PURPOSE: To investigate the in vitro antiplatelet and anti-inflammatory effects of five alkyl hydroxytyrosol (HT) ether derivatives in human whole blood and compare these effects with those of HT. METHODS: Blood samples from healthy volunteers were incubated with HT and HT alkyl ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl). Maximum intensity of platelet aggregation was induced with collagen, arachidonic acid or ADP. Calcium-induced thromboxane B(2) and nitric oxide production, LPS-induced prostaglandin E(2) and nitric oxide production and LPS-induced interleukin 1β production were measured. RESULTS: All compounds inhibited platelet aggregation, thromboxane B(2) and inflammatory mediators in a concentration-dependent manner. The concentrations of each compound that inhibited the corresponding variable by 50 % compared to control samples (IC(50)) were in the range of 10(-7)-10(-6) M for HT hexyl ether; for the other compounds, these values were in the range of 10(-5) M. The IC(50) for thromboxane B(2) production was in the range of 10(-4) M. The effects of HT alkyl ether derivatives were greater than those of HT. These compounds increased nitric oxide production. There was no direct relationship between the effects of these compounds and alkyl chain length. Maximum effects were observed in the C4-C6 range. CONCLUSIONS: Alkyl ether derivatives of HT exert antiplatelet and anti-inflammatory effects that are greater than those of HT.

Progesterone is a physiological agonist for mammalian sperm, modulating its flagellar movement and facilitating the acrosome reaction. To study the initial action of progesterone, we developed a caged analog with a photosensitive group: nitrophenyl-ethanediol, at position 20. Using this compound, we performed Ca2+ imaging of human spermatozoa with stroboscopic illumination and analyzed the effects of progesterone on the intracelular Ca2+ concentration ([Ca2+]i) of beating flagella for the first time. We observed a transient [Ca2+]i increase in the head and the flagellum upon photolysis of the caged progesterone and an increase in flagellar curvature. Detailed kinetic analysis revealed that progesterone elicits an increase in the [Ca2+]i immediately in the flagellum (mid-piece and principal piece), thereafter in the head with a short time lag. This observation is different from the progesterone-induced Ca2+ mobilization in mouse spermatozoa, where the Ca2+ rise initiates at the base of the sperm head. Our finding is mostly consistent with the recent discovery that progesterone activates CatSper channels in human spermatozoa, but not in mouse spermatozoa.

Aspects of the chemical ecology of the black-banded oak borer,(BBOB) Coroebus florentinus (Coleoptera: Buprestidae), were studied. Odors produced by males and females were similar, both qualitatively and quantitatively. Nonanal, decanal, and geranylacetone, identified in the headspace of both sexes, elicited strong electroantennographic responses from male antennae, but not from female antennae. In dual-choice olfactometer experiments, a blend of these three compounds was attractive to both sexes; males responded to decanal alone, while females responded to geranylacetone alone, suggesting that these compounds are responsible for activity of the blend to the respective sexes. Antennae of both sexes responded electroantennographically to the green leaf volatiles (E)-2-hexenal,(E)-2-hexenol, 1-hexanol,(Z)-3-hexenyl acetate, and n-hexyl acetate, all identified from the host plant Quercus suber. In behavioral experiments, only females were attracted to host-plant odors, and in tests with synthetic compounds, females were attracted to (E)-2-hexenol, 1-hexanol, and (Z)-3-hexenyl acetate. It is likely that these compounds play a role in foraging and/or oviposition behavior of BBOB females.

BACKGROUND The aim of the present study is to investigate the effectiveness of terutroban, a selective antagonist of the thromboxane/prostaglandin endoperoxide receptor, in preventing retinal ischaemia in a model of diabetes in rats. METHODS Experimental diabetes was induced with streptozotocin. Rats were distributed into five groups (n = 20):(1) non-diabetic rats,(2) rats with diabetes (DR) treated with vehicle,(3) DR treated with aspirin (2 mg/kg/day p.o.),(4) DR treated with terutroban (5 mg/kg/day p.o.),(5) DR treated with terutroban (30 mg/kg/day p.o.). The follow-up period was 3 months. The main assessment was the percentage of retinal surface covered with vessels permeable to peroxidase. Platelet aggregation, aortic prostacyclin and nitric oxide production, plasma levels of lipid peroxides (thiobarbituric-acid-reactive substances) and 3-nitrotyrosine and serum levels of IL-6 were evaluated. RESULTS Diabetes induced a reduction in retinal vascularity (76.9%), aortic prostacyclin (37.8%) and nitric oxide production (35.0%), and increased platelet aggregation, lipid peroxides, 3-nitrotyrosine. When compared with vehicle-treated DR, terutroban increased the percentage of retinal surface covered by PVPP (38% for terutroban-5 and 61% for terutroban-30), aortic prostacyclin (188% for terutroban-5 and 146% for terutroban-30) and nitric oxide production (320% for terutroban-5 and 390% for terutroban-30). Moreover, terutroban reduced platelet reactivity (27.8–95.1%, according to the inducer), lipid peroxides (60.7% for terutroban-5 and 50.0% for terutroban-30), 3-nitrotyrosine (43.8% for terutroban-5 and 36.8% for terutroban-30) and IL-6 concentration (18.0% for terutroban-30). The effect of terutroban in retinal, nitrosative and aortic parameters was significantly higher than that of aspirin. CONCLUSIONS Terutroban significantly protected retinal vascularity from ischaemia in experimental diabetes, and this result could be attributed not only to its antiplatelet/antithrombotic activities but also to its vascular properties.

Background: The occurrence of hemifacial spasm (HFS) during an episode of migraine has been seldom reported. Here we describe three new cases presenting with HFS in association with migraine attacks. Case results: Three patients (one woman and two men, aged 31-36 years) developed HFS in close temporal relationship with migraine headaches. All of them started having the muscle spasms after pain onset. Two of them had electromyographic evidence of facial nerve damage, and continued having HFS once the pain abated. Conclusions: Migraine attacks may be associated with HFS. The appearance of HFS could be related to migraine activity. A mechanism of central hyperexcitability in connection with nociceptive inputs on the trigeminal nucleus caudalis and/or a dilation of vessels compressing the facial nerve at the root exit zone could lead to the development of HFS in predisposed patients.'Migraine-triggered hemifacial spasm' could possibly be regarded as a complication of migraine.

Willingness to Pay (WTP) for direct market of beef is investigated in two Spanish and two French regions located on both sides of the Pyrenees. Given the novelty of this distribution system, especially in Spain, a Contingent Valuation approach is undertaken, and a double-bounded model is estimated. Different patterns of awareness, use and WTP are found across regions. Likewise, the profile of current and potential users of direct sale chains is investigated. Experience in the different stages involved from choice to final consumption of beef, intensity of varied beef consumption, familiarity with direct market of food in general, and beef in particular, are some of the relevant factors to explain WTP and the probability of getting engaged into a direct distribution system of beef.

We have studied the energetics and structural properties of trans-cinnamic acid (CA), o-, m-, and p-coumaric acids (2-, 3-, and 4-hydroxycinnamic acids), caffeic acid (3,4-dihydroxycinnamic acid), ferulic acid (4-hydroxy-3-methoxycinnamic acid), iso-ferulic acid (3-hydroxy-4-methoxycinnamic acid), and sinapic acid (3,5-dimethoxy-4-hydroxycinnamic acid). The experimental values of Δ(f)H(m)°(g), determined (in kJ·mol(-1)) for CA (-229.8 ± 1.9), p-coumaric acid (-408.0 ± 4.4), caffeic acid (-580.0 ± 5.9), and ferulic acid (-566.4 ± 5.7), allowed us to derive Δ(f)H(m)°(g) of o-coumaric acid (-405.6 ± 4.4), m-coumaric acid (-406.4 ± 4.4), iso-ferulic acid (-565.2 ± 5.7), and sinapic acid (-698.8 ± 4.1). From these values and by use of isodesmic/homodesmotic reactions, we studied the energetic effects of π-donor substituents (-OH and -OCH(3)) in cinnamic acid derivatives and in the respective benzene analogues. Our results indicate that the interaction between -OCH(3) and/or -OH groups in hydroxycinnamic acids takes place without significant influence of the propenoic fragment.

PURPOSE Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy (PST) in postmenopausal women with ER-positive early breast cancer. However, the optimum duration of endocrine PST remains uncertain. METHODS A phase 2 multicentre, open-label trial was conducted to evaluate the efficacy of letrozole over a preoperative period of 4 months to 1 year. Seventy postmenopausal patients (over 65 years) were recruited in four centers. The primary endpoint was to establish the optimal duration of treatment defined as the time required to attain the maximum response by clinical palpation. RESULTS The median age of the group was 79 years (66-91) and the median tumour size 35 mm (range 25-100 mm). No severe adverse events were reported. Fifty-six patients were evaluable for the primary objective. A total of 43 patients (76.8%) achieved an objective response; 29 (51.8%) being partial and 14 (25.0%) complete. The median time to objective response was 3.9 months (95% CI, 3.3-4.5) and the median time to maximum response was 4.2 months (95% CI, 4.0-4.5), although 20 (37.1%) patients achieved the maximal response within 6-12 months. CONCLUSIONS Letrozole shows a high activity and excellent tolerability as neoadjuvant therapy in elderly patients with endocrine-dependent breast cancer. Four to six months of letrozole as PST is an optimum duration with modest benefits thereafter.

While studying the functions of CCM3/PDCD10, a gene encoding an adaptor protein whose mutation results in vascular malformations, we have found that it is involved in a novel response to oxidative stress which results in phosphorylation and activation of the ezrin/radixin/moesin (ERM) family of proteins. This phosphorylation protects cells from accidental cell death induced by oxidative stress. We also present evidence that ERM phosphorylation is performed by the GCKIII kinase Mst4, which is activated and relocated to the cell periphery after oxidative stress. The cellular levels of Mst4 and its activation after oxidative stress depend on the presence of CCM3, as absence of the latter impairs the phosphorylation of ERM proteins and enhances death of cells exposed to reactive oxygen species. These findings shed new light on the response of cells to oxidative stress and identify an important pathophysiological situation in which ERM proteins and their phosphorylation play a significant role.

BACKGROUND The World Health Assembly recently adopted a resolution to urge improved competency in the provision of injury care through medical education. This survey sought to investigate trauma education experience and competency among final year medical students worldwide. METHODS An Internet survey was distributed to medical students and conducted from March 2008 to January 2009. Demographic data and questions pertaining to both instruction and attainment of specific skills in burn and trauma care were assessed. RESULTS There were 776 responses from final year medical students in 77 countries, with at least 10 countries from each economic stratum. Over 93% of final year students reported receiving some form of trauma or burn training, with 79% reporting a minimum compulsory requirement. Students received theoretical instruction without practical exposure. Few felt prepared to undertake basic procedures, such as laceration repair (19%), vascular access (8%), or endotracheal intubation (21%). Over 99% agreed that trauma education should be mandatory, but only half felt prepared to provide basic care. Those from low income and low middle income countries felt better prepared to provide trauma care than students from high middle and high income countries. CONCLUSIONS Trauma education and experience varies among medical students in different countries. Many critical concepts are not formally taught and practical experience with many basic procedures is often lacking. The present study confirms that the trauma care training received by medical students needs to be strengthened in countries at all economic levels.