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1.
Environ Monit Assess ; 191(Suppl 3): 796, 2020 Jan 27.
Article in English | MEDLINE | ID: mdl-31989356

ABSTRACT

Environmental factors along with soil physico-chemical properties play a significant role on the diurnal trend of soil CO2 efflux. Soil CO2 efflux in Indian tropical forests is poorly studied. We studied the soil CO2 efflux in a representative tropical deciduous forest at Katerniaghat Wildlife Sanctuary (KWLS), Uttar Pradesh. The three forest communities namely dry mixed (DMF), Sal mixed (SMF), and Teak plantation (TPF) were selected for measuring soil CO2 efflux in the summer season during April to May 2017 using automated LI-COR 8100 soil CO2 flux system. Soil physico-chemical parameters were also studied in the three abovementioned forest communities. We also measured the different microclimatic variables at forest understorey in all three communities during the summer season. Total day time soil CO2 efflux of 826.70, 1089.24, and 828.94 (µmolCO2 m-2d-1) was observed in TPF, SMF, and DMF respectively. Soil CO2 efflux observed significant differences (P < 0.01) among the three forest communities studied for the summer season in tropical deciduous forest of Terai Himalaya. Average soil CO2 efflux rate (µmol CO2 m-2 s-1) of 4.06 ± 0.36, 5.03 ± 0.45, and 4.37 ± 0.79 was observed in TPF, SMF, and DMF, respectively, which is positively correlated with total organic carbon (TOC) and water holding capacity (WHC) among soil physico-chemical variables. Among microclimatic variables, soil temperature (ST, °C) and air temperature (AT, °C) observed strong positive correlation with day time soil CO2 efflux in all three communities. Significant increase in soil CO2 flux was observed with increasing air and soil temperature (AT and ST) in DMF and SMF. Maximum TOC of 19.23 g Kg-1 was observed in SMF among all communities in the summer season. The result showed that soil CO2 efflux is closely associated with TOC, WHC, AT, and ST for Indian deciduous forest ecosystems.


Subject(s)
Carbon Dioxide , Forests , Soil , Ecosystem , Environmental Monitoring , India , Trees
2.
Environ Monit Assess ; 191(Suppl 3): 797, 2020 Jan 27.
Article in English | MEDLINE | ID: mdl-31989261

ABSTRACT

In this study, we investigated the relationship between soil properties and litter chemistry in three forest communities, i.e., Sal mixed forest (SMF), dry mixed forest (DMF), and teak plantation forest (TPF), in tropical deciduous forest ecosystem in North India. Fresh leaf litter and soil samples were collected at two soil depths (0-15 and 15-30 cm) from all these three forest communities. Litter bag experiment was also conducted to know differences in litter nutrients after its decomposition. The concentrations (mg kg-1) of different nutrients such as sodium (Na) 2.6, potassium (K) 38.5, calcium (Ca) 425, and carbon (C) 45.54% were highest in fresh litter collected from DMF. Total organic carbon (g kg-1) was significantly higher in SMF (19.23) in comparison to DMF (18.41) and TPF (13.61) at 0-15-cm soil depth. Na, K, Ca, available P, total P, available N, and total N were highest in DMF soil. We observed significantly positive correlation between all nutrients of litter and soil. Although soil bulk density (BD) and particle density (PD) showed their significant negative correlation with litter C, total porosity was positively correlated. Similarly, litter Na has its significant negative correlation with BD and positive correlation with PD. The litter chemistry played a significant role in changing soil pH and TOC. All litter nutrients, except total P, have their significant positive correlation with soil pH. Total P, C, and N of litter have their significant positive correlation with total soil organic carbon. This indicates that litter chemistry and soil properties have specific relation among them despite unique species composition in each forest community.


Subject(s)
Ecosystem , Forests , Soil , Carbon , Environmental Monitoring , India , Plant Leaves , Trees
3.
HIV Med ; 16 Suppl 1: 109-18, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25711329

ABSTRACT

OBJECTIVES: Both HIV infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Assessments of vascular function and structure can be used to study the pathogenesis and progression of CVD, including the effects of ART and other interventions. The objective of this report is to understand methods to assess vascular (dys)function and report our experience in the Arterial Elasticity Substudy in the Strategic Timing of AntiRetroviral Treatment (START) trial. METHODS: We review literature and analyze baseline data from the Arterial Elasticity Substudy, which estimated vascular (dys)function through analysis of the diastolic blood pressure (BP) waveform. Linear regression was used to study cross-sectional associations between baseline clinical factors and small or large arterial elasticity. RESULTS: Arterial elasticity measurement was chosen for its improved measurement reproducibility over other methodologies and the potential of small arterial elasticity to predict clinical risk. Analysis of baseline data demonstrates that small artery elasticity is impaired (lower) with older age and differs by race and between geographical regions. No HIV-specific factors studied remained significantly associated with arterial elasticity in multivariate models. CONCLUSIONS: Longitudinal analyses in this substudy will provide essential randomized data with which to study the effects of early ART initiation on the progression of vascular disease among a diverse global population. When combined with future biomarker analyses and clinical outcomes in START, these findings will expand our understanding of the pathogenesis of HIV-related CVD.


Subject(s)
Arteries/physiology , Elasticity , HIV Infections/pathology , Adult , Anti-Retroviral Agents/therapeutic use , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Male , Middle Aged
4.
J Viral Hepat ; 22(1): 25-36, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24506344

ABSTRACT

Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co-infected patients. HCV viral load and 50 biomarkers were analysed at baseline and 27 time points during pegylated interferon-alpha and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co-infected patients. We evaluated biomarker changes from baseline for each time point and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL-1α, IL-12p40, IL-1RA, IP-10, MIG, MIP-1α/1ß, HGF, sCD40L, TRAIL and leptin increased in the first day. IL-12p70, IL-17A, IL-10, GROα, IL-8, MCP-3, IL-4 and M-CSF peaked later during week 1. IL-1α, HGF, IP-10, MIP-1α, TRAIL, sCD40L, IL-10, IL-12p70, MCP-3, FGFb, ENA-78, TGF-ß, IL-2, IFN-γ, IL-6, IL-15, IL-7 and PDGF-BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virologic response. ENA-78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.


Subject(s)
Antiviral Agents/therapeutic use , Biomarkers/blood , HIV Infections/pathology , Hepatitis C, Chronic/pathology , Interferon-alpha/therapeutic use , Ribavirin/therapeutic use , Adolescent , Adult , Aged , Female , HIV Infections/complications , HIV Infections/immunology , Hepacivirus/isolation & purification , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/immunology , Histocytochemistry , Humans , Liver/pathology , Male , Middle Aged , Prospective Studies , Viral Load , Young Adult
5.
J Viral Hepat ; 20(10): 708-14, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24010645

ABSTRACT

Hepatitis C virus (HCV) treatment is rapidly changing but little is known about patients' attitudes and knowledge about HCV. This study used a cross-sectional survey to examine the relationship between HCV knowledge and attitudes towards HCV in patients with HCV mono-infection and HIV/HCV co-infection. Subsequently, an education intervention was developed with an abridged version of the cross-sectional survey administered before and after the education session to assess changes in knowledge and attitudes. 292 people participated in the cross-sectional survey, and 87 people participated in the education intervention. In the cross-sectional survey, the mean knowledge score regarding HCV was low (<50% of the total possible score). Mono-infected and co-infected individuals shared similar knowledge deficits and attitudes towards HCV despite having distinct demographic differences. Attitudes endorsed by patients included the following: 57% feared the consequences of HCV on their life, 37% felt HCV was not fatal, 27% did not believe they needed HCV medication, 21% felt ashamed of having HCV and 16% felt HCV treatment was not important. Attitudes that reflected indifference and shame towards HCV were associated with lower knowledge scores (HCV knowledge score of 15.1 vs. 17.5, P < 0.01 for indifference and 15.3 vs. 17.2 for shame, P = 0.02). The education intervention improved knowledge scores but did not modify the assessed attitudes. Intervention studies are needed to effectively change attitudes towards HCV infection and treatment.


Subject(s)
HIV Infections/complications , Health Knowledge, Attitudes, Practice , Hepatitis C/psychology , Hepatitis C/therapy , Adult , Cross-Sectional Studies , Female , Health Education/methods , Humans , Male , Middle Aged
6.
J Mol Model ; 28(12): 400, 2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36434123

ABSTRACT

TKX-50 (dihydroxylammonium 5,5'-bistetrazolate-1,1'-dioxide) is a recent time invention by Klapotke et. al. in the field of high energy materials, and it outperforms all the existing materials by means of performance parameters. It is rising as potential energetic material due to favorable thermal insensitivity, low toxicity and safe handling. The decomposition temperature (Tmax) values of precursors such as glyoxime (I), 1,2-dichloroglyoxime (II), 1,2-diazidoglyoxime (III), and bistetrazoledihydroxide (IV) and ending products TKX-50 (V) and ABTOX (VI) have been attempted to correlate with the results obtained from molecular electrostatic potentials and band gaps calculated from the difference of ionization potential and electron affinity. The molecular electrostatic potential values of azido attached -NO group of III are much less than that of hydro/chloro attached -NO group of I/II and that of tetrazole groups IV, V, and VI. The band gaps calculated from stability trend in the increasing order of III < II < I < IV < V < VI are well corroborated with stability trend drawn from experimentally determined decomposition temperatures. Further, employing conceptual density functional theory (DFT) molecular descriptors, band gap values were calculated via the difference of ionization potential and electron affinity to understand the thermal stability of TKX-50, ABTOX, and its precursors.

7.
Sci Total Environ ; 793: 148518, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34171804

ABSTRACT

Ozone plays an important role in the thermal structure and chemical composition of the atmosphere. The present study compares the temporal and spatial distributions of Total Column Ozone (TCO) over the Indian sub-continent retrieved from a geostationary Indian National Satellite (INSAT-3D) and Atmospheric Infrared Sounder (AIRS). The INSAT-3D TCO values are also evaluated against the Dobson spectrophotometer observations at two locations. The inter-comparison results reveal a good correlation of 0.8, the bias of -5 DU, and Root Mean Square Error (RMSE) of 15 DU approximately between the TCO retrieved from INSAT-3D and AIRS. The lowest RMSE and highest correlation coefficient were found in the pre-monsoon season. The INSAT-3D and AIRS show reasonable agreement with the RMSE varying between 10 and 30 DU. On the other hand, evaluation of the INSAT-3D TCO with the ground-based observations from Dobson spectrophotometers located at New Delhi and Varanasi showed fair agreement with a maximum monthly mean correlation coefficient of 0.68 and 0.76, respectively, and RMSE varying from 11 to 16 DU for both the stations. The seasonal distribution of TCO and its variation over the Indian region has also been studied using INSAT-3D and AIRS data. The analysis exhibits strong seasonal variations, with higher values in pre-monsoon season and minimum values in winter season. The noticeable seasonal variability of TCO can be attributed to complex combination of photochemical and dynamical processes in the troposphere and stratosphere. The main objectives of the study are to compare the INSAT-3D TCO with two independent ground-based Dobson spectrophotometer observations and Atmospheric Infrared Sounder (AIRS) aboard NASA's Aqua satellite.


Subject(s)
Air Pollutants , Ozone , Air Pollutants/analysis , Atmosphere , Environmental Monitoring , India , Ozone/analysis
8.
Urol Case Rep ; 30: 101130, 2020 May.
Article in English | MEDLINE | ID: mdl-32123665

ABSTRACT

Bladder cancer is the sixth most common malignancy in the United States. Cisplatin combination regimens are first line therapy for patients with metastatic urothelial bladder cancer who are eligible candidates and no treatments have shown to improve outcome compared to chemotherapy for the past 20 years. Significant advances were made in past 2-3 years and the most significant was the introduction of checkpoints inhibitors in bladder cancer treatment. We present a patient diagnosed with metastatic urothelial carcinoma who progressed while on cisplatin/gemcitabine chemotherapy in the form of oligometastasis to the bone. He has achieved a durable complete response with atezolizumab.

9.
Science ; 280(5364): 722-4, 1998 May 01.
Article in English | MEDLINE | ID: mdl-9563945

ABSTRACT

DDT is reductively dechlorinated to DDD and dehydrochlorinated to DDE; it has been thought that DDE is not degraded further in the environment. Laboratory experiments with DDE-containing marine sediments showed that DDE is dechlorinated to DDMU in both methanogenic and sulfidogenic microcosms and that DDD is dehydrochlorinated to DDMU three orders of magnitude more slowly. Thus, DDD does not appear to be an important precursor of the DDMU found in these sediments. These results imply that remediation decisions and risk assessments based on the recalcitrance of DDE in marine and estuarine sediments should be reevaluated.


Subject(s)
Dichlorodiphenyl Dichloroethylene/analogs & derivatives , Dichlorodiphenyl Dichloroethylene/metabolism , Dichlorodiphenyldichloroethane/metabolism , Geologic Sediments/chemistry , Geologic Sediments/microbiology , Anaerobiosis , Bacteria, Anaerobic/metabolism , Biodegradation, Environmental , Chlorine/metabolism , Dichlorodiphenyl Dichloroethylene/analysis , Dichlorodiphenyldichloroethane/analysis , Euryarchaeota/metabolism , Gas Chromatography-Mass Spectrometry
10.
Science ; 181(4102): 869-71, 1973 Aug 31.
Article in English | MEDLINE | ID: mdl-4724077

ABSTRACT

The proton-decoupled natural abundance carbon-13 nuclear magnetic resonance spectrum of the canine sciatic nerve is virtually identical to that of canine adipose tissue and markedly similar to that of liquid triolein. No resonances assignable to cholesterol, glycolipids, or sphingolipids are detectable in the sciatic nerve spectrum despite their abundance in the myelin sheath of this nerve. However, many such resonances are observed in lipid extracts of the nerve. Chronmatographic analysis of specimens of canine and rabbit sciatic nerve has revealed that these contain sufficient triglyceride to account quantitatively for the observed spectrum. Proton nuclear magnetic resonance and spin-labeling results for preparations containing myelin, especially those derived from the peripheral nerve, should be critically examined for experimental artifacts reflecting the triglyceride content.


Subject(s)
Lipids/analysis , Magnetic Resonance Spectroscopy , Sciatic Nerve/analysis , Adipose Tissue/analysis , Animals , Carbon Isotopes , Dogs , Female , Myelin Sheath/analysis , Phospholipids/analysis , Rabbits , Sphingolipids/analysis , Triglycerides/analysis , Triolein/analysis
11.
J Assoc Physicians India ; 57: 332-3, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19702039

ABSTRACT

VATER association is an exceptionally rare condition; however it is associated with multiple rib anomalies, which is one of its unique presentation. We are reporting a case of VATER associated with rib anomalies in various forms like bifid rib, ribbon rib and rudimentary rib.


Subject(s)
Abnormalities, Multiple/diagnostic imaging , Ribs/abnormalities , Adolescent , Female , Humans , Radiography , Ribs/diagnostic imaging , Ultrasonography
12.
J Clin Invest ; 98(7): 1560-7, 1996 Oct 01.
Article in English | MEDLINE | ID: mdl-8833904

ABSTRACT

Smooth muscle cell proliferation and migration is important in arteriosclerosis. In this process, cytokines and growth factors are upregulated and bind to their respective receptors, which in turn stimulate mitogen-activated protein (MAP) kinases. MAP kinases then relay signals to the nucleus that activate quiescent smooth muscle cells. Phosphatases downregulate MAP kinases. We investigated the role of a dual-specificity tyrosine phosphatase, MAP kinase phosphatase-1 (MKP-1), in smooth muscle cell proliferation. MKP-1 expression was high in arterial tissue by Northern analysis, and MKP-1 message was detected mainly in the arterial smooth muscle layer by in situ hybridization. After balloon injury of the rat carotid artery, expression of MKP-1 decreased greatly, whereas that of MAP kinases, especially p44 MAP kinase, increased. The time course of the reduction in MKP-1 message correlated with increased tyrosine phosphorylation and elevated p44 MAP kinase enzymatic activity. In rat arterial smooth muscle cells overexpressing MKP-1, growth was arrested in the G1 phase and entry into the S phase was blocked. A reduction in MKP-1 expression may contribute in part to proliferation of smooth muscle cells after vascular injury, possibly through a decrease in dephosphorylation of p44 MAP kinase.


Subject(s)
Arteries/cytology , Cell Cycle Proteins , Gene Expression Regulation, Enzymologic , Immediate-Early Proteins/biosynthesis , Mitogen-Activated Protein Kinases , Muscle Development , Muscle, Smooth, Vascular/growth & development , Phosphoprotein Phosphatases , Protein Tyrosine Phosphatases/biosynthesis , Angioplasty, Balloon , Animals , Arteries/enzymology , Arteries/growth & development , Arteries/injuries , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Carotid Arteries/cytology , Carotid Arteries/enzymology , Carotid Artery Injuries , Cell Cycle , Dual Specificity Phosphatase 1 , Immediate-Early Proteins/genetics , Male , Mitogen-Activated Protein Kinase 3 , Muscle, Smooth, Vascular/enzymology , Organ Culture Techniques , Phosphorylation , Protein Phosphatase 1 , Protein Tyrosine Phosphatases/genetics , Pulmonary Artery/cytology , Pulmonary Artery/enzymology , Pulmonary Artery/growth & development , Rats , Recombinant Proteins/biosynthesis , Tissue Distribution
13.
Handb Exp Pharmacol ; (176 Pt 2): 285-306, 2006.
Article in English | MEDLINE | ID: mdl-16999230

ABSTRACT

Atherosclerosis depends critically on altered behavior of the intrinsic cells of the artery wall, the endothelial cells and smooth muscle cells, and inflammatory leukocytes that join them in the arterial intima during the atherogenic process. The homeostatic properties of the normal endothelium contribute importantly to maintenance of aspects of arterial health including the appropriate regulation of blood flow, a basal anti-inflammatory state, promotion of fibrinolysis while opposing blood coagulation, and control of the balance of cellular proliferation and death. Alterations in these endothelial homeostatic mechanisms contribute critically to atherogenesis, the progression of this disease, and ist complications. Recent advances have highlighted novel molecular mechanisms that regulate the atheroprotective functions of normal endothelial cells that go awry during atherogenesis. Therapeutic strategies that alter the course of atherosclerosis may act by combating endothelial dysfunction.


Subject(s)
Atherosclerosis/metabolism , Endothelium, Vascular/metabolism , Inflammation/metabolism , Thrombosis/metabolism , Animals , Aspirin/pharmacology , Aspirin/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/pathology , Cell Adhesion Molecules/metabolism , Cyclooxygenase Inhibitors/pharmacology , Cyclooxygenase Inhibitors/therapeutic use , Cytokines/metabolism , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/drug therapy , Inflammation/pathology , Nitric Oxide/metabolism , Prostaglandins I/metabolism , Thrombosis/drug therapy , Thrombosis/pathology
14.
J Assoc Physicians India ; 54: 491-2, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16909701

ABSTRACT

An unusual case of scorpion sting followed by multiple cerebral and cerebellar watershed infarctions is being reported. Myocarditis, hypotension and hypoperfusion infarction is being considered as the possible explanation for this pathology. Hypoperfusion leading to parieto-occipital infarction has been reported earlier, however cerebellar infarction in this context is extremely rare.


Subject(s)
Cerebral Infarction/etiology , Myocarditis/etiology , Scorpion Stings , Scorpions , Spider Bites/complications , Spider Venoms/poisoning , Adult , Animals , Humans , Male
15.
Biochim Biophys Acta ; 818(3): 352-5, 1985 Sep 10.
Article in English | MEDLINE | ID: mdl-4041442

ABSTRACT

X-ray diffraction was used to investigate the lattice structure of aqueous dispersions of two phosphatidyldiacylglycerols and of a phosphatidylcholesterol above and below the chain melting transition temperature. Previously, Noggle et al. (Biochim. Biophys. Acta (1982) 691, 240-248) had investigated these lipids and had concluded on the basis of electron microscopy that the lipids were in a lamellar state above the transition temperature. However, they found the 31P-NMR signals were not characteristic of lamellar phases. It was, therefore, concluded that these lipids were yielding unexpected 31P-NMR spectra. The present X-ray results demonstrate that, in fact, the lipids are not in a lamellar state above the transition temperature and that the 31P-NMR and X-ray data are not necessarily in disagreement. Characteristics of the phases both above and below the chain melt temperature are discussed.


Subject(s)
Cholesterol/analogs & derivatives , Glycerophospholipids , Phosphatidic Acids , Phosphatidylglycerols , Lipid Bilayers , Magnetic Resonance Spectroscopy , Temperature , X-Ray Diffraction
16.
Biochim Biophys Acta ; 814(1): 135-40, 1985 Mar 28.
Article in English | MEDLINE | ID: mdl-3978097

ABSTRACT

Binding of pig pancreatic phospholipase A2 to ternary codispersions of diacylphosphatidylcholine/lysophosphatidylcholine/fatty acid (100:22:22, mole ratio) is monitored by the increase in intrinsic fluorescence intensity of the single tryptophan residue. The fluorescence is quenched by the brominated fatty acid components in the ternary codispersions. The quenching efficiency is in the order: 11,12-dibromo- greater than 9,10-dibromo- greater than 6,7-dibromo- greater than 2-bromo fatty acid. The quenching efficiency of the 9,10-brominated derivatives of the three components in the ternary codispersions is in the order diacylphosphatidylcholine greater than fatty acid greater than lysophosphatidylcholine. Two isomers of diacylphosphatidylcholine with 9,10-dibromo substituents on chain 1 or 2 are equally efficient quenchers. While succinimide also quenches the fluorescence of the free and the membrane bound enzyme, the tryptophan residue in both systems is not accessible to 1-methylnicotinamide. These results are rationalized by a hypothesis that the acyl chains of the substrate interacts with the tryptophan residue of pig pancreatic phospholipase A2, which is readily accessible to water soluble neutral quenchers both in the free and the bound state.


Subject(s)
Lipid Bilayers/metabolism , Pancreas/enzymology , Phospholipases A/metabolism , Phospholipases/metabolism , Tryptophan , Animals , Fluorescence , Isomerism , Phospholipases A2 , Swine
17.
Biochim Biophys Acta ; 814(2): 313-8, 1985 Apr 11.
Article in English | MEDLINE | ID: mdl-3978105

ABSTRACT

Action of pig pancreatic phospholipase A2 on the ternary codispersions of diacylphosphatidylcholine, 1-acyllysophosphatidylcholine and fatty acids is examined. The binding and kinetic constants are found to be the same under a variety of conditions. These parameters and the catalytic turnover number change with the phase-transition temperature of the ternary codispersions, and optimal binding, kinetic and catalytic constants are seen in the phase-transition range where an equilibrium exists between laterally separated phases. The effect of changing the structure of any of the three components is also via a change in the phase-transition temperature of their ternary codispersions. These observations suggest that the binding of pig pancreatic phospholipase A2 to the defect sites on the substrate interface determines the substrate concentration dependence of the initial rate of hydrolysis, and the catalytic turnover by the bound enzyme also depends upon the phase state of the bilayer. An additive-induced stabilization of the defects in the substrate bilayer is postulated to account for the enhanced binding of the enzyme to the bilayer.


Subject(s)
Fatty Acids/pharmacology , Lipid Bilayers/metabolism , Phospholipases A/metabolism , Phospholipases/metabolism , Phospholipids/metabolism , Animals , Chemical Phenomena , Chemistry, Physical , Kinetics , Lysophospholipids , Pancreas/enzymology , Phospholipases A2 , Swine
18.
Biochim Biophys Acta ; 814(2): 319-26, 1985 Apr 11.
Article in English | MEDLINE | ID: mdl-3978106

ABSTRACT

Action of several solutes on the kinetics of phospholipase-A2-catalyzed hydrolysis of the ternary codispersions containing dimyristoylphosphatidylcholine + 1-palmitoyllysophosphatidylcholine + palmitic acid is examined. The kinetics of hydrolysis is interpreted in terms of the ability of the enzyme to bind to the substrate interface. The inhibitory effect of these solutes is correlated with their ability to modify fluorescence intensity of the bound enzyme, to modify the phase-transition profile, and to inhibit aggregation/fusion of the ternary codispersions. Based on these observations, it is suggested that the solutes like n-alkanols, ketamine, alphadolone, alphaxalone, flufenamic acid, tobramycin, mepacrine, EMD 21657 and U-10029A modulate the phase equilibria in the codispersions and thus noncompetitively inhibit the phospholipase action. Inhibition by feverfew extract (Tanacetum parthemium) is also by a similar mechanism. Lipid-soluble drugs as indomethacin had little effect on the kinetics of hydrolysis. All these inhibitors decrease the total extent of hydrolysis of the available substrate. However, none of these inhibitors have any effect on the hydrolysis of monomeric substrate or on the inactivation of the phospholipase A2 by p-bromophenacylbromide. These observations suggest that all these inhibitors do not interact directly with the catalytic site of the free or the bound enzyme, and their effect is primarily on the enzyme-binding sites on the substrate vesicle, that is, by perturbation of lipid-protein interaction.


Subject(s)
Lipid Bilayers/metabolism , Phospholipases A/metabolism , Phospholipases/metabolism , 1-Octanol , Animals , Hexanols/pharmacology , Hydrolysis , Kinetics , Octanols/pharmacology , Pancreas/enzymology , Phospholipases A/antagonists & inhibitors , Phospholipases A2 , Plants, Medicinal , Propanolamines/pharmacology , Sesquiterpenes/pharmacology , Solutions , Swine , Tanacetum parthenium
19.
Biochim Biophys Acta ; 905(1): 1-8, 1987 Nov 27.
Article in English | MEDLINE | ID: mdl-3676302

ABSTRACT

A novel method is described to demonstrate inaccessibility to the bulk aqueous phase of the microinterface between pig pancreatic phospholipase A2 and lipid bilayers to which this protein is bound. The method is based on the fact that the fluorescence emission quantum yields of the tryptophan residue of the protein and of a 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) chromophore attached to a lipid are lower in water as compared to that in deuterated water. The fluorescence emission quantum yield of these chromophores is measured in water and in deuterated water under conditions where the protein is either bound or not bound to the surface of a lipid bilayer containing the dansyl chromophore. Under conditions where the protein is tightly bound to the surface of the bilayer, desolvation of both fluorophores abolishes the observed effect of deuterated water. The tryptophan residue in the bound phospholipase A2 also becomes inaccessible to fluorescence quenching by acrylamide or succinimide. Desolvation of the microinterface is observed only under conditions that are significant for the catalytic action of phospholipase A2 in the scooting mode and not in the hopping mode. Also, under similar conditions, binding of pro-phospholipase A2 to anionic vesicles does not cause dehydration of the microinterface. The mechanistic significance of these observations for lipid-protein interactions, in general, and for interfacial catalysis and interfacial activation, in particular, is discussed.


Subject(s)
Lipid Bilayers/metabolism , Phospholipases A/metabolism , Phospholipases/metabolism , Animals , Fluorescence , Phospholipases A2 , Protein Binding , Swine , Tryptophan
20.
Biochim Biophys Acta ; 980(1): 15-22, 1989 Mar 27.
Article in English | MEDLINE | ID: mdl-2923894

ABSTRACT

Fluorescence emission properties of a cationic indodicarbocyanine dye, NK-529, bound to anionic and zwitterionic vesicles, are examined under a variety of conditions to monitor lateral distribution of anionic amphiphiles in bilayers as a function of their phase properties. The change in the fluorescence properties of NK-529 arises from the binding of the dye to the bilayer that is dominated by ionic interactions when possible, as well as from the self-quenching of the dye bound to bilayers when the surface density of the dye is high. The binding affinity of the dye to anionic interfaces is more than 100-fold higher compared to that in zwitterionic bilayers. The limiting phospholipid/dye ratio in anionic bilayers at low vesicle concentrations is about 3. Thus the density of the bound dye in anionic bilayers can be more than 40-fold higher than that in zwitterionic bilayers, and therefore under such conditions the bound dye is completely self-quenched in vesicles or micelles of anionic phospholipids. The change in the fluorescence emission intensity on incorporation of anionic amphiphiles in zwitterionic bilayers is used to monitor segregation of the anionic amphiphiles. The organizational features of bilayers that cause a change in the fluorescence properties of bound NK-529 show that the lateral distribution of anionic amphiphiles is appreciably influenced not only by the mole fraction of the amphiphile but also in the presence of other additives, and by the gel-fluid thermotropic transition. As shown in the following paper, the fluorescence changes related to self-quenching in anionic bilayers containing NK-529 can be used to understand the organizational changes that occur during the course of interfacial catalysis by phospholipase A2 on zwitterionic bilayers.


Subject(s)
Anions/analysis , Carbocyanines/metabolism , Glycerophospholipids , Lipid Bilayers/analysis , Phospholipids/analysis , Quinolines/metabolism , Cations , Dimyristoylphosphatidylcholine/metabolism , Fluorescent Dyes , Hot Temperature , Lipid Bilayers/metabolism , Liposomes/analysis , Liposomes/metabolism , Micelles , Phosphatidic Acids/metabolism , Phospholipids/metabolism , Salts/pharmacology , Solubility , Spectrometry, Fluorescence , Water
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