Pathogenesis of hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) in Asian elephants (Elephas maximus).

Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is an acute fatal disease in elephants. Despite the fact that the underlying pathogenesis of EEHV-HD has been proposed, it remains undetermined as to what mechanisms drive these hemorrhagic and edematous lesions. In the present study, we have investigated and explained the pathogenesis of acute EEHV-HD using blood profiles of EEHV-HD and EEHV-infected cases, hematoxylin and eosin (H&E) stain, special stains, immunohistochemistry, quantitative polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR). It was found that EEHV genomes were predominantly detected in various internal organs of EEHV-HD cases. Damage to endothelial cells, vasculitis and vascular thrombosis of the small blood vessels were also predominantly observed. Increases in platelet endothelial cell adhesion molecules-1 (PECAM-1)- and von Willebrand factor (vWF)-immunolabeling positive cells were significantly noticed in injured blood vessels. The expression of pro-inflammatory cytokine mRNA was significantly up-regulated in EEHV-HD cases when compared to EEHV-negative controls. We have hypothesized that this could be attributed to the systemic inflammation and disruption of small blood vessels, followed by the disseminated intravascular coagulopathy that enhanced hemorrhagic and edematous lesions in EEHV-HD cases. Our findings have brought attention to the potential application of effective preventive and therapeutic protocols to treat EEHV infection in Asian elephants.

Recent advances in viral vectors in veterinary vaccinology.

Viral vectored vaccines, particularly using vectors such as adenovirus, herpesvirus and poxviruses, are used widely in veterinary medicine, where this technology has been adopted much more quickly than in human medicine. There are now a large number of programmes to develop viral vector vaccine platforms for humans and very similar or identical vectors are being developed for veterinary medicine. The shared experiences of developing these new vaccine platforms across the two disciplines is accelerating progress, a striking example of the value of a 'One Health' approach. In particular, there is growing use of adenoviruses, either replicating or replication-incompetent, to create new vaccines for use in livestock or companion animals. Live replicating avian herpesvirus vectors are increasingly used as vaccines against poultry diseases.

Immuno-PCR in cancer and non-cancer related diseases: a review.

Polymerase chain reaction-amplified immunoassay (immuno-PCR, iPCR) is a method that combines the specificity of an immunological detection method and the sensitivity of a nucleic acid amplification method. In this way, immuno-PCR uses a minimum amount of sample, and allows the detection of rare diseases and those diseases in very early stage (i.e. infectious diseases, degenerative disorders, or neoplastic diseases). The present review was aimed to describe this new methodology and applications to the early detection of cancer and non-cancer related diseases, and discuss about the possibility to detect diverse biomarkers of oncology disorders, such as breast, gastric, colorectal and nasopharynx cancer, and other factors related to the growth of the neoplastic disease.

Multiple effects of bracken fern under in vivo and in vitro conditions.

Several toxic substances have been detected in plants which are responsible for animal and human diseases. Bracken fern (Pteridium aquilinum) is one example, widely distributed in many parts of the world. It is known to cause cancer in humans and other animals. In fact, man can be directly or indirectly exposed to the danger by consuming fern, contaminated water, milk, meat, and spore inhalation. Experimental studies have shown an association between bracken exposure and gastric cancer, and research has shown genotoxic and cytotoxic effects in vitro. This paper describes and reviews toxic, carcinogenic, genotoxic/cytotoxic, and immunomodulatory effects of bracken and included possible toxic agents. The chemistry of Ptaquiloside (PT) reactions is emphasized, along with bracken problems in livestock, possible pathways of exposure in man, and control for human health.

Cancer vaccines: harnessing the potential of anti-tumor immunity.

Although the presence of cancer suggests failure of the immune system to protect against development of tumors, the possibility that immunity can be redirected and focused to generate an anti-tumor response offers great translational possibility. The key to this is identifying antigens likely to be present in any given tumor and functionally critical to tumor survival and growth. Such tumor-associated antigens (TAAs) are varied and optimally should be absent from normal tissue. Of particular interest are TAAs associated with the tumor stroma, as immunity directed against the stroma may restrict the ability of the tumor to grow and metastasize. Important to directing the immune system toward an effect anti-tumor response is the understanding of how TAAs are processed and how the tumor is able to evade immune elimination. The process of immunoediting happens in response to the selective pressure that the immune system places upon tumor cell populations and allows for emergence of tumor cells capable of escaping immune destruction. Efforts to harness the immune system for clinical application has been aided by vaccines based on purified recombinant protein or nucleic acid TAAs. For example, a vaccine for canine melanoma has been developed and approved based on immunization with DNA components of tyrosinase, a glycoprotein essential to melanin synthesis. The performance of cancer vaccines has been aided in some cases when supplemented with immunostimulatory molecules such as interleukin 2 or a novel extracellular matrix vaccine adjuvant. Vaccines with the broadest menu of antigenic targets may be those most likely to succeed against cancer. For this reason, tissue vaccines produced from harvested tumor material may offer significant benefit. With several cancer vaccines on the veterinary and human markets, efforts to understand basic tumor immunology are soon to yield great dividends.

Factors influencing the prevalence of subclinical mastitis in lactating dromedary camels in Riyadh Region, Saudi Arabia.

The purpose of this study was to determine the prevalence of subclinical mastitis in camels in Riyadh, Saudi Arabia and the factors influencing its incidence. A total of 740 quarter milk samples were collected from 47 camel herds belonging to Majahim, Maghatir, Shu'l, and Sufer breeds. California mastitis test (CMT) was used as a screening test for subclinical mastitis. Samples giving negative or trace CMT scores (0) were assigned to healthy quarters, while those giving positive scores of 1+ to 3+ were assigned to subclinically affected quarters. Logistic regression was used to assess the association of breed, parity, and stage of lactation with the prevalence of subclinical mastitis. Milk fat, protein, lactose, solid nonfat percentages and Na, Ca, and K concentrations were compared in CMT-positive versus healthy quarters. One third (33%) of tested quarters had subclinical mastitis based on CMT. The estimated probability of subclinical mastitis with the combined effects of breed, parity, and stage of lactation ranged from 15.8% to 54.6%. The risk of subclinical mastitis increased significantly with parity and with the early stage of lactation. The Shu'l breed had significantly higher prevalence of subclinical mastitis than other breeds. Significant decreases in protein, lactose, and solid nonfat, Ca and K concentrations and increase in Na concentrations were associated with subclinical mastitis. In conclusion, subclinical mastitis is prevalent in Saudi camels, and its incidence is influenced by breed, parity, and stage of lactation.

A biological hazard of our age: bracken fern [Pteridium aquilinum (L.) Kuhn]--a review.

Bracken fern (Pteridium aquilinum) is the fifth most distributed common weed species of the world. Its ecological distribution is very wide, and the plant can grow and spread successfully on many types of soil. The cover of P. aquilinum is--in some cases--remarkable (e.g., in the United Kingdom). Bracken fern contains different poisonous agents: some cyanogen glycosides, factors (agents) of antithiamine character (thermolabile thiaminase and thermostable other compounds) and factors of carcinogenic activity (first of all ptaquiloside). This paper summarises and reviews different toxicological problems and poisonings caused by bracken fern in ruminants (cattle, sheep) and in non-ruminant animals (horses, pigs, rats, mice, etc.). The carcinogenic properties of the norsesquiterpene-type ptaquiloside make bracken fern a potent, living hazard. Recent investigations have shown that ptaquiloside pollution of different soil layers is a distinct possibility. Ptaquiloside may leach from the soil into the drinking water base. This ecotoxicological aspect seems to be the most hazardous phenomenon in relation to P. aquilinum and ptaquiloside. The carcinogenic effect of ptaquiloside is based on its hydrolysis, which leads to the formation of a dienon intermediate. It can produce DNA adducts, which are responsible for inducing carcinoma.

Navy sonar and cetaceans: just how much does the gun need to smoke before we act?

Cetacean mass stranding events associated with naval mid-frequency sonar use have raised considerable conservation concerns. These strandings have mostly involved beaked whales, with common pathologies, including "bubble lesions" similar to decompression sickness symptoms and acoustic traumas. However, other cetacean species have also stranded coincident with naval exercises. Possible mechanisms for the strandings include a behavioral response that causes deep divers to alter their diving behavior, which then results in decompression sickness-like impacts. Current mitigation measures during military exercises are focused on preventing auditory damage (hearing loss), but there are significant flaws with this approach. Behavioral responses, which occur at lower sound levels than those that cause hearing loss, may be more critical. Thus, mitigation measures should be revised. A growing number of international bodies recognize this issue and have urged increasing scrutiny of sound-producing activities, but many national jurisdictions have resisted calls for increased protection.

The toxicology of microcystin-LR: occurrence, toxicokinetics, toxicodynamics, diagnosis and treatment.

Cyanobacterial blooms occur worldwide and present an increasing problem due to eutrophication of lakes. Microcystins, especially microcystin-LR, are microcyclic heptapeptide hepatotoxins and are the most common and potent toxins associated with cyanobacteria. Microcystin is rapidly taken up by hepatocytes through carrier-mediated transport. Once in the hepatocyte, microcystin causes structural damage to the cell indirectly by inhibiting protein phosphorylases 1 and 2A, which are needed for regulation of structural proteins of the cell. Acute liver hemorrhage and death occur with high doses of microcystin-LR, which is also a potent tumor promoter in laboratory rats. The significance of microcystin to human health has been debated; however, poisoning in humans has occurred due to contaminated dialysis water. Microcystin in contaminated drinking water may be the cause of elevated rates of primary liver cancer in some areas of China. Problems with hepatotoxic cyanobacteria have been most seen in livestock. Treatment of confirmed microcystin toxicosis in livestock is likely to be unrewarding, so prevention is important. Wild mammals, birds, fish, insects, and microinvertebrates may also be affected by microcystin.

Deer health and disease.

This paper describes the most significant diseases of farmed deer which have emerged over the last 30 or so years. It describes their characteristic signs, how control measures have evolved, their current status and gives an indication of future diagnostic and control measures. Overall, it shows that wild deer brought into a farming environment have developed some of the production limiting diseases which affect sheep and cattle, such as parasitism and trace element deficiencies. In addition, farmed deer are susceptible to potentially fatal diseases such as tuberculosis, malignant catarrhal fever and yersiniosis. A disease which has recently emerged and has the potential to be more serious than any of the above is Johne's disease. In North America, Chronic Wasting Disease occurs in captive and wild deer in only two states but has the potential to be a serious threat to wild and farmed deer elsewhere if it spreads. The zoonotic risks of diseases affecting deer are discussed, as well as stress, welfare and deer restraint. The productivity of farmed deer can be maximised by using a well-designed deer health programme integrated with good management and feeding.

[Anesthesia and non-conventional transmissible agents (or prion diseases)]. / Anesthésie et agents transmissibles non conventionnels (ou maladies à prions).

The transmissible spongiform encephalopathies (TSE) represent a group of neurodegenerative diseases with lethal outcome. They include Creutzfeldt-Jakob disease (CJD) and kuru, among others in humans, scrapie in sheep and spongiform encephalopathy in cattle (bovine spongiform encephalopathy: BSE). Some are autosomal dominant disorders like CJD, Gerstmann-Straüssler-Scheinker disease (GSS), with point mutation of the prion protein gene. Most of these diseases are idiopathic rather than sporadic, latrogenic CJD could be obtained by central inoculation (neurosurgical instruments or dura mater grafts) or by peripheral inoculation (pituitary hormone therapy). A new variant clinicopathological type of CJD (nvCJD) has been reported. The nvCJD has strain characteristics distinct from other types of CJD, close to those of BSE transmitted (studies with intracerebral inoculation), consistent with BSE being the source of this new disease. All of these spongiform encephalopathies (SE) are characterized by spongiform degeneration of the brain, reactive gliosis in the cortical and subcortical gray matter, neuronal loss and presence of the abnormal isoform of the cellular prion protein (PrPc). In prion disease, PrPc undergoes conformational changes involving a shift from alpha-helix to beta-sheet structure. These neurologic lesions are characterized by major variations from case to case. Neuropathological studies in sporadic CDJ have emphasized phenotypic variations. Clinical presentation with a wide spectrum of manifestations is a rapidly progressive dementia, associated with myoclonus or akinetic mutism and cortical blindness. The clinical course is atypical and when the characteristic triphasic abnormal EEG of CJD is absent, there is an urgent need for a premortem diagnostic test. Histopathological examination of a brain biopsy carries a risk of major morbidity and may miss the site of disease. The 14-3-3 immunoassay of cerebrospinal fluid strongly supports a diagnosis of CJD. Western blot analysis of human tonsil biopsy may allow an early or preclinical diagnosis. It has been suggested that CJD might be transmitted by blood products derived from patients with CJD during the prodromal stage, although CJD linked aetiologically to blood transfusion has not been demonstrated. In animal studies, intracerebral inoculation of infected cells has been associated with development of disease, but never after peripheral inoculation into the blood stream. For the most part of conformational changes of PrPc, the remarkable resistance of the infectious agent (PrP alone or combined) to ordinary sterilising procedures is a major problem. Because of this resistance, current recommendations are to recognize patients at risks and to use disposable medical devices. This is particularly true in anaesthesia during endotracheal intubation, spinal anaesthesia, and to a lesser extent with peripheral nerve blocks. All instruments used for patients with CJD must be destroyed. The economic consequences of these measures have highlighted the essential importance of an early diagnosis.

Proctitis associated with chlamydial infection in a koala.

OBJECTIVE: To describe proctitis associated with chlamydial infection in a koala. DESIGN: A pathological study. ANIMAL: A free living, male koala aged 17 years. PROCEDURE: Rectum was examined histologically and chlamydial organisms visualised using Giminez' stain and an immunoperoxidase staining method using an anti-Chlamydia lipopolysaccharide (genus specific) antibody. RESULTS: An aged koala presented for euthanasia was found to have asymptomatic chronic proctitis, cystitis, prostatitis, urethritis and conjunctivitis associated with chlamydial infection. Inflammation was severe in the terminal rectum and extended into the proximal common vestibule. Chlamydial organisms were visualised in the rectal surface epithelium using Giminez' stain and an immunoperoxidase staining method. Organisms were also detected in the epithelium of the bladder, prostate and urethra. CLINICAL IMPLICATIONS: Possible modes of transmission for the rectal infection are direct sexual transmission or ascending infection by organisms shed from the urogenital tract into the common vestibule. Previously unreported chlamydial proctitis in the koala may represent a potential reservoir of infection for other koalas.

Pneumonic pasteurellosis associated with Pasteurella haemolytica in chipmunks (Tamias sibiricus).

A laboratory study was performed in order to identify the possible cause of death in chipmunks (Tamias sibiricus) imported from China with respiratory disease. Severe congestion, alveolar oedema and fibrinous pleuritis were observed. Biochemical analyses identified the causative organism as Pasteurella haemolytica. An in vitro susceptibility test using various antimicrobial agents revealed sensitivity to beta-lactams (ampicillin and amoxicillin) and streptomycin.

Pathology of stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Québec, Canada.

From June 1983 to May 1986, thirteen carcasses of stranded beluga whales from a polluted area of the St. Lawrence River, Canada were necropsied. High performance liquid chromatography was performed on the brains of three other animals to determine concentrations of benzo a pyrene (BaP). Two juvenile animals had severe multisystemic lesions one of which, a severe necrotizing dermatitis, was associated with a Herpesvirus-like particle. Four adults had five varieties of tumours. An adult had a systemic nocardiosis and a juvenile was affected ty a non 0:1 Vibrio cholerae septicemia. High concentrations of BaP adducts were found in the brains which were analyzed. Occurrence of BaP adducts in the brain of three whales of this population coincides with the high incidence of tumours. This and the previous finding of high concentrations of organochlorine in the tissues of these animals suggest an important role of industrial contaminants in the recent decrease of this population.

A review of wildlife diseases from Scandinavia.

The epidemiological and historical aspects of some important and representative wildlife diseases from Scandinavia are discussed. In noninfectious diseases, examples include cataract in moose (Alces alces), atherosclerosis in hybrid hares (Lepus timidus X L. europaeus), and ethmoid tumors in moose. The epizootiological and historical aspects of the recent epizootics of myxomatosis in European rabbits (Oryctolagus cuniculus) and rabies and sarcoptic mange in red foxes (Vulpes vulpes) are reviewed. The decline and subsequent increase in population abundances of tetraonids including the capercaillie (Tetrao urogallus), black grouse (Lyrurus tetrix), and hazel hen (Tetrastes bonasia) are discussed, and an hypothesis on predation by foxes is presented as a possible explanation for these population fluctuations. The potential impact of environmental pollution on wildlife populations is emphasized with reference to mercury in wildlife from Sweden and the possible effects of cadmium and selenium resulting from acidification. A bibliography of important references is presented pertaining to these and other diseases of wildlife from Scandinavia.