Pharmacological characteristics and species-related variations of β3-adrenergic receptors

Summary— Beta-adrenergic receptors (β/-AR) belong to the large multigenic family of receptors coupled to GTP-binding proteins. Three subtypes have been identified: β₁-, β₂- and β₃-AR. Much of the work delineating the precise pharmacological comparison of the three β-ARs has come from investigations with stably transfected Chinese hamster ovary cells (CHO cells). This review discusses the structure and function of β₃-AR in various species and presents new findings on a number of β₃-AR ligands including carazolol, tertatolol and CL 316,243 which were found to be selective and potent β₃-AR agonists and ZD 2079 and salmeterol which appear to display full but non-subtype selective agonistic activity. Species-related variations of the β₃-AR pharmacology have been shown for propranolol and bupranolol. With the ongoing characterization of the β₃-AR at the molecular and cellular level, and with the advent of computer-assisted molecular modelling to aid in the determination of the three-dimensional structure of the receptor, it is thought that novel β₃-AR compounds will become available with improved selectivity and potency.     

Nasal IgA response in wheezy infants

It is unknown why some infants wheeze during upper respiratory tract infections. One possibility is that secretory IgA, which has a major role in mucosal defence against viral infection, might be deficient in wheezy infants. The nasal IgA response to upper respiratory tract infection in 32 wheezy infants (median age 5.8 months) was compared with nine siblings (median age 2.6 years) who had nasal symptoms only. Nasal lavage was performed during infections and on follow up when free from symptoms, using inulin as a marker of dilution to determine absolute concentrations of IgA in the nasal secretions. The two groups showed a similar increase in total IgA and total protein levels during infection, but secretory IgA concentrations were unchanged. This study shows that wheezy infants have a normal nasal IgA response to infection and that the increase in total IgA during early infection is due to plasma exudation rather than increased production of secretory IgA.     

Gestational age correction for height in preterm children to seven years of age

Correction for gestational age continues to make a difference to the height SD score (SDS) to the age of seven years in very preterm babies. The height SDS for children born at 28 weeks' gestation increased by 0.25 SDS when postconceptual age was used instead of real age. Extrapolating from these results, the effect of correction would be an increase of approximately 0.32 SDS for a seven-year-old of 24 weeks' gestation. Unsatisfactory growth may be masked by a steady or increasing real age SDS in a few children. The risks of stopping using postconceptual age at two or three years include both false confidence in genuine cases of growth retardation and misinterpretation of a decrease in height SDS as evidence of growth retardation. As the number of very preterm babies who survive increases so does the importance of these observations.     

Is Gd-DTPA required for routine cranial MR imaging?

Gadopentetate dimeglumine (gadolinium diethylenetriaminepentaacetic acid [DTPA]) was administered prospectively to 500 consecutive children and adults referred for routine cranial magnetic resonance (MR) imaging over a 4-month period. Pre- and postcontrast images were blindly and independently interpreted by two experienced neuroradiologists. Specific criteria were provided to the readers to define objectively when contrast material enhancement (or lack thereof) would be considered "radiologically helpful." Contrast-enhancing lesions were observed in 99 cases (20%). In only 15 cases (3%) did Gd-DTPA permit detection of lesions not also apparent on the precontrast studies. Contrast enhancement was considered radiologically helpful in 74 of the 99 cases. Lack of enhancement was considered helpful in 112 of the 500 cases (22%). Factors that may indicate increased usefulness of Gd-DTPA include increased patient age, definite lesion seen at computed tomography or precontrast MR imaging, prior craniotomy for tumor, and clinically documented systemic or central nervous system disease. Gd-DTPA should probably be used routinely for cranial MR imaging in most patients, except, perhaps, children and young adults with normal precontrast images.