R.M. Di Giorgio

RAGE‐NF‐κB pathway activation in response to oxidative stress in facioscapulohumeral muscular dystrophy

Objectives –  An increased expression of adenine nucleotide translocator (ANT1), found in facioscapulohumeral muscular dystrophy (FSHD), is known to lead to a decrease in nuclear factor‐κB (NF‐κB) DNA binding and to sensitize muscle cells to oxidative stress and apoptosis. Receptor for advanced glycation end products (RAGE) mediated by NF‐κB activation is involved in proinflammatory pathomechanism and in muscle fiber regeneration in inflammatory myopathies and in limb girdle muscular dystrophy. Oxidative stress can stimulate RAGE‐ NF‐κB pathway. Our purpose was to verify if oxidative stress may induce RAGE‐ NF‐κB pathway activation in FSHD, contributing to the pathogenesis of such a disease.

SUBCELLULAR DISTRIBUTION OF TAURINE AND CYSTEINE SULPHINATE DECARBOXYLASE ACTIVITY IN OX RETINA

Abstract– Taurine levels have been determined in primary and secondary subcellular fractions of ox retina and pigment epithelium.

Effects of Hyper- and Hypoprolactinemia on Glutamate Decarboxylase Activity in Medial Basal Hypothalamus of Male Rat

Haloperidol, sulpiride, domperidone and apomorphine, drugs which influence dopamine (DA) receptors and in turn prolactin (PRL) secretion have been shown to induce parallel changes in medial basal hypothalamic (MBH) glutamate decarboxylase (GAD) activity and serum PRL levels. The possibility that PRL may be involved in the effects of the drugs on MBH GAD activity is suggested in view of the evidence that hypophysectomy completely prevents drug-induced MBH GAD activity changes and that hyperprolactinemia by anterior pituitary homograft results in a significant, although small, change in the enzymatic activity.

Effects of l-DOPA on GABA metabolism in chick brain and retina

Abstract The effects of an oral subacute treatment with l -DOPA on GAD, GABA and GABA-T in chick n. basalis (homologous to the mammalian striatum), brain hemispheres, brain-stem and retina were studied. A significant increase in n. basalis GAD activity associated with an increase in GABA content and decrease of GABA-T activity was shown to occur. Similar effects were observed in the brain-stem except for GABA-T which was stimulated. In contrast, in brain hemispheres, l -DOPA produced a decrease in GAD and GABA-T activity. No changes, however, were observed in GAD activity at the retinal level, whereas GABA-T activity was significantly decreased and GABA content increased. In conclusion, the present experiments show that in some areas of the brain the administration of l -DOPA is able to affect GABA turnover.

Expression of transglutaminase 2 does not differentiate focal myositis from generalized inflammatory myopathies.

Objectives –  Idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), sporadic inclusion‐body myositis (s‐IBM) and focal myositis (FM) are a heterogeneous group of autoimmune disorders of skeletal muscle. An increased transglutaminase 2 (TG2) expression has been found in DM, PM and s‐IBM. The aim of our study was to investigate TG2 expression in FM in comparison with other IIM.

MicroRNA signatures predict dysregulated vitamin D receptor and calcium pathways status in limb girdle muscle dystrophies (LGMD) 2A/2B.

miRNA expression profile and predicted pathways involved in selected limb‐girdle muscular dystrophy (LGMD)2A/2B patients were investigated. A total of 187 miRNAs were dysregulated in all patients, with six miRNAs showing opposite regulation in LGMD2A versus LGMD2B patients. Silico analysis evidence: (1) a cluster of the dysregulated miRNAs resulted primarily involved in inflammation and calcium metabolism, and (2) two genes predicted as controlled by calcium‐assigned miRNAs (Vitamin D Receptor gene and Guanine Nucleotide Binding protein beta polypeptide 1gene) showed an evident upregulation in LGMD2B patients, in accordance with miRNA levels. Our data support alterations in calcium pathway status in LGMD 2A/B, suggesting myofibre calcium imbalance as a potential therapeutic target. Copyright

The localization of phenolic and tyrosyl ring thyroxine deiodination in rat and mouse retina.

To elucidate T(4) metabolism in various cell types of rat retina, 5-monodeiodinating and 5?-monodeiodinating activities were studied in retinal cell layers obtained by selective cytotoxic action of monosodium glutamate on bipolar and ganglion cell layers and by iodoacetate effect on photoreceptor cells. Concomitantly these enzyme activities were studied in C3H/HeN mouse retina genetically deprived of photoreceptor cells. Deiodinase activities were low in rat and mouse retina deprived of photoreceptors. The 5?-monodeiodination rate of T(4) was higher than T(4) tyrosyl ring deiodination in cell layers examined and the highest values were found in the photoreceptor cells. Data support the hypothesis that phenolic and tyrosyl ring deiodinase activities are present in the photoreceptor cells. Their reciprocal changes may regulate the nuclear function which in turn controls the rhythmical renewal of rod outer segments.

7. Effects of Intraventricular γ-Acetylenic-GABA on GABA Concentrations, GABA-T and GAD in Several Areas of the Chick Brain

The great interest in new compounds able to increase GABA concentration in the brain as potential antiepileptic drugs has led to the synthesis of powerful inhibitors of GABA transaminase (GABA-T) e.g. gamma-acetylenic GABA (GAG) and gamma-vinyl-GABA. Present experiments were aimed to study behavioral, electrocortical and biochemical effects of GAG after its intraventricular injection. It has been shown that in chicks the microinjection of GAG into the third cerebral ventricle produced a biphasic behavioral and electrocortical syndrome : an initial phase of behavioral and electrocortical sleep followed by a paradoxycal increase in motor activity and a very intense behavioral and ECoG arousal pattern. In addition intraventricular GAG (0.8 mumol) produced a significant increase 1 and 2 h later in GABA concentration in the diencephalon and brain-stem whereas no changes occurred in other brain areas e.g. cerebral hemispheres, optic lobes. Higher doses (1.6 mumol), produced after 1 h, concomitantly to the increased GABA concentration, a significant GABA-T inhibition and a profound inhibition of glutamate-decarboxylase in the diencephalon and brain-stem. Present experiments may explain the paradoxical behavioral, motor and electrocortical stimulation observed at the time of GABA increase concentration and suggest that a small functional neuronal pool of GABA, more than the whole absolute levels of GABA in a given area of the brain, seems to be involved in the control of GABAergic mediated inhibitory mechanisms.