scholarly journals Cardiac Myosin Autoimmunity in Acute Chagas' Heart Disease

2001 ◽  
Vol 69 (9) ◽  
pp. 5643-5649 ◽  
Author(s):  
Juan S. Leon ◽  
Lisa M. Godsel ◽  
Kegiang Wang ◽  
David M. Engman
Keyword(s):  
Chronic Phase ◽  
Delayed Type Hypersensitivity ◽  
Cardiac Myosin ◽  
Susceptible Host ◽  
Specific Antibodies ◽  
Chagas Heart Disease ◽  
Brazil Strain ◽  
Low Levels ◽  
Stimulation Of

ABSTRACT Infection with Trypanosoma cruzi, the agent of Chagas' disease, may induce antibodies and T cells reactive with self antigens (autoimmunity). Because autoimmunity is generally thought to develop during the chronic phase of infection, one hypothesis is that autoimmunity develops only after long-term, low-level stimulation of self-reactive cells. However, preliminary reports suggest that autoimmunity may begin during acute T. cruzi infection. The goal of the present study was to investigate whether cardiac autoimmunity could be observed during acute T. cruziinfection. A/J mice infected with the Brazil strain of T. cruzi for 21 days developed severe myocarditis, accompanied by humoral and cellular autoimmunity. Specifically, T. cruziinfection induced immunoglobulin G (IgG) autoantibodies and delayed type hypersensitivity (DTH) to cardiac myosin. This autoimmunity resembles that which develops in A/J mice immunized with myosin in complete Freund's adjuvant in that myosin-specific antibodies and DTH responses both develop by 21 days postinfection or postimmunization. While the levels of myosin IgG in T. cruzi-infected mice were slightly lower than those in myosin-immunized mice, the magnitude of myosin DTH in the two groups was statistically equivalent. In contrast, C57BL/6 mice, which are resistant to myosin-induced myocarditis and its associated autoimmunity, developed undetectable or low levels of myosin IgG and did not exhibit myosin DTH or myocarditis upon T. cruzi infection. Therefore, humoral and cellular cardiac autoimmunity can develop during acute T. cruziinfection in the genetically susceptible host.

scholarly journals Modulation of Autoimmunity by Treatment of an Infectious Disease

2007 ◽  
Vol 75 (7) ◽  
pp. 3641-3650 ◽  
Author(s):  
Kenneth V. Hyland ◽  
Juan S. Leon ◽  
Melvin D. Daniels ◽  
Nick Giafis ◽  
LaKitta M. Woods ◽  
...  
Keyword(s):  
Central America ◽  
Antibody Production ◽  
Virulent Strain ◽  
Chronic Phase ◽  
Parasite Load ◽  
Autoimmune Response ◽  
Delayed Type Hypersensitivity ◽  
Cardiac Myosin ◽  
Chagas Heart Disease ◽  
Brazil Strain

ABSTRACT Chagas’ heart disease (CHD), caused by the parasite Trypanosoma cruzi, is the most common form of myocarditis in Central America and South America. Some humans and experimental animals develop both humoral and cell-mediated cardiac-specific autoimmunity during infection. Benznidazole, a trypanocidal drug, is effective at reducing parasite load and decreasing the severity of myocarditis in acutely infected patients. We hypothesized that the magnitude of autoimmunity that develops following T. cruzi infection is directly proportional to the amount of damage caused by the parasite. To test this hypothesis, we used benznidazole to reduce the number of parasites in an experimental model of CHD and determined whether this treatment altered the autoimmune response. Infection of A/J mice with the Brazil strain of T. cruzi leads to the development of severe inflammation, fibrosis, necrosis, and parasitosis in the heart accompanied by vigorous cardiac myosin-specific delayed-type hypersensitivity (DTH) and antibody production at 21 days postinfection. Mice succumbed to infection within a month if left untreated. Treatment of infected mice with benznidazole eliminated mortality and decreased disease severity. Treatment also reduced cardiac myosin-specific DTH and antibody production. Reinfection of treated mice with a heart-derived, virulent strain of T. cruzi or immunization with myosin led to the redevelopment of myosin-specific autoimmune responses and inflammation. These results provide a direct link between the levels of T. cruzi and the presence of autoimmunity and suggest that elimination of the parasite may result in the reduction or elimination of autoimmunity in the chronic phase of infection.

scholarly journals A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization with Trypanosoma cruzi Proteins

2004 ◽  
Vol 72 (6) ◽  
pp. 3410-3417 ◽  
Author(s):  
Juan S. Leon ◽  
Melvin D. Daniels ◽  
Krista M. Toriello ◽  
Kegiang Wang ◽  
David M. Engman
Keyword(s):  
Trypanosoma Cruzi ◽  
Protozoan Parasite ◽  
Autoimmune Response ◽  
Delayed Type Hypersensitivity ◽  
Cardiac Myosin ◽  
Cardiac Damage ◽  
Cardiac Inflammation ◽  
Skeletal Myosin ◽  
Chagas Heart Disease ◽  
Fatal Cardiomyopathy

ABSTRACT Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease, a potentially fatal cardiomyopathy prevalent in Central and South America. Infection with T. cruzi induces cardiac myosin autoimmunity in susceptible humans and mice, and this autoimmunity has been suggested to contribute to cardiac inflammation. To address how T. cruzi induces cardiac myosin autoimmunity, we investigated whether immunity to T. cruzi antigens could induce cardiac myosin-specific autoimmunity in the absence of live parasites. We immunized A/J mice with a T. cruzi Brazil-derived protein extract emulsified in complete Freund's adjuvant and found that these mice developed cardiac myosin-specific delayed-type hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac damage. The induction of autoimmunity was specific since immunization with extracts of the related protozoan parasite Leishmania amazonensis did not induce myosin autoimmunity. The immunogenetic makeup of the host was important for this response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization with T. cruzi extract. Perhaps more interesting, mice immunized with cardiac myosin developed T. cruzi-specific DTH and antibodies. This DTH was also antigen specific, since immunization with skeletal myosin and myoglobin did not induce T. cruzi-specific immunity. These results suggest that immunization with cardiac myosin or T. cruzi antigen can induce specific, bidirectionally cross-reactive immune responses in the absence of detectable cardiac damage.

Planning Micronutrient-Dense Menus in Ontario Long-Term Care Homes: Strategies and Challenges

2020 ◽  
Vol 81 (4) ◽  
pp. 198-203
Author(s):  
Lisa M. Duizer ◽  
Heather H. Keller
Keyword(s):  
Small Volume ◽  
Long Term Care ◽  
Term Care ◽  
Dietary Reference Intakes ◽  
Portion Sizes ◽  
Calcium Magnesium ◽  
Micronutrient Malnutrition ◽  
Low Levels ◽  
Food Consumed

Prevalence of micronutrient malnutrition is high in individuals living in long-term care (LTC) homes with many individuals consuming low levels of vitamins B6, D, and E; folate; calcium; magnesium; and zinc. The focus of this research was to identify strategies and challenges encountered during development of micronutrient-dense menus for use in Ontario LTC homes and to examine costs associated with development of a menu with acceptable micronutrients. Semi-structured open-ended interviews were conducted with 13 menu planners (7 dietitians, 6 nutrition managers) in diverse LTC homes in Ontario. Data were thematically analyzed. A 7-day hypothetical menu meeting all nutrient requirements was developed and costed. Analysis of the interview data showed that menus are planned according to the Canada’s Food Guide (2007) and focus placed on Dietary Reference Intakes of protein, fibre, calcium, and sodium. Little focus is placed on micronutrients. Flexibility in foods offered was important to accommodate the small volume of food consumed. Resident preferences were balanced against nutritional requirements. Challenges included planning for diverse populations, managing portion sizes, and balancing the budget. A hypothetical menu planned to contain adequate levels of all micronutrients is 49% higher in food costs than the amount currently provided to Ontario LTC homes.

Deep brain stimulation of the posterior limb of the internal capsule in the treatment of central poststroke neuropathic pain of the lower limb: case series with long-term follow-up and literature review

2020 ◽  
Vol 133 (3) ◽  
pp. 830-838 ◽  
Author(s):  
Andrea Franzini ◽  
Giuseppe Messina ◽  
Vincenzo Levi ◽  
Antonio D’Ammando ◽  
Roberto Cordella ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Lower Limb ◽  
Internal Capsule ◽  
Posterior Limb ◽  
Vas Score ◽  
The Mean ◽  
Deep Brain ◽  
Stimulation Of

OBJECTIVECentral poststroke neuropathic pain is a debilitating syndrome that is often resistant to medical therapies. Surgical measures include motor cortex stimulation and deep brain stimulation (DBS), which have been used to relieve pain. The aim of this study was to retrospectively assess the safety and long-term efficacy of DBS of the posterior limb of the internal capsule for relieving central poststroke neuropathic pain and associated spasticity affecting the lower limb.METHODSClinical and surgical data were retrospectively collected and analyzed in all patients who had undergone DBS of the posterior limb of the internal capsule to address central poststroke neuropathic pain refractory to conservative measures. In addition, long-term pain intensity and level of satisfaction gained from stimulation were assessed. Pain was evaluated using the visual analog scale (VAS). Information on gait improvement was obtained from medical records, neurological examination, and interview.RESULTSFour patients have undergone the procedure since 2001. No mortality or morbidity related to the surgery was recorded. In three patients, stimulation of the posterior limb of the internal capsule resulted in long-term pain relief; in a fourth patient, the procedure failed to produce any long-lasting positive effect. Two patients obtained a reduction in spasticity and improved motor capability. Before surgery, the mean VAS score was 9 (range 8–10). In the immediate postoperative period and within 1 week after the DBS system had been turned on, the mean VAS score was significantly lower at a mean of 3 (range 0–6). After a mean follow-up of 5.88 years, the mean VAS score was still reduced at 5.5 (range 3–8). The mean percentage of long-term pain reduction was 38.13%.CONCLUSIONSThis series suggests that stimulation of the posterior limb of the internal capsule is safe and effective in treating patients with chronic neuropathic pain affecting the lower limb. The procedure may be a more targeted treatment method than motor cortex stimulation or other neuromodulation techniques in the subset of patients whose pain and spasticity are referred to the lower limbs.

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