Study of chemical sympathectomy in endotoxin-induced lethality and fibrin deposition

Study of chemical sympathectomy in endotoxin-induced lethality and fibrin deposition. Shock and the generalized Shwartzman reaction are well known features of endotoxin which have been shown to involve the sympathetic nervous system. The mechanism of sympathetic nervous system involvement with endotoxin injection was studied in rabbits chemically sympathectomized with 6-hydroxydopamine. Endotoxin, in doses producing a spectrum of morbidity and mortality in normal rabbits, was administered i.v. to chemically sympathectomized, normal, and unilateral renal surgically sympathectomized animals. Chemical sympathectomy produced a significant depletion of tissue norepinephrine which, in endotoxin recipient animals, was associated with a significantly lower mortality rate and greatly decreased fibrin deposition in the lungs and kidneys, despite intravascular coagulation. Unilateral renal sympathectomy afforded protection to the ipsilateral kidney, but data on mortality and systemic fibrin deposition were similar to those reported for normal rabbits given endotoxin. Six-hydroxydopamine prevents significant tissue injury secondary to endotoxin in this experimental model. In addition, the data provide direct evidence that an intact reactive sympathetic nervous system is essential for development of lethal toxicity and generalized Shwartzman reaction due to endotoxin.Etude de la sympathectomie chimique de la lethalité et des dépôts de fibrine chez animaux qui ont reçu l'endotoxine. Le choc et le phénomène de Schwartzman généralisé sont des conséquences bien connues de l'endotoxine et il a été montré que ces réactions impliquent le systéme nerveux sympathique. Le mécanisme de la mise en jeu du système nerveux sympathique par l'injection d'endotoxine a été étudié chez des lapins ayant subi une sympathectomie chimique par la 6-hydroxydopamine. L'endotoxine, aux doses qui déterminent une morbidité et une mortalité chez les lapins normaux, a été administrée par voie intraveineuse à des animaux normaux, ayant subi une sympathectomie chimique ou ayant subi une sympathectomie rénale, chirurgicale et unilatérale. La sympathectomie chimique a produit une déplétion significative de norépinéphrine tissulaire qui, chez les animaux qui ont reçu l'endotoxine, a été associée à une diminution significative de la mortalité et une diminution importante des dépôts de fibrine dans les poumons et les reins malgré la coagulation intravasculaire. La sympathectomie unilatérale a protégé le rein ipsilatéral mais la mortalité et les dépôts systémiques de fibrine ont été semblables à ceux observés chez les lapins normaux qui ont reçu l'endotoxine. La 6-hydroxydopamine diminue de façon significative les altérations tissulaires secondaires à l'endotoxine dans ce modèle expérimental. De surcroît, ces observations apportent la preuve directe de ce qu'un système nerveux sympathique intact et réactif est essentiel pour l'apparition de la léthalité et du phénomène de Schwartzman généralisé consécutifs à l'endotoxine

Photodynamic effect induced by studied photosensitizers in the absence (or in the presence) of poloxamer addition against A549, CT26 and 2H11 cells.

<p>The data are expressed as mean value (N = 12) ±SEM. The label (*) represents statistically significant difference (p<0.05).</p

Chemical structures of investigated photosensitizers.

<p>Chemical structures of investigated photosensitizers.</p

PDI of microorganisms mediated by halogenated porphyrin derivatives.

<p>Cells were incubated with PS for 1 h and exposed (or not) to 10 J/cm² of visible light (420±20 nm). The dashed black line shows viability values for 99.9% (3 logs) inactivation of microorganisms.</p

Photophysical properties of F₂POH, Cl₂POH and Cl₂PEt in EtOH.

<p>Photophysical properties of F₂POH, Cl₂POH and Cl₂PEt in EtOH.</p

Reactive oxygen species generation.

<p>Fluorescence generated from selected ROS probes (10 μM): (a) APF, (b) HPF, (c) DHE, (d) SOSG during irradiation of photosensitizer solution (5 μM, EtOH:PBS <i>ca</i>. 1:99 <i>v/v</i>). Presented data are expressed as mean value (N = 6) ±SEM. The label (*) represents statistically significant difference (P<0.05). The t-test has been used for the statistical significance determination.</p

The restraints used in restrained MD of 1LCY monomer.

<p>The values in the middle column are inferences affixed to tendencies given in Fig 1 B,C in Ref. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161526#pone.0161526.ref038" target="_blank">38</a>].</p

Data collection and refinement statistics.

<p>Data collection and refinement statistics.</p

Modeling statistics of the starting structures.

<p>Modeling statistics of the starting structures.</p

HtrA trimers; PD-PDZ(1) in surface representation.

<p>L3 and the linker are shown as orange threads, L2, L1 and LD as blue threads. (<b>A)</b> wtHtrA2-peptide starting structure in orientation identical to that in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161526#pone.0161526.g003" target="_blank">Fig 3</a> bottom-right. (<b>B)</b> wtHtrA2-peptide after 50 ns MD. (<b>C</b>) active DegP PDB (entry 3CS0 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161526#pone.0161526.ref017" target="_blank">17</a>]) PDZ2 is omitted for clarity. In contrast to <b>A</b> and <b>B</b>, where L3 protrudes outside on the convex side of the trimer, in the active DegP and in other active HtrAs (not shown) L3 enters between PD and PDZ, onto the trimer’s concave, contributing (vide bottom) to the allosteric activation cascade: L3*-LD-L1-L2 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161526#pone.0161526.ref035" target="_blank">35</a>].</p