Preclinical models of Parkinson's disease.

Parkinson's disease is a neurodegenerative disease in which pigmented midbrain neurons progressively die producing a dopamine (DA) deficit in the striatum which manifests as an akinetic movement disorder. Experimentally induced striatal DA depletion in animals is a valid model of parkinsonism. The capacity of certain substances to damage catecholaminergic neurones has been used for a long time to produce DA deficiency in animals.

Successful eradication of methicillin-resistant Staphylococcus aureus (MRSA) intestinal carrier status in a healthcare worker--case report.

We describe bacteriophage therapy in the case of a healthcare worker whose gastrointestinal tract was colonized by methicillin-resistant Staphylococcus aureus (MRSA) with subsequent urinary tract infection caused by the same pathogen. Oral treatment with anti-MRSA phages resulted in eradication of the carrier status.

Convection-enhanced delivery of adeno-associated virus type 2 (AAV2) into the striatum and transport of AAV2 within monkey brain.

Adeno-associated virus type 2 (AAV2)-based vectors are promising transgene carriers for experimental gene therapy treatments of brain diseases. However, detailed evaluation of transgene distribution, trafficking, and transport within the brain is of the utmost importance before applying any type of gene therapy in humans. We examined the distribution of AAV2-thymidine kinase (AAV2-TK) and AAV2-aromatic L-amino acid decarboxylase (AAV2-AADC) in monkey brain after convection-enhanced delivery (CED).

Preclinical models of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which pigmented midbrain neurons progressively die producing a dopamine (DA) deficit in the striatum, which manifests as an akinetic movement disorder. Experimentally induced striatal DA depletion in animals is a valid model of parkinsonism. The capacity of certain substances to damage catecholaminergic neurons has been used extensively to produce DA deficiency in animals.

Ultrastructural study of mother and daughter muscle changes with mitochondrial encephalomyopathy.

We present the light and electron microscopy examinations of skeletal muscle biopsies from a 36-year-old mother and her 13-year-old daughter with mitochondrial encephalomyopathies. Clinical signs and symptoms suggesting mitochondrial disease, such as disseminated neurological symptoms, visual and hearing disturbances, mental disability, exercise intolerance, heart conduction disturbances, short stature, family history, were present in both patients. The mother's niece (8 years old) also died with progressive neurological disorder.

Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach.

Using an approach that combines gene therapy with aromatic l-amino acid decarboxylase (AADC) gene and a pro-drug (l-dopa), dopamine, the neurotransmitter involved in Parkinson's disease, can be synthesized and regulated. Striatal neurons infected with the AADC gene by an adeno-associated viral vector can convert peripheral l-dopa to dopamine and may therefore provide a buffer for unmetabolized l-dopa. This approach to treating Parkinson's disease may reduce the need for l-dopa/carbidopa, thus providing a better clinical response with fewer side effects.

MHC class II positive microglia and lymphocytic infiltration are present in the substantia nigra and striatum in mouse model of Parkinson's disease.

We have studied MHC class II antigen expression and lymphocytic infiltration during dopaminergic neurone degeneration produced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP). Microglial activation was observed in the striatum and in the substantia nigra (SN) in this model. We noticed a marked increase of MHC class II antigen expression on microglia and T-cell recruitment in these regions after MPTP treatment.

The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine intoxication in mouse.

In degenerative disorders of the CNS an immune system involvement in the pathological process is postulated. The MPTP model of Parkinson's disease seem to be a good model for studying an inflammation following toxic neurodegeneration. In this model, microglial and astroglial reactions were previously found around impaired neurons.

Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

We have studied the reaction of glial cells in mice treated with an intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective neurotoxin of dopaminergic nigrostriatal neurons. Signs of injury to the dopaminergic neurons started on the 1st day after MPTP administration and progressed up to the end of the observation time (21st day). A transient microglial reaction was demonstrated from the 1st until the 14th day in the substantia nigra (SN) and striatum.

Microglial reaction in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced Parkinson's disease mice model.

We studied the microglial reaction in mice using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model for Parkinson's disease (PD). Microglial cells were identified by means of the Griffonia simplicifolia lectin (GSA-I-B4). Dopaminergic neurons were marked by tyrosine hydroxylase antibodies.

Cold water stress induced analgesia in unilateral inflammation of the hindpaw in hypertensive and normotensive rats.

Analgesia induced by cold water stress (CWS) was tested in the model of monolateral inflammation in spontaneously hypertensive (SHR), renal hypertensive (RHR) and normotensive Wistar (NR) and Wistar Kyoto (WKY) rats. Unilateral hind paw inflammation was induced by Freund's complete adjuvant (FCA). Four days after inoculation all tested rats exhibited profound analgesia following CWS in both inflamed and non-inflamed paws which reached a maximum immediately after CWS and returned to control values within 15 min.