Gender-specific effects of capsiate supplementation on body weight and bone mineral density: a randomized, double-blind, placebo-controlled study in slightly overweight women.

INTRODUCTION: Overweight and obesity are highly prevalent conditions associated with premature morbidity and mortality worldwide. Capsiate, a nonpungent analogue of capsaicin, binds to TRP vanilloid 1 (TRPV1) receptor, which is involved in adipogenesis, and could be effective as a weight-lowering agent. METHODS: Eighteen slightly overweight women were enrolled in this randomized, double-blind, placebo-controlled study. Nine patients were included in the capsiate intervention group and received 9 mg/day of capsinoids and 9 patients received placebo for 8 weeks. All patients underwent weight and waist circumference assessment before and after treatment. Body composition and bone mineral density (BMD) were also detected by dual-energy X-ray absorptiometry (DXA). RESULTS: Fourteen patients completed the study. The treatment with capsiate or placebo for 8 weeks was not associated with significant changes in weight or waist circumference. After treatment, there was a significant improvement in BMD values measured at the spine in the capsiate group (1.158 vs 1.106 g/cm2, + 4.7%; p = 0.04), but not in the group treated with placebo. Similarly, the capsiate group showed a 9.1% increase (p = 0.05) in the adipose tissue and an 8.5% decrease in lean mass measured at the supraclavicular level, whereas these changes were not statistically significant in the placebo group. CONCLUSIONS: Treatment with capsiate for 8 weeks led to negligible changes in body weight in a small sample of slightly overweight women, but our findings suggest a potential effect of capsaicin on bone metabolism in humans.

Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project.

BACKGROUND: Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking. OBJECTIVE: To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes. METHODS: The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B2 (TxB2) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up. RESULTS: Among 509 adults with IHD (mean age 67 ± 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB2 and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB2 production. CONCLUSION: Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding.

E-learning course improves knowledge in tobacco dependence, electronic nicotine delivery systems and heat-not-burn products in Medical School students.

BACKGROUND: Adequate training in tobacco, nicotine dependence and treatment is lacking in Medical School education. With the rise in popularity of electronic alternatives to cigarettes, future physicians should also be provided with the more recent scientific evidence on these products during their undergraduate studies. We introduced an e-learning course for Medical School students and assessed its effec-tiveness of increasing knowledge on these topics. METHODS: We developed 16 didactic modules divided in 3 courses: tobacco dependence (TDI), treating tobacco dependence (TDII) and electronic products and tobacco control (TDIII). The course was offered to 4th, 5th, and 6th year Medical School students in Italy. To assess learning outcomes, we examined the pre- to post- changes in knowledge scores associated with each course. Paired and independent samples t-tests were performed overall, and among smokers and non-smokers separately. RESULTS: A total of 1318 students completed at least one of the courses; 21% were self-reported smokers. A significant increase in knowledge was observed at the end of TDI (pre-course: 52.1±15.9, post-course: 79.9±13.5, p<0.001), TDII (pre-course: 52.5±13.0, post-course: 66.5±12.0, p<0.001) and TDIII (pre-course: 52.2±15.3, post-course: 76.1±17.7, p<0.001). Smokers showed significantly lower improvements compared to non-smokers. CONCLUSIONS: The e-learning course was effective in increasing knowledge about tobacco dependence, treatments, and electronic ni-cotine products in advanced medical students. Given the fundamental role for healthcare practitioners in encouraging and assisting people in quitting smoking, e-learning may be a useful tool in providing up-to-date and standardized training in the area during Medical School.

Impact of cardiovascular risk factors on incidence and severity of Retinal Vein Occlusion.

PURPOSE: Retinal Vein Occlusion (RVO) is a thrombotic process affecting retinal veins. The purpose of this research is to study demographic characteristics and prevalence of cardiovascular comorbidities among subjects affected by RVO. In addition, authors explore the role of each variable in determining occlusion type and severity. SUBJECTS, MATERIALS AND METHODS: This was a prospective observational study recruiting subjects affected by RVO and secondary macular edema. Exclusion criteria included pre-existing macular edema, recent ocular surgery (<6 months), pregnancy, diagnosis other than RVO, diabetes mellitus type I, any systemic pathology that significantly reduced life expectancy. Each participant was studied through a comprehensive medical history, cardiovascular assessment, blood testing, ocular exam, and macular OCT imaging. RESULTS: A total of 145 eyes, 145 participants, thereof 80 males (55%) and 65 females. (45%) Mean age: 62.5 ± 14.3 SD. 61 eyes (42%) were affected by CRVO and 84 eyes (58%) by BRVO. No statistically significant differences were noted between genders. Hypertension was very prevalent (63%). Dyslipidemia was more associated with BRVO (p = 0.044). Subjects with hypertension had a mean central macular thickness (CMT) of 643 µm against a mean of 489 µm of those without hypertension. (p < 0.05). No other variable was associated with macular edema severity. CONCLUSIONS: Older age and hypertension are strong risk factors for RVO. Dyslipidemia was strongly associated with BRVO. (p=0.044) Hypertension was not only associated with RVO incidence, but also with its severity. In fact, hypertensive subjects had significantly worse macular edema.

Knowledge of nicotine dependence and treatment in clinical practice improved after an e-learning course among medical students.

OBJECTIVE: Tobacco smoking is the leading cause of preventable death in developed countries and smokers should be encouraged to quit. Physicians are instrumental in this, but recent reports suggest inadequate training in medical school. We aimed to assess the knowledge of nicotine dependence and its treatment among Italian medical students. STUDY DESIGN: Prospective observational study. METHODS: We developed an online course consisting of 11 Didactic Modules (6 for Tobacco Dependence I, TDI, and 5 for TDII) on nicotine dependence and treatment. The course was administered to 4th and 5th year medical students in Italy in Academic Years 2016-17 (Course A) and 2017-18 (Course B). A validated questionnaire was used before and after each part in order to measure knowledge of smoking epidemiology, health effects and benefits of giving up smoking ("Score 1", TDI), and effectiveness of cessation treatments ("Score 2", TDII). RESULTS: 324 students took both TDI and TDII and completed all questionnaires (Course A, n = 245; Course B, n = 79). 55 students were current smokers (17%). A significant increase in score 1 and 2 was observed at the end of both TDI (pre-course 47.2±13.1, post-course 66.0±12.3, p <0.0001) and TDII (pre-course 55.6±11.5, post-course 68.1±10.9, p <0.0001). The prevalence of students wishing for a smoke-free medical school significantly increased between the beginning of TDI (74.4%, 241/324) and the end of TDII (88%, 285/324; p <0.0001). CONCLUSIONS: This e-learning course has proven to be an effective tool in teaching students on nicotine dependence and treatment.

The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence.

PURPOSE: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. METHODS: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. RESULTS: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. CONCLUSION: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level.

Platelet Count Does Not Predict Bleeding in Cirrhotic Patients: Results from the PRO-LIVER Study.

OBJECTIVES: Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. METHODS: We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years. RESULTS: A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child-Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800-1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50 × 103/µl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11-3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16-3.62; P=0.013) independently predicted overall bleeding events. CONCLUSIONS: Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

Kidney disease and venous thromboembolism: Does being woman make the difference?

The risk of venous thromboembolism (VTE) is increased across the spectrum of chronic kidney disease (CKD), from mild to more advanced CKD, and typically characterizes nephrotic syndrome (NS). VTE risk in patients with kidney disease may be due to underlying hemostatic abnormalities, including activation of pro-thrombotic factors, inhibition of endogenous anticoagulation systems, enhanced platelet activation and aggregation, and decreased fibrinolytic activity. The mechanisms involved differ depending on the cause of the kidney impairment (i.e. presence of NS or CKD stage). Sex and gender differences, as well as, environmental factors or comorbidities may play a modulating role; however, specific sex and gender data on this topic are still rare. The aim of the present review is to discuss the VTE risk associated with impairment of kidney function, the potential mechanism accounting for it and the impact of sex differences in this clinical setting.

Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?

Patients with cirrhosis can have abnormalities in laboratory tests reflecting changes in primary haemostasis, including bleeding time, platelet function tests, markers of platelet activation, and platelet count. Such changes have been considered particularly relevant in the bleeding complications that occur in cirrhosis. However, several studies have shown that routine diagnostic tests, such as platelet count, bleeding time, PFA-100, thromboelastography are not clinically useful to stratify bleeding risk in patients with cirrhosis. Moreover, treatments used to increase platelet count or to modulate platelet function could potentially do harm. Consequently the optimal management of bleeding complications is still a matter of discussion. Moreover, in the last two decades there has been an increased recognition that not only bleeding but also thrombosis complicates the clinical course of cirrhosis. Thus, we performed a literature search looking at publications studying both qualitative and quantitative aspects of platelet function to verify which primary haemostasis defects occur in cirrhosis. In addition, we evaluated the contribution of qualitative and quantitative aspects of platelet function to the clinical outcome in cirrhosis and their therapeutic management according to the data available in the literature. From the detailed analysis of the literature, it appears clear that primary haemostasis may not be defective in cirrhosis, and a low platelet count should not necessarily be considered as an automatic index of an increased risk of bleeding. Conversely, caution should be observed in patients with severe thrombocytopenia where its correction is advised if bleeding occurs and before invasive diagnostic and therapeutic procedures.

Misdiagnosis in fibromyalgia: a multicentre study.

BACKGROUND: Fibromyalgia (FM) is the second most common cause of visits to rheumatologists after osteoarthritis, and may be difficult to diagnose in many patients. It is associated with various rheumatic disorders such as rheumatoid arthritis, spondyloarthropathies (SpA) and connective tissue disease (CTD), and a late diagnosis or misdiagnosis is a common and underestimated problem. OBJECTIVES: The aim of this study was to investigate the 'underdiagnosis' of FM, and which rheumatic diseases tend to be confused with it. METHODS: The following data were collected at baseline: symptoms, disease duration, physical examination findings, previous and current investigations and management, laboratory tests, tender point count, tender and swollen joint counts, and spinal pain. The clinimetric evaluation included the Fibromyalgia Impact Questionnaire (FIQ) and Fibromyalgia Assessment Status (FAS). RESULTS: The study population consisted of 427 outpatients (418 females and 9 males; mean age 49.3 years; mean disease duration 8.5 years). Fifty-seven patients (13.3%) had been previously misdiagnosed as having other musculoskeletal disorders (MSDs); 370 patients had been previous correctly diagnosed as having FM, or were diagnosed as having it during the course of the study. The FM and MSD groups were comparable in terms of demographic data and referral patterns. Disease duration was longer and the erythrocyte sedimentation rate was higher in the MSD patients, who also had less severe FIQ and lower pain visual analogue scale scores. Moreover, the FIQ and FAS scores correlated in the MS group. CONCLUSIONS: The findings of this study suggest that, although FM is a wellknown clinical entity, differential diagnosis with SpA, CTD and inflammatory arthritis can still be a challenge for rheumatologists and general practitioners.

[Lifestyle and global cardiovascular risk: a prospective study on a borderline hypertensive population]. / Stile di vita e rischio cardiovascolare globale: studio osservazionale su una popolazione di pazienti con ipertensione arteriosa borderline.

BACKGROUND AND AIMS: Arterial hypertension is a well known risk factor for cardiovascular diseases. Today, it is possible to calculate the cardiovascular risk at 10 years with the risk card. The reduction of cardiovascular risk is based on a multi-factorial approach including the lifestyle modification. In Italy, OEC study has calculated that a certain proportion of borderline hypertensives, not eligible for a pharmacological treatment, remain at risk. Borderline arterial hypertension (140-150/90-95 mmHg) in Italian population is documented in 19% of males and 14% of females.: Aim of the study is to examine the efficacy of the lifestyle changes in reducing the global cardiovascular risk in bordeline hypertensives. MATERIALS AND METHODS: 102 patients affected by borderline hypertensive (46 M and 56 F, mean age: 55.6 yrs ) were enclosed in a 12 months prospective study. Three checks were programmed during the follow-up, i.e., at beginning, 6 months and 12 months later. At the start of the study every patient received a list of lifestyle changes to be respected. Pressure arterial systolic and diastolic were obtained at beginning and at the end of successive. At the last check each patient received a questionnaire to be filled up. According to the calculated score, each patient was classified as: non-responder (score: 0-3), partially responder (score: 4-6), responder (score: 7-9). RESULTS: A significant reduction of the globalcardiovascular risk has been observed at the end of the study in both the responders and partially responders. Such a reduction was seen to be due to positive changes in blood pressure and total, HDL, LDL cholesterol. CONCLUSIONS: This study confirmed that a non-pharmacological therapy based on lifestyle changes has to be preventively administered in the presence of a borderline hypertension because of its beneficial effects in reducing the global risk of cardiovascular disease. Therefore, we firmly think that a prompt utilization of a correct lifestyle can sort the triple effect of improving the expectancy of life, ameliorating the quality of life, reducing the social costs of arterial hypertension.

Thromboxane and prostacyclin biosynthesis in heart failure of ischemic origin: effects of disease severity and aspirin treatment.

SUMMARY BACKGROUND: Thromboembolism is a relatively common complication of chronic heart failure (HF) and the place of antiplatelet therapy is uncertain. OBJECTIVES: We characterized the rate of thromboxane and prostacyclin biosynthesis in chronic HF of ischemic origin, with the aim of separating the influence of HF on platelet activation from that of the underlying ischemic heart disease (IHD). PATIENTS AND METHODS: We compared urinary 11-dehydro-thromboxane (TX)B(2), 2,3 dinor 6-keto-PGF(1alpha,) 8-iso-prostaglandin (PG)F(2alpha), and plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), asymmetric dimethylarginine (ADMA), and soluble CD40 ligand (sCD40L), in 84 patients with HF secondary to IHD, 61 patients with IHD without HF and 42 healthy subjects. RESULTS: HF patients not on aspirin had significantly higher urinary 11-dehydro-TXB(2) as compared with healthy subjects (P < 0.0001) and IHD patients not on aspirin (P = 0.028). They also showed significantly higher 8-iso-PGF(2alpha) (P = 0.018), NT-pro-BNP (P = 0.021) and ADMA (P < 0.0001) than IHD patients not on aspirin. HF patients on low-dose aspirin had significantly lower 11-dehydro-TXB(2) (P < 0.0001), sCD40L (P = 0.007) and 2,3-dinor-6-keto-PGF(1alpha) (P = 0.005) than HF patients not treated with aspirin. HF patients in NYHA classes III and IV had significantly higher urinary 11-dehydro-TXB(2) than patients in classes I and II, independently of aspirin treatment (P < 0.05). On multiple linear regression analysis, higher NT-pro-BNP levels, lack of aspirin therapy and sCD40L, predicted 11-dehydro-TXB(2) excretion rate in HF patients (R(2) = 0.771). CONCLUSIONS: Persistent platelet activation characterizes HF patients. This phenomenon is related to disease severity and is largely suppressable by low-dose aspirin. The homeostatic increase in prostacyclin biosynthesis is impaired, possibly contributing to enhanced thrombotic risk in this setting.

Myeloperoxidase overexpression in children with hypercholesterolemia.

BACKGROUND: Studies conducted in healthy children showed that biomarkers of oxidative stress decreased with increasing age from 1 to 11 years. No data have been reported concerning the behavior of age-related oxidative stress in hypercholesterolemic children. OBJECTIVE: Aim of this study was to test if children with hypercholesterolemia have prolonged exposure to enhanced oxidative stress and to study the underlying mechanism. METHODS: We performed a cross-sectional study comparing 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase plasma levels in 95 normocholesterolemic and 95 hypercholesterolemic children. RESULTS: Compared to normocholesterolemic children, those with hypercholesterolemia had higher 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase plasma levels. A correlation analysis of the overall population showed that total cholesterol was directly correlated with 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase. Stepwise linear regression showed that only total cholesterol, 8-hydroxy-2'deoxyguanosine and myeloperoxidase levels predicted oxidized-LDL plasma levels. In normocholesterolemic children oxidized-LDL and myeloperoxidase plasma levels significantly decreased from first (1-5 years) to second (6-9 years) quartile of age. In hypercholesterolemic children 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase plasma levels did not show significant differences among quartiles of age. CONCLUSION: This study shows that an early and persistent oxidative stress is detected in hypercholesterolemic children and that myeloperoxidase up-regulation might play a role.

[Arterial hypertension and cardiovascular risk: need for a combined strategy of intervention]. / Ipertensione arteriosa e rischio cardiovascolare globale: necessità di una strategia d'intervento combinata.

Arterial hypertension represents one of the most common conditions associated with an increased cardiovascular risk. New evidences support the need to adopt a global approach to the treatment of cardiovascular risk in hypertensive subjects by using drugs with proven benefits, not only for blood pressure control, but also for their pleiotropic effects. A greater understanding of the pathogenetic mechanisms of hypertension would provide a better strategy for preventing and treating this condition. Angiotensin II seems to be responsible for triggering vascular inflammation by inducing oxidative stress, resulting in up-regulation of pro-inflammatory mediators that lead to endothelial dysfunction and vascular injury. The interaction of angiotensin II, oxidative stress and endothelial dysfunction might be a target of a new integrated approach with important clinical implications.

CD40/CD40L system and vascular disease.

Several distinct lines of investigation in the context of atherosclerosis dealing with low-grade inflammation, oxidative stress and platelet activation are now emerging, with CD40/CD40L system as the missing link. CD40 ligand is a transmembrane glycoprotein structurally related to tumour necrosis factor-alpha and more than 95% of the circulating CD40L derives from platelets. CD40L appears as a multiplayer of several cell types in the inflammatory network. The peculiarity of CD40L as an inflammatory mediator derived from platelets expands the functional repertoire of platelets from players of haemostasis and thrombosis to powerful amplifiers of inflammation by promoting the release of cytokines and chemokines, cell activation and cell-cell interactions. The multifunctional role of CD40L, as a simultaneous activator of all these systems, further blurs the intricate relationship between such events both in the physiological systems and the pathological derangement occurring in atherothrombosis.

Contribution of platelet-derived CD40 ligand to inflammation, thrombosis and neoangiogenesis.

CD40-CD40L interactions have been involved in inflammation and thrombosis. Several diseases are characterized by inflammation, hypercoagulability and increased prevalence of thromboembolic events. In the past decade, a series of preclinical and clinical studies has provided more insight into the pathogenetic mechanisms linking inflammatory mediators to the activation and regulation of the haemostatic system. In particular, the study of CD40-CD40L interactions has greatly contributed to understanding the role of platelets in a variety of pathophysiological conditions, including atherothrombosis, immuno-inflammatory diseases and, possibly, cancer. A wide variety of preclinical and clinical studies have generated clinical interest in the use of CD40L as a prognostic marker of thrombotic risk. However, the use of sCD40L in clinical studies requires reliable methods. For the correct interpretation of results, clinical and research laboratories and physicians must be aware of the limitations of immunoassays for this cytokine, which underlines the need for standardization of preanalytic conditions. This review will focus on biochemical evidence of CD40L involvement in platelet activation, contribution of platelet-derived CD40L to inflammation, thrombosis and neoangiogenesis, and possible methodological pitfalls regarding the appropriate specimen and preparation for laboratory evaluation of blood soluble CD40L as a biomarker in various human diseases characterized by underlying inflammation, such as atherothrombosis, cancer and immuno-inflammatory diseases.

Endothelial dysfunction and oxidative stress in arterial hypertension.

A large body of evidence indicates that endothelial dysfunction is a characteristic of patients with essential hypertension. By definition, endothelial dysfunction is a functional and reversible alteration of endothelial cells, resulting from impairment in nitric oxide (NO) availability and oxidative stress. Superoxide anion is a major determinant of NO biosynthesis and also acts as a vasoconstrictor. In addition, NO synthase (NOS) can generate superoxide rather than NO in response to atherogenic stimuli ("NOS uncoupling"). Under these circumstances, NOS may become a peroxynitrite generator, leading to a dramatic increase in oxidative stress, since peroxynitrite has additional detrimental effects on vascular function by lipid peroxidation. Increased levels of biomarkers of lipid peroxidation and oxidative stress have been found in patients with hypertension. In particular, patients with hypertension-related microvascular changes showed increased lipid peroxidation and platelet activation when compared with patients with absent or early signs of retinopathy. Furthermore, oxidant stress has been shown to play an important role in promoting a prothrombotic state in the vascular system. For all these reasons, endothelial dysfunction is evoked in hypertensive patients as promotor of vascular progressive damage and atherosclerotic and thrombotic complications through the enhanced oxidative stress of arterial walls. This broadens the cardiovascular risk of hypertensive patients and explains the insufficient role of the strict BP reduction in the prevention of vascular complications, thus opening up new perspectives on the antioxidant properties of currently available antihypertensive drugs and supplementation with antioxidant principles.

Platelet activation in type 2 diabetes mellitus.

The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, pro-thrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population.

Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients.

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.

Joint sonography in asymptomatic patients with HCV correlated hepatitis.

OBJECTIVES: Many different articular symptoms may appear in patients with HCV hepatitis, but in a relatively large number of patients no rheumatic symptoms are present. This sonographic study was undertaken to detect the possible presence of early articular changes in HCV patients without any rheumatic manifestations. METHODS: The knee, hip and shoulder were evaluated in a cohort of 29 consecutive HCV patients without any rheumatic symptoms. Results were compared with those obtained by the evaluation of 29 healthy subjects who were negative for markers of HCV and HBV infections. RESULTS: Results showed the presence of alterations in 96.5% of the patients, with significant differences in comparison to controls (p < 0.0001). Slight inflammatory changes were found in all the joints examined. The knee was involved in 79.3% of the cases, the hip in 27.6% and the shoulder in 89.6%. CONCLUSIONS: Our preliminary study shows the presence of joint changes in the majority of cases. To the best of our knowledge this is the first ultrasonographic study to focus on joint evaluation in patients with HCV hepatitis. Broader epidemiological and virological investigations, in particular for the HCV subtype and HLA genotype, will be required to elucidate the relationship between HCV infection and rheumatic symptoms.