| 71. |
- Rao, Komal Umashankar, et al.
(författare)
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A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.
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| 72. |
- Nijsingh, Niels, 1977, et al.
(författare)
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Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
- 2019
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Ingår i: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation. Methods The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors. Results Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area. Conclusions The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.
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| 73. |
- Saulo, Eleonor C., et al.
(författare)
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Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
- 2008
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Ingår i: Malaria Journal. - London : BioMed Central. - 1475-2875. ; 7, s. 227-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.MethodsStructured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.ResultsAmong 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.ConclusionWTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.
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| 74. |
- Hedna, Khedidja, 1978, et al.
(författare)
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Clinical relevance of alerts from a decision support system, PHARAO, for drug safety assessment in the older adults
- 2019
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 19:1, s. 164-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPHARAO is a decision support system developed to evaluate the risk for a set of either common or serious side-effects resulting from a combination of pharmacodynamic effects from a patient's medications. The objective of this study was to investigate the validity of the risk scores for the common side-effects generated by PHARAO in older patients.MethodsSide-effects included were sedation, constipation, orthostatic symptoms, anticholinergic and serotonergic effects. The alerts generated by PHARAO were tested in 745 persons 65years old. Dispensed prescriptions retrieved from the Swedish prescribed drug register were used to generate the pharmacological risk scores of patients' medications. Symptoms possibly related to side-effects were extracted from medical records data.ResultsThe PHARAO system generated 776 alerts, most often for the risk of anticholinergic symptoms. The total specificity estimates of the PHARAO system were 0.95, 0.89 and 0.78 for high, intermediate and low risk alerts, respectively. The corresponding sensitivity estimates were between 0.12 and 0.37. The negative predictive value was 0.90 and the positive predictive value ranged between 0.20-0.25.ConclusionsThe PHARAO system had a high specificity and negative predictive value to detect symptoms possibly associated with the of patients' medications, while the sensitivity and positive predictive value were low. The PHARAO system has the potential to minimise the risk of over-alerts in combination with a drug-drug interaction alert system, but should be used in connection with a medical evaluation of the patient.
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| 75. |
- Chen, Yu, 1990, et al.
(författare)
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Yeast optimizes metal utilization based on metabolic network and enzyme kinetics
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:12
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Tidskriftsartikel (refereegranskat)abstract
- Metal ions are vital to metabolism, as they can act as cofactors on enzymes and thus modulate individual enzymatic reactions. Although many enzymes have been reported to interact with metal ions, the quantitative relationships between metal ions and metabolism are lacking. Here, we reconstructed a genome-scale metabolic model of the yeast Saccharomyces cerevisiae to account for proteome constraints and enzyme cofactors such as metal ions, named CofactorYeast. The model is able to estimate abundances of metal ions binding on enzymes in cells under various conditions, which are comparable to measured metal ion contents in biomass. In addition, the model predicts distinct metabolic flux distributions in response to reduced levels of various metal ions in the medium. Specifically, the model reproduces changes upon iron deficiency in metabolic and gene expression levels, which could be interpreted by optimization principles (i.e., yeast optimizes iron utilization based on metabolic network and enzyme kinetics rather than preferentially targeting iron to specific enzymes or pathways). At last, we show the potential of using the model for understanding cell factories that harbor heterologous iron-containing enzymes to synthesize high-value compounds such as p-coumaric acid. Overall, the model demonstrates the dependence of enzymes on metal ions and links metal ions to metabolism on a genome scale.
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| 76. |
- Hsiao, Meng-Hsuan, et al.
(författare)
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Design and characterization of a novel amphiphilic chitosan nanocapsule-based thermo-gelling biogel with sustained in vivo release of the hydrophilic anti-epilepsy drug ethosuximide
- 2012
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 161:3, s. 942-948
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Tidskriftsartikel (refereegranskat)abstract
- Thermo-gelling injectable nanogels, with no burst release of loaded drug, were prepared by a simple route by combining self assembled nanocapsules of amphiphilically modified chitosan with glycerophosphate di-sodium salt and glycerol. The potential as a depot drug delivery system was demonstrated in vivo through the therapeutic effect of ethosuximide (ESM) loaded nanogels, suppressing spike wave discharges (SWDs) in Long Evan rat model. Simultaneously clearance of gels from the site of administration was monitored non-invasively using MRI. The gel structure was characterized using TEM and SEM, confirming the gels to be an assembly of nanocapsules and using two-photon microscopy to visualize the network structure. In vitro drug release studies using ESM revealed that the nanogels exhibited extended, mostly Fickian release. Finally, all investigated formulations displayed excellent cytotoxicity data determined by MTT assay using human retinal pigmented epithelium cells. All presented properties are highly desirable for injectable depot gels for drug delivery.
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| 77. |
- Jansson Löfmark, Rasmus, 1979, et al.
(författare)
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Determination of eflornithine enantiomers in plasma by precolumn derivatization with o-phthalaldehyde-N-acetyl-l-cysteine and liquid chromatography with UV detection
- 2010
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Ingår i: BMC Biomedical chromotography. - : Wiley. - 0269-3879 .- 1099-0801. ; 24:7, s. 768-773
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Tidskriftsartikel (refereegranskat)abstract
- A bioanalytical method for indirect determination of eflornithine enantiomers in 75 mu L human plasma has been developed and validated. L- and D-eflornithine were derivatized with o-phthalaldehyde and N-acetyl-L-cysteine to generate diastereomers which were separated on two serially connected Chromolith Performance columns (RP-18e 100 x 4.6 mm i.d.) by a isocratic flow followed by a gradient flow for elution of endogenous compounds. The diastereomers were detected with UV (340 nm). The between-day precisions for L- and D-eflornithine in plasma were 8.4 and 2.3% at 3 mu m, 4.0 and 5.1% at 400 mu m, and 2.0 and 3.7% at 1000 mu m. The lower limit of quantification was determined to be 1.5 mu m, at which precision was 14.9 and 9.9% for 1- and D-eflornithine, respectively.
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| 78. |
- Marina, N., et al.
(författare)
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Potential Clinical Application of Angiotensin 2 Receptor Agonists
- 2015
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Ingår i: The Protective Arm of the Renin Angiotensin System (RAS): Functional Aspects and Therapeutic Implications. - : Elsevier. - 9780128013649 ; , s. 149-153
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Bokkapitel (refereegranskat)abstract
- In this chapter, we explore the factors influencing the selection of a clinical target for the early clinical development of an AT2 (AT2R) agonist for use in man. We discuss the requirements for an Investigational New Drug application. The only available oral AT2R agonist with an extensive preclinical documentation, outlined in previous chapters, is used as the model for this discussion. The growing body of preclinical data in a wide range of areas relevant to clinical applications justifies human proof of concept clinical studies with compound 21 or other AT2R agonists in several indication areas. © 2015 Elsevier Inc.
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| 79. |
- Stryamets, Natalya, et al.
(författare)
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From economic survival to recreation: contemporary uses of wild food and medicine in rural Sweden, Ukraine and NW Russia
- 2015
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Ingår i: Journal of Ethnobiology and Ethnomedicine. - : Springer Science and Business Media LLC. - 1746-4269. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are many ethnobotanical studies on the use of wild plants and mushrooms for food and medicinal treatment in Europe. However, there is a lack of comparative ethnobotanical research on the role of non-wood forest products (NWFPs) as wild food and medicine in local livelihoods in countries with different socio-economic conditions. The aim of this study was to compare the present use of wild food and medicine in three places representing different stages of socio-economic development in Europe. Specifically we explore which plant and fungi species people use for food and medicine in three selected rural regions of Sweden, Ukraine and the Russian Federation.Methods: We studied the current use of NWFPs for food and medicine in three rural areas that represent a gradient in economic development (as indicated by the World Bank), i. e., Smaland high plain (south Sweden), Roztochya (western Ukraine), and Kortkeros (Komi Republic in North West Russia). All areas were characterised by (a) predominating rural residency, (b) high forest coverage, and (c) free access to NWFPs. A total of 205 in-depth semi-structured interviews were conducted with local residents in the three study areas. The collected NWFPs data included (1) the species that are used; (2) the amount harvested, (3) uses and practices (4) changes over time, (5) sources of knowledge regarding the use of NWFPs as wild food and medicine and (6) traditional recipes.Results: In Sweden 11 species of wild plant and fungi species were used as food, and no plant species were used for medicinal purposes. In Ukraine the present use of NWFPs included 26 wild foods and 60 medicinal species, while in Russia 36 food and 44 medicinal species were reported.Conclusions: In the economically less developed rural areas of Ukraine and Russia, the use of NWFPs continues to be an important part of livelihoods, both as a source of income and for domestic use as food and medicine. In Sweden the collection of wild food has become mainly a recreational activity and the use of medicinal plants is no longer prevalent among our respondents. This leads us to suggest that the consumption of wild food and medicine is influenced by the socio-economic situation in a country.
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| 80. |
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