T. gondii infection induces IL-1R dependent chronic cachexia and perivascular fibrosis in the liver and skeletal muscle.

Cachexia is a progressive muscle wasting disease that contributes to death in a wide range of chronic diseases. Currently, the cachexia field lacks animal models that recapitulate the long-term kinetics of clinical disease, which would provide insight into the pathophysiology of chronic cachexia and a tool to test therapeutics for disease reversal. Toxoplasma gondii (T. gondii) is a protozoan parasite that uses conserved mechanisms to infect rodents and human hosts. Infection is lifelong and has been associated with chronic weight loss and muscle atrophy in mice. We have recently shown that T. gondii-induced muscle atrophy meets the clinical definition of cachexia. Here, the longevity of the T. gondii-induced chronic cachexia model revealed that cachectic mice develop perivascular fibrosis in major metabolic organs, including the adipose tissue, skeletal muscle, and liver by 9 weeks post-infection. Development of cachexia, as well as liver and skeletal muscle fibrosis, is dependent on intact signaling through the type I IL-1R receptor. IL-1α is sufficient to activate cultured fibroblasts and primary hepatic stellate cells (myofibroblast precursors in the liver) in vitro, and IL-1α is elevated in the sera and liver of cachectic, suggesting a mechanism by which chronic IL-1R signaling could be leading to cachexia-associated fibrosis.

Eosinophilic Enteritis in Horses with Motor Neuron Disease.

BACKGROUND: Equine motor neuron disease (EMND) is a neuromuscular disorder that affects adult horses. Although EMND has been linked to vitamin E deficiency, its etiopathogenesis is poorly understood. OBJECTIVES: To describe clinical features, laboratory results, and postmortem findings in a series of young horses with motor neuron disease (MND). ANIMALS: A herd of 15 young Andalusian horses with weakness, weight loss, muscle atrophy, and muscle fasciculations related to restricted intake of green forage. METHODS: A case series is presented in which horses were subjected to a clinical examination and plasma vitamin E measurement. Five severely affected horses were euthanized for detailed postmortem examination. Muscle specimens were taken from the M. sacrocaudalis dorsalis medialis and the M. gluteus medius for histopathologic and morphometric evaluation. RESULTS: MND was diagnosed in 5 horses based on clinical signs, low serum levels of vitamin E (0.11 ± 0.05 mg/dL; normal range,: 0.3-1.5 mg/dL), changes in muscle histopathology (neurogenic atrophy), and spinal cord lesions (neuronal chromatolysis in ventral horns). An unexpected postmortem finding was the presence of intestinal inflammation (catarrhal enteritis, edema, and eosinophilic infiltrate) associated with the presence of giant ciliated protozoa in all of the horses. CONCLUSIONS: Although a mechanistic link could not be established, it is hypothesized that intestinal inflammation may have been involved in the decreased absorption of vitamin E, thus favoring the development of MND.

Characterization of a Sarcocystis neurona isolate from a Missouri horse with equine protozoal myeloencephalitis.

Little information is available about antigenic variation of Sarcocystis neurona isolated from horses with equine protozoal myeloencephalitis, nor is there much information available on the specific antibody pattern to S. neurona antigens of horses from different geographic regions where S. neurona isolates have been obtained. This communication reports on the characterization of a new S. neurona isolate, SN-MU1. The isolate was obtained from a 3-year old Thoroughbred that had asymmetrical neurological signs and localized skeletal muscle atrophy. This S. neurona isolate is similar to other S. neurona isolates by molecular analysis of the internal transcribed spacer (ITS-1) region and a random-amplified polymorphic DNA marker, but is phenotypically distinct from the other S. neurona isolates examined. Evaluation of the antibodies from the affected horse and immunohistochemical results suggested that antigenic variation of S. neurona can result in variable antibody-antigen reactivity observed in the S. neurona immunoblot test.

[Chronic trichinosis and neuromuscular diseases. Morphologic and pathogenetic aspects]. / Chronische Trichinose und neuromuskuläre Erkrankungen. Morphologische und pathogenetische Aspekte.

Muscle biopsies were carried out on five patients affected by a chronic neuromuscular disorder, mostly in the form of a spinal muscle atrophy. All patients had suffered from acute trichinellosis many years before, the interval between acute parasitic infection and the appearance of the slowly progressive neuromuscular syndrome being of 21, 13, 35, 26 and 16 years respectively. In biopsy specimens, morphological and enzyme-histochemical changes typical of a progressive neurogenic muscular atrophy were present; in addition, encapsulated but still living, enzyme-positive parasites and signs of focal myositis were detected. The possible pathogenetic correlations between the "chronic" trichinellosis and the "degenerative" neuromuscular disorder are discussed.