Regulation of plasma high-density lipoprotein levels by the ABCA1 transporter and the emerging role of high-density lipoprotein in the treatment of cardiovascular disease

High-density lipoproteins (HDL) protect against cardiovascular disease. HDL removes and transports excess cholesterol from peripheral cells to the liver for removal from the body. HDL also protects low-density lipoproteins (LDL) from oxidation and inhibits expression of adhesion molecules in endothelial cells, preventing monocyte movement into the vessel wall. The ABCA1 transporter regulates intracellular cholesterol levels in the liver and in peripheral cells by effluxing excess cholesterol to lipid-poor apoA-I to form nascent HDL, which is converted to mature alpha-HDL by esterification of cholesterol to cholesteryl esters (CE) by lecithin cholesterol acyltransferase. The hepatic ABCA1 transporter and apoA-I are major determinants of levels of plasma alpha-HDL cholesterol as well as poorly lipidated apoA-I, which interact with ABCA1 transporters on peripheral cells in the process of reverse cholesterol transport. Cholesterol in HDL is transported directly back to the liver by HDL or after transfer of CE by the cholesteryl ester transfer protein (CETP) by the apoB lipoproteins. Current approaches to increasing HDL to determine the efficacy of HDL in reducing atherosclerosis involve acute HDL therapy with infusions of apoA-I or apoA-I mimetic peptides and chronic long-term therapy with selective agents to increase HDL, including CETP inhibitors.     

Sciatic nerve block with lateral popliteal approach for hallux vagus correction. Comparison between 0.5% bupivacaine and 0.75% ropivacaine

AIM: In this study the authors compared the clinical profile of 2 local anesthetic drugs in the sciatic nerve block used during hallux valgus correction, a surgical procedure known to be post-operatively extremely painful. Since hallux valgus correction is painful post-operatively, many attempts have been tried to ensure a long-lasting analgesia. Block of the sciatic nerve appears to be the right choice balancing ease to performance, satisfaction of the patient and duration of action. METHODS: The authors investigated the use of 20 ml of 0.5% bupivacaine or 0.75% ropivacaine regarding the speed of onset, quality and length of duration of sciatic nerve block performed with a lateral popliteal approach. Sixty ASA I-III patients (aged 19-73 years) were enrolled in this trial. Written informed consent was asked and obtained. A 20 G 50 mm Teflon coated Crawford needle, delivering 0.5 mA at 2 Hz, was used to locate and block the sciatic nerve in the popliteal fossa with a lateral approach. RESULTS: Patients in the ropivacaine group required about 13 minutes to achieve a complete block and about 16 minutes were needed in the bupivacaine group for the anesthesia to be complete. The length of analgesia was 16 h for the ropivacaine group and 13 h for the bupivacaine group. This kind of approach to block the sciatic nerve appeared to the authors to be very easy to perform, with the patient lying in a natural position. Surgical anesthesia required less than 30 min in both groups to be ready, while the ropivacaine group had a longer length of analgesia compared to the bupivacaine group. CONCLUSIONS: Patient satisfaction was high in both groups.     

Endomyocardial biopsy guided by electroanatomic voltage mapping in arrhythmogenic right ventricular cardiomyopathy: a case report

A positive endomyocardial biopsy (EMB) is a major diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC). Nevertheless, its sensitivity is low due to the focal nature of the disease. Moreover, myocardial samples are usually taken from the uncommonly involved interventricular septum to minimize the risk of perforation. In this report, we describe a novel bioptical approach for ARVC diagnosis guided by the identification of right ventricle (RV) affected regions by means of electroanatomical voltage mapping.     

Beneficial effects of postmenopausal hormone replacement therapy with transdermal estradiol on sensitivity to activated protein C.

Many hemostatic and fibrinolytic parameters have been evaluated following hormone replacement therapy (HRT) but little is known about its influence on the anticoagulant response to activated protein C (APC-sensitivity). For this purpose, we studied the effect of transdermal 17-beta-estradiol (50 microg/24 h) by a continuous regimen on the APC-sensitivity, in 28 postmenopausal hysterectomized women (mean age, 47 years; range, 44-65 years). We also measured the plasma proteins directly involved in the protein C anticoagulant pathway, such as activities of factor VIII (VIII:C), factor V and free protein S. Von Willebrand factor (vWF) antigen, the carrier protein of factor VIII, was also determined. Blood sampling was done at baseline and after 16-week therapy. A significant increase in the normalized APC-sensitivity ratio (n-APC-SR) values (mean +/- SD: pre-trial, 0.88 +/- 0.14; post-trial, 1.01 +/- 0.12; P < 0.001) and a significant decrease of factor VIII:C plasma levels (pre-trial, 1.13 +/- 0.29 IU/ml; post-trial, 0.98 +/- 0.20 IU/ ml; P = 0.001) were found. No difference was observed in factor V, protein S and vWF plasma levels. Correlation studies demonstrated only a significant negative correlation between the percent change in n-APC-SR and the percent change in factor VIII:C (r = -0.574; P = 0.001). Our findings clearly show that HRT with transdermal estradiol improves the anticoagulant response to APC, probably as a result of a decreased factor VIII:C. We also suggest that a similar but opposite mechanism may occur for perorally administered estrogens used in the HRT. These results may have some clinical implications about the reported increase of the risk for venous thromboembolism following HRT.     

The PFA‐100™ system for the assessment of platelet function in normotensive and hypertensive pregnancies

Platelet function was studied in 30 pregnant women: 14 normotensive (C), and 16 affected by pregnancy‐induced hypertension (PIH). Platelet aggregometry (PA) on platelet‐rich plasma according to Born was compared with the new PFA‐100^? System (Dade International Inc, Miami, USA). This device evaluates platelet function (expressed in seconds as closure time, CT) in anticoagulated whole blood ex vivo at high shear rates. PA (expressed as percentage of light transmission) and CT were measured at baseline and after incubation with L‐Arginine (L‐Arg). MANOVA for repeated measures showed that L‐Arg incubation significantly decreased PA (F=7.2, P < 0.05) and increased CT (F=6.05, P < 0.05) in the whole population of pregnant women. Moreover, we analysed separately both parameters in C and in PIH subjects. No differences in PA were found in both groups, neither at baseline nor after L‐Arginine incubation. In contrast, CT was significantly longer in PIH in comparison to C before (95.9 s vs. 84 s, P < 0.05) as well after (115 s vs. 92 s, P < 0.05) L‐Arginine incubation. Data from PFA‐100^? confirm our previous reports that during pregnancy the L‐Arginine: Nitric Oxide pathway regulates platelet function. In hypertensive patients a significant decrease in platelet function was found by using the PFA‐100^? system.     

Malignant ascites: new concepts in pathophysiology, diagnosis, and management.

Malignant ascites is a manifestation of advanced malignant disease that is associated with significant morbidity. Mainstays of treatment include diuretics and recurrent large volume paracentesis. Although lymphatic obstruction has been considered the major pathophysiologic mechanism behind its formation, recent evidence suggests that immune modulators, vascular permeability factors, and metalloproteinases are contributing significantly to the process. These new observations offer the opportunity for development of new, more targeted therapies for the treatment of malignant ascites. This article uses a clinical case to highlight the problem, then reviews these new concepts in the pathophysiology of malignant ascites formation. The diagnosis and management of this challenging medical problem are subsequently discussed, with emphasis on how these new pathophysiologic insights are being applied to the development of novel therapies that may soon change how we manage this troubling clinical condition.     

Effects of Artemetin on Nitric Oxide Release and Protection against Peroxidative Injuries in Porcine Coronary Artery Endothelial Cells

Artemetin is one of the main components of Achillea millefolium L. and Artemisia absinthium, which have long been used for the treatment of various diseases. To date, however, available information about protective effects of their extracts on the cardiovascular system is scarce. Therefore, we planned to analyze the effects of artemetin on nitric oxide (NO) release and the protection exerted against oxidation in porcine aortic endothelial (PAE) cells. In PAE, we examined the modulation of NO release caused by artemetin and the involvement of muscarinic receptors, β2‐adrenoreceptors, estrogenic receptors (ER), protein‐kinase A, phospholipase‐C, endothelial‐NO‐synthase (eNOS), Akt, extracellular‐signal‐regulated kinases 1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK). Moreover, in cells treated with hydrogen peroxide, the effects of artemetin were examined on cell survival, glutathione (GSH) levels, apoptosis, mitochondrial membrane potential and transition pore opening. Artemetin increased eNOS‐dependent NO production by the involvement of muscarinic receptors, β2‐adrenoreceptors, ER and all the aforementioned kinases. Furthermore, artemetin improved cell viability in PAE that were subjected to peroxidation by counteracting GSH depletion and apoptosis and through the modulation of mitochondrial function. In conclusion, artemetin protected endothelial function by acting as antioxidant and antiapoptotic agent and through the activation of ERK1/2 and Akt. Copyright © 2015 John Wiley & Sons, Ltd.     

Induction of Cytokine Synthesis by Flagella from Gram-Negative Bacteria May Be Dependent on the Activation or Differentiation State of Human Monocytes

We have previously demonstrated that salmonellae, but not Escherichia coli or Yersinia enterocolitica, stimulates tumor necrosis factor alpha (TNFalpha) production in the human promonocytic cell line U38. Subsequent analysis revealed that the TNFalpha-inducing activity of salmonellae was associated with flagellin, a major component of flagella from gram-negative bacteria. In the present study, we have explored the basis for the apparent specificity of action of Salmonella flagella on TNFalpha expression in U38 cells and have extended this analysis to normal human peripheral blood mononuclear cells (PBMC). Flagella from the enteropathogenic E. coli strain E2348/69, Y. enterocolitica JB580, and Pseudomonas aeruginosa PAO1, which did not induce significant levels of TNFalpha production in U38 cells, were as potent as Salmonella flagella in terms of TNFalpha and interleukin 1beta activation in PBMC. However, TNFalpha production in U38 cells was greatly enhanced when these cells were stimulated with flagella from E. coli, Y. enterocolitica, and P. aeruginosa in the presence of a costimulant, phorbol 13-myristate acetate. These findings are consistent with the hypothesis that the activation or differentiation state of a monocyte may have a substantial effect on the cell's responsiveness to flagellum stimulation of cytokine synthesis. Furthermore, these results indicate that cytokine induction in monocytes may be a general property of flagella from gram-negative bacteria.     

Acute ovarian torsion in an infant: diagnostic clues on supine and decubitus abdominal radiographs confirmed by ultrasound

Acute ovarian torsion is an uncommon yet important diagnostic consideration in any female pediatric patient presenting with acute abdominal pain. A 2-month-old infant presented to the emergency department with a several-day history of constipation. Evaluation with plain radiographs demonstrated a subtle yet persistent soft tissue mass in the right pelvis. Follow-up ultrasound revealed characteristic findings for ovarian torsion and subsequent salpingo-oophorectomy was performed confirming the diagnosis. Acute ovarian torsion is an uncommon and frequently overlooked diagnosis in female infants presenting with gastrointestinal or urinary tract symptoms. Careful assessment of plain radiographic findings may aid in the further management of this difficult diagnosis in female infants. Ultrasound is recommended to confirm the diagnosis.     

Extracorporeal shock wave therapy promotes cell proliferation and collagen synthesis of primary cultured human tenocytes

Purpose  

The aim of this study was to investigate whether the effects of extracorporeal shock wave therapy (ESWT) could affect the behavior of primary cultured human tenocytes over a 12-day period.