Effects of hypothyroidism and cholesterol feeding on the clearance of chylomicron remnants in vivo and by rat hepatocyte monolayers

Abstract. The hepatic catabolism of chylomicron remnants in normal rats and in hypothyroid rats which were either normocholesterolaemic or made hypercholesterolaemic by feeding cholesterol and cholic acid was studied in vivo and in hepatocyte monolayers.
In vivo , the clearance of injected chylomicron remnants labelled with either cholesteryl- or retinyl ester was delayed in the hypercholesterolaemic hypothyroid rats, but not in normocholesterolaemic hypothyroid rats.
Cholesteryl-ester-rich hepatocytes from hypercholesterolaemic hypothyroid rats took up remnants less efficiently than did normal hepatocytes. Hepatocytes from normocholesterolaemic hypothyroid rats had a lower cholesteryl ester content and took up remant particles to a greater degree than did normal hepatocytes. When normal hepatocytes were incubated with hypercholesterolaemic serum or with mevalonolactone, which increased cell cholesteryl ester content, there was a slight suppression of remnant uptake. Also, addition of triiodothyronine to hepatocyte monolayers suppressed rather than increased uptake of chylomicron remants in hepatocytes.
Thus, the study suggests that chylomicron remnant uptake by the liver is not inhibited by hypothyroidism per se but by the cholesterol accumulation in hepatocytes that is the consequence of cholesterol and bile acid feeding of the rats. Although the cholesteryl ester content in hepatocytes seems to determine remnant uptake, the regulation of uptake does not seem to be as effective as that of the LDL receptor in extrahepatic cells.     

Novel experimental Pseudomonas aeruginosa lung infection model mimicking long‐term host–pathogen interactions in cystic fibrosis

The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno‐ and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year‐long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non‐mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein‐2 (MIP‐2) and granulocyte colony‐stimulating factor (G‐CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP‐2 and G‐CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non‐mucoid phenotypes.     

Entrapment of a Tined Pacemaker Electrode in the Tricuspid Valve. A Case Report

A tined pacemaker electrode was entrapped in the tricuspid valve apparatus. Nonresponding, sustained ventricular tachycardia, and cardiac arrest necessitated forcible removal of the electrode causing partial avulsion of the tricuspid valve. Hemodynamically insignificant tricuspid regurgitation developed subsequently.     

On the mode of action of the sympathetic fibres on intestinal fluid transport: Evidence for the existence of a glucose-stimulated secretory nervous pathway in the intestinal wall

The effect of sympathetic nerve stimulation or close i. a.infusion of noradrenaline on net fluid transport was investigated on anesthetized cats. In the presence of glucose in the solution perfusing the intestinal lumen the adrenergic mechanisms increased net fluid absorption in normal intestines. Substituting glucose with mannitol in the perfusate abolished this effect of adrenergic stimulation on the net fluid uptake. Furthermore, the effect of noradrenaline on net fluid transport in normal or choleraic intestines was abolished by tetrodotoxin (TTX), a nerve conductivity blocking agent. This suggests that the sympathetic influence is dependent on intraluminal glucose and that noradrenaline exerts its effect mainly via nerves. TTX significantly increased fluid uptake from normal intestines perfused with an isotonic electrolyte solution containing glucose while a considerably smaller effect was seen in intestinal segments perfused with a solution with mannitol. Based on these findings it is proposed that glucose in some way activates intramural nervous reflex(es) in the intestinal wall. According to this hypothesis the enhancement of fluid transport induced by adrenergic stimuli is explained by an inhibition of the glucose-activated nervous secretion     

Effects of physical exercise on serum calcium and parathyroid hormone

The effects of physical exercise on plasma ionized calcium, total serum calcium and parathyroid hormone (PTH) concentrations were evaluated in healthy subjects submitted to work on an ergometer bicycle. When the workload was increased stepwise there was a significant increase (P less than 0.001) in the calcium concentrations (ionized calcium from 1.13 +/- 0.03 (SD) to 1.24 +/- 0.03 mmol 1(-1) and total calcium from 2.35 +/- 0.07 to 2.48 +/- 0.07 mmol 1(-1] when the workload exceeded approximately 65% of the estimated maximum--i.e. a load that caused accumulation in blood of lactic acid. The rise in plasma ionized calcium was, therefore, presumably largely attributed to the acidosis but reduction of plasma volume and influx from extracellular sources might also have contributed. Beta blockade (with oral intake of propranolol) reduced physical capacity, shortened the duration of work and caused less acidosis. These factors were probably responsible for a smaller rise in ionized calcium during beta blockade (7 +/- 4%) than in control studies (21 +/- 5%) without medication in subjects examined during short-term maximal exercise. Long-term (1 h) steady-state work which caused fatigue without producing lactic acidosis did not affect the calcium concentrations. Despite the effects of work on calcium levels there was no discernible suppression of the PTH concentrations. This might have been due to a concomitant stimulation of PTH secretion by work.