Effect of recombinant Lactococcus lactis producing myelin peptides on neuroimmunological changes in rats with experimental allergic encephalomyelitis.

Multiple sclerosis (MS) is a human autoimmune neurodegenerative disease with an unknown etiology. Despite various therapies, there is no effective cure for MS. Since the mechanism of the disease is based on autoreactive T-cell responses directed against myelin antigens, oral tolerance is a promising approach for the MS treatment.

Effect of oral administration of pig spinal cord hydrolysate on clinical and histopathological symptoms of experimental allergic encephalomyelitis in rats.

Oral tolerance is the natural occurring phenomenon of a decreased immune response to previously fed antigens, which prevents induction of a response to dietary antigens. One of the mechanisms is deletion of T lymphocytes reactive to the fed antigen. Knowing that phenomenon, it seems appropriate to engage this mechanism for treatment of autoimmune diseases.

Oral Administration of Lactococcus lactis Expressing Synthetic Genes of Myelin Antigens in Decreasing Experimental Autoimmune Encephalomyelitis in Rats.

Background: Multiple sclerosis is a human autoimmunological disease that causes neurodegeneration. One of the potential ways to stop its development is induction of oral tolerance, whose effect lies in decreasing immune response to the fed antigen. It was shown in animal models that administration of specific epitopes of the three main myelin proteins - myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and proteolipid protein (PLP) - results in induction of oral tolerance and suppression of disease symptoms.

NG2 positive cells of rat spinal cord activated during experimental autoimmune encephalomyelitis are spatially associated with radially oriented astroglia and express p75 receptor: a role for nerve growth factor in oligodendrocyte progenitor migration?

Data have been provided from several studies that support the proposal that the adult oligodendrocyte progenitors migrate into the lesioned areas under conditions of experimental autoimmune encephalomyelitis (EAE). However, the routes of migration of these cells and the governing mechanisms are not clear. In the present studies, we have examined the effect of EAE upon activation of endogenous oligodendroglia progenitors and their spatial distribution in the spinal cord of Lewis rats using immunocytochemical procedures.

Alterations in glutamate transport and group I metabotropic glutamate receptors in the rat brain during acute phase of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many aspects of multiple sclerosis (MS). In MS the immune system attacks the white matter of the brain and spinal cord, leading to disability and paralysis. Neurons, oligodendrocytes and myelin are lost due to the release of cytotoxic cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter glutamate.

Spinal cord hydrolysate ameliorate immunological reaction in experimental allergic encephalomyelitis.

The aim of this study was to use the hydrolysate of pig spinal cord proteins to induce oral tolerance in the animal model of sclerosis multiplex - experimental allergic encephalomyelitis. The female Lewis rats were fed with hydrolysate of pig spinal cord proteins in two doses for one week before immunization, which was induced by injection of guinea pig spinal cord homogenate. At the peak of clinical symptoms (the 13th day post immunization) the rats were sacrificed and the spleen removed.

Matrix metalloproteases activity and ultrastructural changes in the early phase of experimental allergic encephalomyelitis. The effect of oral treatment with spinal cord hydrolysate [correction of hydrolisate] proteins in Lewis rat. The pilot study.

Matrix metalloproteinases (MMPs) are a family of genes of the neutral proteinases that are important to normal development and to a variety of pathological processes including neuroinflammation. In the central nervous system (CNS), MMPs degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and contribute to the neuroinflammatory responses. Their concentration in experimental allergic encephalomyelitis (EAE) increases a few folds and is accompanied by a thinner basal membrane in the early phase of EAE.

Influence of spinal cord protein hydrolysate upon the blood brain barrier changes due to experimental allergic encephalomyelitis in Lewis rats. Ultrastructural study.

A specific protein (antigen) given orally is a known method of introducing tolerance of immunological response to this antigen. This method has recently been reviewed by some authors as a possible tool in the treatment of autoaggressive diseases, such as multiple sclerosis. The experimental allergic encephalomyelitis (EAE) respected animal model for MS was used for the study.

High-affinity NGF receptor in the rat spinal cord during acute and chronic phases of experimental autoimmune encephalomyelitis: a possible functional significance.

The biological effects of Nerve Growth Factor (NGF) are primarily mediated via its high affinity receptor-TrkA. In the present study, we examined the effect of experimental autoimmune encephalomyelitis (EAE) upon the expression of TrkA in neuronal and non-neuronal cells of the spinal cord of Lewis rats during the acute (14 days postimmunization) and chronic (12 months postimmunization) phases of the disease. In the normal spinal cord, both of mature and aged rats, we found TrkA immunoreaction (TrkA-IR) in the motoneurons of the Rexed lamina IX and in both oligo- and astroglia cells.

Protein hydrolysates for oral tolerance.

To induce oral tolerance in multiple sclerosis treatment, we proposed to use the predigested protein of pig spinal cord. The most biologically active composition was obtained from the hydrolysis of an undenaturated homogenate of proteins digested with pepsin. Feeding the rats with our preparation, before or after immunization with MS antigens, strongly reduced development of the experimental autoimmune encephalomyelitis (EAE).

Ultrastructural changes in the central and peripheral nervous system in the rat with experimental allergic encephalomyelitis.

The aim of the study was the evaluation of ultrastructural changes in rats central and peripheral nervous system after the introduction of experimental allergic encephalomyelitis (EAE) and after the treatment with spinal cord protein hydrolysate. Reduced structural disturbances in myelin were found after oral treatment with hydrolysate. In addition, the indications of remyelinization processes have been observed.

Pseudomonas aeruginosa exotoxin A enhances automaticity and potentiates hypoxic depression of isolated rat hearts.

The potent virulence factor exotoxin A, produced by Pseudomonas aeruginosa, has been reported to suppress the synthesis of the alpha-subunit of cardiac Gi protein and may have general effects upon synthesis of other myocardial proteins. To determine whether such exotoxin A actions influence specific functional properties of the intact heart, characteristics of isolated perfused hearts obtained from rats receiving injections of exotoxin A 48 hr before sacrifice were compared with those of rats receiving no exotoxin A. Exotoxin A treatment increased the spontaneous beating rates and potentiated the suppressive effects of hypoxia upon heart rate, left ventricular systolic pressure, and rates of ventricular contraction and relaxation.

Increased 19 kDa protein phosphorylation and protein kinase C activity in pressure-overload cardiac hypertrophy.

The aim of the study was to determine the role of protein kinase C (PKC) in protein phosphorylation in hypertrophied C. myocytes, particularly the phosphorylation of the 19 kDa protein which corresponds to myosin light chains. In myocardial hypertrophy the PKC activity in the cytosolic fraction of tissue homogenate was increased up to 253% of control hearts, and in membrane fraction up to 140% of the control value.

Effect of propranolol upon protein and proteolytic synthesis activity in hypertrophic myocardium.

The aim of the study was to investigate the effect of propranolol upon protein synthesis and degradation processes in cell-free subfractions of rat myocardium in experimental cardiac hypertrophy induced by aortic stenosis. It was found that hypertrophy stimulates incorporation of 3H-amino acids by the postmitochondrial supernatant (PMS) by 17 +/- 4% (mean +/- SE). Propranolol 10 6M inhibited protein synthesis in the control and experimental groups by 37 +/- 5% and 34 +/- 7%, respectively.

Effect of propranolol on the activity of neutral, alkaline and acidic proteases in rat myocardium after aortic stenosis.

The aim of the study was to investigate the effect of propranolol upon the activity of proteases in rat myocardium subjected to aortic stenosis. In acute heart hypertrophy induced by aortic stenosis, the activity of all three proteases in the myocardium does not change significantly. Propranolol in the concentration of 10(-6) to 2 X 10(-4) M inhibited proteolytic activity dependent on neutral proteases.

Increased synthesis of the phosphorylated form of the myosin light chains in cardiac hypertrophy in the rat.

The incorporation rate of [3H]leucine into cardiac myosin subunits was studied in rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. Cardiac myosin was prepared by a modified Shiverick's method on the second and fourth day after constriction. Myosin light chains were separated by urea and subjected to two-dimensional electrophoresis.

Low dose of acetylsalicylic acid prolongs refractory periods in normal cat myocardium.

The effect of acetylsalicylic acid (ASA, Aspisol) upon diastolic threshold and refractory period in normal myocardium was investigated in the experiments on cats. It has been found that ASA given in a dose of 7 mg/kg i.v.

Mitochondrial proliferation in cardiac hypertrophy.

Mitochondrial proliferation was studied in mature female rats following aortic constriction. Mitochondrial DNA (mtDNA) was assayed by a fluorometric method. The conditions for removal of nuclear DNA were developed and verified by assessment of molecular conformation of DNA.

Changes in mitochondrial DNA in cardiac hypertrophy in the rat.

We studied DNA (mtDNA) replication in adult female rat hearts undergoing hypertrophy secondary to constriction of the ascending aorta. MtDNA was measured in isolated mitochondria by a fluorometric method adapted for that purpose. The conditions for removal of contaminating nuclear DNA were developed, and the purity of the mtDNA was assessed from its molecular conformation (open and closed circles) and by renaturation-kinetic analysis.