Maria Luaces-Regueira

Quantitative elastography associated with endoscopic ultrasound for the diagnosis of chronic pancreatitis.

BACKGROUND AND STUDY AIMS Endoscopic ultrasonography (EUS) has become the method of choice for the diagnosis of chronic pancreatitis in clinical practice. However, the criteria allowing the specific diagnosis of the disease, mainly at non-advanced stages, are still under debate. Analysis of tissue stiffness by quantitative EUS-elastography may provide additional relevant information in this setting. The aim of this study was to evaluate the information provided by quantitative EUS-elastography for the diagnosis of chronic pancreatitis. PATIENTS AND METHODS A prospective, consecutive, 1-year study was designed, and included patients who underwent EUS for epigastric pain syndrome or known chronic pancreatitis. EUS-elastography was performed using radial Pentax EUS and Hitachi EUB900. The strain ratio was measured in the head, body, and tail of the pancreas, and the elastographic result was the mean of these three values. EUS criteria of chronic pancreatitis and the Rosemont classification were also evaluated. Data were analyzed by analysis of variance and linear regression; diagnostic accuracy was based on the receiver operating characteristic (ROC) curve analysis. RESULTS A total of 191 patients (mean age 52 years, range 21 - 85; 103 male) were included; 92 (48.2 %) of them were finally diagnosed with chronic pancreatitis. A highly significant direct linear correlation was found between the number of EUS criteria of chronic pancreatitis and the strain ratio (r = 0.813; P < 0.0001). The area under the ROC curve was 0.949 (95 % confidence interval 0.916 - 0.982) and the accuracy of EUS-elastography for diagnosing chronic pancreatitis was 91.1 % (cut-off strain ratio of 2.25). The strain ratio varied significantly in different Rosemont classification groups (P < 0.001). CONCLUSIONS EUS-elastography was an accurate tool for the diagnosis of chronic pancreatitis and provided relevant and objective information to support EUS findings.

Smoking as a risk factor for complications in chronic pancreatitis.

Objectives Several recent studies have demonstrated the association between smoking and chronic pancreatitis (CP). However, less is known about the role of smoking in the development of CP-related complications. Our aim was to investigate the impact of smoking and alcohol consumption on age of onset and complications at CP diagnosis. Methods A cross-sectional case-case study was performed within a prospectively collected cohort of patients with CP. Alcohol consumption and smoking habits were assessed using a standardized questionnaire. Morphologic severity was defined based on endoscopic ultrasound criteria for CP and classified as mild (3–4 criteria), moderate (5–6 criteria), and severe (≥7 criteria or calcifications). Pancreatic exocrine insufficiency (PEI) was diagnosed using the 13C-mixed triglyceride breath test. Odds ratios (OR) with 95% confidence intervals (CI) for CP-related complications were calculated using a case-case design. Results A total of 241 patients were included. Smoking was associated with PEI (OR [95% CI], 2.4 [1.17–5.16]), calcifications (OR [95% CI], 2.33 [1.10–4.95]), and severe morphologic changes (OR [95% CI], 3.41 [1.31–8.85]) but not with pseudocysts or diabetes. Neither smoking nor alcohol consumption was associated with age of onset. Conclusions Tobacco, but not alcohol, is associated with PEI, calcifications, and severe morphologic (≥7 criteria or calcifications) CP at diagnosis. Smoking cessation should be encouraged in patients with CP.

The cAMP effectors PKA and Epac activate endothelial NO synthase through PI3K/Akt pathway in human endothelial cells

ABSTRACT 3′,5′‐Cyclic adenosine monophosphate (cAMP) exerts an endothelium‐dependent vasorelaxant action by stimulating endothelial NO synthase (eNOS) activity, and the subsequent NO release, through cAMP protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) activation in endothelial cells. Here, we have investigated the mechanism by which the cAMP‐Epac/PKA pathway activates eNOS. cAMP‐elevating agents (forskolin and dibutyryl‐cAMP) and the joint activation of PKA (6‐Bnz‐cAMP) and Epac (8‐pCPT‐2′‐O‐Me‐cAMP) increased cytoplasmic Ca2+ concentration ([Ca2+]c) in ≤30% of fura‐2‐loaded isolated human umbilical vein endothelial cells (HUVEC). However, these drugs did not modify [Ca2+]c in fluo‐4‐loaded HUVEC monolayers. In DAF‐2‐loaded HUVEC monolayers, forskolin, PKA and Epac activators significantly increased NO release, and the forskolin effect was reduced by inhibition of PKA (Rp‐cAMPs), Epac (ESI‐09), eNOS (L‐NAME) or phosphoinositide 3‐kinase (PI3K; LY‐294,002). On the other hand, inhibition of CaMKII (KN‐93), AMPK (Compound C), or total absence of Ca2+, was without effect. In Western blot experiments, Serine 1177 phosphorylated‐eNOS was significantly increased in HUVEC by cAMP‐elevating agents and PKA or Epac activators. In isolated rat aortic rings LY‐294,002, but not KN‐93 or Compound C, significantly reduced the vasorelaxant effects of forskolin in the presence of endothelium. Our results suggest that Epac and PKA activate eNOS via Ser 1177 phosphorylation by activating the PI3K/Akt pathway, and independently of AMPK or CaMKII activation or [Ca2+]c increase. This action explains, in part, the endothelium‐dependent vasorelaxant effect of cAMP.

Mechanisms of Action of Kefir in Chronic Cardiovascular and Metabolic Diseases

The gut microbiota maintains a complex mutual interaction with different organs of the host. Whereas in normal conditions this natural community of trillions of microorganisms greatly contributes to the human health, gut dysbiosis is related with onset or worsening of diverse chronic systemic diseases. Thus, the reestablishment of gut microbiota homeostasis with consumption of prebiotics and probiotics may be a relevant strategy to prevent or attenuate several cardiovascular and metabolic complications. Among these functional foods, the synbiotic kefir, which is a fermented milk composed of a mixture of bacteria and yeasts, is currently the most used and has attracted the attention of health care professionals. The present review is focused on reports describing the feasibility of kefir consumption to provide benefits in cardiometabolic diseases, including hypertension, vascular endothelial dysfunction, dyslipidemia and insulin resistance. Interestingly, recent studies show that mechanisms of actions of kefir in cardiometabolic diseases include recruitment of endothelial progenitor cells, improvement of the balance vagal/sympathetic nervous system, diminution of excessive generation of reactive oxygen species, angiotensin converting enzyme inhibition, anti-inflammatory cytokines profile and alteration of the intestinal microbiota. These findings provide a better understanding about the mechanisms of the beneficial actions of kefir and motivate further investigations to determine whether the use of this synbiotic could also be translated into clinical improvements in cardiometabolic diseases.