and the lesion in cattle. the effects of single and multiple intravenous injections of epsilon toxin in three calves aged 6 months were studied. a further calf was inoculated intravenously with saline solution and used as a control. epsilon toxin invariably produced neurological s ...200211814324
clostridium perfringens type d enterotoxaemia in neonatal lambs. 200717558035
in vitro effects of clostridium perfringens type d epsilon toxin on water and ion transport in ovine and caprine intestine.clostridium perfringens type d produces enterotoxaemia in sheep, goats and other animals. the disease is caused by c. perfringens epsilon toxin, and while enterotoxaemia in goats is usually characterized by enterocolitis, the disease in sheep is characterized by systemic lesions (such as lung and brain oedema) with minor and inconsistent changes observed in the intestine. a possible explanation for these differences is that epsilon toxin is more promptly absorbed by sheep than goat intestine. in ...200316887702
the passive protection of lambs against clostridium perfringens type d with semi-purified hyperimmune serum.weaned lambs, having a detectable level of maternal antibodies (1-2 units/ml) against c. perfringens type d, showed protective antitoxin levels lasting for 29 days after receiving a single parenteral dose of 200 units/kg hyperimmune serum. lambs, having no maternal antibodies (less than 0,07 units/ml) to c. perfringens type d but receiving the same dose of hyperimmune serum, maintained protective antibody levels for only 21 days. three weeks after the titres fell below the minimum protective lev ...19882895443
binding of epsilon-toxin from clostridium perfringens in the nervous system.epsilon-toxin (epsilon-toxin), produced by clostridium perfringens type d, is the main agent responsible for enterotoxaemia in livestock. neurological disorders are a characteristic of the onset of toxin poisoning. epsilon-toxin accumulates specifically in the central nervous system, where it produces a glutamatergic-mediated excitotoxic effect. however, no detailed study of putative binding structures in the nervous tissue has been carried out to date. here we attempt to identify specific accep ...200818406080
comparison of four techniques for the detection of clostridium perfringens type d epsilon toxin in intestinal contents and other body fluids of sheep and goats.polyclonal capture enzyme-linked immunosorbent assay (pc-elisa), monoclonal capture elisa (mc-elisa), mouse neutralization test (mnt), and counterimmunoelectrophoresis (ciep), were compared for their ability to detect epsilon toxin in intestinal contents and body fluids of sheep and goats. when used to evaluate intestinal contents of sheep artificially spiked with epsilon prototoxin, pc-elisa detected 0.075 mouse lethal dose (mld)50/ml, whereas the mnt, mc-elisa, and ciep detected 6, 25, and 50 ...200312661718
ulcerative enterocolitis in two goats associated with enterotoxin- and beta2 toxin-positive clostridium perfringens type d.enterotoxemia caused by clostridium perfringens type d in sheep is believed to result from the action of epsilon toxin (etx). however, the sole role of etx in the intestinal changes of the acute and chronic forms of enterotoxemia in goats remains controversial, and the synergistic action of other c. perfringens toxins has been suggested previously. the current study examined 2 goats that were found dead without premonitory clinical signs. gross lesions at necropsy consisted of multifocal fibrino ...200818776108
an alternative to the toxin neutralization assay in mice for the potency testing of the clostridium tetani, clostridium septicum, clostridium novyi type b and clostridium perfringens type d epsilon components of multivalent sheep vaccines.potency testing of veterinary vaccines containing clostridial antigens currently requires the vaccination of laboratory rabbits followed by the determination of specific antitoxin concentration in the rabbit sera by toxin neutralization test in mice. elisas are described as an alternative method to toxin neutralization for the determination of clostridium tetani, clostridium septicum, clostridium novyi type b and clostridium perfringens type d epsilon antitoxins. the assays were found to be rapi ...19911797039
potency against enterotoxemia of a recombinant clostridium perfringens type d epsilon toxoid in ruminants.enterotoxemia, a disease that affects domestic ruminants, is caused mainly by the epsilon toxin from clostridium perfringens type d. its eradication is virtually impossible, control and prophylaxis are based on systematic vaccination of herds with epsilon toxoids that are efficient in inducing protective antibody production. the use of recombinant toxins is one of the most promising of these strategies. this work evaluates the potency of a cl. perfringens type d epsilon toxoid expressed by esche ...201020670910
enterotoxaemia in goats.enterotoxaemia of sheep and goats occurs worldwide, but the condition in goats is poorly understood. the disease in goats is mostly caused by clostridium perfringens type d, although the role of the toxins of this microorganism in the pathogenesis of the disease is not fully understood. the disease occurs in three forms, peracute, acute and chronic, the cardinal clinical sign of the acute and chronic forms being diarrhoea. the main biochemical alterations are hyperglycaemia and glycosuria, while ...19968950829
naturally acquired antibodies against clostridium perfringens epsilon toxin in goats.clostridium perfringens type d-producing epsilon toxin is a common cause of death in sheep and goats worldwide. although anti-epsilon toxin serum antibodies have been detected in healthy non-vaccinated sheep, the information regarding naturally acquired antibodies in ruminants is scanty. the objective of the present report was to characterize the development of naturally acquired antibodies against c. perfringens epsilon toxin in goats. the levels of anti-epsilon toxin antibodies in blood serum ...200818538416
effect of clostridium perfringens epsilon toxin on mdck cells.epsilon toxin is one of the major lethal toxins produced by clostridium perfringens type d and b. it is responsible for a rapidly fatal disease in sheep and other farm animals. many facts have been published about the physical properties and the biological activities of the toxin, but the molecular mechanism of the action inside the cells remains unclear. we have found that the c. perfringens epsilon toxin caused a significant decrease of the cell numbers and a significant enlargement of the mea ...200111549414
histopathological changes in the brain of mice given clostridium perfringens type d epsilon toxin.the distribution, severity and frequency of brain lesions produced in mice by the administration of clostridium perfringens type d epsilon toxin were examined by light microscopy. the granular layer of the cerebellum was the area most frequently affected in mice given single doses of toxin. sequential changes in brain morphology were examined from 1 h to 7 days after injection of toxin. lesions progressed from an initial vasogenic oedema to malacic foci which commonly were focal and bilaterally ...19846088597
virulence plasmid diversity in clostridium perfringens type d isolates.clostridium perfringens type d isolates are important in biodefense and also cause natural enterotoxemias in sheep, goats, and occasionally cattle. in these isolates, the gene (etx) encoding epsilon-toxin is thought to reside on poorly characterized large plasmids. type d isolates sometimes also produce other potentially plasmid-encoded toxins, including c. perfringens enterotoxin and beta2 toxin, encoded by the cpe and cbp2 genes, respectively. in the current study we demonstrated that the etx, ...200717339362
lethal effects of clostridium perfringens epsilon toxin are potentiated by alpha and perfringolysin-o toxins in a mouse model.epsilon toxin (etx) is the most important virulence factor of clostridium perfringens type d. two other important toxins, alpha toxin (cpa) and perfringolysin-o (pfo), are encoded and potentially produced by most c. perfringens type d isolates. the biological effects of these toxins are dissimilar although they are all lethal. since the possible interaction of these toxins during infection is unknown, the effects of cpa and pfo on the lethal activity of etx were studied in a mouse model. mice we ...200817997054
development and application of an oral challenge mouse model for studying clostridium perfringens type d infection.clostridium perfringens type d isolates cause enterotoxemia in sheep, goats, and probably cattle. while the major disease signs and lesions of type d animal disease are usually attributed to epsilon toxin, a class b select agent, these bacteria typically produce several lethal toxins. understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type d isolates. addressing this need, we developed an ...200717562765
clinicopathologic features of experimental clostridium perfringens type d enterotoxemia in cattle.this study was designed to experimentally reproduce enterotoxemia by clostridium perfringens type d in cattle and to characterize the clinicopathologic findings of this disease. fourteen 9-month-old calves were inoculated intraduodenally according to the following schedule: group 1 (n = 4), c. perfringens type d whole culture; group 2 (n = 3), c. perfringens type d washed cells; group 3 (n = 5), c. perfringens type d filtered and concentrated supernatant; group 4 (n = 2), sterile, nontoxic cultu ...200919605912
vaccination of sheep with clostridium perfringens type d vaccines. 195413207581
molecular cloning and expression of epsilon toxin from clostridium perfringens type d and tests of animal immunization.epsilon toxin produced by clostridium perfringens types b and d causes enterotoxemia in sheep, goats and calves. enterotoxemia can cause acute or superacute disease, with sudden death of the affected animal. it provokes huge economic losses when large numbers of livestock are affected. therapeutic intervention is challenging, because the disease progresses very rapidly. however, it can be prevented by immunization with specific immunogenic vaccines. we cloned the etx gene, encoding epsilon toxin ...201020198582
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