Drug-loaded nanocarriers : passive targeting and crossing of biological barriers

Poor bioavailability and poor pharmacokinetic characteristics are some of the leading causes of drug development failure. Therefore, poorly-soluble drugs, fragile proteins or nucleic acid products may benefit from their encapsulation in nanosized vehicles, providing enhanced solubilisation, protection against degradation, and increased access to pathological compartments. A key element for the success of drug-loaded nanocarriers (NC) is their ability to either cross biological barriers themselves or allow loaded drugs to traverse them to achieve optimal pharmacological action at pathological sites. Depending on the mode of administration, NC may have to cross different physiological barriers in their journey towards their target. In this review, the crossing of biological barriers by passive targeting strategies will be presented for intravenous delivery (vascular endothelial lining, particularly for tumour vasculature and blood-brain barrier targeting), oral administration (gastrointestinal lining) and upper airway administration (pulmonary epithelium). For each specific barrier, background information will be provided on the structure and biology of the tissues involved as well as available pathways for nano-objects or loaded drugs (diffusion and convection through fenestration, transcytosis, tight junction crossing, etc.). The determinants of passive targeting − size, shape, surface chemistry, surface patterning of nanovectors − will be discussed in light of current results. Perspectives on each mode of administration will be presented. The focus will be on polymeric nanoparticles and dendrimers although advances in liposome technology will be also reported as they represent the largest body in the drug delivery literature.

Design of Cyclophanes: Synthesis and Study of Photophysical and Biomolecular Recognition Properties

Development of organic molecules that exhibit selective interactions with different biomolecules has immense significance in biochemical and medicinal applications. In this context, our main objective has been to design a few novel functionaIized molecules that can selectively bind and recognize nucleotides and DNA in the aqueous medium through non-covalent interactions. Our strategy was to design novel cycIophane receptor systems based on the anthracene chromophore linked through different bridging moieties and spacer groups. It was proposed that such systems would have a rigid structure with well defined cavity, wherein the aromatic chromophore can undergo pi-stacking interactions with the guest molecules. The viologen and imidazolium moieties have been chosen as bridging units, since such groups, can in principle, could enhance the solubility of these derivatives in the aqueous medium as well as stabilize the inclusion complexes through electrostatic interactions.We synthesized a series of water soluble novel functionalized cyclophanes and have investigated their interactions with nucleotides, DNA and oligonucIeotides through photophysical. chiroptical, electrochemical and NMR techniques. Results indicate that these systems have favorable photophysical properties and exhibit selective interactions with ATP, GTP and DNA involving electrostatic. hydrophobic and pi-stacking interactions inside the cavity and hence can have potential use as probes in biology.

Survival of multi-drug resistant enteropathogenic Escherichia coli and Salmonella paratyphi in Vembanadu lake as a function of saltwater barrier along southwest coast of India

The objective of the study was to evaluate the survival response of multi-drug resistant enteropathogenic Escherichia coli and Salmonella paratyphi to the salinity fluctuations induced by a saltwater barrier constructed in Vembanadu lake, which separates the lake into a freshwater dominated southern and brackish water dominated northern part. Therefore, microcosms containing freshwater, brackish water and microcosms with different saline concentrations (5, 10, 15, 20, 25 ppt) inoculated with E. coli/S. paratyphi were monitored up to 34 days at 20 and 30 WC. E. coli and S. paratyphi exhibited significantly higher (p <0.05) survival at 20 WC compared to 30 WC in all microcosms. Despite fresh/brackish water, E. coli and S. paratyphi showed prolonged survival up to 34 days at both temperatures. They also demonstrated better survival potential at all tested saline concentrations except 25 ppt where a significantly higher (p<0.0001) decay was observed. Therefore, enhanced survival exhibited by the multi-drug resistant enteropathogenic E. coli and S. paratyphi over a wide range of salinity levels suggest that they are able to remain viable for a very long time at higher densities in all seasons of the year in Vembanadu lake irrespective of saline concentrations, and may pose potential public health risks during recreational activities

An assessment of potential public health risk associated with the extended survival of indicator and pathogenic bacteria in freshwater lake sediments

Microcosm studies were performed to evaluate the survival of Escherichia coli, Salmonella paratyphi and Vibrio parahaemolyticus in water and sediment collected from the freshwater region of Vembanad Lake (9 35◦N 76 25◦E) along the south west coast of India. All three test microorganisms showed significantly (p < 0.01) higher survival in sediment compared to overlying water. The survival in different sediment types with different particle size and organic carbon content revealed that sediment with small particle size and high organic carbon content could enhance their extended survival (p < 0.05). The results indicate that sediments of the Lake could act as a reservoir of pathogenic bacteria and exhibit a potential health hazard from possible resuspension and subsequent ingestion during recreational activities. Therefore, the assessment of bacterial concentration in freshwater Lake sediments used for contact and non contact recreation has of considerable significance for the proper assessment of microbial pollution of the overlying water, and for the management and protection of related health risk at specific recreational sites. Besides, assessment of the bacterial concentration in sediments can be used as a relatively stable indicator of long term mean bacterial concentration in the water column above

Potential Exposure Risk Associated with the High Prevalence and Survival of Indicator and Pathogenic Bacteria in the Sediment of Vembanadu Lake, India

Prevalence of faecal coliform bacteria and the survival of Escherichia coli, Vibrio parahaemolyticus and Salmonella paratyphi were studied in the water and sediment from Vembanadu Lake in the presence and absence of protozoan predators. The density of faecal coliform bacteria ranged between mean MPN value 5080–9000/100 ml in water and 110,000–988,000/1 g in sediment (p <0.01), which was 110 times greater than in overlying water. The laboratory microcosm studies revealed that E. coli, V. parahaemolyticus and S. paratyphi showed significantly higher survival (p <0.05) potential in sediment than in overlying water both in the presence and absence of protozoan predators. The results indicate that Vembanadu Lake sediment constitutes a reservoir of pathogenic bacteria and exhibits potential health hazard from possible resuspension and subsequent ingestion during recreational activities. Therefore, assessment of bacterial concentration in freshwater lake sediments used for contact and non-contact recreation is of considerable significance for the proper assessment of microbial pollution of the overlying water and the management and protection of related health risk at specific recreational sites. In addition, assessment of the bacterial concentration in sediments can be used as a relatively stable indicator of long-term mean bacterial concentration in the water column above.

Studies On In Vitfio Production Of Secondary Metabolites From Medicinal Plants

In the light of the very huge demand for natural ephedrine and pseudoephidrine, a search for an angiosperm plant containing the alkaloid ephedrine was made and could locate Sida spp. of malvaceae family. Sida is a large genus of, herbs and shrubs distributed throughout the tropics. About a dozen species occur in India. The medicinally important species known are S.rhombrfolia S.cordata and S.spinosa (Anon, 1972). Among the various species, S.rh0mbIfolia is the most widely used one in the traditional system of medicine. An attempt was made in the present study to develop an ideal bioprocess for the in vitro production of ephedrine from the cell culture system of Sida rhombrfolia Linn. ssp. retusa. The callus and suspension culture were initiated and attempts were made to enhance the yield positively by employing various strategies like mutagenesis, immobilization and addition of precursors, elicitors and penneabilizing agents.

Protease inhibitor from Moringa oleifera with potential for use as therapeutic drug and as seafood preservative

Protease inhibitors are well known to have several applications in medicine and biotechnology. Several plant sources are known to return potential protease inhibitors. In this study plants belonging to different families of Leguminosae, Malvaceae, Rutaceae, Graminae and Moringaceae were screened for the protease inhibitor. Among them Moringa oleifera, belonging to the family Moringaceae, recorded high level of protease inhibitor activity after ammonium sulfate fractionation. M. oleifera, which grows throughout most of the tropics and having several industrial and medicinal uses, was selected as a source of protease inhibitor since so far no reports were made on isolation of the protease inhibitor. Among the different parts of M. oleifera tested, the crude extract isolated from the mature leaves and seeds showed the highest level of inhibition against trypsin. Among the various extraction media evaluated, the crude extract prepared in phosphate buffer showed maximum recovery of the protease inhibitor. The protease inhibitor recorded high inhibitory activity toward the serine proteases thrombin, elastase, chymotrypsin and the cysteine

Socio-economic characterization of integrated cropping systems in urban and peri-urban agriculture of Faisalabad, Pakistan

Faisalabad city is surrounded by agricultural lands, where farmers are growing vegetables, grain crops, and fodder for auto-consumption and local marketing. To study the socioeconomic impact and resource use in these urban and peri-urban agricultural production (UPA) systems, a baseline survey was conducted during 2009–2010. A total of 140 households were selected using a stratified sampling method and interviewed with a structured questionnaire. The results revealed that 96 % of the households rely on agriculture as their main occupation. Thirty percent of the households were owners of the land and the rest cultivated either rented or sharecropped land. Most of the families (70 %) were headed by a member with primary education, and only 10 % of the household head had a secondary school certificate. Irrigationwater was obtained from waste water (37 %), canals (27 %), and mixed alternative sources (36 %). A total of 35 species were cultivated in the UPA systems of which were 65% vegetables, 15% grain and fodder crops, and 5% medicinal plants. Fifty-nine percent of the households cultivated wheat, mostly for auto-consumption. The 51 % of the respondents grew cauliflower (Brassica oleracea L.) and gourds (Cucurbitaceae) in the winter and summer seasons, respectively. Group marketing was uncommon and most of the farmers sold their produce at the farm gate (45 %) and on local markets (43 %). Seeds and fertilizers were available from commission agents and dealers on a credit basis with the obligation to pay by harvested produce. A major problem reported by the UPA farmers of Faisalabad was the scarcity of high quality irrigation water, especially during the hot dry summer months, in addition to lacking adequate quantities of mineral fertilizers and other inputs during sowing time. Half of the respondents estimated their daily income to be less than 1.25 US$ and spent almost half of it on food. Monthly average household income and expenses were 334 and 237 US$, respectively.

Urban and peri-urban agricultural production along railway tracks: a case study from the Mumbai Metropolitan Region

Urban and peri-urban agriculture (UPA) contributes to food security, serves as an opportunity for income generation, and provides recreational services to urban citizens. With a population of 21 Million people, of which 60 % live in slums, UPA activities can play a crucial role in supporting people’s livelihoods in Mumbai Metropolitan Region (MMR). This study was conducted to characterize the railway gardens, determine their role in UPA production, and assess potential risks. It comprises a baseline survey among 38 railway gardeners across MMR characterized by different demographic, socio-economic, migratory, and labour characteristics. Soil, irrigation water, and plant samples were analyzed for nutrients, heavy metals, and microbial load. All the railway gardeners practiced agriculture as a primary source of income and cultivated seasonal vegetables such as lady’s finger (Abelmoschus esculentus L. Moench), spinach (Spinacia oleracea L.), red amaranth (Amaranthus cruentus L.), and white radish (Raphanus sativus var. longipinnatus) which were irrigated with waste water. This irrigation water was loaded with 7–28 mg N l^(−1), 0.3–7 mg P l^(−1), and 8–32 mg K l^(−1), but also contained heavy metals such as lead (0.02–0.06 mg Pb l^(−1)), cadmium (0.03–0.17 mg Cd l^(−1)), mercury (0.001–0.005 mg Hg l^(−1)), and pathogens such as Escherichia coli (1,100 most probable number per 100 ml). Levels of heavy metals exceeded the critical thresholds in surface soils (Cr, Ni, and Sr) and produce (Pb, Cd, and Sr). The railway garden production systems can substantially foster employment and reduce economic deprivation of urban poor particularly slum dwellers and migrant people. However this production system may also cause possible health risks to producers and consumers.

Simultaneous Drying and Separation of Composite Agricultural Material for Hay Processing

In composite agricultural materials such as grass, tee, medicinal plants; leaves and stems have a different drying time. By this behavior, after leaving the dryer, the stems may have greater moisture content than desired, while the leaves one minor, which can cause either the appearance of fungi or the collapse of the over-dried material. Taking into account that a lot of grass is dehydrated in forced air dryers, especially rotary drum dryers, this research was developed in order to establish conditions enabling to make a separation of the components during the drying process in order to provide a homogeneous product at the end. For this, a rotary dryer consisting of three concentric cylinders and a circular sieve aligned with the more internal cylinder was proposed; so that, once material enters into the dryer in the area of the inner cylinder, stems pass through sieve to the middle and then continue towards the external cylinder, while the leaves continue by the inner cylinder. For this project, a mixture of Ryegrass and White Clover was used. The characteristics of the components of a mixture were: Drying Rate in thin layer and in rotation, Bulk density, Projected Area, Terminal velocity, weight/Area Ratio, Flux through Rotary sieve. Three drying temperatures; 40°C, 60° C and 80° C, and three rotation speeds; 10 rpm, 20 rpm and 40 rpm were evaluated. It was found that the differences in drying time are the less at 80 °C when the dryer rotates at 40 rpm. Above this speed, the material adheres to the walls of the dryer or sieve and does not flow. According to the measurements of terminal velocity of stems and leaves of the components of the mixture, the speed of the air should be less than 1.5 m s-1 in the inner drum for the leaves and less than 4.5 m s-1 in middle and outer drums for stems, in such way that only the rotational movement of the dryer moves the material and achieves a greater residence time. In other hand, the best rotary sieve separation efficiencies were achieved when the material is dry, but the results are good in all the moisture contents. The best rotary speed of sieve is within the critical rotational speed, i.e. 20 rpm. However, the rotational speed of the dryer, including the sieve in line with the inner cylinder should be 10 rpm or less in order to achieve the greatest residence times of the material inside the dryer and the best agitation through the use of lifting flights. With a finite element analysis of a dryer prototype, using an air flow allowing speeds of air already stated, I was found that the best performance occurs when, through a cover, air enters the dryer front of the Middle cylinder and when the inner cylinder is formed in its entirety through a sieve. This way, air flows in almost equal amounts by both the middle and external cylinders, while part of the air in the Middle cylinder passes through the sieve towards the inner cylinder. With this, leaves do not adhere to the sieve and flow along drier, thanks to the rotating movement of the drums and the showering caused by the lifting flights. In these conditions, the differences in drying time are reduced to 60 minutes, but the residence time is higher for the stems than for leaves, therefore the components of the mixture of grass run out of the dryer with the same desired moisture content.

Flora medicinal y sus conocimientos asociados : lineamientos para una reglamentación

En este texto se presenta un espacio de intercambio de conocimientos desde una perspectiva científica, técnica y jurídica, para contribuir a la protección de los recursos naturales. Debido a la importancia de establecer mecanismos para proteger la biodiversidad y posibilitar la preservación de los conocimientos asociados especialmente al uso de la flora medicinal, la Línea de Investigación en Política y Legislación, del Grupo de Estudios en Sistemas Tradicionales de Salud de la Facultad de Medicina, y la Línea de Derecho Ambiental y Grupos Étnicos, del Grupo de Derechos Humanos de Jurisprudencia de la Universidad del Rosario, desarrollaron este libro a través del cual la Universidad se propone profundizar en el panorama actual de la reglamentación y política –Internacional, nacional y local—respecto a la flora medicinal y al patrimonio cultural inmaterial asociado a esta.

The regulation of Internet content. A qualitative, Colombian and comparative law study

 The incursion of Internet has created new forms of information and communication. As a result, today’s generation is culturally socialized by the influence of information and communication technologies in their various forms. This has generated a series of characteristics of social and cultural behaviour which are derivative of didactic, academic or recreational use. Nevertheless the use of the Internet from an early age represents not only a useful educational tool; it can constitute a great danger when it is used to access contents unsuitable for their adaptive development. Accordingly, it is necessary to study the legal regulation of internet content and to evaluate how such regulation may affect rights. Further, it is also important to study of the impact and use of this technological tool at level of the familiar unit, to understand better how it can suggest appropriate social mechanisms for the constructive use of Internet. The present investigation involves these two aspects with the purpose of uniting the legal and social perspective in a joint analysis that allows one more a more integral vision of this problem of great interest at the global level. 

Consumo de sustancias psicoactivas en los contextos recreativos entre estudiantes universitarios en Colombia

El consumo de sustancias psicoactivas (SPA) representa un problema de salud pública en Colombia y en el mundo. La población que recurre a este tipo de sustancias es cada vez más joven y sus efectos son potencialmente deletéreos y pueden afectar todas las áreas de ajuste de la persona. Aunque así se ha concebido, esta práctica no siempre está asociada con problemas personales ni con altos grados de estrés. Puede haber otras motivaciones asociadas. Objetivos: los objetivos de este artículo están dirigidos a presentar: (a) la frecuencia relativa de consumo de SPA entre los estudiantes universitarios, (b) las SPA más utilizadas por los estudiantes universitarios y sus diferencias según el sexo y la edad, (c) la relación entre el uso de SPA y los contextos de diversión. Materiales y métodos: este fue un estudio descriptivo correlacional, derivado de un proyecto de investigación italiano, con una muestra de 226 estudiantes de cuatro carreras de una universidad privada de Bogotá, seleccionados por muestreo aleatorio estratificado con asignación proporcional, a quienes se les aplicó una encuesta. Resultados: las SPA de mayor utilización son el alcohol, la nicotina y la marihuana, cuya mayor predominancia se presenta en el sexo masculino. Los resultados son congruentes con la tendencia nacional. Conclusión: el consumo de SPA en la población universitaria es alto y algunos contextos recreativos están asociados con esta conducta.

Poor people and risky business

We try to explain why economic conflicts and illegal business often take place in poor countries. We use the concept of subsistence level of consumption (d) and assume a regular concave utility function for consumption levels higher than d. For consumption levels lower than d utility is constant and equal to zero. Under this framework poor agents are risk-lovers. This result helps to explain why economic conflicts are more likely to appear in poor economies and why poor agents are more willing to undertake illegal business.

Effect of human disturbance on long-term habitat use and breeding success of the European Nightjar, Caprimulgus europaeus

Land managers often respond to declining numbers of target species by creating additional areas of habitat. If these habitats are also subject to human disturbance, then their efforts may be wasted. The European Nightjar (Caprimulgus europaeus) is a ground-nesting bird that is listed as a species of European Conservation Concern. It appears to be susceptible to human disturbance during the breeding season. We examined habitat use and reproductive success over 10 years in a breeding population on 1335 ha of managed land in Nottinghamshire, England. The study site was divided into a heavily disturbed section and a less disturbed section of equal habitat availability, forming a natural long-term experiment. The site is open to the public, and visitor numbers approximately doubled during the study. We found that overall Nightjar density was significantly lower and there were significantly fewer breeding pairs in the heavily disturbed habitat compared with the less disturbed habitat. However, average breeding success per pair, in terms of eggs and fledglings produced, was not significantly different between the two sections across years. Our findings suggest that human recreational disturbance may drastically alter settlement patterns and nest site selection of arriving females in some migratory ground-nesting species and may reduce the utility of apparently suitable patches of remnant and created habitat. Land managers should bear this in mind when creating new areas of habitat that will also be accessible to the public. Our study also highlights the value of long-term population monitoring, which can detect trends that short-term studies may miss.