Comparison of the effects of ramipril versus telmisartan in reducing serum levels of high-sensitivity C-reactive protein and oxidized low-density lipoprotein cholesterol in patients with type 2 diabetes mellitus

The effect of ramipril (an angiotensin [AT]-converting enzyme inhibitor), telmisartan (an AT-II type 1 receptor blocker), or their combination on inflammation and lipid peroxidation was assessed in 37 patients with type 2 diabetes who were free of coronary artery disease. All regimens were associated with a significant reduction of C-reactive protein and oxidized low-density lipoprotein cholesterol serum levels (p <0.001). These results further enlighten the mechanisms underlying the cardiovascular beneficial effect of renin-AT system inhibition.     

Detection of increased temperature of the culprit lesion after recent myocardial infarction: the favorable effect of statins

Background

Increased thermal heterogeneity has been demonstrated in atherosclerotic plaques, with the higher temperature recorded in acute myocardial infarction (MI). Dietary or treatment interventions reduce heat production. The purpose of the present study was to investigate whether increased plaque temperature is maintained for a prolonged period after MI and the role of statin administration.

Methods

We enrolled 55 patients, 29 with recent MI and 26 with chronic stable angina (CSA). Total cholesterol, C-reactive protein (CRP), interleukin-6 (IL-6) and soluble adhesion molecules were measured in the study population. All patients underwent coronary plaque temperature measurements. Temperature difference (ΔT) was designated as the temperature of the culprit atherosclerotic plaque minus the temperature of the proximal healthy vessel wall.

Results

Under treatment with statins were 19 patients with recent MI and 14 with CSA. In patients with recent MI ΔT was 0.19 ± 0.18°C, while in patients with CSA was 0.10 ± 0.08°C (P = .03). Patients treated with statins had lower ΔT compared to untreated patients (0.10 ± 0.11 versus 0.20 ± 0.18°C, P = .01). Treated patients with recent MI had similar ΔT compared to CSA patients treated with statins (0.13 ± 0.13 versus 0.07 ± .06° C, P = .14), while untreated patients with recent MI had substantially increased ΔT compared to untreated patients with CSA (0.28 ± 0.22 versus 0.14 ± 0.10°C, P = .04). ΔT was positively correlated with CRP (R = 0.50, P < .01), IL-6 (R = 0.58, P < .01), and intercellular adhesion molecule-1 (R = 0.40, P = .03) levels.

Conclusion

Increased plaque temperature is observed for an extended period after myocardial infarction, indicating that the inflammatory process is sustained after plaque rupture. Statins have a beneficial effect after MI on plaque temperature.     

Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a key role in energy homeostasis. Like many neuropeptides, it signals through two G protein-coupled receptors. MCH receptor 1 (MCHR1) is the sole receptor expressed in rodents and couples to G(i) and G(q) proteins. Little is known about the intracellular pathways engaged by MCH and its receptor. Using HEK293 cells stably expressing MCHR1, we demonstrate that MCH, acting through MCHR1, antagonizes the action of forskolin, an adenylate cyclase activator that increases intracellular levels of cAMP. MCH also inhibits cAMP induction by the G(s)-coupled beta-adrenergic receptor. Activation of either the G(i)- or G(s)-dependent pathway typically results in ERK phosphorylation in HEK293 cells. In contrast to opposing actions on cAMP synthesis, simultaneous MCH and forskolin treatment results in synergistic activation of ERK. This synergy proceeds through pertussis toxin-independent pathways and requires several enzymatic activities such as protein kinase A, protein kinase C, phospholipase C, and Src kinase. Finally, we provide evidence that such positive interactions are not limited to cell lines but can also be observed in the brain.     

A conserved trimerization motif controls the topology of short coiled coils

In recent years, short coiled coils have been used for applications ranging from biomaterial to medical sciences. For many of these applications knowledge of the factors that control the topology of the engineered protein systems is essential. Here, we demonstrate that trimerization of short coiled coils is determined by a distinct structural motif that encompasses specific networks of surface salt bridges and optimal hydrophobic packing interactions. The motif is conserved among intracellular, extracellular, viral, and synthetic proteins and defines a universal molecular determinant for trimer formation of short coiled coils. In addition to being of particular interest for the biotechnological production of candidate therapeutic proteins, these findings may be of interest for viral drug development strategies.     

Hypercoagulable States in Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) patients have an increased risk for venous thromboembolism, mainly portal venous thrombosis (PVT). The aim of this study was to assess the role of acquired and hereditary thrombotic risk factors in HCC patients. Thirty-one patients with HCC, 30 patients with cirrhosis but without HCC or PVT, and 48 matched healthy controls were studied. Mean levels of plasma protein C, protein S, antithrombin, and serum lipoprotein (a) were significantly lower in patients with HCC and in the cirrhotic group compared to the healthy controls. Mean serum homocysteine levels were significantly higher in patients with HCC compared to cirrhotics and healthy controls. The prevalence of activated protein C resistance, factor V Leiden mutation, prothrombin gene mutation G20210GA, and C677T methylenetetrahydrofolate reductase polymorphism was not significantly different among the three groups. In conclusion, thrombophilic defects are common in HCC patients and they might contribute to the observed thrombotic complications in this malignancy.     

ST-segment depression during vasodilator stress is of minor clinical importance in women with normal myocardial perfusion imaging and low or intermediate risk of coronary artery disease

Purpose  

The prognostic value of electrocardiographic (ECG) ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion scintigraphy (MPS) is based on retrospective studies with controversial results. Moreover, the true incidence of obstructive coronary artery disease (CAD) in these patients is unknown.     

Impaired clearance of apoptotic cells leads to HMGB1 release in the bone marrow of patients with myelodysplastic syndromes and induces TLR4-mediated cytokine production

Excessive pro-inflammatory cytokine production in the bone marrow has been associated with the pathogenesis of myelodysplastic syndromes. We herein investigated the involvement of toll-like receptors and their endogenous ligands in the induction/maintenance of the inflammatory process in the marrow of patients with myelodysplastic syndromes. We evaluated the expression of toll-like receptors in marrow monocytes of patients (n=27) and healthy controls (n=25) by flow-cytometry and also assessed the activation of the respective signaling using a real-time polymerase chain reaction-based array. We measured the high mobility group box-1 protein, a toll-like receptor-4 ligand, in marrow plasma and long-term bone marrow culture supernatants by an enzyme-linked immunosorbent assay and we performed cross-over experiments using marrow plasma from patients and controls in the presence/absence of a toll-like receptor-4 inhibitor to evaluate the pro-inflammatory cytokine production by chemiluminescence. We assessed the apoptotic cell clearance capacity of patients’ macrophages using a fluorescence microscopy-based assay. We found over-expression of toll-like receptor-4 in patients’ marrow monocytes compared to that in controls; this over-expression was associated with up-modulation of 53 genes related to the respective signaling. Incubation of patients’ monocytes with autologous, but not with normal, marrow plasma resulted in over-production of pro-inflammatory cytokines, an effect that was abrogated by the toll-like receptor-4 inhibitor suggesting that the pro-inflammatory cytokine production in myelodysplastic syndromes is largely mediated through toll-like receptor-4. The levels of high mobility group box-1 protein were increased in patients’ marrow plasma and culture supernatants compared to the levels in controls. Patients’ macrophages displayed an impaired capacity to engulf apoptotic cells and this defect was associated with excessive release of high mobility group box-1 protein by dying cells. A primary apoptotic cell clearance defect of marrow macrophages in myelodysplastic syndromes may contribute to the induction/maintenance of the inflammatory process through aberrant release of molecules inducing toll-like receptor-4 such as high mobility group box-1 protein.     

Fibrin glue for sealing the needle track after percutaneous lung biopsy: Part I—experimental study

Purpose Evaluate the effectiveness of fibrin glue for the embolic occlusion of needle tracks following percutaneous lung biopsy (PLB).Methods Twenty-six rabbits underwent computed tomography (CT)-guided PLB using a coaxial system consisting of 19-and 22-gauge needles. Thirteen rabbits were used as controls (group A). In 13 other rabbits (group B), fibrin glue labelled with I¹³¹ fibrinogen and contrast medium was injected into the track. Both groups were examined by CT for the presence and severity of pneumothorax (mild: less than 20%; severe: more than 20%). Group B was also examined scintigraphically and their lungs were studied histologically. Results: In group A, pneumothorax developed in eight animals (61.6%) and was severe in six (46.1%) whereas in group B, pneumothorax developed in five animals (38.5%) and was severe in one (7.7%). Though the difference between the two groups in overall incidence of pneumothorax was not significant (p > 0.1), it was significantly higher (p < 0.025) for severe pneumothorax in group A. No signs of systemic embolism were observed.Conclusions Based on this animal model, fibrin glue is a safe and useful sealant following PLB and reduces the incidence of severe pneumothorax.