GABA, serotonin, muscarinic receptors - their second messengers and transcription factors functional regulation in the brain regions of hypoxic neonatal rats: Resuscitation with glucose, oxygen and epinephrine

The present study was designed to investigate the protective effect of glucose, oxygen and epinephrine resuscitation on impairment in the functional role of GABAergic, serotonergic, muscarinic receptors, PLC, BAX, SOD, CAT and GPx expression in the brain regions of hypoxia induced neonatal rats. Also, the role of hormones - Triiodothyronine (T3) and insulin, second messengers – cAMP, cGMP and IP3 and transcription factors – HIF and CREB in the regulation of neonatal hypoxia and its resuscitation methods were studied. Behavioural studies were conducted to evaluate the motor function and cognitive deficit in one month old control and experimental rats. The efficient and timely supplementation of glucose plays a crucial role in correcting the molecular changes due to hypoxia, oxygen and epinephrine. The sequence of glucose, epinephrine and oxygen administration at the molecular level is an important aspect of the study. The additive neuronal damage effect due to oxygen and epinephrine treatment is another important observation. The corrective measures by initial supply of glucose to hypoxic neonatal rats showed from the molecular study when brought to practice will lead to healthy intellectual capacity during the later developmental stages, which has immense clinical significance in neonatal care.

Adrenergic and Glutamergic Receptor Gene Expression and Their Functional regulation in the Cerebral Cortex of Hypoxia Induced Neonatal Rats:Role of Oxygen,Epinephrine and Glucose Supplementation

In the present work, the role of oxygen, epinephrine and glucose supplementation in regulating neurotransmitter contents, adrenergic and glutamate receptor binding parameters in the cerebral cortex of experimental groups of neonatal rats were investigated. The study of neurotransmitters and their receptors in the cerebral cortex and the EEG pattern in the brain regions of neonatal rats were taken as index for brain damage due to hypoxia, oxygen and epinephrine. Real-Time PCR work was done to confirm the binding parameters. Second messenger, cyclic Adenosine Monophosphate (cAMP) was assayed to find the functional correlation of the receptors. Behavioural studies were carried out to confirm the biochemical and molecular studies. The efficient and timely supplementation of glucose plays a crucial role in correcting the molecular changes due to hypoxia, oxygen and epinephrine. The addictive neuronal damage effect due to oxygen and epinephrine treatment is another important observation. The corrective measures from the molecular study brought to practice will lead to maintain healthy intellectual capacity during the later developmental stages, which has immense clinical significance in neonatal care.

Decreased (x1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

purpose of this study was to investigate the role of brain al-adrenergic receptor binding in the rat model of pancreatic regeneration using 60-70% pancre:dectorny. The a, -adrenergic receptors kinetics was studied in the cerebral cor:cx and brain stem of sham operated . 72 It pan- crea(ectoinised and 7 days pancreatectomised rats. Scar chard analysis with I `I I lprazocin in cerebral cartes and brain stein showed a significant decrease (/' < 0.01). (P < 0.05) in maximal binding ( 1),,,,,) with it significant decrease (P < 0.001 ), ( P < 0.01) in the K,,in 72 It pancreatecto- raised rats compared with sham , respectively . Competition analysis in cerebral cortex and brain stem showed it shift in affinity during pancreatic regeneration . The sympathetic activity was decreased as indicated by the significantly de- increased norepinephrine level in the plasma (P < 0.001), cerebral cortex (P < 0.01) and brain stem (P < 0.001) of 72 h pancreatectomised rats compared to sham . Thus, from our results it is suggested that the central a, -adrenergic receptors have a functional role in the pancreatic regenera- Lion mediated through the sympathetic pathway.

GABAA and GABAB Receptor Gene Expression and Functional Regulation During Pancreatic Regeneration and Insulin Secretion in Rats

The present study demonstrate the functional alterations of the GABAA and GABAB receptors and the gene expression during the regeneration of pancreas following partial pancreatectomy. The role of these receptors in insulin secretion and pancreatic DNA synthesis using the specific agonists and antagonists also are studied in vitro. The alterations of GABAA and GABAR receptor function and gene expression in the brain stem, crebellum and hypothalamus play an important role in the sympathetic regulation of insulin secretion during pancreatic regeneration. Previous studies have given much information linking functional interaction between GABA and the peripheral nervous system. The involvement of specific receptor subtypes functional regulation during pancreatic regeneration has not given emphasis and research in this area seems to be scarce. We have observed a decreased GABA content, down regulation of GABAA receptors and an up regulation of GABAB receptors in the cerebral cortex, brain stem and hypothalamus. Real Time-PCR analysis confirmed the receptor data in the brain regions. These alterations in the GABAA and GABAB receptors of the brain are suggested to govern the regenerative response and growth regulation of the pancreas through sympathetic innervation. In addition, receptor binding studies and Real Time-PCR analysis revealed that during pancreatic regeneration GABAA receptors were down regulated and GABAB receptors were up regulated in pancreatic islets. This suggests an inhibitory role for GABAA receptors in islet cell proliferation i.e., the down regulation of this receptor facilitates proliferation. Insulin secretion study during 1 hour showed GABA has inhibited the insulin secretion in a dose dependent manner in normal and hyperglycaemic conditions. Bicuculline did not antagonize this effect. GABAA agonist, muscimol inhibited glucose stimulated insulin secretion from pancreatic islets except in the lowest concentration of 1O-9M in presence of 4mM glucose.Musclmol enhanced insulin secretion at 10-7 and 10-4M muscimol in presence of 20mM glucose- 4mM glucose represents normal and 20mM represent hyperglycaemic conditions. GABAB agonist, baclofen also inhibited glucose induced insulin secretion and enhanced at the concentration of 1O-5M at 4mM glucose and at 10-9M baclofen in presence of 20mM glucose. This shows a differential control of the GABAA and GABAB receptors over insulin release from the pancreatic islets. During 24 hours in vitro insulin secretion study it showed that low concentration of GABA has inhibited glucose stimulated insulin secretion from pancreatic islets. Muscimol, the GABAA agonist, inhibited the insulin secretion but, gave an enhanced secretion of insulin in presence of 4mM glucose at 10-7 , 10-5 and 1O-4M muscimol. But in presence of 20mM glucose muscimol significantly inhibited the insulin secretion. GABAB agonist, baclofen also inhibited glucose induced insulin secretion in presence of both 4mM and 20mM glucose. This shows the inhibitory role of GABA and its specific receptor subtypes over insulin synthesis from pancreatic bete-islets. In vitro DNA synthesis studies showed that activation of GABAA receptor by adding muscimol, a specific agonist, inhibited islet DNA synthesis. Also, the addition of baclofen, a specific agonist of GABAB receptor resulted in the stimulation of DNA synthesis.Thus the brain and pancreatic GABAA and GABAB receptor gene expression differentially regulates pancreatic insulin secretion and islet cell proliferation during pancreatic regeneration. This will have immense clinical significance in therapeutic applications in the management of Diabetes mellitus.

Dopamine Receptor Subtypes,IP3, cAMP and cGMP Functional Regulation in Parkinsonism Induced by Unilateral Infusion of Rotenone in Rats: Recovery with Bone Marrow Cells,Serotonin and GABA Supplementation

In the present study, the effects of 5-HT, GABA and Bone Marrow Cells infused intranigrally to substantia nigra individually and in combinations on unilateral rotenone infused Parkinsonism induced rats. Scatchard analysis of DA, DA D1 and D2 receptors in the corpus striatum, cerebral cortex, cerebellum, brain stem and hippocampus showed a significant increase in the Brain regions of rotenone infused rat compared to control. Real Time PCR amplification of DA D1, D2, Bax and ubiquitin carboxy-terminal hydrolase were up regulated in the brain regions of rotenone infused rats compared to control. Gene expression studies of -Synuclien, cGMP and Cyclic AMP response element-binding protein showed a significant down regulation in Rotenone infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies.Our study demonstrated that BMC administration alone cannot reverse the above said molecular changes occurring in PD rat. 5-HT and GABA acting through their specific receptors in combination with bone marrow cells play a crucial role in the functional recovery of PD rats. 5-HT, GABA and Bone marrow cells treated PD rats showed significant reversal to control in DA receptor binding and gene expression. 5-HT and GABA have co-mitogenic property. Proliferation and differentiation of cells re-establishing the connections in Parkinson's disease facilitates the functional recovery. Thus, it is evident that 5-HT and GABA along with BMC to rotenone infused rats renders protection against oxidative, related motor and cognitive deficits which makes them clinically significant for cellbased therapy. The BMC transformed to neurons when co-transplanted with 5-HT and GABA which was confirmed with PKH2GL and nestin. These newly formed neurons have functional significance in the therapeutic recovery of Parkinson’s disease.

Muscarinic M1 and M3 Receptors,IP3 and cGMP Functional Regulation in Streptozotocin Induced Diabetic Rats: Insulin and Somatotropin Induced Rejuvenation as a Function of Age

The present study describes that acetylcholine through muscarinic Ml and M3 receptors play an important role in the brain function during diabetes as a function of age. Cholinergic activity as indicated by acetylcholine esterase, a marker for cholinergic function, decreased in the brain regions - the cerebral cortex, brainstem and corpus striatum of old rats compared to young rats. in diabetic condition, it was increased in both young and old rats in cerebral cortex, and corpus striatum while in brainstem it was decreased. The functional changes in the muscarinic receptors were studied in the brain regions and it showed that muscarinic M I receptors of old rats were down regulated in cerebral cortex while in corpus striatum and brainstem it was up regulated. Muscarinic M3 receptors of old rats showed no significant change in cerebral cortex while in corpus striatum and brainstem muscarinic receptors were down regulated. During diabetes, muscarinic M I receptors were down regulated in cerebral cortex and brainstem of young rats while in corpus striatum they were up regulated. In old rats, M I receptors were up regulated in cerebral cortex, corpus striatum and in brainstem they were down regulated. Muscarinic M3 receptors were up regulated in cerebral cortex and brainstem of young rats while in corpus striatum they were down regulated. In old rats, muscarinic M l receptors were up regulated in cerebral cortex, corpus striatum and brainstem. In insulin treated diabetic rats the activity of the receptors were reversed to near control. Pancreatic muscarinic M3 receptor activity increased in the pancreas of both young and old rats during diabetes. In vitro studies using carbachol and antagonists for muscarinic Ml and M3 receptor subtypes confirmed the specific receptor mediated neurotransmitter changes during diabetes. Calcium imaging studies revealed muscarinic M I mediated Ca2 + release from the pancreatic islet cells of young and old rats. Electrophysiological studies using EEG recording in young and old rats showed a brain activity difference during diabetes. Long term low dose STH and INS treated rat brain tissues were used for gene expression of muscarinic Ml, M3, glutamate NMDARl, mGlu-5,alpha2A, beta2, GABAAa1 and GABAB, DAD2 and 5-HT 2C receptors to observe the neurotransmitter receptor functional interrelationship for integrating memory, cognition and rejuvenating brain functions in young and old. Studies on neurotransmitter receptor interaction pathways and gene expression regulation by second messengers like IP3 and cGMP in turn will lead to the development of therapeutic agents to manage diabetes and brain activity.From this study it is suggested that functional improvement of muscarinic Ml, M3, glutamate NMDAR1, mGlu-5, alpha2A, beta2, GABAAa1 and GABAB, DAD2 and 5-HT 2C receptors mediated through IP3 and cGMP will lead to therapeutic applications in the management of diabetes. Also, our results from long term low dose STH and INS treatment showed rejuvenation of the brain function which has clinical significance in maintaining healthy period of life as a function of age.

Synthesis, Characterization and Applications of Modified TiO2 Systems

This thesis is divided in to 9 chapters and deals with the modification of TiO2 for various applications include photocatalysis, thermal reaction, photovoltaics and non-linear optics. Chapter 1 involves a brief introduction of the topic of study. An introduction to the applications of modified titania systems in various fields are discussed concisely. Scope and objectives of the present work are also discussed in this chapter. Chapter 2 explains the strategy adopted for the synthesis of metal, nonmetal co-doped TiO2 systems. Hydrothermal technique was employed for the preparation of the co-doped TiO2 system, where Ti[OCH(CH3)2]4, urea and metal nitrates were used as the sources for TiO2, N and metals respectively. In all the co-doped systems, urea to Ti[OCH(CH3)2]4 was taken in a 1:1 molar ratio and varied the concentration of metals. Five different co-doped catalytic systems and for each catalysts, three versions were prepared by varying the concentration of metals. A brief explanation of physico-chemical techniques used for the characterization of the material was also presented in this chapter. This includes X-ray Diffraction (XRD), Raman Spectroscopy, FTIR analysis, Thermo Gravimetric Analysis, Energy Dispersive X-ray Analysis (EDX), Scanning Electron Microscopy(SEM), UV-Visible Diffuse Reflectance Spectroscopy (UV-Vis DRS), Transmission Electron Microscopy (TEM), BET Surface Area Measurements and X-ray Photoelectron Spectroscopy (XPS). Chapter 3 contains the results and discussion of characterization techniques used for analyzing the prepared systems. Characterization is an inevitable part of materials research. Determination of physico-chemical properties of the prepared materials using suitable characterization techniques is very crucial to find its exact field of application. It is clear from the XRD pattern that photocatalytically active anatase phase dominates in the calcined samples with peaks at 2θ values around 25.4°, 38°, 48.1°, 55.2° and 62.7° corresponding to (101), (004), (200), (211) and (204) crystal planes (JCPDS 21-1272) respectively. But in the case of Pr-N-Ti sample, a new peak was observed at 2θ = 30.8° corresponding to the (121) plane of the polymorph brookite. There are no visible peaks corresponding to dopants, which may be due to their low concentration or it is an indication of the better dispersion of impurities in the TiO2. Crystallite size of the sample was calculated from Scherrer equation byusing full width at half maximum (FWHM) of the (101) peak of the anatase phase. Crystallite size of all the co-doped TiO2 was found to be lower than that of bare TiO2 which indicates that the doping of metal ions having higher ionic radius into the lattice of TiO2 causes some lattice distortion which suppress the growth of TiO2 nanoparticles. The structural identity of the prepared system obtained from XRD pattern is further confirmed by Raman spectra measurements. Anatase has six Raman active modes. Band gap of the co-doped system was calculated using Kubelka-Munk equation and that was found to be lower than pure TiO2. Stability of the prepared systems was understood from thermo gravimetric analysis. FT-IR was performed to understand the functional groups as well as to study the surface changes occurred during modification. EDX was used to determine the impurities present in the system. The EDX spectra of all the co-doped samples show signals directly related to the dopants. Spectra of all the co-doped systems contain O and Ti as the main components with low concentrations of doped elements. Morphologies of the prepared systems were obtained from SEM and TEM analysis. Average particle size of the systems was drawn from histogram data. Electronic structures of the samples were identified perfectly from XPS measurements. Chapter 4 describes the photocatalytic degradation of herbicides Atrazine and Metolachlor using metal, non-metal co-doped titania systems. The percentage of degradation was analyzed by HPLC technique. Parameters such as effect of different catalysts, effect of time, effect of catalysts amount and reusability studies were discussed. Chapter 5 deals with the photo-oxidation of some anthracene derivatives by co-doped catalytic systems. These anthracene derivatives come underthe category of polycyclic aromatic hydrocarbons (PAH). Due to the presence of stable benzene rings, most of the PAH show strong inhibition towards biological degradation and the common methods employed for their removal. According to environmental protection agency, most of the PAH are highly toxic in nature. TiO2 photochemistry has been extensively investigated as a method for the catalytic conversion of such organic compounds, highlighting the potential of thereof in the green chemistry. There are actually two methods for the removal of pollutants from the ecosystem. Complete mineralization is the one way to remove pollutants. Conversion of toxic compounds to another compound having toxicity less than the initial starting compound is the second way. Here in this chapter, we are concentrating on the second aspect. The catalysts used were Gd(1wt%)-N-Ti, Pd(1wt%)-N-Ti and Ag(1wt%)-N-Ti. Here we were very successfully converted all the PAH to anthraquinone, a compound having diverse applications in industrial as well as medical fields. Substitution of 10th position of desired PAH by phenyl ring reduces the feasibility of photo reaction and produced 9-hydroxy 9-phenyl anthrone (9H9PA) as an intermediate species. The products were separated and purified by column chromatography using 70:30 hexane/DCM mixtures as the mobile phase and the resultant products were characterized thoroughly by 1H NMR, IR spectroscopy and GCMS analysis. Chapter 6 elucidates the heterogeneous Suzuki coupling reaction by Cu/Pd bimetallic supported on TiO2. Sol-Gel followed by impregnation method was adopted for the synthesis of Cu/Pd-TiO2. The prepared system was characterized by XRD, TG-DTG, SEM, EDX, BET Surface area and XPS. The product was separated and purified by column chromatography using hexane as the mobile phase. Maximum isolated yield of biphenyl of around72% was obtained in DMF using Cu(2wt%)-Pd(4wt%)-Ti as the catalyst. In this reaction, effective solvent, base and catalyst were found to be DMF, K2CO3 and Cu(2wt%)-Pd(4wt%)-Ti respectively. Chapter 7 gives an idea about the photovoltaic (PV) applications of TiO2 based thin films. Due to energy crisis, the whole world is looking for a new sustainable energy source. Harnessing solar energy is one of the most promising ways to tackle this issue. The present dominant photovoltaic (PV) technologies are based on inorganic materials. But the high material, low power conversion efficiency and manufacturing cost limits its popularization. A lot of research has been conducted towards the development of low-cost PV technologies, of which organic photovoltaic (OPV) devices are one of the promising. Here two TiO2 thin films having different thickness were prepared by spin coating technique. The prepared films were characterized by XRD, AFM and conductivity measurements. The thickness of the films was measured by Stylus Profiler. This chapter mainly concentrated on the fabrication of an inverted hetero junction solar cell using conducting polymer MEH-PPV as photo active layer. Here TiO2 was used as the electron transport layer. Thin films of MEH-PPV were also prepared using spin coating technique. Two fullerene derivatives such as PCBM and ICBA were introduced into the device in order to improve the power conversion efficiency. Effective charge transfer between the conducting polymer and ICBA were understood from fluorescence quenching studies. The fabricated Inverted hetero junction exhibited maximum power conversion efficiency of 0.22% with ICBA as the acceptor molecule. Chapter 8 narrates the third order order nonlinear optical properties of bare and noble metal modified TiO2 thin films. Thin films were fabricatedby spray pyrolysis technique. Sol-Gel derived Ti[OCH(CH3)2]4 in CH3CH2OH/CH3COOH was used as the precursor for TiO2. The precursors used for Au, Ag and Pd were the aqueous solutions of HAuCl4, AgNO3 and Pd(NO3)2 respectively. The prepared films were characterized by XRD, SEM and EDX. The nonlinear optical properties of the prepared materials were investigated by Z-Scan technique comprising of Nd-YAG laser (532 nm,7 ns and10 Hz). The non-linear coefficients were obtained by fitting the experimental Z-Scan plot with the theoretical plots. Nonlinear absorption is a phenomenon defined as a nonlinear change (increase or decrease) in absorption with increasing of intensity. This can be mainly divided into two types: saturable absorption (SA) and reverse saturable absorption (RSA). Depending on the pump intensity and on the absorption cross- section at the excitation wavelength, most molecules show non- linear absorption. With increasing intensity, if the excited states show saturation owing to their long lifetimes, the transmission will show SA characteristics. Here absorption decreases with increase of intensity. If, however, the excited state has strong absorption compared with that of the ground state, the transmission will show RSA characteristics. Here in our work most of the materials show SA behavior and some materials exhibited RSA behavior. Both these properties purely depend on the nature of the materials and alignment of energy states within them. Both these SA and RSA have got immense applications in electronic devices. The important results obtained from various studies are presented in chapter 9.

Adrenergic and muscarinic receptor subtypes functional regulation during diabetogenesis: Effect of curcumin and vitamin D3 pre-treatment

In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.

A study on the performance of flexible pavements on mature soil subgrades

The country has witnessed tremendous increase in the vehicle population and increased axle loading pattern during the last decade, leaving its road network overstressed and leading to premature failure. The type of deterioration present in the pavement should be considered for determining whether it has a functional or structural deficiency, so that appropriate overlay type and design can be developed. Structural failure arises from the conditions that adversely affect the load carrying capability of the pavement structure. Inadequate thickness, cracking, distortion and disintegration cause structural deficiency. Functional deficiency arises when the pavement does not provide a smooth riding surface and comfort to the user. This can be due to poor surface friction and texture, hydro planning and splash from wheel path, rutting and excess surface distortion such as potholes, corrugation, faulting, blow up, settlement, heaves etc. Functional condition determines the level of service provided by the facility to its users at a particular time and also the Vehicle Operating Costs (VOC), thus influencing the national economy. Prediction of the pavement deterioration is helpful to assess the remaining effective service life (RSL) of the pavement structure on the basis of reduction in performance levels, and apply various alternative designs and rehabilitation strategies with a long range funding requirement for pavement preservation. In addition, they can predict the impact of treatment on the condition of the sections. The infrastructure prediction models can thus be classified into four groups, namely primary response models, structural performance models, functional performance models and damage models. The factors affecting the deterioration of the roads are very complex in nature and vary from place to place. Hence there is need to have a thorough study of the deterioration mechanism under varied climatic zones and soil conditions before arriving at a definite strategy of road improvement. Realizing the need for a detailed study involving all types of roads in the state with varying traffic and soil conditions, the present study has been attempted. This study attempts to identify the parameters that affect the performance of roads and to develop performance models suitable to Kerala conditions. A critical review of the various factors that contribute to the pavement performance has been presented based on the data collected from selected road stretches and also from five corporations of Kerala. These roads represent the urban conditions as well as National Highways, State Highways and Major District Roads in the sub urban and rural conditions. This research work is a pursuit towards a study of the road condition of Kerala with respect to varying soil, traffic and climatic conditions, periodic performance evaluation of selected roads of representative types and development of distress prediction models for roads of Kerala. In order to achieve this aim, the study is focused into 2 parts. The first part deals with the study of the pavement condition and subgrade soil properties of urban roads distributed in 5 Corporations of Kerala; namely Thiruvananthapuram, Kollam, Kochi, Thrissur and Kozhikode. From selected 44 roads, 68 homogeneous sections were studied. The data collected on the functional and structural condition of the surface include pavement distress in terms of cracks, potholes, rutting, raveling and pothole patching. The structural strength of the pavement was measured as rebound deflection using Benkelman Beam deflection studies. In order to collect the details of the pavement layers and find out the subgrade soil properties, trial pits were dug and the in-situ field density was found using the Sand Replacement Method. Laboratory investigations were carried out to find out the subgrade soil properties, soil classification, Atterberg limits, Optimum Moisture Content, Field Moisture Content and 4 days soaked CBR. The relative compaction in the field was also determined. The traffic details were also collected by conducting traffic volume count survey and axle load survey. From the data thus collected, the strength of the pavement was calculated which is a function of the layer coefficient and thickness and is represented as Structural Number (SN). This was further related to the CBR value of the soil and the Modified Structural Number (MSN) was found out. The condition of the pavement was represented in terms of the Pavement Condition Index (PCI) which is a function of the distress of the surface at the time of the investigation and calculated in the present study using deduct value method developed by U S Army Corps of Engineers. The influence of subgrade soil type and pavement condition on the relationship between MSN and rebound deflection was studied using appropriate plots for predominant types of soil and for classified value of Pavement Condition Index. The relationship will be helpful for practicing engineers to design the overlay thickness required for the pavement, without conducting the BBD test. Regression analysis using SPSS was done with various trials to find out the best fit relationship between the rebound deflection and CBR, and other soil properties for Gravel, Sand, Silt & Clay fractions. The second part of the study deals with periodic performance evaluation of selected road stretches representing National Highway (NH), State Highway (SH) and Major District Road (MDR), located in different geographical conditions and with varying traffic. 8 road sections divided into 15 homogeneous sections were selected for the study and 6 sets of continuous periodic data were collected. The periodic data collected include the functional and structural condition in terms of distress (pothole, pothole patch, cracks, rutting and raveling), skid resistance using a portable skid resistance pendulum, surface unevenness using Bump Integrator, texture depth using sand patch method and rebound deflection using Benkelman Beam. Baseline data of the study stretches were collected as one time data. Pavement history was obtained as secondary data. Pavement drainage characteristics were collected in terms of camber or cross slope using camber board (slope meter) for the carriage way and shoulders, availability of longitudinal side drain, presence of valley, terrain condition, soil moisture content, water table data, High Flood Level, rainfall data, land use and cross slope of the adjoining land. These data were used for finding out the drainage condition of the study stretches. Traffic studies were conducted, including classified volume count and axle load studies. From the field data thus collected, the progression of each parameter was plotted for all the study roads; and validated for their accuracy. Structural Number (SN) and Modified Structural Number (MSN) were calculated for the study stretches. Progression of the deflection, distress, unevenness, skid resistance and macro texture of the study roads were evaluated. Since the deterioration of the pavement is a complex phenomena contributed by all the above factors, pavement deterioration models were developed as non linear regression models, using SPSS with the periodic data collected for all the above road stretches. General models were developed for cracking progression, raveling progression, pothole progression and roughness progression using SPSS. A model for construction quality was also developed. Calibration of HDM–4 pavement deterioration models for local conditions was done using the data for Cracking, Raveling, Pothole and Roughness. Validation was done using the data collected in 2013. The application of HDM-4 to compare different maintenance and rehabilitation options were studied considering the deterioration parameters like cracking, pothole and raveling. The alternatives considered for analysis were base alternative with crack sealing and patching, overlay with 40 mm BC using ordinary bitumen, overlay with 40 mm BC using Natural Rubber Modified Bitumen and an overlay of Ultra Thin White Topping. Economic analysis of these options was done considering the Life Cycle Cost (LCC). The average speed that can be obtained by applying these options were also compared. The results were in favour of Ultra Thin White Topping over flexible pavements. Hence, Design Charts were also plotted for estimation of maximum wheel load stresses for different slab thickness under different soil conditions. The design charts showed the maximum stress for a particular slab thickness and different soil conditions incorporating different k values. These charts can be handy for a design engineer. Fuzzy rule based models developed for site specific conditions were compared with regression models developed using SPSS. The Riding Comfort Index (RCI) was calculated and correlated with unevenness to develop a relationship. Relationships were developed between Skid Number and Macro Texture of the pavement. The effort made through this research work will be helpful to highway engineers in understanding the behaviour of flexible pavements in Kerala conditions and for arriving at suitable maintenance and rehabilitation strategies. Key Words: Flexible Pavements – Performance Evaluation – Urban Roads – NH – SH and other roads – Performance Models – Deflection – Riding Comfort Index – Skid Resistance – Texture Depth – Unevenness – Ultra Thin White Topping