George Vrentzos

Adiponectin Promotes Endotoxin Tolerance in Macrophages by Inducing IRAK-M Expression

High levels of plasma adiponectin are associated with low levels of inflammatory markers and cardioprotection. The mechanism via which adiponectin exerts its anti-inflammatory effect is yet unknown. In the present study, we demonstrate that globular adiponectin (gAd) induces the expression of the inactive isoform of IL-1R-associated kinases (IRAK), IRAK-M. Homologous deletion of IRAK-M in IRAK-M−/− mice abolished the tolerogenic properties of gAd because pretreatment of IRAK-M−/− macrophages with gAd did not suppress LPS-induced proinflammatory cytokine production. GAd activated the MAPKs MEK1/2 and ERK1/2 in macrophages via their upstream regulator Tpl2. Activation of ERK1/2 via Tpl2 appeared necessary for the induction of IRAK-M because gAd did not induce IRAK-M in Tpl2−/− macrophages or in macrophages pretreated with the MEK1/2 inhibitor UO126. In addition, activation of PI3K and Akt1 also appeared necessary for the induction of IRAK-M by gAd, because treatment of Akt1−/− macrophages or pretreatment of macrophages with the PI3K inhibitor wortmannin abolished gAd-induced IRAK-M expression. Analysis of IRAK-M expression in human peripheral blood cells confirmed that serum adiponectin was negatively associated with IRAK-M and responsiveness to LPS. In conclusion, our data demonstrate that IRAK-M is a major mediator of gAd-induced endotoxin tolerance in primary macrophages, expression of which depends on the activation of Tpl2/ERK and PI3K/Akt1 signaling pathways.

Subclinical Hypothyroidism and Lipid Abnormalities in Older Women Attending a Vascular Disease Prevention Clinic: Effect of Thyroid Replacement Therapy

The authors evaluated the frequency and type of lipid disorders associated with subclinical hypothyroidism (SH) in older women referred to their university vascular disease prevention clinic. They also assessed the results of thyroid replacement therapy. Fasting serum lipid profiles and thyroid function tests were measured in 333 apparently healthy women (mean age: 71.8 ±7 years). These women were divided into 3 groups: group I: 60-69 years old (n =132); group II: 70-79 years old (n =153); group III: 80-89 years old (n = 48). SH was defined as a serum thyrotropin concentration higher than 3.20 mIU/mL with a normal free thyroxine concentration. The prevalence of SH was 7.5%. Thyrotropin was higher than 3.20 mU/mL in 25 women; 7 (5.3%), 14 (9.2%), and 4 (8.3%) in groups I, II, and III, respectively. Low-density lipoprotein cholesterol (LDL-C) concentrations were higher in the women with SH (p = 0.037). The mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL- C ratio, lipoprotein (a) (Lp[a]), apolipoprotein A-I (apo AI) apolipoprotein B100 (apo B) and apo B/apo A ratio were higher and triglycerides (TG) were lower, compared with those with normal levels of thyrotropin. However, none of these differences reached significance. Restoration of euthyroid status (thyroxine: 50-100 μg/day) in 17 SH women significantly improved TC (p=0.017), LDL-C (p=0.014), TC/HDL-C (p=0.05), LDL-C/HDL-C (p=0.03), apo B (p=0.013), and Lp(a) (p= 0.0005) values. SH is relatively common in older women attending a vascular disease prevention clinic. Thyroid hormone replacement therapy significantly improved serum lipids. In particular, the reduction in LDL-C and Lp(a) concentrations may be of clinical benefit.

Effect of Antihypertensive Treatment on PlasmaFibrinogen and Serum HDL Levelsin Patients with Essential Hypertension

The influence of hypertension, and its treatment, on circulating lipid and fibrinogen (Fib) concentrations in patients with essential hypertension was investigated. The lipid profile and Fib levels were measured in 353 patients (131 men) with essential hypertension. Their median age was 60 years (range: 18-85 years). All patients had normal results from liver, renal, and thyroid function tests. There were 162 patients (45.9%) who were not receiving antihypertensive treatment. Of the remaining patients, 117 were taking ‘lipid-hostile’ (β-blockers, thiazide diuretics) antihypertensives and 74 were taking ‘lipid-neutral’ (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin-II receptor blockers) agents. Patients who were taking ‘lipid-hostile’ antihypertensive drugs had significantly higher plasma Fib concentrations when compared with those taking ‘lipid-neutral’ antihypertensives or those not receiving antihypertensive treatment. These differences were not attributable to established factors that influence plasma Fib levels, since when smokers and patients with diabetes mellitus and/or vascular disease were excluded, the difference remained significant. In addition, in these more homogeneous groups, patients receiving ‘lipid-neutral’ treatment had significantly higher serum high-density lipoprotein (HDL) cholesterol levels when compared with both those taking ‘lipid-hostile’ antihypertensives and untreated ones. There were no significant differences in the other lipid variables, independently of the presence/absence or the type of antihypertensives. These results suggest that antihypertensive drugs have additional effects, beyond lowering blood pressure, on other vascular risk factors, like Fib and HDL. These effects may depend on the type of drug used.

Prevalence of metabolic syndrome according to different definitions in a hypertensive population.

Aims: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Several definitions of MetS have been proposed. The aim of the present study was to estimate and compare the prevalence of MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association-National Heart Lung and Blood Institute (AHA-NHLBI), International Diabetes Federation (IDF) and the more recent Joint Interim Statement (JIS) definitions in patients attending a hypertension clinic. Methods: The records of patients referred to the hypertension clinic at the University Hospital (Heraklion, Crete) from January 2001 to June 2009 were screened retrospectively. A total 384 patients (146 men) were included in the study. Results: The prevalence of MetS according to the IDF and JIS definitions was significantly higher compared with that of the NCEP ATP III in both genders (IDF: P = .009 and P = .002, JIS: P = .002 and P = 0.001 for men and women, respectively); this was the case for the AHA-NHLBI definition only among women (P = .03). All MetS components differed significantly (P from < .0001 to .02) between patients with and without MetS for all definitions. Conclusions: The prevalence of MetS varies considerably depending on the definition used in a hypertensive population in a Mediterranean country. These differences will influence risk assessment.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) with erythema nodosum and anterior scleritis. A case report.

A 53‐year‐old Greek housewife was admitted to hospital because of painful erythematous lesions on the lower ( Fig. 1 ) and upper ( Fig. 2 ) extremities in association with painful ocular hyperemia. These symptoms were preceded by an upper respiratory infection with persistent high‐grade fever for about 1 week. Erythematous lesions had appeared 3 days previous to admission. Her medical history included two previous episodes of erythema nodosum (unknown etiology), essential hypertension treated with perindopril 4 mg/day, diabetes mellitus type II under diet only, and multinodular goiter under treatment with thyroxine 0.1 mg/day.

Diet, serum homocysteine levels and ischaemic heart disease in a Mediterranean population

Homocysteine (Hcy) is recognised as a risk factor for IHD. Serum Hcy is negatively correlated with serum folate levels, the main sources of which are fruits, vegetables and legumes. The present case-control study was designed to examine the relationship between serum Hcy levels and IHD and to assess the role of dietary factors in the southern Mediterranean population of Crete, Greece. Serum Hcy, folate, vitamin B12, creatinine and glucose levels and a full lipid profile were measured in 152 patients with established IHD, median age 64 (range 33-77) years, and 152 healthy control subjects, age- and sex-matched. Dietary data were assessed using a 3 d food intake record. Compared with controls, patients with IHD had significantly higher daily intakes of vitamin B12 and MUFA and significantly lower intakes of carbohydrate, fibre, folate, cholesterol, n-3 fatty acids and total trans unsaturated fatty acids. Moreover, patients had significantly higher serum Hcy, vitamin B12 and creatinine levels, but significantly lower folate. Serum folate concentrations in both groups had a significant positive correlation with dietary fibre consumption and a significant inverse correlation with vitamin B12 intake. IHD patients should be encouraged to increase their daily dietary intake of fibre, folate and n-3 fatty acids, which are significant components of the traditional Cretan Mediterranean diet. Where dietary folate intake is inadequate, folate supplements are recommended to reduce elevated Hcy levels.

Measuring the burden of herpes zoster and post herpetic neuralgia within primary care in rural Crete, Greece

BackgroundResearch has indicated that general practitioners (GPs) have good clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within clinical practice in a country with limited resources for primary care and general practice. The objective of the current study was to assess the burden of HZ and post herpetic neuralgia (PHN) within rural general practices in Crete, Greece.MethodsThe current study took place within a rural setting in Crete, Greece during the period of November 2007 to November 2009 within the catchment area in which the Cretan Rural Practice-based Research Network is operating. In total 19 GPs from 14 health care units in rural Crete were invited to participate, covering a total turnover patient population of approximately 25, 000 subjects. For the purpose of this study an electronic record database was constructed and used as the main tool for monitoring HZ and PHN incidence. Stress related data was also collected with the use of the Short Anxiety Screening Test (SAST).ResultsThe crude incidence rate of HZ was 1.4/1000 patients/year throughout the entire network of health centers and satellite practices, while among satellite practices alone it was calculated at 1.3/1000 patients/year. Additionally, the standardised incidence density within satellite practices was calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ and PHN, the latter were found to have lower levels of anxiety, as assessed through the SAST score (17.4 ± 3.9 vs. 21.1 ± 5.7; p = 0.029).ConclusionsThe implementation of an electronic surveillance system was feasible so as to measure the burden of HZ and PHN within the rural general practice setting in Crete.

Association of serum total homocysteine with the extent of ischemic heart disease in a Mediterranean cohort.

High total homocysteine (tHcy) concentrations increase coronary disease risk. Therefore, the authors examined the relation between tHcy concentrations and the number of stenotic arteries in patients with ischemic heart disease (IHD). They enrolled 155 patients with IHD (135 men) who had undergone selective coronary angiography during the previous 2 years. These patients were divided into 4 groups according to the number of vessels (0, 1, 2, and 3) with ≥70% stenosis. They also reviewed the major coronary risk factors for each patient (age, gender, hypertension, diabetes mellitus, dyslipidemia, cigarette smoking, obesity), and measured serum concentrations of tHcy, folate, vitamin B12 and lipids. There was a significant positive correlation (rs=0.19; p=0.017; n=155) between tHcy serum concentration and the extent of coronary atherosclerosis, expressed by the number of coronary arteries with significant stenosis. Moreover, the number of affected vessels displayed a significant positive correlation with the presence of diabetes mellitus (rs=0.30; p<0.0001; n=155) and serum concentrations of lipoprotein (a) (rs=0.25; p<0.05; n=67) and a negative correlation with apolipoprotein A-I serum concentration (rs=-0.27; p<0.01; n=67). In this study, the serum concentrations of tHcy correlated with the extent of coronary atherosclerosis, independently of other classical risk factors, with the exception of diabetes mellitus.

A case of eosinophilic gastroenteritis with severe peripheral eosinophilia

Eosinophilic gastroenteritis is a rare heterogeneous disorder of undetermined etiology that is characterized by eosinophilic infiltration of the gastrointestinal tissues and various clinical manifestations. We report an uncommon case of eosinophilic gastroenteritis involving a patient with a short history of mild upper abdominal pain, severe peripheral eosinophilia (absolute eosinophil count of > 5,000 cells per microL), and ascites. The patient was treated successfully with a course of methylprednisolone.

Low molecular weight heparin (nadroparine) versus oral anticoagulant (acenocoumarol) in the long-term treatment of deep venous thrombosis: comparison of efficacy, safety and hospitalisation period in 105 patients

SUMMARY Objective: To evaluate and compare the efficacy and safety of low molecular weight heparin (LMWH) (nadroparine) and acenocoumarol in the treatment of deep venous thrombosis (DVT). Methods: A retrospective study of the case notes of 105 patients (68 men) with established DVT who had been hospitalised during a 6-year period in a university hospital department. Results: Among 105 patients, 65 received nadroparine and the remaining intravenous unfractionated heparin (UH) as initial treatment. Twenty-seven patients out of 65 continued their treatment with nadroparine and the remaining 78 patients (38 initially treated with LMWH and 40 with UH) with acenocoumarol. The average hospital stay for those on LMWH treatent was 2.2 ± 1.4 days in comparison to 6.4 ± 1.2 days for those treated with acenocoumarol (p < 0.001). During the home-based phase of treatment, 14 patients were re-admitted to hospital for recurrent DVT; ten and four of those treated with acenocoumarol and LMWH, respectively (p = NS). Haemorrhagic complications occurred in 12 of the patients who received acenocoumarol and in one of those on LMWH (p = NS). Conclusions: The patients who received LMWH had a significantly lower duration of hospitalisation than those who received acenocoumarol. There were no significant differences between the administration of LMWH and acenocoumarol in terms of efficacy or safety in patients with DVT.