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SummaryPlatelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1–independent mechanism.

Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100 mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1 ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB23.1 ng/ml and (2) TxB23.1 ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r = 0.76619).

Objective: Body image dissatisfaction is common in treatment-seeking patients with obesity. We aimed to investigate the effects of obesity management on body image in patients with obesity attending Italian medical centers for weight loss programs. Research Methods and Procedures: A total of 473 obese patients seeking treatment in 13 Italian medical centers (80% females; age, 45.9 ± standard deviation 11.0 years; BMI, 36.8 ± 5.7 kg/m2) were evaluated at baseline and after a 6-month weight loss treatment. Body uneasiness, psychiatric distress, and binge eating were tested by Body Uneasiness Test (BUT, Part A), Symptom CheckList-90 (SCL-90), and Binge Eating Scale (BES), respectively. Results: At 6-month follow-up, the percentage weight loss was significantly higher in men (9.0 ± 6.3%) than in women (6.8 ± 7.3%; p = 0.010). Both men and women had a significant improvement in BUT Global Severity Index and in all of the BUT subscales with the exception of the Compulsive Self-Monitoring subscale. Linear regression analysis selected baseline psychological and behavioral measures (global score of BUT and SCL-90) and improved psychiatric distress and binge eating as independent predictors of changes in basal body dissatisfaction in females, whereas in males, changes were associated only with baseline BUT-Global Severity Index score, binge eating, and its treatment-associated improvement. Pre-treatment BMI and BMI changes did not enter the regression. Discussion: Obesity treatment, even with a modest degree of weight loss, is associated with a significant improvement of body image, in both females and males. This effect depends mainly on psychological factors, not on the amount of weight loss.

OBJECTIVE: To investigate the psychometric properties of the Body Uneasiness Test (BUT) in a large sample of subjects with obesity seeking treatment. BUT is a 71-item self-report questionnaire in two parts: BUT-A which measures weight phobia, body image concerns, avoidance, compulsive self-monitoring, detachment and estrangement feelings towards one's own body (depersonalization); and BUT-B, which looks at specific worries about particular body parts or functions. METHODS: We recruited a clinical sample of 1,812 adult subjects (age range 18-65 years, females 1,411, males 401) with obesity (Body Mass Index, BMI > or = 30 kg/m2) and a normal weight (BMI value between 18.5 and 25 kg/m2) non-clinical sample of 457 adult subjects (females 248, males 209) with an Eating Attitudes Test-26 (EAT-26) score under the cut-off point 20 (scores > or = 20 indicate possible cases of eating disorders). RESULTS: The exploratory and confirmatory analyses confirmed a structural five-factor model for BUT-A and an eight-factor model for BUT-B. Internal consistency was satisfactory. Concurrent validity with Binge Eating Scale (BES) and Three-Factor Eating Questionnaire (TFEQ) was evaluated. The authors calculated mean values for BUT scores in adult (18-65 years) patients with obesity, and evaluated the influence of gender, age and BMI. Females obtained statistically significant higher scores than males in all age groups and in all classes of obesity; patients with obesity, compared with normal weight subjects, generally obtained statistically significant higher scores, but few differences could be attributed to the influence of BMI. CONCLUSION: The BUT can be a valuable multidimensional tool for the clinical assessment of body uneasiness in obesity; the scores of its sub-scales do not show a linear correlation with BMI values.

The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine.

New ergoline derivatives exhibiting antiulcer and antisecretory activities were synthesized and tested. Stereochemical modification of the ergoline skeleton was found to influence the selective activity of the compounds.

The synthesis and the antihypertensive activity in rats of a series of 6-methylergolin-8 beta-yl-propionic acid derivatives are reported. The prolactin lowering activity (nidation inhibition test) in rats and the acute toxicity in mice were also studied as a measure of the specificity and safety of the potential antihypertensive compounds. From the structure-activity considerations reported here it is clear how modifications at the C8 side chain can improve the selectivity of the antihypertensive effects, whilst introducing substituents in other positions of the ergoline skeleton afforded unfavourable results in this respect. Compound 5, namely 2(R,S)-cyano-3-(6-methylergolin-8 beta-yl)-propionamide, emerged as the most interesting antihypertensive derivative.