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- Berggren, Kristina, 1971, et al.
(författare)
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3-Aminopiperidine Based Peptide Analogues as the First Selective Noncovalent Inhibitors of the Bacterial Cysteine Protease IdeS
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:6, s. 2549-2560
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Tidskriftsartikel (refereegranskat)abstract
- A series of eight peptides corresponding to the amino acid sequence of the hinge region of IgG and 17 newly synthesized peptide analogues containing a piperidine moiety as a replacement of a glycine residue were tested as potential inhibitors of the bacterial IgG degrading enzyme of Streptococcus pyogenes, IdeS. None of the peptides showed any inhibitory activity of IdeS, but several piperidine-based analogues were identified as inhibitors. Two different analysis methods were used: an SDS-PAGE based assay to detect IgG cleavage products and a surface plasmon resonance spectroscopy based assay to quantify the degree of inhibition. To investigate the selectivity of the inhibitors for IdeS, all compounds were screened against two other related cysteine proteases (SpeB and papain). The selectivity results show that larger analogues that are active inhibitors of IdeS are even more potent as inhibitors of papain, whereas smaller analogues that are active inhibitors of IdeS inhibit neither SpeB nor papain. Two compounds were identified that exhibit high selectivity against IdeS and will be used for further studies.
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| 2. |
- Berggren, Kristina, 1971, et al.
(författare)
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Synthesis and biological evaluation of reversible inhibitors of IdeS, a bacterial cysteine protease and virulence determinant
- 2009
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 17:9, s. 3463-3470
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Tidskriftsartikel (refereegranskat)abstract
- Analogues of the irreversible protease inhibitors TPCK and TLCK have been synthesized and tested as inhibitors of the bacterial cysteine protease IdeS excreted by Streptococcus pyogenes. Eight compounds were identified as inhibitors of IdeS in an in vitro assay. The most potent compounds contained an aldehyde function, thus acting as efficient reversible inhibitors, nitrile and azide derivatives showed moderate activity. (C) 2009 Elsevier Ltd. All rights reserved.
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| 3. |
- Arnrup, Kristina, et al.
(författare)
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A short-term follow-up of treatment outcome in groups of uncooperative child dental patients.
- 2004
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Ingår i: European journal of paediatric dentistry : official journal of European Academy of Paediatric Dentistry. - 1591-996X. ; 5:4, s. 216-224
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate the short-term follow-up outcome in four subgroups of uncooperative child dental patients referred to a specialist paediatric dental clinic in Sweden. METHODS: Seventy children, classified into four groups (based on fear, temperament, behaviour and verbal intelligence), were followed-up at their public dental clinics after termination of specialist dental treatment. Questionnaire assessments of children's dental and general fear, parental dental fear, emotional stress, locus of control and parenting efficacy were made by parents pre and post treatment and at follow-up and were analysed within and between groups. At follow-up, parents rated their children's coping and procedure stress, while treatment acceptance was rated by the dentists. RESULTS: Decreases in child dental fear were maintained at follow-up, although a third of children still had moderate or high dental fear. For those children who had been classified into the externalising, impulsive group, an increased risk of non-acceptance (RR=3.7) was indicated. The risk of dental fear at follow-up was increased for the group of fearful, inhibited children (RR=3.8). For the study group as a whole a poorer follow-up outcome could be predicted by avoidance behaviour (OR 12.9-16.6) and moderate or high post treatment dental fear (OR 6.5- 21.3). CONCLUSIONS: Fearful, inhibited child dental patients may need, due to dental fear, extra attention even after successful dental treatment at a specialist clinic. Externalising, impulsive children constitute a special challenge for dentistry. The continued need for adjusted management after termination of specialist treatment can be predicted from avoidance behaviour and post treatment dental fear scores.
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| 6. |
- Balldin, Jan, 1935, et al.
(författare)
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Gamma-glutamyltransferase in alcohol use disorders: Modification of decision limits in relation to treatment goals?
- 2010
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Ingår i: Scandinavian journal of clinical and laboratory investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 70:2, s. 71-74
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Serum gamma-glutamyltransferase (GGT) is recommended as a marker for alcohol use disorders by the Swedish National Guidelines for Addiction, although it has a low sensitivity and specificity. GGT is inexpensive and easily accessible but additional knowledge is required on how to use the marker in patients with various levels of alcohol intake. Levels of GGT were obtained from 37 male social drinkers (< 100 grams pure alcohol weekly) and 18 former alcohol-dependent males with long-term (6 +/- 5 years) abstinence. Reproducibility was calculated through repeated blood samplings. Mean serum activity of GGT, in former alcohol-dependent males, was 0.26 microkat/L with an intra-class correlation coefficient of 0.85. In social drinkers, these figures were 0.34 microkat/L and 0.92, respectively. In treatment of males, with the goal of abstinence, upper reference limit is suggested to be 0.40 microkat/L. Goals of non-harmful drinking (< 100 grams weekly) suggest higher limits (0.62 microkat/L). Thirty percent increase of GGT should be suggestive of relapse.
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| 7. |
- Balldin, Jan, 1935, et al.
(författare)
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TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years.
- 2018
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 53:3, s. 216-220
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence.The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for.At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival.An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender.We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.
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