Anders Tunek

AstraZeneca (Sweden)

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Cecilia Schelin

Lund University

Bengt Jergil

Lund University

Franz Oesch

Johannes Gutenberg University Mainz

Maths Berlin

Lund University

Karin Sjödin

Örebro University

L Svensson

AstraZeneca (Sweden)

Anders Hallberg

Uppsala University

Khanh Bui

Unité Matériaux et Transformations

Carl Petersson

Merck (Germany)

P. Bentley

Regulus Therapeutics (United States)

Cooperative Institutions

Lund University

Karolinska Institutet

AstraZeneca (Sweden)

National Institutes of Health

University of Michigan–Ann Arbor

Uppsala University

AstraZeneca (United Kingdom)

National Institute of Environmental Health Sciences

The University of Texas Southwestern Medical Center

National Cancer Institute

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Airway Inflammation in Smokers with Nonobstructive and Obstructive Chronic Bronchitis

American Review of Respiratory Disease (1993)

Margareta Linden Jørgen Rasmussen Eeva Piitulainen Anders Tunek Mikael Larson

To assess the manifestation and location of airway inflammation in smokers with chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD), we lavaged the airways of 12 smokers with CB and 11 smokers with COPD and coexisting CB (OCB). For comparison, the airways of 5 asymptomatic smokers (AS) and 10 healthy nonsmokers (HNS) were lavaged. In all cases, the first lavage aliquot, labeled "bronchial lavage" (BL), was processed separately from the four subsequent aliquots, which were combined and labeled "bronchoalveolar lavage" (BAL). The composition of BL and BAL fluids indicated an ongoing inflammatory process in the airways of all three groups of smokers. CB patients with obstruction had significantly lower concentrations of inflammatory cells in the BL and BAL fluids compared with subjects with nonobstructed CB. Furthermore, airway obstruction, indicated by a reduced FEV1, was significantly correlated with the concentrations of glutathione (p < 0.001), myeloperoxidase (MPO; p < 0.01), and eosinophil cationic protein (ECP; p < 0.01) in BAL fluids. Taken together, these findings suggest that the manifestations of inflammation present in the airways of smokers with CB are different in those who have developed obstruction compared with those who have not.

Chronic bronchitis

Airway obstruction

10.1164/ajrccm/148.5.1226

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Citations (190)

Investigation of the Possible Dopaminergic Toxicity of 1‐Methyl‐3‐phenyl‐1,2,3,6‐tetrahydropyridine, an Isomer to the Neurotoxin MPTP

Pharmacology & Toxicology (1991)

Kristina Nilsson Anders HaUberg Erik Pileblad Anders Tunek

Abstract: 1‐Methyl‐3‐phenyl‐1,2,3,6‐tetrahydropyridine (M‐3‐PTP) is an analogue to the Parkinson‐producing dopaminergic toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). M‐3‐PTP, and simple analogues thereof, are versatile intermediates in organic synthesis. The present study was undertaken to investigate the possible dopaminergic toxicity of M‐3‐PTP. Male albino mice were injected with 50 mg/kg of either MPTP or M‐3‐PTP and dopamine (DA) and its metabolites were determined 2 hr and 7 days after the administration. Two hr after MPTP profound acute changes in brain DA metabolism were found, i.e. an approximately 50% reduction in the concentration of DA together with a 10‐fold increase in the level of 3‐methoxytyramine. Seven days after MPTP, DA and metabolites were markedly reduced which is consistent with a degeneration of the dopaminergic neurones. In contrast M‐3‐PTP produced no acute or long‐term alterations in the concentrations of DA and its metabolites in mouse brain. Furthermore, in vitro experiments show that M‐3‐PTP does not inhibit monoamine oxidase B. Thus, the present data show that M‐3‐PTP is devoid of dopaminergic toxicity in mouse brain and is not likely to produce Parkinson's disease in humans. The lack of toxicity is probably explained by the low affinity of M‐3‐PTP for monoamino oxidase B.

MPTP

Neurotoxin

Monoamine oxidase B

10.1111/j.1600-0773.1991.tb00406.x

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Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes.

PubMed (1997)

Anders Tunek Karin Sjödin Gösta Hallström

Microsomes from human lung and liver catalyze the formation of fatty acid esters of budesonide, a glucocorticoid used for inhalation treatment of asthma. The conjugation was dependent on coenzyme A and ATP. Addition of free fatty acids to the incubations affected the pattern of metabolites, but ester formation was observed also without such addition. Budesonide oleate, palmitate, linoleate, palmitoleate, and arachidonate were identified as metabolites. The fatty acid conjugates of budesonide were shown to be substrates for lipase in vitro, thus budesonide is regainable from the conjugates. The data suggest that an equilibrium between budesonide and these pharmacologically inactive lipoidal conjugates will be established in tissues at repeated exposure to budesonide. Since the fatty acid conjugates most likely will be retained intracellularly for a longer time than unchanged budesonide, the duration of tissue exposure to budesonide will depend partly on the rate of lipase-catalyzed hydrolysis of the conjugates. The findings in this study provide a possible explanation for the efficacy of budesonide in mild asthmatics also when inhaled once daily.

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Metabolism and pharmacokinetic optimization strategies in drug discovery

Elsevier eBooks (2013)

Peter Ballard Patrick Brassil Khanh Bui Hugues Dolgos Carl Petersson

10.1016/b978-0-7020-4299-7.00010-x

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Citations (9)

Toxic effects on mouse bone marrow caused by inhalation of benzene

Archives of Toxicology (1982)

Kristina Toft Tor Olofsson Anders Tunek Maths Berlin

Inhalation exposure

10.1007/bf00317008

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Citations (34)

Metabolism of N-acetyl-l-cysteine Some structural requirements for the deacetylation and consequences for the oral bioavailability

Biochemical Pharmacology (1989)

Karin Sjödin Elisibeth Nilsson Anders Hallberg Anders Tunek

Intestinal mucosa

Cysteine Metabolism

10.1016/0006-2952(89)90677-1

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Citations (103)

N‐isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis

European Respiratory Journal (1999)

Ann Ekberg‐Jansson M. Larson William MacNee Anders Tunek Lars Wahlgren

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.

Chronic bronchitis

10.1034/j.1399-3003.1999.13d22.x

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Citations (34)

A rapid and sensitive method for determination of covalent binding of benzo[a]pyrene to proteins

Chemico-Biological Interactions (1981)

Håkan Wallin Cecilia Schelin Anders Tunek Bengt Jergil

Xenobiotic

10.1016/0009-2797(81)90157-5

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Citations (38)

Hydrolysis of 3H-bambuterol, a carbamate prodrug of terbutaline, in blood from humans and laboratory animals in vitro