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ABT-761 attenuates bronchoconstriction and pulmonary inflammation in rodents.

https://arctichealth.org/en/permalink/ahliterature15808
Source
J Pharmacol Exp Ther. 1997 Mar;280(3):1366-73
Publication Type
Article
Date
Mar-1997
Author
R L Bell
R R Harris
P E Malo
J B Bouska
T K Shaughnessy
K I Hulkower
C D Brooks
G W Carter
Author Affiliation
Immunosciences Research Area, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Source
J Pharmacol Exp Ther. 1997 Mar;280(3):1366-73
Date
Mar-1997
Language
English
Publication Type
Article
Keywords
Animals
Arachidonate 5-Lipoxygenase - antagonists & inhibitors
Bronchoconstriction - drug effects
Enzyme Inhibitors - pharmacology - therapeutic use
Eosinophils - pathology
Guinea Pigs
Humans
Hydroxyurea - analogs & derivatives - pharmacology - therapeutic use
In Vitro
Leukotriene E4 - antagonists & inhibitors
Macaca fascicularis
Male
Mice
Muscle Contraction - drug effects
Pneumonia - drug therapy - pathology
Rats
Abstract
Our primary goal has been to discover leukotriene biosynthesis inhibitors with characteristics that are appropriate for use as clinical agents. The success of the use of zileuton in the treatment of asthma led us to explore further the use of the N-hydroxyurea class of 5-lipoxygenase inhibitors as longer-acting compounds with good lung penetration. A variety of in vitro and in vivo methods were used to evaluate a large number of compounds, from which ABT-761 [(R)-N-(3-(5-(4-fluorophenylmethyl)thien-2-yl)-1-methyl-2-pr opynyl)-N-hydroxyurea] was selected for study. ABT-761 exhibited potent and selective inhibition of leukotriene formation both in vitro and in vivo. More importantly, the compound potently inhibited antigen-induced bronchospasm in guinea pigs when given either prophylactically or therapeutically. In addition, ABT-761 was a potent inhibitor of eosinophil influx into the lungs of Brown Norway rats. These data provide added support for the role of leukotrienes in both bronchospasm and eosinophilic inflammation and characterize ABT-761 as a particularly potent inhibitor of leukotrienes formed in pulmonary tissues. These data combined with the excellent pharmacokinetic characteristics of the compound indicate its potential use in the treatment of leukotriene-dependent human disease.
PubMed ID
9067325 View in PubMed
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[A case of human infection with brucellosis from a cat]

https://arctichealth.org/en/permalink/ahliterature36213
Source
Zh Mikrobiol Epidemiol Immunobiol. 1993 Jul-Aug;(4):66-8
Publication Type
Article
Author
L P Repina
A I Nikulina
I A Kosilov
Source
Zh Mikrobiol Epidemiol Immunobiol. 1993 Jul-Aug;(4):66-8
Language
Russian
Publication Type
Article
Keywords
Adult
Animals
Brucella - isolation & purification - pathogenicity
Brucellosis - epidemiology - microbiology - transmission - veterinary
Cat Diseases - epidemiology - microbiology - transmission
Cats
Child
Child, Preschool
Disease Vectors
English Abstract
Female
Guinea Pigs
Humans
Male
Mice
Rural Population - statistics & numerical data
Siberia - epidemiology
Virulence
Abstract
The epidemiological study of a focus of Brucella infection revealed that an outbreak of brucellosis occurred in a small town, and the source of this infection was a domestic cat. As the result of contacts with this cat, six persons, among them three children aged 3, 8 and 12 years, had brucellosis. In all these patients acute brucellosis was diagnosed. Simultaneously with the clinical manifestations of the disease, a rise in antibody titer from 1:50 to 1:1,600 was observed. Brucella cultures isolated from the blood of one of the patients and from the internal organs of the cat exhibited the properties, similar to those of "rodent" strains, i. e. their differential signs permit their classification with B. suis, serovar 5.
PubMed ID
8067119 View in PubMed
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[A cytomorphological basis for the correction of radiation-induced immunodeficiencies and hematopoietic depression using thymus and bone marrow peptides]

https://arctichealth.org/en/permalink/ahliterature46586
Source
Arkh Patol. 1993 Mar-Apr;55(2):50-3
Publication Type
Article
Author
O K Khmel'nitskii
I I Grintsevich
V A Kotov
S V Seryi
Source
Arkh Patol. 1993 Mar-Apr;55(2):50-3
Language
Russian
Publication Type
Article
Keywords
Accidents, Radiation
Adjuvants, Immunologic - therapeutic use
Adolescent
Adult
Animals
Comparative Study
Drug Combinations
Drug Evaluation
Drug Evaluation, Preclinical
English Abstract
Female
Guinea Pigs
Hematopoiesis - drug effects - radiation effects
Humans
Immunologic Deficiency Syndromes - drug therapy - etiology - pathology
Male
Middle Aged
Peptides - therapeutic use
Power Plants
Radiation Injuries - complications - drug therapy - pathology
Radiation Injuries, Experimental - complications - drug therapy - pathology
Thymus Hormones - therapeutic use
Ukraine
Abstract
The correction of radiation-induced immunodeficiency and hematopoiesis depression in clinical setting (100 patients) and in experiments (160 animals) by peptide preparations of the thymus and bone marrow (thymalin, hemalin, thymogemine and synthetic thymalin analog thymogen) has been studied. Administration of the bone marrow and thymus recovery of damage to the thymus, bone marrow, spleen and lymph nodes, improved the function of circulating neutrophilic granulocytes. Thymalin was able to compensate for immune disturbances and reduce manifestations of asthenia.
PubMed ID
7980063 View in PubMed
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[Age-related changes in inotropic effects of noradrenaline and acetylcholine on the myocardium of guinea pigs]

https://arctichealth.org/en/permalink/ahliterature11882
Source
Fiziol Zh. 1992 May-Jun;38(3):11-8
Publication Type
Article
Author
S H Kaz'min
S B Dudka
Source
Fiziol Zh. 1992 May-Jun;38(3):11-8
Language
Ukrainian
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Aging - physiology
Animals
Atrial Function
Comparative Study
Culture Media
Depression, Chemical
English Abstract
Guinea Pigs
Heart Atria - drug effects
Heart Ventricles - drug effects - physiology
In Vitro
Models, Cardiovascular
Myocardial Contraction - drug effects - physiology
Norepinephrine - pharmacology
Papillary Muscles - drug effects - physiology
Abstract
The inotropic effects of noradrenaline (10(-7)-10(-5) M) and acetylcholine (10(-8)-10(-6) M) were studied in experiments carried out on preparations of the right atria and on papillary muscles of the right ventricle in adult (4-5 months) and old (18-24 months) guinea pigs. An age-related decrease in inotropic noradrenaline effects and the displacement of dose-effect relationships to the right was revealed. Similar changes of the dose-related effects of acetylcholine superfused against the background of noradrenaline action were observed. The direct inotropic action of the acetylcholine did not change with ageing. A lack of the essential atrial-ventricular differences in age-related changes in myocardial reactivity is apparently very significant for support of effective functional coupling of cardiac chambers in ageing.
PubMed ID
1499755 View in PubMed
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[Alfa-subunit composition of neuronal nicotinic acetylcholine receptors of the submucosal plexus in the guinea-pig small intestine]

https://arctichealth.org/en/permalink/ahliterature45770
Source
Fiziol Zh. 2004;50(4):73-8
Publication Type
Article
Date
2004
Author
O O Hryhorov
M V Skok
V I Skok
Source
Fiziol Zh. 2004;50(4):73-8
Date
2004
Language
Ukrainian
Publication Type
Article
Keywords
Acetylcholine - pharmacology
Action Potentials - drug effects
Animals
Cells, Cultured
English Abstract
Guinea Pigs
Immunohistochemistry
Intestine, Small - innervation
Neurons - metabolism - physiology
Patch-Clamp Techniques
Protein Subunits - metabolism
Receptors, Nicotinic - metabolism
Submucous Plexus - cytology - drug effects - metabolism
Abstract
The alpha-subunit composition of nicotinic acetylcholine receptors (nAChRs) in the submucosal plexus of the guinea-pig ileum were studied using the whole-cell patch-clamp technique and affinity-purified antibodies (Abs) against alpha3-, alpha4, alpha5 and alpha7-subunits of nAChRs. The independent addition of anti-alpha3 and anti-alpha5 Abs to extracellular bath solution induced depression of the acetylcholine (ACh)-evoked currents by 60% +/- 1.56% and 65% +/- 1.62% correspondingly. Successive application of anti-alpha5 Abs in the presence of anti-alpha3 Abs did not have any additional blocking effect on ACh-evoked currents. Anti-alpha7 Abs evoked depression of Ach-induced currents by 24% +/- 1.51% in 80% of investigated neurons and by 67% +/- 1.5% in 20% of neurons. The addition of anti-alpha4 Abs to extracellular bath solution did not have effect on membrane currents of the investigated neurons. Our data provide evidence of participation of alpha3-, alpha5 and alpha7-containing receptors in the response to ACh. Alpha3- and alpha5-subunits are associated in the same functional nAChRs that provide greater part of response to ACh in the most of submucosal neurons. However, in some neurones alpha7-containing nAChRs provide greater part of response to agonist.
PubMed ID
15460030 View in PubMed
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Allergic encephalomyelitis in the reputedly resistant Brown Norway strain of rats.

https://arctichealth.org/en/permalink/ahliterature57966
Source
J Immunol. 1975 Feb;114(2 Pt 1):597-601
Publication Type
Article
Date
Feb-1975
Author
S. Levine
R. Sowinski
Source
J Immunol. 1975 Feb;114(2 Pt 1):597-601
Date
Feb-1975
Language
English
Publication Type
Article
Keywords
Adjuvants, Immunologic
Animals
Antigens - administration & dosage
Encephalomyelitis, Autoimmune, Experimental - immunology - pathology
Freund's Adjuvant
Genotype
Guinea Pigs
Immunization
Iron
Nerve Tissue Proteins - immunology
Pertussis Vaccine
Rats
Rats, Inbred BN - immunology
Rats, Inbred Strains - immunology
Spinal Cord - immunology
Abstract
Brown Norway (BN) rats are much less susceptible to experimental allergic encephalomyelitis (EAE) than Lewis rats. Nevertheless, BN rats developed severe EAE, even paralysis, when immunized with rat spinal cord and carbonyl iron adjuvant. Complete Freund's adjuvant (CFA) was much less effective. The use of both CFA and pertussis vaccine with rat cord was moderately, but not consistently, effective. Guinea pig spinal cord was weakly encephalitogenic to BN rats with all adjuvant combinations. We were not able to produce EAE in BN rats with purified myelin basic protein from either rat or guinea pig. Inoculations directly into lymph nodes or into the blood stream proved that the low susceptibility of BN rats was not due to lack of absorption from the site of inoculation, but may be related to peculiarities of processing antigen in draining lymph nodes. The severity of EAE in F1 hybrids was intermediate between the BN and Lewis parental strains when tested with an immunizing procedure of appropriate strength. The fact that F1 hybrids were less reactive than Lewis mandates modification of the theory that susceptibility to EAE is inherited through a single autosomal dominant gene.
PubMed ID
1120901 View in PubMed
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209 records – page 1 of 21.