Red cell adhesion molecules, foetal haemoglobin and endothelial factors in sickle cell disorders

Sickle cell anaemia (SS) is a haemoglobinopathy involving production of sickle haemoglobin (HbS, β⁶Glu-->Val), which is able to polymerise leading to vaso-occlusion. Hydroxyurea (HU) treatment increases foetal haemoglobin (HbF) levels but decreases vaso-occlusion and red cell adhesion molecule (AM) expression, and therefore improves clinical symptoms. In this thesis, the contribution of AMs, HbF and endothelial factors to the severity of sickle cell disease has been studied. Flow cytometry for measurement of HbF-containing red cells (F⁺cells), AM-expressing red cells (AM⁺cells) and reticulocytes (retics) was developed and validated using single-, double- and triple-colour staining procedures. The AMs examined were CD36, CD41 and CD49d. F⁺cells are increased in SS patients over normal control subjects. In the controls, the percentage of F⁺mature red cells (%F⁺MRCs) is equal to %F⁺retics leading to an enrichment ratio (ER = %F⁺MRCs / %F⁺retics) close to 1.0, indicating no survival advantage of F⁺cells. However in SS patients, the ER is about 1.5-2.5 indicating a survival advantage of F⁺cells. AM⁺cells in SS patients are also increased over the controls. In both the controls and SS patients, the AM⁺cell depletion ratio (AMDR = %AM⁺MRCs / %AM⁺retics) is decreased to less than 0.05, indicating a rapid shedding of AMs from reticulocytes during maturation. This shedding is confirmed by a reduction of %AM⁺cells to undetectable levels after 5 days of reticulocytes in culture. In HU-treated SS patients, F⁺cell increment and AM⁺cell reduction are found. The %AM⁺retics for pre- and post-HU treatment is not different, suggesting that AM⁺cell reduction is dependent on the reduction of reticulocytes. In the controls, proportion of F⁺cells expressing AMs is higher than F⁺cells, indicating that F⁺cells are more primitive. In SS patients, these proportions are similar. However, in HU-treated SS patients, the proportion of F⁺cells expressing AMs is lower than F⁺cells, confirming that F⁺cells survive longer so that they have more time to shed more AMs. This finding is similar in both reticulocyte and MRC populations. Vascular endothelial growth factor (VEGF) may be involved in vasoocclusion. It is significantly increased in SS patients. VEGF is able to induce nitric oxide metabolite (NOx) release. However in this thesis, NOx levels were not increased in SS patients and no correlation was found between NOx and VEGF levels. No relationship was observed between VEGF and either erythropoietin or Hb levels, suggesting that VEGF increment may not be due to generalised anaernia. Increases in soluble endothelial selectin (sE-Selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1) found in SS patients indicate endothelial activation. Beta-thromboglobulin (BTG) and platelet factor 4 (PF4) were also increased in SS patients, due to local platelet activation in vivo. Platelets as well as endothelial cells contain VEGF, therefore the increased VEGF levels in SS could be a consequence of local ischaernia resulting from vaso-occlusion and local platelet and endothelial cell activation

A High Prevalence of Hepatitis C Virus Infection Among The Human Immunodeficiency Virus Seropositive Blood Donors in Chiang Mai, Thailand

We report the results of serological survey of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections among the human immunodeficiency virus (HIV) seropositive and seronegative blood donors in Chiang Mai, Thailand. Anti-HCV were positive in 17 out of 276 anti-HIV seropositive blood donors (6.2%) and six out of 844 anti-HIV seronegative blood donors (0.7%). HBs-Ag were positive in 20 out of 276 anti-HIV seropositive blood donors (7.2%) and 68 out of 844 anti-HIV seronegative blood donors (8.1%). These findings suggest that anti-HIV seropositive population belongs to a high risk group of HCV infection and there are similar transmission routes between HIV and HCV infections

How royals feasted in the court of Pedro I of Castile: A contribution of stable isotope study to medieval history

Study of the human remains of King Pedro I of Castile (1334–1369), his wife Queen Maria of Padilla (c. 1334– 1361), and three other members of his family offered the possibility to investigate the diet of an elite in the me dieval Iberian Peninsula by analyzing δ15N and δ13C values in collagen samples of their bones. Two medieval archeological samples were selected for comparative purposes: a Christian sample (n = 5) from Palacios de la Sierra (Burgos), and a Muslim sample (n = 5) from La Torrecilla (Granada). Results obtained were compared with published data on other medieval populations of the Iberian Peninsula with the aim of improving knowl edge on the diet of medieval populations, especially elite groups. Differences in the consumption of C3 and C4 plants were observed between Christians and Muslims, as previously reported. δ15N values indicated social class differences. The diet of the Royal Family was characterized by mainly C3 plants and an extremely high an imal protein intake characteristic of carnivores. These results are consistent with historical data on the life cir cumstances of this family.Proyecto HAR2016-75788-P del Gobierno de Españ

Diet and food strategies in a southern al-Andalusian urban environment during Caliphal period, ecija, Sevilla

The Iberian medieval period is unique in European history due to the widespread socio-cultural changes that took place after the arrival of Arabs, Berbers and Islam in 711 AD. Recently, isotopic research has been insightful on dietary shifts, status, resource availability and the impact of environment. However, there is no published isotopic research exploring these factors in southern Iberian populations, and as the history of this area differs to the northern regions, this leaves a significant lacuna in our knowledge. This research fills this gap via isotopic analysis of human (n = 66) and faunal (n = 13) samples from the 9th to the 13th century Écija, a town renowned for high temperatures and salinity. Stable carbon (δ13C) and nitrogen (δ15N) isotopes were assessed from rib collagen, while carbon (δ13C) values were derived from enamel apatite. Human diet is consistent with C3 plant consumption with a very minor contribution of C4 plants, an interesting feature considering the suitability of Écija to C4 cereal production. δ15N values vary among adults, which may suggest variable animal protein consumption or isotopic variation within animal species due to differences in foddering. Consideration of δ13C collagen and apatite values together may indicate sugarcane consumption, while moderate δ15N values do not suggest a strong aridity or salinity effect. Comparison with other Iberian groups shows similarities relating to time and location rather than by religion, although more multi-isotopic studies combined with zooarchaeology and botany may reveal subtle differences unobservable in carbon and nitrogen collagen studies alone.OLC is funded by Plan Galego I2C mod.B (ED481D 2017/014). The research was partially funded by the projects “Galician Paleodiet” and by Consiliencia network (ED 431D2017/08) Xunta de GaliciaS

Isotopic evidence for dietary diversity at the mediaeval Islamic necropolis of Can Fonoll (10th to 13th centuries CE), Ibiza, Spain

The diet of the population interred at the Islamic necropolis of Can Fonoll, Ibiza, Spain, which was in use between the 10th and 13th centuries AD, is reconstructed from the carbon (δ13C) and nitrogen (δ15N) stable isotope ratios of bone collagen from 112 individuals. The mean ± sd (1σ) δ13C (− 19.0 ± 1.3‰) and δ15N (10.3 ± 0.8‰) values of the Can Fonoll population indicate a diet based largely on terrestrial C3 resources. However, the wide range of both δ13C (− 20.6‰ to − 8.6‰) and δ15N (7.0‰ to 12.1‰) values attested at Can Fonoll indicate significant variation in individual diet. The elevated δ13C values of a small proportion of the individuals buried at Can Fonoll are consistent with the consumption of a large proportion of, or dependence on, C4 resources, such as millet. Comparison of the δ13C and δ15N values of the Can Fonoll population with those of other mediaeval populations from the Balearic Islands and mainland Spain highlights a wide range of stable isotope values, which reflects not only significant differences in diet but also points to widespread mobility within the Mediterranean Basin

Exploring diet and society in medieval Spain : new approaches using stable isotope analysis

The multi-faith society of medieval Iberia, where Muslims, Christians and Jews co-existed under changing religious political rule, provides a novel setting for the study of diet. This thesis employs carbon (δ13C) and nitrogen (δ15N) isotope analysis to explore variability in diet and resource exploitation between faiths, localities and through time under Muslim and later Christian rule and places the isotopic data in the context of other historical and archaeological evidence. Isotope analysis was performed on bone collagen from 126 animals and 210 humans representing Muslims and Christians, sampled from sites in Jaca, Zaragoza, Albarracín, Valencia, Gandía and Benipeixcar (c.11th -16th centuries AD) that follow a geographical transect from the Pyrenees to the Mediterranean coast, through Aragón and Valencia. Results indicate humans from all locations consumed a diet based on terrestrial plant and animal protein, with a possible input of aquatic resources at Zaragoza, Valencia and Gandía. There were no consistent differences in diet between faiths, however differences were present between contemporaneous populations of Muslims and Christians in Benipeixcar and Gandía and successive populations of Muslims and Christians in Valencia. A north-south, inland-coastal trend was revealed in the exploitation of C4 plants (millet, sorghum, possibly sugarcane for cattle fodder) which made a significant contribution to the diets of some animals and humans, particularly in the south. Social status and the rural/urban nature of settlements influenced the extent of this exploitation. Dietary diversity was observed in Valencia, particularly in the Islamic period and the presence of immigrants among the populations of this city and Jaca is hypothesised. Sex-based differences in diet were present at some, but not all sites. Variable isotope ratios for animals at almost all sites demonstrates the variety of animal husbandry practices and ecological niches that were exploited during the medieval period in Spain.EThOS - Electronic Theses Online ServiceGBUnited Kingdo