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Background: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. Objective: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. Methods: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. Results: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). Conclusions: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective. [ABSTRACT FROM AUTHOR]

Disturbances in haemodynamic, biochemical and enzymatic factors have been observed in chronic venous diseases (CVD). These changes lead to the development of varices, telangiectasies and skin disorders. They affect vessels, blood, skin tissues and cells. It is now possible to describe their time course and interdependance of these changes. Orthostatism pressure on vein wall may lead to fluid leakage and oedema, these resulting in vein enlargement. These processes may be further influenced by genetic or acquired risk factors. Skin microvessels suffer more from hypoxia than from hypertension. Indeed, hypoxia affects not only endothelial cells, but also red and white blood cells and modifies particularly, but not exclusively, TGF‐β1 production. This substance is, an important modulator of zinc dependent‐metallo‐proteinases and their tissue inhibitor of metallo‐proteinases (TIMP) in the skin. Imbalance in this enzymatic system seems to lead either to sclerosis or ulcer. Of course, other biochemical events (also in this review) play a role in vessel wall and skin deterioration in CVD. The aim of the present review is to assess the role of pathophysiological factors in CVD and the influence of different therapies, including the venotropic agent calcium dobesilate, on some of these haemodynamic or biochemical aspects. [ABSTRACT FROM AUTHOR]

Long-term metabolic changes in vein tissue of the limbs and feet have been reported in the course of chronic venous insufficiency (CVI). Low fibrinolytic potential was first demonstrated using fibrin-embedded vein rings (Todd's biopsy), then in blood via increased euglobulin lysis time. This defect is especially pronounced when blood is taken from foot veins of patients with grades 5 and 6 of CVI or skin lesions. Haemorrheological disorders such as increased blood viscosity and red cell aggregation, related mainly to high fibrinogen levels, have also been shown in patients with CVI. Such disorders, particularly observed in blood from foot veins, play an important role in the interaction between the blood cell components and the vessel wall. More recently, the margination and adhesion of white cells to the endothelium and the subsequent activation of white cells have been assumed. Adhesion molecules such as ICAM-1, VCAM-1 and P-selectin have been identified surrounding skin ulceration. There is also evidence that markers of neutrophil degranulation reach high levels in blood taken from foot veins after exposure to experimental venous hypertension. White cell activation results in elevated plasma levels of L-selectin, increased production of oxygen free radicals, pseudopods, CD11b integrin, platelet-monocyte aggregates and abnormal lymphocyte L-selectin. Increased nitric oxide, presumably due to monocyte activation, as well as increased urine haemosiderin related to skin microvessel leakage have also been reported. VCAM-1 and metalloproteinase MMP9 activity have been stated as sensitive markers in relation to endothelium activation and white cell trapping, which follows hypoxia and/or alterations in wall shear stress, mainly in skin venulae and in the region of valves. [ABSTRACT FROM AUTHOR]

Ten populations of Radopholus similis from various locations and one population of Radopholus sp. from Indonesia were tested for their reproductive fitness and specific pathogenicity on Musa AAA, Cavendish cv. Poyo under controlled experimental conditions in a constant environment chamber. In addition, five of these populations were tested on Musa AAA, Ibota cv. Yangambi. Reproductive fitness of the populations tested on the two cultivars, measured as the ratio of the final number of nematodes per root system (Pf) to the number of nematodes inoculated (Pf), differed significantly. Greatest fitness was observed among R. similis populations collected from banana in different African countries (Cameroon, Uganda and the Ivory Coast) and one population from arecanut in Sri Lanka. In contrast, a population from tea in Sri Lanka and the population of Radopholus sp. from turmeric in Indonesia were the least fit. Specific pathogenicity was estimated at 8 weeks and 12 weeks after inoculation using three plant growth parameters: fresh root weight, fresh shoot weight and plant height, compared to uninfected control plants. Reduction in plant root weight was the best indicator of pathogenicity. While the R. similis populations from Uganda and the Ivory Coast were highly pathogenic, other populations with great reproductive fitness (i.e. isolates from Cameroon and Sri Lanka) did not significantly reduce root weight. In cv. Poyo, no linear correlation was found between final numbers of nematodes per gram of root (Pf) and the decrease of root weight. [ABSTRACT FROM AUTHOR]

A flow cytometry method has been introduced into the routine investigation of whole bone marrow samples following red blood cell lysis on the basis of a primary CD45/side scatter (SSC) gating procedure. Blast cells were first identified by CD45/SSC gating in 74 cases of acute myeloid leukemia (AML) and the results were compared to a conventional FSC/SSC gating procedure and to MGG-staining smears. The percentages of blast cells in these samples as defined by the morphological analysis of MGG smears correlated better with the values determined by CD45/SSC gating (r = 0.94) than with the blast cell counts recorded with FSC/SSC gating (r = 0.76). These findings were not surprising because while CD45 expression was regularly lower on leukemic blasts than on normal lymphoid and monocytic cells, the FCS/SSC characteristics of these populations were overlapping. In 53 samples, the blast cell populations were also analyzed with a panel of FITC-conjugated monoclonal antibodies that were utilized in double labeling with CD45-PE. We show that the CD45/SSC gating procedure improved phenotypic determination of the blast cells in three ways: (1) by discriminating between leukemic blast cells and residual normal cells; (2) by excluding normal cells from the phenotypic analysis of leukemic blast cells; and (3) by identifying blast cell heterogeneity in many cases of leukemia on the basis of different CD45 display. Moreover, this immunophenotyping procedure on whole bone marrow samples also allowed an efficient discrimination between the various cell lineages and facilitated the analysis of leukemic blasts present in low proportions. [ABSTRACT FROM AUTHOR]

Patients with a particular thrombotic profile may be at greater risk of myocardial infarction during coronary artery bypass graft surgery. The thrombotic profile of 50 patients admitted to hospital with stable angina pectoris was determined prior to haemodynamic investigation. ECG results and determination of cardiac enzymes showed that 12 patients had suffered a perioperative myocardial infarction. These patients had a higher mean atherosclerotic score (42.1 ± 10.5 vs 32.9 ± 13, P<0.02), a longer aortic cross clamp time (59 ± 15.2 vs 45.7 ± 16.3 min, P < 0.05), lower serum levels of protein C (101.2±26 vs 124.7+ 31.4%, P<0.05) and tissue plasminogen activator (322 ± 580 vs 2307±2830 IU ml, P<0.01). There were no differences between the two groups in Jenkin's coronary score, the number and type of grafts, ejection fraction, left ventricular end-diastolic pressure, lipid profile or levels of markers of platelet release. In addition to a more severe distal coronary atheroma and a longer aortic cross-clamp time, patients with impaired endothelial fibrinolytic activity appeared to be at greater risk of myocardial infarction during coronary artery bypass graft surgery. [ABSTRACT FROM PUBLISHER]

Investigates a Plasmodium falciparum infection following an allogeneic bone-marrow transplantation in Toulouse, France. Development of fever and signs of mental confusion; Use of tetracycline due to the risk of multidrug-resistant strain of P. falciparum; Detection of malarial parasites.

Background: A worldwide increased incidence of HM has been marked in recent decades. Therefore, to update epidemiological characteristics of HM in a French West Indies territory, we have performed analysis through Martinique's population-based cancer registry database., Methods: We included cancer case data, from 2009-2018, coded in strict compliance with international standards set by International Agency for Research on Cancer. We calculated standardized incidence rates, cumulative rate (ages 0-74), and temporal trends for cases and deaths using the global population standard, by sex and five age group. Mortality rates were obtained from the French Epidemiology Center on Medical Causes of Death (CépiDc)., Results: One thousand forty seven new cases and 674 deaths from HM were recorded, of which 501 MM (47.8%), 377 LMNH (36%), 123 LAM (11.8%), and 46 LH (4.4%) were reported in both sexes. MM is one of the hematological malignancies with the highest incidence in Martinique among men. Temporal trends of incidence rates for all HM decreased overall in both sexes, except for MM in men. There is significant variability in mortality rates for both sexes. In addition, over the period, the temporal trends of mortality rates for all HMs has decreased overall. Gender-specific rates, between 2009 and 2018, showed that all lymphoid HM have a multimodal distribution curve that increased with age., Conclusions: Characteristics of HM in Martinique over the reporting periods differ from mainland France. Higher incidences have been observed, particularly for MM, and non-significant sub-mortality is observed compared to mainland France. Moreover, temporal distribution of mortality and incidence trends had decreased over the reporting periods except for MM. Our results showed similarities with African-Americans groups in United States and in particular an equivalence in the frequency distribution of diagnosed HM. However, SMR remains lower compared to US black ethnic groups. Our results contributed to expanding knowledge on the epidemiology of HM with Caribbean data., (© 2023. The Author(s).)

Our knowledge of the diversity of eukaryotic viruses has recently undergone a massive expansion. This diversity could influence host physiology through yet unknown phenomena of potential interest to the fields of health and food production. However, the assembly processes of this diversity remain elusive in the eukaryotic viromes of terrestrial animals. This situation hinders hypothesis-driven tests of virome influence on host physiology. Here, we compare taxonomic diversity between different spatial scales in the eukaryotic virome of the mosquito Culex pipiens . This mosquito is a vector of human pathogens worldwide. The experimental design involved sampling in five countries in Africa and Europe around the Mediterranean Sea and large mosquito numbers to ensure a thorough exploration of virus diversity. A group of viruses was found in all countries. This core group represented a relatively large and diverse fraction of the virome. However, certain core viruses were not shared by all host individuals in a given country, and their infection rates fluctuated between countries and years. Moreover, the distribution of coinfections in individual mosquitoes suggested random co-occurrence of those core viruses. Our results also suggested differences in viromes depending on geography, with viromes tending to cluster depending on the continent. Thus, our results unveil that the overlap in taxonomic diversity can decrease with spatial scale in the eukaryotic virome of C. pipiens . Furthermore, our results show that integrating contrasted spatial scales allows us to identify assembly patterns in the mosquito virome. Such patterns can guide future studies of virome influence on mosquito physiology., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Basic knowledge on the biology and epidemiology of equine strongylid species still needs to be improved to contribute to the design of better parasite control strategies. Nemabiome metabarcoding is a convenient tool to quantify and identify species in bulk samples that could overcome the hurdle that cyathostomin morphological identification represents. To date, this approach has relied on the internal transcribed spacer 2 (ITS-2) of the ribosomal RNA gene, with a limited investigation of its predictive performance for cyathostomin communities. Using DNA pools of single cyathostomin worms, this study aimed to provide the first elements to compare performances of the ITS-2 and a cytochrome c oxidase subunit I (COI) barcode newly developed in this study. Barcode predictive abilities were compared across various mock community compositions of two, five and 11 individuals from distinct species. The amplification bias of each barcode was estimated. Results were also compared between various types of biological samples, i.e ., eggs, infective larvae or adults. Bioinformatic parameters were chosen to yield the closest representation of the cyathostomin community for each barcode, underscoring the need for communities of known composition for metabarcoding purposes. Overall, the proposed COI barcode was suboptimal relative to the ITS-2 rDNA region, because of PCR amplification biases, reduced sensitivity and higher divergence from the expected community composition. Metabarcoding yielded consistent community composition across the three sample types. However, imperfect correlations were found between relative abundances from infective larvae and other life-stages for Cylicostephanus species using the ITS-2 barcode. While the results remain limited by the considered biological material, they suggest that additional improvements are needed for both the ITS-2 and COI barcodes., Competing Interests: The authors declare that they have no competing interests., (© 2023 Courtot et al.)

Background: Equine strongyles encompass more than 64 species of nematode worms that are responsible for growth retardation and the death of animals. The factors underpinning variation in the structure of the equine strongyle community remain unknown., Methods: Using horse-based strongyle community data collected after horse deworming (48 horses in Poland, 197 horses in Ukraine), we regressed species richness and the Gini-Simpson index upon the horse's age, faecal egg count, sex and operation of origin. Using the Ukrainian observations, we applied a hierarchical diversity partitioning framework to estimate how communities were remodelled across operations, age groups and horses. Lastly, strongyle species counts collected after necropsy (46 horses in France, 150 in Australia) were considered for analysis of their co-occurrences across intestinal compartments using a joint species distribution modelling approach., Results: First, inter-operation variation accounted for > 45% of the variance in species richness or the Gini-Simpson index (which relates to species dominance in communities). Species richness decreased with horse's age (P = 0.01) and showed a mild increase with parasite egg excretion (P < 0.1), but the Gini-Simpson index was neither associated with parasite egg excretion (P = 0.8) nor with horse age (P = 0.37). Second, within-host diversity represented half of the overall diversity across Ukrainian operations. While this is expected to erase species diversity across communities, community dissimilarity between horse age classes was the second most important contributor to overall diversity (25.8%). Third, analysis of species abundance data quantified at necropsy defined a network of positive co-occurrences between the four most prevalent strongyle genera. This pattern was common to necropsies performed in France and Australia., Conclusions: Taken together, these results show a pattern of β-diversity maintenance across age classes combined with positive co-occurrences that might be grounded by priority effects between the major species., (© 2023. The Author(s).)

The nature and strength of interactions entertained among helminths and their host gut microbiota remain largely unexplored. Using 40 naturally infected Welsh ponies, we tracked the gut microbiota-cyathostomin temporal dynamics and stability before and following anthelmintic treatment and the associated host blood transcriptomic response. High shedders harbored 14 species of cyathostomins, dominated by Cylicocyclus nassatus . They exhibited a highly diverse and temporal dynamic gut microbiota, with butyrate-producing Clostridia likely driving the ecosystem steadiness and host tolerance toward cyathostomins infection. However, anthelmintic administration sharply bent the microbial community. It disrupted the ecosystem stability and the time-dependent network of interactions, affecting longer term microbial resilience. These observations highlight how anthelmintic treatments alter the triangular relationship of parasite, host, and gut microbiota and open new perspectives for adding nutritional intervention to current parasite management strategies., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Alternative strategies to chemical anthelmintics are needed for the sustainable control of equine strongylids. Bioactive forages like sainfoin ( Onobrychis viciifolia ) could contribute to reducing drug use, with the first hints of in vitro activity against cyathostomin free-living stages observed in the past. We analysed the effect of a sainfoin-rich diet on cyathostomin population and the efficacy of oral ivermectin treatment. Two groups of 10 naturally infected horses were enrolled in a 78-day experimental trial. Following a 1-week adaptation period, they were either fed with dehydrated sainfoin pellets (70% of their diet dry matter) or with alfalfa pellets (control group) for 21-days. No difference was found between the average fecal egg counts (FECs) of the two groups, but a significantly lower increase in larval development rate was observed for the sainfoin group, at the end of the trial. Quantification of cyathostomin species abundances with an ITS-2-based metabarcoding approach revealed that the sainfoin diet did not affect the nemabiome structure compared to the control diet. Following oral ivermectin treatment of all horses on day 21, the drug concentration was lower in horses fed with sainfoin, and cyathostomin eggs reappeared earlier in that group. Our results demonstrated that short-term consumption of a sainfoin-rich diet does not decrease cyathostomin FEC but seems to slightly reduce larval development. Consumption of dehydrated sainfoin pellets also negatively affected ivermectin pharmacokinetics, underscoring the need to monitor horse feeding regimes when assessing ivermectin efficacy in the field.

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.

Fasciolosis is a worldwide spread parasitosis mainly caused by the trematode Fasciola hepatica. This disease is particularly important for public health in tropical regions, but it can also affect the economies of many developed countries due to large infections in domestic animals. Although several studies have tried to understand the transmission by studying the prevalence of different host species, only a few have used population genetic approaches to understand the links between domestic and wildlife infections. Here, we present the results of such genetic approach combined with classical parasitological data (prevalence and intensity) by studying domestic and wild definitive hosts from Camargue (southern France) where fasciolosis is considered as a problem. We found 60% of domestic hosts (cattle) infected with F. hepatica but lower values in wild hosts (nutria, 19%; wild boars, 4.5%). We explored nine variable microsatellite loci for 1,148 adult flukes recovered from four different populations (non-treated cattle, treated cattle, nutria and wild boars). Populations from the four groups differed, though we found a number of migrants particularly non-treated cattle and nutria. Overall, we detected 729 different multilocus genotypes (from 783 completely genotyped individuals) and only 46 genotypes repeated across samples. Finally, we experimentally infected native and introduced intermediate snail hosts to explore their compatibility with F. hepatica and assess the risks of fasciolosis expansion in the region. The introduced species Galba truncatula and Pseudosuccinea columella attained the higher values of overall compatibility in relation to the European species. However, concerning the origin, sympatric combinations of G. truncatula were more compatible (higher prevalence, intensity and survival) than the allopatric tested. According to our results, we should note that the assessment of epidemiological risks cannot be limited to a single host-parasite system, but should focus on understanding the diversity of hosts in the heterogeneous environment through space and time., (© 2020 Wiley-VCH GmbH.)

Because human immunodeficiency virus (HIV)-infected patients control Epstein-Barr virus (EBV) replication poorly, we hypothesized that reactive hemophagocytic syndrome (HS) in these patients may be associated with poor control of EBV. The files of 314 patients with a suspected diagnosis of HS were retrospectively reviewed. EBV viral load at the time of HS was compared between HIV-positive and -negative patients. A confirmed diagnosis of HS was made in 162 patients [109 males, median age 48 (35-62) years]. Among them, 61 (38%) were HIV positive [median HIV viral load 3.2 (1.6-5.5) log/ml, median CD4 count 94 (28-190)/mm(3)]. The median EBV viral load was significantly higher in HIV-positive than in HIV-negative patients [4.0 (2.9-4.6) vs 2.5 (0-4.2) log/ml, p = 0.002]. It was higher both in patients with hematological malignancy-associated HS [4.0 (2.9-4.4) vs 2.9 (0-4.9) log/ml, p = 0.03] and in patients with infection-associated HS [3.9 (0-4.9) vs 0 (0-4.1) log/ml, p = 0.14]. However, EBV viral load was not significantly higher in HIV-infected patients with confirmed HS than in HIV-infected patients for whom HS was unlikely [4.0 (2.9-4.6) vs 3.9 (2.6-4.1) log/ml, p = 0.48].The high EBV viral load observed in HIV-infected patients with HS may be more likely to reflect the chronic HIV infection than to be the direct trigger of HS.

Objective: Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy., Methods: Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugénie-les-Bains., Results: Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2% were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2%) no longer had metabolic syndrome (95%CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5% of the 97 included (95%CI [39.5;59.4])., Conclusions: Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group., (© 2013 Société Française de Pharmacologie et de Thérapeutique.)

Objective: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC)., Patients and Methods: Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m(2) twice daily, days 1-14; docetaxel 75 mg/m(2), day 1) or ET (epirubicin 75 mg/m(2), day 1; docetaxel 75 mg/m(2), day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design., Results: Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months' median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience., Conclusion: Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy., (Copyright © 2011 S. Karger AG, Basel.)

Background: Cardiovascular mortality is especially low in southwest France (the French Paradox). In previous experimental studies, we found that alcohol-free extracts of armagnac could inhibit human platelet function in vitro and experimental thrombosis in vivo. To test the possible relevance of these findings, we tested the effects of daily use of small quantities of armagnac against same alcohol strength, polyphenol-free vodka in healthy volunteers., Method: Randomized controlled trial comparing 5-year old armagnac (30 ml/day for 2 weeks) to same alcoholic strength vodka, in 20 healthy volunteers, on platelet aggregation induced by ADP, collagen, and thrombin, as well as bleeding time, partial thromboplastin time (pTT), and plasma lipids during and after consumption. Platelet testing was done blind., Results: After 14 days, ADP-induced platelet aggregation was inhibited more in armagnac (-31+/-3.2% compared to pretreatment values, p<.01) than in vodka (-11.0+/-6.8%, NS) users (p<.05, armagnac vs. vodka). A rebound increase of aggregation was found 2 weeks later in vodka but not in armagnac users. The same pattern was found for thrombin-induced aggregation, including post-treatment rebound. No effect was found on collagen-induced aggregation, bleeding time, pTT, or plasma lipids., Conclusion: The chronic ingestion of moderate quantities of armagnac modified platelet aggregation to ADP in healthy volunteers. The difference with the effects of same alcohol degree vodka is in favour of an effect of the nonalcoholic fraction in the effects of armagnac, rather than just alcohol. All spirits may not be equal for cardioprotection.

Recent in vitro studies, clinical trials and epidemiological studies have suggested possible interactions between aspirin and other cyclo-oxygenase (COX) inhibitors, such as ibuprofen of the COX-2 inhibitors celecoxib and rofecoxib. The objective of this study was to test the effects of aspirin (1, 2.5 and 5 mg/kg), and ibuprofen (4 and 15 mg/kg), diclofenac (2.5 mg/kg), flurbiprofen (2 mg/kg), celecoxib (7.5 mg/kg), and rofecoxib (1 mg/kg), alone or combined on a rat model of arterial thrombosis. Drugs were given orally daily for 7 days, before insertion of an arterio-venous shunt thrombosis system, left in place for 15 min. Main parameter was thrombus weight. Five to 12 rats were used per experiment, and 35 controls overall. Aspirin inhibited thrombus formation in a dose-dependent manner. All NSAIDS given alone also inhibited thrombus formation to approximately the same level as aspirin 1 mg/kg/day. Ibuprofen, celecoxib and rofecoxib inhibited the effects of aspirin, but not diclofenac or flurbiprofen. The interactions with aspirin do not seem to affect all NSAIDs to equal levels. The clinical impact of this needs to be confirmed in adequately powered clinical trials or pharmaco-epidemiological studies.

During chronic venous insufficiency (CVI), several microvascular functional abnormalities, due to venous hypertension, develop. To look for blood rheological consequences of venous hypertension "VH", whole blood viscosity and its main determinants were measured in 11 normal controls and 36 patients with CVI exposed to a short-term experimental VH. Patients were subdivided into 2 groups according to the severity of their disease. Blood was taken from a foot vein before and after VH, which was induced by appling a pneumatic tourniquet to 100 mmHg for 15 minutes. Whole blood viscosity at low and high shear rates, red blood cell (RBC) aggregation, RBC rigidity, plasma viscosity and proteins as well as red and white blood cell (WBC) counts were recorded. Patients at baseline, i.e., before application of the tourniquet, showed several hemorheological abnormalities such as an increased RBC aggregation, increased low shear rate viscosity, and a significant elevation in plasma fibrinogen level. Patients with more severe CVI had more marked hemorheological changes. The short term VH in patients led to further aggravation of these changes. There were also at baseline lower values, however not significantly, of hematocrit and RBC count, suggesting that hemoconcentration is not a feature of CVI. These same parameters were slightly, however not significantly, increased after VH, indicating a fluid escape into the extravascular space. A significant fall in WBC count was also observed after VH, in keeping with the white cell trapping hypothesis. In conclusion, even a short-term VH is able to induce several hemorheological impairments, which are probably involved in the failure of the microcirculation and hence the initiation of tissue damage in patients with CVI., (Copyright 2004 IOS Press)

Introduction: The "French paradox", a low cardiovascular mortality compared to the prevalent risk factors, has been attributed to the regular use of red wine, and to the polyphenols it contains. These have among other effects an antioxidant and antithrombotic effect. The French paradox is maximal in southwest France, a region which is the region of production of armagnac, an oak cask aged spirit also rich in polyphenols., Method: We tested the effects of a freeze-dried extract of 12-year-old armagnac (EA88) on in vitro human platelet adhesion, and on aggregation induced by collagen or ADP, in the presence or absence of hypoxanthine-xanthine oxidase (HX/XO), at concentrations ranging from 5 x 10(-9) to 5 x 10(-3) g/l, after 15-60 min incubation. We also tested the effects of 2-week oral treatment with 1, 5 and 25 mg/kg EA88 in a rat arteriovenous shunt thrombosis model., Results: EA88 inhibited ADP-induced but not collagen-induced human platelet aggregation in vitro in a concentration- and incubation time-dependent manner, which was greater in the presence of HX/XO. In vivo, giving rats a daily oral dose of EA88 for 2 weeks inhibited thrombus formation in a dose-dependent manner, for doses consistent with the habitual human use of armagnac., Conclusion: Armagnac extract EA88 had an antiplatelet and antithrombotic effect that if confirmed in man could contribute to explain the intensity of the French paradox in southwest France.

Background: Rolling of leukocytes at the surface of the vascular endothelium is a prerequisite for a subsequent firm adhesion, particularly the slow rolling appearing on ELAM CD62E. Therefore, it may be considered that increasing the rolling velocities should be a precise therapeutic target in clinical situations where leukocytes accumulate, mainly venous and arterial ischaemia., Methods: Human neutrophils were allowed to flow on endothelial HUVECs, with and without 4 hours interleukin-1alpha activation, the cells having or not been incubated with INO5042 anti-inflammatory drug. Under a mean shear-stress of 2 dyn/cm(2), rollers and stickers were identified and quantified, using a video-camera and picture analysing software., Results: When the drug had been added to endothelial cells a shift of velocities was observed towards fast speeds (from 3-5 to 7-11 microm/sec). The same results was significantly found when neutrophils, alone or along with endothelium, had been submitted to the drug, the number of stickers and rollers beeing reduced as well. Finally, such a precise pharmacological method proved efficient to detect the exact mechanism of INO5042 on white cell adhesion.

In a previous study, we had shown that freeze-dried extracts of 12-year-old Armagnac could inhibit ADP-induced platelet aggregation in a dose- and duration-dependent manner, and reduce thrombus weight in an experimental rat arteriovenous shunt thrombosis model after 2-week oral treatment. Polyphenol content could however vary with age and origin of the brandy, and the onset and offset of the effect were not defined. To this end, we studied the effects of extracts of 5-, 10- and 15-year-old Armagnac from two different producers at 1, 5 and 25 mg/kg orally for 15 days, on the same rat arteriovenous shunt thrombosis model. We then studied the effects of 1, 3, 7 and 15 days of oral treatment with 5 mg/kg extracts of a 5-year-old Armagnac, and the effect 1, 3 and 7 days after a 1-week oral treatment of the same extract at the same dose. There was a dose-dependent decrease in thrombus weight, which was similar for both Armagnac origins for all ages. Extracts of 5- and 10-year-old Armagnac were similar, and more potent than extracts from 15-year-old Armagnac. There was a progressive decrease in thrombus weight over duration of treatment to 7 days, to about 50% of initial thrombus weight. The effect disappeared within 3 days after stopping a 7-day treatment. We confirm the dose-, age- and duration-dependent inhibition of arteriovenous shunt thrombosis in vivo by Armagnac extracts in rats.

Numerous compounds acting on the venous system have been developed over the last 50 years, including and often associating flavonoids, pycnogenols, saponosides, nucleosides and bilobatides. Some products have proved highly successful such as Cyclo 3 Fort (Fabroven), Phlebodril, made of ruscus extract (flavonoids, saponins), hesperidin-methyl-chalone and ascorbic acid. This presentation is an attempt to classify the scientifically proven mechanisms of such substances. All selected substances have been tested in clinical trials for their action on the symptoms of chronic venous insufficiency (CVI), leg pain and edema. As the distensibility of the leg veins is the main pathological factor determined by plethysmogaphy, it was at first thought that leg pain would be related to it. But observations have shown that this factor is often unrelated to the enlargement of the veins but rather to a whole chain of factors. The effects of different drugs on venous distensibility, rheological disorders, the prevention of wall dystrophy and action on the microcirculation are examined.

The Healthy People 2010 objectives call for the elimination of racial disparities in health, along with reductions in several multifactorial perinatal outcomes. Evidence-based interventions have been the focus of discussion to date. We propose a 6-component framework based on knowledge from the social, medical, psychological, and epidemiological literatures to guide development of interventions to reduce preterm delivery and eliminate disparities. Pilot testing and rigorous evaluation of the interventions developed from this framework are encouraged.

Hyperhomocysteinaemia is a risk factor for premature atherosclerosis and venous thromboembolic disease. Supplementation with folic acid and vitamin B6 has been shown to decrease plasma homocysteine but data fail to assess an effect on the progression of vascular disease. We measured plasma homocysteine and two markers of endothelial injury (plasma soluble thrombomodulin and von Willebrand factor) at baseline and after 3 months of treatment with folic acid and vitamin B6. After this treatment there was a significant decrease in fasting soluble thrombomodulin (-15 ng/ml, 95%CI 5-22.2). Von Willebrand factor was significantly raised after methionine load at baseline but did not significantly rise after supplementation.