Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism.

The theory of bifurcating vascular systems predicts vessel diameters that are related to optimality criteria like minimization of pumping energy or of building material. However, mechanisms for producing the postulated optimality have not been described so far, and quantitative data on bifurcation diameters during development are scarce. We used an embryonic vascular bed that rapidly grows and adapts to changing hemodynamic conditions, the chicken chorioallantoic membrane (CAM), and correlated vascular cast and tissue section morphology with in vivo time-lapse video monitoring. The bifurcation exponent delta and associated parameters were quantitatively assessed in arterial and venous microvessels ranging in diameter from 30 to 100 microm. We observed emergence of optimality by means of intussusception, i.e., formation of transvascular tissue pillars. In addition to intussusceptive microvascular growth (IMG = expansion of capillary networks) and intussusceptive arborization (IAR = formation of feeding vessels from capillaries) the observed intussusception at bifurcations represents a third variant of nonsprouting angiogenesis. We call it intussusceptive branching remodeling (IBR). IBR occurred in vessels of considerable diameter by means of two alternative mechanisms: either through pillars arising close to a bifurcation, which increased in girth until they merged with the connective tissue in the bifurcation angle; or through pillars arising at some distance from the bifurcation point, which then expanded by formation of ingrowing tissue folds until they became connected to the tissue of the bifurcation angle. Morphologic evidence suggests that IBR is a wide-spread phenomenon, taking place also in lung, intestinal, kidney, eye, etc., vasculature. Irrespective of the mode followed, IBR led to a branching pattern close to the predicted optimum, delta = 3.0. Significant differences were observed between delta at arterial bifurcations (2.70 to 2.90) and delta at venous bifurcations (2.93 to 3.75). IBR, by means of eccentric pillar formation and fusion, was also involved in vascular pruning. Experimental changes in CAM hemodynamics (by locally increasing blood flow) induced onset of IBR within less than 1 hr. Our study provides morphologic and quantitative evidence that a similar cellular machinery is used for all three variants of vascular intussusception, IMG, IAR, and IBR. It thus provides a mechanism of efficiently generating complex blood transport systems from limited genetic information. Differential quantitative outcome of IBR in arteries and veins, and the experimental induction of IBR strongly suggest that hemodynamic factors can instruct embryonic vascular remodeling toward optimality.     

The effect of etching on bacterial microleakage of an adhesive composite restoration.

OBJECTIVES: The incidence of bacterial microleakage, pulp inflammation and necrosis associated with dentine etching treatments prior to restoration are not known. Consequently, to resolve some of the controversy surrounding the effects and importance of vital dentine etching, the authors investigated these factors. METHODS: 110 standardised class V cavities were cut into buccal dentine, without exposing the pulp of teeth scheduled for extraction for orthodontic reasons. Cavities were either left unetched, or etched with the non-equivalent treatments of phosphoric acid gel for 60s or Ethylenediaminetetraacetic acid (EDTA) for 30s, prior to placement of composite resin. Teeth were collected and pulp responses were evaluated according to ISO guidelines, using pathohistomorphometric analysis and ANOVA statistics. RESULTS: Etching was found to be correlated to bacterial microleakage (p=0.0001) and tertiary dentine formation (p=0.0023). Bacterial microleakage was correlated to inflammatory activity (p=0.0001). The frequency of bacterial microleakage was: no etching (65%), EDTA (51%) and phosphoric acid (PA) (20%). SIGNIFICANCE: Vital dentine etching treatment is of extreme importance for the placement of RC to minimise bacterial microleakage. PA etching proved to be more effective at preventing bacterial microleakage than non-etching, and etching with EDTA.     

Effect of gradual rise in plasma calcium concentration on the impairment of atrioventricular nodal conduction due to verapamil

The possible reversal by calcium of the inhibitory action of verapamil on the atrioventricular (AV) node was investigated in anesthetized, atropinized dogs, with cardiac pacing. The His bundle potentials were recorded by endocavitory electrode and the AV node effective refractory period measured by the extrastimulus method. Calcium infusion was effective against the impairment of AV nodal conduction induced by verapamil, provided it remained moderate: the gradual rise in the plasma calcium concentration counteracted the effects of an infusion of verapamil on conduction time and effective refractory period in the AV node, as long as it did not exceed 5 mmol/L. However, beyond this level, calcium appeared less and less capable of reversing the effects of verapamil. Thus, the protective action of calcium had a bell-shaped dose-response curve, with the optimum at 5 mmol/L. This biphasic influence is consistent with the opposite opinions previously given concerning the antagonism between calcium and calcium blockers, depending on whether hypercalcemia brought into play was mild or major. In any case, the prominent role played by calcium in the slow inward current in the AV node accounts for the antagonism, observed in vivo, between calcium and verapamil. The pacemaker activity of the sinoatrial (SA) node was less influenced by both calcium blocker and calcium.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Alcohol controls and Aboriginal society: The effects of the Northern Territory restricted areas legislation

The “restricted areas” provisions of the Northern Territory Liquor Act constitute a preventative policy aimed at reducing the effects of alcohol abuse, particularly on Aboriginal communities. Under the provisions, communities can apply to be declared “dry” or semi-restricted with respect to liquor. Since their inception in 1979, the provisions have given rise to continuing controversy. This paper addresses some of the issues associated with the controversy. Patterns of alcohol consumption on “dry”, semi-restricted and unrestricted communities are compared, and the incidence of apprehension for public drunkenness before and after restricted area declarations is examined. The paper also discusses the provisions under which vehicles implicated in acts of illicit “grog-running” are forfeited to the NT Government. It is concluded that the restricted area provisions are associated with reduced levels of alcohol consumption and apprehensions for drunkenness, and are therefore beneficial in outcome. However, it is also argued that at present the provisions are flawed in that, while some aspects serve to promote community control over alcohol consumption, other elements have the effect of undermining community control and responsibility.