RESUMO
Against a background of intensifying climate-induced disturbances, the need to enhance the resilience of forests and forest management is gaining urgency. In forest management, multiple trade-offs exist between different demands as well as across and within temporal and spatial scales. However, methods to assess resilience that consider these trade-offs are presently lacking. Here we propose a hierarchical framework of principles, criteria, and indicators to assess the resilience of a social-ecological system by focusing on the mechanisms behind resilience. This hierarchical framework balances trade-offs between mechanisms, different parts of the social-ecological system, ecosystem services, and spatial as well as temporal scales. The framework was developed to be used in a participatory manner in forest management planning. It accounts for the major parts of the forest-related social-ecological system and considers the multiple trade-offs involved. We demonstrate the utility of the framework by applying it to a landscape dominated by Norway spruce (Picea abies (L.) Karst.) in Central Europe, managed for three different management goals. The framework highlights how forest resilience varies with the pursued management goals and related management strategies. The framework is flexible and can be applied to various forest management contexts as part of a participatory process with stakeholders. It thus is an important step towards operationalizing social-ecological resilience in forest management systems.
Assuntos
Ecossistema , Florestas , Europa (Continente) , Noruega , Mudança ClimáticaRESUMO
The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber-film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.
Assuntos
Desamino Arginina Vasopressina/farmacologia , Muco/química , Nanofibras/química , Nanotecnologia , Adesividade , Animais , Preparações de Ação Retardada/farmacologia , Relação Dose-Resposta a Droga , Nanofibras/ultraestrutura , Saliva , SuínosRESUMO
Nicotine replacement therapy (NRT) formulations for oromucosal administration induce a delayed rise in nicotine blood levels as opposed to the immediate nicotine increase obtained from cigarette smoking, this being a shortcoming of the therapy. Here, we demonstrate that α-lactalbumin/polyethylene oxide (ALA/PEO) electrospun nanofibers constitute an efficient oromucosal delivery system for fast-onset nicotine delivery of high relevance for acute dosing NRT applications. In vitro, nicotine-loaded nanofibers showed fast disintegration in water, with a weight loss up to 40% within minutes, and a faster nicotine release (26.1 ± 4.6% after 1 min of incubation) of the loaded nicotine compared to two relevant marketed NRT formulations with a comparable nicotine dose (i.e., 7.9 ± 5.1 and 2.2 ± 0.3% nicotine was released from a lozenge and a sublingual tablet, respectively). Model-fitting of the release data indicated that the release mechanism of nicotine from the hydrophilic nanofibers was possibly governed by more than one type of release phenomena. Remarkably, ex vivo studies using porcine buccal mucosa demonstrated a more efficient permeation of the nicotine released from the nanofibers [flux of 1.06 ± 0.22 nmol/(cm2·min)] compared to when dosing even a ten-fold concentrated nicotine solution [flux of 0.17 ± 0.14 nmol/(cm2·min)]. Moreover, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MS) imaging of ex vivo porcine buccal mucosa exposed to nicotine-loaded nanofibers clearly revealed higher amounts of nicotine throughout the epithelium, as well as in the lamina propria and submucosa of the tissue. Our findings suggest that nicotine-loaded ALA/PEO nanofibers have potential as a mucosal, fast-releasing, and biocompatible delivery system for nicotine, which can overcome the limitations of the currently marketed NRTs.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Lactalbumina/química , Boca/efeitos dos fármacos , Nanofibras/química , Nicotina/administração & dosagem , Nicotina/farmacocinética , Abandono do Hábito de Fumar/métodos , Administração Bucal , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Células Epiteliais/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Humanos , Mucosa Bucal/efeitos dos fármacos , Suínos , Distribuição Tecidual , Dispositivos para o Abandono do Uso de TabacoRESUMO
Providing insight on decisions to hunt and trade bushmeat can facilitate improved management interventions that typically include enforcement, alternative employment, and donation of livestock. Conservation interventions to regulate bushmeat hunting and trade have hitherto been based on assumptions of utility- (i.e., personal benefits) maximizing behavior, which influences the types of incentives designed. However, if individuals instead strive to minimize regret, interventions may be misguided. We tested support for 3 hypotheses regarding decision rules through a choice experiment in Tanzania. We estimated models based on the assumptions of random utility maximization (RUM) and pure random regret maximization (P-RRM) and combinations thereof. One of these models had an attribute-specific decision rule and another had a class-specific decision rule. The RUM model outperformed the P-RRM model, but the attribute-specific model performed better. Allowing respondents with different decision rules and preference heterogeneity within each decision rule in a class-specific model performed best, revealing that 55% of the sample used a P-RRM decision rule. Individuals using a P-RRM decision rule responded less to enforcement, salary, and livestock donation than did individuals using the RUM decision rule. Hence, 3 common strategies, enforcement, alternative income-generating activities, and providing livestock as a substitute protein, are likely less effective in changing the behavior of more than half of respondents. Only salary elicited a large (i.e. elastic) response, and only for one RUM class. Policies to regulate the bushmeat trade based solely on the assumption of individuals maximizing utility, may fail for a significant proportion of the sample. Despite the superior performance of models that allow both RUM and P-RRM decision rules there are drawbacks that must be considered before use in the Global South, where very little is known about the social-psychology of decision making.
Efecto de las Reglas de Decisión en los Experimentos de Selección sobre la Cacería y el Mercado de la Carne de Animales Silvestres Resumen La obtención de conocimiento del porqué se elige cazar o comerciar con carne de animales silvestres puede facilitar mejoras en el manejo de las intervenciones que típicamente incluyen el cumplimiento de leyes, el empleo alternativo y la donación de ganado. Las intervenciones de conservación para regular la cacería y el comercio hasta ahora han estado basadas en suposiciones de comportamiento de maximización de la utilidad (es decir, los beneficios personales), las cuales influyen sobre los tipos de incentivos que son diseñados. Sin embargo, si los individuos en lugar de eso buscan minimizar el arrepentimiento, las intervenciones pueden ser erróneas. Evaluamos el apoyo para tres hipótesis con respecto a las reglas de decisión mediante un experimento de selección en Tanzania. Estimamos los modelos con base en las suposiciones de la maximización aleatoria de la utilidad (MAU) y la maximización aleatoria pura del arrepentimiento (MAPA) y las combinaciones de estas. Uno de estos modelos tuvo una regla de decisión específica de atributo y otro modelo tuvo una regla de decisión específica de clase. El modelo MAU tuvo un mucho mejor desempeño que el modelo MAPA, pero el modelo específico de atributo fue el que tuvo el mejor desempeño de todos. El mejor desempeño se observó cuando permitimos a los respondientes con diferentes reglas de decisión y con heterogeneidad de preferencia dentro de cada regla de decisión en un modelo específico de clase, lo que revela que el 55% de las muestras usaron una regla de decisión MAPA. Los individuos que usaron una regla de decisión MAPA respondieron menos al cumplimiento de leyes, el salario y la donación de ganado que aquellos individuos que usaron la regla de decisión MAU. Por esto, las tres estrategias comunes (cumplimiento de leyes, actividades alternativas generadoras de ingresos y el sustento de ganado como sustituto de la proteína) probablemente sean menos efectivas en el cambio del comportamiento de más de la mitad de los respondientes. Solamente el salario provocó una respuesta elástica, y solamente fue para una clase MAU. Las políticas que regulan el mercado de la carne de animales silvstres basadas solamente en la suposición de que los individuos maximizan la utilidad pueden fallar para una proporción significativa de la muestra. A pesar del desempeño superior de los modelos que permiten las reglas de decisión MAU y MAPA, existen desventajas que deben ser consideradas antes del uso de los modelos en el hemisferio sur, en donde se conoce muy poco sobre la psicología social de las decisiones.
Assuntos
Comportamento de Escolha , Conservação dos Recursos Naturais , Animais , Emprego , Humanos , Gado , TanzâniaRESUMO
OBJECTIVE: Burning mouth syndrome (BMS) is a chronic oral pain condition with unknown aetiology but assumed to involve peripheral/central neuropathological and immune-mediated inflammatory factors. We aimed at characterizing inflammatory and neurogenic profiles and oral symptomatology of patients with BMS based on response to a local anaesthetic lozenge. METHODS: Patients with BMS were divided into an Effect (n = 13), No effect (n = 8) or Unspecified (n = 2) group according to their response to a local anaesthetic lozenge on oral pain. Inflammation was assessed in blood plasma and saliva by analyses of IL-6, IL-8, IL-17A, IL-23 and TNF-α levels. The degree of inflammation and distribution of oestrogen receptor, NGF, NGF-receptor, TRPV-1 and IL-17F in buccal mucosal tissue were investigated by immunohistochemistry. RESULTS: Immunoreactivity to the oestrogen receptor was most intense in the Effect group, whereas the No effect group tended to have higher plasma levels of the pro-inflammatory cytokines. CONCLUSIONS: Our findings indicate that the response to treatment with local anaesthesia enables subgrouping of patients with BMS according to the potential pathogenic mechanisms. Effect of local anaesthesia indicates a peripheral neuropathology involving lack of oestrogen and upregulation of oestrogen receptors, and no effect indicates a systemic inflammation-induced mechanism leading to increased levels of plasma cytokines.
Assuntos
Anestésicos Locais/administração & dosagem , Síndrome da Ardência Bucal/tratamento farmacológico , Administração Oral , Citocinas/análise , Citocinas/sangue , Humanos , Receptores de Estrogênio/fisiologia , Saliva/químicaRESUMO
Many oral mucosal conditions cause considerable and prolonged pain that to date has been difficult to alleviate via topical delivery, and the use of injection causes many patients dental anxiety and needle-prick pain. Therefore, developing a noninjectable drug delivery system as an alternative administration procedure may vastly improve the health and wellbeing of these patients. Recent advances in the development of mucoadhesive electrospun patches for the direct delivery of therapeutics to the oral mucosa offer a potential solution, but as yet, the release of local anesthetics from this system and their uptake by oral tissue have not been demonstrated. Here, we demonstrate the fabrication of lidocaine-loaded electrospun fiber patches, drug release, and subsequent uptake and permeation through the porcine buccal mucosa. Lidocaine HCl and lidocaine base were incorporated into the electrospun patches to evaluate the difference in drug permeation for the two drug compositions. Lidocaine released from the lidocaine HCl-containing electrospun patches was significantly quicker than from the lidocaine base patches, with double the amount of drug released from the lidocaine HCl patches in the first 15 min (0.16 ± 0.04 mg) compared to that from the lidocaine base patches (0.07 ± 0.01 mg). The permeation of lidocaine from the lidocaine HCl electrospun patches through ex vivo porcine buccal mucosa was also detected in 15 min, whereas permeation of lidocaine from the lidocaine base patch was not detected. Matrix-assisted laser desorption ionization-mass spectrometry imaging was used to investigate localization of lidocaine within the oral tissue. Lidocaine in the solution as well as from the mucoadhesive patch penetrated into the buccal mucosal tissue in a time-dependent manner and was detectable in the lamina propria after only 15 min. Moreover, the lidocaine released from lidocaine HCl electrospun patches retained biological activity, inhibiting veratridine-mediated opening of voltage-gated sodium channels in SH-SY5Y neuroblastoma cells. These data suggest that a mucoadhesive electrospun patch may be used as a vehicle for rapid uptake and sustained anesthetic drug delivery to treat or prevent oral pain.
Assuntos
Anestésicos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Lidocaína/farmacocinética , Mucosa Bucal/efeitos dos fármacos , Absorção pela Mucosa Oral/fisiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacocinética , Administração Bucal , Anestésicos/administração & dosagem , Animais , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Dor Facial/tratamento farmacológico , Humanos , Lidocaína/administração & dosagem , Mucosa Bucal/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Suínos , Distribuição Tecidual , Veratridina/farmacologia , Agonistas do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagemRESUMO
Modern Portfolio Theory is a well-established method in economic research for considering the risks and returns in asset allocations and the potential benefits of diversification for risk averse agents. Thus, it is a useful tool for guiding sustainability discourse under uncertain future states. Existing discussions around the method's use in environmental research have evolved during over the 75 years of its application, leading to a continued renewal of perspectives on utilising it. We classify the environmental questions where portfolio theory has been applied, and critically discuss the methodological approaches taken; providing a stepping stone for future use of the method. This article provides a framework for its application in environmental research using the following questions: 1) what is the type of research or management question and objective(s) of the decision-maker(s); 2) what are the definitions of the assets to be included in the portfolio; 3) what are the ways that returns are valued, discounted, distributed and weighted; 4) what is the most appropriate way for risks to be accounted for and managed, including the selection of the appropriate model and taking into account risk preferences; and 5) what are the definitions of constraints in the programming problem.
Assuntos
Modelos Teóricos , IncertezaRESUMO
Improved nicotine permeability across buccal mucosa may enable more effective oromucosal nicotine replacement therapy products. It is essential to know the location and composition of the main barrier for drug diffusion to enhance the drug permeability. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is a rapidly evolving technique that can be used to image the spatial distribution of drugs and drug metabolites in tissue cryo-sections, without prior labeling of the drug. In this study, the distribution of nicotine and mannitol in porcine buccal mucosa was imaged with 10 µm spatial resolution after apical as well as submucosal application of the drugs in order to localize the main permeability barrier(s). This was supported by ex vivo permeability studies across separated porcine buccal epithelium and submucosa. Lastly, the metabolism of nicotine in porcine buccal mucosa was evaluated by imaging of the main metabolite, cotinine. The results showed that the main permeability barrier to both nicotine and mannitol was located in the outer fourth of the epithelium. Further, it was shown that cotinine was sparsely distributed in excised porcine buccal mucosa, indicating that nicotine metabolism in excised porcine buccal mucosa was negligible. MALDI MSI was shown to be a useful method for imaging spatial distribution of drugs in buccal mucosa.
Assuntos
Imagem Molecular/métodos , Mucosa Bucal/metabolismo , Nicotina/metabolismo , Agentes de Cessação do Hábito de Fumar/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Administração Bucal , Animais , Cotinina/metabolismo , Manitol/metabolismo , Modelos Animais , Mucosa Bucal/diagnóstico por imagem , Nicotina/administração & dosagem , Nicotina/análogos & derivados , Permeabilidade , Agentes de Cessação do Hábito de Fumar/administração & dosagem , Sus scrofaRESUMO
PURPOSE: The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS: The impact of sodium taurodeoxycholate (STDC), sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone® on the permeability of [3H]-nicotine and [14C]-mannitol (a paracellular marker) across porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The distribution of nicotine, mannitol and permeation enhancers was imaged using using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). RESULTS: Despite STDC significantly increasing permeability of [14C]-mannitol, no enhancing effect was seen on [3H]-nicotine permeability with any of the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability, likely due to nicotine being retained in the donor compartment. The permeability results were complemented by the spatial distribution of nicotine and mannitol determined with MALDI MSI. CONCLUSIONS: The buccal permeability of nicotine was affected in an enhancer specific manner, suggesting that nicotine primarily diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo permeability studies and to be a useful qualitative tool for visualizing drug and penetration enhancer distribution in buccal mucosa.
Assuntos
Excipientes/farmacologia , Mucosa Bucal/metabolismo , Nicotina/farmacocinética , Absorção pela Mucosa Oral/efeitos dos fármacos , Agentes de Cessação do Hábito de Fumar/farmacocinética , Administração Bucal , Animais , Bochecha , Composição de Medicamentos/métodos , Excipientes/química , Modelos Animais , Mucosa Bucal/efeitos dos fármacos , Nicotina/administração & dosagem , Permeabilidade , Abandono do Hábito de Fumar/métodos , Agentes de Cessação do Hábito de Fumar/administração & dosagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sus scrofaRESUMO
In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer-coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes with promising mucoadhesive properties for drug delivery to the oral cavity. The following polymers were tested: chitosan, low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), amidated pectin (AM-pectin), Eudragit, poly(N-isopropylacrylamide-co-methacrylic acid) (p(NIPAAM-co-MAA)), hydrophobically modified hydroxyethyl cellulose (HM-HEC), and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). With chitosan as an exception, all the systems exhibited no significant effect on cell viability and permeability at the considered concentrations. Additionally, all the formulations showed to a varying degree an interaction with mucin (BSM type I-S); the positively charged formulations exhibited the strongest interaction, while the negatively and neutrally charged formulations displayed a moderate or low interaction. The ability to interact with mucin makes all the liposomal formulations promising for oromucosal administration. Although the chitosan-coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity.
Assuntos
Quitosana/química , Lipossomos/química , Boca/metabolismo , Mucinas/química , Pectinas/química , Linhagem Celular , Sobrevivência Celular , Celulose/análogos & derivados , Celulose/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/farmacologia , Nanopartículas/química , Tamanho da Partícula , Permeabilidade , Propriedades de SuperfícieRESUMO
The participation of private landowners in conservation is crucial to efficient biodiversity conservation. This is especially the case in settings where the share of private ownership is large and the economic costs associated with land acquisition are high. We used probit regression analysis and historical participation data to examine the likelihood of participation of Danish forest owners in a voluntary conservation program. We used the results to spatially predict the likelihood of participation of all forest owners in Denmark. We merged spatial data on the presence of forest, cadastral information on participation contracts, and individual-level socioeconomic information about the forest owners and their households. We included predicted participation in a probability model for species survival. Uninformed and informed (included land owner characteristics) models were then incorporated into a spatial prioritization for conservation of unmanaged forests. The choice models are based on sociodemographic data on the entire population of Danish forest owners and historical data on their participation in conservation schemes. Inclusion in the model of information on private landowners' willingness to supply land for conservation yielded at intermediate budget levels up to 30% more expected species coverage than the uninformed prioritization scheme. Our landowner-choice model provides an example of moving toward more implementable conservation planning.
Assuntos
Biodiversidade , Conservação dos Recursos Naturais/economia , Propriedade , Comportamento de Escolha , FlorestasRESUMO
Selection of excipients for drug formulations requires both intellectual and experimental considerations as many of the used excipients are affected by physiological factors, e.g., they may be digested by pancreatic enzymes in the gastrointestinal tract. In the present paper we have looked systematically into the differences between Kolliphor ELP, EL, and RH40 and how they affect the bioavailability of fenofibrate, through pharmacokinetic studies in rats and in vitro lipolysis studies. The study design was made as simple as possible to avoid confounding factors, for which reason the tested formulations only comprised an aqueous micellar solution of the model drug (fenofibrate) in varying concentrations (2-25% (w/v)) of the three tested surfactants. Increased concentrations of Kolliphor ELP and EL led to increased fenofibrate AUC0-24h values. For the Kolliphor RH40 formulations, an apparent fenofibrate absorption optimum was seen at 15% (w/v) surfactant, displaying both the highest AUC0-24h and Cmax. The reduced absorption of fenofibrate from the formulation containing the highest level of surfactant (25% w/v) was thought to be caused by some degree of trapping within Kolliphor RH40 micelles. In vitro, Kolliphor ELP and EL were found to be more prone to digestion than Kolliphor RH40, though not affecting the in vivo results. The highest fenofibrate bioavailability was attained from formulations with high Kolliphor ELP/EL levels (25% (w/v)), indicating that these surfactants are the better choice for solubilizing fenofibrate in order to increase the absorption upon oral administration. Due to drug dependent effects of the different types of Kolliphor, more studies are recommended in order to understand which type of Kolliphor is best suited for a given drug.
Assuntos
Fenofibrato/administração & dosagem , Polietilenoglicóis/química , Tensoativos/química , Administração Oral , Animais , Área Sob a Curva , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão , Excipientes , Absorção Intestinal , Lipídeos , Lipólise , Masculino , Micelas , Tamanho da Partícula , Veículos Farmacêuticos , Ratos , Ratos Sprague-Dawley , Solubilidade , Óleo de Soja/químicaRESUMO
Regulation of illegal bushmeat trade is a major conservation challenge in Africa. We investigated what factors are most likely to induce actors in the bushmeat trade to shift to an alternative occupation by conducting a choice experiment with 325 actors in the bushmeat trade in the Kilombero Valley, Tanzania. Specifically, we asked respondents to choose between hunting or trading bushmeat and alternative salary-paying work, in a set of hypothetical scenarios where the attributes of these alternatives were varied and included measures of command and control, price of substitute meat, daily salary in the work option, and whether or not cows were donated to the respondent. We modeled the choice contingent on socioeconomic characteristics. The magnitude of fines and patrolling frequency had a significant but very low negative effect on the probability of choosing to engage in hunting or trading bushmeat compared with the salary of an alternative occupation. Donation of livestock and the price of substitute meats in the local market both affected the choice significantly in a negative and a positive direction, respectively. The wealthier a household was the more likely the respondent was to choose to continue hunting or trading bushmeat. On the margin, our results suggest that given current conditions in the Kilombero Valley on any given day 90% of the respondents would choose salary work at US$3.37/day over their activities in the bushmeat trade, all else equal.
Assuntos
Comportamento de Escolha , Conservação dos Recursos Naturais , Carne , Animais , Conservação dos Recursos Naturais/economia , Humanos , Mamíferos , Carne/economia , Modelos Teóricos , Fatores Socioeconômicos , Inquéritos e Questionários , TanzâniaRESUMO
The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55 ± 5 and 35 ± 5 min) were significantly different to the buccal anaesthetised groups (120 ± 0 and 165 ± 15 min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7 ± 4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.
Assuntos
Metoprolol/administração & dosagem , Metoprolol/farmacocinética , Absorção pela Mucosa Oral/fisiologia , Porco Miniatura/metabolismo , Adesivos , Anestesia , Animais , Disponibilidade Biológica , Química Farmacêutica , Estado de Consciência , Estudos Cross-Over , Formas de Dosagem , Concentração de Íons de Hidrogênio , Injeções Intravenosas , Masculino , Metoprolol/sangue , Modelos Animais , Suínos , ComprimidosRESUMO
The world is currently facing uncertainty caused by environmental, social, and economic changes and by political shocks. Fostering social-ecological resilience by enhancing forests' ability to provide a range of ecosystem services, including carbon sequestration, habitat provision, and sustainable livelihoods, is key to addressing such uncertainty. However, policy makers and managers currently lack a clear understanding of how to operationalise the shaping of resilience through the combined challenges of climate change, the biodiversity crisis, and changes in societal demand. Based on a scientific literature review, we identified a set of actions related to ecosystem services, biodiversity conservation, and disturbance and pressure impacts that forest managers and policy makers should attend to enhance the resilience of European forest systems. We conclude that the resilience shaping of forests should (1) adopt an operational approach, which is currently lacking, (2) identify and address existing and future trade-offs while reinforcing win-wins and (3) attend to local particularities through an adaptive management approach.
Assuntos
Biodiversidade , Mudança Climática , Conservação dos Recursos Naturais , Florestas , Conservação dos Recursos Naturais/métodos , Agricultura Florestal/métodos , Ecossistema , Sequestro de Carbono , Europa (Continente)RESUMO
The mucus layer in the small intestine is generally regarded as a barrier to drug absorption. However, the mucus layer is a complex system, and presently, only a few studies have been conducted to elucidate its physicochemical properties. The current study hypothesizes that the mucus layer contains solubility-enhancing surfactants and thus might aid the oral absorption of poorly water-soluble drugs. Mucus was sampled from sections of the small intestine of fasted rats to analyze the rheological properties and determine the mucus pH and concentrations of proteins and endogenous surfactants, i.e., bile salts, polar lipids, and neutral lipids. The mucus layer in the two proximal sections of the small intestine exhibited different rheological properties such as higher zero-shear viscosity and lower loss tangent and higher protein concentrations compared to all subsequent sections of the small intestine. The pH of the mucus layer was stable at ~ 6.5 throughout most of the small intestine, but increased to 7.5 in the ileum. The bile salt concentrations increased from the duodenum (16.0 ± 2.2 mM) until the mid jejunum (55.1 ± 9.5 mM), whereas the concentrations of polar lipids and neutral lipids decreased from the duodenum (17.4 ± 2.2 mM and 37.8 ± 1.6 mM, respectively) until the ileum (4.8 ± 0.4 mM and 10.7 ± 1.1 mM, respectively). In conclusion, the mucus layer of the rat small intestine contains endogenous surfactants at levels that might benefit solubilization and absorption of orally administered poorly water-soluble drugs.
RESUMO
We study climate uncertainty and how managers' beliefs about climate change develop and influence their decisions. We develop an approach for updating knowledge and beliefs based on the observation of forest and climate variables and illustrate its application for the adaptive management of an even-aged Norway spruce (Picea abies L. Karst) forest in the Black Forest, Germany. We simulated forest development under a range of climate change scenarios and forest management alternatives. Our analysis used Bayesian updating and Dempster's rule of combination to simulate how observations of climate and forest variables may influence a decision maker's beliefs about climate development and thereby management decisions. While forest managers may be inclined to rely on observed forest variables to infer climate change and impacts, we found that observation of climate state, e.g. temperature or precipitation is superior for updating beliefs and supporting decision-making. However, with little conflict among information sources, the strongest evidence would be offered by a combination of at least two informative variables, e.g., temperature and precipitation. The success of adaptive forest management depends on when managers switch to forward-looking management schemes. Thus, robust climate adaptation policies may depend crucially on a better understanding of what factors influence managers' belief in climate change.
Assuntos
Picea/química , Árvores , Mudança Climática , Monitoramento Ambiental , AlemanhaRESUMO
Oromucosal administration is an attractive non-invasive route. However, drug absorption is challenged by salivary flow and the mucosa being a significant permeability barrier. The aim of this study was to design and investigate a multi-layered nanofiber-on-foam-on-film (NFF) drug delivery system with unique properties and based on polysaccharides combined as i) mucoadhesive chitosan-based nanofibers, ii) a peptide loaded hydroxypropyl methylcellulose foam, and iii) a saliva-repelling backing film based on ethylcellulose. NFF displays optimal mechanical properties shown by dynamic mechanical analysis, and biocompatibility demonstrated after exposure to a TR146 cell monolayer. Chitosan-based nanofibers provided the NFF with improved mucoadhesion compared to that of the foam alone. After 1 h, >80 % of the peptide desmopressin was released from the NFF. Ex vivo permeation studies across porcine buccal mucosa indicated that NFF improved the permeation of desmopressin compared to a commercial freeze-dried tablet. The findings demonstrate the potential of the NFF as a biocompatible drug delivery system.
Assuntos
Quitosana , Nanofibras , Animais , Suínos , Quitosana/química , Desamino Arginina Vasopressina , Celulose/química , Sistemas de Liberação de Medicamentos , Mucosa Bucal , Peptídeos , Administração BucalRESUMO
Dextran sulfate sodium (DSS) is commonly used to induce colitis in rats. While the DSS-induced colitis rat model can be used to test new oral drug formulations for the treatment of inflammatory bowel disease, the effect of the DSS treatment on the gastrointestinal tract has not been thoroughly characterized. Additionally, the use of different markers to assess and confirm successful induction of colitis is somewhat inconsistent. This study aimed to investigate the DSS model to improve the preclinical evaluation of new oral drug formulations. The induction of colitis was evaluated based on the disease activity index (DAI) score, colon length, histological tissue evaluation, spleen weight, plasma C-reactive protein, and plasma lipocalin-2. Furthermore, the study investigated how the DSS-induced colitis affected the luminal pH, lipase activity, and concentrations of bile salts, polar lipids, and neutral lipids. For all evaluated parameters, healthy rats were used as a reference. The DAI score, colon length, and histological evaluation of the colon were effective disease indicators in DSS-induced colitis rats, while spleen weight, plasma C-reactive protein, and plasma lipocalin-2 were not. The luminal pH of the colon and bile salt- and neutral lipid concentrations in regions of the small intestine were lower in DSS-induced rats compared to healthy rats. Overall, the colitis model was deemed relevant for investigating ulcerative colitis-specific formulations.