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Key words: atherosclerosis, inflammation, intima-media thickness, PPARγ, statins. IntroductionAtherosclerosis is a complex process that progresses through various functional and morphological alterations in the vessel wall, cumulating in overt cardiovascular disease. Measurement of the intima-media thickness (IMT) of the common carotid artery (CCA) by ultrasound has been established as a reliable screening tool for atherosclerosis and has been shown to predict the risk for stroke and ischaemic heart disease.1 Further, increased arterial stiffness measured by applanation tonometry is predictive for stroke, myocardial infarction and other macrovascular complications.2 In addition to these vascular measurements, laboratory markers of lipid metabolism, inflammation, adhesion molecules and new laboratory markers characterise the metabolic syndrome. Recently, intact proinsulin and adiponectin have been established as criteria of the metabolic syndrome and as predictors of cardiovascular risk in this high-risk population. 3,4The most common intervention to contain the atherosclerotic process and to reduce cardiovascular risk is treatment with 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, or statins. 5,6 Besides lowering of plasma lipids, treatment with statins has been shown to exert several pleiotropic effects, including a reduction in IMT and an improvement in arterial elasticity. 7,8 During recent years, increasing attention has been paid to the role of insulin resistance and the metabolic syndrome in the development of atherosclerosis and cardiovascular disease. Peroxisome proliferator-activated receptor (PPAR)γ agonists (thiazolidinediones), such as pioglitazone, are a class In a recent study, pioglitazone in addition to simvastatin treatment was shown to improve insulin resistance, to inhibit low-grade inflammation and to improve the overall cardiovascular risk profile even in non-diabetic patients with cardiovascular disease (CVD). 15,16 The aim of this study was to evaluate the effect of pioglitazone in addition to atorvastatin compared to atorvastatin alone on intimamedia thickness, vascular elasticity and several cardiovascular risk markers in a non-diabetic patient population at cardiovascular risk. MethodsThis study was a two-centre, prospective, double-blind, placebo-controlled trial, evaluating the effects of pioglitazone in addition to atorvastatin on IMT, arterial stiffness, endothelial function and several laboratory markers predictive for cardiovascular risk. The study was performed according to the Declaration of Helsinki and Good Clinical Practice, it was approved by the local ethical review board and all patients gave their written informed consent prior to study entry.Patients and study procedure Non-diabetic patients at increased cardiovascular risk, defined as those with an IMT greater than 0.8 mm and a previous medical history of myocardial infarction, coronary angiography with proven CVD, unstable angina pectoris, cervical or leg vessels with atherosclerotic alterations demon...

Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

Abstract. The effect of ACTH administration for 1—5 days on the morphology and steroidogenic capability of sheep adrenal tissue has been examined. During this period of treatment there was a gradual decline in the in vitro conversion of 3H-labelled precursors to products of solely zona glomerulosa origin (aldosterone and 18-hydroxycorticosterone) while conversion to products of zona fasciculata origin (17-hydroxyprogesterone, 11-deoxycortisol and cortisol) was stimulated throughout. Conversion to DOC, 18-hydroxydeoxycorticosterone and corticosterone (steroids produced by both the zona glomerulosa and the zona fasciculata) declined after initial stimulation. Within 2—3 days of the commencement of treatment, the zona glomerulosa showed a progressive decrease in cell number associated with disruption of cords and cell separation. Ultrastructurally, it was found that typical zona glomerulosa cells had almost disappeared. The majority of residual cells in this area had a structure intermediate between zona glomerulosa and zona fasciculata cells. The similarity in time-course of the alterations in both the morphological and biosynthetic characteristics suggests that the decline in aldosterone output caused by ACTH administration to sheep results from the loss of adrenal zona glomerulosa cells, predominantly due to selective cellular degeneration.