The localizations of carnosine, nerve growth factor (NGF) receptor and tyrosine hydroxylase (TH) were studied in the embryonic and postnatal rat olfactory bulb and epithelium by means of single- and double-immunostaining methods. Tyrosine hydroxylase ontogeny was also evaluated at the mRNA level by in situ hybridization. All these molecules were expressed in the olfactory bulb but with different developmental patterns and cellular localization: carnosine immunoreactivity is seen from embryonic day 17 in primary olfactory neurons scattered in the nasal cavity and in fibres projecting from them to the olfactory bulb. Nerve growth factor-receptor immunoreactivity associated with small glial-like cells is visible in some glomeruli starting from the second day of postnatal life. At postnatal day 10 NGF-receptor immunoreactivity is extended to all glomeruli. Periglomerular neurons expressing TH mRNA and protein are present prenatally and their number sharply increases during the early postnatal development. Double-staining methods show that TH and NGF-receptor immunoreactivity do not overlap in cell bodies and processes. In addition, NGF-receptor immunoreactivity is not colocalized with carnosine. These findings definitely exclude NGF-receptor expression in periglomerular and primary olfactory neurons, suggesting that at least part of NGF-receptor expression in the olfactory bulb is associated with glial cells. In addition, they provide the first immunohistochemical data on carnosine ontogeny and confirm at the mRNA level previous studies on the ontogeny of TH protein.

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PubMedDate not supplied

Efficacy, tolerability, and effects on quality of life of inhaled salmeterol and oral theophylline in patients with mild-to-moderate chronic obstructive pulmonary disease. SLMT02 Italian Study Group.

The aims of management in mild-to-moderate stable chronic obstructive pulmonary disease (COPD) are to improve symptoms and quality of life (QOL), reduce decline in lung function, prevent and treat complications, increase survival while maintaining QOL, and minimize the adverse effects of treatment. Bronchodilator therapy is the keystone of improving COPD symptoms and functional capacity. The primary objective of this open-label study was to compare the efficacy and tolerability of salmeterol 50 microg BID administered by metered-dose inhaler versus oral, titrated, sustained-release theophylline BID, both given for 3 months to patients with a clinical history of chronic bronchitis. The secondary objectives of the study were to evaluate the safety profile of the two drugs for an additional 9-month period and to assess changes in QOL both within and between treatment groups, using the 36-Item Short Form (SF-36) Health Survey. One hundred seventy-eight outpatients (122 men, 56 women; mean age, 56 +/- 12.9 years; mean body weight, 76.1 +/- 11.8 kg) were randomized to the two treatment groups. Patients receiving salmeterol showed significant improvement in mean morning peak expiratory flow rate (16.56 L/min) over the 3-month period compared with patients receiving theophylline (P = 0.02). Salmeterol also significantly increased the percentage of symptom-free days and nights with no additional salbutamol requirement (P < 0.01). A significant difference was found between increases in forced expiratory volume in 1 second compared with baseline for salmeterol compared with theophylline throughout the initial 3-month period (0.13, 0.16, and 0.16 L at months 1, 2, and 3, respectively) and during the additional 9 months. The incidence of adverse events was similar in the two groups (salmeterol, 49.5%; theophylline, 49.4%), with a lower percentage of pharmacologically predictable adverse events in patients receiving salmeterol (4%) compared with those receiving theophylline (14.8%). Both drugs improved QOL, as measured by effects on the eight aspects of life experience analyzed by the SF-36 questionnaire. Salmeterol therapy was effective in more aspects, and the improvements seen in each were numerically greater than those seen with theophylline therapy. Statistically different changes between the two treatment groups were reported for physical functioning, changes in health perception, and social functioning (P = 0.02, P = 0.03, and P = 0.004, respectively). These data suggest that inhaled salmeterol 50 microg BID was more effective and better tolerated than oral, titrated theophylline and allowed better long-term control of airways obstruction and symptoms with improved lung function in patients with COPD.

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PubMedDate not supplied

Inhibitory cerebellar circuits: GAD immunoreactivity in the frog cerebellum.

The presence of GABAergic structures in the frog cerebellum with simple nervous circuits was investigated with an immune serum raised against glutamic acid decarboxylase (GAD). GAD immunoreactivity is detectable in all the cerebellar layers. The most obvious difference in comparison with mammals is the scarcity of GAD-positive terminal boutons on Purkinje cells and this is consistent with neurophysiological data indicating that the inhibition on frog Purkinje cells is weaker than in mammals. However, there are numerous GAD synapses on cerebellar and vestibular nuclei. A large number of GAD immunoprecipitates are present in the molecular and granular layers, though their morphological organization is different from that in mammals. In the upper part of the molecular layer GAD immunoreactive cells and fibres form a plexus-like structure and in the internal granule layer immunoreactive varicosities are not arranged in the ring-like assemblies of mammals.

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