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BETA
Wadell, Göran
Alternative names
Publications (10 of 67) Show all publications
Islam, M. K. K., Strand, M., Saleeb, M., Svensson, R., Baranczewski, P., Artursson, P., . . . Evander, M. (2018). Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound. Scientific Reports, 8, Article ID 1925.
Open this publication in new window or tab >>Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1925Article in journal (Refereed) Published
Abstract [en]

Rift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. In vitro, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. In vitro, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 in vitro together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in in vivo efficacy models that may lead to further drug development for human use.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-144950 (URN)10.1038/s41598-018-20362-9 (DOI)000423663100004 ()29386590 (PubMedID)
Available from: 2018-02-22 Created: 2018-02-22 Last updated: 2018-09-14Bibliographically approved
Jacobsson, S., Larsson, P., Johansson, G., Norberg, M., Wadell, G., Hallmans, G., . . . Söderberg, S. (2017). Leptin independently predicts development of sepsis and its outcome. Journal of Inflammation, 14, Article ID 19.
Open this publication in new window or tab >>Leptin independently predicts development of sepsis and its outcome
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2017 (English)In: Journal of Inflammation, ISSN 1476-9255, E-ISSN 1476-9255, Vol. 14, article id 19Article in journal (Refereed) Published
Abstract [en]

Background: Sepsis is a life-threatening condition and obesity is related to the clinical outcome. The underlying reasons are incompletely understood, but the adipocyte derived hormones leptin and adiponectin may be involved.

Methods: Patients aged 18 years or more with documented first time sepsis events were included in a nested case-referent study if they had participated in previous health surveys. Two matched referents free of known sepsis were identified. Circulating levels of leptin and adiponectin were determined in stored plasma, and their impact on a future sepsis event and its outcome was evaluated.

Results: We identified 152 patients (62% women) with a sepsis event and a previous participation in a health survey. Eighty-three % had also blood samples from the acute event. Hyperleptinemia at health survey associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00) and with hospital death. After adjustment for BMI leptin remained associated with sepsis in men, but not in women. High levels in the acute phase associated with increased risk for in hospital death in women (OR 4.18, 95% CI 1.17-15.00), while being protective in men (OR 0.05, 95% CI 0.01-0.48). Furthermore, leptin increased more from baseline to the acute phase in men than in women. Adiponectin did not predict sepsis and did not relate to outcome.

Conclusions: Hyperleptinemia independently predicted the development of sepsis and an unfavourable outcome in men, and inertia in the acute response related to worse outcome.

Place, publisher, year, edition, pages
London: BioMed Central, 2017
Keywords
Sepsis, Leptin, Adiponectin, Obesity, Case-referent study, Sex
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-140039 (URN)10.1186/s12950-017-0167-2 (DOI)000410649100001 ()28919840 (PubMedID)
Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2019-05-23Bibliographically approved
Toriola, A. T., Tolockiene, E., Schock, H., Surcel, H.-M., Zeleniuch-Jacquotte, A., Wadell, G., . . . Lukanova, A. (2014). Free beta- human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer. Future Oncology, 10(3), 377-384
Open this publication in new window or tab >>Free beta- human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer
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2014 (English)In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 10, no 3, p. 377-384Article in journal (Refereed) Published
Abstract [en]

Background: We investigated whether the free -human chorionic gonadotropin (free -hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods: Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results: The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free -hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion: In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free -hCG does not appear to provide any additional information.

Keywords
breast cancer, free -human chorionic gonadotropin, human chorionic gonadotropin, nested case-control study, pregnancy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-90464 (URN)10.2217/FON.13.208 (DOI)000331698600011 ()
Available from: 2014-07-07 Created: 2014-06-23 Last updated: 2018-06-07Bibliographically approved
Strand, M., Carlsson, M., Uvell, H., Islam, K., Edlund, K., Cullman, I., . . . Almqvist, F. (2014). Isolation and characterization of anti-adenoviral secondary metabolites from marine actinobacteria. Marine Drugs, 12(2), 799-821
Open this publication in new window or tab >>Isolation and characterization of anti-adenoviral secondary metabolites from marine actinobacteria
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2014 (English)In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 12, no 2, p. 799-821Article in journal (Refereed) Published
Abstract [en]

Adenovirus infections in immunocompromised patients are associated with high mortality rates. Currently, there are no effective anti-adenoviral therapies available. It is well known that actinobacteria can produce secondary metabolites that are attractive in drug discovery due to their structural diversity and their evolved interaction with biomolecules. Here, we have established an extract library derived from actinobacteria isolated from Vestfjorden, Norway, and performed a screening campaign to discover anti-adenoviral compounds. One extract with anti-adenoviral activity was found to contain a diastereomeric 1:1 mixture of the butenolide secondary alcohols 1a and 1b. By further cultivation and analysis, we could isolate 1a and 1b in different diastereomeric ratio. In addition, three more anti-adenoviral butenolides 2, 3 and 4 with differences in their side-chains were isolated. In this study, the anti-adenoviral activity of these compounds was characterized and substantial differences in the cytotoxic potential between the butenolide analogs were observed. The most potent butenolide analog 3 displayed an EC50 value of 91 μM and no prominent cytotoxicity at 2 mM. Furthermore, we propose a biosynthetic pathway for these compounds based on their relative time of appearance and structure.

Place, publisher, year, edition, pages
MDPI, 2014
Keywords
adenovirus; antiviral; natural products; secondary metabolites; marine actinobacteria; extract screening; butenolides
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-86525 (URN)10.3390/md12020799 (DOI)000335745100011 ()24477283 (PubMedID)
Available from: 2014-03-03 Created: 2014-02-28 Last updated: 2018-06-08Bibliographically approved
Greber, U. F., Arnberg, N., Wadell, G., Benko, M. & Kremer, E. J. (2013). Adenoviruses: from pathogens to therapeutics: a report on the 10th International Adenovirus Meeting. Cellular Microbiology, 15(1), 16-23
Open this publication in new window or tab >>Adenoviruses: from pathogens to therapeutics: a report on the 10th International Adenovirus Meeting
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2013 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 15, no 1, p. 16-23Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-67056 (URN)10.1111/cmi.12031 (DOI)000314586600002 ()
Available from: 2013-03-24 Created: 2013-03-12 Last updated: 2018-06-08Bibliographically approved
Salzer, J., Nyström, M., Hallmans, G., Stenlund, H., Wadell, G. & Sundström, P. (2013). Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels. Multiple Sclerosis Journal, 19(12), 1587-1591
Open this publication in new window or tab >>Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels
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2013 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 12, p. 1587-1591Article in journal (Refereed) Published
Abstract [en]

Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.

Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.

Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.

Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.

Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.

Place, publisher, year, edition, pages
Sage Publications, 2013
Keywords
Multiple sclerosis, Case control study, Risk factors in epidemiology, Epstein-Barr virus (EBV), Epstein-Barr Nuclear Antigen-1 (EBNA-1), Vitamin D (25[OH]D)
National Category
Neurology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-63746 (URN)10.1177/1352458513483888 (DOI)000325696100008 ()
Available from: 2013-02-11 Created: 2013-01-07 Last updated: 2018-06-08Bibliographically approved
Salzer, J., Hallmans, G., Nyström, M., Stenlund, H., Wadell, G. & Sundström, P. (2013). Smoking as a risk factor for multiple sclerosis. Multiple Sclerosis, 19(8), 1022-1027
Open this publication in new window or tab >>Smoking as a risk factor for multiple sclerosis
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2013 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1022-1027Article in journal (Refereed) Published
Abstract [en]

Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.

Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.

Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.

Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).

Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

Place, publisher, year, edition, pages
Sage Publications, 2013
Keywords
Multiple sclerosis, case control study, risk factors in epidemiology, smoking
National Category
Neurology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-63742 (URN)10.1177/1352458512470862 (DOI)000327373300008 ()23257617 (PubMedID)
Note

First published online December 20th, 2012.

Available from: 2013-01-11 Created: 2013-01-07 Last updated: 2018-06-08Bibliographically approved
Salzer, J., Hallmans, G., Nyström, M., Stenlund, H., Wadell, G. & Sundström, P. (2013). Vitamin A and systemic inflammation as protective factors in multiple sclerosis. Multiple Sclerosis, 19(8), 1046-1051
Open this publication in new window or tab >>Vitamin A and systemic inflammation as protective factors in multiple sclerosis
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2013 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1046-1051Article in journal (Refereed) Published
Abstract [en]

Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS).

Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation.

Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders.

Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95).

Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology. 

Place, publisher, year, edition, pages
Sage Publications, 2013
Keywords
Multiple sclerosis, case-control study, risk factors in epidemiology, vitamin a, retinol, c-reactive protein, CRP, hygiene hypothesis
National Category
Neurology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-64211 (URN)10.1177/1352458512472752 (DOI)000327373300011 ()23334316 (PubMedID)
Available from: 2013-01-21 Created: 2013-01-21 Last updated: 2018-06-08Bibliographically approved
Strand, M., Islam, K., Edlund, K., Öberg, C. T., Allard, A., Bergström, T., . . . Wadell, G. (2012). 2-[4,5-Difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, an antiviral compound with activity against acyclovir-resistant isolates of herpes simplex virus type 1 and 2. Antimicrobial Agents and Chemotherapy, 56(11), 5735-5743
Open this publication in new window or tab >>2-[4,5-Difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, an antiviral compound with activity against acyclovir-resistant isolates of herpes simplex virus type 1 and 2
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2012 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, no 11, p. 5735-5743Article in journal (Refereed) Published
Abstract [en]

Herpes simplex viruses (HSV-1 and HSV-2) are responsible for life-long latent infections in humans, with periods of viral reactivation associated with recurring ulcerations in the orofacial and genital tract. In immunosuppressed patients and neonates, HSV infections are associated with severe morbidity, and in some cases even mortality. Today, acyclovir is the standard therapy for management of HSV infections. However, the need for novel antiviral agents is apparent since HSV isolates resistant to acyclovir therapy are frequently isolated in immunosuppressed patients. In this study, we assessed the anti-HSV activity of the anti-adenoviral compounds 2-[2-(2-benzoylamino)-benzoylamino]benzoic acid, (Benzavir-1) and 2-[4,5-difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, (Benzavir-2) on HSV-1 and HSV-2. Both compounds were active against both viruses. Importantly, Benzavir-2 had similar potency to acyclovir against both HSV types and it was active against clinical acyclovir-resistant HSV isolates.

Place, publisher, year, edition, pages
American Society Microbiology, 2012
Keywords
Herpes simplex virus, HSV, inhibitor, 2-[2-(benzoylamino)benzoylamino]benzoic acid, antiviral, Benzavir
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-60354 (URN)10.1128/AAC.01072-12 (DOI)000310055800039 ()22908173 (PubMedID)
Available from: 2012-10-09 Created: 2012-10-09 Last updated: 2018-06-08Bibliographically approved
Dicks, M. D., Spencer, A. J., Edwards, N. J., Wadell, G., Bojang, K., Gilbert, S. C., . . . Cottingham, M. G. (2012). A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS ONE, 7(7), e40385
Open this publication in new window or tab >>A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 7, p. e40385-Article in journal (Refereed) Published
Abstract [en]

Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less exposed in order to circumvent preexisting anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunological comparison of multiple adenoviral vectors, we optimised a method for accurate determination of infectious titre, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estimation. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clinical trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titre >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clinical use.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-57749 (URN)10.1371/journal.pone.0040385 (DOI)000306406700026 ()
Available from: 2012-08-20 Created: 2012-08-14 Last updated: 2018-06-08Bibliographically approved
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