Publications by authors named "Saravanan Natarajan"

20 Publications

  • Page 1 of 1

Effects of co-administration of pharmacopoeia formulations and with CAT-I antitubercular drugs in rats.

J Complement Integr Med 2021 May 10. Epub 2021 May 10.

ICMR-National Institute for Research in Tuberculosis (NIRT), Chennai, Tamil Nadu, India.

Objectives: Tuberculosis continues to be a major public health problem globally, despite incredible advancements in healthcare system. In system of medicine, (QTS) and (AHB) have been traditionally used for tuberculosis like conditions. The study was aimed to investigate the effects of co-administration of QTS and AHB with category I first line antitubercular drugs (CAT-I) on the indices of liver and kidney function in rats.

Methods: QTS and AHB were prepared individually and mixed to achieve final compound pharmacopoeia formulation (UPF). The human equivalent doses for rats were calculated and administered with and without CAT-I. The effects of the formulations on serum indices of kidney and liver function, hematological markers and plasma CAT-I drug levels were estimated at 14th, 60th & 180th days of treatment.

Results: The administration of UPF, CAT-I and UPF + CAT-I altered the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) and haematological markers. These alterations were within permissible range and randomly distributed among groups during various time points. Administration of CAT-I alone resulted in moderate histopathological changes which were completely abrogated in CAT-I + UPF co-administered animals. The co-administration of UPF with CAT-I improved the plasma peak rifampicin (RIF) levels, without altering the liver and kidney functions.

Conclusions: The co-administration of UPF with ATT improved liver and kidney functions and increased the plasma levels of RIF. These beneficial findings provide a scope to evaluate the pharmacokinetic studies in humans.
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http://dx.doi.org/10.1515/jcim-2020-0262DOI Listing
May 2021

Vitamin B12-Immobilized Graphene Oxide for Efficient Electrocatalytic Carbon Dioxide Reduction Reaction.

ChemSusChem 2020 Nov 14;13(21):5620-5624. Epub 2020 Oct 14.

Carbon Dioxide Research and Green Technology Centre, Vellore Institute of Technology University, Vellore, 632 014, India.

A naturally occurring water-soluble cobalt-complex cyanocobalamin (Vitamin B12) has been identified as a new and efficient electrocatalyst for the CO -to-CO reduction reaction in aqueous solution. Heterogeneous B12-electrocatalysts prepared by a simple electrochemical immobilization technique on graphene-oxide (GO)-modified glassy carbon and carbon paper (CP) electrodes, without any non-degradable polymer-binders, showed a highly stable and well-defined surface-confined redox peak at E'=-0.138 V vs. RHE with a surface-excess value, Γ =4.28 nmol cm . This new electrocatalyst exhibits 93 % Faradaic efficiency for CO -to-CO conversion at an electrolysis potential, -0.882 V vs. RHE (an optimal condition) with a high current density, 29.4 mA cm and turn-over-frequency value, 5.2 s , without any surface-fouling problem, in 0.5 m KHCO . In further, it follows an eco-friendly, sustainable and water-based approach with the involvement of biodegradable and non-toxic chemicals/materials like B12, GO and CP.
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http://dx.doi.org/10.1002/cssc.202001378DOI Listing
November 2020

Rapid and efficient chiral method development for lamivudine and tenofovir disoproxil fumarate fixed dose combination using ultra-high performance supercritical fluid chromatography: A design of experiment approach.

J Chromatogr A 2020 Aug 2;1625:461257. Epub 2020 Jun 2.

Analytical Research and Development, Biocon Bristol Myers Squibb Research & Development Centre (BBRC), Syngene International Limited, Bangalore 560099, India. Electronic address:

Fixed dose combination (FDC) of tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) is one of the most preferred FDC for the treatment of acquired immunodeficiency syndrome (AIDS)/human immunodeficiency virus (HIV) infection. To the best of authors' knowledge there are no reported methods for chiral purity estimation of both drugs simultaneously from a FDC. The current study was focused on the development of a single chiral method uisng supercritical fluid chromatography (SFC) for separation of stereoisomers of TDF and 3TC combination employing design of experiment (DoE) approach. Method development was planned in three steps by using different experimental designs for each step. I-optimal, Taguchi orthogonal array and face-centred central composite designs (CCD) were employed for primary parameter selection, secondary parameter screening and final method optimization, respectively. All six stereoisomers were separated in a 10 minute run on Chiralpak IA column with carbon di-oxide /methanol (containing 0.5 % v/v n-butylamine) as mobile phase at 1.5 mL/min in gradient mode. The optimized method was verified for performance through establishing specificity, precision, linearity, accuracy, limit of quantification, and solution stability. Resolution between each isomeric pair was more than 1.5. The method was found to be linear from 1.5 µg/mL to 7.5 µg/mL for 3TC and 7.5 µg/mL to 37.5 µg/mL for TDF stereoisomers. The R values for all the linearity curves for undesired isomers were greater than 0.995. The method proved to be rapid, reproducible and efficient to quantify stereoisomers of both drugs in a single run.
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http://dx.doi.org/10.1016/j.chroma.2020.461257DOI Listing
August 2020

Electrocatalytic Reduction of CO to Ethylene by Molecular Cu-Complex Immobilized on Graphitized Mesoporous Carbon.

Small 2020 Jun 28;16(25):e2000955. Epub 2020 May 28.

Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Seoul, 08826, Republic of Korea.

The electrochemical reduction of carbon dioxide (CO ) to hydrocarbons is a challenging task because of the issues in controlling the efficiency and selectivity of the products. Among the various transition metals, copper has attracted attention as it yields more reduced and C2 products even while using mononuclear copper center as catalysts. In addition, it is found that reversible formation of copper nanoparticle acts as the real catalytically active site for the conversion of CO to reduced products. Here, it is demonstrated that the dinuclear molecular copper complex immobilized over graphitized mesoporous carbon can act as catalysts for the conversion of CO to hydrocarbons (methane and ethylene) up to 60%. Interestingly, high selectivity toward C2 product (40% faradaic efficiency) is achieved by a molecular complex based hybrid material from CO in 0.1 m KCl. In addition, the role of local pH, porous structure, and carbon support in limiting the mass transport to achieve the highly reduced products is demonstrated. Although the spectroscopic analysis of the catalysts exhibits molecular nature of the complex after 2 h bulk electrolysis, morphological study reveals that the newly generated copper cluster is the real active site during the catalytic reactions.
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http://dx.doi.org/10.1002/smll.202000955DOI Listing
June 2020

Molecular wiring of glucose oxidase enzyme with Mn polypyridine complex on MWCNT modified electrode surface and its bio-electrocatalytic oxidation and glucose sensing.

Methods Enzymol 2020 31;630:249-262. Epub 2019 Oct 31.

Nano and Bioelectrochemistry Research Laboratory, Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, India; Carbon Dioxide Research and Green Technology Centre, Vellore Institute of Technology, Vellore, India. Electronic address:

A simple method for molecular wiring of glucose oxidase (GOx) enzyme with a low cost Mn polypyridine complex, Mn(phen)Cl, carboxylic acid functionalized multiwalled carbon nanotube (f-MWCNT) and Nafion (Nf), which is useful for glucose oxidation and sensing application in pH 7 phosphate buffer solution, has been demonstrated. In the typical preparation, f-MWCNT, Mn(phen)Cl, Nafion and GOx solution/suspension were successfully drop-casted as layer-by-layer on a cleaned glassy carbon electrode and potential cycled using cylic voltametric (CV) technique. In this preparation procedure, the Mn(phen)Cl complex is in-situ converted as a dimer complex, Mn(phen)(O)(Cl). A cooperative interaction based on π-π, covalent, ionic, hydrophilic and hydrophobic are operated in the bioelectrode for molecular wiring and electron-transfer shutting reaction. The modified electrode is designated as GCE/[email protected](phen)(O)(Cl)[email protected] CV response of the bioelectrode showed a defined redox peak current signal at an apparent standard electrode potential, E'=0.55V vs Ag/AgCl. Upon exposure of glucose, the modified electrode showed a current linearity in a range, 0-6mM with a current sensitivity value, 349.4μAmMcm by CV and a current linearity in a window, 50-550μM with a current sensitivity, 316.8μAmMcm at applied biased potential, 0.65V vs Ag/AgCl by amperometric i-t methods. Obtained glucose oxidation current sensitivity values are relatively higher than Os-complex based transducer systems.
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http://dx.doi.org/10.1016/bs.mie.2019.10.024DOI Listing
December 2020

Persistent Mullerian Duct Syndrome: A Single-Center Experience.

J Indian Assoc Pediatr Surg 2018 Oct-Dec;23(4):203-205

Department of Pediatric Surgery, Government Mohan Kumaramangalam Medical College, Salem, Tamil Nadu, India.

Context: Persistent Mullerian duct syndrome (PMDS) is a rare disorder. It is a type of male pseudohermaphroditism, usually presenting as "Hernia Uteri Inguinalis".

Aims: This study aims to present our experience of PMDS, over a 7-year period.

Settings And Design: Our center is a tertiary care facility, situated in Tamil Nadu, a southern state of India.

Subjects And Methods: This is a retrospective study. The study period was from 2007 to 2015. Seven cases presented during that period. The difficulties in diagnosis, treatment options discussed, along with a review of literature are presented.

Results: Seven cases of PMDS presented over 8 years. Only four were diagnosed preoperatively. Mullerian remnants were excised in five cases.

Conclusions: PMDS is rare. Orchiopexy should be the goal of treatment.
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http://dx.doi.org/10.4103/jiaps.JIAPS_61_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182940PMC
November 2018

Involvement of high-valent manganese-oxo intermediates in oxidation reactions: realisation in nature, nano and molecular systems.

Nano Converg 2018 4;5(1):18. Epub 2018 Jul 4.

Department of Materials Science and Engineering, Seoul National University, Seoul, 151-744 South Korea.

Manganese plays multiple role in many biological redox reactions in which it exists in different oxidation states from Mn(II) to Mn(IV). Among them the high-valent manganese-oxo intermediate plays important role in the activity of certain enzymes and lessons from the natural system provide inspiration for new developments of artificial systems for a sustainable energy supply and various organic conversions. This review describes recent advances and key lessons learned from the nature on high-valent Mn-oxo intermediates. Also we focus on the elemental science developed from the natural system, how the novel strategies are realised in nano particles and molecular sites at heterogeneous and homogeneous reaction conditions respectively. Finally, perspectives on the utilisation of the high-valent manganese-oxo species towards other organic reactions are proposed.
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http://dx.doi.org/10.1186/s40580-018-0150-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061251PMC
July 2018

Malnutrition: Modulator of Immune Responses in Tuberculosis.

Front Immunol 2017 18;8:1316. Epub 2017 Oct 18.

National Institute for Research in Tuberculosis, Chennai, India.

Nutrition plays a major role in the management of both acute and chronic diseases, in terms of body's response to the pathogenic organism. An array of nutrients like macro- and micro-nutrients, vitamins, etc., are associated with boosting the host's immune responses against intracellular pathogens including (). These nutrients have an immunomodulatory effects in controlling the infection and inflammation process and nutritional deficiency of any form, i.e., malnutrition may lead to nutritionally acquired immunodeficiency syndrome, which greatly increases an individual's susceptibility to progression of infection to disease. This narrative review looks at the various mechanisms by which nutrition or its deficiency leads to impaired cell mediated and humoral immune responses, which in turn affects the ability of an individual to fight infection or disease. There is very little evidence in the literature that any specific food on its own or a specific quantity can alter the course of TB disease or be effective in the treatment of malnutrition. Further clinical trials or studies will be needed to recommend and to better understand the link between malnutrition, tuberculosis, and impaired immunity.
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http://dx.doi.org/10.3389/fimmu.2017.01316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651251PMC
October 2017

Delayed Presentation of Congenital Colonic Stenosis.

J Indian Assoc Pediatr Surg 2017 Jul-Sep;22(3):191-192

Department of Pediatric Surgery, G.M.K. Medical College, Salem, Tamil Nadu, India.

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http://dx.doi.org/10.4103/jiaps.JIAPS_232_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473314PMC
July 2017

Impact of obesity with impaired glucose tolerance on retinal degeneration in a rat model of metabolic syndrome.

Mol Vis 2017 14;23:263-274. Epub 2017 Apr 14.

National Institute of Nutrition, Hyderabad, India.

Purpose: Metabolic syndrome (MetS) is associated with several degenerative diseases, including retinal degeneration. Previously, we reported on progressive retinal degeneration in a spontaneous obese rat (WNIN/Ob) model. In this study, we investigated the additional effect of impaired glucose tolerance (IGT), an essential component of MetS, on retinal degeneration using the WNIN/GR-Ob rat model.

Methods: The retinal morphology and ultrastructure of WNIN/GR-Ob and age-matched littermate lean rats were studied by microscopy and immunohistochemistry. The retinal transcriptome of WNIN/GR-Ob was compared with the respective lean controls and with the WNIN/Ob model using microarray analysis. Expression of selected retinal marker genes was studied via real-time PCR.

Results: Progressive loss of photoreceptor cells was observed in WNIN/GR-Ob rats with an onset as early as 3 months. Similarly, thinning of the inner nuclear layer was observed from 6 months in these rats. Immunohistochemical analysis showed decreased levels of rhodopsin and postsynaptic density protein-95 (PSD-95) proteins and increased levels of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and calretinin in WNIN/GR-Ob rats compared with the age-matched lean controls, further supporting cellular stress/damage and retinal degeneration. The retinal transcriptome analysis indicated altered expression profiles in both the WNIN/GR-Ob and WNIN/Ob rat models compared to their respective lean controls; these pathways are associated with activation of pathways like cellular oxidative stress response, inflammation, apoptosis, and phototransduction, although the changes were more prominent in WNIN/GR-Ob than in WNIN/Ob animals.

Conclusions: WNIN/GR-Ob rats with added glucose intolerance developed retinal degeneration similar to the parent line WNIN/Ob. The severity of retinal degeneration was greater in WNIN/GR-Ob rats compared to WNIN/Ob, suggesting a possible role for IGT in this model. Hence, the WNIN/GR-Ob model could be a valuable tool for investigating the impact of MetS on retinal degeneration pathology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398884PMC
January 2018

Dietary ginger improves glucose dysregulation in a long-term high-fat high-fructose fed prediabetic rat model.

Indian J Exp Biol 2017 Mar;55(3):142-50

The rapid increase in global diabetes burden with its associated morbidity and mortality is a major health concern for humans. Prediabetes is a condition which predispose a person not only to diabetes but also to the associated complications including morbidity even in the absence of an apparant hyperglycemia. However, appropriate dietary intervention may not only prevent but also improve one’s condition as diet is the major contributor to such metabolic disorders. Here, we investigated the effect of dietary ginger (Zingiber officinale Roscoe) on the markers of insulin resistance and pathophysiology in a diet-induced prediabetic rat model. Male Sprague-Dawley (SD) rats were fed the following diets: control (5% groundnut oil + 65 % corn starch), high fat high fructose (HFHF; 25% beef tallow + 35 % fructose) and HFHF with 3 % ginger (HFHFG) for eight months. Plasma markers of insulin resistance, lipid profile, oral glucose tolerance (OGTT; 2nd and 5th month), intraperitoneal insulin tolerance (ITT), plasma total antioxidant capacity (TAC), liver histology and pancreatic immunohistochemistry (IHC) were examined. The impaired OGTT, ITT and insulin sensitivity indices with observed hyperinsulinemia and hypertriglyceridemia suggest that HFHF feeding resulted in prediabetes in rats. HFHF feeding also decreased insulin secretion in the pancreas, increased lipid accumulation in liver and total oxidants in plasma. The effects of HFHF feeding on glucose regulation, pathophysiology of pancreas and liver; total oxidative stress were improved by ginger feeding. The present study demonstrated thatlong-term HFHF feeding induces prediabetes in experimental rats while dietary ginger neutralizes the HFHF induced impairment in glucose regulation, dyslipidemia, and oxidative stress.
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March 2017

Torsion of Accessory Hepatic Lobe.

J Indian Assoc Pediatr Surg 2017 Jan-Mar;22(1):55-56

Department of Paediatric Surgery, Government Mohan Kumaramangalam Medical College, Salem, Tamil Nadu, India.

An accessory hepatic lobe is a rare congenital anomaly that can undergo torsion and present as an acute surgical emergency. A 5-year-old child admitted as acute abdomen, on laparotomy found to have torsion of accessory lobe of liver, is being reported.
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http://dx.doi.org/10.4103/0971-9261.194628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217145PMC
January 2017

Antibacterial and antifouling activities of chitosan/TiO2/Ag NPs nanocomposite films against packaged drinking water bacterial isolates.

Environ Sci Pollut Res Int 2016 Oct 7;23(19):19529-40. Epub 2016 Jul 7.

Centre for Nanobiotechnology, VIT University, Vellore, 632 014, India.

TiO2 and Ag NPs are widely used as antibacterial agents against many bacterial pathogens. Chitosan (polymer) itself acts as a strong antibacterial agent. Hence, chitosan/TiO2/Ag NPs incorporated nanocomposite film was prepared against packed drinking water bacterial strains. A concentration-dependent increase in the reduction of cell viability was observed in all the isolates under UV-C and dark exposure conditions. The bacteria consortium showed greater resistance against antibacterial effects of chitosan/TiO2/Ag nanocomposite as compared to single isolates. Glycocalyx test and mass assessment conclude the effective antibacterial activity by inhibiting bacterial adhesion on the film surface. The release of LDH and generation of ROS act as the predominant antibacterial mechanism induced by TiO2/Ag NPs. Surface characterization of chitosan/TiO2/Ag nanocomposite was studied by FTIR and XRD analyses and SEM analysis after interaction with the bacteria.
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http://dx.doi.org/10.1007/s11356-016-7102-6DOI Listing
October 2016

Anesthetic management of staged thoracoscopic repair of bilateral eventration of diaphragm in a neonate.

Anesth Essays Res 2016 Jan-Apr;10(1):118-21

Department of Conservative and Endodontics, KSR Institute of Dental Sciences and Research, Tiruchengode, Tamil Nadu, India.

Congenital eventration of the diaphragm is a rare disorder, the perioperative management of which is challenging. The introduction of thoracoscopic repair of these defects has considerably reduced the perioperative morbidity and mortality in these patients. In spite of the advantages of thoracoscopy which include smaller chest incisions, reduced postoperative pain, and more rapid postoperative recovery compared with thoracotomy, it is still inherent with complications unique to it. A clear understanding of the pathophysiologic changes, potential complications and institution of appropriate monitoring and good planning is essential for the safe conduct of thoracoscopic procedures in neonates. We describe the anesthetic management of staged thoracoscopic repair of bilateral congenital eventration of the diaphragm in a neonate.
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http://dx.doi.org/10.4103/0259-1162.165497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767072PMC
March 2016

Crystal structure of bis-(acetato-κO)di-aqua-(2,2'-bi-pyridine-κ(2) N,N')manganese(II).

Acta Crystallogr Sect E Struct Rep Online 2014 Sep 13;70(Pt 9):m326-7. Epub 2014 Aug 13.

National Centre for Catalysis Research, Department of Chemistry, Indian Institute of Technology-Madras, Chennai 600 036, India.

In the title monomeric manganese(II) complex, [Mn(CH3COO)2(C10H8N2)(H2O)2], the metal ion is coordinated by a bidentate 2,2'-bi-pyridine (bpy) ligand, two water mol-ecules and two axial acetate anions, resulting in a highly distorted octa-hedral environment. The aqua ligands are stabilized by the formation of strong intra-molecular hydrogen bonds with the uncoordinated acetate O atoms, giving rise to pseudo-bridging arrangement of the terminal acetate groups. In the crystal, the mol-ecules form [010] zigzag chains via O-H⋯O hydrogen bonds involving the aqua ligands and acetate O atoms. Further, the water and bpy ligands are trans to each other, and are arranged in an off-set fashion showing inter-molecular π-π stacking between nearly parallel bi-py rings, the centroid-centroid separations being 3.8147 (12) and 3.9305 (13) Å.
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http://dx.doi.org/10.1107/S1600536814017814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186102PMC
September 2014

Biomimetic iron(III) complexes of facially and meridionally coordinating tridentate 3N ligands: tuning of regioselective extradiol dioxygenase activity in organized assemblies.

Dalton Trans 2014 May;43(18):6828-41

School of Chemistry, Bharathidasan University, Tiruchirappalli - 620 024, Tamil Nadu, India.

Four mononuclear iron(III) complexes of the type [Fe(L)Cl3] 1-4, where L is a tridentate 3N ligand such as (2-pyridin-2-ylethyl)(pyridin-2-ylmethyl)amine (L1), (methyl)(2-pyridin-2-ylethyl)(pyridin-2-ylmethyl)amine (L2), bis(pyridin-2-ylethyl)amine (L3), and (1-methyl-1H-imidazol-2-ylmethyl)(pyridin-2-ylethyl)amine (L4), have been isolated and studied as functional models for catechol dioxygenase enzymes. In [Fe(L2)Cl3] 2, the ligand L2 is coordinated facially to iron(III) whereas in [Fe(L1)Cl3] 1 and [Fe(L4)Cl3] 4 the ligands L1 and L4 are coordinated meridionally. In DCM, CH3CN and aqueous SDS, CTAB and TX-100 micellar media, the positions of both the low and high energy catecholate-to-iron(III) LMCT bands (465-530, 690-860 nm) observed for the 3,4-di-tert-butylcatecholate (DBC(2-)) adducts of the iron(III) complexes vary in the order 2 > 1 > 3 > 4, which reflects the influence of the stereoelectronic factors, mode of coordination and the chelate ring size formed by the tridentate ligands. Spectral and electrochemical studies disclose the formation and location of the cationic adducts as solvated [Fe(L)(DBC)(H2O)](+) species mostly in the aqueous micellar pseudophases of SDS and TX-100 and in the aqueous phase of CTAB micellar solution. The [Fe(L)(DBC)Cl] adducts of 1, 3 and 4, generated in situ, afford major amounts of intradiol cleavage products (17.0-70.0%) and smaller amounts of extradiol (1.2-4.2%) products with varying extradiol to intradiol cleavage product selectivity (E/I: 1, 0.08 : 1; 3, 0.02 : 1; 4, 0.3 : 1). On the other hand, interestingly, the adduct [Fe(L2)(DBC)Cl] of 2 generated in DCM yields a major amount of extradiol (54.0%) and a lower amount (18.3%) of the intradiol cleavage products (E/I, 3 : 1). Remarkably, in aqueous SDS micellar media, it shows exclusive extradiol cleavage products (79.4%) while all the other complexes show very low selectivity (E/I: 1, 0.03 : 1; 2, 79.4 : 0, 3, 0.06 : 1, 4, 0.06 : 1), suggesting the suitability of SDS medium for 2 to elicit exclusive extradiol cleavage. The TX-100 micellar medium also provides a suitable hydrophobic environment for 2 to elicit extradiol cleavage. However, in CTAB micellar medium, 2 shows cleavage selectivity lower than others. Also, the rate of dioxygenation is higher in SDS micellar medium than in DCM, and is dependent upon the chelate ring size.
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http://dx.doi.org/10.1039/c3dt52350kDOI Listing
May 2014

Benefits of early glycemic control by insulin on sensory neuropathy and cataract in diabetic rats.

Indian J Exp Biol 2013 Jan;51(1):56-64

Department of Cell and Molecular Biology, Madras Diabetes Research Foundation, Dr.Mohan's Diabetes Specialties Centre & IDF Centre of Education, Gopalapuram, Chennai 600 086, India.

While there is an emphasis on the early glycemic control for its long-term benefits in preventing microvascular complications of diabetes, the biochemical mechanisms responsible for the long-lasting effects are not clearly understood. Therefore the impact of early insulin (EI) versus late insulin (LI) treatment on diabetic sensory neuropathy and cataract in streptozotocin-induced diabetic Wistar male rats were evaluated. EI group received insulin (2.5 IU/animal, once daily) treatment from day 1 to 90 while LI group received insulin from day 60 to 90. Early insulin treatment significantly reduced the biochemical markers like glucose, triglyceride, glycated hemoglobin, thiobarbituric acid reactive substances, advanced glycation end products and ratio of reduced glutathione and oxidized glutathione in diabetic rats. The late insulin treatment failed to resist the biochemical changes in diabetic rats. Diabetic rats developed sensory neuropathy as evidenced by mechanical and thermal hyperalgesia and showed a higher incidence and severity of cataract as revealed by slit lamp examination. Early insulin treatment protected the rats from the development of neuropathy and cataract, but late insulin administration failed to do so. The results demonstrate the benefits of early glycemic control in preventing neuropathy and cataract development in diabetic rats.
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January 2013

Dietary trans fatty acids alter diaphragm phospholipid fatty acid composition, triacylglycerol content and glucose transport in rats.

Br J Nutr 2005 Jun;93(6):829-33

National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania P.O, Hyderabad 500 007, India.

The present study evaluates the effect of dietary trans fatty acids on diaphragm phospholipid fatty acid composition, intramyocellular triacylglycerol content and insulin-stimulated glucose uptake in comparison with dietary saturated fatty acids. Male weanling WNIN rats were divided into three groups and fed for 3 months on one of the following diets containing 10 % oil differing in fatty acid composition: control diet, saturated fatty acid diet and trans fatty acid diet. Dietary trans fatty acids increased the intramyocellular triacylglycerols and decreased the ratio of 20 : 4n-6 to 18 : 2n-6 and long-chain PUFA levels (20 %) in diaphragm phospholipids, indicating inhibition of PUFA biosynthesis. However, saturated fatty acids decreased both 18 : 2n-6 and 20 : 4n-6 without change in the ratio. Trans fatty acid-induced alterations in diaphragm phospholipid fatty acid composition and intramyocellular triacylglycerol content were associated with decreased insulin-stimulated glucose transport in the diaphragm. These observations suggest that dietary trans fatty acids decrease diaphragm insulin sensitivity, possibly due to increased intramyocellular triacylglycerol accumulation and decreased long-chain PUFA in phospholipids.
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http://dx.doi.org/10.1079/BJN20051442DOI Listing
June 2005

Differential effects of dietary saturated and trans-fatty acids on expression of genes associated with insulin sensitivity in rat adipose tissue.

Eur J Endocrinol 2005 Jul;153(1):159-65

Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania PO, Hyderabad- 500 007, AP India.

Objective: Trans-fatty acids (TFAs) are formed during partial hydrogenation of vegetable oils and are shown to be more atherogenic than saturated fatty acids (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that the effects of these fatty acids on insulin sensitivity could be mediated through an alteration in gene expression. In the current study we have investigated the effects of dietary TFAs or SFAs on expression of genes associated with insulin sensitivity in rat adipose tissue.

Design And Methods: Male weanling Wistar/NIN rats were divided into four groups and fed one of the following diets containing 10% fat (g/100 g diet) differing only in the fatty acid composition for 3 months: control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA + 1% LA) and TFA diet 2 (1.5% TFA + 2% LA). The mRNA expression of peroxisome proliferator-activated receptor gamma (PPARgamma), lipoprotein lipase (LPL), glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA to understand the beneficial effects of LA over the effects of TFA.

Results: Both dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated PPARgamma and LPL. The effects of dietary TFA on PPARgamma and resistin were not counteracted by increased LA (TFA diet 2).

Conclusion: The effects of SFAs on the aforementioned genes except PPARgamma could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPARgamma and resistin could be associated with insulin resistance in TFA-fed rats. These findings suggest that dietary SFAs and TFAs alter the expression of different genes associated with insulin sensitivity in adipose tissue.
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http://dx.doi.org/10.1530/eje.1.01946DOI Listing
July 2005

Substituting dietary linoleic acid with alpha-linolenic acid improves insulin sensitivity in sucrose fed rats.

Biochim Biophys Acta 2005 Mar;1733(1):67-75

Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania P.O., Hyderabad-500 007, A.P., India.

This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with alpha-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with approximately 6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.
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http://dx.doi.org/10.1016/j.bbalip.2004.12.003DOI Listing
March 2005