R A Smallwood

AIDS and the gastroenterologist

The acquired immunodeficiency syndrome (AIDS) epidemic has spread during the last decade to virtually every country.”’ By the end of the 1980s the total number of cases reported to the World Health Organization (WHO) had reached 200 000, which almost certainly represented a substantial under-reporting of the disease.2 The WHO estimates the true cumulative incidence of AIDS to be > 500000.’ Table 1 shows the cumulative incidence of AIDS in countries with the highest case loads. It is apparent that no region of the world remains unscathed, although in Asia and the Pacific, with the possible exception of Australia, the spread of AIDS appears to have lagged behind that in other continents. Three major patterns of spread of human immunodeficiency virus (HIV) infection have been defined.’ Pattern I resulted from extensive spread in the 1970s and early 1980s amongst homosexual/ bisexual males, so that the male : female ratio is 10 : 1. Paediatric cases are therefore unusual in this group, although there is increasing spread among populations of intravenous drug users. Overall prevalence of HIV infection is less than 1%. This pattern prevails in North America, Western Europe and Australia. Pattern 11, where spread was also extensive in the 1970s and early 1980s, resulted mainly from heterosexual activity. The male : female ratio is 1 : 1, and paediatric cases of AIDS are common. Here, the overall prevalence of HIV infection is greater than 1%. This pattern is typified by sub-Saharan Africa. Pattern I11 is seen in many countries in which HIV infection did not occur until the mid 1980s. Few AIDS cases have been reported, mostly in people who have been to Table 1 highest case burden*

Transfer of acipimox across the isolated perfused human placenta

The placental transfer of the new lipid-lowering agent, acipimox was investigated in the isolated perfused human placenta. Placentas obtained at caesarean section were perfused for 120 min, with both maternal and fetal circuits in closed recycling mode. Acipimox was added to either the maternal circuit alone (five experiments) or to both maternal and fetal circuits simultaneously (five experiments) to achieve initial concentrations of 5 micrograms/ml. Antipyrine (20 micrograms/ml) and l-(14C)-leucine (250 microM) were added in like fashion as reference compounds. Two hours after addition to the maternal circuit alone antipyrine was close to equilibrium across the placenta, but equilibration of acipimox was incomplete (fetal/maternal ratio = 0.58 +/- 0.11). Maternal to fetal placental clearance of acipimox (0.80 +/- 0.18 ml/min) was 25 per cent of antipyrine clearance. After simultaneous administration to both maternal and fetal circuits the l-(14C)-leucine fetal/maternal ratio was 1.44 +/- 0.13 at 120 min, whereas maternal and fetal concentrations of acipimox and antipyrine were at equilibrium for the duration of the experiment (fetal/maternal ratio of acipimox at 120 min = 1.10 +/- 0.06). This study shows that acipimox is transferred across the human placenta by diffusion at a slow rate. The low permeability of the placenta may afford some protection to the fetus from acipimox administered to the mother in vivo.

Hepatic Kupffer cell function: the efficiency of uptake and intracellular degradation of 14C-labelled mitochondria is reduced in aged rats

Uptake from the circulation and subsequent intracellular degradation of foreign and potentially harmful substances are key functions of hepatic Kupffer cells. While ageing is generally associated with decreased clearance by the reticulo-endothelial system, the effect of ageing on specific Kupffer cell functions is poorly understood. This study measured the ability of Kupffer cells of isolated perfused rat livers from young and old rats to both phagocytose and subsequently degrade exogenous radiolabelled mitochondria. Using electron microscopy and stereological techniques it was determined that there was no change in the volume density of Kupffer cells between 2 and 24 months, implying that the size of the Kupffer cell population increased (along with the total liver size) with age. However, despite this increase size there was no parallel increase in the capacity of the liver to take up or degrade radiolabelled mitochondria, implying that, in aged rats, Kupffer cell uptake and intracellular degradation was less efficient.

High-performance liquid chromatographic method to resolve and determine lipopolysaccharide sub-groups of Escherichia coli endotoxin in isolated perfused rat liver perfusate

A high-performance liquid chromatographic method was developed for resolving heterogeneous preparations of fluorescently labelled endotoxin derived from Escherichia coli (Serotype 0111:B4) into separate lipopolysaccharide sub-groups. The endotoxin was chromatographed on an analytical gel permeation column using a mobile phase of acetonitrile (20%, v/v) and 100 mM phosphate buffer (pH 7.75). Four fluorescent peaks were resolved, representing sub-groups of markedly different molecular sizes. Three of the four sub-groups contained the core polysaccharide 2-keto-3-deoxyoctonate, confirming that they contained lipopolysaccharide. Fluorescein isothiocyanate (FITC)-labelled endotoxins derived from Vibrio cholerae and Salmonella minnesota chromatographed using the same system eluted with distinctly different patterns of peaks from each other and from E. coli. Extraction of E. coli FITC-endotoxin from a buffer solution using a phenol-diethyl ether method and subsequent chromatography allowed the determination of three of the four fluorescent sub-groups over the concentration range 1-15 micrograms/ml.