Thyroid hormones are now recognized to change in different disease states with important consequences on severity and prognosis of disease. However, little is known about thyroid hormones' alterations in acute liver failure (ALF). To study the changes in thyroid hormones and cardiac thyroid receptors during ALF, we subjected seven female pigs to surgical liver devascularization. Liver function biochemical markers, thyroid hormones, endogenous opioids, malondialdehyde (MDA), and interleukins 1 and 6 were measured in serum for 24 h postoperatively. Heart biopsies were harvested at the end of the experiment. Baseline heart biopsies were taken from five additional animals. Serum thyroxin (T(4)) and triiodothyronine (T(3)) levels markedly decreased, whereas free-triiodothyronine and thyroxin-stimulating hormone levels did not change. T(4) and T(3) levels correlated with the degree of liver failure and with MDA and interleukin-6 levels. Beta-endorphin levels initially increased, whereas levels of leucine-enkephalin did not change. Thyroid hormone receptor-alpha1 protein expression in the heart decreased 1.6-fold after ALF, whereas myocardial myosin isoform expression remained unchanged. The downregulation of T(4) and T(3) levels during ALF seems to correlate well with the severity of disease. This downregulation related to inflammation and oxidative stress and resulted in changes in myocardial thyroid receptors.

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Inflammation is involved in the development of atherosclerosis. The CC chemokine receptor 5 (CCR5) initiates chemotaxis and modulates the inflammation secondary to atherosclerosis and related vascular diseases. The CCR5 Δ32 polymorphism influences the expression of CCR5 on the cell surface. The purpose of this study was to examine the effect of the Δ32 polymorphism in ischaemic cerebrovascular disease (ICVD). The CCR5 Δ32 polymorphism was genotyped in 1462 individuals: 562 ischaemic stroke (IS), 97 transient ischaemic attack (TIA) and in 803 healthy controls. All 659 ICVD patients were categorized according to the Trial of Org 10172 in Acute Stroke Treatment aetiological classification. The investigated subtypes were large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO) and cryptogenic disease (CRYPT). Genotyping was performed with the TaqMan polymerase chain reaction. The Δ32 allele was less frequent in CE patients compared with LAA (OR, 0.4; 95% CI, 0.24–0.79; P = 0.008), SAO (OR, 0.5; 95% CI, 0.29–0.84; P = 0.01), CRYPT (OR, 0.5; 95% CI, 0.28–0.82; P = 0.008) and controls (OR, 0.5; 95% CI, 0.36–0.82; P = 0.002). Multiple logistic regression analysis showed that the Δ32 allele is associated with a lower risk for cardioembolic ICVD (OR 0.5; 95% CI, 0.28–0.75; P = 0.002) when compared with ICVD of other causes. The Δ32 polymorphism of CCR5 may differentiate cardioembolism from the remaining causes of ICVD.