Taurolithocholate-induced inhibition of biliary lipid and protein excretion in the rat.

Taurolithocholate (TLC), a natural bile salt, induces selective impairment on canalicular membrane of the hepatocyte, which seems to be a major determinant of its cholestatic effect in experimental animals. In order to extend existing studies about the effects of TLC on bile secretion, we examined in TLC-treated rats the biliary excretion of compounds that are transported to canalicular membrane via vesicles, such as lipids and proteins. The single intravenous injection of TLC (3 mumol/100 g body wt.) inhibited transiently the biliary bile salt excretion, while the biliary excretion of lipids (i.e., cholesterol and phospholipids) and proteins remained inhibited even though the biliary excretion and composition of bile salts were normalized. Under such a condition, TLC also inhibited the transcellular vesicular pathway to the exogenous protein horseradish peroxidase entry into bile, without altering the paracellular biliary access of the protein. The hepatic uptake of horseradish peroxidase was unaffected by TLC-treatment. The results indicate that TLC can inhibit the biliary excretion of compounds that reach the canaliculus via a vesicular pathway, such as lipids and proteins, by a mechanism not related to a defective bile salt excretion. Possible explanations for these findings are discussed.     

Comparison of hepatic, renal and intestinal bilirubin UDP-glucuronyl transferase activities in rat microsomes

1. Bilirubin UDP-glucuronyltransferase activity and its dependence on substrate concentrations in rat liver, renal cortex and intestinal mucosa microsomes were studied. 2. Bilirubin monoglucuronide synthesis from unconjugated bilirubin was a higher capacity, lower affinity step in comparison with bilirubin diglucuronide formation in the three tissues tested. 3. Bilirubin glucuronide formation in liver microsomes showed a higher capacity but a lower affinity than extrahepatic ones. Renal cortex and intestinal mucosa exhibited similar kinetics parameters. 4. In vitro bilirubin glucuronidation in renal cortex and intestinal mucosa was quantitatively important as compared with the hepatic one.     

Changes in HL-A antigen profiles on SV40-transformed human fibroblasts

The histocompatibility antigen profile of human fibroblasts transformed with SV40 virus has been investigated by determining their ability to specifically absorb HL-A alloantisera. Four out of four human adult skin fibroblast lines acquired, after SV40 transformation, the ability to absorb the HL-A alloantiserum VICTOR directed against the specificities HL-A5, W5. On the contrary, none of six embryonic fibroblast lines showed any qualitative or quantitative change of their HL-A antigenic profile. Similarly, murine, monkey and hamster cells could not absorb the activity of the HL-A alloantiserum VICTOR after SV40 transformation. It is suggested that the ‘new HL-A antigen’ specificity on human fibroblasts after SV40 transformation may be due to either a cross-reaction between HL-A specificities and antigenic structures present on glycoprotein(s) coded by the viral genome and expressed on the cell or to a change in the regulating mechanism of the expression of histocompatibility antigens on the cell surface, should the genetic information for all the HL-A specificities be present in the cell genome.     

Regional expiratory flow limitation studied with Technegas in asthma.

Regional expiratory flow limitation (EFL) may occur during tidal breathing without being detected by measurements of flow at the mouth. We tested this hypothesis by using Technegas to reveal sites of EFL. A first study (study 1) was undertaken to determine whether deposition of Technegas during tidal breathing reveals the occurrence of regional EFL in induced bronchoconstriction. Time-activity curves of Technegas inhaled during 12 tidal breaths were measured in four asthmatic subjects at control conditions and after exposure to inhaled methacholine at a dose sufficient to abolish expiratory flow reserve near functional residual capacity. A second study (study 2) was conducted in seven asthmatic subjects at control and after three increasing doses of methacholine to compare the pattern of Technegas deposition in the lung with the occurrence of EFL. The latter was assessed at the mouth by comparing tidal with forced expiratory flow or with the flow generated on application of a negative pressure. Study 1 documented enhanced and spotty deposition of Technegas in the central lung regions with increasing radioactivity during tidal expiration. This is consistent with increased impaction of Technegas on the airway wall downstream from the flow-limiting segment. Study 2 showed that both methods based on analysis of flow at the mouth failed to detect EFL at the time spotty deposition of Technegas occurred. We conclude that regional EFL occurs asynchronously across the lung and that methods based on mouth flow measurements are insensitive to it.     

Allozymic variability in Centaurea tenorei Guss. ex Lacaita and in other species of C. parlatoris Heldr. group (Asteraceae)

ABSTRACT

The genetic diversity in Centaurea tenorei Guss. ex Lacaita, an endemic species of the “Penisola Sorrentina” (Campania region, Italy), was assessed by comparing the allozymic polymorphisms of its populations, hitherto considered as different formae of this taxon. These forms are discontinuously distributed along the coasts (C. tenorei fo. maritima) and on the internal reliefs (fo. tenorei and fo. montaltensis). Based on unpublished data, C. tenorei fo. tenorei is diploid while the others are tetraploid. In order to compare C. tenorei with the Italian congeneric, strictly related species, this analysis was extended to at least one population of all the other species enclosed in the C. parlatoris Heldr. group, in particular C. parlatoris, C. scannensis and C. ambigua, all known to be diploid. Our results point to a very low genetic diversity (He=0.08; 0.14) in fo. tenorei and fo. montaltensis, while fo. maritima (He=0.26) exhibits levels of allozymic variability similar to those observed in the other populations examined. Moreover, Wright's F statistics suggest a high inbreeding level (F_is=0.42) and a low genetic flow (F_st=0.34) among C. tenorei populations. We propose that the differences among the three forms of C. tenorei may depend upon their population size, mating system and different ploidy level. However, since they fail to form a unique group in the cluster analysis, it is suggested that a probable reticulate evolution obscures the relationships among the examined taxa, which, in any case, started to diverge only in recent times.     

Thiamine pyrophosphatase activity in a fraction rich in golgi-like structures from crushed sciatic nerve of the cat

—The activity of thiamine pyrophosphatase was determined in segments and segment subfractions from normal and crushed sciatic nerves of the cat. Activity of the enzyme was increased in segments near the site of compression. The highest activity of the enzyme was in a fraction rich in tubular and vesicular elements resembling those observed in intact compressed nerves. On morphological grounds these structures have been interpreted as originating from Golgi-like structures.