Increased responsiveness to histamine after propranolol in subjects with asthma nonresponsive to the bronchoconstrictive effect of propranolol

Eight nonsmoking subjects with asthma, nonresponsive to the bronchoconstrictive effect of oral propranolol, were studied. The airway response to increasing concentrations of histamine aerosol was assessed by measuring FEV1. The threshold provocative dose of histamine needed to cause a 20% fall in starting FEV1 (PD20) was measured by log dose-response curve. Histamine challenge was performed in duplicate after premedication with placebo or 40 mg of propranolol on separate days. The mean starting FEV1 did not change significantly after placebo and after propranolol administration. The mean PD20 values after propranolol (0.37 mg/ml and 0.32 mg/ml, respectively, for the first and the second challenge) were significantly lower (p less than 0.01) than mean control PD20 values (1.36 mg/ml and 1.48 mg/ml, respectively, for the first and the second challenge). These results indicate that propranolol increases airway responsiveness to histamine, even in those subjects with asthma in whom propranolol has little bronchoconstrictive effect.     

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.     

Scleroglucan/borax: characterization of a novel hydrogel system suitable for drug delivery

A new hydrogel, with scleroglucan using borax as a crosslinker, has been prepared. The physical gel has been loaded with a model molecule (theophylline) and the release of the drug from the gel was evaluated. The same system was used to prepare tablets and the delivery of theophylline in different environmental conditions (HCl and SIF) was determined. A recent theoretical approach has been applied to the dissolution profiles obtained from the tablets and a satisfactory agreement has been found with the experimental data. Furthermore, the diffusion coefficient of the model molecule was evaluated according to a suitable strategy that was tested on two set of data obtained with different set-ups (permeation and diffusion experiments). A simplified mathematical approach allows to reduce the two-dimensional problem of the Fick's second law in a one-dimensional system leading to a much easier handling of the data without loosing the accuracy of the original problem in two dimensions. The characterization of the gel has been also carried out following the kinetics of swelling in terms of water uptake.     

Control of myocardial tissue components and cardiocyte organelles in pressure-overload hypertrophy of the cat right ventricle

Previous studies have demonstrated that there is a disproportionate increase in connective tissue in right ventricular myocardium subjected to pressure-overload hypertrophy associated with depressed cardiac contractility. While the myocardium is primarily responsive to load, the aim of the present study was to determine whether catecholamines also modulate the response of myocardial tissue components and cardiocyte organelles in pressure-overload-induced cardiac hypertrophy. Four experimental groups of cats were examined: (1) a sham-operated control group, (2) a group which had their pulmonary arteries banded in order to induce a pressure overload, (3) a group which had been subjected to the same pressure overload, but in addition had β-adrenoceptor blockade produced prior to and during the pressure overloading, and (4) a group which had been subjected to the same pressure overload, but in addition had α-adrenoceptor blockade produced prior to and maintained during the pressure overloading. As in our previous study, there was a significant and equivalent degree of right ventricular hypertrophy in all experimental groups with pressure overload when assessed either as the ratio of right ventricular weight to body weight or as cardiocyte cross-sectional area. At the light microscopic level, the disproportionate increase in the volume density of myocardial connective tissue seen in banded animals was completely prevented by either α- or β-adrenoceptor blockade. At the electron microscopic level, there was a reduction in the mitochondrial and myofibrillar volume fractions following β-adrenoceptor blockade. The results of this study provide evidence for a modulatory role of catecholamines in the control of myocardial connective-tissue proliferation in pressure-overload-induced cardiac hypertrophy. There is also evidence to support the role of the adrenergic nervous system in regulating cardiocyte subcellular organelles, independent of the regulation of cardiocyte size.     

The atrioventricular node and bundle in the ferret heart: A light and quantitative electron microscopic study

The cells of the atrioventricular (AV) junction in the ferret heart were examined using light microscopy, a wax-model reconstruction and quantitative electron microscopy to determine their organization and characteristics. A series of subdivisions of the specialized tissues of the AV junction was apparent at both the light and electron microscopic levels. A transitional zone was observed interposed between the atrial muscle cells and the AV node. The AV node consisted of a coronary sinus portion, a superficial portion and a deep portion. The AV bundle had a segment above the anulus fibrosus, a segment which penetrated the right fibrous trigone, a non-branching segment below the anulus fibrosus and a branched segment. At the ultrastructural level the AV junctional conduction tissues had fewer irregularly oriented myofibrils than did working atrial myocardial cells. T-tubules, present in atrial muscle cells, were not observed in the modified muscle cells of the AV node and bundle. Conventional intercalated discs also were not observed between the cells of the AV node or the AV bundle. Atrial myocardial cells had the highest percentage of the plasma membrane occupied by desmosomes, fasciae adherentes and gap junctions. The AV bundle cells had the highest percentage of appositional surface membrane and a relatively large fraction of plasma membrane occupied by gap junctions. Cells of the superficial portion of the AV node had the smallest percentage of the plasma membrane composed of gap junctions, desmosomes or fasciae adherentes, as well as the smallest fraction of the cell membrane apposed to adjacent cells. The stereological data indicate that the most useful distinguishing characteristic between atrial muscle cells and conduction cells was that a smaller percentage of the conduction cell sarcoplasm was occupied by mitochondria and myofibrils. The most useful characteristics that could be used to differentiate between the regions of the AV junctional conduction tissues were the amounts and types of surface membrane specializations in the respective cell types.     

The impact of decentralisation on the performance of health care systems: a non-linear relationship

The European Journal of Health Economics - This paper examines the role of institutions—notably the degree of administrative decentralisation across levels of government—in health care...     

Effects of intraperitoneal Ringer's lactate instillation and infusion on postsurgical adhesion formation

We compared the effects of continuous Ringer's lactate infusion and Ringer's lactate instillation on postsurgical adhesion formation in the rat model. The results show that intraperitoneal Ringer's lactate instillation reduces postsurgical adhesions. However, its efficacy is not improved by additional infusion of Ringer's lactate.