[Prions, infections and confusions in the "transmissible" spongiform encephalopathies. The other evidence-based science. III. Review]. / Priones, infecciones y confusiones en las encefalopatías espongiformes "trasmisibles". Ciencia basada en la otra evidencia III. Revisión.

There are some neurological disorders with a pathological hallmark called spongiosis which include Creutzfeld-Jakob disease and its new variant, the Gertsmann-Straussler-Scheinker Syndrome and the Fatal Familial Insomnia in humans; and Scrapie and Bovine Spongiform Encephalopathy, among others, in animals. The etiological agent has been considered either transmissible or hereditary or both. Curiously, this agent has no nucleic acids, is impossible to filter, is resistant to inactivation by chemical means, has not been cultured and is unobservable at electron microscopy. All of these facts have led to some researches to claim that these agents are similar to viruses appearing in computers. However, after almost fifty years of research, is still not possible to explain why and how such elements produce the diseases commented about. On the contrary, during these years have been possible to know that these entities called slow viral infections, transmissible amyloidosis, transmissible dementia, transmissible spongiform encephalopathies or prion diseases appear in individuals with genetical predispositions exposed to several worldwide immunological stressors. The possibility that prions are the consequence and not the cause of these diseases in animals and man is day by day more reliable, and supports the suggestion that a systematic intoxication due to pesticides as well as mycotoxin ingestion, produced mainly by different molds such as Aspergillus, Penicillium or Fusarium, seem to be the true etiology of these neurodegenerative disorders.

[The infectiousness of 18- to 20-kd proteins isolated from the brain of people who have died from amyotrophic leukospongiosis]. / Infektsionnost' belkov 18--20 kd, vydelennykh iz mozga liudei, umershikh ot amiotroficheskogo leikospongioza.

Specific globular structures, 10-12 nm in diameter, having a high resistance to various physicochemical factors and infectivity have been isolated for the first time from the brain of 2 patients, who died of amyotrophic leukospongiosis (AL). It has been shown that these globules contain infectious major protease-resistant protein with a molecular weight of about 18-20 kD. The findings indicate the unique nature of a disease and they open new aspects of AL etiopathogenesis.

[The induction by the influenza virus A/H1N1 (serovariant Hsw1N1) and its glycoproteins of congenital pathology in mice]. / Induktsiia virusom grippa A/H1N1 *serovariant Hsw1N1) i ego glikoproteidami vrozhdennoi patologii u myshei.

Influenza A/H1N1 (serovariant Hsw1N1) virus, a sum of isolated glycoproteins, separately neuraminidase "heads", inoculated into white random-bred female mice, induced in some of the offsprings the pathology clinically and pathomorphologically similar to previously described slow virus infection. At the same time, the pathology in the offsprings caused by the antigenic virus variant under study was characterized by complete absence of fur and more dynamic progress of the disease. It is quite obvious that glycoproteins, particularly neuraminidase, are the molecular biological basis of dystrophic and degenerative changes in the organs of baby mice due to desialization and increased fluidity of capillary endothelium membranes and, possibly, CNS and other organ cells.

Spongiform encephalopathies in Cervidae.

The known host range of naturally-occurring transmissible spongiform encephalopathies has expanded in recent years to include wild ruminants. Chronic wasting disease (CWD) occurs in mule deer (Odocoileus hemionus hemionus) and Rocky Mountain elk (Cervus elaphus nelsoni) in Colorado and Wyoming, United States of America. These species belong to the family Cervidae. Cases have occurred primarily in captive animals but a few affected free-ranging animals have been identified. Clinical disease in both species is characterised by progressive weight loss, behavioural alterations and excessive salivation. In deer polydipsia and polyuria also commonly occur. Significant lesions are confined to the central nervous system and consist of spongiform change in grey matter, intraneuronal vacuolation, astrocytosis and amyloid plaques. Inflammatory reaction is absent. The origin of this disease is not known. In contrast to the cases of spongiform encephalopathy recognised in five species of antelope (family Bovidae) in British zoological parks, which are an extension of the current bovine spongiform encephalopathy epizootic, CWD is not the result of food-borne exposure to the infectious agent. CWD appears to be maintained within captive populations by lateral and, possibly, maternal transmission. Spongiform encephalopathies in wild ruminants are currently geographically isolated and involve relatively small numbers of animals. However, these potentially transmissible diseases could be of greater importance in the future and should be viewed with concern in the light of international movements of wild ruminants and the current expansion of the game farming and ranching industry in many parts of the world.

Scrapie-like encephalopathy in a greater kudu (Tragelaphus strepsiceros) which had not been fed ruminant-derived protein.

A 19-month-old greater kudu (Tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. No macroscopic abnormalities were detected on post mortem examination but a scrapie-like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. Negative stain electron microscopy of proteinase K-treated detergent extracts of tissue from the brain stem revealed the presence of scrapie associated fibrils, and a 25 to 28 kDa band comparable with that identified as abnormal PrP (prion protein) from the brains of domestic cattle with spongiform encephalopathy was detected using rabbit antiserum raised against mouse PrP. The animal was born nine months after the statutory ban on the inclusion of ruminant-derived protein in ruminant feeds and, as no other possible sources of the disease were apparent, it appears likely that the infection was acquired from the dam.

Correlation between milk and dairy product consumption and multiple sclerosis prevalence: a worldwide study.

Multiple sclerosis (MS) epidemiology suggests that different factors are involved in the clinical expression of the disease. Alimentary cofactors have already been considered, but mainly theoretically. We have studied the relationship between MS prevalence and dairy product consumption in 27 countries and 29 populations all over the world, with Spearman's correlation test. A good correlation between liquid cow milk and MS prevalence (rho = 0.836) was found; this correlation was highly significant (p < 0.001). A low but still significant correlation was obtained with cream or butter consumption (rho = 0.619 and rho = 0.504, respectively). No correlation was found for cheese. These results suggest that liquid cow milk could contain factor(s) - no longer present in the processed milk - influencing the clinical appearance of MS. The possible role of some dairy by-products is discussed in the light of a multifactorial etiology of MS.

Prions / Prions

Os autores se propöem a revisar alguns aspectos básicos sobre os prions, alertando sobre a possível participaçäo destes na etiología de algumas enfermidades degenerativas do sistema nervoso

Human and experimental spongiform encephalopathies: recent progress in pathogenesis.

The spongiform encephalopathies belong to the group of "slow virus infections" of the nervous system, characterized by a long incubation period, a protracted course and involvement of the nervous system with a lethal outcome. In contrast to the conventional virus infections, such as visna in sheep and progressive multifocal leukoencephalopathy (PML) in humans, the etiological agent for the spongiform encephalopathies has not been clearly defined. The known forms in animals are scrapie in sheep and goats, transmissible mink encephalopathy, and chronic wasting disease of mule deer and elk. In humans, the three known forms are Kuru, now mainly of historical interest, Creutzfeldt-Jakob (CJ) disease and the syndrome of Gerstmann-Straussler-Scheinker (GSS). An important feature of these diseases is the lack of an immune response by the host, which is reflected in the absence of inflammatory infiltrates in the affected tissues. In this editorial the two most important hypotheses on the etiology and pathogenesis of this group of conditions will be discussed. The "prion" hypothesis considers the possibility that a protein, derived from a normal component of the neuronal membranes may have a leading role, not only in the infectivity and transmissibility of these diseases, but in the pathological changes that ensue. A single host gene would code for both the normal and altered proteins. The altered protein would be partially insoluble and would result in the deposition of fibrils and rods which would precipitate in the form of amyloid. Since the involved protein would be coded for by the host, there would be no immune response against it.(ABSTRACT TRUNCATED AT 250 WORDS)

Bovine spongiform encephalopathy: epidemiological studies on the origin.

The results of further epidemiological studies of bovine spongiform encephalopathy (BSE) support the previous findings that the onset of exposure of the cattle population to a scrapie-like agent, sufficient to result in clinical disease, occurred in 1981/82. The onset of this exposure was related to the cessation, in all but two rendering plants, of the hydrocarbon solvent extraction of fat from meat and bone meal. A further possible explanation, related to the geographical variation in the reprocessing of greaves to produce meat and bone meal, was identified for the geographical variation in the incidence of BSE.

The nutritional contribution to bovine spongiform encephalopathy.

Evidence that changes in feeding style alter the membrane fatty acid composition of ruminant tissue is presented here by comparing zoo giraffe with the same species from their natural habitat. The membrane changes seen are similar to those used experimentally to make animals susceptible to basic brain protein and encephalomalacia. Similar membrane responses have been noted in cattle. Use of animal protein and increased nitrogen in cattle feeds would lead to a relative deficiency of essential fatty acids in the cell membranes and hence reduced membrane stability. By analogy with crazy chick disease (nutritional encephalomalacia) and experimental encephalomyelitis in rats, the possibility that the changes in animals feeds would have depleted cattle tissue membranes and made them susceptible to BSE is discussed. The assumption being made is that the principle of a requirement of essential fatty acids for neural integrity and immune system function would apply to cattle as well as to other species.

Bovine spongiform encephalopathy--a new disease transmissable to humans?

Current concerns about the cattle disease bovine spongiform encephalopathy do not appear to take cognisance of the parallel with scrapie, the similar/identical disease of sheep/goats. This has existed for 200 years, and clearly involved a longstanding consumption of meat/offal from affected animals, but apparently without consequential human disease. A summary is given of the characteristics of the human and animal spongiform encephalopathy diseases and their causative agents. The conclusion of the official Southwood Report that the bovine disease is caused by the inclusion of sheep scrapie material in cattle fodder is critically discussed: an alternative mechanism is proposed for its emergence.