In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes.

Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations- 1 μM (10(-3) mol/m(3)), 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD). The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA]) was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance-expansion of Treg cells and lymphocyte apoptosis-was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog

Genetic Basis of Myocarditis: Myth or Reality?

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An intergenerational approach in the promotion of balance and strength for fall prevention: a mini-review

The risk of sustaining a fall is particularly high in children and seniors. Deficits in postural control and muscle strength either due to maturation, secular declines or biologic aging are two important intrinsic risk factors for falls. During life span, performance in variables of static postural control follows a U-shaped curve with children and seniors showing larger postural sway than healthy adults. Measures of dynamic postural control (i.e. gait speed) as well as isometric (i.e. maximal strength) and dynamic muscle strength (i.e. muscular power) follow an inverted U-shaped curve during life span, again with children and seniors showing deficits compared to adults. There is evidence that particularly balance and resistance training are effective in counteracting these neuromuscular constraints in both children and seniors. Further, these training regimens are able to reduce the rate of sustaining injuries and falls in these age groups. An intergenerational intervention approach is suggested to enhance the effectiveness of these training programs by improving compliance and increasing motivation of children and seniors exercising together. Thus, the objectives of this mini-review are: (1) to describe the epidemiology and etiology of falls in children and seniors; (2) to discuss training programs that counteract intrinsic fall risk factors by reducing the rate of falling, and (3) to present an intergenerational approach that has the potential to make training programs even more effective by including children and seniors together in one exercise group