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Selected AbstractsSensors for the Detection and Quantification of Bacterial Contamination in Water for Human Use,ADVANCED ENGINEERING MATERIALS, Issue 5 2010Raquel Barbosa Queirós The deterioration of water quality by Cyanobacteria cause outbreaks and epidemics associated with harmful diseases in Humans and animals because of the toxins that they release. Microcystin-LR is one of the hepatotoxins most widely studied and the World Health Organization, recommend a maximum value of 1,µg,L,1 in drinking water. Highly specific recognition molecules, such as molecular imprinted polymers are developed to quantify microcystins in waters for human use and shown to be of great potential in the analysis of these kinds of samples. The obtained results were auspicious, the detection limit found, 1.5,µg,L,1, being of the same order of magnitude as the guideline limit recommended by the WHO. This technology is very promising because the sensors are stable and specific, and the technology is inexpensive and allows for rapid on-site monitoring. [source] Evidence-based (S3) guideline for the treatment of psoriasis vulgaris , Update: "Therapeutic options" and "Efalizumab"JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2010Alexander Nast Summary In February 2009, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) had recommended the suspension of efalizumab's (Raptiva®) marketing authorization, because its benefits in the treatment of psoriasis were modest, while there was a risk of serious side effects in patients receiving the medicine, including the occurrence of progressive multifocal leukoencephalopathy (PML). The guideline group has changed the guideline accordingly. [source] Carrying Capacity and Potential Production of Ungulates for Human Use in a Mexican Tropical Dry ForestBIOTROPICA, Issue 4 2007Salvador Mandujano ABSTRACT Data are provided on the carrying capacity and potential production for sustainable human use of white-tailed deer (Odocoileus virginianus) and collared peccary (Pecari tajacu) in a protected tropical dry forest at Chamela on the Pacific coast of Mexico. In this paper, the carrying capacity was defined as the equilibrium density plus the number of animals removed by predators. The equilibrium point was estimated from the density dependent relationship between the finite population growth rate and the current density according to a logistic model. Annual density was estimated using the line transect method. Carrying capacity estimates were 16.5 to 17.2 deer/km2 and 9.3,9.5 peccaries/km2, representing a combined biomass of 841,874 kg/km2. A potential production for human use of 2.1 deer/km2 and 4.4 peccaries/km2 was estimated employing the model of Robinson and Redford (1991). The data suggest that, in the protected tropical dry forest of Chamela, the density and biomass of wild ungulates can maintain a similar or greater density and biomass than other Neotropical forests. To obtain an accurate estimation of the maximum sustainable yield (MSY), it is necessary to consider predation. From a management point of view, it is important to consider that carrying capacity varies as a function of the rainfall pattern. RESUMEN Se presentan datos acerca de la capacidad de carga y la producción potencial del venado cola blanca (Odocoileus virginianus) y pecarí de collar (Pecari tajacu) para aprovechamiento humano en un bosque tropical seco de Chamela en la costa Pacífica de México. En este trabajo se definió capacidad de carga como la densidad en el punto de equilibrio del crecimiento poblacional más el número de animales removidos por los depredadores. La densidad en equilibrio se estimó a partir de la relación de denso-dependencia entre la tasa finita de crecimiento poblacional y la densidad anual de acuerdo al modelo logístico. La densidad anual se estimó empleando el método de transecto de línea. La capacidad de carga se estimó en 16.5 a 17.2 venados/km2 y 9.3 a 9.5 pecaries/km2, y una biomasa combinada de 841 a 874 kg/km2. Empleando el modelo de Robinson y Redford (1991) se estimó una producción potencial para aprovechamiento humano de 2.1 venados/km2 y 4.4 pecaries/km2. Los datos indican que en bosque tropical seco protegido de Chamela la densidad y biomasa de los ungulados silvestres puede ser similar o mayor en comparación con otros bosques neotropicales. Para obtener una estimación precisa de la cosecha máxima sostenible es importante considerar el efecto de la depredación. Desde una perspectiva de manejo, se debe incorporar la variación en la capacidad de carga en función del patrón de lluvias. [source] Profiling invasive fish species: the importance of phylogeny and human useDIVERSITY AND DISTRIBUTIONS, Issue 4 2005Carles Alcaraz ABSTRACT Understanding the ecological differences between native and invasive species is of considerable scientific and practical interest. We examined such differences between native and invasive inland fish species from the Iberian Peninsula in order to analyse the importance of phylogenetic correction and variability (in addition to central tendency). We collected 26 quantitative and qualitative variables on the ecology, life-history traits and human use of the 69 inland fish species of the Iberian Peninsula, including native, invasive and migratory species. The taxonomic distribution of invasive fish species deviated significantly from world freshwater richness and in contrast to native species, invasive fish belongs to only five taxonomic orders but to a wide spectrum of families not native to the Iberian Peninsula. Because the life-history traits were highly dependent on taxonomy, the results, with or without applying phylogenetic methods, differed and after accounting for phylogeny, invasive species displayed higher and wider latitude in general and a different reproductive season mainly among salmonids and cyprinids. Human use was also significantly different between native and invasive fish species and produced more variability in life-history traits of invasive species and uneven taxonomic distribution because of the high diversity of species introduced. We show that accounting for taxonomy and studying variability in addition to central tendency is important in the comparison of life-history traits between native and invasive species. [source] Role of Genetic Refuges in the Restoration of Native Gene Pools of Brown TroutCONSERVATION BIOLOGY, Issue 4 2009ROSA M. ARAGUAS introgresión de piscifactoría; pautas de manejo; acervos génicas nativas; refugios genéticos; repoblación de peces Abstract:,Captive-bred animals derived from native, alien, or hybrid stocks are often released in large numbers in natural settings with the intention of augmenting harvests. In brown trout (Salmo trutta), stocking with hatchery-reared non-native fish has been the main management strategy used to maintain or improve depleted wild brown trout populations in Iberian and other Mediterranean regions. This measure has become a serious threat to the conservation of native genetic diversity, mainly due to introgressive hybridization. Aware of this risk, the agency responsible for management of brown trout in the eastern Pyrenees (Spain) created "brown trout genetic refuges" to preserve the integrity of brown trout gene pools in this region. Within refuge areas, the prerefuge status with respect to fishing activities has been maintained, but hatchery releases have been banned completely. We evaluated this management strategy through a comparison of the stocking impact on native populations that accounted for stocking histories before and after refuge designations and fishing activities. In particular we examined the relevant scientific, cultural, and political challenges encountered. Despite agency willingness to change fishery policies to balance exploitation and conservation, acceptance of these new policies by anglers and genetic monitoring of refuge populations should also be considered. To improve management supported by genetic refuges, we suggest focusing on areas where the public is more receptive, considering the situation of local native diversity, and monitoring of adjacent introgressed populations. We recommend the use of directional supportive breeding only when a population really needs to be enhanced. In any case, management strategies should be developed to allow for protection within the context of human use. Resumen:,Animales criados en cautiverio derivados de individuos nativos, exóticos o híbridos a menudo son liberados en grandes cantidades en ambientes naturales con la intención de incrementar su explotación. En la trucha común (Salmo trutta), la repoblación con peces no nativos criados en granjas ha sido la principal estrategia de manejo utilizada para mantener o mejorar poblaciones naturales de trucha común en la Peninsula Ibérica y otras regiones Mediterráneas. Esta medida se ha convertido en una seria amenaza para la conservación de la diversidad genética nativa, debido principalmente a la hibridación introgresiva. Consciente de este riesgo, la agencia responsable del manejo de la trucha común en los Pirineos orientales (España) creó"refugios genéticos de trucha común" para preservar la integridad de las acervos genéticos de trucha común en esta región. Dentro de las áreas de refugio, se ha mantenido el estatus previo al refugio con respecto a las actividades pesqueras pero las liberaciones de peces de piscifactoría han sido completamente prohibidas. Evaluamos esta estrategia de manejo mediante la comparación del impacto de la repoblación sobre las poblaciones nativas que registraron historias de repoblación antes y después de la designación de refugios y de actividades pesqueras. En particular, examinamos los significativos retos científicos, culturales y políticos que encontramos. A pesar de la disponibilidad de la agencia para cambiar las políticas de pesca hacia un equilibrio entre la explotación y la conservación, también se debe considerar la aceptación de estas nuevas políticas por los pescadores y el monitoreo genético de las poblaciones en los refugios. Para mejorar el manejo en los refugios genéticos sugerimos centrarse en las áreas donde el público es más receptivo, considerando la situación de la diversidad nativa local y el monitoreo de las poblaciones introgresadas adyacentes. Recomendamos la utilización de la cría de apoyo direccional solo cuando una población realmente requiera ser mejorada. En cualquier caso, se deberían desarrollar estrategias de manejo para permitir la protección en el contexto del uso por el hombre. [source] Profiling invasive fish species: the importance of phylogeny and human useDIVERSITY AND DISTRIBUTIONS, Issue 4 2005Carles Alcaraz ABSTRACT Understanding the ecological differences between native and invasive species is of considerable scientific and practical interest. We examined such differences between native and invasive inland fish species from the Iberian Peninsula in order to analyse the importance of phylogenetic correction and variability (in addition to central tendency). We collected 26 quantitative and qualitative variables on the ecology, life-history traits and human use of the 69 inland fish species of the Iberian Peninsula, including native, invasive and migratory species. The taxonomic distribution of invasive fish species deviated significantly from world freshwater richness and in contrast to native species, invasive fish belongs to only five taxonomic orders but to a wide spectrum of families not native to the Iberian Peninsula. Because the life-history traits were highly dependent on taxonomy, the results, with or without applying phylogenetic methods, differed and after accounting for phylogeny, invasive species displayed higher and wider latitude in general and a different reproductive season mainly among salmonids and cyprinids. Human use was also significantly different between native and invasive fish species and produced more variability in life-history traits of invasive species and uneven taxonomic distribution because of the high diversity of species introduced. We show that accounting for taxonomy and studying variability in addition to central tendency is important in the comparison of life-history traits between native and invasive species. [source] ,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] Liposomes for entrapping local anesthetics: A liposome electrokinetic chromatographic studyELECTROPHORESIS, Issue 9 2010Jana Lokajová Abstract Bupivacaine is a lipophilic, long-acting, amide class local anesthetic commonly used in clinical practice to provide local anesthesia during surgical procedures. Several cases of accidental overdose with cardiac arrest and death have been reported since bupivacaine was introduced to human use. Recent case reports have suggested that Intralipid (Fresenius Kabi) is an effective therapy for cardiac toxicity from high systemic concentrations of, e.g. bupivacaine, even though the mechanism behind the interaction is not fully clear yet. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances in vivo. In this study, the in vitro interaction of local anesthetics (bupivacaine, prilocaine, and lidocaine) with Intralipid or lipid vesicles containing phosphatidylglycerol, phosphatidylcholine, cardiolipin, cholesterol, and N -palmitoyl- D - erythro -sphingosine (ceramide) was determined by liposome electrokinetic chromatography. The interactions were evaluated by calculating the retention factors and distribution constants. Atomic force microscopy measurements were carried out to confirm that the interaction mechanism was solely due to interactions between the analytes and the moving pseudostationary phase and not by interactions with a stationary lipid phase adsorbed to the fused-silica wall. The heterogeneity of the liposomes was also studied by atomic force microscopy. The liposome electrokinetic chromatography results demonstrate that there is higher interaction between the drugs and negatively charged liposome dispersion than with the commercial Intralipid dispersion. [source] Assessment of genotoxicity in rats treated with the antidiabetic agent, pioglitazoneENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2008Abdulkerim Bedir Abstract Pioglitazone (PIO), a member of the thiazolidinedione class of antidiabetic agents, specifically targets insulin resistance. Drugs of this class act as ligands for the gamma subtype of the peroxisome proliferator-activated receptor. Although troglitazone, another drug in this class, displayed unacceptable hepatotoxicity, PIO was approved for human use by the U.S. Food and Drug Administration. To our knowledge, there are no published reports on the genotoxicity of PIO; however, the package insert indicates that it has minimal genotoxicity. In this study, we used the comet assay to investigate the DNA damage in the peripheral blood and liver cells of rats treated with PIO. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily for 14 days by oral gavage with 0, 10, 20, and 40 mg/kg/day PIO. A dose-dependent increase in DNA damage, as assessed by % tail DNA, was observed in both hepatocytes and blood lymphocytes of the PIO-treated groups, with significant increases detected between the rats treated with all the doses of PIO and the control, and between the rats treated with different PIO doses (P < 0.005 to P < 0.0001). Treating nuclei from the exposed animals with an enzyme cocktail containing Fpg and Endonuclease III prior to performing the comet assay increased the level of DNA damage, which reflects oxidized purine and pyrimidine. Taken together, our data indicate that PIO is able to dose-dependently induce DNA damage in both the liver and blood lymphocytes of rats, which is partially due to the generation of oxidative lesions. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Sensors for the Detection and Quantification of Bacterial Contamination in Water for Human Use,ADVANCED ENGINEERING MATERIALS, Issue 5 2010Raquel Barbosa Queirós The deterioration of water quality by Cyanobacteria cause outbreaks and epidemics associated with harmful diseases in Humans and animals because of the toxins that they release. Microcystin-LR is one of the hepatotoxins most widely studied and the World Health Organization, recommend a maximum value of 1,µg,L,1 in drinking water. Highly specific recognition molecules, such as molecular imprinted polymers are developed to quantify microcystins in waters for human use and shown to be of great potential in the analysis of these kinds of samples. The obtained results were auspicious, the detection limit found, 1.5,µg,L,1, being of the same order of magnitude as the guideline limit recommended by the WHO. This technology is very promising because the sensors are stable and specific, and the technology is inexpensive and allows for rapid on-site monitoring. [source] Long-term land-cover changes in the Belgian Ardennes (1775,1929): model-based reconstruction vs. historical mapsGLOBAL CHANGE BIOLOGY, Issue 7 2002C. C. Petit Abstract Understanding long-term human-environment interactions requires historical reconstruction of past land-cover changes. The objective of this study is to reconstruct past land-use and land-cover changes in a rural municipality of the Belgian Ardennes over the last 250 years. Two approaches were compared. The first approach produced backward projections based on a mechanistic model which computes the demand for different land uses under the assumption of an equilibrium between the production and consumption of resources. The second approach involved using a series of historical maps to extract directly land-use areas. A stochastic Markov chain model was also used to project backward missing land-cover data in the time series. The consistency between the results obtained with the different approaches suggests that land-use area can be successfully reconstructed on the basis of the mechanistic model, under conditions of a subsistence farming system and a closed economy. Land-use/cover changes in the Belgian Ardennes from 1775 to 1929 were more driven by the interventionist measures of the Belgian government and by technological progress than by the ,pressure' of the growing population and livestock. Thanks to agricultural intensification, a decrease in land under human use was supporting increasing human and livestock populations from 1846 to 1880. Reforestation has accelerated since the mid-19th century. This case study illustrates the highly dynamic and non-linear character of land-use change trajectories over long time periods and their strong interactions with the history of societies. [source] MF59® -adjuvanted vaccines for seasonal and pandemic influenza prophylaxisINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 6 2008Angelika Banzhoff Abstract, Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross-reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non-adjuvanted pre-pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre-pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross-reactive immunogenicity. MF59®, the first oil-in-water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59-adjuvanted seasonal influenza vaccine (Fluad®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non-adjuvanted vaccines, and to provide cross-reactive immunity against divergent influenza strains. Similar results have been generated with a MF59-adjuvanted H5N1 pre-pandemic vaccine, which showed higher and broader immunogenicity compared with non-adjuvanted pre-pandemic vaccines. [source] Environmental risk assessment of human pharmaceuticals in the European Union: A case study with the ,-blocker atenololINTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue S1 2010Anette Küster Abstract ,-Adrenergic receptor blockers (,-blockers) are applied to treat high blood pressure, ischemic heart disease, and heart rhythm disturbances. Due to their widespread use and limited human metabolism, ,-blockers are widely detected in sewage effluents and surface waters. ,-Adrenergic receptors have been characterized in fish and other aquatic animals, so it can be expected that physiological processes regulated by these receptors in wild animals may be affected by the presence of ,-blockers. Because ecotoxicological data on ,-blockers are scarce, it was decided to choose the ,-blocker atenolol as a case study pharmaceutical within the project ERAPharm. A starting point for the assessment of potential environmental risks was the European guideline on the environmental risk assessment of medicinal products for human use. In Phase I of the risk assessment, the initial predicted environmental concentration (PEC) of atenolol in surface water (500,ng L,1) exceeded the action limit of 10,ng L,1. Thus, a Phase II risk assessment was conducted showing acceptable risks for surface water, for groundwater, and for aquatic microorganisms. Furthermore, atenolol showed a low potential for bioaccumulation as indicated by its low lipophilicity (log KOW,=,0.16), a low potential for exposure of the terrestrial compartment via sludge (log KOC,=,2.17), and a low affinity for sorption to the sediment. Thus, the risk assessment according to Phase II-Tier A did not reveal any unacceptable risk for atenolol. Beyond the requirements of the guideline, additional data on effects and fate were generated within ERAPharm. A 2-generation reproduction test with the waterflea Daphnia magna resulted in the most sensitive no-observed-effect concentration (NOEC) of 1.8,mg L,1. However, even with this NOEC, a risk quotient of 0.003 was calculated, which is still well below the risk threshold limit of 1. Additional studies confirm the outcome of the environmental risk assessment according to EMEA/CHMP (2006). However, atenolol should not be considered as representative for other ,-blockers, such as metoprolol, oxprenolol, and propranolol, some of which show significantly different physicochemical characteristics and varying toxicological profiles in mammalian studies. Integr Environ Assess Manag 2010;6:514,523. © 2009 SETAC [source] Polymeric Materials for Gene Delivery and DNA VaccinationADVANCED MATERIALS, Issue 8 2009David N. Nguyen Abstract Gene delivery holds great potential for the treatment of many different diseases. Vaccination with DNA holds particular promise, and may provide a solution to many technical challenges that hinder traditional vaccine systems including rapid development and production and induction of robust cell-mediated immune responses. However, few candidate DNA vaccines have progressed past preclinical development and none have been approved for human use. This Review focuses on the recent progress and challenges facing materials design for nonviral DNA vaccine drug delivery systems. In particular, we highlight work on new polymeric materials and their effects on protective immune activation, gene delivery, and current efforts to optimize polymeric delivery systems for DNA vaccination. [source] Strategies for developing multi-epitope, subunit-based, chemically synthesized anti-malarial vaccinesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5b 2008M. E. Patarroyo ,,Introduction ,,P. falciparum invasion of RBCs ,,Merozoite proteins involved in invading erythrocytes ,,Erythrocyte proteins involved in merozoite invasion ,,The state of current worldwide anti-malarial vaccine approaches ,,A rational approach towards developing subunit-based synthetic vaccines ,,The immune response elicited by conserved HABPs ,,Structural analysis of native and modified HABPs ,,Secondary structure analysis ,,Native and modified HABP 3D structure explains some immunological phenomena ,,Supporting the haplotype , and allele-conscious TCR concept ,,Modified HABPs' 3D structure revealed a fit into HLA molecules ,,Conclusion Abstract An anti-malarial vaccine against the extremely lethal Plasmodium falciparum is desperately needed. Peptides from this parasite's proteins involved in invasion and having high red blood cell-binding ability were identified; these conserved peptides were not immun genic or protection-inducing when used for immunizing Aotus monkeys. Modifying some critical binding residues in these high-activi binding peptides' (HABPs') attachment to red blood cells (RBC) allowed them to induce immunogenicity and protection against expermental challenge and acquire the ability to bind to specific HLA-DRp1* alleles. These modified HABPs adopted certain characterist structural configurations as determined by circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) associated with certain HLA-DR,1* haplotype binding activities and characteristics, such as a 2-Å-distance difference between amino acids fitting into HLA-DRp1 Pockets 1 to 9, residues participating in binding to HLA-DR pockets and residues making contact with the TCR, suggesting haplotyp and allele-conscious TCR. This has been demonstrated in HLA-DR-like genotyped monkeys and provides the basis for designing high effective, subunit-based, multi-antigen, multi-stage, synthetic vaccines, for immediate human use, malaria being one of them. [source] Expression of p16INK4a in peripheral blood T-cells is a biomarker of human agingAGING CELL, Issue 4 2009Yan Liu Summary Expression of the p16INK4a tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16INK4a expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16INK4a expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16INK4a, but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16INK4a expression did not independently correlate with gender or body-mass index, but was significantly associated with tobacco use and physical inactivity. In addition, p16INK4a expression was associated with plasma interleukin-6 concentration, a marker of human frailty. These data suggest that p16INK4a expression in PBTL is an easily measured, peripheral blood biomarker of molecular age. [source] Behavioral responses of nesting birds to human disturbance along recreational trailsJOURNAL OF FIELD ORNITHOLOGY, Issue 2 2010Jennifer R. Smith-Castro ABSTRACT The presence of recreational trails can impact breeding birds either indirectly by altering habitat or the movement patterns of predators or directly if the presence of humans disturbs birds. We examined the behavioral responses of nesting female Northern Cardinals (Cardinalis cardinalis) to human disturbance using both experimental and observational approaches. From April to August 2006 and 2007, we monitored Northern Cardinal nests in 18 riparian forests in Ohio, USA. Two experimental trials were conducted at each nest (N= 63), with Flight Initiation Distance (FID, the distance at which a bird flushed from the nest) recorded as we approached nests by walking directly toward them and by walking along trails located variable distances from nests. We also measured flight initiation distance (FID) when nests were approached during routine nest checks (N= 160). Cardinals were six times more likely to flush when nests were approached directly, and females on higher nests were less likely to flush regardless of distance to trail. FID was not significantly influenced by the distance of nests from trails. We found no association between nest survival and the tendency of birds to flush. Rather, nest survival was best explained by nest height. Thus, our findings suggest that the responses of birds to human use of recreational trails have only short-term effects, with no apparent effects of on nest survival. Because the reaction of birds to humans in our study depended on how nests were approached, studies where FID is used as an indicator of sensitivity to human disturbance and is determined by direct approaches may overestimate the potential impact of trails on nesting birds. RESUMEN Los senderos recreativos pueden tener impactos indirectos a las aves reproductoras por la modificación del hábitat o por la alteración de los patrones de movimiento de los depredadores y tambien pueden tener impactos directos por la perturbación de las actividades humanas. Las respuestas del comportamiento de las hembras de la especie Cardinalis cardinalis a la perturbación humana fueron estudiados usando métodos experimentales y observacionales que aplicaron la Distancia del Comienzo de Vuelo (FID por sus siglas en inglés) como una medida de sensibilidad. De Abril , Agosto de los años 2006 y 2007, monitoreamos nidos de Cardinalis cardinalis en 18 sitios de bosque ripario en Ohio, EEUU. Realizamos dos pruebas experimentales para cada nido (N= 63), así que se registró FID para cada nido cuando se hizo un acercamiento al nido o directamente o por el sendero. Adicionalmente, recopilamos la FID para los acercamientos directos durante los chequeos rutinarios de los nidos (N= 160). Era seis veces mas probable que las aves volarían cuando se hizo el acercamiento al nido directamente, que cuando un observador pas' por el sendero. Era menos probable que las aves volarían de los nidos altos, pero la tendencia de volar no era relacionada a la distancia al sendero. La FID no estaba relacionada significativamente a la distancia al sendero ni a la altura del nido. No encontramos ninguna asociación entre sobrevivencia del nido y la tendencia de volar; sino la mejor explicación para el éxito de la anidación fue solo la altura del nido. Por lo tanto, estos resultados sugieren que las respuestas del comportamiento de las aves al uso recreativo de los senderos representan efectos de corto plazo y con pocas consecuencias importantes a la reproducción. Como la reaccion de las aves a los humanos dependia de la manera en que se hicieron los acercamientos, los estudios que utilizan la respuesta de la FID a los acercamientos directos como un indicador de sensibilidad a la perturbación humana podrían sobreestimar los impactos potenciales de los senderos en los nidos. [source] Biological and Cultural Anthropology of a Changing Tropical Forest: A Fruitful Collaboration across SubfieldsAMERICAN ANTHROPOLOGIST, Issue 2 2006REBECCA HARDIN In this article, we integrate approaches from biological and cultural anthropology to describe changing relationships between humans and animals in the Dzanga-Ndoki Park and Dzanga-Sangha Dense Forest Reserve (RDS), Central African Republic (CAR). Recent decades have seen a rapid proliferation of human activities, with striking tensions between logging and conservation economies. Our data suggest that certain animals and humans initially adapted successfully to these forest uses, and that local residents have crafted culturally rich new ways of living in the forest. However, our longitudinal data indicate animal declines and expanding frontiers of increasingly intensive human use. These trends are altering previous territorial arrangements and coming to undermine today's remarkably rich spectrum of human,animal encounters there. Our combined approach offers an alternative to increasingly distinct method and theory between anthropology's subfields. We sketch a research agenda for integrated anthropological attention to environmental change, especially to transformations in human,animal interactions and entanglements. [source] MORE THAN ONE WAY TO STUDY A BUILDING: APPROACHES TO PREHISTORIC HOUSEHOLD AND SETTLEMENT SPACEOXFORD JOURNAL OF ARCHAEOLOGY, Issue 3 2006MARION CUTTING Summary. This article reviews a number of research methodologies used to record household and settlement architecture and assesses their value in the investigation of the human use of prehistoric built space. It exemplifies, through case studies, five broad approaches to, and research techniques associated with, the investigation of such architecture. These approaches are: architectural form; the spatial distribution of activities; continuity and standardization; the relationship between built and non-built space; and human patterns of movement. Then, drawing mainly on Near Eastern, and particularly Anatolian, material, it shows how a sixth approach, the use of ethnographic observation and analogy, provides insights into functional and seasonal variations in spatial use, patterns of movement and social organization. It identifies seven categories of data collection and nine observations drawn from the ethnographic material which together provide an investigative and interpretative framework for the study of early farming communities in the Near East and elsewhere. [source] Tool hoards and Neolithic use of the landscape in north-eastern IrelandOXFORD JOURNAL OF ARCHAEOLOGY, Issue 1 2004Douglas B. Bamforth Summary. Archaeologists frequently suggest that the Neolithic occupants of Ireland and Britain may not have been fully settled farmers, but were, instead, at least partially nomadic pastoralists. However, human use of any landscape is more complex than the current debate suggests, and this debate has included few systematic studies designed to evaluate this issue in detail. This paper examines hoards (or ,caches') of flaked stone tools in County Antrim, Ireland, to consider the links between anticipatory tool storage and human land-use patterns. Our data imply regular human movements over the study area, possibly linked to transhumant use of different altitudinal zones, with functionally and, sometimes, technologically specific classes of tools stored in different areas. However, the larger context of data on the Irish Neolithic clearly indicates that these movements were part of a way of life centred on permanent horticultural homesteads. [source] Hydrogels as smart biomaterialsPOLYMER INTERNATIONAL, Issue 9 2007ich Kope Abstract Hydrogels were the first biomaterials rationally designed for human use. Beginning with the pioneering work of Wichterle and Lím on three-dimensional polymers that swell in water, we review the design, synthesis, properties, and applications of hydrogels. The field of hydrogels has moved forward at a dramatic pace. The development of suitable synthetic methods encompassing traditional chemistry to molecular biology has been used in the design of hydrogels mimicking basic processes of living systems. Stimuli-sensitive hydrogels, hydrogels with controlled degradability, genetically engineered poly(amino acid) polymers reversibly self-assembling in precisely defined three-dimensional structures, and hybrid polymers composed of two distinct classes of molecules are just some examples of these exciting novel biomaterials. The biocompatibility of hydrogels and their applications from implants to nanomaterials are also reviewed. Copyright © 2007 Society of Chemical Industry [source] The journey of Indian GLP programme,looking back and forwardQUALITY ASSURANCE JOURNAL, Issue 1 2009V. Amalan Stanley Abstract The Indian GLP (Good Laboratory Practice) compliance monitoring programme has successfully brought the task of implementing the programme to the foreground where full OECD (Organization for Economic Cooperation and Development) membership is about to happen. It has been a long journey, more than five years for the programme to arrive at this juncture, succeeding through sheer commitment and will of the Science and Technology initiatives under which the programme has been implemented. Considering the spontaneous and natural challenges that are bound to make the effort of implementing the GLP compliance programme tougher for any country, the progress made by the Indian GLP programme can be considered very rapid. Though the dawn of full OECD membership for the Indian GLP programme is imminent the paper deals with the details of the journey it has traveled so far and the challenges ahead, commending the commitment of the efforts of the GLP MA (Monitoring Authority) as well as the preparedness of the test facilities. This paper discusses the GLP policy aspects that favoured the growth of the programme among non-member adherents, such as the allowance for getting GLP certification by GLP MA abroad. It also deals with the challenge of harmonizing the policies of the internal agencies that have direct influence on the implementation of the GLP programme, other than legalizing the GLP aspects as there are various government departments in India dealing with the regulatory aspects of specific drug products for human use or that are of chemical in origin. There are data requirements made mandatory by these institutions on pre-clinical or non-clinical safety evaluation of those products, which invariably necessitate studies conducted in compliance with the principles of GLP. The paper concludes with the emphasis that there is a primary need for harmony as well as legal or judicial underpinnings under the umbrella of a national GLP Monitoring Authority, a gray area to be essentially tackled with foresight, to earn credibility on the international front. Copyright © 2009 John Wiley & Sons, Ltd. [source] REVIEW ARTICLE: Status of Contraceptive VaccinesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Rajesh K. Naz Problem, This is a review of anti-sperm contraceptive vaccines (CV), and synthesis of human scFv antibodies that can be used as immunocontraceptives. Method of study, Various methods of proteomics and genomics, peptide synthesis, phage display technology, and antibody engineering were used to obtain multi-epitope vaccines and human scFv antibodies from immunoinfertile and vasectomized men. The present review primarily focuses on the effect of multi-epitope vaccines and Izumo on fertility, and synthesis and characterization of sperm specific human scFv antibodies. Results, The immunization with Izumo peptides causes a contraceptive effect in female mice. The efficacy is enhanced by combination vaccination, including peptides based on other sperm antigens. Using phage display technology, we were able to synthesize at least four novel scFv antibodies with unique complementarity determining regions (CDRs) that reacted with specific fertility-related sperm antigens. These antibodies inhibited human sperm function in vitro, and their immunocontraceptive effect in vivo by these antibodies is currently being investigated. Conclusion, The multi-epitope vaccines may provide an efficacious and viable approach to contraception. The human scFv antibodies, if they block fertility in vivo, may provide unique and novel immunocontraceptives, the first of its kind for human use. The multi-epitope CV and preformed engineered antibodies of defined specificity may obliterate the concern related to inter-individual variability of the immune response. [source] Differences in benthic cover inside and outside marine protected areas on the Great Barrier Reef: influence of protection or disturbance history?AQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 7 2009Monique R. Myers Abstract 1.Marine protected areas (MPAs) are being used increasingly to manage and protect marine resources. Most studies of MPAs have focused on fish. In this study, the influence of MPA protection on coral reef benthic organisms on the Great Barrier Reef (GBR) was investigated. In addition, the interaction between protection and natural disturbance history was examined. 2.Differences in benthic cover inside and outside MPAs were assessed at 15 pairs of Protected and General Use reefs on the GBR using annual monitoring data from the Australian Institute of Marine Science's Long-Term Monitoring Programme (LTMP). At each reef, benthic cover was determined using a benthic video survey at three sites, with each site consisting of five 50,m transect lines separated by at least 250,m running parallel to the reef crest at 6,9,m depth. 3.Benthic cover was related to both protection status and disturbance history, but natural perturbations exerted a stronger influence on benthic cover than did protection status. The influence of natural perturbation was most noticeable for hard coral. 4.Most reefs where no natural disturbance events had occurred (,undisturbed reefs') had higher hard coral cover and lower soft coral cover than General Use reefs. While the high levels of hard coral on Protected reefs may be a result of protection status, it might also have resulted from selection bias that occurred during the initial zoning of the Great Barrier Reef Marine Park (i.e. managers may have given protection status to reefs with high coral cover). 5.These results are likely influenced by the relatively low intensity of human use, both on the Great Barrier Reef in general and at the particular monitoring sites studied. Over time, as local populations and tourism increase, the effect of protection may become more evident at LTMP sites. Copyright © 2009 John Wiley & Sons, Ltd. [source] Perfluorocarbon-Based Oxygen Carriers: Review of Products and TrialsARTIFICIAL ORGANS, Issue 8 2010Camila Irene Castro Abstract A viable blood substitute is still of great necessity throughout the world. Perfluorocarbon-based oxygen carriers (PFCOCs) are emulsions that take advantage of the high solubility of respiratory gases in perfluorocarbons (PFCs). Despite attractive characteristics, no PFCOC is currently approved for clinical uses. Some PFCOCs have failed due to secondary effects of the surfactants employed, like Fluosol DA, whereas others to adverse cerebrovascular effects on cardiopulmonary bypass, such as Oxygent. Further in-depth, rigorous work is needed to overcome the annotated failures and to obtain a safe PFCOC approved for human use. The aim of this study is to review in detail the most-used PFCOCs, their formulation, and preclinical and clinical trials, and to reflect upon causes of failure and strategies to overcome such failures. [source] Carrying Capacity and Potential Production of Ungulates for Human Use in a Mexican Tropical Dry ForestBIOTROPICA, Issue 4 2007Salvador Mandujano ABSTRACT Data are provided on the carrying capacity and potential production for sustainable human use of white-tailed deer (Odocoileus virginianus) and collared peccary (Pecari tajacu) in a protected tropical dry forest at Chamela on the Pacific coast of Mexico. In this paper, the carrying capacity was defined as the equilibrium density plus the number of animals removed by predators. The equilibrium point was estimated from the density dependent relationship between the finite population growth rate and the current density according to a logistic model. Annual density was estimated using the line transect method. Carrying capacity estimates were 16.5 to 17.2 deer/km2 and 9.3,9.5 peccaries/km2, representing a combined biomass of 841,874 kg/km2. A potential production for human use of 2.1 deer/km2 and 4.4 peccaries/km2 was estimated employing the model of Robinson and Redford (1991). The data suggest that, in the protected tropical dry forest of Chamela, the density and biomass of wild ungulates can maintain a similar or greater density and biomass than other Neotropical forests. To obtain an accurate estimation of the maximum sustainable yield (MSY), it is necessary to consider predation. From a management point of view, it is important to consider that carrying capacity varies as a function of the rainfall pattern. RESUMEN Se presentan datos acerca de la capacidad de carga y la producción potencial del venado cola blanca (Odocoileus virginianus) y pecarí de collar (Pecari tajacu) para aprovechamiento humano en un bosque tropical seco de Chamela en la costa Pacífica de México. En este trabajo se definió capacidad de carga como la densidad en el punto de equilibrio del crecimiento poblacional más el número de animales removidos por los depredadores. La densidad en equilibrio se estimó a partir de la relación de denso-dependencia entre la tasa finita de crecimiento poblacional y la densidad anual de acuerdo al modelo logístico. La densidad anual se estimó empleando el método de transecto de línea. La capacidad de carga se estimó en 16.5 a 17.2 venados/km2 y 9.3 a 9.5 pecaries/km2, y una biomasa combinada de 841 a 874 kg/km2. Empleando el modelo de Robinson y Redford (1991) se estimó una producción potencial para aprovechamiento humano de 2.1 venados/km2 y 4.4 pecaries/km2. Los datos indican que en bosque tropical seco protegido de Chamela la densidad y biomasa de los ungulados silvestres puede ser similar o mayor en comparación con otros bosques neotropicales. Para obtener una estimación precisa de la cosecha máxima sostenible es importante considerar el efecto de la depredación. Desde una perspectiva de manejo, se debe incorporar la variación en la capacidad de carga en función del patrón de lluvias. [source] Recovery of a Subtropical Dry Forest After Abandonment of Different Land Uses,BIOTROPICA, Issue 3 2006Sandra Molina Colón ABSTRACT We studied the ecological characteristics of 45,50-yr-old subtropical dry forest stands in Puerto Rico that were growing on sites that had been deforested and used intensively for up to 128 yr. The study took place in the Guánica Commonwealth Forest. Our objective was to assess the long-term effects of previous land use on this forest,i.e., its species composition, structure, and functioning. Previous land-use types included houses, farmlands, and charcoal pits. Stands with these land uses were compared with a nearby mature forest stand. The speed and path of forest recovery after deforestation and land-use abandonment depended on the conditions of the land. Study areas where land uses had removed the forest canopy and altered soil conditions (houses and farmlands) required a longer time to recover and had a different species composition than study areas where land uses retained a forest canopy (charcoal pits). Different forest attributes recovered at different rates. Crown area index, stem density, and litterfall rate recovered faster than stemwood and root, biomass, tree height, and basal area. Where previous land uses removed the canopy, Leucaena leucocephala, a naturalized alien pioneer species, dominated the regrowth. Native species dominated abandoned charcoal pits and mature forest. The change in species composition, including the invasion of alien species, appears to be the most significant long-term effect of human use and modification of the landscape. RESUMEN Estudiamos las características ecológicas de rodales de un bosque seco subtropical en Puerto Rico que tenían 45-50 años de recuperación después de haber sido usados intensamente durante 128 años. El estudio se realizó en el Bosque Estatal de Guánica. Nuestro objetivo fue el de evaluar los efectos a largo plazo de los distintos tipos de usos del terreno en la composición de especies, la estructura y el funcionamiento. Los usos de terreno en el pasado incluyeron viviendas, terrenos agrícolas y carboneras. Estos rodales fueron comparados con un rodal de bosque maduro en un área cercana. La rápidez de recuperación y la manera en cómo sucede depende de las condiciones del terreno después de ser abandonado. Las áreas de estudio en las que se había removido el dosel y alterado las condiciones del suelo (casas y terrenos agrícolas) necesitaron más tiempo para recuperarse y reflejaron una composición de suelo diferente a las áreas de estudio donde el dosel se mantuvo (carboneras). Los diferentes atributos forestales se recuperaban a ritmos diferentes. El índice del área foliar de la copa, la densidad de tallos y la caída de hojarasca se recuperaron más rápido que la biomasa de tallos y raíces, la altura de los árboles y el área basal. La especie pionera naturalizada, Leucaena leucocephala (Lam.) de Wit-Fabaceae, fue la especie dominante en los bosques donde se habia removido el dosel. Las especies nativas dominaban las carboneras abandonadas y el bosque maduro. El cambio en la composición de especies e incluso la invasión de especies foráneas, parece ser el efecto a largo plazo más significativo del uso humano y de la modificación del paisaje. [source] Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot studyBIPOLAR DISORDERS, Issue 6 2007Carlos A Zarate Jr Objectives:, Considerable preclinical biochemical and behavioral data suggest that protein kinase C inhibition would bring about antimanic effects. Notably, the structurally highly dissimilar antimanic agents lithium and valproate, when administered in therapeutically relevant paradigms, attenuate protein kinase C inhibition function. There is currently only one relatively selective protein kinase C inhibitor that crosses the blood,brain barrier available for human use , tamoxifen. Our group recently conducted a single-blind study with tamoxifen in acute mania and found that it significantly decreased manic symptoms within a short period of time (3,7 days). In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania. Methods:, In a double-blind, placebo-controlled study, 16 subjects with bipolar disorder, manic or mixed, with or without psychotic features, were randomly assigned to receive tamoxifen (20,140 mg/day; n = 8) or placebo (n = 8) for three weeks. Primary efficacy was assessed by the Young Mania Rating Scale. Results:, Subjects on tamoxifen showed significant improvement in mania compared to placebo as early as five days, an effect that remained significant throughout the three-week trial. The effect size for the drug difference was very large (d = 1.08, 95% confidence interval 0.45,1.71) after three weeks (p = 0.001). At study endpoint, response rates were 63% for tamoxifen and 13% for placebo (p = 0.12). Conclusions:, Antimanic effects resulted from a protein kinase C inhibitor; onset occurred within five days. Large, controlled studies with selective protein kinase C inhibitors in acute mania are warranted. [source] Innate immunity and biodefence vaccinesCELLULAR MICROBIOLOGY, Issue 11 2003Nicholas M. Valiante Summary Host defence in vertebrates is achieved by the integration of two distinct arms of the immune system: the innate and adaptive responses. The innate response acts early after infection (within minutes), detecting and responding to broad cues from invading pathogens. The adaptive response takes time (days to weeks) to become effective, but provides the fine antigenic specificity required for complete elimination of the pathogen and the generation of immunologic memory. Antigen-independent recognition of pathogens by the innate immune system leads to the rapid mobilization of immune effector and regulatory mechanisms that provide the host with three critical advantages: (i) initiating the immune response (both innate and adaptive) and providing the inflammatory and co-stimulatory context for antigen recognition; (ii) mounting a first line of defence, thereby holding the pathogen in check during the maturation of the adaptive response; and (iii) steering the adaptive immune system towards the cellular or humoral responses most effective against the particular infectious agent. The quest for safer and more effective vaccines and immune-based therapies has taken on a sudden urgency with the increased threat of bioterrorism. Only a handful of vaccines covering a small proportion of potential biowarfare agents are available for human use (e.g. anthrax and small pox) and these suffer from poor safety profiles. Therefore, next generation biodefence-related vaccines and therapies with improved safety and the capacity to induce more rapid, more potent and broader protection are needed. To this end, strategies to target both the innate and adaptive immune systems will be required. [source] Induction of carbohydrate-specific antibodies in HLA-DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human useCHEMICAL BIOLOGY & DRUG DESIGN, Issue 3 2003S. Vichier-Guerre Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor-associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte-associated antigens (HLA). In order to stimulate a T-cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B-cell epitope (Tn antigen: , -GalNAc-Ser) covalently linked to peptides corresponding to the Pan DR ,universal' T-helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA-DR1, and HLA-DR4). A strong T-cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use. [source] |