Single and combined impacts of irradiation and surgery on lymphatic vasculature and fibrosis associated to secondary lymphedema.

Lymphedema (LD) refers to a condition of lymphatic dysfunction associated with excessive fluid accumulation, fibroadipose tissue deposition and swelling. In industrialized countries, LD development mainly results from a local disruption of the lymphatic network by an infection or cancer-related surgery (secondary LD). In the absence of efficient therapy, animal models are needed to decipher the cellular and molecular mechanisms underlying LD and test putative drugs. In this study, we optimized and characterized a murine model of LD that combines an irradiation of the mice hind limb and a radical surgery (lymph node resection associated to lymphatic vessel ligation). We investigated the respective roles of irradiation and surgery in LD formation by comparing their impacts, alone or in combination (with different intervention sequences), on eight different features of the pathology: swelling (paw thickness), indocyanine green (ICG) clearance, lymphatic vasculature remodeling, epidermal and dermal thickening, adipocyte accumulation, inflammatory cell infiltration and collagen deposition. This study supports the importance of radiation prior to surgery to experimentally induce a rapid, severe and sustained tissue remodeling harboring the different hallmarks of LD. We provide the first experimental evidence for an excessive deposition of periostin (POSTN) and tenascin-C (TNC) in LD. Through a computerized method of digital image quantification, we established the spatial map of lymphatic expansion, as well as collagen, POSTN and TNC deposition in papillary and reticular dermis of lymphedematous skins. This mouse model is available to study the patho-physiology of LD and test potential therapeutic targets.

Interleukin-10 microsatellite variants and the risk of acute coronary syndrome among Tunisians.

The objective of the study was to investigate the association of interleukin (IL)-10 promoter microsatellite polymorphisms, linked with altered IL-10 secretion, with the susceptibility to acute coronary syndrome (ACS) in adult Tunisian patients. We genotyped 291 ACS patients and 291 age-, gender- and ethnically matched control subjects for the microsatellites IL-10R [X78437.2g.5325CA(11_15)] and IL-10G [X78437.2g.8134CA(14_29)] by PCR-based assays. Haplotypes were reconstructed using maximum likelihood method. Regression analysis was used in determining the risk imparted by specific IL-10 genotypes and haplotypes. A significant decrease in IL-10G12 (24 CA repeats) (P<0.001; OR=0.465) and IL-10G15 (27 CA repeats) (P=0.043; OR=0.232), and a significant increase in the low IL-10 producer allele, IL-10R3 (14 CA repeats) (P=0.049; OR=1.461), microsatellites were seen in the ACS group compared with controls. Of the possible 14 haplotypes constructed, there was an enrichment of the R2G9 (13CA vs. 21CA) haplotype in controls [P=0.019; adjusted OR (95% CI)=0.67 (0.48-0.94)] and R2G15 (13CA vs. 27CA) haplotype in cases [P=0.042; adjusted OR (95% CI)=5.29 (1.06-26.30)], thus assigning a protective and susceptible nature to these haplotypes respectively. The differential association of IL-10 microsatellite alleles and haplotypes with ACS suggests that IL-10 contributes to ACS pathogenesis. While the functional attributes of these microsatellite markers remain to be seen, it is likely that they have distinct functional properties (altered IL-10 secretion), which in turn affect the susceptibility to ACS development.

[Subjective blockage in Parkinson's disease]. / Blocages subjectifs au cours de la maladie de Parkinson.

UNLABELLED: Akinetic symptoms or off-period motor signs in patients with Parkinson's disease and motor fluctuations can be associated with subjective symptoms. A systematic interview was conducted in a series of 24 patients. Sixteen out of 24 (67 p. cent) experienced these subjective symptoms as on-off non motor symptoms that were classified in three groups: energy lost consistent with a severe asthenia, perceptive and cognitive alterations, and emotional troubles such as panic and depression. These phenomenons could be combined in some patients and were sometimes asynchron to akinesia. In some patients (six cases reported), they occurred without any akinesia but could totally inhibit patients daily activities, and so could be described as subjective off-period . Frequently, the patients did not distinguish them from motor disability. Their persistence, after subthalamic nucleus stimulation or intrastriatal transplant, could interfere with functional results, even though akinetic symptoms had disappeared. CONCLUSION: subjective phenomenons during off-periods are frequent. Their frequency is underestimated due to a non-targeted examination. Subjective off-periods are symptoms of Parkinson's disease, partly independent from off motor symptoms, and important to consider in evaluation of therapeutics, especially surgery.

Factor V Leiden: detection in whole blood by ASA PCR using an additional mismatch in antepenultimate position.

Factor V Leiden mutation was initially detected in thrombophilic patients and relatives by PCR RFLP (Restriction Fragment Length Polymorphism) according to Bertina (1). This technique presents some drawbacks and the current trend is to simplify the diagnosis. We describe a technique of Allele Specific Amplification (ASA) which is optimized in terms of reliability: an additional mismatch in antepenultimate position enables to obtain the same specificity as PCR RFLP. Furthermore, coamplification of internal control warrants an optimal sensitivity. All the PCR have been simplified: the DNA extraction improvement allows to analyse the genotype with only a few microliters of whole blood whatever the anticoagulant and the procedure of preservation (freezing, dried blood spots, storage at +4 degrees C for several days). This technique saves time. Moreover, full automation of the ASA technique may be shortened thanks to the lack of extraction and the positive/negative reading of the PCR signal.

Expression of ACC oxidase antisense gene inhibits ripening of cantaloupe melon fruits.

The plant hormone ethylene plays a major role in the ripening of climacteric fruit. We have generated transgenic cantaloupe Charentais melons expressing an antisense ACC oxidase gene; ACC oxidase catalyzes the last step of ethylene biosynthesis. Ethylene production of transgenic fruit was < 1% of control untransformed fruit, and the ripening process was blocked both on and off the vine. The antisense phenotype could be reversed by exogenous ethylene treatment. Analysis of antisense ACC oxidase melons indicated that the ripening process includes ethylene-dependent and ethylene-independent pathways. Because the transgenic line we generated displays extended storage life and improved quality, it has a promising potential for commercial development.