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1.
J Biol Regul Homeost Agents ; 24(1): 41-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20385070

RESUMEN

Diabetic nephropathy (DN) is a severe and life-threatening complication of long-standing diabetes. As one of the main causes of end-stage renal disease, the prevention and treatment of DN in early stage, and the slowing down of DN progression are of utmost importance and are topics of several ongoing research studies. Nutraceuticals endowed with antioxidant-anti-inflammatory properties may offer an opportunity of integrative treatment for this condition. Male Wistar rats were randomly assigned to two groups. One group of rats (diabetic group) received a single tail-vein injection of STZ compound (50 mg/kg) under light anaesthesia. A protective dose of 0.5 ml of 5 percent dextrose was given intraperitoneally 30 min before the administration of STZ. One diabetic group was fed a normal pellet diet (group A) while group B was fed the diet added with DTS (panax pseudoginseng, eucommia ulmoides), (Kyotsu Jigyo, Tokyo, Japan) in the proportion of 50/25 (percent weight/weight), at the dose of 50 mg/kg/day throughout the experimental period. At the end of 8 weeks, 24-hour urine was collected for the measurement of the albumin concentration: blood samples were collected for serum biochemistry and the rats were sacrificed for kidney measurement of oxidative stress and histomorphological features. Nephrin and Macrophage Chemoattractant Protein-1 (MCP-1) gene expression were also assessed by fluorescence real-time quantitative PCR after RNA extraction and cDNA synthesis. STZ-treated animals showed significantly increased in lipid peroxidation in the kidney and in proteinuria. DTS supplementation did not affect plasma glucose but significantly decreased malonyldialdehyde (MDA) plasma level and the overall redox parameters together with a partial mitigation of proteinuria. Histological analysis showed also that DTS significantly reduced the glomerular volume together with glomerulosclerosis and interstitial fibrosis score (p less than 0.05), the latter two being correlated to proteinuria (p less than 0.05). DTS supplementation also enabled a reduction of diabetes-induced decrease of nephrin mRNA expression and a 67 percent reduction of MCP-1 mRNA up-regulation (p less than 0.01). Taken altogether, these data show that, besides the mandatory control of glycemia, intervention with a nutraceutical with antioxidant and anti-inflammatory properties may have beneficial effects when integrated in the mainstream of the therapeutic regimen.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Panax , Fitoterapia , Animales , Secuencia de Bases , Glucemia/metabolismo , Quimiocina CCL2/genética , Cartilla de ADN/genética , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Femenino , Peroxidación de Lípido/efectos de los fármacos , Masculino , Proteínas de la Membrana/genética , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar
2.
Clin Exp Allergy ; 38(12): 1875-81, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19037964

RESUMEN

BACKGROUND: IL-33, an IL-1-like cytokine, is a ligand for IL1RL1, which is an important effector molecule of type 2 T helper responses. Although IL-33/IL1RL1 interaction has been suggested to be important in induction of allergic airway inflammation, serum levels of IL-33 and the genetic influences of the polymorphisms of IL-33 in human allergic diseases are unclear. OBJECTIVE: The aim of this study was to examine whether the serum IL-33 level and polymorphisms in IL-33 are associated with Japanese cedar (JC) pollinosis, the most common form of allergic rhinitis, and a major public health problem, in Japan. METHODS: We performed linkage disequilibrium (LD) mapping of the gene using the HapMap database, and two selected tag single nucleotide polymorphisms were genotyped. We conducted an association study of IL-33 (JC pollinosis, n=170; normal controls, n=100) and measured the IL-33 levels in sera of the 270 subjects by ELISA. RESULTS: Serum levels of IL-33 were significantly higher in patients with JC pollinosis (P=0.0018) than in controls. In genetic association analysis, we found a positive association between the polymorphism and JC pollinosis (P=0.048). CONCLUSION: Our results support a role for IL-33 in the pathogenesis of JC pollinosis.


Asunto(s)
Alérgenos/efectos adversos , Cryptomeria/inmunología , Interleucinas/sangre , Interleucinas/genética , Polen/efectos adversos , Rinitis Alérgica Estacional/inmunología , Adulto , Susceptibilidad a Enfermedades , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina E/sangre , Interleucina-33 , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Rinitis Alérgica Estacional/sangre , Rinitis Alérgica Estacional/genética , Adulto Joven
3.
Diabetes Obes Metab ; 10(7): 574-85, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17645561

RESUMEN

AIMS: We investigated the effect of the water extract of Salacia oblonga (SOE), an ayurvedic antidiabetic and antiobesity medicine, on obesity and diabetes-associated cardiac hypertrophy and discuss the role of modulation of cardiac angiotensin II type 1 receptor (AT(1)) expression in the effect. METHODS: SOE (100 mg/kg) was given orally to male Zucker diabetic fatty (ZDF) rats for 7 weeks. At the end-point of the treatment, the hearts and left ventricles were weighed, cardiomyocyte cross-sectional areas were measured, and cardiac gene profiles were analysed. On the other hand, angiotensin II-stimulated embryonic rat heart-derived H9c2 cells and neonatal rat cardiac fibroblasts were pretreated with SOE and one of its prominent components mangiferin (MA), respectively. Atrial natriuretic peptide (ANP) mRNA expression and protein synthesis and [(3)H]thymidine incorporation were determined. RESULTS: SOE-treated ZDF rats showed less cardiac hypertrophy (decrease in weights of the hearts and left ventricles and reduced cardiomyocyte cross-sectional areas). SOE treatment suppressed cardiac overexpression of ANP, brain natriuretic peptide (BNP) and AT(1) mRNAs and AT(1) protein in ZDF rats. SOE (50-100 microg/ml) and MA (25 micromol) suppressed angiotensin II-induced ANP mRNA overexpression and protein synthesis in H9c2 cells. They also inhibited angiotensin II-stimulated [(3)H]thymidine incorporation by cardiac fibroblasts. CONCLUSIONS: Our findings demonstrate that SOE decreases cardiac hypertrophy in ZDF rats, at least in part by inhibiting cardiac AT(1) overexpression. These studies provide insights into a potential cardioprotective role of a traditional herb, which supports further clinical evaluation in obesity and diabetes-associated cardiac hypertrophy.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Cardiomegalia/tratamiento farmacológico , Extractos Vegetales/farmacología , Raíces de Plantas/química , Receptor de Angiotensina Tipo 1/efectos de los fármacos , Salacia/química , Animales , Cardiomegalia/etiología , Diabetes Mellitus Experimental/complicaciones , Expresión Génica/efectos de los fármacos , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/efectos de los fármacos , Masculino , Medicina Ayurvédica , Péptidos Natriuréticos/genética , Obesidad/complicaciones , ARN Mensajero/genética , Ratas , Ratas Zucker , Receptor de Angiotensina Tipo 1/genética , Xantonas/análisis
4.
Ann Hepatol ; 5(4): 268-72, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17151579

RESUMEN

The aim of this study was to investigate the effects of the herbal compound YHK on hepatocarcinogenesis induced by diethylntrosamine (DEN) in Sprague Dawley rats. Rats were randomly divided into 3 groups and followed up for 15 weeks. Groups 1 was given standard food and represented the healthy control. Liver preneoplastic foci were induced using the DEN method in groups 2 and 3 (20 rats each). However, group 3 was concomitantly given 50mg/kg/day of YHK. For quantitative assessment of liver preneoplastic foci, the placental form of glutathione-S-transferase (GST-P) positive foci were measured using immunohistochemical staining and image analysis. Treatment using DEN caused a significant decrease in body weight and increase in liver weight compared to the control group while concomitant supplementation with YHK prevented body weight loss and liver weight increase. As compared to DENonly treated rats, the group given YHK showed a significant decrease in the number, size and volume of GSTP- positive foci. Moreover, co-administration of YHK significantly reduced the incidence, number, size and volume of hepatocellular carcinoma. Anti-inflammatory, anti-fibrotic as well as antioxidative properties of this compound are mechanisms which are likely to be advocated for to explain its protective effect. It is concluded that herbal compound YHK by preventing hepatocarcinogenesis in DEN-induced liver preneoplastic lesions in rats has the potential to a large clinical application as a functional food.


Asunto(s)
Anticarcinógenos/uso terapéutico , Carcinoma Hepatocelular/prevención & control , Neoplasias Hepáticas Experimentales/prevención & control , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Animales , Carcinoma Hepatocelular/patología , Dietilnitrosamina , Gutatión-S-Transferasa pi/metabolismo , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas Experimentales/patología , Ratas , Ratas Sprague-Dawley
5.
Ann N Y Acad Sci ; 1067: 408-13, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16804019

RESUMEN

T-maze test-selected prematurely senescent mice (PSM) were allocated into two groups: (A) those given DTS (150 mg/kg) orally for 30 days and (B) untreated PSM with age-matched fast T-maze performers as control. After sacrifice, the liver and kidney were analyzed for catalase (CAT) activity, glutathione peroxidase (GPx), superoxide dismutase (SOD), malondyaldehyde (MDA), and plasma thiols. Untreated PSM showed decreased plasma thiols and tissue level of CAT, SOD, GPx, with higher MDA (P < 0.01 vs. fast performers), while DTS (Denshichi-Tochiu-Sen) significantly improved glutathione and cysteine (P < 0.05) and tissue concentration of the above parameters (P < 0.05). Such preliminary data suggest that DTS mitigated oxidative damage in PSM, with likely action on the cytoplasm and mitochondrial matrix.


Asunto(s)
Envejecimiento/metabolismo , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Sulfonamidas/farmacología , Tiadiazoles/farmacología , Animales , Catalasa/sangre , Glutatión Peroxidasa/sangre , Glutatión Reductasa/sangre , Riñón/irrigación sanguínea , Riñón/enzimología , Riñón/metabolismo , Hígado/irrigación sanguínea , Hígado/enzimología , Hígado/metabolismo , Malondialdehído/análisis , Ratones , Ratones Endogámicos BALB C , Oxidación-Reducción , Estrés Oxidativo , Fitoterapia , Distribución Aleatoria , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis
6.
Ann N Y Acad Sci ; 1067: 414-9, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16804020

RESUMEN

Twenty-month-old Swiss mice were allocated into three groups: (A) control; (B) infected group; and (C) infected but treated with 5 mg of the phytocompound MMT. Mice were infected intranasally with 30 microL of 75 HA viral units. MMT markedly blunted the nasal signs of virus infection and the febrile response. Formazan-positive cells, lung and plasma lipoperoxides, and TNF-alpha in lung tissue increased during viral infection, but improvement was seen in the MMT-treated group (P < 0.05). MMT also normalized SOD, catalase activities, and ascorbic acid and determined a significant decrease of lung but not nasal viral titer, although nasal inflammatory infiltrate dropped significantly. MMT has potential clinical applications with and has an excellent safety profile even in old animals.


Asunto(s)
Envejecimiento/metabolismo , Antioxidantes/administración & dosificación , Suplementos Dietéticos , Infecciones por Orthomyxoviridae/dietoterapia , Administración Oral , Animales , Ácido Ascórbico/análisis , Líquido del Lavado Bronquioalveolar/química , Catalasa/análisis , Quimiocina CCL5/análisis , Modelos Animales de Enfermedad , Esquema de Medicación , Pulmón/enzimología , Pulmón/metabolismo , Pulmón/virología , Ratones , Infecciones por Orthomyxoviridae/virología , Distribución Aleatoria , Superóxido Dismutasa/análisis , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisis , Carga Viral
7.
Rejuvenation Res ; 9(2): 338-41, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16706665

RESUMEN

Hepatocytes isolated from 20- and 4-month Wistar rats and cultured with or without alpha-linolenic acid (LNA) were then added with nutraceutical YHK or sylibin before the test with iron or copper. Overall, YHK proved to be more effective than sylibin in Fe/Cu-induced peroxidative damage on normal and LNA-loaded hepatocytes (p < 0.05). YHK exerted a significant protection against DPPH radical-scavenging activity in the "old" group (p versus sylibin) and against lipophilic generators in both age groups (p < 0.05 versus sylibin). Both compounds were ineffective on age-related increase of surface-charge density. These preliminary data suggest that age per se enhances the vulnerability of hepatocytes to xenobiotics, whereas some safe nutraceuticals seem to exert significant protective effects.


Asunto(s)
Suplementos Dietéticos , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Xenobióticos/farmacología , Animales , Células Cultivadas , Hepatocitos , Peroxidación de Lípido , Lisosomas/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Albúmina Sérica Bovina , Ácido alfa-Linolénico
8.
J Nutr Sci Vitaminol (Tokyo) ; 47(3): 213-21, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11575576

RESUMEN

Effects of tomato juice supplementation on the carotenoid concentration in lipoprotein fractions and the oxidative susceptibility of LDL were investigated in 31 healthy Japanese female students. These subjects were randomized to one of three treatment groups; Control, Low and High. The Control, Low and High groups consumed 480 g of a control drink, 160 g of tomato juice plus 320 g of the control drink, and 480 g of tomato juice, providing 0, 15 and 45 mg of lycopene, respectively, for one menstrual cycle. The ingestion of tomato juice, rich in lycopene but having little beta-carotene, increased both lycopene and beta-carotene. Sixty-nine percent of lycopene in plasma was distributed in the LDL fraction and 24% in the HDL fraction. In the Low group, the lycopene concentration increased 160% each in the VLDL+IDL, LDL and HDL fractions (p<0.01). In the High group, the lycopene concentration increased 270% each in the VLDL+IDL and LDL fractions, and 330% in the HDL fraction (p<0.01). Beta-carotene also increased 120% and 180% in LDL fractions of the Low and the High groups, respectively. Despite these carotenoid increases in LDL, the lag time before oxidation was not prolonged as compared with that of the Control group. The propagation rate decreased significantly after consumption in the High group. Multiple regression analysis showed a positive correlation between lag time changes and changes in the alpha-tocopherol concentration per triglyceride in LDL, and a negative correlation between propagation rate changes and changes in the lycopene concentration per phospholipid in LDL. These data suggest that alpha-tocopherol is a major determinant in protecting LDL from oxidation, while lycopene from tomato juice supplementaion may contribute to protect phospholipid in LDI, from oxidation. Thus, oral intake of lycopene might be beneficial for ameliorating atherosclerosis.


Asunto(s)
Antioxidantes/metabolismo , Bebidas , Carotenoides/metabolismo , Lipoproteínas LDL/metabolismo , Solanum lycopersicum , beta Caroteno/metabolismo , Adulto , Arteriosclerosis/prevención & control , Carotenoides/análisis , Carotenoides/sangre , Carotenoides/uso terapéutico , Femenino , Humanos , Lipoproteínas/química , Licopeno , Solanum lycopersicum/química , Oxidación-Reducción , beta Caroteno/sangre , beta Caroteno/uso terapéutico
9.
Neuroradiology ; 43(6): 448-52, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11465755

RESUMEN

We performed multivariate analysis of regional differences and normal age-related changes in metabolites in the lentiform nucleus and frontal lobe, as measured by proton MRS. The cerebrospinal fluid (CSF) in the measurement area was estimated and the metabolite concentration adjusted. The concentration of N-acetylaspartate (NAA) in the lentiform nucleus decreased with ageing (F = 4.11, P < 0.01), but that in the frontal lobe did not change (F = 0.93, P = 0.45). This is in marked contrast with pathological dementia, such as Alzheimer's disease. In this multivariate analysis, the normal change in metabolism with ageing differed depending on the cerebral region, suggesting that metabolite concentrations, especially that of NAA may be useful metabolic indices for discriminate normal ageing from pathological dementia.


Asunto(s)
Envejecimiento/fisiología , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Cuerpo Estriado/metabolismo , Demencia/diagnóstico , Lóbulo Frontal/metabolismo , Espectroscopía de Resonancia Magnética , Adulto , Anciano , Líquido Cefalorraquídeo , Cuerpo Estriado/fisiología , Femenino , Lóbulo Frontal/fisiología , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia
10.
J Toxicol Sci ; 26 Suppl 1: 231-42, 2001 May.
Artículo en Japonés | MEDLINE | ID: mdl-11400315

RESUMEN

S-1090, a cefmatilen hydrochloride hydrate, is being developed as a cephalosporin antibiotic for oral use. Immunogenicity, hypersensitivity-eliciting antigenicity and immunological cross-reactivity with other antibiotics were evaluated by active systemic anaphylaxis (ASA) test, passive cutaneous anaphylaxis (PCA) test and enzyme-linked immunosorbent assay (ELISA) using guinea pigs and mice/rats. In addition, in vitro direct Coombs' test was also performed to examine the possibility of hemolytic anemia in clinical use. Immunogenicity of S-1090 was not observed in guinea pigs after repeated immunization with S-1090 by ASA or PCA tests. Even in ELISA, only weak antibody production against S-1090 was found in some guinea pigs from the intraperitoneal groups showing the antibody titers only 10(1) to 10(2). When the sera collected from C3H/He mice and C57BL/6J mice immunized with S-1090 were tested for immunogenicity, rat PCA was elicited in a C3H/He mouse serum by S-1090 and antibodies against S-1090 were detected in a C57BL/6J mouse serum by ELISA. When adjuvant was used in mice and guinea pigs, the production of antibody against S-1090 was less frequent in comparison with other antibiotics such as cefmetazole (CMZ) and cefotiam (CTM). When hypersensitivity-eliciting antigenicity of S-1090 was examined using S-1090 as an eliciting antigen in ASA and PCA tests, positive ASA and PCA were observed in guinea pigs and positive PCA in a C3H/He mouse. Hypersensitivity-eliciting antigenicity was also observed in other reference antibiotics, i.e. cephalothin (CET), CMZ and CTM. Immunological cross-reactivity among S-1090, penicillin G (PCG), CET, CMZ and CTM was tested by ASA and PCA tests. S-1090 was found to immunologically cross-react only with CET in guinea pigs. In the present study, immunological cross-reactivities were also noted between PCG and CET, PCG and CMZ, PCG and CTM, and between CET and CMZ. In in vitro direct Coombs' test using human red blood cells, S-1090.Na, PCG and CET gave positive reactions at the final concentrations of 40 mg/mL, 20 to 40 mg/mL and 2.5 to 10 mg/mL, respectively.


Asunto(s)
Antígenos/inmunología , Cefalosporinas/inmunología , Hipersensibilidad a las Drogas/etiología , Animales , Cefmetazol/inmunología , Cefotiam/inmunología , Cefalotina/inmunología , Prueba de Coombs , Reacciones Cruzadas , Femenino , Cobayas , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Anafilaxis Cutánea Pasiva , Penicilina G/inmunología
11.
J Cardiovasc Pharmacol ; 36(6): 687-92, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11117366

RESUMEN

This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation.


Asunto(s)
Ácido Ascórbico/farmacología , Arteria Ilíaca/fisiología , Isquemia/fisiopatología , Aceite de Soja/farmacología , Vasodilatación/efectos de los fármacos , Animales , Colesterol/sangre , Circulación Coronaria/efectos de los fármacos , Perros , Inhibidores Enzimáticos/farmacología , Emulsiones Grasas Intravenosas/farmacología , Femenino , Arteria Ilíaca/anatomía & histología , Infusiones Intravenosas , Masculino , Nitratos/sangre , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III , Nitritos/sangre , Aceite de Soja/administración & dosificación , Triglicéridos/sangre , omega-N-Metilarginina/farmacología
12.
Biol Pharm Bull ; 23(9): 1055-8, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10993204

RESUMEN

The effects of Fujibitol, a preparation of crude drugs in wide clinical use for treatment of chronic rhinitis and empyema, on experimental allergic rhinitis in rats were studied. Fujibitol inhibited nasal allergic symptoms, i.e. sneezing and nasal rubbing, induced by antigen in sensitized animals. An increase in dye leakage into the nasal cavity induced by antigen was also inhibited by Fujibitol. On the other hand, no inhibitory effects were observed on either the nasal allergic symptoms or increase in dye leakage into the nasal cavity induced by histamine. However, Fujibitol was effective in inhibiting histamine release from the nasal cavity induced by antigen. Oxatomide used as positive control drug showed potent inhibitory effects on nasal symptoms and dye leakage into the nasal cavity induced by histamine and antigen. These results suggested that Fujibitol showed a remarkable protective effect against experimental rhinitis induced by antigen via inhibition of histamine release from the nasal cavity.


Asunto(s)
Antialérgicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Rinitis Alérgica Perenne/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Liberación de Histamina/efectos de los fármacos , Masculino , Piperazinas/uso terapéutico , Plantas Medicinales , Ratas , Ratas Wistar
13.
Int Arch Allergy Immunol ; 122(2): 137-42, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10878492

RESUMEN

BACKGROUND: Dietary sources of alpha-linolenic acid, such as perilla seed oil, may have the capacity to inhibit the generation of leukotrienes (LTs) by leucocytes in patients with asthma, as has been reported with the consumption of other long-chain n-3 fatty acids. METHODS: The factors affecting the suppression of leukotriene (LT) C4 generation by leucocytes were examined by comparing the clinical features of patients with asthma who had been given dietary perilla seed oil (n-3 fatty acids). Group A consisted of patients in whom the leucocyte generation of LTC4 was suppressed by dietary perilla seed oil. Group B consisted of those in whom LTC4 generation was not suppressed. RESULTS: LTC4 generation by leucocytes decreased significantly in group A after 2 (p < 0.05) and 4 weeks (p < 0.05); conversely, it increased significantly in group B after 4 weeks (p < 0.05). The two study groups differed significantly in terms of LTC4 generation by leucocytes after 4 weeks of dietary supplementation (p < 0.05). Ventilatory parameters such as peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) increased significantly after 4 weeks of dietary supplementation in group A (p < 0.05). Values of PEF, FVC, FEV(1) and maximum expiratory flow at 25% of the forced vital capacity (V(25)) differed significantly between groups A and B prior to dietary supplementation. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and phospholipid were significantly decreased by dietary supplementation in group A after 4 weeks. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL cholesterol and phospholipid differed significantly between the two study groups prior to dietary supplementation. Serum levels of triglyceride and LDL cholesterol differed significantly between the two study groups after 4 weeks of dietary supplementation. CONCLUSIONS: Dietary supplementation with perilla seed oil in selected patients with asthma suppresses the generation of LTC4 and is associated with clinical features such as respiratory function and lipometabolism.


Asunto(s)
Anticarcinógenos/farmacología , Asma/sangre , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Leucotrieno C4/biosíntesis , Lípidos/sangre , Ácido alfa-Linolénico/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Asma/fisiopatología , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Suplementos Dietéticos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Leucotrieno C4/sangre , Masculino , Flujo Espiratorio Medio Máximo/efectos de los fármacos , Persona de Mediana Edad , Fosfolípidos/sangre , Aceites de Plantas/farmacología , Triglicéridos/sangre , Capacidad Vital/efectos de los fármacos
15.
J Biol Chem ; 274(52): 37041-5, 1999 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-10601261

RESUMEN

Galanin is a widely distributed neuropeptide with a variety of physiological functions. Three galanin receptor subtypes, GALR1, GALR2, and GALR3, have been reported. We isolated a novel galanin-like peptide (GALP) from porcine hypothalamus by observing its activity for increasing [(35)S]GTPgammaS binding to a membrane preparation of GALR2-transfected cells. The peptide had 60 amino acid residues and a non-amidated C terminus. The amino acid sequence of GALP-(9-21) was completely identical to that of galanin-(1-13). A cloned porcine GALP cDNA indicated that GALP was processed from a 120-amino acid GALP precursor protein. The structures of rat and human GALP-(1-60) were deduced from cloned cDNA, which indicated that the amino acid sequences 1-24 and 41-53 were highly conserved between humans, rats, and pigs. Receptor binding studies revealed that porcine GALP-(1-60) had a high affinity for the GALR2 receptor (IC(50) = 0.24 nM) and a lower affinity for the GALR1 receptor (IC(50) = 4.3 nM). In contrast, galanin showed high affinity for the GALR1 (IC(50) = 0.097 nM) and GALR2 receptors (IC(50) = 0.48 nM). GALP is therefore an endogenous ligand that preferentially binds the GALR2 receptor, whereas galanin is relatively non-selective.


Asunto(s)
ADN Complementario/aislamiento & purificación , Galanina/aislamiento & purificación , Hipotálamo/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células CHO , Clonación Molecular , Cricetinae , ADN Complementario/química , Galanina/genética , Humanos , Datos de Secuencia Molecular , Ratas , Receptores de Galanina , Receptores de Neuropéptido/agonistas , Porcinos
16.
Immunopharmacology ; 43(1): 11-21, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10437652

RESUMEN

We previously reported that restraint stress impairs the antitumor immune responses through its suppressive effect on the Th1-type cytokine production from CD4+ T cells. In this study, we investigated a potential of Hochu-ekki-to (TJ-41:Bu-Zhong-Yi-Qi-Tang) to restore stress-induced immunosuppression. The oral administration of TJ-41 was able to improve a decreased cellularity in the lymph node and spleen and to improve an inhibition of tumor-specific Th1-type cytokine production, both of which were induced by repeated restraint stress in tumor-bearing mice. The oral administration of TJ-41 also induced a partial recovery of the antitumor cytolytic activity in the stress-burdened tumor-bearing mice. More importantly, the growth of tumors in stress-burdened preimmunized mice was obviously inhibited by TJ-41, and resulted in tumor-free state in 75% of the mice. Regarding the mechanisms by which TJ-41 restored the antitumor responses in stress-burdened mice, we found that the serum levels of corticosterone and interleukin-12 were normalized by TJ-41. In addition, the expression of CD80 and CD86, which both decreased in the stress-burdened mice, was restored to the normal level by TJ-41. Taken together, our results indicate that the oral administration of TJ-41 is able to restore the antitumor T cell responses in stress-burdened tumor-bearing mice by normalizing the serum corticosterone, interleukin-12 and the expression of costimulatory molecules.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Tolerancia Inmunológica/efectos de los fármacos , Estrés Fisiológico/tratamiento farmacológico , Estrés Fisiológico/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Corticosterona/sangre , Citotoxicidad Inmunológica/efectos de los fármacos , Femenino , Técnicas In Vitro , Interleucina-12/sangre , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/sangre , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/inmunología , Estrés Fisiológico/sangre , Células Tumorales Cultivadas
17.
Biochemistry ; 38(26): 8299-303, 1999 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-10387075

RESUMEN

The role of the HELLGH (residues 450-455) motif in the sequence of rat dipeptidyl peptidase III (EC 3.4.14.4) was investigated by replacing Glu451 with an alanine or an aspartic acid residue and by replacing His450 and His455 with a tyrosine residue by site-directed mutagenesis. Mutated cDNAs were expressed three or four times in Escherichia coli, and the resulting proteins were purified to apparent homogeneity. None of the expressed mutated proteins exhibited DPP III activity. The mutants of Glu451 contained 1 mol of zinc per mole of protein, but mutants His450 and His455 did not contain significant amounts of zinc as determined by atomic absorption spectrometry. The Leu453-deleted enzyme (having the zinc aminopeptidase motif HExxH-18-E) had almost the same order of binding affinity (for Arg-Arg-2-naphthylamide) as the wild-type enzyme, but the specificity constant was about 10%. These results provide evidence that the suitable number of amino acids included between Glu451 and His455 is three residues for the enzyme activity and confirm that residues His450, His455, and Glu451 are involved in zinc coordination and catalytic activity.


Asunto(s)
Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/fisiología , Hígado/enzimología , Fragmentos de Péptidos/fisiología , Zinc/metabolismo , Secuencia de Aminoácidos , Animales , Catálisis , ADN Complementario/aislamiento & purificación , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/química , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/aislamiento & purificación , Activación Enzimática/genética , Escherichia coli/genética , Ácido Glutámico/genética , Histidina/genética , Humanos , Leucina/genética , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Ratas , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Zinc/química
18.
Biochem J ; 329 ( Pt 2): 275-82, 1998 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-9425109

RESUMEN

We have purified dipeptidyl peptidase III (EC 3.4.14.4) from human placenta. It had a pH optimum of 8.8 and readily hydrolysed Arg-Arg-beta-naphthylamide. Monoamino acid-, Gly-Phe-, Gly-Pro- and Bz-Arg-beta-naphthylamides were not hydrolysed at all. The enzyme was inhibited by p-chloromercuriphenylsulphonic acid, metal chelators and 3,4-dichloroisocoumarin and contained 1 mol of zinc per mol of enzyme. The zinc dissociation constant was 250 fM at pH 7. 4 as determined by the zinc binding study. We isolated, by immunological screening of a Uni-ZAP XR cDNA library constructed from rat liver mRNA species, a cDNA clone with 2633 bp encoding the rat enzyme. The longest open reading frame encodes a 827-residue protein with a theoretical molecular mass of 92790 Da. Escherichia coli SOLR cells were infected with the pBluescript phagemid containing the cloned cDNA and established the overexpression of a protein that hydrolysed Arg-Arg-beta-naphthylamide. The recombinant protein was purified and the amino acid sequence of the protein was confirmed. We presumed that the putative zinc-binding domain involved in catalysis was present in the recombinant enzyme. It was a novel zinc-binding motif in that one amino acid residue was inserted into the conserved HEXXH motif characteristic of the metalloproteinases.


Asunto(s)
Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , ADN Complementario , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/química , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Femenino , Humanos , Datos de Secuencia Molecular , Placenta/enzimología , Unión Proteica , Ratas , Ratas Wistar , Homología de Secuencia de Aminoácido , Zinc/metabolismo
19.
Arerugi ; 46(6): 511-9, 1997 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-9277002

RESUMEN

To evaluate the effects of complex spa therapy (swimming training in a hot spring pool + fango therapy + inhalation of iodine salt solution) on psychological factors, three psychological examinations; CMI (Cornell Medical Index), SDS (Self-Rating Depression Scale) and CAI (Comprehensive Asthma Inventory); were given 25 patients with bronchial asthma (10 male, 15 female, mean age 60 years), and the results of these examinations were compared before and after spa therapy. 1. Physical symptoms, respiratory system and CIJ symptoms by CMI were significantly improved after spa therapy, however the improvement of psychical symptoms was not significant. 2. In SDS, 11 of 25 patients showed more than 40 points, indicating depressive state. The number of such patients decreased from 11 to 2 and the mean SDS score significantly improved from 38.7 to 34.2 after spa therapy. 3. Conditioning, suggestion, fear of expectation, frustration, flight into illness, negative attitudes towards prognosis, and decreased motivation towards therapy by CAI were significantly reduced after spa therapy, with the reduction in negative attitudes towards prognosis and decreased motivation towards therapy being relatively large. Furthermore, CAI score, which is the average of the categories in CAI, was also significantly decreased from 37.9 to 28.4 after spa therapy. These results suggested that complex spa therapy improves psychological factors in patients with bronchial asthma.


Asunto(s)
Asma/psicología , Asma/terapia , Balneología , Anciano , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/etiología , Trastorno Depresivo/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Psicológicas
20.
Appl Human Sci ; 15(6): 281-6, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9008982

RESUMEN

Folk wisdom suggests that chicken extract is useful for recovery from physical and mental fatigue. To explore this question, the physiological effect of Brand's Essence of Chicken (BEC), a popular chicken extract used as a traditional remedy, was assessed during recovering from mental stress. We quantitated the blood levels of stress-related substances, and examined the task performance and subjects' mood states during mental workloads. Subjects were 20, healthy male students who have never tasted BEC. They took two bottles of BEC or a placebo (70 ml/bottle) daily in the morning for 7 days. On the final experimental day, two mental workload tests were performed: (A) a mental arithmetic test (MAT; 1600 trials of two or three figure-addition or subtraction for 40 min). (B) a short-term memory test (SMT; 20 trials of memorizing 9 digit numbers). Blood was collected before and after each workload task. After the mental workload, the recovery of mean cortisol level of subjects who consumed BEC was significantly faster than that for those consuming the placebo. The task performance of subjects performing the MAT and SMT was also improved with BEC consumption compared with placebo. According to the profile of mood state questionnaire, subjects felt more active and less fatigued during the workload when they took BEC regularly. We conclude that the extract of chicken has the potential to metabolize stress-related substance in blood and to promote recovery from mental fatigue.


Asunto(s)
Pollos , Fatiga Mental/terapia , Productos Avícolas/normas , Adolescente , Adulto , Afecto , Animales , Humanos , Hidrocortisona/sangre , Masculino , Memoria/fisiología , Fatiga Mental/sangre , Fatiga Mental/fisiopatología , Estrés Psicológico , Análisis y Desempeño de Tareas
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