פרסומים

Drug penetration through the skin is significant for both transdermal and dermal delivery. One mechanism that has attracted attention over the last two decades is the transport pathway of nanoparticles via hair follicle, through the epidermis, directly to the pilosebaceous unit and blood vessels. Studies demonstrate that particle size is an important factor for drug penetration. However, in order to gain more information for the purpose of improving this mode of drug delivery, a thorough understanding of the optimal physical particle properties is needed. In this study, we fabricated fluorescently labeled gold nanoparticles (GNP) with a tight control over the size and shape. The effect of the particles' physical parameters on follicular penetration was evaluated histologically. We used horizontal human skin sections and found that the optimal size for polymeric particles is 0.25 ?m. In addition, shape penetration experiments revealed gold nanostars' superiority over spherical particles. Our findings suggest the importance of the particles' physical properties in the design of nanocarriers delivered to the pilosebaceous unit.

Drug penetration through the skin is significant for both transdermal and dermal delivery. One mechanism that has attracted attention over the last two decades is the transport pathway of nanoparticles via hair follicle, through the epidermis, directly to the pilosebaceous unit and blood vessels. Studies demonstrate that particle size is an important factor for drug penetration. However, in order to gain more information for the purpose of improving this mode of drug delivery, a thorough understanding of the optimal physical particle properties is needed. In this study, we fabricated fluorescently labeled gold nanoparticles (GNP) with a tight control over the size and shape. The effect of the particles' physical parameters on follicular penetration was evaluated histologically. We used horizontal human skin sections and found that the optimal size for polymeric particles is 0.25 $μ$m. In addition, shape penetration experiments revealed gold nanostars' superiority over spherical particles. Our findings suggest the importance of the particles' physical properties in the design of nanocarriers delivered to the pilosebaceous unit.

Drug penetration through the skin is significant for both transdermal and dermal delivery. One mechanism that has attracted attention over the last two decades is the transport pathway of nanoparticles via hair follicle, through the epidermis, directly to the pilosebaceous unit and blood vessels. Studies demonstrate that particle size is an important factor for drug penetration. However, in order to gain more information for the purpose of improving this mode of drug delivery, a thorough understanding of the optimal physical particle properties is needed. In this study, we fabricated fluorescently labeled gold nanoparticles (GNP) with a tight control over the size and shape. The effect of the particles' physical parameters on follicular penetration was evaluated histologically. We used horizontal human skin sections and found that the optimal size for polymeric particles is 0.25 $μ$m. In addition, shape penetration experiments revealed gold nanostars' superiority over spherical particles. Our findings suggest the importance of the particles' physical properties in the design of nanocarriers delivered to the pilosebaceous unit.

Tropospheric ozone (O3) is widely recognized as the cause of substantial yield and quality reduction in crops. Most of the previous studies focused on the exposure of wheat cultivars to elevated O3 levels. Our main objectives were to: (i) investigate the consistency of wheat cultivars’ physiological responses across two different realistic O3 levels; and (ii) compare these physiological responses with those under short acute O3 exposure. Three commercially available hard spring wheat cultivars bred under semiarid and Eastern Mediterranean conditions were exposed to two different O3 levels during two consecutive seasons (2016–2018)—36 and 71 ppbv 7 h mean O3 mixing ratios in open-top chambers. The results were compared to those following short acute O3 exposure (102.8 ppbv, 7 h mean for 10 days) in a greenhouse. Non-stomatal responses were significantly more pronounced than stomatal responses in all cultivars under different levels of O3. The specific cultivar was observed as the most O3-tolerant under all experiments. The fact that the same cultivar was found remarkably tolerant to the local semiarid ambient conditions according to other studies and to O3 exposure based on the present study supports a link between cultivar resistance to drought conditions and O3.

Short-day photoperiod (SDPP; 8 h light:16 h dark) during the dry period increases milk production compared with long-day photoperiod (LDPP; 16 h light:8 h dark). We hypothesized that the impact of photoperiod on lactation is mediated by alterations in the circadian system. Twelve Saanen goats were blocked at dry off into SDPP (n = 6) and LDPP (n = 6) treatments and mammary biopsies were taken in the middle of light and dark phases at 3 wk prepartum and 5 wk postpartum. Total RNA was isolated, and the expression of clock genes was analyzed by qPCR. SDPP goats produced more milk than LDPP goats (3.15 +/- 0.04 vs. 2.7 +/- 0.05 kg/d). In the 24 h period, LDPP goats had a greater body temperature than SDPP goats at 3 wk prepartum (39.6 +/- 0.06 vs. 39.3 +/- 0.1 degrees C) and 5 wk postpartum (40.1 +/- 0.15 vs. 39.7 +/- 0.1 degrees C). Cosinor analysis revealed that physiological state affected body temperature mesor (P< 0.001), peak (P< 0.01), amplitude (P< 0.05), and phase (P< 0.001). Plasma prolactin was 20, 10, and 17-fold higher in LDPP than in SDPP goats at 3 wk prepartum, 3 wk postpartum and 5 wk postpartum, respectively. Cosinor analysis revealed that photoperiod affected prolactin mesor (P< 0.0001), peak (P< 0.0001), trough (P< 0.001), amplitude (P< 0.01), and the peak to trough ratio (P< 0.01). Mammary expression of a core clock gene, PER1, was affected by the light-dark phase and the photoperiod treatment (P< 0.05). It also exhibited a photoperiod-physiological state interaction. Changes in the circadian rhythms with the onset of lactation and photoperiod manipulation support further studies of their role in the regulation of milk yield.

Over the last century, eosinophils have been regarded ambiguously either as 'friends' or 'foes'. Recent developments have greatly enhanced our understanding of the role and function of eosinophils in health and disease. Pathogenic eosinophilic inflammation can lead to severe diseases in various organs, such as the gastrointestinal tract, airways, heart and skin. In a 2-day focus workshop of the German Society for Allergology and Clinical Immunology (DGAKI), the state of the art was discussed and practical recommendations for diagnosis and treatment of eosinophilic diseases, with a particular focus on new biologics, such as anti-interleukin 5 and anti-interleukin 5R, were derived.

Over the last century, eosinophils have been regarded ambiguously either as ‘friends' or ‘foes'. Recent developments have greatly enhanced our understanding of the role and function of eosinophils in health and disease. Pathogenic eosinophilic inflammation can lead to severe diseases in various organs, such as the gastrointestinal tract, airways, heart and skin. In a 2-day focus workshop of the German Society for Allergology and Clinical Immunology (DGAKI), the state of the art was discussed and practical recommendations for diagnosis and treatment of eosinophilic diseases, with a particular focus on new biologics, such as anti-interleukin 5 and anti-interleukin 5R, were derived.

Abstract Coronavirus disease 2019 and related lockdown policies in 2020 shocked food industry firms? supply chains in developing regions. Firms ?pivoted? to e-commerce to reach consumers and e-procurement to reach processors and farmers. ?Delivery intermediaries? copivoted with food firms to help them deliver and procure. This was crucial to the ability of the food firms to pivot. The pandemic was a ?crucible? that induced this set of fast-tracking innovations, accelerating the diffusion of e-commerce and delivery intermediaries, and enabling food industry firms to redesign, at least temporarily, and perhaps for the long term, their supply chains to be more resilient, and to weather the pandemic, supply consumers, and contribute to food security. We present a theoretical model to explain these firm strategies, and then apply the framework to classify firms? practical strategies. We focus on cases in Asia and Latin America. Enabling policy and infrastructural conditions allowed firms to pivot and copivot fluidly.

The exposure of plants to pharmaceuticals via treated wastewater irrigation and biosolid application presents an important route of chronic exposure of crops to a wide variety of bioactive pollutants. This paper presents a novel approach which aims to improve our understanding of the interactions of bioactive pollutants with plants through the concept of plant pharmacology and two main sub-divisions: (i) plant pharmacokinetics which describes the fate of exogenous xenobiotics in the plant based on the processes of absorption, distribution, metabolism and accumulation (ADMA), processes that are analogous to pharmacokinetics in animals; and (ii) plant pharmacodynamics that proposes that exogenous xenobiotics interact with plant enzymes and biochemical pathways, establishing a relationship with pharmacological concepts and emphasizing the importance of exposure-response interactions. The concept of plant pharmacology and its two subdivisions provide a foundation for the development of in-depth knowledge regarding the fate of xenobiotics in plants and establishing plant pharmacokinetic-pharmacodynamic models that include both the ADMA processes and time-dependent response of the plant to these compounds. This concept provides a new perspective on pharmacovigilance, focusing on plant-xenobiotic compound interactions, and a conceptual framework for understanding the fate and interactions of these bioactive molecules in agricultural systems, to enable more accurate risks assessments of environmental and human health.

The exposure of plants to pharmaceuticals via treated wastewater irrigation and biosolid application presents an important route of chronic exposure of crops to a wide variety of bioactive pollutants. This paper presents a novel approach which aims to improve our understanding of the interactions of bioactive pollutants with plants through the concept of plant pharmacology and two main sub-divisions: (i) plant pharmacokinetics which describes the fate of exogenous xenobiotics in the plant based on the processes of absorption, distribution, metabolism and accumulation (ADMA), processes that are analogous to pharmacokinetics in animals; and (ii) plant pharmacodynamics that proposes that exogenous xenobiotics interact with plant enzymes and biochemical pathways, establishing a relationship with pharmacological concepts and emphasizing the importance of exposure-response interactions. The concept of plant pharmacology and its two subdivisions provide a foundation for the development of in-depth knowledge regarding the fate of xenobiotics in plants and establishing plant pharmacokinetic-pharmacodynamic models that include both the ADMA processes and time-dependent response of the plant to these compounds. This concept provides a new perspective on pharmacovigilance, focusing on plant-xenobiotic compound interactions, and a conceptual framework for understanding the fate and interactions of these bioactive molecules in agricultural systems, to enable more accurate risks assessments of environmental and human health.

Purpose To determine feasibility of plant-derived recombinant human collagen type I (RHCI) for use in corneal regenerative implants Methods RHCI was crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to form hydrogels. Application of shear force to liquid crystalline RHCI aligned the collagen fibrils. Both aligned and random hydrogels were evaluated for mechanical and optical properties, as well as in vitro biocompatibility. Further evaluation was performed in vivo by subcutaneous implantation in rats and corneal implantation in Gottingen minipigs. Results Spontaneous crosslinking of randomly aligned RHCI (rRHCI) formed robust, transparent hydrogels that were sufficient for implantation. Aligning the RHCI (aRHCI) resulted in thicker collagen fibrils forming an opaque hydrogel with insufficient transverse mechanical strength for surgical manipulation. rRHCI showed minimal inflammation when implanted subcutaneously in rats. The corneal implants in minipigs showed that rRHCI hydrogels promoted regeneration of corneal epithelium, stroma, and nerves; some myofibroblasts were seen in the regenerated neo-corneas. Conclusion Plant-derived RHCI was used to fabricate a hydrogel that is transparent, mechanically stable, and biocompatible when grafted as corneal implants in minipigs. Plant-derived collagen is determined to be a safe alternative to allografts, animal collagens, or yeast-derived recombinant human collagen for tissue engineering applications. The main advantage is that unlike donor corneas or yeast-produced collagen, the RHCI supply is potentially unlimited due to the high yields of this production method. Lay Summary A severe shortage of human-donor corneas for transplantation has led scientists to develop synthetic alternatives. Here, recombinant human collagen type I made of tobacco plants through genetic engineering was tested for use in making corneal implants. We made strong, transparent hydrogels that were tested by implanting subcutaneously in rats and in the corneas of minipigs. We showed that the plant collagen was biocompatible and was able to stably regenerate the corneas of minipigs comparable to yeast-produced recombinant collagen that we previously tested in clinical trials. The advantage of the plant collagen is that the supply is potentially limitless.

Pt(IV) complexes are designed as prodrugs that are intended to overcome resistance. Pt(IV) prodrugs are activated inside cancer cells releasing cytotoxic Pt(II) drugs as well as two axial ligands that can be used to confer favorable pharmacological properties to the prodrug. The ligands can be innocent spectators, cancer targeting agents or bioactive moieties. The choice of axial ligands determines the chemical and pharmacological properties of the prodrugs. Over the years, several approaches were employed in attempts to increase the selectivity of the prodrugs to cancer cells and to utilize multi-action prodrugs to overcome resistance. In this review, we critically examine several of these approaches in order to evaluate the validity of some of the working hypotheses that are driving the current research.

Pt(IV) complexes are designed as prodrugs that are intended to overcome resistance. Pt(IV) prodrugs are activated inside cancer cells releasing cytotoxic Pt(II) drugs as well as two axial ligands that can be used to confer favorable pharmacological properties to the prodrug. The ligands can be innocent spectators, cancer targeting agents or bioactive moieties. The choice of axial ligands determines the chemical and pharmacological properties of the prodrugs. Over the years, several approaches were employed in attempts to increase the selectivity of the prodrugs to cancer cells and to utilize multi-action prodrugs to overcome resistance. In this review, we critically examine several of these approaches in order to evaluate the validity of some of the working hypotheses that are driving the current research.

Our aim is to propose guidelines for the analysis of political personalization and personalized politics in general and for behavioural personalization in particular. The first guideline is based on our understanding that personalization comes at the cost of party politics. It suggests that in order to classify politics as more or less personalized, we must compare it to an alternative party-oriented politics. Based on a synthesis of existing theoretical work, the second guideline suggests three analytical dimensions to clarify the multidimensional concept of personalization: arena, level and character. Arena refers to where personalization takes place; level refers to whose power or independence is changing; and character refers to how personalization is manifested. Furthermore, we present the contributions of this symposium and explain how they follow the two guidelines and advance our understanding and knowledge of behavioural political personalization. [ABSTRACT FROM AUTHOR]