Alastair A. Macdonald

The proapoptotic effects of sulindac, sulindac sulfone and indomethacin are mediated by nucleolar translocation of the RelA(p65) subunit of NF-κB

Understanding the mechanisms that underlie the antitumour activity of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer will allow the development of more effective and specific chemopreventative agents. Modulation of the NF-κB pathway has been implicated as a key effector of the antitumour effect of aspirin, but the effects of non-aspirin NSAIDs on this pathway have yet to be fully defined. Here, we demonstrate that sulindac, sulindac sulfone and indomethacin activate the NF-κB pathway in colorectal cancer cells, as determined by western blot analysis of cytoplasmic levels of IκBα and immunocytochemical analysis of nuclear NF-κB/RelA. Furthermore, we show that all of these NSAIDs induce nucleolar translocation of the RelA subunit of NF-κB. Using RelA deleted for the previously described nucleolar localization signal, we demonstrate that this response is causally involved in the apoptotic effects of these agents. Finally, we demonstrate that NSAID-mediated nucleolar translocation of RelA is associated with downregulation of NF-κB-driven transcription and of the NF-κB target gene, ICAM-1. These data identify nucleolar translocation of RelA and the associated repression of the NF-κB-driven transcription as a central molecular mechanism of NSAID-mediated growth inhibition and apoptosis. As well as providing new understanding of the molecular determinants of RelA function, these findings also have relevance to the development of novel chemotherapeutic and chemopreventative agents.

Immunohistochemical Study on the Distribution of Endocrine Cells in the Gastrointestinal Tract of the Babirusa, Babyrousa babyrussa (Suidae)

The distribution and relative frequency of endocrine cells in the gastrointestinal tract of the babirusa were studied immunohistochemically using the avidin‐biotin‐peroxidase complex method. Thirteen types of gut endocrine cells were detected; they were immunoreactive for chromogranin, serotonin, somatostatin, gastrin, bovine pancreatic polypeptide (BPP), glucagon, secretin, cholecystokinin (CCK), methionine–enkephalin–Arg6–Gly7–Leu8 (MENK8), motilin, gastric inhibitory polypeptide (GIP) and peptide tyrosine tyrosine (PYY). Cells that were immunoreactive for chromogranin, serotonin, somatostatin and glucagon were found in all portions of the gastrointestinal tract. MENK8‐immunoreactive cells were observed in the stomach and small intestine. Gastrin‐immunoreactive cells were detected in the pyloric region and duodenum. PYY‐immunoreactive cells were found in the small and large intestine. Cells immunoreactive for motilin, CCK, GIP, and secretin were observed in the proximal small intestine and those immunoreactive for neurotensin were found only in the ileum. Although the distribution pattern of endocrine cells in the gastrointestinal tract of babirusa was similar to those reported for pig, restricted distribution of several endocrine cells, gastrin, BPP, MENK8, motilin, CCK, GIP, secretin and neurotensin and wider distribution of glucagon and PYY were observed in the babirusa. The unexpected presence of MENK8 in all glandular regions of the stomach and PYY in the small intestine was also noted. The distribution of gut endocrine cells might be related to the regulatory characteristics of the babirusa digestive tract.

Notes on placentation in the Suina.

We examined the gross and microscopic anatomy of placental tissues and umbilical cords from six species representing the three living families of the Suina. These species included, of the Suidae, the wart hog (Phacochoerus aethiopicus), the giant forest hog (Hylochoerus meinertzhageni), the domestic pig (Sus scrofa), and the banded pig of Malaysia (Sus scrofa vittatus); of the Tayassuidae, the white-lipped peccary (Tayassu pecari); of the Hippopotamidae, the hippopotamus (Hippopotamus amphibius) and the pigmy hippopotamus (Choeropsis liberiensis). All these species have a diffuse epitheliochorial placenta. The chorion is folded, and has on its surface rows of shallow ripples or villi, interrupted by round, oval or irregularly shaped areolae. Placental capillaries indent the epithelial layer covering the tops and sides of the interareolar villi, but not the columnar cell layer lying in the troughs between these villi or covering the areolae. Cuboidal cells cover the crests of the villi in the Suidae and Hippopotamidae, whereas in the Tayassuidae the epithelium is syncytial in appearance. The similarities in placental structure between the six species are more apparent than the differences. Suidae and Tayassuidae have smooth umbilical cords containing two arteries and one vein; those of the Hippopotamidae are pustule-encrusted and contain two arteries and two veins.

Application of Sus scrofa microsatellite markers to wild suiformes

Stewart Lowden1∗, H.A. Finlayson2, A.A. Macdonald1, A.C. Downing2, S.J. Goodman3, K. Leus4, L. Kaspe5, E. Wahyuni5 & A.L. Archibald2 1Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH9 1QH, UK; 2Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, UK; 3The Zoological Society of London, Regent’s Park, London NW1 4RY, UK; 4Centre for Research and Conservation, Royal Zoological Society of Antwerp, Koningin Astridplein 26, 2018 Antwerpen, Belgium; 5Kebun Binatang Surabaya, Jl. Setail 1, Surabaya, Indonesia (*Author for correspondence: E-mail: s.lowden@ed.ac.uk; Fax: 0131 650 6576)

The neurohypophysial hormones

Abstract Release of oxytocin and vasopressin during parturition in a number of domestic animals including the pig, sheep, goat and mare is discussed. The pattern is essentially similar in all species studied, oxytocin concentrations being low or undetectable in late pregnancy and increasing during labour until maximum concentrations are found with delivery of the fetus. Relatively little change in the circulating concentrations of vasopressin has been noted. Secretion of neurohypophysial hormones in the ovine and porcine fetus is also described, data from acute and chronically catheterised preparations being presented. While oxytocin release is unaffected by the stimuli employed, haemorrhage results in vasopressin release, the concentrations achieved being related to the pH of the blood. Hypoxia is confirmed as an effective stimulus of vasopressin release.

From babirusa (Babyrousa babyrussa) to domestic pig: the nutrition of swine

Interest in the nutrition of wild and captive wild animals has grown exponentially during the last few years. In the past, the amount of research carried out on domesticated animals, mainly geared towards improving economic efficiency of production of meat and dairy products, vastly outweighed research performed on wild animals. During the last two decades heightened public awareness of the need for nature conservation and for respect for animal welfare have brought new reasons for, and meaning to, further research in the fields of both domestic and wild animal nutrition. As natural habitat becomes more and more fragmented and as wild animals are more and more confined to protected wildlife areas designated by man, a thorough knowledge of the feeding ecology of the wild animals living in these areas becomes essential for the successful conservation of these species. Furthermore, assisting nature conservation now constitutes one of the main goals of modem zoos

The effects of gestational age and chronic fetal decapitation on arterial blood pressure in the pig fetus.

Blood pressure was measured in anaesthetized pig fetuses decapitated at 40-43 days of gestation and in intact fetuses between 35 and 112 days of gestation (term is 114 days). In the intact fetuses arterial blood pressure increased significantly from 0.8 +/- 0.1 kPa (mean +/- SEM) at 35 days to 5.8 +/- 0.2 kPa at 112 days (P less than 0.05). The arterial blood pressure of decapitated fetuses was similar to that of intact fetuses at 70 days of gestation (2.7 +/- 0.4 kPa vs. 2.5 +/- 0.1 kPa, respectively) but did not change with increasing gestational age thereafter. Hence in late gestation (greater than 90-100 days) the arterial blood pressure of the decapitated fetuses was significantly less than that of intact fetuses (P less than 0.05). These observations demonstrate that the control of blood pressure in the pig varies with gestational age and suggest that the developmental changes occurring after about 100 days gestation require tissues within the head.

Glucose, lactate and oxygen metabolism in the fetal pig during late gestation

Using [U‐14C]glucose tracer, rates of umbilical uptake, utilization and production of glucose, and of CO2 production from glucose carbon, were measured in seven chronically catheterized fetal pigs, when the sow was in the fed state, between 100 and 113 days of gestation (term, 114 +/− 2 days). At the same time, rates of umbilical O2 and lactate uptake were determined in all seven fetuses by the Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization and CO2 production from glucose carbon were 38.4 +/‐ 4.2, 41.3 +/− 5.2 and 126.9 +/− 12.6 mumol min‐1 (kg fetal body weight)‐1, respectively (n = 7), No glucose production was therefore detected in the fetuses. Production of CO2 from glucose carbon accounted for 37.3 +/− 3.4% (n = 7) of the umbilical O2 uptake, which averaged 340 +/− 13 mumol min‐1 kg‐1 (n = 7). There was also significant umbilical lactate uptake in the fetal piglets when the sow was in the fed state (32.6 +/− 10.4 mumol min‐1 kg‐1, n = 7, P < 0.05). No significant changes in fetal glucose, O2 or lactate metabolism were observed with increasing age towards term. The fetal rates of glucose metabolism and of umbilical uptake of O2 and lactate were not correlated with fetal blood glucose level. Hence, glucose is used for both oxidative and non‐oxidative metabolism in utero and is an important, although not the sole, source of carbon for metabolic processes in the fetal pig during late gestation.

A Lectin Histochemical Study on the Testis of the Babirusa, Babyroussa babyrussa (Suidae)

The distribution of lectin bindings in the testis of babirusa, Babyrousa babyrussa (Suidae) was studied histochemically using 10 biotinylated lectins, Peanut agglutinin (PNA), Ricinus communis agglutinin (RCA I), Dolichos biflorus agglutinin (DBA), Vicia villosa agglutinin (VVA), Soybean agglutinin (SBA), Wheat germ agglutinin (WGA), Lens culinaris agglutinin (LCA), Pisum sativum agglutinin (PSA), Concanavalin A(Con A) and Ulex europaeus agglutinin (UEA I). Nine of 10 lectins showed a variety of staining patterns in the seminiferous epithelium and interstitial cells. The acrosome of Golgi‐, cap‐ and acrosome‐phase spermatids displayed various PNA, RCA I, VVA, SBA and WGA bindings, indicating the presence of glycoconjugates with d‐galactose, N‐acetyl‐d‐galactosamine and N‐acetyl‐d‐glucosamine sugar residues respectively. No affinity was detected in the acrosome of late spermatids. LCA, PSA and Con A which have affinity for d‐mannose and d‐glucose sugar residues were positive in the cytoplasm of spermatids and spermatocytes. DBA was positive only in spermatogonia. In addition to DBA, positive binding in spermatogonia was found for VVA, WGA and Con A, suggesting the distribution of glycoconjugates with N‐acetyl‐d‐galactosamine, N‐acetyl‐d‐glucosamine, d‐mannose and d‐glucose sugar residues. Sertoli cells were stained intensely with RCA I, WGA and Con A. In Leydig cells, RCA I and Con A were strongly positive, while WGA, LCA and PSA reactions were weak to moderate. The present findings showed that the distribution pattern of lectin binding in the testis of babirusa is somewhat different from that of pig or other mammals reported previously.

Anatomy and histology of the babirusa(Babyrousa babyrussa) stomach

Stomachs from six adult and one 12-month-old babirusa (Babyrousa babyrussa) were collected from zoological gardens. The babirusa stomach was larger than that of the domestic pig (Sus scrofa), and possessed a large diverticulum ventriculi. Its gastric glands were confined to a small, easily identifiable unit at the end of the corpus ventriculi, and the connections between the different stomach parts were wide and unrestricted, with the exception of the well-defined connection between the diverticulum ventriculi and the fundus ventriculi. Microscopically, the structure of the cardiac, gastric and pyloric glands was similar to that of Sus scrofa. However, the mucusproducing cardiac glands of babirusa occupied a larger area within the stomach (> 70% versus 33%). The pH in the lumen of the cardiac gland area lay between 5.3 and 6.4 and micro-organisms were found here. It was hypothesised that the babirusa is a nonruminant foregut-fermenting frugivore/concentrate selector.