Garuda 5 (khyung lnga)

This article focuses on ethnographic work conducted at the Men-Tsee-Khang (Dharamsala, India) on Garuda 5 (khyung lnga), a commonly prescribed Tibetan medical formula. This medicine’s efficacy as a painkiller and activity against infection and inflammation is largely due to a particularly powerful plant, known as ‘virulent poison’ (btsan dug) as well as ‘the great medicine’ (sman chen), and identified as a subset of Aconitum species. Its effects, however, are potentially dangerous or even deadly. How can these poisonous plants be used in medicine and, conversely, when does a medicine become a poison? How can ostensibly the same substance be both harmful and helpful? The explanation requires a more nuanced picture than mere dose dependency. Attending to the broader ‘ecologies of potency’ in which these substances are locally enmeshed, in line with Sienna Craig’s Efficacy and the Social Ecologies of Tibetan Medicine (2012), provides fertile ground to better understand the effects of Garuda 5 and how potency is developed and directed in practice. I aim to unpack the spectrum between sman (medicine) and dug (poison) in Sowa Rigpa by elucidating some of the multiple dimensions which determine the activity of Garuda 5 as it is formulated and prescribed in India. I thus embrace the full spectrum of potency— the ‘good’ and the ‘bad,’ the ‘wanted’ and the ‘unwanted’—without presuming the universal validity of biomedical notions of toxicity and side effects

Challenging the Biomedical Notion of ‘Active Substance’

Sowa Rigpa (Tibetan medicine) has been practiced across vast regions of Central and South Asia for centuries. In this medical tradition, it is common practice to dynamically adapt the mainly herbal formulas according to the regional flora and local conditions, and to use local variants of ingredients. Consequently, one Tibetan ingredient name within a specific formula can signify a variety of therapeutically fitting botanical items, which appear quite different from the perspective of modern taxonomy. This has led many researchers to understand the botanical plasticity of Tibetan medical formulas as misidentifications. We develop an alternative approach, exploring the advantages of this plasticity as a necessary practice to fulfill economic and therapeutic needs. This perspective piece questions the biomedical paradigm of single ‘active substances,’ since botanically unrelated plants with different chemical compositions can be similarly therapeutically effective. From a systems biology perspective, network pharmacology lets us understand the correspondence of illness and medicine as a semiotic process in which herbal formulations act via their ‘pleiotropic signatures’: complex webs of signal pathways that connect and act on multiple levels of organization in the body

Alternative pharmaceuticals: The technoscientific becomings of Tibetan medicines in-between India and Switzerland

This doctoral dissertation forges and explores connections, flows and frictions between two seemingly unrelated manufacturers of Tibetan medicines: Men-Tsee-Khang, the Tibetan Medical and Astrological Institute in Dharamsala (Himachal Pradesh, India), and PADMA AG in Wetzikon (Zürich, Switzerland). Adopting a translocal, multispecies approach by positioning plant-medicines as the central actors in this ethnography, I trace how four plants - aru, ruta, tserngön and bongnak - become part of medicine in and between these two establishments of Sowa Rigpa of similar age and output volume, situated in highly diverse contexts at a stereotypical 'periphery' and 'core' of Western technoscience respectively. Inspired by Science and Technology Studies and by Pordié and Gaudillière's (2014a) 'reformulation regime' of industrial Ayurvedic proprietary products, I analyse the on-going material, technoscientific, and regulatory reformulations of Tibetan materia medica as they are actualised in contemporary recipes based on classical texts. In this thesis, I describe how both PADMA and Men-Tsee-Khang refer to Tibetan medical texts yet also rely on botanical taxonomy for plant identification. Both face the uncertainties of sourcing raw materials in bulk from growers and traders on the Indian market, skilfully mass-produce pills by means of machines for grinding, mixing, sieving and packaging, and depend on in-house laboratory analyses and each-other's expertise in the construction of hybrid 'qualities'. They are also forced to interact with technomedical conceptions of drug safety and toxicity, and with European medicine and food registration legislation to varying degrees. I argue that in performing this series of technoscientific reformulations, Tibetan medicines are becoming 'alternative pharmaceuticals': liminal, paradoxical yet politically subversive things oscillating betwixt and between tradition and modernity, orthodoxy and innovation, East and West. Men-Tsee-Khang and PADMA could thus be interpreted as two possible instantiations of a quasi-industrial techno-Sowa Rigpa, but only if one distinguishes 'Big' from 'Small Alternative' Pharma, and never without leaving crucial contradictions and identity politics behind

The impact of roughness elements on sediment fluxes in coastal dunes and dune valleys: solving the puzzle for Spanjaards Duin

In 2009 a new dune area called Spanjaards Duin was constructed in front of the Delfland Coast. Spanjaards Duin was created as a compensation measure for the expected increase in nitrogen deposition from the expansion of the Rotterdam harbour (Maasvlakte 2). The predefined compensation goal is to reach 6 ha of moist dune slack vegetation and 10 ha of dry grey dune in 2033. This is pursued by creating favourable abiotic conditions for natural vegetation establishment (van der Meulen et al., 2014). Sediment fluxes affect establishment and growth of vegetation and shape the dune landscape. Therefore, there is need to know how sediment fluxes behave in Spanjaards Duin

Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier

BACKGROUND: The sphingosine 1-phosphate (S1P) receptor modulator FTY720P (Gilenya®) potently reduces relapse rate and lesion activity in the neuroinflammatory disorder multiple sclerosis. Although most of its efficacy has been shown to be related to immunosuppression through the induction of lymphopenia, it has been suggested that a number of its beneficial effects are related to altered endothelial and blood–brain barrier (BBB) functionality. However, to date it remains unknown whether brain endothelial S1P receptors are involved in the maintenance of the function of the BBB thereby mediating immune quiescence of the brain. Here we demonstrate that the brain endothelial receptor S1P(5) largely contributes to the maintenance of brain endothelial barrier function. METHODS: We analyzed the expression of S1P(5) in human post-mortem tissues using immunohistochemistry. The function of S1P(5) at the BBB was assessed in cultured human brain endothelial cells (ECs) using agonists and lentivirus-mediated knockdown of S1P(5). Subsequent analyses of different aspects of the brain EC barrier included the formation of a tight barrier, the expression of BBB proteins and markers of inflammation and monocyte transmigration. RESULTS: We show that activation of S1P(5) on cultured human brain ECs by a selective agonist elicits enhanced barrier integrity and reduced transendothelial migration of monocytes in vitro. These results were corroborated by genetically silencing S1P(5) in brain ECs. Interestingly, functional studies with these cells revealed that S1P(5) strongly contributes to brain EC barrier function and underlies the expression of specific BBB endothelial characteristics such as tight junctions and permeability. In addition, S1P(5) maintains the immunoquiescent state of brain ECs with low expression levels of leukocyte adhesion molecules and inflammatory chemokines and cytokines through lowering the activation of the transcription factor NFκB. CONCLUSION: Our findings demonstrate that S1P(5) in brain ECs contributes to optimal barrier formation and maintenance of immune quiescence of the barrier endothelium

Does same session EUS-guided tissue acquisition and ERCP increase the risk of pancreatitis in patients with malignant distal biliary obstruction?

Background: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography-guided tissue acquisition (EUS-TA) are increasingly performed in the same session in patients with malignant biliary obstruction. In this retrospective analysis, we investigated adverse events (AE) after same session ERCP and EUS-TA. Methods: Patients with malignant distal biliary obstruction who underwent EUS-TA and/or ERCP with self-expandable metal stent (SEMS) placement from January 2015 to April 2020 were included. Primary outcome was post-procedural pancreatitis (PPP). Secondary outcomes were other procedure-related AE. Results: We included 494 patients, of which 118 patients (24%) underwent same session EUS-TA+ERCP, 51 patients (10%) underwent separate session EUS-TA & ERCP, 90 patients (18%) ERCP-only and 235 patients (48%) EUS-TA only. PPP occurred in 22 patients (19%) after same session EUS-TA+ERCP and in 6 patients (12%) after separate EUS-TA & ERCP (p = 0.270). When adjusted for other known risk factors (i.e., difficult procedure), the difference in PPP remained non-significant (adjusted odds ratio 1.74 (95%-CI 0.65-4.67, p = 0.268). The incidence of other AE was similar, although the overall AE rate was significantly higher after same session EUS-TA+ERCP (36% vs. 20%, p = 0.030). Conclusion: Same session EUS-TA+ERCP did not significantly increase the incidence of PPP, although overall AE were significantly higher. These data warrant further prospective studies.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Prognostically useful gene-expression profiles in acute myeloid leukemia

BACKGROUND: In patients with acute myeloid leukemia (AML) a combination of methods must be used to classify the disease, make therapeutic decisions, and determine the prognosis. However, this combined approach provides correct therapeutic and prognostic information in only 50 percent of cases. METHODS: We determined the gene-expression profiles in samples of peripheral blood or bone marrow from 285 patients with AML using Affymetrix U133A GeneChips containing approximately 13,000 unique genes or expression-signature tags. Data analyses were carried out with Omniviz, significance analysis of microarrays, and prediction analysis of microarrays software. Statistical analyses were performed to determine the prognostic significance of cases of AML with specific molecular signatures. RESULTS: Unsupervised cluster analyses identified 16 groups of patients with AML on the basis of molecular signatures. We identified the genes that defined these clusters and determined the minimal numbers of genes needed to identify prognostically important clusters with a high degree of accuracy. The clustering was driven by the presence of chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular genetic mutations (CEBPA), and abnormal oncogene expression (EVI1). We identified several novel clusters, some consisting of specimens with normal karyotypes. A unique cluster with a distinctive gene-expression signature included cases of AML with a poor treatment outcome. CONCLUSIONS: Gene-expression profiling allows a comprehensive classification of AML that includes previously identified genetically defined subgroups and a novel cluster with an adverse prognosis