Involvement of eicosanoids in the hypothermic response to lipopolysaccharide during endotoxemia in rats

Hypothermia is one of the prominent features of the acute phase response to endotoxin (LPS). This study was undertaken to elucidate the effects of the COX-inhibitor Indomethacin (INDO) and the selective FLAP inhibitor MK-886 on LPS-induced hypothermia, mortality and increase in production of hypothalamic prostaglandin E(2) (PGE(2)) and leukotriene during endotoxemia.It has been demonstrated that INDO and MK-886 significantly attenuate the hypothermia induced by LPS, but MK-886 has a lesser (protective) effect than INDO. Only INDO was found to attenuate significantly the hyperthermic response to LPS. Furthermore, INDO significantly reduced the elevation in hypothalamic PGE(2) levels. MK-886 significantly reduced the elevation in hypothalamic leukotriene production only when LPS was given in a dose of 1mg/kg. Both drugs failed to reduce the elevation in plasma TNF-alpha and mortality induced by LPS.We conclude that in rats, febrile response to endotoxin involves many inflammatory mediators. However, it seems that PGE(2) and leukotrienes do not have a pivotal role in the mechanism of LPS-induced mortality.     

High affinity targets of protein kinase inhibitors have similar residues at the positions energetically important for binding

Inhibition of protein kinase activity is a focus of intense drug discovery efforts in several therapeutic areas. Major challenges facing the field include understanding of the factors determining the selectivity of kinase inhibitors and the development of compounds with the desired selectivity profile. Here, we report the analysis of sequence variability among high and low affinity targets of eight different small molecule kinase inhibitors (BIRB796, Tarceva, NU6102, Gleevec, SB203580, balanol, H89, PP1). It is observed that all high affinity targets of each inhibitor are found among a relatively small number of kinases, which have similar residues at the specific positions important for binding. The findings are highly statistically significant, and allow one to exclude the majority of kinases in a genome from a list of likely targets for an inhibitor. The findings have implications for the design of novel inhibitors with a desired selectivity profile (e.g. targeted at multiple kinases), the discovery of new targets for kinase inhibitor drugs, comparative analysis of different in vivo models, and the design of "a-la-carte" chemical libraries tailored for individual kinases.     

Structural and functional analysis of the C-terminal STAS (sulfate transporter and anti-sigma antagonist) domain of the Arabidopsis thaliana sulfate transporter SULTR1.2

The C-terminal region of sulfate transporters from plants and animals belonging to the SLC26 family members shares a weak but significant similarity with the Bacillus sp. anti-anti-sigma protein SpoIIAA, thus defining the STAS domain (sulfate transporter and anti-sigma antagonist). The present study is a structure/function analysis of the STAS domain of SULTR1.2, an Arabidopsis thaliana sulfate transporter. A three-dimensional model of the SULTR1.2 STAS domain was built which indicated that it shares the SpoIIAA folds. Moreover, the phosphorylation site, which is necessary for SpoIIAA activity, is conserved in the SULTR1.2 STAS domain. The model was used to direct mutagenesis studies using a yeast mutant defective for sulfate transport. Truncation of the whole SULTR1.2 STAS domain resulted in the loss of sulfate transport function. Analyses of small deletions and mutations showed that the C-terminal tail of the SULTR1.2 STAS domain and particularly two cysteine residues plays an important role in sulfate transport by SULTR1.2. All the substitutions made at the putative phosphorylation site Thr-587 led to a complete loss of the sulfate transport function of SULTR1.2. The reduction or suppression of sulfate transport of the SULTR1.2 mutants in yeast was not due to an incorrect targeting to the plasma membrane. Both our three-dimensional modeling and mutational analyses strengthen the hypothesis that the SULTR1.2 STAS domain is involved in protein-protein interactions that could control sulfate transport.     

The Introduced Green Alga Caulerpa Taxifolia Continues to Spread in the Mediterranean

The tropical green alga Caulerpa taxifolia in the Mediterranean has spread steadily since its introduction in 1984. At the end of 2000, approximately 131km² of benthos had been colonized in 103 independent areas along 191km of coastline in six countries (Spain, France, Monaco, Italy, Croatia and Tunisia). Large regions neighboring the invaded areas appear favorable to further colonization, and there is thus no reason to believe that spreading will slow down in the years to come.     

TeleOphta: Machine learning and image processing methods for teleophthalmology

A complete prototype for the automatic detection of normal examinations on a teleophthalmology network for diabetic retinopathy screening is presented. The system combines pathological pattern mining methods, with specific lesion detection methods, to extract information from the images. This information, plus patient and other contextual data, is used by a classifier to compute an abnormality risk. Such a system should reduce the burden on readers on teleophthalmology networks.     

Muscular response to the therapist and symptomatic improvement during biofeedback for tension headache.

The relationship between muscular response to the therapist's presence and symptomatic improvement was studied during biofeedback. Thirty-two patients suffering from tension headaches received muscular biofeedback training of six sessions plus a follow-up session two months later. Patients' electro-myographic frontal response was measured prior to treatment both with and without the therapist present. A relationship was found between symptomatic improvement at follow-up and muscular response to the therapist's presence before treatment: patients showing a decrease of at least 10% in muscular tension response to the presence of their future therapist improved more regarding headache intensity than the patients showing increase or smaller variation of their EMG. A significant correlation of .59 was found between the frontal EMG response to therapist presence during the evaluation session and headache improvement at follow-up. The results suggest that the decrease of muscular tension during the first contact with the therapist could be an indicator of good prognosis, possibly because of an immediate positive therapeutic relationship and/or favorable expectancies concerning future benefit of treatment.     

Vascular clamping in liver surgery: physiology, indications and techniques

This article reviews the historical evolution of hepatic vascular clamping and their indications. The anatomic basis for partial and complete vascular clamping will be discussed, as will the rationales of continuous and intermittent vascular clamping. Specific techniques discussed and described include inflow clamping (Pringle maneuver, extra-hepatic selective clamping and intraglissonian clamping) and outflow clamping (total vascular exclusion, hepatic vascular exclusion with preservation of caval flow). The fundamental role of a low Central Venous Pressure during open and laparoscopic hepatectomy is described, as is the difference in their intra-operative measurements. The biological basis for ischemic preconditioning will be elucidated. Although the potential dangers of vascular clamping and the development of modern coagulation devices question the need for systemic clamping; the pre-operative factors and unforseen intra-operative events that mandate the use of hepatic vascular clamping will be highlighted.