Regulation of lipocalin prostaglandin-D synthase expression by interleukin-1β in human chondrocytes

L'arthrose est une maladie multifactorielle complexe. Parmi les facteurs impliqués dans sa pathogénie, les certains prostaglandines exercent un rôle inflammatoire et d’autres un rôle protecteur. La prostaglandine D2 (PGD2) est bien connue comme une PG anti-inflammatoire, qui est régulée par l’enzyme «Lipocalin prostaglandine D-synthase». Avec l’inflammation de l'arthrose, les chondrocytes essaient de protéger le cartilage en activant certaines voies de récupération dont l'induction du gène L-PGDS. Dans cette étude, nous étudions la voie de signalisation impliquée dans la régulation de l'expression du (L-PGDS) sur les chondrocytes traités avec différents médiateurs inflammatoires. Le but de projet: Nous souhaitons étudier la régulation de la L-PGDS dans le but de concevoir des approches thérapeutiques qui peuvent activer la voie intrinsèque anti-inflammatoire. Méthode et conclusions: In vivo, l'arthrose a été suivie en fonction de l’âge chez la souris ou chirurgicalement suivant une intervention au niveau des genoux de souris. Nous avons confirmé les niveaux d’expression de L-PGDS histologiquement et par immunohistochimie. In vitro, dans les chondrocytes humains qui ont été traités avec différents médiateurs de l'inflammation, nous avons observé une augmentation de l’expression de la L-PGDS dose et temps dépendante. Nous avons montré, in vivo et in vitro que l’inflammation induit une sécrétion chondrocytaire de la L-PGDS dans le milieu extracellulaire. Enfin, nous avons observé la production de différentes isoformes de la L-PGDS en réponse à l'inflammation.

Dopamine Receptor Gene Expression In Streptozotocin Induced Diabetic Rats And Its Role In Insulin Secretion

Diabetes Mellitus is a metabolic disorder associated with insulin deficiency, which not.only affects the carbohydrate metabolism but also is associated with various central and peripheral complications. Chronic hyperglycemia during diabetes mellitus is a major initiator of diabetic microvascular complications like retinopathy, neuropathy, The central nervous system (CNS) neurotransmitters play an important role in the regulation of glucose homeostasis. These neurotransmitters mediate rapid intracellular communications not only within the central nervous system but also in the peripheral tissues. They exert their function through receptors present in both neuronal and non neuronal cell surface that trigger second messenger signaling pathways. Dopamine is a neurotransmitter that has been implicated in various central neuronal degenerative disorders like Parkinson's disease and behavioral diseases like Schizophrenia. Dopamine is synthesised from tyrosine, stored in vesicles in axon terminals and released when the neuron is depolarised. Dopamine interacts with specific membrane receptors to produce its effect. Dopamine plays an important role both centrally and peripherally. The recent identification of five dopamine receptor subtypes provides a basis for understanding dopamine's central and peripheral actions . Dopamine receptors are classified into two major groups : DA D1 like and DA D2 like. Dopamine D1 like receptors consists of DA D1 and DA D5 receptors . Dopamine D2 like receptors consists of DA D2, DA D3 and DA D4 receptors. Stimulation of the DA D1 receptor gives rise to increased production of cAMP. Dopamine D2 receptors inhibit cAMP production, but activate the inositol phosphate second messenger system . Impairment of central dopamine neurotransmission causes muscle rigidity, hormonal regulation , thought disorder and cocaine addiction. Peripheral dopamine receptors mediate changes in blood flow, glomerular filtration rate, sodium excretion and catecholamine release. The dopamine D2 receptors increased in the corpus striatum and cerebral cortex but decreased in the hypothalamus and brain stem indicating their involvement in regulating insulin secretion. Dopamine D2 receptor which has a stimulatory effecton insulin secretion decreased in the pancreatic islets during diabetes. Our in vitro studies confirmed the stimulatory role of dopamine D2 receptors in stimulation of glucose induced insulin secretion. A detailed study at the molecular level on the mechanisms involved in the role of dopamine in insulin secretion, its functional modification could lead to therapeutic interventions that will have immense clinical importance.

Speech Analysis using Modern Techniques of Nonlinear Dynamics

Medical fields requires fast, simple and noninvasive methods of diagnostic techniques. Several methods are available and possible because of the growth of technology that provides the necessary means of collecting and processing signals. The present thesis details the work done in the field of voice signals. New methods of analysis have been developed to understand the complexity of voice signals, such as nonlinear dynamics aiming at the exploration of voice signals dynamic nature. The purpose of this thesis is to characterize complexities of pathological voice from healthy signals and to differentiate stuttering signals from healthy signals. Efficiency of various acoustic as well as non linear time series methods are analysed. Three groups of samples are used, one from healthy individuals, subjects with vocal pathologies and stuttering subjects. Individual vowels/ and a continuous speech data for the utterance of the sentence "iruvarum changatimaranu" the meaning in English is "Both are good friends" from Malayalam language are recorded using a microphone . The recorded audio are converted to digital signals and are subjected to analysis.Acoustic perturbation methods like fundamental frequency (FO), jitter, shimmer, Zero Crossing Rate(ZCR) were carried out and non linear measures like maximum lyapunov exponent(Lamda max), correlation dimension (D2), Kolmogorov exponent(K2), and a new measure of entropy viz., Permutation entropy (PE) are evaluated for all three groups of the subjects. Permutation Entropy is a nonlinear complexity measure which can efficiently distinguish regular and complex nature of any signal and extract information about the change in dynamics of the process by indicating sudden change in its value. The results shows that nonlinear dynamical methods seem to be a suitable technique for voice signal analysis, due to the chaotic component of the human voice. Permutation entropy is well suited due to its sensitivity to uncertainties, since the pathologies are characterized by an increase in the signal complexity and unpredictability. Pathological groups have higher entropy values compared to the normal group. The stuttering signals have lower entropy values compared to the normal signals.PE is effective in charaterising the level of improvement after two weeks of speech therapy in the case of stuttering subjects. PE is also effective in characterizing the dynamical difference between healthy and pathological subjects. This suggests that PE can improve and complement the recent voice analysis methods available for clinicians. The work establishes the application of the simple, inexpensive and fast algorithm of PE for diagnosis in vocal disorders and stuttering subjects.

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.

Cholinergic receptor subtypes functional regulation in spinal cord injured monoplegic rats

The present study deals with the Cholinergic Receptor subtypes functional regulation in spinal cord injured monoplegic rats: Effect of 5-HT GABA and bone marrow cells.Spinal cord injury causes permanent and irrevocable motor deficits and neurodegeneration. Disruption of the spinal cord leads to diminished transmission of descending control from the brain to motor neurons and ascending sensory information. Behavioural studies showed deficits in motor control and coordination in SCI rats. Cholinergic system plays an important role in SCI, the evaluation of which provides valuable insight on the underlying mechanisms of motor deficit that occur during SCI. The cholinergic transmission was studied by assessing the muscarinic and nicotinic receptors; cholinergic enzymes- ChAT and AChE; second messenger enzyme PLC; transcription factor CREB and second messengers - IP3, cAMP and cGMP. We observed a decrease in the cholinergic transmission in the brain and spinal cord of SCI rats. The disrupted cholinergic system is the indicative of motor deficit and neuronal degeneration in the spinal cord and brain regions. SCI mediated oxidative stress and apoptosis leads to neuronal degeneration in SCI rats. The decreased expression of anti oxidant enzymes – SOD, GPx and neuronal cell survival factors - BDNF, GDNF, IGF-1, Akt and cyclin D2 along with increased expression of apoptotic factors – Bax, caspase-8, TNFa and NF-kB augmented the neuronal degeneration in SCI condition. BMC administration in combination with 5-HT and GABA in SCI rats showed a reversal in the impaired cholinergic neurotransmission and reduced the oxidative stress and apoptosis. It also enhanced the expression of cell survival factors in the spinal cord region. In SCI rats treated with 5-HT and GABA, the transplanted BMC expressed NeuN confirming that 5-HT and GABA induced the differentiation and proliferation of BMC to neurons in the spinal cord. Neurotrophic factors and anti-apoptotic elements in SCI rats treated with 5-HT and GABA along with BMC rendered neuroprotective effects accompanied by improvement in behavioural deficits. This resulted in a significant reversal of altered cholinergic neurotransmission in SCI. The restorative and neuro protective effects of BMC in combination with 5-HT and GABA are of immense therapeutic significance in the clinical management of SCI.

Assessment of the global intelligence and selective cognitive capacities in preterm 8-year-old children

Resumen tomado de la publicaci??n

Alteración de la atención y concentración en estudiantes de medicina que realizan turnos de noche

El sueño, es indispensable para la recuperación, física, mental y de procesos como la consolidación de memoria, atención y lenguaje. La privación de sueño (PS) incide en la atención y concentración. La PS es inherente a la formación médica, pero no es claro el papel de los turnos nocturnos en estudiantes, porque no cumplen con un objetivo académico, pero hay relación con disminución de la salud, productividad, accidentes, y alteraciones en diversas actividades. Está descrito el impacto de la PS sobre la capacidad de aprendizaje y aspectos como el ánimo y las relaciones interpersonales. MÉTODOS: Se realizó un estudio analítico observacional de cohorte longitudinal, con tres etapas de medición a 180 estudiantes de Medicina de la Universidad del Rosario, que evaluó atención selectiva y concentración mediante la aplicación de la prueba d2, validada internacionalmente para tal fin. RESULTADOS: Se estudiaron 180 estudiantes, 115 mujeres, 65 hombres, entre los 18 y 26 años (promedio 21). Al inicio del estudio dormían en promedio 7,9 horas, cifra que se redujo a 5,8 y 6,3 en la segunda y tercera etapa respectivamente. El promedio de horas de sueño nocturno, disminuyó en el segundo y tercer momento (p<0,001); Además se encontró mediante la aplicación de la prueba d2, que hubo correlación significativa directa débil, entre el promedio de horas de sueño, y el promedio del desempeño en la prueba (r=0.168, p=0.029) CONCLUSIONES: La PS, con períodos de sueño menores a 7,2 horas, impactan de manera importante la atención selectiva, la concentración

El perfil criminal del asesino en serie colombiano desde la perspectiva psicodinámica. Una revisión de literatura

El objetivo de la presente investigación consiste en describir las características de un asesino en serie colombiano desde la perspectiva psicodinámica. En este sentido, el abordaje teórico realizado en este trabajo se compone inicialmente de una concepción de asesinos en serie, posteriormente se hace una revisión acerca de las bases biológicas y los factores sociales del homicida serial, igualmente, se explican tres teorías psicodinámicas a trabajar (Sigmund Freud y Erick Erickson). Finalmente, se hace mención dentro de la investigación a la comparación casuística de los asesinos en serie, teniendo en cuenta a cuatro asesinos en serie mediante el abordaje psicodinámico. Por otra parte, a nivel metodológico, el tipo de estudio realizado es descriptivo con un corte cualitativo y un diseño no experimental, basado en la revisión de fuentes bibliográficas. Como producto se pretende hacer una aproximación al perfil correspondiente de la personalidad de un asesino en serie colombiano mediante las teorías psicodinámicas.

Convergencia de vías de señalización en un modelo de apoptosis

La sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.

Uso del gas como recurso estratégico en la política exterior rusa. Análisis de caso Ucrania periodo 2000-2010

Estudio de caso que busca evaluar el uso del gas natural dentro de la política exterior rusa como recurso estratégico en las relaciones con Ucrania. Se describe y analiza cómo la importancia geoestratégica de Ucrania genera una percepción de seguridad y relevancia económica en Rusia, por esta razón la Federación utiliza el gas natural como mecanismo de presión frente al Estado ucraniano para satisfacer sus intereses nacionales en función de los elementos mencionados anteriormente.Todo lo anterior a través de la Teoría del Heartland desarrollada por Halford Mackinder y El Concepto de Área Pivote de Zbigniew Brzezinski para determinar cómo se genera la importancia del Estado ucraniano frente a Rusia

Quien puede, quiera... quien puede, quiera : (gram??tica en el AVE)

Resumen basado en el de la publicaci??n. Encuentro con el t??tulo: 'La gram??tica en el aula' organizado por el Instituto Cervantes de N??poles

Evaluaci??n de un programa psicopedag??gico para la mejora de la atenci??n en estudiantes de educaci??n primaria

Resumen basado en el de la publicaci??n

Estudo in vivo sobre a influência do fototipo na resposta da pele humana ao contacto com lauril sulfato de sódio

O Lauril Sulfato de Sódio (LSS) é um tensioactivo aniónico utilizado em muitas formas farmacêuticas, que apresenta, no entanto, algum potencial de irritação. Também por esse motivo o LSS é utilizado como agente provocador em diversos micrométodos de exploração in vivo da fisiopatologia da pele. Factores como a idade, sexo, hidratação da pele, região anatómica, afectam a resposta da pele ao contacto com LSS, O objectivo deste estudo foi estudar a influência do fototipo na recuperação da integridade da pele humana ao contacto com LSS. Após selecção dos voluntários (n=12) com base nos seus fototipos (Grupo I : Fototipo III-IV e Grupo II: Fototipo V-VI) foi aplicado um penso contendo uma solução de LSS a 2% no antebraço, durante 24h(D0. Após remoção do penso, os voluntários foram sujeitos (D1,D2,D7) a exame dermatológico e à medição das variáveis biométricas: perda de água trans-epidermica, hidratação (por 2 métodos complementares) grau de eritema e fluxo sanguíneo local. Os resultados mostram que existem diferenças entre os dois grupos para a PTEA, LDF e grau de eritema, sugerindo uma maior susceptibilidade para os fototipos mais claros e uma maior rapidez de recuperação para os fototipos mais elevados.

A atitude dos alunos face à inclusão dos seus pares com deficiência

RESUMO: A escola actual encontra-se perante o desafio de responder com afectividade às necessidades educativas especiais de uma população cada vez mais heterogénea, onde se adopte um modelo de atendimento adequado a cada um. Neste contexto, consideramos os alunos, os professores e os encarregados de educação elementos chave de todo o processo, sobre os quais recaem responsabilidades acrescidas na concretização da filosofia inclusiva. O presente estudo tem como objectivo averiguar a atitude dos alunos face à inclusão dos seus pares com deficiência, determinando o modo como estes percepcionam as atitudes dos professores e dos pais face à inclusão de alunos com NEE de carácter permanente, vantagens e desvantagens da inclusão de alunos com NEE de carácter permanente e a cooperação entre alunos com e sem deficiência, tendo em conta a tipologia da deficiência (motora e mental). No caso do nosso estudo, contámos com a participação de 520 alunos (N= 270 género feminino e N=250 do género masculino), uma amostra distribuída pelo 2ºciclo, 3º ciclo e secundário dos distritos de Setúbal e Lisboa. A recolha de dados concretizou-se pela aplicação do AID – EF, questionário da autoria de Ramos Leitão, 2011.Esta metodologia de recolha e tratamento de informação permitiu-nos concluir que, na opinião dos alunos ditos normais a atitude dos professores face à inclusão de alunos com NEE de carácter permanente (dimensão d1), não varia em função da tipologia da deficiência (deficiência motora e mental). Da mesma forma, não foram encontradas diferenças significativas entre os dois grupos (deficiência motora e mental), na opinião dos alunos ditos normais, no que respeita às vantagens da inclusão dos alunos com NEE de carácter permanente (dimensão d2). Na opinião dos alunos ditos normais os resultados demonstraram que a cooperação entre alunos com e sem deficiência (dimensão d3), varia em função da tipologia da deficiência (deficiência motora e mental), apontando esses resultados para uma maior cooperação entre os alunos ditos normais e os seus pares com deficiência mental. Não foram igualmente encontradas diferenças significativas no que respeita às desvantagens da inclusão dos alunos com NEE de carácter permanente (dimensão 4), quando temos em consideração a tipologia da deficiência (deficiência motora e mental). Da mesma forma, na opinião dos alunos normais ditos normais a atitude dos pais face à inclusão de alunos com NEE de carácter permanente (dimensão d5) não variam em função da tipologia da deficiência (deficiência motora e mental).ABSTRACT: Currently the school is faced with the challenge of responding affectionately to the special educational needs of an increasingly heterogeneous population, where a standard model is adopted for each individual. In this context, we consider the students, teachers and guardians, key elements in the whole process, over which fall increased responsibilities in the implementation of the inclusive philosophy. The present study aims to determine the attitude of students towards the inclusion of peers with disabilities, determining how they perceive the attitudes of teachers and parents towards the inclusion of pupils with permanent special education needs, advantages and disadvantages of including students with permanent special education needs and the cooperation between students with and without disabilities, taking into account the type of disability (mental and motor). In the case of our study, we had the participation of 520 students (N = 270 N = female and 250 male), a sample distributed to the 2nd cycle, 3rd cycle and Secondary schools in the districts of Setúbal and Lisbon. The data collected was enabled by the application of the IDA - EF, questionnaire by Ramos Leitão, 2011. This methodology of collecting and processing information allowed us to conclude that, in the opinion of the so-called normal students the teachers´ attitude towards the inclusion of pupils with permanent special education needs (dimension d1) does not vary according to the type of disability (motor and mental). Likewise, no significant differences were found between the two groups (mental and motor), in the opinion of the so-called normal students, with regard to the benefits of the inclusion of pupils with permanent special education needs (dimension d2). In the opinion of the so-called normal students, the results demonstrated that the cooperation between students with and without disabilities (dimension d3), vary depending on the type of disability (mental and motor), these results pointing to a greater cooperation between the so-called normal students and their peers with mental disabilities. There were also no significant differences with respect to the disadvantages of inclusion of pupils with permanent special education needs (dimension d4), when we take into account the type of disability (mental and motor). Similarly, in the opinion of the so-called normal students, the parents´ attitude towards the inclusion of pupils with permanent special education needs (dimension d5) does not vary according to the type of disability (mental and motor).

Effects of Delta9-tetrahydrocannabivarin on [35S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes

BACKGROUND AND PURPOSE: We have recently shown that the phytocannabinoid Delta9-tetrahydrocannabivarin (Delta9-THCV) and the CB1 receptor antagonist AM251 increase inhibitory neurotransmission in mouse cerebellum and also exhibit anticonvulsant activity in a rat piriform cortical (PC) model of epilepsy. Possible mechanisms underlying cannabinoid actions in the CNS include CB1 receptor antagonism (by displacing endocannabinergic tone) or inverse agonism at constitutively active CB1 receptors. Here, we investigate the mode of cannabinoid action in [35S]GTPgammaS binding assays. EXPERIMENTAL APPROACH: Effects of Delta9-THCV and AM251 were tested either alone or against WIN55,212-2-induced increases in [35S]GTPgammaS binding in mouse cerebellar and PC membranes. Effects on non-CB receptor expressing CHO-D2 cell membranes were also investigated. KEY RESULTS :Delta9-THCV and AM251 both acted as potent antagonists of WIN55,212-2-induced increases in [35S]GTPgammaS binding in cerebellar and PC membranes (Delta9-THCV: pA2=7.62 and 7.44 respectively; AM251: pA2=9.93 and 9.88 respectively). At micromolar concentrations, Delta9-THCV or AM251 alone caused significant decreases in [35S]GTPgammaS binding; Delta9-THCV caused larger decreases than AM251. When applied alone in CHO-D2 membranes, Delta9-THCV and AM251 also caused concentration-related decreases in G protein activity. CONCLUSIONS AND IMPLICATIONS: Delta9-THCV and AM251 act as CB1 receptors antagonists in the cerebellum and PC, with AM251 being more potent than Delta9-THCV in both brain regions. Individually, Delta9-THCV or AM251 exhibited similar potency at CB1 receptors in the cerebellum and the PC. At micromolar concentrations, Delta9-THCV and AM251 caused a non-CB receptor-mediated depression of basal [35S]GTPgammaS binding.