Despina Perrea

The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus:

Background Diabetes mellitus (DM) and chronic inflammation are strongly related to increased cardiovascular risk. The purpose of this study was to evaluate whether an aerobic training programme would ameliorate inflammatory and anti-inflammatory markers in patients with type 2 DM. Design Interventional study. Methods A total of 60 overweight individuals with type 2 DM, but without vascular complications, were randomly assigned to either a 6-month aerobic exercise training programme (four times/week, 45-60 min/session), designated as exercise group, or to the control group. All participants were on an oral antidiabetic regimen and none was receiving lipid-lowering medications. Anthropometric parameters, cardiorespiratory fitness, glycaemic and lipid profiles, high sensitivity C-reactive protein (hs CRP), adiponectin, interleukin (IL)-10, IL-18, tumour necrosis factor (TNF)-a, insulin, reciprocal index of homoeostasis model assessment (HOMA-IR), body fat and blood pressure (BP) were measured at baseline and at the end of the study. Results In comparison with baseline and control group, exercise-treated patients improved glucose control, lipid profile, exercise capacity (Vo2 peak) and exhibited decreased insulin resistance and systolic BP considerably (P < 0.05). Plasma adiponectin, TNF-α and body weight changed slightly across treatment (P > 0.05), whereas diastolic BP and fat mass tended to decrease (P = 0.071 and 0.061, respectively). Exercise training reduced hs CRP (from 0.48 ± 0.16 to 0.29 ± 0.2 mg/dl; P = 0.04) and IL-18 (from 315.19 ± 122.76 to 203.77 ± 96.02 pg/ml; P = 0.02). Moreover, exercise provided anti-inflammatory protection through IL-10 increment (P = 0.039) and IL-18/IL-10 ratio downregulation (P = 0.014). In multiple regression analysis, alteration in IL-18 was independently correlated with hs CRP and Vo2 peak changes (P < 0.05). Conclusion Aerobic exercise training without significant weight loss improves metabolic profile and exerts anti-inflammatory effects in patients with type 2 DM. Eur J Cardiovasc Prev Rehabil 14: 837-843

Smart health: A context-aware health paradigm within smart cities

The new era of mobile health ushered in by the wide adoption of ubiquitous computing and mobile communications has brought opportunities for governments and companies to rethink their concept of healthcare. Simultaneously, the worldwide urbanization process represents a formidable challenge and attracts attention toward cities that are expected to gather higher populations and provide citizens with services in an efficient and human manner. These two trends have led to the appearance of mobile health and smart cities. In this article we introduce the new concept of smart health, which is the context-aware complement of mobile health within smart cities. We provide an overview of the main fields of knowledge that are involved in the process of building this new concept. Additionally, we discuss the main challenges and opportunities that s-Health would imply and provide a common ground for further research.

Matrix Metalloproteinases and Diabetic Vascular Complications

Diabetes mellitus (DM) is associated with an increased incidence of cardiovascular events and microvascular complications. These complications contribute to the morbidity and mortality associated with DM. There is increasing evidence supporting a role for matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases—TIMPs) in the atherosclerotic process. However, the relationship between MMPs/TIMPs and diabetic angiopathy is less well defined. Hyperglycemia directly or indirectly (eg, via oxidative stress or advanced glycation products) increases MMP expression and activity. These changes are associated with histologic alterations in large vessels. On the other hand, low proteolytic activity of MMPs contributes to diabetic nephropathy. Within atherosclerotic plaques an imbalance between MMPs and TIMPs may induce matrix degradation, resulting in an increased risk of plaque rupture. Furthermore, because MMPs enhance blood coagulability, MMPs and TIMPs may play a role in acute thrombotic occlusion of vessels and consequent cardiovascular events. Some drugs can inhibit MMP activity. However, the precise mechanisms involved are still not defined. Further research is required to demonstrate the causative relationship between MMPs/TIMPs and diabetic atherosclerosis. It also remains to be established if the long-term administration of MMP inhibitors can prevent acute cardiovascular events.

Is obesity linked to aging? Adipose tissue and the role of telomeres

Obesity is a condition in which excess or abnormal fat accumulation may present with adverse effects on health and decreased life expectancy. Increased body weight and adipose tissue accumulation amplifies the risk of developing various age-related diseases, such as cardiovascular disease, type 2 diabetes mellitus, musculoskeletal disorders, respiratory diseases and certain types of cancer. This imbalance in body composition and body weight is now recognized as a state of increased oxidative stress and inflammation for the organism. Increasing oxidative stress and inflammation affect telomeres. Telomeres are specialized DNA-protein structures found at the ends of eukaryotic chromosomes and serve as markers of biological aging rate. They also play a critical role in maintaining genomic integrity and are involved in age-related metabolic dysfunction. Erosion of telomeres is hazardous to healthy cells, as it is a known mechanism of premature cellular senescence and loss of longevity. The association of telomeres and oxidative stress is evident in cultured somatic cells in vitro, where oxidative stress enhances the process of erosion with each cycle of replication. Shorter telomeres have been associated with increasing body mass index, increased adiposity, and more recently with increasing waist to hip ratio and visceral excess fat accumulation. Furthermore, many of the metabolic imbalances of obesity (e.g. glycemic, lipidemic, etc.) give rise to organ dysfunction in a way that resembles the accelerated aging process. This article is a non-systematic review of the evidence linking obesity and accelerated aging processes as they are regulated by telomeres.

Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa.

ABSTRACT Clarithromycin was administered intravenously to 55 rabbits to evaluate its effect on experimental sepsis caused by multidrug-resistant Pseudomonas aeruginosa. Acute pyelonephritis was induced after ligation of the right ureter and injection of 108 CFU of the test isolate per kg of body weight into the renal pelvis. The animals were divided into six groups: group A, controls; group B, rabbits that received one intravenous dose of 80 mg of clarithromycin per kg concomitantly with bacterial challenge; group C, rabbits that received two doses of clarithromycin, the second one of which was given 2 h after the first one; group D, rabbits that received 15 mg of amikacin per kg; group E, rabbits that received one dose of clarithromycin and amikacin; and group F, rabbits that received two doses of clarithromycin and amikacin. Serum endotoxin levels were estimated by the QCL-1000 Limulus amoebocyte lysate assay, tumor necrosis factor alpha (TNF-α) levels were measured by a bioassay, and malondialdehyde (MDA) levels were measured by the thiobarbiturate assay. Viable bacterial counts in various tissue samples were also assessed. The mean survival times of the animals in groups A, B, C, D, E, and F were 4.50, 7.69, 4.07, 4.55, 11.55, and 11.60 days, respectively (P = 0.033 for group D versus group F, P = 0.006 for group D versus group E, P = not significant for group B versus group E, P = 0.042 for group C versus group F). Serum endotoxin levels were similar between groups at all sampling times; TNF-α and MDA levels in groups B, C, E, and F decreased significantly over follow-up. The numbers of viable bacterial cells in the infected kidney were similar among the groups; those in the liver, spleen, lungs, and mesenteral lymph nodes were significantly decreased in groups B, E, and F compared to those in groups A and D. It is concluded that a prolongation of survival in animals with experimental sepsis caused by multidrug-resistant P. aeruginosa was achieved after coadministration of clarithromycin and amikacin and that the increased survival was probably attributable to the immunomodulatory properties of clarithromycin.

Regional and directional variations in the mechanical properties of ascending thoracic aortic aneurysms

This study aimed to assess regional and directional differences in the mechanical properties of ascending thoracic aortic aneurysms (ATAA). Whole fresh ATAA were taken from twelve patients, undergoing elective surgical repair, and cut into tissue specimens. These were divided into groups according to direction and region, and subjected to uniaxial testing beyond rupture. In the majority of tests, the inner layers of the aortic wall ruptured first; failure stress (measure of tissue strength) and peak elastic modulus (measure of tissue stiffness) were significantly higher circumferentially in all regions. Marked heterogeneity was evident in the mechanical properties of ATAA, with the anterior region longitudinally being the weakest and least stiff of all regions. No correlation was found between failure stress and ATAA diameter or patient age. Failure stress showed inverse correlations with wall thickness and direct correlations with peak elastic modulus. The current information, relating to regional and directional differences, may provide a better understanding of the mechanism responsible for the development of circumferential tears of the inner aortic wall layers in ATAA dissections.

Antithrombotic and Antiatherosclerotic Properties of Olive Oil and Olive Pomace Polar Extracts in Rabbits

Olive oil polar lipid (OOPL) extract has been reported to inhibit atherosclerosis development on rabbits. Olive pomace polar lipid (PPL) extract inhibits PAF activity in vitro and the most potent antagonist has been identified as a glycerylether-sn-2-acetyl glycolipid with common structural characteristics with the respective potent antagonist of OOPL. The aim of this study was to investigate the effect of PPL on early atherosclerosis development on rabbits and to compare it with the antiatherosclerotic effect of OOPL. OOPL and PPL inhibition potency, towards both PAF action and PAF binding, was tested in vitro on washed rabbit platelets. Consequently, rabbits were divided into three groups (A, B, and C). All groups were fed atherogenic diet for 22 days. Atherogenic diets in groups B and C were enriched with OOPL and PPL, respectively. At the end of the experimental time, rabbits were euthanized and aortic samples were examined histopathologically. OOPL and PPL inhibited PAF-induced aggregation, as well as specific PAF binding, with PPL being more potent. Free and bound PAF levels and PAF-AH activity were significantly elevated at the end of the experimental time. Plasma total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides levels were also found increased. Groups B and C exhibited significantly increased values of EC50 compared to group A. Histopathological examination revealed that the development of early atherosclerosis lesions in groups B and C were significantly inhibited compared to group A. Significant differences were noted in the early atherosclerosis lesions between groups B and C, thus indicating that PPL exhibit its anti-atherosclerotic activity by blocking PAF receptor. Specific PAF antagonists with similar in vitro and in vivo bioactivity to those that have been previously reported in OOPL exist in PPL.

Improvement of skin-graft survival after autologous transplantation of adipose-derived stem cells in rats

BACKGROUND Skin grafts are frequently used for a variety of indications in plastic and reconstructive surgery. Their necrosis is a common complication, while different therapies have been proposed. Currently, adipose-derived stem cells (ASCs) hold great promise for their angiogenic potential and role during tissue repair. In this study, autologous transplantation of ASCs was used in skin grafts in rats to determine if it increases angiogenesis, skin-graft survival and wound healing. METHODS ASCs were isolated, cultured, labelled with fluorescent dye and injected under full-thickness skin grafts in 10 rats (group 1), while 10 others served as controls (group 2). Skin grafts were analysed after 1 week. Collagens framework was assessed with Massons trichrome stain and angiogenesis with von Willebrand factor (vWF) immunohistochemistry. In addition, immunohistochemical staining intensity of vascular endothelial growth factor (VEGF) and transforming growth factor b3 (TGFb3) was assessed in all grafts. RESULTS Mean area of graft necrosis was significantly less in group 1 than in group 2 (6.12% vs. 32.62%, p<0.01). Statistically significant increase of microvessel density, collagen density, VEGF and TGFb3 expression was noted in group 1 compared with group 2 (all: p<0.01). CONCLUSIONS These findings suggest that autologous ASCs transplantation increases full-thickness skin-graft survival and shows promise for use in skin-graft surgery. This might be both due to in situ differentiation of ASCs into endothelial cells and increased secretion by ASCs of growth factors, such as VEGF and TGFb3 that enhance angiogenesis and wound healing.

Combination pharmacotherapy in the treatment of experimental cardiac arrest

STUDY OBJECTIVES Full recovery after cardiopulmonary resuscitation (CPR) is poor. We hypothesized that the coadministration of epinephrine, a beta-blocker such as atenolol, and a calcium sensitizer such as levosimendan during CPR would improve survival and postresuscitation myocardial function. METHODS Ventricular fibrillation was induced in 60 piglets, which were left untreated for 8 minutes before attempted resuscitation. Animals were randomized into 4 groups (n = 15), to receive epinephrine (group E), epinephrine + atenolol (group E + A), epinephrine + levosimendan (group E + L) and epinephrine + atenolol + levosimendan (group E + A + L) during CPR. Electrical defibrillation was attempted 2 minutes after drug administration. RESULTS Five animals in group E survived for 48 hours in comparison to 8 animals in groups E + A and E + L and 12 animals in group E + A + L. Postresuscitation cardiac output was significantly better in the animals of group E + A + L. Troponin I remained significantly lower in groups E + A and E + A + L. Serum astroglial protein (S-100) and neuron-specific enolase values in group E + L and E + A + L were statistically lower than those measured in groups E and E + A during the entire observation period. The neurologic alertness score was higher in group E + A + L compared to groups E and E + A. CONCLUSIONS The administration of a drug combination of epinephrine + atenolol + levosimendan, when given during CPR, in a pig model of cardiac arrest, results in improved 48-hour survival and improves postresuscitation cardiac function.

Adiponectin and resistin plasma levels in healthy individuals with prehypertension.

Prehypertension seems to be related to increased cardiovascular risk in healthy subjects, while hypoadiponectinemia and hyperresistinemia may contribute to insulin resistance and accelerated atherogenesis. This study investigated whether plasma levels of adiponectin (known to increase insulin sensitivity) and resistin (a protein possibly involved in inflammatory activities) are affected in healthy individuals with prehypertension, and to compare the findings to those of healthy normotensives matched for age, gender, and body mass index. Twenty‐six (14 men and 12 women) healthy individuals with prehypertension (mean age, 52±5 years; mean body mass index, 23±1.5 kg/m2) and 24 healthy normotensives (13 men and 11 women; mean age 53±6 years; body mass index 23.2±1.4 kg/m2) were studied. The adiponectin and resistin plasma levels were determined by the enzyme‐linked immunosorbent assay method. Plasma resistin levels were significantly higher, while adiponectin plasma levels were significantly lower, in prehypertensive subjects compared with normotensive subjects (10.62?3.17 ng/mL vs. 6.72±3.15 ng/mL and 6.26±2.18 μg/mL vs. 12.12±4.8 μg/mL; p<0.01, respectively). The findings suggest that healthy individuals with prehypertension have significantly higher resistin plasma levels and significantly lower adiponectin plasma levels compared with healthy normotensives. These findings may represent another possible mechanism that may increase the cardiovascular risk in this special group of patients, needing further investigation.