Intrabrain transplantation of chromaffin cell aggregates of the Zuckerkandl's organ, an extra-adrenal paraganglion that has never been tested for antiparkinsonian treatment, induced gradual improvement of functional deficits in parkinsonian rats. These beneficial effects were related to long survival of grafted cells, striatal reinnervation, and enhancement of dopamine levels in grafted striatum. Grafted cells were not dopaminergics, but they expressed glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-β1. These factors were detected in the host striatal tissue, indicating that chromaffin cells secreted them after grafting. Because glial cell line-derived neurotrophic factor possesses neurorestorative properties over dopaminergic neurons, and transforming growth factor-β1is a cofactor that potentiates the neurotrophic actions of GDNF, functional regeneration was likely caused by the chronic trophic action of neurotrophic factors delivered by long-surviving grafted cells. This work should stimulate research on the clinical applicability of transplants of the Zuckerkandl's organ in Parkinson's disease.
Normal in vitro thyroid peroxidase (TPO) iodide oxidation activity was completely inhibited by a hydrolyzed TPO preparation (0.15 mg/ ml) or hydrolyzed bovine serum albumin (BSA, 0.2 mg/ml). A pancreatic hydrolysate of casein (trypticase peptone, 0.1 mg/ml) and some amino acids (cysteine, tryptophan and methionine, 50 µM each) also inhibited the TPO iodide oxidation reaction completely, whereas casamino acids (0.1 mg/ml), and tyrosine, phenylalanine and histidine (50 µM each) inhibited the TPO reaction by 54% or less. A pancreatic digest of gelatin (0.1 mg/ml) or any other amino acid (50 µM) tested did not significantly decrease TPO activity. The amino acids that impair iodide oxidation also inhibit the TPO albumin iodination activity. The inhibitory amino acids contain side chains with either sulfur atoms (cysteine and methionine) or aromatic rings (tyrosine, tryptophan, histidine and phenylalanine). Among the amino acids tested, only cysteine affected the TPO guaiacol oxidation reaction, producing a transient inhibition at 25 or 50 µM. The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM, while no such effect was observed when the cofactor (H 2 O 2 ) concentration was increased. The inhibitory substances might interfere with the enzyme activity by competing with its normal substrates for their binding sites, binding to the free substrates or reducing their oxidized form.
Spreading Depression (SD) is an answer of the nervous tissue to a different type of local stimulus. The knolled of this phenomenon is fundamental for the correct treatment migraine .We analyze the effects of antiepileptic drugs, on the spreading depression (SD) in isolated retina of chick'. We studied five drugs with proven effect on GABAergic transmission: Topiramate, Valproate semisodium, Gabapentin, Lamotrigine and Levetiracetam. Chicks´retinas were kept in superfusion chamber, with Ringer's reference solution. the amplitude, the deflagration threshold (after chemical stimulus with KCl-) and the absolute refractory period of the SD, with and without the drugs were analyzed. Subsequently, the speed and amplitude parameters, also with and without the drugs, were analyzed in vivo . In addition, the GABA-transaminase enzyme activity was determined. Analysis of variance was used to determine the activity of GABA-transaminase.We verified that all the drugs, particularly Topiramate reduce the speed and amplitude in a dose-dependent and reversed manner, in vitro as well as in vivo. All the drugs also increase, in a reversible form, the deflagration threshold for the SD, after chemical stimulus with KC-, in specific concentrations. It was also verified, that all the drugs increase, in a reversible form, the absolute refractory period. Topiramate was considered the most effective drug. The enzyme GABA-transaminase displayed slight decrease activity.These results reinforce the notion that SD is a subjacent and relevant factor for the pathophysiology of migraine . the treatment of this pathology must emphasizes the use of antiepileptic drugs, in special Topiramate.
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