Efficacy of very-low-dose betamethasone on neurological symptoms in ataxia-telangiectasia.

BACKGROUND: Ataxia-telangiectasia (A-T) is a non-curable neurodegenerative disorder, associated with progressive neurological dysfunction, oculocutaneous telangiectasia, immunodeficiency, predisposition to cancer and radiosensitivity. A recent study documented improvement in neurological symptoms after a short-term therapy with betamethasone in patients with A-T. Aim of this study was to evaluate the minimum therapeutically effective dosage of betamethasone on neurological symptoms of A-T. METHODS: Six responsive patients with A-T, received two 20-day cycles of oral betamethasone at 0.01 and 0.03 mg/kg/day (10% and 30% of the previously used full dosage), each followed by a 20-day washout period. Clinical and laboratory evaluations were carried out at T0 and at the end of each cycle. Neurological assessment was performed through the Scale for the Assessment and Rating of Ataxia (SARA). The glucocorticoid-induced leucine zipper (GILZ) and glucocorticoid receptor (GR) RNA expression were evaluated before and during the trial through real-time PCR. RESULTS: SARA scores significantly improved in all patients at the dosage of 0.03 mg/kg/day. In particular, three patients exhibited an improvement in 5/8 variables and two patients of 7 and 8 variables, respectively. Furthermore, the clinical improvement was already evident after the lower dosage. The basal GILZ and GR RNA expression were significantly lower in patients than in controls. GILZ expression increased in all patients after the beginning of the therapy, whereas no correlation between GR and the response was found. CONCLUSION: Our data indicate that betamethasone is effective in A-T at a minimal dosage and that GILZ may be a useful biomarker of the clinical response. This study provides Class IIIA evidence that betamethasone at very low dosage is effective in improving neurological signs of patients affected with ataxia-telangiectasia.

In ataxia-teleangiectasia betamethasone response is inversely correlated to cerebellar atrophy and directly to antioxidative capacity.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by alterations of the A-T mutated (ATM) gene. Although A-T is a non-curable disease, we, previously, documented a clear improvement of cerebellar functions during a short-term betamethasone trial. The aim of this study was to define the underlying biochemical mechanism. METHODS: In six A-T patients receiving a short-term steroid therapy, intracellular glutathione (GSH) levels were evaluated with a colorimetric assay. The lipid peroxidation level and reactive oxygen species (ROS) production were evaluated using commercial assays. All the parameters were compared with the improvement of cerebellar functions expressed as delta (Delta) of the Scale for the Assessment and Rating of Ataxia (SARA). RESULTS: We observed an inverse correlation between Delta SARA and the severity of cerebellar atrophy and between the latter and basal GSH values. Four of the five patients with the highest Delta SARA also had the highest GSH values. Moreover, even though basal ROS values were comparable in patients and controls, in the only patient studied at different time-points of therapy, a remarkable reduction in ROS levels was documented. CONCLUSION: We suggest that antioxidative mechanisms play a role in favouring the improvement of cerebellar functions observed in A-T patients receiving a short-term betamethasone trial.

Absorption of phenolic acids in humans after coffee consumption.

Despite extensive literature describing the biological effects of polyphenols, little is known about their absorption from diet, one major unresolved point consisting of the absorption of the bound forms of polyphenols. In this view, in the present work we studied the absorption in humans of phenolic acids from coffee, a common beverage particularly rich in bound phenolic acids, such as caffeic acid, ferulic acid, and p-coumaric acid. Coffee brew was analyzed for free and total (free + bound) phenolic acids. Chlorogenic acid (5'-caffeoylquinic acid), a bound form of caffeic acid, was present in coffee at high levels, while free phenolic acids were undetectable. After alkaline hydrolysis, which released bound phenolic acids, ferulic acid, p-coumaric acid, and high levels of caffeic acid were detected. Plasma samples were collected before and 1 and 2 h after coffee administration and analyzed for free and total phenolic acid content. Two different procedures were applied to release bound phenolic acids in plasma: beta-glucuronidase treatment and alkaline hydrolysis. Coffee administration resulted in increased total plasma caffeic acid concentration, with an absorption peak at 1 h. Caffeic acid was the only phenolic acid found in plasma samples after coffee administration, while chlorogenic acid was undetectable. Most of caffeic acid was present in plasma in bound form, mainly in the glucuronate/sulfate forms. Due to the absence of free caffeic acid in coffee, plasma caffeic acid is likely to be derived from hydrolysis of chlorogenic acid in the gastrointestinal tract.

Diagnostic significance of the carcino-embryonal antigen in gynecologic neoplasia.

The carcino-embryonal antigen has been studied in 35 patients affected by malignant gynaecologic neoplasia (cervical, endometrial, vulval) and, for control, in 16 patients affected by small tumors of the genital area. In other 9 patients the day to day variability has been studied. Two determinants, before and after therapy were performed on every patient, and in many cases afterwards. The analysis of the results show the scarce reliability of the episodic C.E.A. determination of the plasma. The use of this parameter in the follow-up of malignant neoplasias gynaecologic can only be reserved in cases with high basic values and in which the therapy reduces the plasmic level significantly.