Gaba Receptor Gene Expression during Rat Liver Cell Proliferation and Its Function in Hepatocyte Cultures

The present thesis is an attempt to understand the role of GABA, GABAA and GABAB receptors in the regulation of liver cell proliferation using in vivo and in vitro models. The work also focuses on the brain GABAergic changes associated with normal and neoplastic cell growth in liver and to delineate its regulatory function. The investigation of mechanisms involving mitogenic models without cell necrosis may contribute our knowledge about both on cell growth, carcinogenesis, liver pathology and treatment. Objectives of the present study are, to induce controlled liver cell proliferation by partial hepatectomy and lead nitrate administration and uncontrolled cell proliferation by N-nitrosodiethylamine treatment in male Wistar rats, the changes in the content of GABA, GABAA,GABAB in various rat brain regions. To study the GABAA and GABAB receptor changes in brain stem, hypothalamus, cerebellum and cerebral cortex during the active cortex during the period of active DNA synthesis in liver of different experimental groups. The changes in GABAA and GABAB receptor function of the brain stem, hypothalamus and cerebellum play an important role sympathetic regulation of cell proliferation and neoplastic growth in liver. The decrease in GABA content in brain stem, hypothalamus and cerebellum during regeneration and neoplasia in liver. The time course of brain GABAergic changes was closely correlated with that of heptic DNA synthesis. The functional significance of these changes was further explored by studying the changes in GABAA and GABAB receptors in brain.

Serotonin Receptor Gene Expression And Insulin Function In Streptozotocin Induced Diabetic Rats

Recent studies have established a fimctional correlation of serotonergic and adrenergic function in the brain regions with insulin secretion in diabetic rats (Vahabzadeh et al., 1995). Administration of 5-HT”. agonist 8-OH-DPAT to conscious rats caused an increase in blood glucose level. This increase in blood glucose is due to inhibition of insulin secretion by increased circulating EPI (Chaouloff et al., 1990a; Chaouloff et al., 1990d; Chaoulo1T& Jeanrenaud, 1987). The increase in EPI is brought about by increased sympathetic stimulation. This increase can lead to increased sympatho-medullary stimulation thereby inhibiting insulin release (Bauhelal & Mir, 1993, Bauhelal & Mir, 1990a; Chaouloffet al., 1990d). Also, studies have shown that Gi protein in the liver has been decreased in diabetes which will increase gluconeogenesis and glycogenolysis thereby causing hyperglycaemia (Pennington, 1987). Serotonergic control is suggested to exert different effects on insulin secretion according to the activation of different receptor subclasses (Pontiroli et al., 1975). In addition to this mechanism, the secretion of insulin is dependent on the turnover ratio of endogenous 5-hydroxy tryptophan (5-HTP) to 5-HT in the pancreatic islets (Jance er al., 1980). The reports so far stated does not explain the complete mechanism and the subclass of 5-HT receptors whose expression regulate insulin secretion in a diabetic state. Also, there is no report of a direct regulation of insulin secretion by 5-HT from the pancreatic islets even though there are reports stating that the pancreatic islets is a rich source of 5-HT (Bird et al., 1980). Therefore, in the present study the mechanism by which 5-HT and its receptors regulate insulin secretion from pancreatic [3-cells was investigated. Our results led to the following hypotheses by which 5-HT and its receptors regulate the insulin secretion.

Adrenergic and serotonergic function in dna synthesis during rat liver regeneration and in hepatocyte cultures

The adult mammalian liver is predominantly in a quiescent state with respect to cell division. This quiescent state changes dramatically, however, if the liver is injured by toxic, infectious or mechanic agents (Ponder, 1996). Partial hepatectomy (PH) which consists of surgical removal of two-thirds of the liver, has been used to stimulate hepatocyte proliferation (Higgins & Anderson 1931). This experimental model of liver regeneration has been the target of many studies to probe the mechanisms responsible for liver cell growth control (Michalopoulos, 1990; Taub, 1996). After PH most of the remaining cells in the renmant liver respond with co-ordinated waves of DNA synthesis and divide in a process called compensatory hyperplasia. Hence, liver regeneration is a model of relatively synchronous cell cycle progression in vivo. In contrast to hepatomas, cell division is terminated under some intrinsic control when the original cellular mass has been regained. This has made liver regeneration a useful model to dissect the biochemical and molecular mechanisms of cell division regulation. The liver is thus, one of the few adult organs that demonstrates a physiological growth rewonse (Fausto & Mead, 1989; Fausto & Webber, 1994). The regulation of liver cell proliferation involves circulating or intrahepatic factors that are involved in either the priming of hepatocytes to enter the cell cycle (Go to G1) or progression through the cell cycle. In order to understand the basis of liver regeneration it is mandatory to define the mechanisms which (a) trigger division, (b) allow the liver to concurrently grow and maintain dilferentiated fimction and (c) terminate cell proliferation once the liver has reached the appropriate mass. Studies on these aspects of liver regeneration will provide basic insight of cell growth and dilferentiation, liver diseases like viral hepatitis, toxic damage and liver transplant where regeneration of the liver is essential. In the present study, Go/G1/S transition of hepatocytes re-entering the cell cycle after PH was studied with special emphasis on the involvement of neurotransmitters, their receptors and second messenger function in the control of cell division during liver regeneration

A Study on the Reversed Lack of Memory Property and its Generalizations

In this thesis, the concept of reversed lack of memory property and its generalizations is studied.We we generalize this property which involves operations different than the ”addition”. In particular an associative, binary operator ” * ” is considered. The univariate reversed lack of memory property is generalized using the binary operator and a class of probability distributions which include Type 3 extreme value, power function, reflected Weibull and negative Pareto distributions are characterized (Asha and Rejeesh (2009)). We also define the almost reversed lack of memory property and considered the distributions with reversed periodic hazard rate under the binary operation. Further, we give a bivariate extension of the generalized reversed lack of memory property and characterize a class of bivariate distributions which include the characterized extension (CE) model of Roy (2002a) apart from the bivariate reflected Weibull and power function distributions. We proved the equality of local proportionality of the reversed hazard rate and generalized reversed lack of memory property. Study of uncertainty is a subject of interest common to reliability, survival analysis, actuary, economics, business and many other fields. However, in many realistic situations, uncertainty is not necessarily related to the future but can also refer to the past. Recently, Di Crescenzo and Longobardi (2009) introduced a new measure of information called dynamic cumulative entropy. Dynamic cumulative entropy is suitable to measure information when uncertainty is related to the past, a dual concept of the cumulative residual entropy which relates to uncertainty of the future lifetime of a system. We redefine this measure in the whole real line and study its properties. We also discuss the implications of generalized reversed lack of memory property on dynamic cumulative entropy and past entropy.In this study, we extend the idea of reversed lack of memory property to the discrete set up. Here we investigate the discrete class of distributions characterized by the discrete reversed lack of memory property. The concept is extended to the bivariate case and bivariate distributions characterized by this property are also presented. The implication of this property on discrete reversed hazard rate, mean past life, and discrete past entropy are also investigated.

MQFD: A Model for Synergizing TPM and QFD

This thesis presents the methodology of linking Total Productive Maintenance (TPM) and Quality Function Deployment (QFD). The Synergic power ofTPM and QFD led to the formation of a new maintenance model named Maintenance Quality Function Deployment (MQFD). This model was found so powerful that, it could overcome the drawbacks of TPM, by taking care of customer voices. Those voices of customers are used to develop the house of quality. The outputs of house of quality, which are in the form of technical languages, are submitted to the top management for making strategic decisions. The technical languages, which are concerned with enhancing maintenance quality, are strategically directed by the top management towards their adoption of eight TPM pillars. The TPM characteristics developed through the development of eight pillars are fed into the production system, where their implementation is focused towards increasing the values of the maintenance quality parameters, namely overall equipment efficiency (GEE), mean time between failures (MTBF), mean time to repair (MTIR), performance quality, availability and mean down time (MDT). The outputs from production system are required to be reflected in the form of business values namely improved maintenance quality, increased profit, upgraded core competence, and enhanced goodwill. A unique feature of the MQFD model is that it is not necessary to change or dismantle the existing process ofdeveloping house ofquality and TPM projects, which may already be under practice in the company concerned. Thus, the MQFD model enables the tactical marriage between QFD and TPM.First, the literature was reviewed. The results of this review indicated that no activities had so far been reported on integrating QFD in TPM and vice versa. During the second phase, a survey was conducted in six companies in which TPM had been implemented. The objective of this survey was to locate any traces of QFD implementation in TPM programme being implemented in these companies. This survey results indicated that no effort on integrating QFD in TPM had been made in these companies. After completing these two phases of activities, the MQFD model was designed. The details of this work are presented in this research work. Followed by this, the explorative studies on implementing this MQFD model in real time environments were conducted. In addition to that, an empirical study was carried out to examine the receptivity of MQFD model among the practitioners and multifarious organizational cultures. Finally, a sensitivity analysis was conducted to find the hierarchy of various factors influencing MQFD in a company. Throughout the research work, the theory and practice of MQFD were juxtaposed by presenting and publishing papers among scholarly communities and conducting case studies in real time scenario.

Toxicity, accumulation and depuration of heavy metalsin the brown mussel perna indica

In this thesis certain important aspects of heavy metal toxicity have been worked out. Recent studies have clearly shown that when experimental media contained more than one heavy metals, such metals could conspicuously influence the toxic reaction of the animals both in terms of quantity and nature. The experimental results available on individual metal toxicity show that, in majority of such results, unrealistically high concentrations of dissolved metals are involved. A remarkable number of factors have been shown to influence metal toxicity such as various environmental factors particularly temperature and salinity, the condition of the organism and the ability of some of the marine organisms to adapt to metallic contamination. Further, some of the more sensitive functions like embryonic and larval development, growth and fecundity, oxygen utilization and the function of various enzymes are found to be demonstrably sensitive in the presence of heavy metals. However, some of the above functions could be compensated for by adaptive process. If it is assumed that the presence of a single metal in higher concentrations could affect the life function of marine animals, more than one metal in the experimental media should manifest such effects in a greater scale. Commonly known as synergism or more than additivity, majority of heavy metals bring about synergistic reaction .The work presented in this thesis comprises lethal and sublethal toxicities of different salt forms of copper and silver on the brown mussel Perna indica. during the present investigation sublethal concentrations of copper and silver in their dent effects on survival, oxygen consumption, filtration, accumulation and depuration on Perna indica. The results are presented under different sections to make the presentation meaningful .

Criminal justice system in pondicherry - a comparative critical study of the past and the presen

The Union Territory of Pondicherry prior to its merger with the Indian Union was a French Colony. The erstwhile territory of Pondicherry along with its hamlets, namely, KARAIKKAL, MAHE and YANAM was administered by the French Regime. Before it was established by French in 1 6 74 A.D. it was part of Vijayanagara Empire. Prior to this, Pondicherry was a part of the Kingdom of Chola and Pallava Kings. During French Regime, the laws which were in force in France in relation to administration of civil and criminal justice were extended to the erstwhile Territory of Pondicherry. Thus while Pondicherry stood influenced by the Inquisitorial system since the beginning of the 18th century, the neighboring states forming part of the Indian Union since Independence came under the Influence of the British system, viz. accusatorial system. The territory of Pondicherry, for administrative reasons, came to be merged with the Indian Union in the early 60's. Following the merger, the Indian administration sought to extent its own laws from time to time replacing erstwhile French Laws, however, subject to certain savings. Thus the transitional period witnessed consequential changes in the administration of the territory, including the sphere of judicial system. Since I 963, the Union Territory of Pondicherry was brought under the spell of the Indian Legal System The people in Pondicherry ' thus have had the benefit of experiencing both the svstems. Their experiences will be of much help to those who undertake comparative studies in law. The plus and minus points of the respective systems help one to develop a detachment that helps independent evaluation of the svstents. The result of these studies could be relevant in revitalising our criminal systems.The present system is evaluated in the light of the past system. New dimensions are added by way' of an empirical study also.

Analytical Studies on Diffusion and lntermittency in Chaotic Maps

The study of simple chaotic maps for non-equilibrium processes in statistical physics has been one of the central themes in the theory of chaotic dynamical systems. Recently, many works have been carried out on deterministic diffusion in spatially extended one-dimensional maps This can be related to real physical systems such as Josephson junctions in the presence of microwave radiation and parametrically driven oscillators. Transport due to chaos is an important problem in Hamiltonian dynamics also. A recent approach is to evaluate the exact diffusion coefficient in terms of the periodic orbits of the system in the form of cycle expansions. But the fact is that the chaotic motion in such spatially extended maps has two complementary aspects- - diffusion and interrnittency. These are related to the time evolution of the probability density function which is approximately Gaussian by central limit theorem. It is noticed that the characteristic function method introduced by Fujisaka and his co-workers is a very powerful tool for analysing both these aspects of chaotic motion. The theory based on characteristic function actually provides a thermodynamic formalism for chaotic systems It can be applied to other types of chaos-induced diffusion also, such as the one arising in statistics of trajectory separation. It was noted that there is a close connection between cycle expansion technique and characteristic function method. It was found that this connection can be exploited to enhance the applicability of the cycle expansion technique. In this way, we found that cycle expansion can be used to analyse the probability density function in chaotic maps. In our research studies we have successfully applied the characteristic function method and cycle expansion technique for analysing some chaotic maps. We introduced in this connection, two classes of chaotic maps with variable shape by generalizing two types of maps well known in literature.

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.