4 research outputs found
Recommended from our members
A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness
Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and  PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI
Selective Cobalt-Catalyzed Reduction of Terminal Alkenes and Alkynes Using (EtO)<sub>2</sub>Si(Me)H as a Stoichiometric Reductant
While attempting
to effect Co-catalyzed hydrosilylation of β-vinyl
trimethylsilyl enol ethers, we discovered that, depending on the silane,
solvent, and the method of generation of the reduced cobalt catalyst,
a highly efficient and selective reduction or hydrosilylation of an
alkene can be achieved. This paper deals with this reduction reaction,
which has not been reported before in spite of the huge research activity
in this area. The reaction, which uses the air-stable [2,6-bisÂ(aryliminoyl)Âpyridine)]ÂCoCl<sub>2</sub> activated by 2 equiv of NaEt<sub>3</sub>BH as the catalyst
(0.001–0.05 equiv) and (EtO)<sub>2</sub>SiMeH as the hydrogen
source, is best run at ambient temperature in toluene and is highly
selective for the reduction of simple unsubstituted 1-alkenes and
the terminal double bonds in 1,3- and 1,4-dienes, β-vinyl ketones,
and silyloxy dienes. The reaction is tolerant of various functional
groups such as bromide, alcohol, amine, carbonyl, di- or trisubstituted
double bonds, and water. Highly selective reduction of a terminal
alkyne to either an alkene or alkane can be accomplished by using
stoichiometric amounts of the silane. Preliminary mechanistic studies
indicate that the reaction is stoichiometric in the silane and both
hydrogens in the product come from the silane
Control of Selectivity through Synergy between Catalysts, Silanes, and Reaction Conditions in Cobalt-Catalyzed Hydrosilylation of Dienes and Terminal Alkenes
Readily
accessible (<sup><i>i‑</i>Pr</sup>PDI)ÂCoCl<sub>2</sub> [<sup><i>i‑</i>Pr</sup>PDI = 2,6-<i>bis</i>(2,6-diisopropylphenyliminoethyl)Âpyridine] reacts with
2 equiv of NaEt<sub>3</sub>BH at −78 °C in toluene to
generate a catalyst that effects highly selective anti-Markovnikov
hydrosilylation of the terminal double bond in 1,3- and 1,4-dienes.
Primary and secondary silanes such as PhSiH<sub>3</sub>, Ph<sub>2</sub>SiH<sub>2</sub>, and PhSiÂ(Me)ÂH<sub>2</sub> react with a broad spectrum
of terminal dienes without affecting the configuration of the other
double bond. When dienes conjugated to an aromatic ring are involved,
both Markovnikov and anti-Markovnikov products are formed. The reaction
is tolerant of various functional groups such as an aryl bromide,
aryl iodide, protected alcohol, and even a silyl enol ether. Reactions
of 1-alkene under similar conditions cleanly lead to a mixture of
Markovnikov and anti-Markovnikov hydrosilylation products, where the
ratio of the products increasingly favors the latter, as the size
of the 2,6-substituents in the iminoylaryl group becomes larger. The
complex (<sup><i>i‑</i>Pr</sup>PDI)ÂCoCl<sub>2</sub> gives exclusively the linear silane for a wide variety of terminal
alkenes. Mechanistic studies suggest a pathway that involves a key
role for an in situ-generated metal hydride, (<b>L</b>)ÂCoÂ(I)-H.
Exclusive reduction of the terminal double bond (vis-à-vis
hydrosilylation) when (EtO)<sub>2</sub>SiÂ(Me)H is used in the place
of PhSiH<sub>3</sub> is explained on the basis of an alternate silane-mediated
decomposition path for the linear CoÂ(I)-alkyl intermediate
Recommended from our members
A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness
Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and  PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI