Discriminative stimulus effects of serotonin agonists, neutral antagonists, and inverse agonists in pigeons: perspectives on intrinsic efficacy measurements in vivo

Rationale  

The extended ternary complex theory of receptor function states a ligand can be classified as an inverse agonist, agonist, or neutral antagonist based on its ability to preferentially stabilize the inactive conformation, the active conformation, or to have no preference for conformational state, respectively.     

Identification of multiple constitutive and inducible hepatic cytochrome P450 enzymes in market weight swine.

Constitutive swine enzymes analogous to human/rat cytochrome P450 (CYP) isoforms 1A2, 2A6, 2B1/2/6, 2D6, 2E1, 3A1, and 4A1/3 were detected by Western blot analysis. Swine 2E1 has a molecular weight greater than rat 2E1; swine 2B2 has a molecular weight similar to human 2B6. An induction cocktail containing beta-naphthoflavone, phenobarbital, and dexamethasone induced immunoreactive homologs of 1A1, 1A2, 2B1, 2B2, 3A1, and 3A2. Although the P450 content was increased by induction, there was no difference in the Soret lambda(max). Swine 1A1 has a lower molecular weight than swine 1A2 and rat 1A1. A swine 2B1 homolog was seen after induction, with a molecular weight that was lower than rat 2B1 but higher than swine 2B2. Induction did not augment swine 2B2 levels. The 3A homologs have molecular weights similar to their rodent counterparts. Following induction, swine 3A1 levels increased and were accompanied by the appearance of swine 3A2. Induction had no effect on expression of 2A6, 2B6, 2D6, 2E1, or 4A1/3. Enzyme induction increased the specific activities (nmol/min/mg) of substrates specific for 1A (7 of 7 substrates tested), 2A (2/2), 2B (5/5), 2C (1/3), 2D (3/4), 2E (3/3), 3A (3/5), and 4A (1/1). Although the specific activities of the 2E substrates increased, the turnover number for hydroxylation of chlorzoxazone was unchanged and that of p-nitrophenol and aniline were depressed in induced pigs. These results show that swine CYP isoforms are similar to those identified in human and rodents, but they are also different in many ways.     

Using Surveillance Data to Inform Community Action: The Effect of Alcohol Sale Restrictions on Intentional Injury-related Ambulance Pickups

Youth violence disproportionately affects inner city, urban minority communities in the USA. This article illustrates the use of surveillance data to inform and evaluate community action directed at this serious problem. Community efforts in response to surveillance data indicating high rates of violence surrounding convenience stores with unrestricted alcohol beverage licenses provided a natural experiment to examine the impact of imposing licensing restrictions on intentional injury rates. Rates of ambulance pickups for intentional injuries in the 15- to 24-year-old population in five census tracts where alcoholic beverage sales were restricted were compared to five census tracts with similar demographic characteristics near stores where restrictions were not instituted. Time periods included an 18-month baseline period, a 6-month period during which restrictions were in effect in the intervention communities, and an 18-month period following lifting of this restriction resulting from legal action by store owners. The monthly average rate of ambulance pickups for violent injuries showed a significantly greater baseline-to-intervention phase decrease in the intervention communities (i.e., from 19.6 to 0 per 1,000) than in the control communities (i.e., 7.4 to 3.3 per 1,000). This rate subsequently increased to 11.4 in the intervention communities after the restriction was removed. This study illustrates the potential value of surveillance data for guiding community mobilization efforts and for evaluating the impact of such efforts. It also demonstrates the potential impact of restricting inexpensive, single-serve alcoholic beverages on rates of violence.     

Arteriovenous fistula of the vertebral artery in a female infant with hypotonia and cephalocorporal disproportion

Background: Congenital arteriovenous fistulas are exceptional in childhood and imply a therapeutic challenge. Case report: A 9‐month‐old female infant was studied for cephalocorporal disproportion, hypotonia, progressive muscular atrophy and hyperreflexia. Computed tomography of the brain and electroencephalography were normal. Electromyographic patterns suggested proximal myopathic involvement. A continuous murmur with systolic reinforcement was audible in the neck. Angioresonance detected intracranial aneurysmal dilatations behind the bulbo‐medullary junction and cerebral panangiography evidenced a direct vertebrovertebral fistula with extra‐ and intra‐cranial varices and extreme medullary compression. Occlusion of the afferent vessel to the aneurismal sack was successfully achieved with a mixture of Histoacryl and 75% lipiodol via a microcatheter. Conclusion: Clinical signs of an arteriovenous fistula may be atypical. Considerable cephalocorporal disproportion and a bruit in the cervical or retromastoidal regions must suggest its existence. Complete obliteration with endovascular embolization permits somatic and neurological recovery.