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Thyroid Hormone Augmentation in Treatment-Refractory Depression
Gabriela V Obrocea,Richard A Margolin,Tai P Yoo 대한정신약물학회 2008 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.6 No.1
Objective:Partial response or no response to a single antidepressant trial is not uncommon in the pharmacotherapy of depressive disorders, and resistance to even aggressive treatment regimens, known as treatment-refractory depression (TRD), is an important clinical problem. The additive value of thyroid hormones in this context has been explored over many years, but their utility remains uncertain. The purpose of this paper is therefore to clarify the potential role of thyroid augmentation in treatment-refractory depression, in the light of contemporary pathophysiologic knowledge and the utility of other approaches. Methods:A literature search on thyroid augmentation studies in depression, including TRD, was conducted, using MEDLINE (National Library of Medicine), accessed via the PubMed portal. Results:The review examined the published literature from 1996 to 2005. Several randomized studies and a larger number of uncontrolled investigations which used both Triiodothyronine (T3) and Levothyroxine (T4) in the treatment of affective disorders were identified. Conclusion:The review supports the use of T4 and T3 in TRD, particularly in women suffering from depression and in bipolar depression. While, there is evidence linking thyroid function to affective disorders, the putative mechanisms underlying the action of these hormones in depression suggest promising directions for future research on thyroid treatments for TRD.
Lee, Young ,Ae,Yun, Byeong ,Hwa,Kim, Seog ,K.,Margolin, Yelena,Dedon, Peter ,C.,Geacintov, Nicholas ,E.,Shafirovich, Vladimir WILEY-VCH Verlag 2007 Chemistry Vol.13 No.16
<P>Peroxynitrite is produced during inflammation and combines rapidly with carbon dioxide to yield the unstable nitrosoperoxycarbonate, which decomposes (in part) to CO<SUB>3</SUB><SUP>.−</SUP> and <SUP>.</SUP>NO<SUB>2</SUB> radicals. The CO<SUB>3</SUB><SUP>.−</SUP> radicals oxidize guanine bases in DNA through a one-electron transfer reaction process that ultimately results in the formation of stable guanine oxidation products. Here we have explored these mechanisms, starting with a spectroscopic study of the kinetics of electron transfer from 20–22mer double-stranded oligonucleotides to CO<SUB>3</SUB><SUP>.−</SUP> radicals, together with the effects of base sequence on the formation of the end-products in runs of one, two, or three contiguous guanines. The distributions of these alkali-labile lesions were determined by gel electrophoresis methods. The cascade of events was initiated through the use of 308 nm XeCl excimer laser pulses to generate CO<SUB>3</SUB><SUP>.−</SUP> radicals by an established method based on the photodissociation of persulfate to sulfate radicals and the oxidation of bicarbonate. Although the Saito model (Saito et al., J. Am. Chem. Soc. 1995, 117, 6406–6407) predicts relative ease of one-electron oxidations in DNA, following the trend 5′-⋅⋅⋅GGG⋅⋅⋅ > 5′-⋅⋅⋅GG⋅⋅⋅ > 5′-⋅⋅⋅G⋅⋅⋅, we found that the rate constants for CO<SUB>3</SUB><SUP>.−</SUP>-mediated oxidation of guanines in these sequence contexts (k<SUB>5</SUB>) showed only small variation within a narrow range [(1.5–3.0)×10<SUP>7</SUP> M<SUP>−1</SUP> s<SUP>−1</SUP>]. In contrast, the distributions of the end-products are dependent on the base sequence context and are higher at the 5′-G in 5′-⋅⋅⋅GG⋅⋅⋅ sequences and at the first two 5′-guanines in the 5′-⋅⋅⋅GGG⋅⋅⋅ sequences. These effects are attributed to a combination of initial hole distributions among the contiguous guanines and the subsequent differences in chemical reaction yields at each guanine. The lack of dependence of k<SUB>5</SUB> on sequence context indicates that the one-electron oxidation of guanine in DNA by CO<SUB>3</SUB><SUP>.−</SUP> radicals occurs by an inner-sphere mechanism.</P> <B>Graphic Abstract</B> <P>Rates of one-electron oxidation of guanine in DNA by carbonate radicals do not depend on sequence context: The sequence-dependent damage at guanine sites (see figure) is attributed to a combination of initial hole distributions among the contiguous guanines and the subsequent differences in chemical reaction yields at each guanine. <img src='wiley_img/09476539-2007-13-16-CHEM200601434-content.gif' alt='wiley_img/09476539-2007-13-16-CHEM200601434-content'> </P>
INSIGHT INTO THE GROWTH MECHANISM OF WS2 NANOTUBES IN THE SCALED-UP FLUIDIZED-BED REACTOR
R. TENNE,A. ZAK,L. SALLACAN-ECKER,A. MARGOLIN,M. GENUT 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2009 NANO Vol.4 No.2
The growth mechanism of WS2 nanotubes in the large-scale fluidized-bed reactor is studied in greater detail. This study and careful parameterization of the conditions within the reactor lead to the synthesis of large amounts (50–100 g/batch) of pure nanotubes, which appear as a fluffy powder, and (400–500 g/batch) of nanotubes/nanoplatelets mixture (50:50), where nanotubes usually coming in bundles. The two products are obtained simultaneously in the same reaction but are collected in different zones of the reactor, in a reproducible fashion. The characterization of the nanotubes, which grow catalyst-free, by a number of analytical techniques is reported. The majority of the nanotubes range from 10 to 50 micron in length and 20–180 nm in diameter. The nanotubes reveal highly crystalline order, suggesting very good mechanical behavior with numerous applications.
MoS2 FULLERENE-LIKE NANOPARTICLES AND NANOTUBES USING GAS-PHASE REACTION WITH MoCl5
F. L. DEEPAK,MAYA BAR-SADAN,RESHEF TENNE,ALEXANDER MARGOLIN,INNA WIESEL,RONIT POPOVITZ-BIRO 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2006 NANO Vol.1 No.2
Inorganic fullerene-like (IF) nanoparticles of MoS2 were synthesized using gas-phase reaction starting from MoCl5 and H2S. The IF-MoS2 nanoparticles are spherical and in some cases faceted with diameters in general ranging between 20 and 80 nm. The IF-MoS2 nanoparticles have large hollow cores, filled in some cases with amorphous material. Various parameters have been investigated to understand the growth and formation of the IF-MoS2 nanoparticles. The parameters that have been studied include flow rates of the various carrier gases, temperature at which the reaction was carried out, time of the reaction and heating of the precursor material. The best set of conditions wherein maximum yields of the IF-MoS2 nanoparticles are obtained have been identified. Additionally, annealing the as-obtained samples or heating them in a mixture of H2 along with H2S improves the crystallinity and reduces the amorphous material filling in the core. Apart from the fullerene-like nanoparticles under certain experimental conditions nanotubes of MoS2 have also been obtained nonetheless in small yields.
Chapuis, Aude G.,Lee, Sylvia M.,Thompson, John A.,Roberts, Ilana M.,Margolin, Kim A.,Bhatia, Shailender,Sloan, Heather L.,Lai, Ivy,Wagener, Felecia,Shibuya, Kendall,Cao, Jianhong,Wolchok, Jedd D.,Gree The Rockefeller University Press 2016 The Journal of experimental medicine Vol.213 No.7
<P>Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8<SUP>+</SUP> cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21–primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4. Long-term persistence and sustained anti-tumor activity of transferred CTL, as well as responses to nontargeted antigens, confirmed mutually beneficial effects of the combined treatment. In this first-in-human study, Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually.</P>