다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

/pdf/lipid-peroxidation-production-metabolism-and-signaling-234bwmyps5.pdf

Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

Bilateral orchiectomy has been performed in adult albino rats and tissue lipid profiles were compared with the controls. Both the reproductive and non-reproductive tissues and serum accumulated lipid with suppressed lipolysis on orchiectomy. The levels of triglycerides and cholesterol were elevated in all the tissues of orchiectomized rats. The phospholipid content of epididymis was significantly depleted, while the same was elevated in non-reproductive tissues.

Tissue lipid profiles in orchiectomized albino rats.

Computational Analysis of Interactions of Argadin with Chitotriosidase, Chitinase and Acidic Mammalian Chitinase: Hints for Specific Inhibitor Design

The present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein X, R1, R2, R3, R4, R5, R6, m and n are as defined in the detailed description. The present invention also relates to pharmaceutical compositions containing one or more compounds of the formula (I), as well as methods of treating or preventing diseases and/or disorders mediated by aberrant or undesired expression of one or more lipoxygenases (LOXs) using such compounds or compositions.

Heterocyclic compounds as lipoxygenase inhibitors

Although, non-steroidal anti-inflammatory drugs (NSAIDS), have been used in the treatment of various inflammatory diseases, their usage is limited by the side effects produced by them, thereby necessitating the need for searching new molecular entities. A number of aryl and heteroaryl substituted acetic acids such as Diclofenac 1, Lumiracoxib 2, Lonazolac 3, Etodolac 4 have been commercialized as NSAIDS. Several imidazoazines have been reported to possess significant pharmacological activities. Otsuka et al. isolated a number of 1,4-benzoxazinone derivatives from the roots of Coix lachryma – jobi which have been used in treatment of neuralgia, rheumatism and inflammatory diseases. Furthermore, recently several 2-substituted benzoxazinones have been reported as smooth muscle relaxants, anticoagulant and antibacterial agents. In addition, a new series of benzoxazinones were reported useful in the treatment of type 2 diabetes which does not contain thiazolidenedione. In view of these observations and in continuation of our work on new benzoxazines, it was considered of interest to synthesize some new imidazobenzoxazinyl acetic acids and evaluate their COX-2 inhibitor activity. Methyl α-(3,4-dihydro-3-oxo-2H-1,4-benzoxazin2-yl)acetates 5 required as starting materials in the present work, were prepared by the reaction of substituted 2-aminophenols with maleic anhydride in refluxing methanol in the presence of triethylamine according to the procedure described earlier. Reaction of 5 with various ω-haloacetophenones in refluxing acetone in the presence of anhydrous potassium carbonate and tetrabutylammonium bromide as phase transfer catalyst gave the N-alkylated benzoxazinones 6 in excellent yields. H NMR spectra of 6 exhibited characteristic signals around δ 3.76-3.78 (CO2CH3), 2.98-3.06 (2 × dd, CH2CO2CH3), 5.0-5.03 (m, OCH) and 5.31-5.34(ABq, -NCH2-CO) apart from other aromatic protons. IR spectra of 6 exhibited characteristic ester, amide and ketone carbonyl in the region 1735, 1690 cm. Cyclocondensation of 6 in acetic acid in presence of ammonium acetate gave the targeted imidazobenzoxazinyl acetates 7 in good yields (IR 1737 cm). Hydrolysis of representative 7 in aqueous methanolic NaOH furnished the corresponding acetic acids 8 as colourless crystalline solids (Scheme I). Structures of compounds 7 were established based on their H NMR, IR, mass spectra and correct elemental analyses. In the H NMR spectra of 7, the ester group appeared as a singlet at δ 3.76, the methylene protons of ester group appeared as two sets of double doublets at δ 3.06 and 3.42 whereas OCH proton appeared as a double doublet at δ 5.74 apart from C1-imidazoproton (δ 7.4-7.5, singlet) and other aromatic protons.

Synthesis of 4H‐Imidazo[2,1‐c][1,4]benzoxazin‐4‐yl Acetic Acids and Esters as Possible COX‐2 Inhibitors.

Sheep uterine tissue is rich in the enzyme 5-lipoxygenase (5-LOX) that generates 5-hydroperoxyeicosatetraenoic acid (5-HPETE) on incubation with arachidonic acid (AA). The present study focuses on the ability of the enzyme 5-LOX to further act as 5, 6 leukotriene A4 (LTA 4 ) synthase using 5-HPETE as a substrate. On incubation of 5-LOX with 5-HPETE and analysis of products on reversed-phase high-performance liquid chromatography, a prominent peak with a characteristic conjugated triene peak having absorption maxima of 261, 271, and 281 nm appeared. Based on cochromatography, the peak was identified as 5(S), 6(S)-dihydroxyeicosatetraenoic acid (5[S], 6[S]-diHETE), the non-enzymatic product of 5, 6 LTA 4 . As the synthesis of 5,6-LTA 4 from 5-HPETE requires 8-LOX activity, the present study demonstrates the dual LOX, 5- and 8-LOX activity for uterine 5-LOX, that is, 5-,6- LTA 4 synthase in sheep uterus. In addition, endogenous 5,6-LTC 4 , the glutathione conjugate of 5,6-LTA 4 , was also observed in the sheep uterine homogenate, further demonstrating the synthesis of 5,6-LTA 4 in the sheep uterine tissue.

https://jabonline.in/admin/php/uploads/779_pdf.pdf

Pallu Reddanna

Papers

Tissue lipid profiles in orchiectomized albino rats.

Computational Analysis of Interactions of Argadin with Chitotriosidase, Chitinase and Acidic Mammalian Chitinase: Hints for Specific Inhibitor Design

Heterocyclic compounds as lipoxygenase inhibitors

Synthesis of 4H‐Imidazo[2,1‐c][1,4]benzoxazin‐4‐yl Acetic Acids and Esters as Possible COX‐2 Inhibitors.

Model for metabolism of arachidonic acid by 5-lipoxygenase as 5, 6-LTA4 synthase in the sheep uterus: Evidence from in vitro studies