Catecholamine receptor binding in rat kidney: effect of aging

Binding to several receptors was compared in kidneys from 3- and 24-month-old rats. In crude membrane preparations of aged rat kidneys, the number of beta 2-adrenergic receptors was significantly reduced but the number of total beta-adrenoceptors was unchanged. The high-affinity alpha 1-adrenoceptor component was significantly reduced in old rats, whereas the low-affinity component was unchanged. The number of alpha 2-adrenoceptors showed a non-significant decrease. 3H-spiperone binding sites were similar in young and old rats. For each receptor binding the KD values were the same in young and old animals. The D1 dopamine receptor was significantly reduced in old rats. In our experiments, age-related changes of specific binding sites in the kidney were selective for some receptors studied and did not seem to be due to general aging-induced membrane modifications. Moreover, the renal and central receptors were sensitive to aging differently in the same animal model.     

Tests for the determination of the effect of antimitotic products on immune reactions

The differences reported by various authors in regard to the inhibitory effect of the same antimitotic product on the production of antibodies, may be attributable in particular to the antigen used and to the technique of administration of the product. These differences have made it necessary to work out a test that is not subject to criticism in these respects.

After an investigation of the cytological reactions provoked in the mouse by various antigens, the authors have singled out three of these antigens: human albumin, the poliomyelitis virus and an allogeneic skin graft. The hyperbasophilic cells which are predominantly present in the lymphoid centres are, respectively, lymphocytes for the first, plasmocytes for the second and histiocytes for the third of these antigens.

In view of the different mechanisms of action that are possible with the different antimitotic products the authors used three methods of administration: entirely `before' the antigenic stimulus; total dose administered entirely `after' the antigenic stimulus; total dose administered partially `before' and partially `after' the antigenic stimulus.

     

The pathogenesis of molybdenum cofactor deficiency, its delay by maternal clearance, and its expression pattern in microarray analysis

Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease, for which until now no effective therapy is available. The biochemical hallmark of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which results in elevated sulfite and diminished sulfate levels throughout the organism. In humans, Moco-deficiency results in neurological damage, which is apparent in untreatable seizures and various brain dysmorphisms. We have recently described a murine model for Moco-deficiency, which reflects all enzyme and metabolite changes observed in the patients, and an efficient therapy using a biosynthetic precursor of Moco has been established in this animal model. We now analyzed these mice in detail and excluded morphological brain damage, while expression analysis with microarrays indicates a massive cell death program. This neuronal damage appears to be triggered by elevated sulfite levels and is ameliorated in affected embryos by maternal clearance.     

Anorectic effect of fenfluramine isomers and metabolites: Relationship between brain levels and in vitro potencies on serotonergic mechanisms

A study of the possible molecular mechanisms of action by which the isomers and metabolites of fenfluramine increase serotonin transmission, leading to anorectic activity, is presented. The actual brain levels of fenfluramine and norfenfluramine isomers after administration of equi-anorectic doses to rats are compared with their potencies in affecting serotonergic mechanisms in vitro. Isomers and metabolites of fenfluramine can have the same pharmacological action by influencing serotonin uptake, release and binding in a quantitatively different manner.     

Bilateral dental fusion of the upper central incisors: a multidisciplinary approach

The multidisciplinary treatment of a case of bilateral dental fusion of the upper central incisors with maxillary constriction, crowding, and palatal inversion of one of the lateral incisors is reported. The rarity with which this anomaly appears, along with its complex characteristics, often make it extremely difficult to treat. It requires the involvement of different specialists to find the most suitable treatment for each individual patient. CLINICAL SIGNIFICANCE: This particular case of bilateral dental fusion required the involvement of orthodontists, periodontists, endodontists, and restorative specialists. For the individual evaluation of these extremely complex cases, the esthetic and functional results to be reached must be assessed compared to treatment times and biologic and economical costs. The long-term prognoses of these complex therapies also must be borne in mind.