Investigation on key molecular targets responsible for antidiabetic properties of Symplocos cochinchinensis (Lour.) S. Moore

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia with disturbances in carbohydrate, protein and lipid metabolism resulting from defects in insulin secretion, insulin action or both. Currently there are 387 million people with diabetes worldwide and is expected to affect 592 million people by 2035. Insulin resistance in peripheral tissues and pancreatic beta cell dysfunction are the major challenges in the pathophysiology of diabetes. Diabetic secondary complications (like liver cirrhosis, retinopathy, microvascular and macrovascular complications) arise from persistent hyperglycemia and dyslipidemia can be disabling or even life threatening. Current medications are effective for control and management of hyperglycemia but undesirable effects, inefficiency against secondary complications and high cost are still serious issues in the present prognosis of this disorder. Hence the search for more effective and safer therapeutic agents of natural origin has been found to be highly demanding and attract attention in the present drug discovery research. The data available from Ayurveda on various medicinal plants for treatment of diabetes can efficiently yield potential new lead as antidiabetic agents. For wider acceptability and popularity of herbal remedies available in Ayurveda scientific validation by the elucidation of mechanism of action is very much essential. Modern biological techniques are available now to elucidate the biochemical basis of the effectiveness of these medicinal plants. Keeping this idea the research programme under this thesis has been planned to evaluate the molecular mechanism responsible for the antidiabetic property of Symplocos cochinchinensis, the main ingredient of Nishakathakadi Kashayam, a wellknown Ayurvedic antidiabetic preparation. A general introduction of diabetes, its pathophysiology, secondary complications and current treatment options, innovative solutions based on phytomedicine etc has been described in Chapter 1. The effect of Symplocos cochinchinensis (SC), on various in vitro biochemical targets relevant to diabetes is depicted in Chapter 2 including the preparation of plant extract. Since diabetes is a multifactorial disease, ethanolic extract of the bark of SC (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90 % ethanol) were evaluated by in vitro methods against multiple targets such as control of postprandial hyperglycemia, insulin resistance, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPPxxi IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition, insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F and reduced triglyceride accumulation in 3T3-L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence of bioactives (beta-sitosterol, phloretin 2’glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test (OGTT) to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. Chapter 3 highlights the beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) against hyperglycemia associated secondary complications in streptozotocin (60 mg/kg body weight) induced diabetic rat model. Proper sanction had been obtained for all the animal experiments from CSIR-CDRI institutional animal ethics committee. The experimental groups consist of normal control (NC), N + SCE 500 mg/kg bwd, diabetic control (DC), D + metformin 100 mg/kg bwd, D + SCE 250 and D + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited significant glucose lowering effect and decreased HOMA-IR, % HbA1c, lens AR activity, and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug. xxii The possible molecular mechanism behind the protective property of S. cochinchinensis against the insulin resistance in peripheral tissue as well as dyslipidemia in in vivo high fructose saturated fat diet model is described in Chapter 4. Initially animal were fed a high fructose saturated fat (HFS) diet for a period of 8 weeks to develop insulin resistance and dyslipidemia. The normal diet control (ND), ND + SCE 500 mg/kg bwd, high fructose saturated fat diet control (HFS), HFS + metformin 100 mg/kg bwd, HFS + SCE 250 and HFS + SCE 500 were the experimental groups. SCEs and metformin were administered daily for the next 3 weeks and sacrificed at the end of 11th week. At the end of week 11, HFS rats showed significantly abnormal glucose and insulin tolerance, HOMA-IR, % HbA1c, adiponectin, lipid profile, liver glycolytic and gluconeogenic enzyme activities, liver and muscle triglyceride accumulation compared to ND. HFS rats also exhibited increased level of plasma inflammatory cytokines, upregulated mRNA level of gluconeogenic and lipogenic genes in liver. HFS exhibited the increased expression of GLUT-2 in liver and decreased expression of GLUT-4 in muscle and adipose. SCE treatment also preserved the architecture of pancreas, liver, and kidney tissues. Treatment with SCE reversed the alterations of biochemical parameters, improved insulin sensitivity by modifying gene expression in liver, muscle and adipose tissues. Overall results suggest that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with antiglycation and antioxidant activities.

The role of ligneous vegetation for livestock nutrition in the sub-Sahelian and Sudanian zones of West Africa: Potential effects of climate change

Climate change and variability in sub-Saharan West Africa is expected to have negative consequences for crop and livestock farming due to the strong dependence of these sectors on rainfall and natural resources, and the low adaptive capacity of crops farmers, agro-pastoralist and pastoralists in the region. The objective of this PhD research was to investigate the anticipated impacts of expected future climate change and variability on nutrition and grazing management of livestock in the prevailing extensive agro-pastoral and pastoral systems of the Sahelian and Sudanian zones of Burkina Faso. To achieve this, three studies were undertaken in selected village territories (100 km² each) in the southern Sahelian (Taffogo), northern Sudanian (Nobere, Safane) and southern Sudanian (Sokouraba) zone of the country during 2009 and 2010. The choice of two villages in the northern Sudanian zone was guided by the dichotomy between intense agricultural land use and high population density near Safane, and lower agricultural land use in the tampon zone between the village of Nobere and the National Park Kaboré Tambi of Pô. Using global positioning and geographical information systems tools, the spatio-temporal variation in the use of grazing areas by cattle, sheep and goats, and in their foraging behaviour in the four villages was assessed by monitoring three herds each per species during a one-year cycle (Chapter 2). Maximum itinerary lengths (km/d) were observed in the hot dry season (March-May); they were longer for sheep (18.8) and cattle (17.4) than for goats (10.5, p<0.05). Daily total grazing time spent on pasture ranged from 6 - 11 h with cattle staying longer on pasture than small ruminants (p<0.05). Feeding time accounted for 52% - 72% of daily time on pasture, irrespective of species. Herds spent longer time on pasture and walked farther distances in the southern Sahelian than the two Sudanian zones (p<0.01), while daily feeding time was longer in the southern Sudanian than in the other two zones (p>0.05). Proportional time spent resting decreased from the rainy (June - October) to the cool (November - February) and hot dry season (p<0.05), while in parallel the proportion of walking time increased. Feeding time of all species was to a significantly high proportion spent on wooded land (tree crown cover 5-10%, or shrub cover >10%) in the southern Sahelian zone, and on forest land (tree crown cover >10%) in the two Sudanian zones, irrespective of season. It is concluded that with the expansion of cropland in the whole region, remaining islands of wooded land, including also fields fallowed for three or more years with their considerable shrub cover, are particularly valuable pasturing areas for ruminant stock. Measures must be taken that counteract the shrinking of wooded land and forests across the whole region, including also active protection and (re)establishment of drought-tolerant fodder trees. Observation of the selection behaviour of the above herds of cattle and small ruminant as far as browse species were concerned, and interviews with 75 of Fulani livestock keepers on use of browse as feed by their ruminant stock and as remedies for animal disease treatment was undertaken (Chapter 3) in order to evaluate the consequence of climate change for the contribution of browse to livestock nutrition and animal health in the extensive grazing-based livestock systems. The results indicated that grazing cattle and small ruminants do make considerable use of browse species on pasture across the studied agro-ecological zones. Goats spent more time (p<0.01) feeding on browse species than sheep and cattle, which spent a low to moderate proportion of their feeding time on browsing in any of the study sites. As far as the agro-ecological zones were concerned, the contribution of browse species to livestock nutrition was more important in the southern Sahelian and northern Sudanian zone than the southern Sudanian zone, and this contribution is higher during the cold and hot dry season than during the rainy season. A total of 75 browse species were selected on pasture year around, whereby cattle strongly preferred Afzelia africana, Pterocarpus erinaceus and Piliostigma sp., while sheep and goats primarily fed on Balanites aegyptiaca, Ziziphus mauritiana and Acacia sp. Crude protein concentration (in DM) of pods or fruits of the most important browse species selected by goats, sheep and cattle ranged from 7% to 13% for pods, and from 10% to 18% for foliage. The concentration of digestible organic matter of preferred browse species mostly ranged from 40% to 60%, and the concentrations of total phenols, condensed tannins and acid detergent lignin were low. Linear regression analyses showed that browse preference on pasture is strongly related to its contents (% of DM) of CP, ADF, NDF and OM digestibility. Interviewed livestock keepers reported that browse species are increasingly use by their grazing animals, while for animal health care use of tree- and shrub-based remedies decreased over the last two decades. It is concluded that due to climate change with expected negative impact on the productivity of the herbaceous layer of communal pastures browse fodder will gain in importance for animal nutrition. Therefore re-establishment and dissemination of locally adapted browse species preferred by ruminants is needed to increase the nutritional situation of ruminant stock in the region and contribute to species diversity and soil fertility restoration in degraded pasture areas. In Chapter 4 a combination of household surveys and participatory research approaches was used in the four villages, and additionally in the village of Zogoré (southern Sahelian zone) and of Karangasso Vigué (northern Sudanian zone) to investigate pastoralists’ (n= 76) and agro-pastoralists’ (n= 83) perception of climate change, and their adaptation strategies in crop and livestock production at farm level. Across the three agro-ecological zones, the majority of the interviewees perceived an increase in maximum day temperatures and decrease of total annual rainfall over the last two decades. Perceptions of change in climate patterns were in line with meteorological data for increased temperatures while for total rainfall farmers’ views contrasted the rainfall records which showed a slight increase of precipitation. According to all interviewees climate change and variability have negative impacts on their crop and animal husbandry, and most of them already adopted some coping and adaptation strategies at farm level to secure their livelihoods and reduce negative impacts on their farming system. Although these strategies are valuable and can help crop and livestock farmers to cope with the recurrent droughts and climate variability, they are not effective against expected extreme climate events. Governmental and non-governmental organisations should develop effective policies and strategies at local, regional and national level to support farmers in their endeavours to cope with climate change phenomena; measures should be site-specific and take into account farmers’ experiences and strategies already in place.

El mercado móvil de telecomunicaciones en Colombia ante externalidades de red

Si bien la generalidad de los mercados de telefonía móvil se consideran suficientemente competidos, los mercados en los que el operador más grande supera ampliamente en participación de mercado a sus seguidores constituyen un motivo de preocupación para sus respectivas autoridades regulatorias y de competencia. El análisis económico del problema ha llevado a que exista una cantidad creciente de literatura relacionada, principalmente con el propósito de analizar la persistencia de la asimetría en las cuotas de mercado. Tal es el caso del mercado móvil de telecomunicaciones en Colombia, donde la Comisión de Regulación de Comunicaciones ha sostenido que a la luz del problema de competencia que se origina por la unión de una participación de mercado considerablemente asimétrica y el diferencial de precios, el operador más grande adquiere una ventaja competitiva considerable frente a los demás operadores en el mercado, y por lo tanto es un operador con poder significativo de mercado, u operador con posición dominante. Por lo anterior, el presente trabajo evalúa la imposición de algunas medidas regulatorias con el fin de verificar si estas contribuyen a generar una mayor competencia en el mercado, y mejores condiciones para los operadores competidores.

Marco conceptual para el análisis y comprensión de la política pública distrital en salud y educación para la población en condición de desplazamiento

El Distrito Capital de Bogotá se ha convertido en constante receptor de población en estado de desplazamiento forzado, y dada la condición de extrema vulnerabilidad de la población desplazada, no sólo por el hecho mismo del desplazamiento forzado, sino también porque en la mayor parte de los casos se trata de personas tales como mujeres cabeza de familia, menores de edad, personas de la tercera edad y minorías étnicas, ha persistido en el tiempo la violación de los derechos de la población en condición de desplazamiento, las autoridades competentes han implementado políticas públicas para establecer los correctivos suficientes y con ello superar las violaciones detectadas, a pesar de la insuficiencia de recursos económicos dada la evolución y magnitud del fenómeno de desplazamiento forzado.

Llamamiento en garantía con fines de repetición: problemas de su aplicación en el derecho colombiano

Estudio sobre el llamamiento en garantía con fines de repetición, como mecanismo jurídico para exigir la responsabilidad patrimonial de los agentes estatales, enfocado en las causas de su ineficacia y sus posibles correctivos.

La protección jurídica del canal de distribución

Analiza la función económica de distribución comercial, da un recorrido general de la figura para presentar los remedios jurídicos del distribuidor en el Derecho colombiano.

A juridical-practical framework for the investigation of crimes against granting of public housing services

The public service enterprises are victims of crimes and felonies which may reduce their capacity to perform their functions. These enterprises expend much money and effort in order to prevent those criminal behaviors. For this reason they ask from the authorities more efficient measures against crime; however, such enterprises may feel that they are not being given sufficient importance and/or remedies in dealing with such crime. The aim paper of this is not to study the problem from de substantive criminal law point of view. Rather, this paper’s goal is to study the Colombia’s Rules of Criminal Procedure, which regulate the investigation of this kind of crime. The article will look particularly at the competency of the relevant authorities at the investigative stages. Finally, it will make some recommendations regarding a proper route towards the investigation of these criminal behaviors.

La reafirmación de los recursos administrativos como requisito de procedibilidad en Ley 1437 de 2011: una posición privilegiada de la administración pública en Colombia frente a los particulares

La problemática que aborda este trabajo comprende el análisis de las implicaciones y del significado de la reafirmación del trámite de los recursos administrativos como un requisito de procedibilidad que el particular debe agotar para poder acudir a la jurisdicción administrativa cuando pretende dirimir una controversia originada en una decisión adoptada por una autoridad pública. Nos preguntamos, si con ello, se cumplió todo aquello que inspiró a los precursores de la expedición del nuevo código de procedimiento administrativo y de lo contencioso administrativo. La investigación se desarrolló a partir de un plan de trabajo divido en dos partes. En la primera, se analizó la doble connotación que caracteriza a los recursos administrativos, así como la evolución, la efectividad y la importancia de aquellos de cara a los privilegios de la administración pública. También se abordaron las modificaciones que el legislador ha efectuado a esta herramienta de autocontrol de las decisiones administrativas y la jurisprudencia expedida por el Consejo de Estado y la Corte Constitucional en esta materia. En la segunda parte, con el fin de establecer si la reafirmación del agotamiento del recurso de apelación como requisito de procedibilidad para acudir a la jurisdicción administrativa, traduce los propósitos del legislador al expedir el nuevo código administrativo y de lo contencioso administrativo, se plasmaron aspectos que debieron considerarse en esta reforma, en el marco de las tendencias de un Estado Social de Derecho y de la problemática de la congestión judicial que intenta afrontar el legislador. En ese marco, se explicaron los aspectos que permitieron constatar que los propósitos del legislador se desdibujaron al mantener la obligatoriedad de agotar los recursos administrativos para que el particular pueda someter una controversia a la jurisdicción administrativa.

Resonancia magnética cardiaca: medidas lineales y volumétricas en adultos sanos

Introducción: La gran mayoría de las medidas de normalidad utilizadas para la interpretación de resonancia cardiaca son extrapoladas de las medidas de ecocardiografía. Los limitados registros de medidas de normalidad se encuentran ajustados en poblaciones extranjeras, no hay registros en latinoamericanos. Objetivo: Determinar las dimensiones cardiacas utilizando resonancia magnética en una población de personas sin antecedente médicos con repercusión cardiaca para lograr una muestra de valores que permitan ajustar las medidas de normalidad utilizadas por nuestro servicio. Materiales y métodos: se analizaron 45 sujetos sanos con edad comprendida entre los 21 y 45 años, las adquisiciones se realizaron utilizando un equipo de RM de 1,5 teslas, el análisis de las imágenes se realizó mediante el programa Cardiac Volume Vx. Se evaluaron múltiples parámetros morfofuncionales a través de análisis estadístico por medio del sistema SPSS versión 23. Resultados: Mediciones obtenidas de ventrículo izquierdo principales fueron volumen diastólico en mujeres de 62 ml +/- 7.1 y en hombres de 65 ml +/- 11.2 y fracción de eyección de 60 % +/- 5 en mujeres y de 62 % +/- 9 en hombres. En ventrículo derecho el volumen diastólico final se encontró 81.8 ml +/- 14.6 en mujeres y 100 ml +/- 24.8 en hombres y fracción de eyección de 53 % +/- 17 en mujeres y de 45 % +/- 12 en hombres. Volumen de fin de diástole de 50 +/- 12.7 ml en mujeres y de 49 ml +/- 19 ml en hombres y fracción de eyección de aurícula izquierda de 55 % +/- 0.08 en mujeres y de 50 % +/- 0.07 en hombres. Volumen de fin de diástole de 44.1 ml +/- 18.5 en mujeres y de 49.2 ml +/- 22.9 en hombres y fracción de eyección de aurícula derecha de 50 % +/- 11 en mujeres y de 45 % +/- 8 en hombres. Se obtuvieron otras medidas lineales y volumétricas adicionales de cavidades cardiacas y de grandes vasos supracardiacos. Conclusiones: se describen los valores de referencia de los parámetros morfofuncionales de las cavidades cardiacas y de vasos supracardiacos. El sexo fue tenido en cuenta como covariable relacionada con la modificación de los parámetros evaluados. Se sugieren variaciones en las medidas de cavidades cardiacas para la población estudiada relacionada con aclimatación crónica a la altitud de la ciudad de Bogotá.

A imprensa e a farmácia : publicidade e medicamentos no século XIX

A influência da Publicidade na sociedade do século XIX foi notória. Utilizando a Imprensa como veículo de eleição, a Publicidade disseminou ideias, cultura, hábitos, elegância e bom gosto. Mas mais importante do que isso, a Publicidade gerou mercados, aumentou a demanda, intensificou a produção e reduziu preços. O desenvolvimento tecnológico adveio da Revolução Industrial permitiu tornar as técnicas publicitárias mais atractivas ao observador e futuro consumidor. A utilização de figuras, inicialmente a preto e branco e posteriormente a cores, foi um excelente exemplo disso. Os anúncios publicitários a medicamentos, alguns deles de fórmula secreta, foram uma prática comum no século XIX. E dessa forma, seduzidos pelo sucesso que esses anúncios tinham na população, os charlatães rapidamente tomaram consciência de que podiam lucrar bastante com as suas fórmulas “milagrosas”. O sector farmacêutico viu, de forma indirecta, a Publicidade transformar o sector, visto que foi através da industrialização da produção dos remédios secretos que se obteve as especialidades farmacêuticas.

Comercio exterior y defensa comercial en Brasil: un balance del período 2003-2009 (Tema Central)

El comercio exterior brasileño y la utilización de instrumentos de defensa comercial por parte del gobierno están asociados con las características de la economía brasileña y la política comercial desarrollada en el país. Con el propósito de investigar esta relación se analizan, en la primera parte, las características primordiales del comercio en el período 2003-2009, que incluye los siete años completos del Gobierno Lula da Silva. La segunda parte presenta y discute las cifras de la actividad de defensa comercial del país y relaciona la tendencia del flujo de las importaciones comerciales con los datos de apertura de procedimientos de defensa comercial. Por último, se efectuan observaciones finales acerca de los datos y análisis elaborado.

spotlight europe 20120/05, August 2012: Confronting the crisis

The euro crisis has not gone away on holiday. In fact, it continues to generate a never-ending string of horrific headlines. Where is it all going to end? In this article we describe the proposed remedies that are currently being discussed, and what blue and red eurobonds, euro bills, FIRE and the debt redemption fund can actually achieve.

Construction management contracts: law and practice

The context of construction management (CM) reveals that this method of procurement is as much a management philosophy as a contract structure. It is important to consider legal and contractual issues in this context. The interplay between management and law is complex and often misunderstood. Before considering specific issues, the use of contractual remedies in business agreements is discussed. In addition, the extent to which standardising a form of contract detracts or contributes to the success of projects is also considered. The dearth of judicial decisions, and the lack of a standard form, render it difficult to be specific about legal issues. Therefore, the main discussion of legal issues is centred around a recently completed research project which involved eliciting the views of a cross-section of experienced construction management clients, consultants and trade contractors. These interviews are used as the basis for highlighting some of the most important legal points to consider when setting up CM projects. The interviews revealed that the advantage of CM is the proximity of the client to the trade contractors and the disadvantage is that it depends on a high degree of professionalism and experience; qualities which are unfortunately difficult to find in the UK construction industry.

Truth - the essential dimension of ethics in scholarship, teaching, learning and research

The introduction of metrics, league tables, performance targets, research assessment exercises and a range of other pressures placed by society, funding bodies and employers on scholars, teachers and students have resulted in diminished value being placed on the essential ethical criterion of truth. The impact of reduced valuation for truth has a huge impact on the standing of science and not least horticultural science in the eyes of the general public at a time when this should be a primary concern. This contribution discusses examples of the impact of diminished valuation of truth, the causes of this phenomenon, the results that come from this situation and remedies that are needed.

Differences in perceived risks and benefits of herbal, over-the-counter conventional, and prescribed conventional, medicines, and the implications of this for the safe and effective use of herbal products

Objectives: To investigate people's views about the efficacy and specific risks of herbal, over-the-counter (OTC) conventional, and prescribed conventional medicines, and their likelihood of taking a second (herbal or OTC conventional) product in addition to a prescribed medicine. Methods: Experiment 1 (1 factor within-participant design); Experiment 2 (1 factor between-participant design). Convenience samples of general population were given a hypothetical scenario and required to make a number of judgements. Results: People believed herbal remedies to be less effective, but less risky than OTC and prescribed conventional medicines. Herbal medicines were not seen as being safer simply because of their easier availability. Participants indicated that they would be more likely to take a herbal medicine than a conventional OTC medicine in addition to a prescribed medicine, and less likely to consult their doctor in advance. Conclusion: People believe that herbal medicines are natural and relatively safe and can be used with less caution. People need to be given clear information about the risks and benefits of herbal medicines if they are to use such products safety and effectively. (c) 2006 Elsevier Ltd. All rights reserved.