RESUMO
BACKGROUND/AIM: We investigated the inhibitory action of medium molecular weight heparinyl phenylalanine (MHF) on type I hypersensitivity in comparison with medium molecular weight heparinyl arginine (MHR). MATERIALS AND METHODS: MHF and MHR were synthesized from heparin (HE) to decrease the side-effect of HE based on its anticoagulant action and used in this study. RESULTS: MHF demonstrated a significant inhibitory action on 48-h homologous passive cutaneous anaphylaxis in rats. Although MHF did not affect the death of mice injected with a lethal dose of histamine, it significantly prolonged the survival time of mice administered a lethal dose of compound 48/80. On the other hand, MHR did not inhibit type I hypersensitivity. CONCLUSION: The inhibitory action of MHF on the type I allergic reaction was due to a reduction or delay in histamine release from mast cells. MHF may be a potent anti-allergic agent.
Assuntos
Anticoagulantes/administração & dosagem , Histamina/toxicidade , Hipersensibilidade Imediata/tratamento farmacológico , Fenilalanina/administração & dosagem , Anafilaxia/sangue , Anafilaxia/tratamento farmacológico , Anafilaxia/patologia , Animais , Anticoagulantes/síntese química , Anticoagulantes/química , Arginina/administração & dosagem , Arginina/síntese química , Arginina/química , Modelos Animais de Doenças , Heparina/síntese química , Heparina/química , Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/patologia , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Peso Molecular , Fenilalanina/síntese química , Fenilalanina/química , RatosRESUMO
BACKGROUND/AIM: The aim of this study was to examine the inhibitory action of medium molecular weight heparinyl amino acid derivatives (MHADs) on scorpion venom (SV)-induced acute pulmonary edema. MATERIALS AND METHODS: SV was injected into the tail vein of rats after MHAD pre-treatment. An hour later, lungs were removed from each experimental animal, followed by measurement of the lung/body index (LBI) and Na+/K+ ratio of the pulmonary tissue as indices for acute pulmonary edema. RESULTS: Medium molecular weight heparinyl arginine (MHR)-administered rats exhibited significantly lower LBI and Na+/K+ ratios compared to control rats. Although the mechanism of inhibitory action of MHR on pulmonary edema is unclear, MHR inhibited the vascular permeability increase by SV because both LBI and Na+/K+ ratio of the pulmonary tissue remained at almost normal values. CONCLUSION: MHR may prevent scorpion venom-induced acute pulmonary edema and thus makes a good candidate for clinical use.
Assuntos
Arginina/farmacologia , Edema Pulmonar/etiologia , Edema Pulmonar/patologia , Venenos de Escorpião/efeitos adversos , Animais , Arginina/química , Permeabilidade Capilar/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Peso Molecular , Tamanho do Órgão/efeitos dos fármacos , Potássio/metabolismo , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/metabolismo , Ratos , Sódio/metabolismoRESUMO
We investigated the radical scavenging ability of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF) and medium molecular weight heparinyl leucine (MHL) in the blood of mice. The extracellular superoxide dismutase (EC-SOD) activity was measured according to the method by Oyanagui and Sato. As a result, HE significantly increased the EC-SOD activity with a significant prolongation of activated partial thromboplastin time (APTT), while MHF and MHL significantly increased the EC-SOD activity without a prolongation of APTT. Dose-response curve at 20 min after the injection of each compound indicated a bell-shape. Changes in the plasma EC-SOD activity of mice after the administration of HE, MHF and MHL (10 mg/kg/10 ml) were investigated time-dependently. The plasma EC-SOD activity peaked at 5 min after the administration of all compounds. These results indicated that MHF and MHL show a radical scavenging ability by increasing the EC-SOD activity and MHF may be a candidate for clinical use.
Assuntos
Fibrinolíticos/farmacologia , Heparina/farmacologia , Fenilalanina/química , Superóxido Dismutase/metabolismo , Animais , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Espaço Extracelular/enzimologia , Fibrinolíticos/química , Heparina/química , Leucina/química , Masculino , Camundongos Endogâmicos ICR , Peso Molecular , Tempo de Tromboplastina Parcial , Superóxido Dismutase/sangue , Fatores de TempoRESUMO
We investigated the radical-scavenging effects of heparin (HE), medium molecular weight heparinyl phenylalanine (MHF), and medium molecular weight heparinyl leucine (MHL) using ischemic paw edema in mice. We also examined the activated partial thromboplastin time (APTT) of mice that were administered these compounds as an index of their side-effects. HE had a preventative effect and significant reduced ischemic paw edema. However, its effect was not dose-dependent and the dose-response curve was bell-shaped. The effective dose of HE also exhibited a prolonged APTT. Pretreatment using MHF and MHL were effective against ischemic paw edema without a prolonged APTT. Remarkably, the action of MHF was not only preventively, but also therapeutically active. These results suggest that MHF and MHL are superior to HE as safe radical scavengers in vivo.
Assuntos
Edema/prevenção & controle , Fibrinolíticos/farmacologia , Heparina/administração & dosagem , Isquemia/prevenção & controle , Leucina/química , Fenilalanina/química , Animais , Heparina/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Peso Molecular , Tempo de Tromboplastina ParcialRESUMO
A series of 2-(2-aminothiazol-4-yl)benzo[b]furan and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives were prepared, and their leukotriene B(4) inhibitory activity and growth inhibitory activity in cancer cell lines were evaluated. Several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors and growth inhibition to human pancreatic cancer cells MIA PaCa-2. 3-(4-Chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 8b showed the most potent and selective inhibition for the human BLT(2) receptor, and its IC(50) value was smaller than that of the selected positive control compound, ZK-158252. 3-(4-Chlorophenyl)-2-[2-[(dimethylamino)methyleneamino]-5-(2-hydroxyethyliminomethyl)thiazol-4-yl]-5-methoxybenzo[b]furan 9a displayed growth inhibitory activity towards MIA PaCa-2.
Assuntos
Antineoplásicos/química , Benzofuranos/química , Neoplasias Pancreáticas/tratamento farmacológico , Receptores do Leucotrieno B4/antagonistas & inibidores , Tiazóis/química , Animais , Antineoplásicos/uso terapêutico , Benzofuranos/uso terapêutico , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Receptores do Leucotrieno B4/efeitos dos fármacosRESUMO
Compared to workers on land, seamen working on the ocean are given only limited disease treatment. The aim of this paper is to clarify the actual condition of diseases among such seamen in an effort to improve measures that promote their health. We analyzed 51,641 cases of diseases that were reported to the Ministry of Land, Infrastructure and Transport from 1986 to 2000. The most prevalent diseases included disorders of the digestive system, followed by those of the musculoskeletal and the circulatory systems. The proportions of the three disease types were shown to vary by the type of work, ship, and occupation. One of the reasons for the variation in incidence between type of work and ship might result from differences in the voyage period in the given year. In explaining the varied incidences between occupations we hypothesize that differences in work systems and contents may be important variables to consider. It will be necessary to clarify the lifestyle and living environment of seamen to suggest appropriate measures for combating diseases prevalent in this population.