Effect of ethanol on mouse cerebral cortical beta-adrenergic receptors

Low concentrations of ethanol (10-100 mM), added to assays in vitro, altered agonist (isoproterenol) binding to mouse cerebral cortical beta-adrenergic receptors in a reversible manner. Ethanol decreased the affinity of the high affinity form of the receptor for isoproterenol but had no effect on the affinity of the low affinity form of the receptor, the proportion of high and low affinity forms of the receptor, the total number of agonist-binding sites, or antagonist binding. The selective effect of ethanol on the properties of the high affinity agonist-binding site suggested that ethanol alters the characteristics of the complex of the receptor and Gs, the guanine nucleotide-binding protein. In cerebral cortical membranes of mice that had ingested ethanol chronically, isoproterenol binding data were best fit by a one-site model, even in the absence of guanine nucleotides. This change, when considered together with previously reported changes in adenylate cyclase activity, is reminiscent of heterologous desensitization of the beta-adrenergic receptor. Thus, both acute and chronic ethanol administration may produce changes in adrenergic function in brain.     

Comparison between traditional 2-dimensional cephalometry and a 3-dimensional approach on human dry skulls.

The cephalogram is the standard used by orthodontists to assess skeletal, dental, and soft tissue relationships. This approach, however, is based on 2-dimensional (2D) views used to analyze 3-dimensional (3D) objects. The purpose of this project was to evaluate and compare a 3D imaging system and traditional 2D cephalometry for accuracy in recording the anatomical truth as defined by physical measurements with a calibrated caliper. Thirteen skeletal landmarks were located by both radiographic methods on 9 dry human skulls. Intraclass correlation (0.995), variance (0.054 mm(2)), and standard deviation (SD) (0.237 mm) were averaged over 76 measurements and derived from precision calipers to establish these physical measurements as a reliable gold standard to make comparisons of the 2D and 3D radiographic methods. The results showed great variability of the 2D from the gold standard, with the range varying from -17.68 mm (underestimation of Gn-Zyg R) to +15.52 mm (overestimation of Zyg L-Zyg R). In contrast, the 3D method (Sculptor, Glendora, Calif) indicated a range of the SD from -3.99 (underestimation) mm to +2.96 mm (overestimation). The 3D evaluation was much more precise, within approximately 1 mm of the gold standard. These results indicate that, when the actual distance is measured on a human skull in its true dimensions of 3D space, the Sculptor program, by using a 3D method, is more precise and 4 to 5 times more accurate than the 2D approach. Evaluating distances in 3D space with a 2D image grossly exaggerates the true measure and offers a distorted view of craniofacial growth. There is an inherent problem of representing a linear measure occupying a 3D space with a 2D image.     

Response of joint capsule neurons to axial stress and strain during dynamic loading in cat

1. Experiments were conducted to test the hypothesis that the responses of joint capsule mechanoreceptors better encode tissue stress or tissue strain. The experimental model was a small ligament from the cat knee capsule, which was stretched uniaxially in vitro. Experiments were done with either force or displacement as the controlled variable, and with steps, sinusoids, or pseudorandom Gaussian noise (PGN) as the input function. 2. The strength of coupling between neural discharge and both strain and stress was quantified during step experiments using linear correlation coefficients. The correlation between the frequency of neural discharge and stress was 0.93 +/- 0.09 (SD). The correlation between frequency of neural discharge and strain was -0.91 +/- 0.06. The magnitudes of these correlation coefficients were not significantly different. 3. The strength of coupling between neural discharge and both strain and stress during sinusoidal and PGN experiments was quantified by the use of an information theoretic statistic, transinformation. Out of 282 sinusoidal runs, transinformation between neural discharge and stress was significantly greater than transinformation between strain and neural discharge 241 times. Transinformation between strain and neural discharge was significantly greater 15 times. 4. During PGN experiments, transinformation between stress and neural discharge was greater than transinformation between strain and neural discharge in all 19 experimental runs. 5. Conditional transinformation between strain and neural discharge, given stress, was calculated for all sinusoidal and pseudorandom experiments. This statistic was greater than zero in 268 out of 289 experimental runs, indicating that a component of strain independent of stress is being signaled in the neural discharge.     

Mandibular displacement in Angle Class II, Division 2 malocclusion

The effect of the treatment of Angle Class II, Division 2 malocclusion was studied in 22 children by x-ray cephalometry and by recording the relation between the retruded and the intercuspal mandibular positions. The treatment was performed in three phases. In the first phase the upper incisors were proclined, and the deep bite was corrected with an upper removable plate. In the second phase the distal occlusion was corrected with an activator. The result was retained in the third phase with a second activator designed for retention. The relation between the retruded (RCP) and the intercuspal (ICP) mandibular positions was recorded with wax bites and dental casts mounted in a modified gnathothesiometer. The anteroposterior distance between RCP and ICP was large before the start of the treatment. The distance was unchanged after proclination of the upper incisors and correction of the deep bite but decreased after correction of the distal occlusion and increased again somewhat during the retention phase. The proclination of the upper incisors and the correction of the deep bite (phase one of the treatment) did not result in mandibular anterior positioning. This fact and the results of the recordings of the relation between RCP and ICP were interpreted as evidence that the mandible is not posteriorly displaced in Class II, Division 2 malocclusion.     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.

Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist.