Boldine prevents the inflammatory response of cardiac fibroblasts induced by SGK1-NFκB signaling pathway activation.

Cardiac fibroblasts (CF) are mesenchymal-type cells responsible for maintaining the homeostasis of the heart's extracellular matrix (ECM). Their dysfunction leads to excessive secretion of ECM proteins, tissue stiffening, impaired nutrient and oxygen exchange, and electrical abnormalities in the heart. Additionally, CF act as sentinel cells in the cardiac tissue microenvironment, responding to various stimuli that may affect heart function. Deleterious stimuli induce an inflammatory response in CF, increasing the secretion of cytokines such as IL-1ß and TNF-α and the expression of cell adhesion molecules like ICAM1 and VCAM1, initially promoting damage resolution by recruiting immune cells. However, constant harmful stimuli lead to a chronic inflammatory process and heart dysfunction. Therefore, it is necessary to study the mechanisms that govern CF inflammation. NFκB is a key regulator of the cardiac inflammatory process, making the search for mechanisms of NFκB regulation and CF inflammatory response crucial for developing new treatment options for cardiovascular diseases. SGK1, a serine-threonine protein kinase, is one of the regulators of NFκB and is involved in the fibrotic effects of angiotensin II and aldosterone, as well as in CF differentiation. However, its role in the CF inflammatory response is unknown. On the other hand, many bioactive natural products have demonstrated anti-inflammatory effects, but their role in CF inflammation is unknown. One such molecule is boldine, an alkaloid obtained from Boldo (Peumus boldus), a Chilean endemic tree with proven cytoprotective effects. However, its involvement in the regulation of SGK1 and CF inflammation is unknown. In this study, we evaluated the role of SGK1 and boldine in the inflammatory response in CF isolated from neonatal Sprague-Dawley rats. The involvement of SGK1 was analyzed using GSK650394, a specific SGK1 inhibitor. Our results demonstrate that SGK1 is crucial for LPS- and IFN-γ-induced inflammatory responses in CF (cytokine expression, cell adhesion molecule expression, and leukocyte adhesion). Furthermore, a conditioned medium (intracellular content of CF subject to freeze/thaw cycles) was used to simulate a sterile inflammation condition. The conditioned medium induced a potent inflammatory response in CF, which was completely prevented by the SGK1 inhibitor. Finally, our results indicate that boldine inhibits both SGK1 activation and the CF inflammatory response induced by LPS, IFN-γ, and CF-conditioned medium. Taken together, our results position SGK1 as an important regulator of the CF inflammatory response and boldine as a promising anti-inflammatory drug in the context of cardiovascular diseases.

Utility of the AM-PAC "6 Clicks" Basic Mobility and Daily Activity Short Forms to Determine Discharge Destination in an Acute Stroke Population.

IMPORTANCE: The American Heart Association and American Stroke Association recommend early identification of level of rehabilitative care as a priority after stroke. OBJECTIVE: To evaluate the utility of the Activity Measure for Post-Acute Care (AM-PAC) "6 Clicks" Daily Activity and Basic Mobility forms to determine the next level of rehabilitation after hospitalization for adults with stroke. DESIGN: Retrospective cohort design using medical records from 2015 to 2016. SETTING: Major urban hospital. PARTICIPANTS: Patients admitted to the stroke service, with a confirmed stroke, who were seen by a physical or occupational therapist; who had a 6 Clicks Basic Mobility or Daily Activity score at initial evaluation; and who were discharged to home, an acute inpatient rehabilitation facility (IRF), or a subacute skilled nursing facility (SNF). OUTCOMES AND MEASURES: Length of stay and discharge destination. RESULTS: Seven hundred four participants (M age = 68.28 yr; 51.21% female) were included. Analysis of variance and receiver operating characteristic curves were performed. Daily Activity scores were highest for home discharge, lower for IRF discharge, and lowest for SNF discharge; Basic Mobility showed a similar pattern. Cutoff values distinguishing home from further inpatient rehabilitation were 44.50 for Basic Mobility and 39.40 for Daily Activity scores (area under the curve [AUC] = .82 for both forms), with scores of 34.59 (AUC = 0.64) and 31.32 (AUC = 0.67) separating IRF from SNF, respectively. CONCLUSIONS AND RELEVANCE: Therapists should incorporate 6 Clicks scores into their discharge planning. What This Article Adds: This research demonstrates the utility of an outcome measure in the acute care setting that assists in planning discharge destination for patients with stroke.

Clinical outcomes of a beveled tip, ultra-high speed, 25-gauge pars plana vitrectomy system.

OBJECTIVE: To report the clinical outcomes of a 25-gauge, beveled-tip, 10,000 cuts-per-minute (cpm) microincisional vitrectomy surgery (MIVS) system. METHODS: Prospective case series of eyes undergoing primary pars plana vitrectomy (PPV) for common vitreoretinal indications. Main outcome measures were: rate of achieving surgical objectives, operative times, number of surgical steps, use of ancillary instruments, corrected distance visual acuity (CDVA), and adverse events (AE). RESULTS: The surgical objectives were achieved in all eyes. Mean total operative time (TOT), core, shave and total vitrectomy times were 1891 ± 890, 204 ± 120, 330 ± 320, 534 ± 389 s, respectively. Mean number of surgical steps was 4.3 ± 1.5. Mean number of ancillary instruments used was 4.5 ± 1.9. Mean CDVA improved by 0.53 ± 0.56 logMAR units (P < 0.001) 3 months postoperatively. AE included elevated IOP (8%), hypotony (6%), and re-detachment (2%). Majority (82%) had no postoperative discomfort. The number of surgical steps demonstrated a positive correlation with TOT (p < 0.05), number of ancillary instruments used (p < 0.05), and postoperative Day 1 IOP (p < 0.05). The number of times ancillary instrumentation was used demonstrated a positive correlation with TOT (p < 0.05). CONCLUSION: Beveled-tip, 10,000 cpm MIVS system effectively and safely performs common VR procedures of varying complexity and may reduce operative times and use of ancillary instrumentation.

Diabetic cardiomyopathy.

The relationship between diabetes and heart failure is complex and bidirectional. Nevertheless, the existence of a cardiomyopathy attributable exclusively to diabetes has been and is still the subject of controversy, due, among other reasons, to a lack of a consensus definition. There is also no unanimous agreement in terms of the physiopathogenic findings that need to be present in the definition of diabetic cardiomyopathy or on its classification, which, added to the lack of diagnostic methods and treatments specific for this disease, limits its general understanding. Studies conducted on diabetic cardiomyopathy, however, suggest a unique physiopathogenesis different from that of other diseases. Similarly, new treatments have been shown to play a potential role in this disease. The following review provides an update on diabetic cardiomyopathy.

Miocardiopatía diabética / Diabetic cardiomyopathy

La relación entre la diabetes y la insuficiencia cardiaca es compleja y bidireccional. No obstante, la existencia de una miocardiopatía como entidad propia y atribuible exclusivamente a la diabetes ha sido y es motivo de controversia hoy día. Esto es debido, entre otros motivos, a la ausencia de una definición de consenso. Tampoco existe unanimidad en cuanto a los hallazgos fisiopatogénicos presentes en la miocardiopatía diabética ni en su clasificación. Esto añadido a la ausencia de métodos diagnósticos propios o de tratamientos específicos en la enfermedad, limita el conocimiento general de la patología. Sin embargo, los estudios realizados en miocardiopatía diabética sugieren una fisiopatogenia propia diferenciada de la de otras entidades. De la misma manera, nuevos tratamientos han demostrado tener un papel potencial en esta enfermedad. En la siguiente revisión realizamos una actualización de la miocardiopatía diabética (AU)

The relationship between diabetes and heart failure is complex and bidirectional. Nevertheless, the existence of a cardiomyopathy attributable exclusively to diabetes has been and is still the subject of controversy, due, among other reasons, to a lack of a consensus definition. There is also no unanimous agreement in terms of the physiopathogenic findings that need to be present in the definition of diabetic cardiomyopathy or on its classification, which, added to the lack of diagnostic methods and treatments specific for this disease, limits its general understanding. Studies conducted on diabetic cardiomyopathy, however, suggest a unique physiopathogenesis different from that of other diseases. Similarly, new treatments have been shown to play a potential role in this disease. The following review provides an update on diabetic cardiomyopathy (AU)

Do patients' characteristics influence their healthcare concerns?-A hospital care survey.

BACKGROUND: Hospital performance is often monitored by surveys that assess patient experiences with hospital care. Certain patient characteristics may shape how some aspects of hospital care are viewed and reported on surveys. OBJECTIVE: The aim of the study was to examine factors considered important to patients and determine whether there were differences in answers based on age, gender, or educational level. METHODS: Cross-sectional study based on a hospital survey developed via literature review and specialist recommendations. This study included randomly selected patients 18 years or older who were recently admitted to the hospital or admitted more than 50 days before the survey was being applied. Survey domains included age, gender, educational level, factors considered important for the health care in a hospital setting and sources of information about hospital quality used by each subject. Answers description and statistical analysis using Fisher exact test were performed. RESULTS: The survey was applied to 262 patients who were admitted under different services. The most important concern reported was the risk of getting a hospital-acquired infection (67.18%), followed by understanding explanation from the doctors' plans (64.12%) and doctors' ability to listen carefully (58.78%). Women are more concerned about their risk of falling (p = 0.03). Patients older than 65 years find important that the doctors explain everything in a way they can easily understand (p = 0.02), while lower educated patients consider most if the doctor treats them with courtesy and respect (p = 0.0027). CONCLUSION: Patient characteristics have an effect on how hospital care is perceived. Regardless of the characteristics of the population, the risk of getting an infection was the main concern overall, so it is important that hospitals promote actions to prevent it and share them with patients.

Similar hepatoprotective effectiveness of Diphenyl diselenide and Ebselen against cisplatin-induced disruption of metabolic homeostasis and redox balance in juvenile rats.

Cisplatin is an antineoplastic drug well recognized for its success in the battle against several types of cancer in adult, juvenile, and child populations. Meanwhile, this drug is also famous due to its serious side effects, such as hepatotoxicity. This study evaluated the hepatoprotective effectiveness of Diphenyl Diselenide (PhSe)2 and Ebselen in a model of cisplatin-induced toxicity in juvenile rats. Juvenile Wistar rats received a single intraperitoneal (i.p) injection of cisplatin (6 mg/kg) or saline solution, at postnatal day (PND) 21. Ebselen (11 mg/kg) or (PhSe)2 (12 mg/kg) was intragastrically (i.g) administered in rats from PND 21 to PND 25. At PND 26, the blood and liver were collected for the biochemistry assays. A single administration of cisplatin was enough to alter the makers of hepatic function (an increase of AST activity) and the blood lipid profile (an increase of cholesterol and triglycerides, TG). The cisplatin-induced metabolic disruption was demonstrated by the increase of hepatic glycogen and TG contents and hexokinase, glucose-6-phosphatase, and tyrosine aminotransferase activities; a decrease of citrate synthase activity and the levels of GLUT-2. Cisplatin-induced hepatic oxidative stress was characterized by an increase in reactive oxygen species, TBARS, protein carbonyl, and Nox levels as well as the decrease in NPSH levels. Ebselen and (PhSe)2 were effective against all alterations caused by this chemotherapy medication. The present findings highlight the (PhSe)2 and Ebselen similar hepatoprotective effectiveness against cisplatin-induced disruption of metabolic homeostasis and redox balance in juvenile rats.

Catamenial rectal bleeding due to invasive endometriosis: a case report.

BACKGROUND: Although gastrointestinal involvement is the most common site for extra-genital endometriosis, deep infiltrative endometriosis, which affects the mucosal layer, is very rare. CASE PRESENTATION: We present a case of a 41-year-old white woman with cyclic rectal bleeding. Magnetic resonance imaging was done, together with colonoscopy and histologic staining of biopsied samples, which led to the final diagnosis of intestinal invasive endometriosis with recto-sigmoid stricture. Our patient was treated symptomatically with stool softeners. CONCLUSION: This case provides a rare example of catamenial bleeding. It is important to keep invasive endometriosis on the differential diagnosis whenever a premenopausal woman has cyclical rectal bleeding.

Galectin-3 Is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes.

INTRODUCTION: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. METHODS: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. RESULTS: Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113-195) vs. 133 (105-173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5-10.5) vs. 7.8 (5.9-9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81-6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07-2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04-1.42); p = 0.017 and HR 1.23 (1.05-1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. CONCLUSION: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.

Diabetic cardiomyopathy. / Miocardiopatía diabética.

The relationship between diabetes and heart failure is complex and bidirectional. Nevertheless, the existence of a cardiomyopathy attributable exclusively to diabetes has been and is still the subject of controversy, due, among other reasons, to a lack of a consensus definition. There is also no unanimous agreement in terms of the physiopathogenic findings that need to be present in the definition of diabetic cardiomyopathy or on its classification, which, added to the lack of diagnostic methods and treatments specific for this disease, limits its general understanding. Studies conducted on diabetic cardiomyopathy, however, suggest a unique physiopathogenesis different from that of other diseases. Similarly, new treatments have been shown to play a potential role in this disease. The following review provides an update on diabetic cardiomyopathy.

Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases.

Gestational diabetes mellitus (GDM) is defined as the presence of high blood glucose levels with the onset, or detected for the first time during pregnancy, as a result of increased insulin resistance. GDM may be induced by dysregulation of pancreatic ß-cell function and/or by alteration of secreted gestational hormones and peptides related with glucose homeostasis. It may affect one out of five pregnancies, leading to perinatal morbidity and adverse neonatal outcomes, and high risk of chronic metabolic and cardiovascular injuries in both mother and offspring. Currently, GDM diagnosis is based on evaluation of glucose homeostasis at late stages of pregnancy, but increased age and body-weight, and familiar or previous occurrence of GDM, may conditionate this criteria. In addition, an earlier and more specific detection of GDM with associated metabolic and cardiovascular risk could improve GDM development and outcomes. In this sense, 1st-2nd trimester-released biomarkers found in maternal plasma including adipose tissue-derived factors such as adiponectin, visfatin, omentin-1, fatty acid-binding protein-4 and retinol binding-protein-4 have shown correlations with GDM development. Moreover, placenta-related factors such as sex hormone-binding globulin, afamin, fetuin-A, fibroblast growth factors-21/23, ficolin-3 and follistatin, or specific micro-RNAs may participate in GDM progression and be useful for its recognition. Finally, urine-excreted metabolites such as those related with serotonin system, non-polar amino-acids and ketone bodies, may complete a predictive or early-diagnostic panel of biomarkers for GDM.

Outcomes of treatment with sirolimus for non-infectious uveitis: a meta-analysis and systematic review.

BACKGROUND: Uveitis is a group of intraocular inflammatory diseases whose primary treatment involves immunosuppression. Although corticosteroids (CSs) remain the mainstay therapy, sirolimus is among the recently studied immunomodulatory drugs for treating noninfectious uveitis (NIU). OBJECTIVE: The aim of this review was to assess and summarize the updated evidence on the outcomes of treatment with sirolimus for NIU. MATERIALS AND METHODS: Two reviewers conducted a systematic search on November 5, 2018, of electronic databases (EMBASE, MEDLINE, and The Cochrane Library) and clinical trial registers having no restrictions on language or publication date. The primary outcome was uveitis activity as measured by vitreous haze (VH), while the secondary outcomes included central macular thickness (CMT), best-corrected visual acuity (BCVA), CS-sparing effect, IOP elevation, and other adverse events. A meta-analysis was conducted on selected studies with appropriate clinical and methodological homogeneity. RESULTS: Seven studies were included and reviewed. Four randomized clinical trials were eligible for meta-analysis: SAVE 2013, One-year outcomes of the SAVE study, SAVE 2 2016, SAKURA 2016. The pooled proportions of inflammation control (VH improvement) were 38% (95% CI 16.19%-62.66%) during a 6-month follow-up and 49.97% (95% CI 16.19%-83.03%) during a 6- to 12-month follow-up with the latter showing a significantly higher response rate (p=0.0472). BCVA improvement was 62.2% (95% CI 33.17%-87.11%) during a 6-month follow-up and 56.86% (95% CI 20.91%-89.05%) during a 6- to 12-month follow-up with no significant difference between the two (p=0.3705). Increased IOP remained at 7.11% (95% CI 3.46%-12.68%) for both a 6-month follow-up and up to a 12-month follow-up duration. The CS-sparing effect of sirolimus was also well demonstrated. A reduction in CMT was observed, and only minor drug-related adverse events were reported in all the studies reviewed. CONCLUSION: This review provided evidence that sirolimus is a promising treatment option for controlling inflammatory activity, improving visual acuity, and sparing CS use with minor adverse events for NIU.

Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: role of GLP-1 isoforms in Glut4 receptor trafficking.

BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG). Hearts and plasma were isolated for biochemical approaches. Cultured cardiomyocytes were examined for receptor distribution after incretin stimulation in high fatty acid or high glucose media. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18FDG assimilation and diastolic dysfunction. However, sitagliptin improved hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced 18FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal translocation of the glucose transporter-4 (Glut4), in detriment of the fatty acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal translocation were also increased after GLP-1 stimulation in high-fatty acid incubated cardiomyocytes. PI3K/Akt and AMPKα were involved in this response. Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar effects. CONCLUSIONS: Besides of its anti-hyperglycemic effect, sitagliptin-enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by shifting fatty acid to glucose utilization in the cardiomyocyte, and thus, improving cardiac efficiency and reducing lipolysis.

Snapping Pes Anserinus and the Diagnostic Utility of Dynamic Ultrasound.

Snapping pes anserinus syndrome is an often encountered cause of medial knee snapping. It results from impingement and translation of the gracilis tendon or semitendinosus tendon over the osseous structures of the knee during active flexion and extension. Ultrasonography is often the diagnostic imaging test of choice in cases of mechanical snapping. We report 2 cases of painful snapping pes anserinus and highlight the value of dynamic ultrasound in making an accurate diagnosis so as to direct care.

Sun exposure influences the prognostic power of components of mineral metabolism in patients with coronary artery disease.

BACKGROUND AND AIM: Calcidiol (vitamin D metabolite) plasma levels vary with sun exposure (SE). However, it is not known if SE influences its prognostic ability. We have studied the effect of SE on plasma levels of the components of mineral metabolism (calcidiol, fibroblast growth factor-23 [FGF-23], parathormone [PTH], and phosphate [P]) and on their prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: We studied prospectively 704 patients with stable CAD. Clinical variables and baseline calcidiol, FGF-23, PTH, and P plasma levels were assessed. We divided the population in two subgroups, according to the period of plasma extraction: High SE (HSE) (April-September) and low SE (LSE) (October-March). The outcome was the development of acute ischemic events (acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Mean follow-up was 2.15 ± 0.99 years. Calcidiol and P levels were higher in HSE group. In the whole population, calcidiol (HR = 0.84 for each 5 ng/ml increase, 95% CI = 0.71-0.99; p = 0.038) and FGF-23 (HR = 1.14 for each 100 RU/ml increase, 95% CI = 1.05-1.23; p = 0.009) were predictors of the outcome, along with age, hypertension, body-mass index, peripheral artery disease, and P levels. In the LSE subgroup, calcidiol (HR = 0.75; 95% CI = 0.57-0.99; p = 0.034) and FGF-23 (HR = 1.34; 95% CI = 1.13-1.58; p = 0.003) remained as predictors of the outcome. In the HSE group calcidiol and FGF-23 had not independent prognostic value. CONCLUSIONS: In patients with stable CAD, low calcidiol and high FGF-23 plasma levels predict an adverse prognosis only when the sample is obtained during the months with LSE. SE should be taken into account in the clinical practice.

Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes.

Nowadays, obesity is seriously increasing in most of the populations all over the world, and is associated with the development and progression of high-mortality diseases such as type-2 diabetes mellitus (T2DM) and its subsequent cardiovascular pathologies. Recent data suggest that both body fat distribution and adipocyte phenotype, can be more determinant for fatal outcomes in obese patients than increased general adiposity. In particular, visceral adiposity is significantly linked to long term alterations on different cardiac structures, and in developed forms of myocardial diseases such as hypertensive and ischaemic heart diseases, and diabetic cardiomyopathy. Interestingly, this depot may be also related to epicardial fat accumulation through secretion of lipids, adipokines, and pro-inflammatory and oxidative factors from adipocytes. Thus, visceral adiposity and its white single-lipid-like adipocytes, are risk factors for different forms of heart disease and heart failure, mainly in higher degree obese subjects. However, under specific stimuli, some of these adipocytes can transdifferentiate to brown multi-mitochondrial-like adipocytes with anti-inflammatory and anti-apoptotic proprieties. Accordingly, in order to improve potential cardiovascular abnormalities in obese and T2DM patients, several therapeutic strategies have been addressed to modulate the visceral and epicardial fat volume and phenotypes. In addition to lifestyle modifications, specific genetic manipulations in adipose tissue and administration of PPARγ agonists or statins, have improved fat volume and phenotype, and cardiovascular failures. Furthermore, incretin stimulation reduced visceral and epicardial fat thickness whereas increased formation of brown adipocytes, alleviating insulin resistance and associated cardiovascular pathologies.

Diagnostic approaches for diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiac dysfunction which affects approximately 12% of diabetic patients, leading to overt heart failure and death. However, there is not an efficient and specific methodology for DCM diagnosis, possibly because molecular mechanisms are not fully elucidated, and it remains asymptomatic for many years. Also, DCM frequently coexists with other comorbidities such as hypertension, obesity, dyslipidemia, and vasculopathies. Thus, human DCM is not specifically identified after heart failure is established. In this sense, echocardiography has been traditionally considered the gold standard imaging test to evaluate the presence of cardiac dysfunction, although other techniques may cover earlier DCM detection by quantification of altered myocardial metabolism and strain. In this sense, Phase-Magnetic Resonance Imaging and 2D/3D-Speckle Tracking Echocardiography may potentially diagnose and stratify diabetic patients. Additionally, this information could be completed with a quantification of specific plasma biomarkers related to related to initial stages of the disease. Cardiotrophin-1, activin A, insulin-like growth factor binding protein-7 (IGFBP-7) and Heart fatty-acid binding protein have demonstrated a stable positive correlation with cardiac hypertrophy, contractibility and steatosis responses. Thus, we suggest a combination of minimally-invasive diagnosis tools for human DCM recognition based on imaging techniques and measurements of related plasma biomarkers.

Parathormone Levels Are Independently Associated with the Presence of Left Ventricular Hypertrophy in Patients with Coronary Artery Disease.

BACKGROUND: Abnormalities of mineral metabolism and inflammation may affect the cardiovascular system. We have assessed the relationship of left ventricular hypertrophy (LVH) with inflammation and mineral metabolism. METHODS: LVH was measured in 146 outpatients with stable coronary artery disease (SCAD) using echocardiography. Calcidiol (a vitamin D metabolite), parathyroid hormone (PTH), fibroblast growth factor-23, high-sensitivity C-reactive protein, MCP-1 (monocyte chemoattractant protein-1), galectin-3, NGAL (neutrophil gelatinase-associated lipocalin), and sTWEAK (soluble TNF-related weak inducer of apoptosis) plasma levels were studied. RESULTS: LVH, defined as septal thickness ≥11 mm, was present in 19.9% of cases. These patients were older [75.0 (61.0-81.0) vs 64.0 (51.0-76.0) years; p=0.002], had higher prevalence of left ventricular ejection fraction (LVEF)>40%, and had higher PTH [84.7 (59.6-104.7) vs 63.2 (49.2-85.2) pg/ml; p=0.007], galectin-3 [9.6 (8.0-11.1) vs 8.3 (6.9-9.9) ng/ml; p=0.037], and NGAL (208.5±87.6 vs 173.9±73.4 ng/ml; p=0.031) plasma levels than those without LVH. Glomerular filtration rate was lower in patients with LVH than in those without it (65.1±20.0 vs 74.7±19.9 mL/min/1.73 m2; p=0.021). There were no significant differences in hypertension (79.3 vs 68.4%; p=0.363) or sex between both groups. Variables showing differences based on univariate analysis and hypertension were entered into a logistic regression analysis. Only age [odds ratio (OR) =1.052 (1.011-1.096); p=0.013], PTH plasma levels [OR=1.017 (1.003-1.031); p=0.021], and LVEF>40% [OR=7.595 (1.463-39.429); p=0.016] were independent predictors of LVH. CONCLUSIONS: In patients with SCAD, elevated PTH levels are independently associated with the presence of LVH. Further studies are needed to elucidate the role of PTH in the development of myocardial hypertrophy.

Updating experimental models of diabetic cardiomyopathy.

Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients.

Activation of toll-like receptors and inflammasome complexes in the diabetic cardiomyopathy-associated inflammation.

Diabetic cardiomyopathy is defined as a ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and hypertension. Hyperglycemia, hyperlipidemia, and insulin resistance are major inducers of the chronic low-grade inflammatory state that characterizes the diabetic heart. Cardiac Toll-like receptors and inflammasome complexes may be key inducers for inflammation probably through NF-κB activation and ROS overproduction. However, metabolic dysregulated factors such as peroxisome proliferator-activated receptors and sirtuins may serve as therapeutic targets to control this response by mitigating both Toll-like receptors and inflammasome signaling.