Can traditionally administered home remedies be recommended? An assessment of 287 herbal home remedies for cattle, sheep, goats, pigs and horses, collected in the Swiss Canton of Graubuenden

Introduction: In Switzerland, the administration of medicinal plants to livestock is almost completely confined to the use of home remedies. To save this traditional knowledge, which has been handed down through word of mouth, a project aims to collect this information from different regions of Switzerland. Grison home remedies have been evaluated to decide whether or not they can be recommended. Methods: 32 current or former Grison livestock keepers (average age 59 years) provided information on the home remedies they use or have used to maintain the health of their cattle, sheep, goats, pigs and horses and to treat them. The data collection was conducted by interview (28 on-site, 3 by phone, 1 in writing) with a standardised questionnaire about collecting medicinal plants, and preparing and administrating home remedies for farm animals. Only home remedies containing plants, lichens or products deriving from them were assessed by a practising veterinarian and a pharmacist. Results: Grison livestock keepers mentioned 407 home remedies. The assessment included 287 herbal home remedies with 346 different indications. The investigations resulted in classification into 3 categories: (1) 278 indications that can be recommended, provided, in some cases, changes were made to either their preparation or administration. (2) 17 indications that could not be assessed and (3) 51 indications where their use is not recommended at all. Overall, 122 different, mainly herbal ingredients were used in the home remedies assessed. The most frequently applied herbal drugs are shown in the table, including their legal status for use in food-producing animals and the results of the assessment. Discussion/Conclusion: To enable livestock keepers to gain access to traditional knowledge, experts need to make recommendations for appropriate preparation and application of home remedies, to provide advice on necessary precautions and information on the legal situation for use on farm animals

Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4⁺CD25^HIFoxp3⁺regulatory T cells and expanded melanoma-specific CD8⁺T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.</p> <p>Methods</p> <p>In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[¹⁸F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.</p> <p>Results</p> <p>After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; <it>p </it>value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.</p> <p>Conclusions</p> <p>These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00299689">NCT00299689</a></p

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Studies on Lake Erie's littoral algae; Host specificity and temporal periodicity of epiphytic diatoms

Substratum specificity and temporal periodicity of the attached diatom flora upon three aquatic vascular plants and an artificial substratum were examined in three Lake Erie marshes. No qualitative or quantitative specificity for substrata was observed. Variability of diatom assemblage structure within replicate samples of a particular substratum type was as great as, or greater than, variability between substrata. Diatom assemblages upon dowel rod displayed a mid to late summer density maximum. Variability of density maxima upon natural substrata was attributed to different growth rates of the host macrophytes. Diatom assemblages within each sampling site possessed a distinct temporal periodicity indicating that factors affecting diatom growth are heterogeneous in distribution throughout Lake Erie's littoral zone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42923/1/10750_2004_Article_BF00013712.pd

Insights into APC/C: from cellular function to diseases and therapeutics

Anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin-protein ligase that targets different substrates for ubiquitylation and therefore regulates a variety of cellular processes such as cell division, differentiation, genome stability, energy metabolism, cell death, autophagy as well as carcinogenesis. Activity of APC/C is principally governed by two WD-40 domain proteins, Cdc20 and Cdh1, in and beyond cell cycle. In the past decade, the results based on numerous biochemical, 3D structural, mouse genetic and small molecule inhibitor studies have largely attracted our attention into the emerging role of APC/C and its regulation in biological function, human diseases and potential therapeutics. This review will aim to summarize some recently reported insights into APC/C in regulating cellular function, connection of its dysfunction with human diseases and its implication of therapeutics

The Free Slave: Morality, Neostoicism, and Publishing Strategy in Emanuel d’Aranda’s Algiers and It’s Slavery (1640–82)

To what extent did commercial editions differ from the original tales authors brought home from their captivity, and how can we explain the modifications? This essay addresses this question based on Emanuel d’Aranda’s Algiers and It’s Slavery (1656), of which not only several seventeenth-century editions exist, but also the original manuscript. Comparing the manuscript to the various print editions and examining these in the context of contemporary literary-philosophical trends, the history of Algiers and It’s Slavery offers unique insight into the intricate process of turning the experience of captivity into a narrative suitable for a wide audience

Freshwater Mussel Assemblages at the Lotic-Lentic Interface Along Lake Erie

Where a stream enters a large lake, the mouth represents a transitional environment that is neither truly lotic nor lentic in nature and therefore is likely to affect the fauna present. Theory on habitat area and stream size predicts that species richness will increase farther downstream as watershed size increases, but as stream gradient and thus flow rate declines, stream mouths present a different and understudied habitat. Freshwater mussels in the family Unionidae are in decline, and therefore understanding how they respond across diverse habitats is also critical. We sampled mussel assemblages from 2010 to 2012 in the lower reaches of twelve small tributaries and two large embayments of the western and central basins of Lake Erie, where watershed size ranged from 10 to 4000 km . These watersheds were assessed for land use by remote sensing and for basic water chemistry and the composition of their benthos by standard protocols. Evidence of native unionid mussels occurred in all watersheds, with 14 species found alive, which make up 75% of mussel species still present throughout Lake Erie. A species-area relationship occurred, although the effect was weaker than that present for flowing streams in the region. Additionally, the habitat and corresponding assemblages were characterized as depositional in nature, which logically follow high agricultural land use and corresponding high levels of turbidity and the proportion of silt and clay. Therefore, the lake environment influenced mussel assemblages, yet these conditions appear to limit dreissenid mussels in river mouths.