Citizen science participation in research in the environmental sciences: key factors related to projects' success and longevity.

The potential impacts of citizen science initiatives are increasing across the globe, albeit in an imbalanced manner. In general, there is a strong element of trial and error in most projects, and the comparison of best practices and project structure between different initiatives remains difficult. In Brazil, the participation of volunteers in environmental research is limited. Identifying the factors related to citizen science projects' success and longevity within a global perspective can contribute for consolidating such practices in the country. In this study, we explore past and present projects, including a case study in Brazil, to identify the spatial and temporal trends of citizen science programs as well as their best practices and challenges. We performed a bibliographic search using Google Scholar and considered results from 2005-2014. Although these results are subjective due to the Google Scholar's algorithm and ranking criteria, we highlighted factors to compare projects across geographical and disciplinary areas and identified key matches between project proponents and participants, project goals and local priorities, participant profiles and engagement, scientific methods and funding. This approach is a useful starting point for future citizen science projects, allowing for a systematic analysis of potential inconsistencies and shortcomings in this emerging field.

Effects of riparian vegetation restoration and environmental context on ecosystem functioning in tropical streams of southeastern Brazil.

Tropical stream ecosystems are under increasing human pressure, making the development of effective restoration approaches and expanding knowledge in this field urgent. This study evaluated the impact of riparian vegetation restoration and environmental context on stream ecosystem functioning by measuring key ecosystem functions - gross primary production (GPP), ecosystem respiration (ER), and nutrient uptake of ammonium and soluble reactive phosphorus - across ten tropical streams in southeastern Brazil. The streams represented a gradient from clearcut areas (impacted reaches) to relatively pristine conditions (reference reaches), including intermediate stages of vegetation recovery (restored reaches). In the short-term (~15-20 years after restoration), restoration led to reduced GPP akin to reference reaches. Yet, ER did not show the anticipated increase, suggesting a longer timeframe is necessary for restored streams to emulate the functional characteristics of reference reaches. Additionally, the restored reaches did not achieve the nutrient uptake efficiencies observed in both impacted and reference reaches, pointing to a partial recovery of ecosystem function. This study suggests that while riparian vegetation restoration contributes positively to certain aspects of stream function, environmental variables less related to this type of restoration, such as discharge and hydromorphology, significantly influence stream ecosystem functioning, highlighting the importance of considering environmental context in restoration efforts. A more holistic approach, possibly encompassing broader hydromorphological and habitat enhancements, is needed to fully restore ecological processes in these vital ecosystems. These insights are critical for informing future tropical stream restoration projects, advocating the use of ecosystem function metrics as comprehensive indicators of ecological recovery and restoration success.

Contiguous urban rivers should not be necessarily submitted to the same management plan: the case of Tietê and Pinheiros Rivers (São Paulo-Brazil).

The management of urban water resources plays an important role for developing countries. The Tietê and Pinheiros Rivers (São Paulo, Brazil) are affected by domestic and industrial effluents and by the diffuse pollution. This research aimed to quantify 134 variables in the water of Tietê and Pinheiros Rivers (approximately 7,200 and 6,600 analyses, respectively) from August 2007 to December 2008. The idea was to verify if the fact that both rivers are located in the same basin is enough to consider the application of a single management plan for both. Data showed that the rivers presented significant anthropogenic interference. The results suggested that such rivers must be subjected to individual management plans since there were exclusive occurrences (variables that were only detected in one of the rivers). Moreover, there was a statistically significant difference between rainy and dry periods for eleven variables (p*<0.05, ANOVA), reinforcing the special importance of the temporal component within the monitoring program. It is expected that this study subsidize environmental recovery programs in the Tietê River, to which is recommendable to focus on prosecution of illegal wastewater releases, and in the Pinheiros River, to which special attention is suggested to the pollution derived from the pesticides load to the water body.

Defining nutrient and biochemical oxygen demand baselines for tropical rivers and streams in São Paulo State (Brazil): a comparison between reference and impacted sites.

Determining reference concentrations in rivers and streams is an important tool for environmental management. Reference conditions for eutrophication-related water variables are unavailable for Brazilian freshwaters. We aimed to establish reference baselines for São Paulo State tropical rivers and streams for total phosphorus (TP) and nitrogen (TN), nitrogen-ammonia (NH(4) (+)) and Biochemical Oxygen Demand (BOD) through the best professional judgment and the trisection methods. Data from 319 sites monitored by the São Paulo State Environmental Company (2005 to 2009) and from the 22 Water Resources Management Units in São Paulo State were assessed (N = 27,131). We verified that data from different management units dominated by similar land cover could be analyzed together (Analysis of Variance, P = 0.504). Cumulative frequency diagrams showed that industrialized management units were characterized by the worst water quality (e.g. average TP of 0.51 mg/L), followed by agricultural watersheds. TN and NH(4) (+) were associated with urban percentages and population density (Spearman Rank Correlation Test, P < 0.05). Best professional judgment and trisection (median of lower third of all sites) methods for determining reference concentrations showed agreement: 0.03 & 0.04 mg/L (TP), 0.31 & 0.34 mg/L (TN), 0.06 & 0.10 mg-N/L (NH(4) (+)) and 2 & 2 mg/L (BOD), respectively. Our reference concentrations were similar to TP and TN reference values proposed for temperate water bodies. These baselines can help with water management in São Paulo State, as well as providing some of the first such information for tropical ecosystems.

Long-term ecotoxicological effects of ciprofloxacin in combination with caffeine on the microalga Raphidocelis subcapitata.

Ciprofloxacin (CIP) is an antimicrobial "pseudo-persistent" in aquatic ecosystems. Once dispersed in the water compartments, it can also affect the microalgae. Thus, the evaluation of its long-term ecotoxicological effects is necessary. CIP interactions with other pharmaceuticals are not well known. In this study, we investigated the toxic effects of CIP alone and combined with caffeine (CAF), using the modified Gompertz model parameters and the chlorophyll-a production of the microalga Raphidocelis subcapitata as endpoints, throughout a 16-day exposure assay. The exposure to CIP alone led to significant reductions of the growth rate and the cell density of the microalgae compared to control groups. The combination with CAF lowered the adverse effects of CIP to R. subcapitata. However, as the toxicity is dynamic, our results indicated that the toxic effects in respect to the studied endpoints changed throughout the exposure period, reinforcing the need for longer-term ecotoxicity assessments.

Isolated intraorbital schwannoma arising from the abducens nerve.

CASE REPORT: A case of isolated schwannoma of the orbit, arising from the terminal branches of the abducens nerve to the lateral rectus muscle, is reported. The patient presented with a painless proptosis of the left eye. DISCUSSION: Preoperative diagnosis of benign intraorbital neoplasm was made by means of CT and MR scans; the mass was radically excised through a microsurgical lateral orbitotomy and the pathological examination revealed a schwannoma. Features of orbital schwannoma are described, together with some details concerning the surgical strategy and the history of the evolution of the lateral orbitotomy.

Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism.

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation.

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.

[What do we know about obesity?]. / Cosa sapere sul problema obesità?

The prevalence of obesity is increasing rapidly in most industrialized countries and it is known that obesity is associated with increased risk of cardiovascular morbidity and mortality. Commonly, obesity is defined by the Body Mass Index (BMI). However, BMI fails to consider body fat distribution. The relationship between the risk of metabolic-cardiovascular diseases and body fat distribution indices, rather than measures of the degree of body fatness as expressed by BMI, has long been recognized. Clinical and epidemiological research has found waist circumference to be the best anthropometric indicator of both total body fat and intra-abdominal fat mass. Android obesity is associated with metabolic syndrome and increased cardiovascular risk through molecular mechanisms possibly linking the metabolic syndrome to hemostatic and vascular abnormalities. Obesity guidelines suggest the need for weight reduction using behavioural change to reduce caloric intake and increasing physical activity. A realistic goal for weight reduction is to reduce body weight by 5% to 10% over a period of 6 to 12 months. Combined intervention of a low calories diet, increased physical activity, and behaviour therapy provides better outcomes for long-term weight reduction and weight maintenance than programs that use only one or two of these modalities. The anorexiant drugs affect neurotransmitters in the brain. The sibutramine has norepinephrine and serotonin effects. Orlistat has a different mechanism of action: the reduction of fat absorption. Recently, the blockade of the endocannabinoid system with rimonabant may be a promising new strategy.

Aspirin, platelets, and cancer: The point of view of the internist.

Growing evidence suggests the beneficial effect of aspirin against some types of cancer, particularly of the gastrointestinal tract, and it has been provided for an effect both in cancer prevention as well as in survival improvement of cancer patients. Aspirin benefits increase with duration of treatment, especially after 10years of treatment. The inhibition of platelet activation at sites of gastrointestinal mucosal lesions could be the primary mechanism of action of low-dose aspirin. Indeed, the formation of tumor cell-induced platelet aggregates may favor immune evasion, by releasing angiogenic and growth factors, and also by promoting cancer cell dissemination. Moreover, platelets may contribute to aberrant COX-2 expression in colon carcinoma cells, thereby contributing to downregulation of oncosuppressor genes and upregulation of oncogenes, such as cyclin B1. Platelet adhesion to cancer cells leads also to an increased expression of genes involved in the EMT, such as the EMT-inducing transcription factors ZEB1 and TWIST1 and the mesenchymal marker vimentin. The aspirin-mediated inactivation of platelets may restore antitumor reactivity by blocking the release of paracrine lipid and protein mediators that induce COX-2 expression in adjacent nucleated cells at sites of mucosal injury. Thus, recent findings suggest interesting perspectives on "old" aspirin and NSAID treatment and/or "new" specific drugs to target the "evil" interactions between platelets and cancer for chemoprevention.

Prolonged maternal separation induces undernutrition and systemic inflammation with disrupted hippocampal development in mice.

OBJECTIVE: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. METHODS: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. RESULTS: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and dentate gyrus. Furthermore, PMS reduced hippocampal aspartate, glutamate, and gamma-aminobutyric acid levels, as compared with unseparated controls. CONCLUSION: These findings suggest that PMS causes significant growth deficits and alterations in hippocampal morphology and neurotransmission.

Fractional conversion of thromboxane B2 to urinary 11-dehydrothromboxane B2 in man.

Thromboxane (TX) B2, the chemically stable hydration product of pro-aggregatory TXA2, undergoes two major pathways of metabolism in man, resulting in the formation of 2.3-dinor-TXB2 and 11-dehydro-TXB2, respectively. We have measured the excretion of the latter during the infusion of exogenous TXB2 over a 50-fold dose range in order to examine the fractional conversion of TXB2 to urinary 11-dehydro-TXB2 and to re-assess the rate of entry of endogenous TXB2 into the circulation. Four healthy male volunteers received 6-h intravenous infusions of the vehicle alone and TXB2 at 0.1, 1.0 and 5.0 ng.kg-1.min-1 in random order. They were pretreated with aspirin 325 mg/d in order to suppress endogenous TXB2 production. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured before, during and up to 24 h after the infusions and in aspirin-free periods, by means of NICI-GC/MS-validated radioimmunoassays. Aspirin treatment suppressed urinary 11-dehydro-TXB2 by 91%. The fractional elimination of 11-dehydro-TXB2 was independent of the rate of TXB2 infusion and averaged 6.8 +/- 0.7%, as compared to 6.4 +/- 0.9% for 2,3-dinor-TXB2. Interpolation of 11-dehydro-TXB2 values obtained in aspirin-free periods onto the linear relationship between the quantities of infused TXB2 and the amount of metabolite excreted in excess of control values (y = 0.0058x, r = 0.94, P less than 0.001) permitted calculation of the mean rate of entry of endogenous TXB2 into the circulation as 0.12 ng.kg-1.min-1. We conclude that: (a) urinary 11-dehydro-TXB2 is at least as abundant a conversion product of exogenously infused TXB2 as 2,3-dinor-TXB2; (b) its excretion increases linearly as a function of the rate of entry of TXB2 into the circulation up to approx. 40-fold the calculated rate of secretion of endogenous TXB2; (c) the latter is consistent with previous estimates based on monitoring of the beta-oxidation pathway of TXB2 metabolism.

In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.

BACKGROUND: Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2alpha, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation. METHODS AND RESULTS: Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2alpha and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non-insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion. CONCLUSIONS: We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina.

BACKGROUND: Unstable angina is associated with enhanced lipid peroxidation and reduced antioxidant defenses. We have previously reported aspirin failure in the suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane 8-iso-prostaglandin (PG)F(2alpha), a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis. METHODS AND RESULTS: Urine samples were obtained from patients with unstable angina (n=32), stable angina (n=32), or variant angina (n=4) and from 40 healthy subjects for the measurement of immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2). 8-Iso-PGF(2alpha) excretion was significantly higher in patients with unstable angina (339+/-122 pg/mg creatinine) than in matched patients with stable angina (236+/-83 pg/mg creatinine, P:=0.001) and control subjects (192+/-71 pg/mg creatinine, P:<0.0001). In patients with unstable angina, 8-iso-PGF(2alpha) was linearly correlated with 11-dehydro-TXB(2) excretion (rho=0.721, P:<0.0001) and inversely correlated with plasma vitamin E (rho=-0.710, P:=0. 004). Spontaneous myocardial ischemia in patients with variant angina or ischemia elicited by a stress test in patients with stable angina was not accompanied by any change in 8-iso-PGF(2alpha) excretion, thus excluding a role of ischemia per se in the induction of increased F(2)-isoprostane production. CONCLUSIONS: These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.

Oxidative stress and platelet activation in homozygous homocystinuria.

BACKGROUND: Severe hyperhomocysteinemia due to cystathionine beta-synthase deficiency (CbetaSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F(2alpha), a platelet-active product of arachidonic acid peroxidation, is enhanced in CbetaSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion. METHODS AND RESULTS: Urine and blood samples were obtained from patients with homozygous CbetaSD (n=13) and age-matched healthy subjects. Urinary 8-iso-PGF(2alpha) excretion was significantly higher in CbetaSD patients than in control subjects (640+/-384 versus 213+/-43 pg/mg creatinine; P=0.0015) and correlated with plasma homocysteine (rho=0.398, P=0.0076). Similarly, urinary 11-dehydro-TXB(2) excretion was enhanced in CbetaSD (1166+/-415 versus 324+/-72 pg/mg creatinine; P=0.0015) and correlated with urinary 8-iso-PGF(2alpha) (rho=0.362, P=0.0153). Vitamin E supplementation (600 mg/d for 2 weeks) was associated with a statistically significant increase in its plasma levels (from 16.6+/-4.6 to 40.4+/-8.7 micromol/L, P=0.0002) and with reductions in 8-iso-PGF(2alpha) (from 790+/-159 to 559+/-111 pg/mg creatinine, P=0.018) and 11-dehydro-TXB(2) (from 1273+/-383 to 913+/-336 pg/mg creatinine, P=0.028). A statistically significant inverse correlation was found between urinary 8-iso-PGF(2alpha) and plasma vitamin E levels (rho=-0.745, P=0.0135). CONCLUSIONS: The results of the present study suggest that enhanced peroxidation of arachidonic acid to form bioactive F(2)-isoprostanes may represent an important mechanism linking hyperhomocysteinemia and platelet activation in CbetaSD patients. Moreover, they provide a rationale for dose-finding studies of vitamin E supplementation in this setting.

Effects of vitamin E supplementation on F(2)-isoprostane and thromboxane biosynthesis in healthy cigarette smokers.

BACKGROUND: Increased formation of 8-iso-prostaglandin (PG) F(2alpha) and thromboxane (TX) A(2), potent agonists of platelet and vascular thromboxane (TH)/PGH(2) receptors, has been detected in cigarette smokers. We performed a randomized, double-blind, placebo-controlled study of the effects of vitamin E (300, 600, and 1200 mg/d, each dose for 3 consecutive weeks) on 8-iso-PGF(2alpha) and TXA(2) biosynthesis in 46 moderate cigarette smokers. METHODS AND RESULTS: Urinary immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2), plasma vitamin E, and serum TXB(2) were measured by previously validated techniques. Baseline urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion averaged 241+/-78 and 430+/-293 pg/mg creatinine, respectively. Urinary 8-iso-PGF(2alpha) was significantly correlated with 11-dehydro-TXB(2) (r=0.360, n=138, P<0.0001). Baseline plasma vitamin E levels averaged 20.6+/-4.9 micromol/L and were inversely correlated with urinary 11-dehydro-TXB(2) (r=-0.304, P=0.039) but not with 8-iso-PGF(2alpha) (r=-0.227, P=0.129). Vitamin E supplementation caused a dose-dependent increase in its plasma levels that reached a plateau at 600 mg (42.3+/-11.2 micromol/L, P<0. 001). This was not associated with any statistically significant change in urinary 8-iso-PGF(2alpha) or 11-dehydro-TXB(2) excretion. CONCLUSIONS: Supplementation with pharmacological doses of vitamin E has no detectable effects on lipid peroxidation and thromboxane biosynthesis in vivo in healthy subjects with a mild degree of oxidant stress. These findings are consistent with the hypothesis that the basal rate of lipid peroxidation is a major determinant of the response to vitamin E supplementation and have implications for the use of vitamin E in healthy subjects as well as for the design and interpretation of clinical trials of antioxidant intervention.

Association between circulating adiponectin and interleukin-10 levels in android obesity: effects of weight loss.

OBJECTIVE: Adiponectin inhibits vascular inflammation and increases IL-10 mRNA expression in human macrophages. Thus, we investigated the possible relationship between plasma adiponectin and IL-10 levels and the effects of a diet-induced moderate weight loss on both cytokines. PATIENTS AND STUDY DESIGN: Plasma adiponectin and IL-10 levels were analyzed in 64 android [body mass index (BMI), > 28 kg/m2; waist to hip ratio (WHR), > or = 0.86] and 20 gynoid [BMI, > 28 kg/m2; WHR, < 0.86] obese healthy women. Android obese women (49 +/- 14 yr) had a mean BMI of 37.1 +/- 5.3 kg/m2, similar to that of gynoid obese women (49 +/- 11 yr; BMI, 33.4 +/- 2.6 kg/m2). Twenty nonobese control women (46 +/- 11 yr; BMI, 25.2 +/- 2.2 kg/m2) were also studied. In 15 android obese women, measurements were repeated after a 12-wk diet period (1200 kcal/d). RESULTS: Median adiponectin [5.2 (range, 3.3-7.8) vs. 12.1 (9.7-13.9) vs. 15.0 (12.6-18.2) microg/ml; P < 0.0001] and IL-10 [1.8 (1.2-3.3) vs. 3.5 (2.9-4.3) and vs. 4.1 (3.5-4.8) pg/ml; P < 0.0001] levels were lower in android vs. gynoid vs. nonobese women. Among android obese women, low adiponectin levels were independently related (P < 0.0001) to decreased IL-10 levels, independently of BMI, WHR, or insulin resistance. No significant change in either median adiponectin or IL-10 levels was observed after body weight reduction (8 +/- 4 kg; P < 0.01), although percent changes in adiponectin paralleled those in IL-10 (P < 0.05). CONCLUSIONS: Android obesity is associated with a concomitant reduction of IL-10 and adiponectin levels. However, the antiinflammatory status of obesity might require prolonged periods of energy-restricted diets to revert to normal.

Circulating immune complexes and platelet thromboxane synthesis in patients with insulin-dependent (type I) diabetes mellitus.

Platelets from diabetic subjects with circulating immune complexes (CIC) synthesized greater amounts of thromboxane than did platelets from CIC-negative patients or controls. In view of the known action of CIC on platelet function, a relationship between these two factors may be suggested in the initiation and progression of microangiopathy in diabetes.

Long-term treatment with the dual antithromboxane agent picotamide decreases microalbuminuria in normotensive type 2 diabetic patients.

Picotamide both inhibits thromboxane synthetase and acts as a thromboxane antagonist at the receptor level. We investigated the long-term effect of picotamide on urinary albumin excretion (UAE) at rest and induced by exercise in 30 type 2 diabetic patients who were normotensive and had microalbuminuria while at rest. The subjects of our study had a mean age of 52.5 +/- 1.6 years, BMI of 28.5 +/- 0.7 kg/m2, diabetes duration of 9.1 +/- 1.8 years, and HbA1c of 7.0 +/- 0.8%. The study was a randomized double-blind placebo-controlled trial. The patients were randomly allocated to receive for 1 year either picotamide, 300 mg, 3 tablets/day, or placebo, 3 tablets/day. The patients were asked to visit our outpatient clinic after 1, 3, 6, 9, and 12 months of treatment. At all times, blood pressure, microalbuminuria at rest, blood glucose, serum creatinine, serum picotamide, and creatinine clearance were measured; at baseline and after 6 and 12 months, all patients underwent submaximal physical exercise. After 6 months of picotamide, baseline and exercise-induced microalbuminuria were significantly decreased (up to one-third) as compared with the baseline and placebo level, with no further drops at month 12 of picotamide treatment. On placebo treatment, UAE at rest and after exercise was slightly increased compared with baseline values. The effects of picotamide occurred without significant side effects or changes in either blood pressure levels or glycometabolic control. Our study is the first long-term intervention trial in type 2 diabetes showing that an antithromboxane agent is able to decrease microalbuminuria, which in this disease is a dual marker of macro- and microangiopathy. Our findings suggest an important role for thromboxane in the pathophysiology of microalbuminuria in diabetes; moreover, we hypothesize that antithromboxane agents may have a place in the treatment/prevention of both macro- and microvascular complications in type 2 diabetic patients.

Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus.

Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.