| 1. |
- Odin, I. S., et al.
(författare)
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Synthesis of New N-Acyl-1,2,3-triazole Chalcones and Determination of Their Antibacterial Activity
- 2020
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Ingår i: Doklady. Chemistry. - : MAIK NAUKA/INTERPERIODICA/SPRINGER. - 0012-5008 .- 1608-3113. ; 492:2, s. 89-92
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Tidskriftsartikel (refereegranskat)abstract
- Previously unknown N-acyl derivatives of 1,2,3-triazole chalcones have been prepared by the acylation of the potassium salts of 4-(3-oxo-3-phenylprop-1-en-1-yl)-5-phenyl-1,2,3-triazolides with carboxylic acid chlorides. The introduction of theN-acyl residue into the heterocyclic moiety of 1-aryl-3-(1H-1,2,3-triazol-4-yl)prop-2-en-1-ones has been shown to afford compounds with antibacterial activity.
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| 2. |
- Cirulli, Elizabeth T., et al.
(författare)
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A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury
- 2019
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 156:6, s. 1707-1716
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility.METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings.RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01.CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
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| 3. |
- Svenningsson, P., et al.
(författare)
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A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:6, s. 1046-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 mu M on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. (c) 2020 International Parkinson and Movement Disorder Society
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| 4. |
- Volkmann, J, et al.
(författare)
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Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease : an evidence-based review
- 2013
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 260:11, s. 2701-2714
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Tidskriftsartikel (refereegranskat)abstract
- Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.
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| 5. |
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| 6. |
- Ballagi, A E, et al.
(författare)
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Platelet-derived growth factor receptor expression after neural grafting in a rat model of Parkinson's disease
- 1994
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Ingår i: Cell Transplantation. - 0963-6897 .- 1555-3892. ; 3:6, s. 453-460
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) has trophic effect on dopaminergic neurons in vitro. We have previously shown dynamic changes in the expression of PDGF in embryonic mesencephalic grafts and surrounding host striatal tissue following intracerebral transplantation in a rat model of Parkinson's disease. In this study the expression of the PDGF receptors was examined in the same model using immunohistochemistry. Most ventral mesencephalic (VM) cells from E13-E15 rat embryos possessed both PDGF alpha- and beta-receptors before implantation. Double immunofluorescence staining revealed that about 10% of the cells also expressed tyrosine hydroxylase (TH). The PDGF alpha-receptor was detectable in the graft up to 1 wk after transplantation but had disappeared at 3 wk. In the host tissue, scattered glial cells were positive for the alpha-receptor but the expression was unchanged following transplantation. The beta-receptor expression almost completely disappeared from the grafted tissue by 4 h following transplantation, and only a few cells of the host striatum showed immunoreactivity. However, after 3 wk beta-receptor positive cells were again detectable in the graft. These cells appeared to be endothelial cells as identified by an antibody against von Willebrand's factor. Our data suggest that PDGF might act locally on embryonic dopaminergic cells in an autocrine or juxtacrine manner before and shortly after transplantation, and on surrounding glial cells in a paracrine manner after transplantation. Furthermore, PDGF-BB might influence neovascularization in the graft.
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| 7. |
- Sahlstrom, T., et al.
(författare)
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Workforce participation and activities in Parkinson's disease patients receiving device-aided therapy
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 138:1, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Many countries have an aging population, and it is thus likely that Parkinson's disease (PD) will become an increasing health problem. It is important to ensure this group can use their resources in the best way possible, including remaining in the work market. This study aimed to investigate workforce participation and daily activities among patients with PD receiving device-aided therapy to provide new knowledge that may be used to inform decisions about these therapy options.Materials and Methods:This was a retrospective, descriptive quantitative pilot study, including 67 patients with PD from 3 centers in Sweden and Denmark. Included patients were younger than 67years at the time of introduction of device-aided therapy. Eligible patients were identified by the Swedish national Parkinson patient registry or by the treating neurologist. Quantitative interviews were made by telephone.Results:A majority of the patients could perform the same, or more, amount of activities approximately 5years after the introduction of device-aided therapy. A small number of patients receiving deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel (LCIG) were able to increase their work capacity within 1year of initiating device-aided therapy and a remarkably high share could still work at the end-point of this study, approximately 15years since the diagnosis of PD.Conclusions:Device-aided therapy may sustain or increase daily activities and workforce participation in patients with PD who have not yet reached retirement age. There is need for prospective studies, both quantitative and qualitative, to confirm these results.
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