Adventitial stripping does not strip the adventitia

This study investigates the process of stripping the adventitia off a blood vessel, which is a normal procedure prior to performing a microvascular anastomosis. In five rats, the common carotid and the superficial femoral arteries of one side were stripped sharply, whereas the arteries of the other side were left unstripped to serve as controls. In a further set of five rats, the arteries were stripped bluntly. Immediately following stripping, experimental and control arterial segments were removed. Histology of cross sections of the segments was studied. In no case was there complete removal of the adventitia. When stripped and control arterial sections were compared, no significant difference between cross-sectional adventitial areas could be demonstrated. Morphologic study revealed that stripping mainly removes large collagen fibers from the adventitia. The small collagen fibrils that are still in place fan out in such a way that although considerable tissue is removed, the volume that the adventitia occupies remains the same. Stripping the adventitia does not cause complete removal of the adventitia, and in this study no significant reduction in the adventitial volume could be found. Stripping does, however, allow a better view of the cut edge of the vessel wall under an operating microscope. Since blunt stripping could cause damage to other vessel wall layers, sharp stripping is to be preferred.     

Moderate alcohol consumption and loss of cerebellar Purkinje cells

OBJECTIVE: To examine the dose-response effect of alcohol consumption on the number of cerebellar Purkinje cells. DESIGN: A prospective necropsy study combined with detailed reports on use of alcohol from a relative or friend. The number of Purkinje cells was counted in the anterior midsagittal section of the cerebellar vermis, the area of which was measured by computer assisted morphometry. SETTING: Department of forensic medicine, University of Helsinki. SUBJECTS: 66 men, aged 35 to 69 years, subjected to medicolegal necropsy because of sudden or violent death. The average all year daily alcohol consumption over the year was 0 to 10 g in 17 men, 11 to 80 g in 24 men, and more than 80 g in 25 men. MAIN OUTCOME MEASURES: Number of Purkinje cells, alcohol consumption. RESULTS: The numbers and density of Purkinje cells in the cross section of vermis showed a consistent but weak decrease with increasing daily alcohol intake but not with age. A wide variation in the cell counts was observed, especially in men drinking more than 80 g, suggesting differences in the susceptibility to effects of alcohol. Compared with men drinking 40 g or less, a long term moderate consumption of an average of 41 to 80 g daily was associated with a significant average loss of 242 (95% confidence interval 45 to 439) Purkinje cells (15.2%) from a mean of 1583 to 1341 cells. In those drinking 81 to 180 g the average loss was 535 (259 to 811) cells (33.4%) to a mean of 1048 cells. The density of cells in the cross section of vermis also fell significantly by 0.9 cell/mm (0.1 to 1.7) when the daily consumption exceeded 40 g and by 1.4 cell/mm (0.3 to 2.5) when the intake was 81 to 180 g. Only three cases (4.5%) in the series showed macroscopical cerebellar atrophy. CONCLUSION: Long term intake of moderate doses of alcohol daily for 20-30 years may damage the cerebellum before the onset of macroscopical atrophy. Despite distinct individual differences an all year average daily alcohol intake of 41-80 g results in a risk of significant loss of Purkinje cells.     

Increase of 5-HT7 (serotonin-7) and 5-HT1A (serotonin-1A) receptor mRNA expression in rat hippocampus after adrenalectomy

Kinematic and electromyographic (EMG) analysis of a target-directed, maximal velocity movement was used to investigate the effects of high-force eccentric exercise on the neuromuscular control of elbow flexion. Ten non-weight-trained females [19.6 (1.6) years old] performed 50 maximal velocity elbow flexion movements from 0 to 1.58 rad (90 degrees), as rapidly as possible in response to a light stimulus, while kinematic and triphasic EMG parameters were measured. This was done three times pre-exercise, immediately and 1, 2, 3, 4, and 5 days following the 50 maximal eccentric elbow flexion actions. The eccentric exercise caused lengthening of kinematic parameters including total movement time and time to peak velocity. The EMG elements of the biceps brachii (b.) motor time, time to peak EMG, biceps b. burst duration, and the latency period between biceps b. and triceps b. bursts were lengthened post-exercise. These changes persisted for up to 5 days post-exercise. The exercise also caused a large increase in serum creatine kinase (CK) activity. It was concluded that high-force eccentric exercise in this population caused prolonged changes in neuromuscular control that were a function of exercise-induced disruption of the skeletal muscle. Compensation in the central motor program was such that the components of the triphasic EMG pattern were systematically lengthened.     

Automated docking of glucosyl disaccharides in the glucoamylase active site

To better understand the molecular basis of glucomylase selectivity, low-energy conformers of glucosyl disaccharides obtained from relaxed-residue conformational mapping were flexibly docked into the glucoamylase active site using AutoDock 2.2. This procedure ensures that significant conformational space is searched and can produce bound structures comparable to those obtained by protein crystallography. alpha-Linked glucosyl disaccharides except alpha,alpha-trehalose dock easily into the active site while exclusively beta-linked disaccharides do not, explaining why only the former are glucoamylase substrates. The optimized docking modes are similar at the nonreducing end of the different substrates. Individual atomic energies of intermolecular interaction allow the definite identification of key hydroxyl groups for each substrate. This approach confirmed the versatility of the second subsite of the glucoamylase active site in binding different substrates.     

The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid

The gamma-aminobutyric acid type A (GABAA) receptor is a transmitter-gated ion channel mediating the majority of fast inhibitory synaptic transmission within the brain. The receptor is a pentameric assembly of subunits drawn from multiple classes (alpha1-6, beta1-3, gamma1-3, delta1, and epsilon1). Positive allosteric modulation of GABAA receptor activity by general anesthetics represents one logical mechanism for central nervous system depression. The ability of the intravenous general anesthetic etomidate to modulate and activate GABAA receptors is uniquely dependent upon the beta subunit subtype present within the receptor. Receptors containing beta2- or beta3-, but not beta1 subunits, are highly sensitive to the agent. Here, chimeric beta1/beta2 subunits coexpressed in Xenopus laevis oocytes with human alpha6 and gamma2 subunits identified a region distal to the extracellular N-terminal domain as a determinant of the selectivity of etomidate. The mutation of an amino acid (Asn-289) present within the channel domain of the beta3 subunit to Ser (the homologous residue in beta1), strongly suppressed the GABA-modulatory and GABA-mimetic effects of etomidate. The replacement of the beta1 subunit Ser-290 by Asn produced the converse effect. When applied intracellularly to mouse L(tk-) cells stably expressing the alpha6beta3gamma2 subunit combination, etomidate was inert. Hence, the effects of a clinically utilized general anesthetic upon a physiologically relevant target protein are dramatically influenced by a single amino acid. Together with the lack of effect of intracellular etomidate, the data argue against a unitary, lipid-based theory of anesthesia.     

Neuropsychological asymmetry in Alzheimer's disease: verbal versus visuoconstructional deficits across stages of dementia

The incidence of clinically apparent asymmetric profiles of neuropsychological deficits in Alzheimer's disease (AD) patients similar to those reported in the PET literature is currently unclear. This study investigated lateral neuropsychological asymmetry using principal component factor analysis in a sample of 153 patients diagnosed with probable AD. Using factor scores, patients were classified into groups exhibiting asymmetric or symmetric profiles of neuropsychological deficits. In the analysis of lateral asymmetry, 27.5% of patients were classified as asymmetric (10% verbally and 17% visuospatially). Consistent with reports of continued asymmetry beyond the mild dementia stage, asymmetry was exhibited in the mild, moderate, and severely demented groups. These findings of neuropsychological asymmetry across stages of dementia are consistent with the picture of significant neuropsychological heterogeneity in AD that has been emerging in the decade.