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.

Modelling and Analysis of Bivariate Lifetime Data using Reversed Hazard Rates

Department of Statistics, Cochin University of Science and Technology

Anomalous profile of a self-reversed resonance line from Ba+ in a laser produced plasma from YBa2Cu307

A laser produced plasma from the multielement solid target YBa2Cu3O7 is generated using 1.06 μm, 9 ns pulses from a Q-switched Nd:YAG laser in air at atmospheric pressure. A time resolved analysis of the profile of the 4554.03 Å resonance line emission from Ba II at various laser power densities has been carried out. It has been found that the line has a profile which is strongly self-reversed. It is also observed that at laser power densities equal to or exceeding 1.6×1011 W cm−2, a third peak begins to develop at the centre of the self-reversed profile and this has been interpreted as due to the anisotropic resonance scattering (fluorescence). The number densities of singly ionized barium ions evaluated from the width of the resonance line as a function of time delay with respect to the beginning of the laser pulse give typical values of the order of 1019 cm−3. The higher ion concentrations existing at smaller time delays are seen to decrease rapidly. The Ba II ions in the ground state resonantly absorb the radiation and this absorption is maximum around 120 ns after the laser pulse.

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration using 60-70% pancreatectomy. The 5-HT and 5-HT2c receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (B^,ax) without any change in Kd in 72 h pancreatectomised rats compared with sham. The decreased Bmax reversed to sham level by 7 days after pancreatectomy. In brain stem , Scatchard analysis showed a significant decrease (p < 0.01) in Bax with a significant increase (p < 0.01) in Kd. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT2C receptor in the brain has a functional regulatory role in the pancreatic regeneration. (Mol Cell Biochem 272: 165-170, 2005)

Decreased a2-adrenergic receptor in the brain stem and pancreatic islets during pancreatic regeneration in weanling rats

Sympathetic stimulation inhibits insulin secretion. a2-Adrenergic receptor is known to have a regulatory role in the sympathetic function. We investigated the changes in the a2-adrenergic receptors in the brain stein and pancreatic islets using [3H]Yohimbine during pancreatic regeneration in weanling rats. Brain stem and pancreatic islets of experimental rats showed a significant decrease (p<0.001) in norepinephrine (NE) content at 72 h after partial pancreatectomy. The epinephrine (EPI) content showed a significant decrease (p<0.001) in pancreatic islets while it was not detected in brain stem at 72 h after partial pancreatectomy. Scatchard analysis of [3H]Yohimbine showed a significant decrease (p<0.05) and Kd at 72 h after partial pancreatectomy in the brain stem. In the pancreatic islets, Scatchard analysis of [3H]Yohimbine showed a signiinfiBca'nnatx decrease (p<0.001) in B,nax and Kd (p<0.05) at 72 h after partial pancreatectomy. The binding parameters reversed to near sham by 7 days after pancreatectomy both in brain stein and pancreatic islets. This shows that pancreatic insulin secretion is influenced by central nervous system inputs from the brain stem. In vitro studies with yohimbine showed that the a2-adrenergic receptors are inhibitory to islet DNA synthesis and insulin secretion. Thus our results suggest that decreased a2-adrenergic receptors during pancreatic regeneration functionally regulate insulin secretion and pancreatic 13-cell proliferation in weanling rats.

Kinetic Parameters of Thymidine Kinase and DNA Synthesis During Liver Regeneration: Role Ofthyroid Hormones

The role of thyroid hormones in DNA synthesis and in the activity of Thymidille kinase (TK), a key regulatory enzyme of DNA synthesis was studied in proliferating hepatocytes in vivo. Liver regeneration after partial hepatectomy was used as a model for controlled cell division in rats having different thyroid status - euthyroid, hypothyroid and 3,3',5'-triiodo-L-thyronine (T))-heated hypothyroid. Partial hepatectomy caused a significant elevation of DNA synthesis (p<0.01) in all the three groups compared to their sham-operated counterparts. Hypothyroid liepatectomised animals showed significantly lower (p<0.01) level of DNA synthesis than euthyroid hepatectomised animals. A single subcutaneous close of 1'3 to hypothyroid shamoperated animals resulted in a significant increase (p<0.01) of DNA synthesis in the intact liver. 17tis was comparable to the level of DNA synthesis occurring in regenerating liver of euthyroid animals. In hypothyroid hepatectomised animals, "1'3 showed an additive effect on l)NA synthesis and this group exhibited maximum level of DNA synthesis (p<0.0I ). Studies of the kinetic parameters of TK show that the Michelis-Menten constant, (K111) of TK for thymidine was altered by the thyroid status. K11 increased significantly (p<0.01) in untreated hypothyroid animals when compared to the euthyroid rats. '13 treatment of hypothyroid animals reversed this effect and this group showed the lowest value for K111 (p<0.01). Thus our results indicate that thyroid hormones can influence DNA synthesis during liver regeneration and they may regulate the activity of enzymes such as 17rymidine kinase which are important for DNA synthesis and hence cell division.

Alterations in the muscarinic M I and M3 receptor gene expression in the brain stem during pancreatic regeneration and insulin secretion in weanling rats

Muscarinic M1 and M3 receptor changes in the brain stem during pancreatic regeneration were investigated. Brain stem acetylcholine esterase activity decreased at the time of regeneration . Sympathetic activity also decreased as indicated by the norepinephrine (NE) and epinephrine (EPI) content of adrenals and also in the plasma. Muscarinic Ml and M3 receptors showed reciprocal changes in the brain stem during regeneration. Muscairnic M1 receptor number decreased at time of regeneration without any change in the affinity. High affinity M3 receptors showed an increase in the number. The affinity did not show any change . The number of low affinity receptors decreased with decreased Kd at 72 hours after partial pancreatectomy. The Kd reversed to control value with a reversal of the number of receptors to near control value . Gene expression studies also showed a similar change in the mRNA level of Ml and M3 receptors . These alterations in the muscarinic receptors regulate sympathetic activity and maintain glucose level during pancreatic regeneration. Central muscarinic M1 and M3 receptor subtypes functional balance is suggested to regulate sympathetic and parasympathetic activity, which in turn control the islet cell proliferation and glucose homeostasis.

Decreased GyBAA Receptor Function in the Brain Stem during Pancreatic Regeneration in Rats

Gamma amino outyric acid is a major inhibitory neurotrarsr titter in the central nervous system. In the preset study sv, Have investigate(' the alteration of GABA receptor, In t he hrain stem of rats during pancreatic regeneration. Three groups of rats were used for the study: sham operated, 72 It and 7 days partially pancreatectonnsea. GABA was (juan- (ified by [H]GABA receptor iispiacement method. GABA receptor kin: 10, pat at i et•ers were studied by using the binding of F'.](iAhA as ligand to the Triton X-100 treated me,i1,;-:mes a1,J displacement with unlabelled GABA. GhRA,v receptor activity was studied by using the [` -1 h3cuculline and displacement with unlabellecV euculline. ;.\13A content significantly decreased (1' < (1.(101 ) it, 0-e brain stern during the regeneration of pancreas. 'I hl, high affinity (IAI3A receptor binding sho?:ed it sigii'f cant decrease in 131„.,\ (P < 11.01) and K,I 1).05) n 72 h and 7 days after partial pancreatee 'timv. ";:flhicuculline hin(Iing showed it signih eat, 'le ( r(, :,e in /Jn1,s and K,I (P < 0.001) in 72 h pa^.rcreaw,, mised rats when compared with sham wt--tt' as P,n and K,I reversed to near sham after 7 da,s of pancreatectomv. The results sugge,) that GAB A throur,r; ('GABA receptors in brain Atcem has a regulatory uie during active regeneration of pancreas which will have inunense clinical significance in the treatment of cliahetcs.

ALPHA2 Adrenergic and High Affinity Serotonergic Receptor Changes in the Brain Stem of Streptozotocin induced Diabetic Rats

The brain stems (13S) of streptozotocin (STZ)-diabetic rats were studied lo see the changes in neurotransmitter content and their receptor regulation. The norepinephrine (NE) content determined in the diabetic brain stems did ^ control. an E showed la while PI turnover hri content increased significantly compared N^r eNveFa o the recep significant increase. The alpha2 adrenergic receptor IneP utisoulinntreat d ratsetheNE contentt dec^ sled was significantly reduced during diabetes. in versedcto reanorm sed ulcrea e tK reatment the state. while EPI content remained increased as in die diabetic B,, for a]pha2 adrenergic receptors slw^nificantly while Unlabelled clonidine inhibited [31-I]NE binding in BS of control, diabetic and insulin treated ulations bindi diabetic rats showed that alpha2 adrenergicre^ punks cojnidiabetic animal the ligand bound sites with Hill slopes significantly away from unity. weaker to the low affinity site than in controls. Insulin treatment reversed[ this allumbmn to control levels. The displacement analysis using (-)-epinephrine age in control and diabetic animals revealed two populations of receptor affinidtyo=tat ss. In control animals, when GTP analogue added with epinephrine, the curve nagnlde caofnfitnroit yS model; but in the diabetic BS this effect `not aobserved. In bintact oth the diabetic data thus showlthat the effects of monovalent cations on affinity alphaz adrenergic receptors have a reduced affinity v due in stem ialtered Itscppeomson(5- regulation. The serotonin (5-HT) coat hydroxy) tryptophan (5-HTP) showed an increase and its breakdown metabolite (5-hydroxy) indoleacetic acid (5-I{IAA) showed a significant decrease. This showed that in serotonergic which l nerves there is a disturbance in both synthetic and breankduomwnbers pretma'med ana increased 5-HT. The high affinity serotonin receptor um ese serotonerg decrease in the receptor affinity. The insulin ^treatmentsturtiy showsha decreased serotonergic receptor kinetic parameters to control level. receptor function. These changes in adrenergic and serotonergic receptor function were suggested to be important in insulin function during STZ diabetes.

Effect of Aegle Marmelose Leaf Extract on Allbxan Induced Diabetic Rats

Alloxan induced diabetic animal model was sed to evaluate the potential antidiabetic effect of ie aqueous leaf extract of Aegle marmelose. Insuinjection and oral treatment of Aegle marmelose of extract to the alloxan induced rats maintained ;e animal weight near to the control rats whereas ,,ere was a significant decrease in weight in alloxan •duced rats. Insulin injection and oral treatment the leaf extract reversed the decrease of protein )ntent in all the organs studied except the pancas. Glucose level was maintained near to the co- :rol levels in the insulin injected and leaf extract Bated alloxan diabetic rats. A significant increased ucose tolerance was observed in animals orally ven the leaf extract prior to the experiment. The suits indicate that there is an increased utilization glucose in the Aegle marmelose leaf extract treed rats.

Alterations in brainstem a2 adrenoreceptor activity in pyridoxine-deficient rat model of hypertension

Moderate pyridoxine deficiency in adult male Sprague-Dawley rats results in significant hypertension, associated with a general sympathetic stimulation , including an increase in the turnover of norepinephrine in the heart. Treatment of these rats with pyridoxine reversed blood pressure to normal within 24 h. Treatment of pyridoxine-deficient rats with clonidine or x-methyl dihydroxyphenylalanine (x-methyl DOPA) also reduced the blood pressure of these animals to normal . There was also a significant increase in the Bma, of high and low affinity [3H]p-amino-clonidine binding to crude synaptosomal membrane preparations of the brain stem of deficient rats indicating chronic underexposure of)(, adrenoreceptors to endogenous norepinephrin.

Brain 5HT2A Receptor Regulation by Tryptophan Supplementation in Streptozotocin Diabetic Rats

5-HT2A receptor binding parameters were studied in the cerebral cortex and brain stem of control, diabetic, insulin, insulin + tryptophan and tr3yptophan treated streptozotocin diabetic rats. Scatchard analysis using selective antagonist, [-H](±)2,3-dimethoxyphenyl-l-[2-(4-piperidine)- methanol] ([3H]MDL100907) in cerebral cortex of diabetic rats showed a significant decrease in dissociation constant (Kd) without any change in maximal binding (Bm). Competition binding studies in cerebral cortex using ketanserin against [3H]MDL100907 showed the appearance of an additional site in the low affinity region during diabetes. In the brain stem, Scatchard analysis showed a significant increase in Bmax and Kd. Displacement studies showed a shift in the receptor affinity towards a low affinity state. All these altered parameters in diabetes were reversed to control level by insulin, insulin + tryptophan and tryptophan treatments. Tryptophan treatment is suggested to reverse the altered 5-HT2Abinding and blood glucose level to control status by increasing the brain 5-HT content.

Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT 2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats

5-Hydroxytryptamine2A (5-HT2A) receptor kinetics was studied in cerebral cortex and brain stem of streptozotocin (STZ) induced diabetic rats. Scatchard analysis with [3H] (±) 2,3dimethoxyphenyl-l-[2-(4-piperidine)-methanol] ([3H]MDL100907) in cerebral cortex showed no significant change in maximal binding (Bmax) in diabetic rats compared to controls. Dissociation constant (K) of diabetic rats showed a significant decrease (p < 0.05) in cerebral cortex, which was reversed to normal by insulin treatment. Competition studies of [3H]MDL100907 binding in cerebral cortex with ketanserin showed the appearance of an additional low affinity site for 5-HT2A receptors in diabetic state, which was reversed to control pattern by insulin treatment. In brain stem, scatchard analysis showed a significant increase (p < 0.05) in Bmax accompanied by a significant increase (p < 0.05) in Kd. Competition analysis in brain stem also showed a shift in affinity towards a low affinity State for 5-HT2A receptors. All these parameters were reversed to control level by insulin treatment. These results show that in cerebral cortex there is an increase in affinity of 5-HT2A receptors without any change in its number and in the case of brain stem there is an increase in number of 5HT2A receptors accompanied by a decrease in its affinity during diabetes. Thus, from the results we suggest that the increase in affinity of 5-HT2A receptors in cerebral cortex and upregulation of 5-HT2A receptors in brain stem may lead to altered neuronal function in diabetes.

Testicular Function in Biotin-Deficient Adult Rats

We have studied testicular function in the biotin- deficient rat biochemically and morphologically. Serum testosterone and luteinizing hormone (LH) levels were decreased significantly in the deficient rats. Administration of biotin or gonadotropins to the deficient rats reversed this decrease in serum testosterone. There was no difference in the serum cholesterol level between the control and biotin-deficient rats. A significant degree of sloughing of seminiferous tubule germinal epithelium was noticed in the biotin-deficient rat testes. Biotin treatment of biotindeficient rats reversed this condition whereas testosterone treatment was without any effect. The development and maintenance of morphological and functional integrity of the seminiferous tubules appears to require a biotin-mediated step in addition to testosterone.

Sympathetic Stimulation and Hypertension in the Pyridoxine-Deficient Adult Rat

Pyridoxal phosphate is the coenzyme of various decarboxylases involved in the formation of monoamine neurotransmitters such as y-aminobutyric acid , serotonin , dopamine, and norepinephrine . Adult male Sprague-Dawley rats placed on a pyridoxine -deficient diet for 8 weeks showed significant hypertension compared with pyridoxine -supplemented controls . Hypothalamic contents of pyridoxal phosphate , y-aminobutyric acid, and serotonin in the pyridoxine - deficient rats were significantly lower than those in pyridoxine -supplemented controls . Hypertension was associated with sympathetic stimulation . Treatment of pyridoxine-deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 hours, with concomitant restorations of hypothalamic serotonin and y-aminobutyric acid as well as the return of plasma norepinephrine and epinephrine to normal levels . Also, pyridoxine treatment reversed the hypothalamic hypothyroidism observed in pyridoxine -deficient rats . These results indicate an association between pyridoxine deficiency and sympathetic stimulation leading to hypertension.