Impact of the Thr789Ala variant of the von Willebrand factor levels, on ristocetin co-factor and collagen binding capacity and its association with coronary heart disease in patients with diabetes mellitus type 2.

A Thr789Ala variant in the von Willebrand Factor (vWF) gene is associated with increased vWF plasma concentrations and might therefore affect the risk of coronary heart disease (CHD) in the general population. Patients with type 2 diabetes have an increased risk for premature atherosclerosis and are characterized by alterations of the coagulation system. However, it is not known whether the Thr789Ala variant in the vWF gene contributes to the increased CHD risk in patients with type 2 diabetes. We therefore investigated the potential relationship between the Thr789Ala variant in the vWF gene and the occurrence of CHD in 356 patients with type 2 diabetes, either with (DM+/CHD+, n = 204) or without evidence for CHD (DM+/CHD-, n = 152). In addition, two control groups without type 2 diabetes, with (DM-/CHD+, n = 22) or without CHD (DM-/CHD-, n = 100), were investigated. Individuals with the vWF Thr789Ala variant have significantly higher von Willebrand factor plasma concentrations (p < 0.001). In addition, ristocetin co-factor was significantly increased in vWF Thr789Ala variant carriers (p < 0.05). Ristocetin co-factor levels and collagen binding capacity were also increased in individuals affected with either type 2 diabetes, CHD or both (DM+/CHD+, DM+/CHD-, DM-/CHD+) as compared to healthy controls (DM-/CHD-) (p < 0.001). However, we did not find an association between the vWF Thr789Ala variant and the occurrence of CHD in patient with type 2 diabetes (p = 0.34). In conclusion, although the Thr789Ala vWF gene variant is associated with increased plasma concentrations of vWF, ristocetin co factor levels and collagen binding capacity in patients with type 2 diabetes and CHD, a direct effect of this variant on the occurrence of CHD in patients with type 2 diabetes, could not be detected.     

Structure and dynamics of polyelectrolyte-surfactant complexes as revealed by solid state NMR

¹³C-CP/MAS-NMR (cross-polarization magic angle spinning), 2D-WISE (wideline separation experiment) and ¹H-spin diffusion experiments allow to gain new insight into the structure and dynamics of solid polyelectrolyte-surfactant complexes, a material with pronounced mesophase formation. Experiments were performed on two different complexes of polystyrene sulfonate and octadecyltrimethylammonium or tetradecyltrimethylammonium counterions, PSS-C₁₈ and PSS-C₁₄. The strong mobility differences between the ionic and alkyl phase in the lamellar complex PSS-C₁₈ are reflected in the NMR behavior: in the surfactant tails, a mobility gradient towards the terminal methyl group is observed. This fact as well as a high content of gauche conformations suggest a non-interdigitating morphology of the tails at room temperature. The behavior changes during cooling below an endothermic transition centered at 255 K where a high trans content and a homogenization of the side chain dynamics is observed. We attribute this transition which is invisible in the X-ray experiments to the formation of a highly transoid, interdigitated phase of the surfactant tails which is however not crystallized in a classical sense. ¹H-spin diffusion experiments allow to estimate the distance between mobile and immobile regions of the sample. For the complex PSS-C₁₄, the length scale determined by NMR is essentially that of the primary lamellar structure. For PSS-C₁₈, a characteristic length of the density fluctuations within the proposed undulated lamellar structure is estimated.     

Enkephalin enhances responsiveness to perforant path input while decreasing spontaneous activity in the dentate gyrus

The opioid peptide [D-Ala2-Met5]-enkephalin-amide (DAMEA) was electrophoretically applied to the dentate gyrus in vivo to investigate opioid effects on evoked responsiveness to perforant path input and on spontaneous granule cell activity. DAMEA increased the amplitude of population spikes evoked by stimulation of the perforant path, and decreased sequential (recurrent or feed-forward) inhibition as determined by a paired-pulse paradigm. However, DAMEA concurrently inhibited spontaneous activity of individual granule cells. The effects of DAMEA on population and unit responses were antagonized by intravenous naloxone. These results confirm previous findings of opioid enhanced responsiveness to perforant path input and decreased sequential inhibition, but demonstrate a paradoxical inhibition of spontaneous unit activity by opioids in the granule cell layer.     

Entamoeba histolytica induces human neutrophils to form NETs

Entamoeba histolytica invades the intestine and other organs during the pathogenesis of amoebiasis. In the early stages, the host organism responds with an inflammatory infiltrate composed mostly of neutrophils. It has been reported that these immune cells, activated by E. histolytica, exert a protective role by releasing proteolytic enzymes and generating reactive oxygen/nitrogen species (ROS/RNS) and antimicrobial peptides. It is now known that neutrophils also produce neutrophil extracellular traps (NETs), which are able to damage and kill pathogens. Studies have shown that intracellular protozoan pathogens, including Toxoplasma gondi, Plasmodium falciparum and Leishmania spp, induce neutrophils to release NETs and are damaged by them. However, the action of this mechanism has not been explored in relation to E. histolytica trophozoites. Through scanning electron, epifluorescence microscopy and viability assays, we show for first time that during in vitro interaction with E. histolytica trophozoites, human neutrophils released NETs that covered amoebas and reduced amoebic viability. These NETs presented histones, myeloperoxidase and decondensed chromatin. The results suggest that NETs participate in the elimination of the parasite.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.