OSAS in children.

BACKGROUND: Major risk factors for obstructive sleep apnea syndrome (OSAS) in children include adenotonsillar hypertrophy, neuromuscular disease and syndromes such as Down's or Pierre-Robin's syndrome; there is currently no consensus concerning diagnosis and therapy. METHODS: The study analyses 40 children, aged 2 through 14 years, with macroscopic tonsillar hypertrophy (without recurrent tonsillitis but with OSAS) underwent adenotonsillectomy. Parents were invited to indicate the intensity of their children's symptomatology using a subjective evaluation scale, each patient underwent cephalometric analysis and polysomnography (PSG) before and after surgery. RESULTS: The subjective scale of symptoms passed from 3.01 before treatment to 0.42 after treatment, rhinomanometry, passed from 3.456 to 0.896 p after 1 month the surgical operation (P<0.05). The polysomnography showed a resolution of the number of obstructive events in 37 patients and a reduction in 3 patients and RDI index fell from a mean of 26.9-2.6 after therapy. The average of oxygen saturation changed from 79% before treatment to 95% after therapy. CONCLUSIONS: Adenotonsillectomy plays a major role in the treatment of OSAS.

Betahistine dihydrochloride in the treatment of peripheral vestibular vertigo.

The present study compares the efficacy and safety of betahistine dihydrochloride to that of a placebo in recurrent vertigo resulting from Meniere's disease (MD) or in paroxysmal positional vertigo (PPV) of probable vascular origin. The design was double-blind, multicentre and parallel-group randomised. Eleven Italian centres enrolled 144 patients: 75 of the patients were treated with betahistine (41 MD/34 PPV) and 69 with placebos (40 MD/29 PPV). The betahistine dosage was 16 mg twice per day for 3 months. Compared to the placebo, betahistine had a significant effect on the frequency, intensity and duration of vertigo attacks. Associated symptoms and the quality of life also were significantly improved by betahistine. Both the physician's judgement and the patient's opinion on the efficacy and acceptability of the treatment were in agreement as to the superiority of betahistine. The effective and safe profile of betahistine in the treatment of vertigo due to peripheral vestibular disorders was confirmed.

Affinity binding of a vampire bat plasminogen activator to SEC resins.

DSPAalpha1 is a recombinant form of the vampire bat plasminogen activator which we have produced in mammalian cell culture. During the development of a recovery process for DSPAalpha1 we observed an unexpected binding interaction between this protein and several types of gel filtration chromatography resins. Under typical operating conditions using neutral pH buffers, we found that DSPA flows through the sizing resin and is fractionated, as expected, according to its molecular size. However, DSPA applied under certain acidic conditions (

Studies on the cytochrome P-450 catalyzed ring alpha-carbon oxidation of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

In vitro metabolic studies have established that rat liver cytochromes P-450IIB1 and P-450IA1 but not rabbit liver cytochrome P-450IIB4 catalyze the oxidation of the Parkinsonian inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the corresponding dihydropyridinium (MPDP+) and pyridinium (MPP+) species. Kinetic experiments with the most effective isozyme, cytochrome P-450IA1, indicate that the reaction proceeds at a moderate velocity [Vmax = 20.1 nmol/(min.nmol of P-450IA1)] and high Km (0.87 mM). Furthermore, kinetic deuterium isotope effect measurements provided DV and D(V/K) values of 2.99 and 1.04, respectively. A comparison with the corresponding values for the monoamine oxidase B (MAO-B) catalyzed reaction (4.37 and 9.35, respectively) suggests that either these enzymes catalyze the ring alpha-carbon oxidation of MPTP by different pathways or that the initial one-electron transfer to generate an aminium radical intermediate previously proposed for both enzyme systems is reversible in the case of MAO-B and irreversible in the case of cytochrome P-450IA1.

Deuterium isotope effect measurements on the interactions of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidase B.

Kinetic deuterium isotope effects for the noncompetitive, intermolecular monoamine oxidase B-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the corresponding 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+ were found to be 3.55 on Vmax and 8.01 on Vmax/Km with MPTP-6,6-d2 as the deuterated substrate. Similar values were obtained with MPTP-2,2,6-d4 and MPTP-CD3-2,2,6,6-d4. The deuterium isotope effect for the electrochemical oxidation of 1 mM MPTP-2,2,6,6-d4 was only 1.35. These results indicate that the monoamine oxidase B-catalyzed oxidation of this substrate may not proceed via a reaction pathway involving alpha-carbon deprotonation of an aminium radical intermediate. Isotope effect measurements also established that the rate of inactivation of monoamine oxidase B by MPTP is unaffected by replacement of the C-6 methylene protons with deuterons, but is retarded by replacement of the C-2 methylene protons (DKi = 1.9). The mechanism-based inactivation of monoamine oxidase B by MPTP, therefore, is likely to mediated by a species derived from the enzyme-generated 2,3-dihydropyridinium oxidation product.