Studies on IL-18 in HIV infection : effects of the cytokine on intestinal integrity, and platelets as a new source of the cytokine

L'interleukine IL-18 (IL-18), un membre de la famille de l’IL-1, est une cytokine pro-inflammatoire multifonctionnelle. Elle est produite par les monocytes, les macrophages, les cellules dendritiques, les cellules épithéliales, les kératinocytes et le cortex surrénal dans le corps humain. Cette cytokine est d'abord produite comme une protéine précurseure inactive, qui est par la suite clivée en une forme mature par la caspase-1 activée. La caspase, en elle-même, existe comme précurseur inactif dans les cellules humaines et requiert l'assemblage d'inflammasomes pour son activation. L'IL-18 pour joue un rôle clé dans la médiation des conditions inflammatoires. Notre laboratoire et d'autres ont montré que l'infection par le VIH est accompagnée d'une augmentation des taux circulants d'IL-18 avec une diminution des niveaux de son antagoniste, l'interleukine-18 binding protein (IL-18BP). Dans cette thèse, nous démontrons pour que l'IL-18 est également produite et sécrétée par les plaquettes humaines lors de leur activation. Les plaquettes contiennent des composants de l'inflammasome. Ils assemblent et activent la caspase-1, qui ensuite traite le précurseur de l'IL-18 dans sa forme mature au cours du processus d'activation des plaquettes. La cytokine est synthétisée de novo lors de l'activation des plaquettes. Contrairement à l'IL-18, les plaquettes expriment constitutivement l’IL-18BP, et la libèrent de manière constitutive, ainsi que lors de l'activation. L'IL-18 et l'IL-18BP sont colocalisés avec CD63, un marqueur pour les granules α des plaquettes. L'IL-18 libéré des plaquettes constitue la source principale de cette cytokine dans la circulation humaine chez les individus sains. Nous avons identifié des concentrations faibles de cette cytokine dans les lysats de plaquettes chez les individus infectés par le VIH par rapport à ceux en santé. D'autre part, les concentrations ont été augmentées dans le sérum et le plasma pauvre en plaquettes chez les individus infectés. Des résultats similaires ont été obtenus avec l'IL-18BP dans les lysats de plaquettes d'individus sains et infectés par le VIH. Cependant, des quantités plus faibles de cet antagoniste ont été trouvées dans le sérum et le plasma pauvre en plaquettes d'individus infectés par le VIH par rapport à ceux en santé. Nos résultats ont des implications importantes pour les maladies inflammatoires chroniques dans laquelle une activité accrue de l'IL-18 joue un rôle pathogène. Le VIH est également accompagné par une inflammation intestinale et une diminution de l'intégrité intestinale, mesurée par la réparation de la muqueuse, la régénération et la perméabilité. Cependant, on en sait peu sur la relation entre le niveau élevé de l'IL-18 associé à l'infection au VIH et la perméabilité intestinale: ceci n'a jamais été étudié. Dans cette thèse, nous démontrons le rôle du virus et sa protéine Tat à augmenter la production d'IL-18 chez deux lignées de cellules épithéliales intestinales (HT29 et Caco2) ainsi qu'une diminution de l'IL-18BP. L'IL-18 induit une hyperperméabilité de la barrière épithéliale en perturbant à la fois les jonctions serrées et adhérentes, et ce, en modulant l'expression et la distribution de l'occludine, de claudine-2 et de la bêta-caténine. Une désorganisation de l'actine F a également été observée dans les cellules lors de l'incubation avec l'IL-18. Les mêmes observations ont été faites avec la protéine Tat du VIH-1. Après une incubation prolongée, l'IL-18 a causé la mort des cellules intestinales et induit l'apoptose par l'activation de la caspase-1 et la caspase-3. Fait intéressant, les taux plasmatiques de lipopolysaccharides chez trois catégories différentes de patients au VIH (ART-naïf, ART-traitée et contrôleurs élite) sont en corrélation avec les niveaux plasmatiques de l'IL-18. Enfin, nous avons étudié la voie de signalisation à travers laquelle l'IL-18 induit une perméabilité intestinale accrue. En bref, nos études identifient les plaquettes comme une source importante d'IL-18, et leur activation lors d'une infection à VIH contribue à des concentrations accrues de cette cytokine. Le virus entraine également l'augmentation de la production de cytokines par les cellules épithéliales intestinales. L'activité biologique accrue de ces cytokines contribue à la pathogenèse du sida en augmentant la perméabilité intestinale et en causant la mort des cellules intestinales. L'IL-18 pourrait servir de cible moléculaire pour retarder la progression du sida et réduire l'inflammation chronique dans un stade précoce d'une infection à VIH.

Studies on the Synthesis and Transformations of A Few Dibenzoylalkene – Type Systems

The aim of the study is to synthesise several dibenzoylakene-type systems such as acenaphthenone-2-ylidene ketones 47 and phenanthrenone-9-ylidene ketones 48 by the condensation reaction of acenaphthenequinone and phenanthrenequinone with methyl ketones. Here studies the thermal and photochemical transformations of acenaphthaenone-2-ylidene ketones 3a-c.These acenaphthenone –2-ylidene ketones underwent extensive decomposition on heating. The objectives of present study is to synthesise acenaphthenone-2-ylidene ketones by the Claisen-Schmidt condensation of acenaphthenequinone and methyl ketones, it is to synthesise phenanthrenone –9-ylidene ketones by the Claisen-Schmidt condensation of phenanthrequinone and methyl ketones, thermal studies on acenaphthenone-2-ylidene ketones and phenanthrenone-9-ylidene ketones, photochemical studies on acenaphthenone-2-ylidene ketones and phenanthrenone –9-ylidene ketones to establish the generality of dibenzoyalkene rearrangement. Cyclic voltammetric studies on these dibezoyalkenes to compare their redox behaviour with that of the cis and trans isomers of dibenzoyl-ethylene, dibenzoylstilbene. These results should provide some information about their reactivity, and to assess and exploit the potential of these systems as quinonemethides. This study conclude that a number of new dibenzolalkene-type systems have been synthesized by the Claisen-Schmidt condensation of 1,2-diketones such as phenanthequinone and acenaphthenequinone with methyl ketones. Some of these compounds have been shown to undergo interesting photochemical transformations. Based on the results it is conclude that phenanthjrenone-9-ylidene ketones are excellent Michael acceptors. Methanol adds to these to yield the corresponding furanols. These furanols are unstable and are slowly converted to phenanthro-2 (3H)-furanones.

Studies On Supported Cobalt (Ii), Nickel (Ii) and Copper (Ii) Complexes Of O-Phenylenediamine and Schiff Bases Derived from 3-Hydroxyquinoxaline-2-Carboxaldehyde

The thesis deals with the synthesis, characterization and catalytic activity studies of supported cobalt(ii), nickel(II) and copper(II) complexes of O-phenylenediamine and Schiff bases derived from 3-hydroxyquinoxaline -2-carboxaldehyde. Zeolite encapsulation and polymer anchoring was employed for supporting the complexes. The characterization techniques proved that the encapsulation as well as polymer supporting has been successfully achieved. The catalytic activity studies revealed that the activities of the simple complexes are improved upon encapsulation. Various characterization techniques are used such as, chemical analysis, EPR, magnetic measurements, FTIR studies, thermal analysis, electronic spectra, XRD, SEM, surface area, and GC.The present study indicated that the that the mechanism of oxidation of catechol and DTBC by hydrogen peroxide is not altered by the change in the coordination sphere around the metal ion due to encapsulation. This fact suggests outer sphere mechanism for the reactions. The catalytic activity by zeolite encapsulated complex was found to be slower than that by the neat complex. The slowing down of the reaction in the zeolite case is probably due to the constraint imposed by the zeolite framework. The rate of DTBC ( 3,5-di-tert-butylchatechol)oxidation was found to be greater than the rate of catechol oxidation. This is obviously due to the presence of electron donating tertiary butyl groups.

Studies on the Antiulcerogenic and Antihepatotoxic Potential of Chitosan and Glucosamine in Experimental Rats

The present study examined the antiulcer effect of glucosamine on mucosal antioxidant defense system in ibuprofen-induced peptic ulcer in male albino rats. The results of the present study indicate that the pre-oral administration of chitosan and glucosamine maintain near to the normal status the activities of the mucosal antioxidant enzymes and the level of GSH (Glutathione), which protect mucosa against oxidative damage by decreasing the lipid peroxidation and strengthening the mucosal barrier, and which are the first line of defense against exogenous ulcerogenic agents. In this study indicate that the oral pre-treatment of chitosan and glucosamine can prevent ibuprofen-induced peptic ulcer in rats.This study can be concluded that co-administration of chitsosan and glucosamine can effectively prevent the isonized and rifampicin induced hepatotoxicity in rats.Comparatively, chitosan was found to have better results than glucosamine in alleviating the hepatic disorders.

Studies on Rubber Composition as Passive Acoustic Materials in Underwater Electro Acoustic Tranducer Technology and Their aging Characteristic

The research work has been in the area of compounding and characterization of rubbers for use in under water electro acoustic transducers. The study also covers specific material system such as encapsulation materials, baffle material, seal material, etc. Life prediction techniques of under water rubbers in general have been established with reference to more than one functional property. Ranges of passive materials, besides the active sensing material go into the construction of underwater electro acoustic transducers. Reliability of the transducer is critically dependent on these passive materials. Rubbers are a major class of passive materials. The present work concentrates on these materials. Conventional rubbers are inadequate to meet many of the stringent function specific requirements. There exists a large gap of information in the rubber technology of underwater rubbers, particularly relating to underwater electro acoustic transducers. This study is towards filling up the gaps of information in this crucial area. Water intake into rubber is considered as the single most important issue for the long-term performance of rubbers, especially Neoprene. In this study, the cause and effects of a range of parameters affecting the water absorption by diffusion and permeation have been investigated.

Studies on the Role of Sediments on the Nutrient Dynamics and Fertility of Kuttanad Waters

In the present study the nutrient dynamics and fertility of Kuttanad waters is addressed. Kuttanad represent a wetland system with considerable agricultural activities. The hydrographical features of the Kuttanad waters are controlled by discharges from Manimala, Meenachil, Pamba, Achencoil and Muvattupuzha rivers and also by tidal intrusions of saline waters from Cochin backwaters during summers. The fertility of these water bodies were significantly high and supported good agricultural production. Kuttanad water forms the southern part of this aquatic systems and is considered as the most productive zones. As a part of the management scheme for a higher agricultural activity, the Thannermukkam bund was constructed to block and regulate the intrusion of saline water. The increased use of artificial fertilizers along with stagnant character of the water body in this area has resulted in sharp decline in the water quality, productivity and aquatic resources.

Studies on Ilmenite of Chavara and Manavalakurichi Deposites, Southwest Coast of India

The present work attempts to trace the variation in the physical and chemical behavior of ilmenite, since its release from country rocks and subsequent transportation to the coast through the progressive weathering environments of laterite, sedimentary rocks, rivers and estuarine systems. Since the hinterland of the study area consists of crystalline and sedimentary rocks and their weathered forms (laterites), the contribution of each lithological system to the beach placer is attempted. The results of the study show that the most magnetic fraction contains more content of altered phases than the relatively unweathered fractions. The fractions separated above 0.35A define a high grade of ilmenite ore enriched in Ti content. The lattice volume generally decreases with alteration. The magnetic studies revels that the Chavara ilmenite are found to be made up to low magnetic crops with about 46% of the bulk ilmenite constituted by fractions separated at above 0.35A. In the Manavalakurichi ilmenite on the other hand, around 91% of the beach ilmenite is made of fractions separated at or below 0.3A

STUDIES ON THE QUALITY AND PROCESS CONTROL FACTORS DURING THE PRODUCTION AND STORAGE OF SALTED DRIED FISH PRODUCTS

In this study the quality and process control factors during the production and storage of salted dried fish products. The study reveals that quantity of dry fish production in the state is decreasing and dry fish processing industry should be encouraged by central and state governments. The dry and wet salting may be carried out to a period of 4 to 8 hours respectively and time may depend on temperature, size, and concentration of medium. Demand is an unavoidable factor for sale of fish. The packed dry salted lots kept at room temperature are useful only for 20 days. The refrigerator- stored lots had more storage life and nutritional content are good up to 3 months. The cold storage stored dry salted lot had more storage life than the wet salted lot. The use of preservatives in salting is encouraged to reduce pH. The low temperature preservation maintains the nutritional value and quality for long period. It further encourages the labeling of nutritional value of dry fish as in tinned products.

STUDIES ON THE STRESS FLUCTUATIONS IN SHEARED STOKESIAN SUSPENSIONS USING CHAOS THEORY AND NONLINEAR DYNAMICS

The thesis report results obtained from a detailed analysis of the fluctuations of the rheological parameters viz. shear and normal stresses, simulated by means of the Stokesian Dynamics method, of a macroscopically homogeneous sheared suspension of neutrally buoyant non-Brownian suspension of identical spheres in the Couette gap between two parallel walls in the limit of vanishingly small Reynolds numbers using the tools of non-linear dynamics and chaos theory for a range of particle concentration and Couette gaps. The thesis used the tools of nonlinear dynamics and chaos theory viz. average mutual information, space-time separation plots, visual recurrence analysis, principal component analysis, false nearest-neighbor technique, correlation integrals, computation of Lyapunov exponents for a range of area fraction of particles and for different Couette gaps. The thesis observed that one stress component can be predicted using another stress component at the same area fraction. This implies a type of synchronization of one stress component with another stress component. This finding suggests us to further analysis of the synchronization of stress components with another stress component at the same or different area fraction of particles. The different model equations of stress components for different area fraction of particles hints at the possible existence a general formula for stress fluctuations with area fraction of particle as a parameter

Studies on the Synthesis and Transformations of a Few 2(3H)- and 3(2H)-Furanones

The thesis entitled studies on the synthesis and transformations of a few 2(3H)- and 3(2H)- furanones. Furanones represent an interesting class of heterocyclic compounds, which constitute the central ring system of many natural products. The derivatives of furan is divided, depending on their structure 2(3H)-furanones(I), 2(5H)-furanones(II), and 3(2H)-furanones(III). Systems I&II are unsatured gama lactones known as ‘butenolides’. Compounds of this type also known as ‘crotonolactones’ based on the parent crotonic acid. In conclusion a number of 2(3H)-and 3(2H)- furanones were synthesized from dibenzoylalkene precursors and were characterized on the basis of spectral analytical and X-ray data. On direct irradiation 3,3-bis(4-chloropheneyl)-5-aryl-3H-furan -2-ones underwent decarbonylation to yield the corresponding alpha, beta- unsaturated carbonyl compounds and upon sensitized irradiation they underwent dimersation arising through a 2+2 cycloaddition reaction. Our studies on 3(2H)-furanones revealed that these compounds are thermally stable, while they undergo extensive decomposition to intractable mixtures under the influence of light. Similarly, the novel dibenzoylalkenes- type systems containing hetroatomatic rings synthesized by us also underwent extensive decomposition under the influence of heat. Some of the 3(2H)-furanones synthesized by us exhibit remarkable anti-proliferative activity.

Studies on the Nature and Chemistry of Sediments and Water of Periyar and Chalakudy Rivers, Kerala, India

The present study is an attempt to address issues related to sediment properties like texture, mineralogy and geochemistry as well as water quality of two important rivers of central Kerala-the Periyar and the Chalakudy rivers. The main objectives of the study are to investigate the textural and mineralogical characteristics as well as transportation and depositional mechanisms of the sediments of Periyar and Chalakudy rivers, to find out the geochemical variability of organic carbon, phosphorus and certain major (Na,K,Ca and Mg) and minor/trace(Mn,Pb,Ni,Cr, and Zn) elements in the bulk sediments and mud fraction of these rivers, to evaluate the status of heavy metal pollution registered in the sediments of these rivers, to assess the physico-chemical characteristics and water quality of Periyar and Chalakudy rivers and to estimate the dissolved nutrient flux through the Periyar and Chalakudy rivers into the receiving coastal waters. The granulometric characteristics as well as statistical parameters of the sediments of Periyar and Chalakudy rivers depend on the flow pattern controlled by the gradient of the terrain. Compared to Periyar, fluctuations in the dispersal of particles are more in Chalakudy river. In Periyar river, the P and Fe in bulk sediments show a positive correlation with C-org, while in Chalakudy river, both the elements are related to THM concentration. In general, C-org, Fe and P Shows an increasing trend downstream. In Periyar river, the P and Fe in bulk sediments show a positive correlation with C-org, while in Chalakudy river, both the elements are related to THM concentration. Among these two rivers, the pollution of water is several fold higher in Periyar river due to influx due to influx of considerable quantity of liquid and solid wastes of industrial/domestic/urban origin. Nutrient analysis reveals 2-3 times increase in N and P during monsoon season whereas SiO2-Si shows a decreasing trend.

Studies on the Dielectric Properties of Poly (o-toluidine) and Poly(o-toluidine-aniline) Copolymer

Poly(o-toluidine) (PoT) and poly(o-toluidine co aniline) were prepared by using ammonium persulfate initiator, in the presence of 1M HCI. It was dried under different conditions: room temperature drying (48 h), oven drying (at 50°C for 12 h), or vacuum drying (under vacuum, at room temperature for 16 h). The dielectric properties, such as dielectric loss, conductivity, dielectric constant, dielectric heating coefficient, loss tangent, etc., were studied at microwave frequencies. A cavity perturbation technique was used for the study. The dielectric properties were found to be related to the frequency and drying conditions. Also, the copolymer showed better properties compared to PoT alone.

STUDIES ON THE DIELECTRIC BEHAVIOUR OF POLYPYRROLE AND ITS COMPOSITES WITH POLY (VINYL CHLORIDE)

Polypyrrole/poly (vinyl chloride) semi-interpenenzrtirtg networks of different compositions are prepared using anunonitun per sulfate initiator at room temperature in pellet.form and lilrrt form and their dielectric properties are studied at different microwave frequencies. An HP 8510 Vector network analyzer interfaced with a computer is used. The cavity-perturbation technique is employed for the study

Studies on Thermoplastic Elastomer Based on Linear Low-Density Polyethylene and Latex Product Waste Modified with Thiocarbanilide

Latex waste like glove waste was effectively modified using a new reclaiming agent, thiocarbanilide. This modified waste was blended with linear low-density polyethylene (LLDPE) to develop a novel thermoplastic elastomer. Both uncrosslinked and dynamically crosslinked blends were prepared and their properties were studied. The results were found to be comparable to those of conventional thermoplastic elastomers.