9 research outputs found
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
Dynamics of Radical Ion Pairs following Photoinduced Electron Transfer in Solvents with Low and Intermediate Polarities
Fluorescence
quenching of <i>p</i>-xylene, naphthalene,
or pyrene by fumaronitrile in apolar solvents and in solvents of intermediate
polarities leads to weakly fluorescent radical ion pairs. This emission
is assigned to ion pairs in close contact on the basis of their solvent
polarity dependence, kinetics, and thermodynamics. The temperature-dependence
of the intensity and fluorescence emission maxima of ion pairs in
methyl acetate reveals that they have decay channels competitive with
their thermal equilibration. The results presented in this work are
consistent with the direct formation of contact ion pairs in weakly
polar solvents and in solvents of intermediate polarities as the result
of bimolecular photoinduced electron transfer reactions between aromatic
hydrocarbons and nitriles. The implications of these findings in free-energy
relationships of electron transfer reactions are discussed
Chemical structures of investigated photosensitizers.
<p>Chemical structures of investigated photosensitizers.</p
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
Photophysical properties of F<sub>2</sub>POH, Cl<sub>2</sub>POH and Cl<sub>2</sub>PEt in EtOH.
<p>Photophysical properties of F<sub>2</sub>POH, Cl<sub>2</sub>POH and Cl<sub>2</sub>PEt in EtOH.</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/cm<sup>2</sup> of visible light (420±20 nm). The dashed black line shows viability values for 99.9% (3 logs) inactivation of microorganisms.</p
One Peptide Reveals the Two Faces of α‑Helix Unfolding–Folding Dynamics
The
understanding of fast folding dynamics of single α-helices
comes mostly from studies on rationally designed peptides displaying
sequences with high helical propensity. The folding/unfolding dynamics
and energetics of α-helix conformations in naturally occurring
peptides remains largely unexplored. Here we report the study of a
protein fragment analogue of the C-peptide from bovine pancreatic
ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts
a highly populated helical conformation in aqueous solution. <sup>1</sup>H NMR and CD structural studies of RN80 showed that α-helix
formation displays a pH-dependent bell-shaped curve, with a maximum
near pH 5, and a large decrease in helical content in alkaline pH.
The main forces stabilizing this short α-helix were identified
as a salt bridge formed between Glu-2 and Arg-10 and the cation−π
interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2
or protonation of His-12 are essential for the RN80 α-helix
stability. In the present study, RN80 folding and unfolding were triggered
by laser-induced pH jumps and detected by time-resolved photoacoustic
calorimetry (PAC). The photoacid proton release, amino acid residue
protonation, and unfolding/folding events occur at different time
scales and were clearly distinguished using time-resolved PAC. The
partial unfolding of the RN80 α-helix, due to protonation of
Glu-2 and consequent breaking of the stabilizing salt bridge between
Glu-2 and Arg-10, is characterized by a concentration-independent
volume expansion in the sub-microsecond time range (0.8 mL mol<sup>–1</sup>, 369 ns). This small volume expansion reports the
cost of peptide backbone rehydration upon disruption of a solvent-exposed
salt bridge, as well as backbone intrinsic expansion. On the other
hand, RN80 α-helix folding triggered by His-12 protonation and
subsequent formation of a cation−π interaction leads
to a microsecond volume contraction (−6.0 mL mol<sup>–1</sup>, ∼1.7 μs). The essential role of two discrete side
chain interactions, a salt bridge, and in particular a single cation−π
interaction in the folding dynamics of a naturally occurring α-helix
peptide is uniquely revealed by these data
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
Phthalocyanine Labels for Near-Infrared Fluorescence Imaging of Solid Tumors
Diamagnetic metal
complexes of phthalocyanines with <i>n</i>-butoxyl groups
in all the α-benzo positions of the macrocycle
skeleton, MPc(OBu)<sub>8</sub>, have strong near-infrared absorptions
and intense fluorescences that are Stokes shifted by more than 15
nm. Interestingly, the silicon complex <b>6</b> is also remarkably
photostable and nontoxic. The use of <b>6</b> in the fluorescence
imaging of BALB/c mice bearing a 4T1-luc2 tumor in the mammary fat
pad unambiguously revealed the presence of the tumor when it was only
1 mm in diameter and was not visible with the naked eye. Compound <b>6</b> has an intrinsic ability to accumulate in the tumor, adequate
spectroscopic properties, and excellent stability to function as a
NIR fluorescent label in the early detection of tumors