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1.
Lett Appl Microbiol ; 73(3): 383-391, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34173250

RESUMO

This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.


Assuntos
Reabsorção Óssea , Osteoclastos , Animais , Diferenciação Celular , Feminino , Lactobacillus , Camundongos , NF-kappa B
2.
J Laryngol Otol ; 125(3): 246-50, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21054911

RESUMO

OBJECTIVE: To define the clinical and audiological features of normal-hearing tinnitus patients with spontaneous otoacoustic emissions, and to evaluate the role of spontaneous otoacoustic emissions in tinnitus generation. MATERIALS AND METHODS: Thirty-two patients with spontaneous otoacoustic emissions were compared with 29 patients without spontaneous otoacoustic emissions, regarding clinical and audiological aspects. RESULTS: The mean age of the study group subjects was significantly lower, and they experienced the kindling effect less frequently than the control group. The mean tinnitus handicap inventory score of the study group was considerably higher than that of the controls, although the difference was not statistically significant. The study group had significantly quieter tinnitus, and higher transient evoked and distortion product otoacoustic emission responses, compared with the control group. CONCLUSIONS: Normal-hearing tinnitus patients with spontaneous otoacoustic emissions have different clinical and audiological characteristics, compared with those without spontaneous otoacoustic emissions. Appropriate evaluation and treatment should be considered at an early stage in these patients.


Assuntos
Potenciais Evocados Auditivos , Células Ciliadas Auditivas Externas , Audição/fisiologia , Excitação Neurológica/fisiologia , Emissões Otoacústicas Espontâneas/fisiologia , Zumbido/fisiopatologia , Estimulação Acústica , Adulto , Distribuição por Idade , Audiometria de Tons Puros , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Hiperacusia/fisiopatologia , Masculino , Índice de Gravidade de Doença , Distribuição por Sexo , Zumbido/etiologia
3.
Poult Sci ; 89(2): 203-16, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20075271

RESUMO

This study was conducted to compare growth performance, gut morphometry, and parameters of local and systemic immunity in broiler chickens fed for 22 consecutive days with a diet supplemented with Bacillus spp. as direct-fed microbials (DFM), a commercial product incorporating 3 DFM, or a nonsupplemented diet. Direct-fed microbials did not significantly modify BW gain and most failed to affect serum antibody levels in response to immunization with a recombinant Eimeria protein. However, altered intestinal morphometric measurements were readily apparent in DFM-fed chickens as revealed by increased villus height and crypt depth compared with non-DFM-fed controls. In addition, serum levels of alpha-1-acid glycoprotein as an inflammatory marker were reduced in DFM-fed birds, whereas splenic lymphocyte proliferation, intestine intraepithelial lymphocyte subpopulations, and cytokine mRNA levels in intraepithelial lymphocytes were increased, decreased, or unchanged compared with controls depending on the DFM used. These results provide a rational scientific basis for future studies to investigate DFM as immunomodulating agents to enhance host protective immunity against enteric pathogens in broiler chickens.


Assuntos
Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Trato Gastrointestinal/anatomia & histologia , Trato Gastrointestinal/fisiologia , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bacillus subtilis , Proliferação de Células , Suplementos Nutricionais , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Linfócitos/citologia , Linfócitos/fisiologia , Orosomucoide/genética , Orosomucoide/metabolismo , RNA Mensageiro/metabolismo , Baço/citologia , Aumento de Peso
4.
Poult Sci ; 89(1): 68-81, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20008804

RESUMO

Among dietary phytonutrients, carvacrol, cinnamaldehyde, and Capsicum oleoresin are well known for their antiinflammatory and antibiotic effects in human and veterinary medicine. To further define the molecular and genetic mechanisms responsible for these properties, broiler chickens were fed a standard diet supplemented with either of the 3 phytochemicals and intestinal intraepithelial lymphocytes were examined for changes in gene expression by microarray analysis. When compared with chickens fed a nonsupplemented standard diet, carvacrol-fed chickens showed altered expression of 74 genes (26 upregulated, 48 downregulated) and cinnamaldehyde led to changes in the levels of mRNAs corresponding to 62 genes (31 upregulated, 31 downregulated). Most changes in gene expression were seen in the Capsicum-fed broilers with 98 upregulated and 156 downregulated genes compared with untreated controls. Results from the microarray analysis were confirmed by quantitative real-time PCR with a subset of selected genes. Among the genes that showed >2.0-fold altered mRNA levels, most were associated with metabolic pathways. In particular, with the genes altered by Capsicum oleoresin, the highest scored molecular network included genes associated with lipid metabolism, small molecule biochemistry, and cancer. In conclusion, this study provides a foundation to further investigate specific chicken genes that are expressed in response to a diet containing carvacrol, cinnamaldehyde, or Capsicum oleoresin.


Assuntos
Acroleína/análogos & derivados , Células Epiteliais/metabolismo , Mucosa Intestinal/citologia , Monoterpenos/farmacologia , Extratos Vegetais/farmacologia , Acroleína/farmacologia , Animais , Capsicum/química , Galinhas , Biologia Computacional , Cimenos , Células Epiteliais/efeitos dos fármacos , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/química , Reação em Cadeia da Polimerase , Análise Serial de Proteínas
5.
Br J Pharmacol ; 154(5): 1073-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18536755

RESUMO

BACKGROUND AND PURPOSE: Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4'-[[pentanoyl (phenyl) amino]methyl]-1,1'-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). EXPERIMENTAL APPROACH: A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. KEY RESULTS: Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose-response curve for compound A showed peaks at around 0.005-0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT(2) receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice. CONCLUSIONS AND IMPLICATIONS: Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor antagonists.


Assuntos
Araquidonato 12-Lipoxigenase/metabolismo , Comportamento Animal , Prurido/metabolismo , Receptores do Leucotrieno B4/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/metabolismo , Animais , Antipruriginosos/farmacologia , Comportamento Animal/efeitos dos fármacos , Capsaicina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Álcoois Graxos/farmacologia , Glicóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Naltrexona/farmacologia , Prurido/induzido quimicamente , Prurido/prevenção & controle , Receptores do Leucotrieno B4/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tetrazóis/farmacologia , Gravação em Vídeo
6.
Clin Exp Allergy ; 38(5): 794-804, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18261158

RESUMO

BACKGROUND: Novel approaches are being explored to develop new therapies for various allergic diseases. Complementary and alternative medicines are considered to be promising avenues for the development of such new therapies. OBJECTIVES: To investigate the effect of many Korean plants on the IgE-mediated allergic response in mast cells and in vivo, and its mechanism of action. MATERIALS AND METHODS: The anti-allergic activity was tested by evaluating effects on degranulation of mast cells in culture and passive cutaneous anaphylaxis (PCA) in vivo. Its mechanism of action was investigated by immunoblotting analysis, immunoprecipitation, RT-PCR, and other molecular biological approaches in mast cells. RESULTS: We screened approximately 100 natural plant extracts collected in Korea for in vitro anti-allergic activity. The leaf extract of Camellia japonica (LECJ) exhibited the most potent effect on degranulation in antigen-stimulated rodent and human mast cells. LECJ reversibly inhibited degranulation in a dose-dependent manner, with IC(50) values of approximately 50 microg/mL for the mast cells, and it also suppressed the expression and secretion of TNF-alpha and IL-4 in rat basophilic leukaemia-2H3 mast cells. In agreement with its in vitro activity, LECJ significantly inhibited mast cell-mediated PCA in an animal model. LECJ inhibited activating phosphorylation of tyrosine Y371 on Syk kinase, indicating that LECJ inhibits the activity of Src-family kinases in mast cells. In the in vitro kinase assay, LECJ directly inhibited Lyn kinase, the major Src-family kinase in the cells. It also suppressed Akt and MAP kinases, which are critical for the production of various pro-inflammatory cytokines in mast cells. In high-performance liquid chromatography analysis, quercetin-3-beta-D-glucoside and eugenol were identified as the major active components. CONCLUSION: The present results strongly suggest that the anti-allergic activity of LECJ is mediated through inhibiting degranulation and allergic cytokine secretion by inhibition of Src-family kinase in mast cells and it may be useful for the treatment of mast cell-related immediate and delayed allergic diseases.


Assuntos
Camellia/química , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Animais , Basófilos , Degranulação Celular , Células Cultivadas , Ativação Enzimática , Humanos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Immunoblotting , Imunoglobulina E/imunologia , Imunoprecipitação , Coreia (Geográfico) , Mastócitos/enzimologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva , Extratos Vegetais/química , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Quinase Syk , Quinases da Família src/antagonistas & inibidores
7.
Allergy ; 60(8): 1029-33, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15969683

RESUMO

BACKGROUND: Results from epidemiologic studies have shown that childhood atopy is probably a hereditary disorder, because the offspring of affected parents have a higher risk of developing atopy. Among the atopic population, some subjects are sensitized to only one class of allergens (monosensitized), while other subjects are sensitized to more than one class of allergens (polysensitized). The aim of this study was to investigate whether atopy profile (monosensitization/polysensitization) in children is linked to the same conditions in their parents. METHODS: We evaluated sensitization to five classes of aeroallergens (house dust mites, animal danders, pollens, molds, and cockroach) by skin prick testing in a group of 494 children with suspicious allergic symptoms and in their parents. RESULTS: The frequency of parental atopy was highest (51.6%) in polysensitized children (n = 189), intermediate (37.1%) in monosensitized children (n = 178), and was lowest (22.4%) in nonsensitized children (n = 127). The proportion of polysensitized subjects among atopic parents was significantly higher for polysensitized children (45.6%) than for monosensitized children (31.1%). Polysensitized children were found to more frequently have one or both parents polysensitized (32.3%, 7.4%) than monosensitized children (18.5%, 2.2%) with odds ratios of 2.09 (95% CI: 1.29-3.40) and 3.48 (1.12-10.78), respectively, whereas the likelihood of having one or two monosensitized parents was not increased for polysensitized children. CONCLUSION: Our data suggest a familial coincidence of atopy profile in terms of monosensitization and polysensitization, although the relative importance of genetic or environmental influence should be studied further.


Assuntos
Alérgenos/imunologia , Hipersensibilidade/genética , Pais , Animais , Criança , Baratas/imunologia , Feminino , Fungos/imunologia , Humanos , Hipersensibilidade/epidemiologia , Incidência , Masculino , Pólen/imunologia , Pyroglyphidae , Testes Cutâneos
8.
Arch Pharm Res ; 24(5): 427-30, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11693545

RESUMO

The antioxidant activity of Lactuca scariola (Compositae) was investigated by measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl) radical. The methanolic extract of the aerial parts of Lactuca scariola showed strong radical scavenging activity. The EtOAc soluble fraction exhibited a stronger activity than the others, and was purified by silica gel and Sephadex LH-20 column chromatography. Quercetin-3-O-beta-D-glucopyranoside, luteolin-7-O-beta-D-glucopyranoside, luteolin, quercetin and kaempferol, together with 1beta,13-dihydrolactucin were isolated from the EtOAc soluble fraction as active ingredients.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Asteraceae/química , Bepridil/análogos & derivados , Picratos , Antioxidantes/isolamento & purificação , Bepridil/química , Compostos de Bifenilo , Cromatografia Líquida , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Espectroscopia de Ressonância Magnética , Extratos Vegetais/análise , Solventes , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
9.
Bioorg Med Chem ; 9(11): 3013-21, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11597484

RESUMO

New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.


Assuntos
Inibidores de Fosfodiesterase/síntese química , Piperazinas/síntese química , Piperazinas/farmacologia , 3',5'-GMP Cíclico Fosfodiesterases , Animais , Ácidos Carboxílicos/química , Bovinos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Avaliação Pré-Clínica de Medicamentos , Disfunção Erétil/tratamento farmacológico , Humanos , Concentração Inibidora 50 , Isoenzimas/efeitos dos fármacos , Isoenzimas/metabolismo , Masculino , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/efeitos dos fármacos , Diester Fosfórico Hidrolases/metabolismo , Piperazinas/química , Purinas , Coelhos , Citrato de Sildenafila , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonas
10.
Hypertension ; 38(2): 166-70, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11509470

RESUMO

Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10, respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Tosse/tratamento farmacológico , Compostos Ferrosos/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Adulto , Idoso , Tosse/sangue , Tosse/induzido quimicamente , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ferritinas/sangue , Hematócrito , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade
11.
Arch Pharm Res ; 24(3): 249-55, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11440086

RESUMO

We studied the effect of aqueous extract of Magnolia officinalis bark (Magnoliaceae) (MOAE) on the immediate hypersensitivity reaction. MOAE (0.01 to 1 g/kg) dose-dependently inhibited compound 48/80 induced systemic anaphylaxis in rats. MOAE (0.1 and 1 g/kg) also significantly inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction. When MOAE was pretreated at concentrations ranging from 0.01 to 1 g/kg, the levels of plasma histamine were reduced in a dose-dependent manner. MOAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-dinitrophenyl (DNP) IgE. The level of cyclic AMP (cAMP) in RPMC, when MOAE was added, significantly increased compared with that of the normal control. Moreover, MOAE (0.01 to 1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that MOAE inhibits immediate hypersensitivity reaction in vivo and in vitro.


Assuntos
Antialérgicos/uso terapêutico , Hipersensibilidade Imediata/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Animais , AMP Cíclico/biossíntese , Liberação de Histamina/efeitos dos fármacos , Indicadores e Reagentes , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/biossíntese , p-Metoxi-N-metilfenetilamina/antagonistas & inibidores , p-Metoxi-N-metilfenetilamina/farmacologia
12.
Bioorg Med Chem ; 9(6): 1609-16, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11408180

RESUMO

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.


Assuntos
Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/efeitos dos fármacos , Piperazinas/química , 3',5'-GMP Cíclico Fosfodiesterases , Animais , Bovinos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Avaliação Pré-Clínica de Medicamentos , Concentração Inibidora 50 , Modelos Moleculares , Estrutura Molecular , Inibidores de Fosfodiesterase/síntese química , Piperazinas/farmacologia , Purinas , Coelhos , Citrato de Sildenafila , Relação Estrutura-Atividade , Sulfonas
13.
Drug Metab Dispos ; 29(7): 945-9, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11408358

RESUMO

2-Amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)- purine (SK1899) was tested as an oral prodrug for penciclovir. SK1899 was administered orally to rats and dogs at doses up to 2 and 0.68 mmol/kg, respectively. SK1899 was well absorbed, and the major metabolites detected in plasma and urine were penciclovir, the active antiviral compound, and 6-deoxypenciclovir (M4) in both species. In rats, SK1899 was rapidly and extensively metabolized to penciclovir, which reached the peak plasma concentration (C(max)) of 39.5 microM at 0.5 h after 0.2-mmol/kg dosing. The area under the plasma concentration-time curve (AUC) for penciclovir was 57.5 microM x h. After an oral dose of 0.034 mmol/kg to dogs, extensive conversion of SK1899 to penciclovir also occurred with slower rate of formation of penciclovir from M4 than in rats. The mean C(max) and AUC for penciclovir were 4.5 microM at 2.7 h and 28.2 microM x h, respectively. The 0- to 24-h urinary recovery of penciclovir represented 36.1 and 36.3% of dose to rats and dogs, respectively. Radioactivity was found in fetuses following an oral administration of [(14)C]SK1899 to pregnant rats, but no significant accumulation was observed. Although substantial milk transfer of [(14)C]SK1899 occurred in rats, the radioactivity in milk was rapidly cleared. The values of C(max), AUC, and urinary recovery of penciclovir after dosing with SK1899 to rats and dogs were similar or slightly higher than those from famciclovir. These data indicate that introduction of an isopropoxy carbonate group into one of the two hydroxyl groups of M4 did not significantly alter the oral bioavailability of penciclovir compared with famciclovir.


Assuntos
Aciclovir/análogos & derivados , Aciclovir/farmacocinética , Antivirais/farmacocinética , Pró-Fármacos/farmacocinética , Purinas/farmacocinética , Animais , Área Sob a Curva , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Guanina , Masculino , Leite/química , Gravidez , Ratos , Ratos Sprague-Dawley
14.
Pharmacol Res ; 43(4): 405-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11352546

RESUMO

We investigated the effect of water extract of Solanum melongena(SMWE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. Oral administration of SMWE (1 g kg(-1)) completely inhibited compound 48/80-induced anaphylactic reaction. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. Oral administration of SMWE (0.01--1 g kg(-1)) significantly inhibited passive cutaneous anaphylactic reaction activated by anti-DNP IgE to between 83.10 +/- 1.67% and 70.17 +/- 2.17%. SMWE (0.01--1 mg ml(-1)) also inhibited histamine release activated by compound 48/80 to between 93 +/- 2.65 and 70 +/- 1.50%. Moreover, SMWE (0.01--1 mg ml(-1)) had a significant inhibitory effect on IgE-induced tumor necrosis factor (TNF)-alpha secretion from rat peritoneal mast cells. These results indicate that SMWE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-alpha secretion from mast cells.


Assuntos
Anafilaxia/tratamento farmacológico , Anafilaxia/imunologia , Fatores Biológicos/farmacologia , Fatores Biológicos/uso terapêutico , Magnoliopsida/química , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Administração Oral , Anafilaxia/induzido quimicamente , Animais , Fatores Biológicos/administração & dosagem , Dinitrofenóis/imunologia , Modelos Animais de Doenças , Histamina/metabolismo , Imunoglobulina E/imunologia , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Ratos , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/antagonistas & inibidores , p-Metoxi-N-metilfenetilamina/farmacologia
15.
Immunopharmacol Immunotoxicol ; 23(1): 107-17, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11322643

RESUMO

The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of 1 g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases.


Assuntos
Anafilaxia/prevenção & controle , Hipersensibilidade/prevenção & controle , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Anafilaxia/induzido quimicamente , Animais , Western Blotting , Células Cultivadas , Dinitrofenóis/farmacologia , Relação Dose-Resposta a Droga , Eleutherococcus , Ensaio de Imunoadsorção Enzimática , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/metabolismo , Imunoensaio/métodos , Imunoglobulina E/imunologia , Interleucina-6/metabolismo , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ratos , Ratos Wistar , p-Metoxi-N-metilfenetilamina/administração & dosagem , p-Metoxi-N-metilfenetilamina/farmacologia
16.
Kidney Int ; 59(5): 1821-33, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11318953

RESUMO

BACKGROUND: Cystinuria has been proposed to be an inherited defect of apical membrane transport systems for cystine and basic amino acids in renal proximal tubules. Although the mutations of the recently identified transporter BAT1/b(0,+)AT have been related to nontype I cystinuria, the function and localization of human BAT1 (hBAT1)/b(0,+)AT have not been well characterized. METHODS: The cDNA encoding hBAT1 was isolated from human kidney. Fluorescence in situ hybridization was performed to map the hBAT1 gene on human chromosomes. Tissue distribution and localization of expression were examined by Northern blot and immunohistochemical analyses. hBAT1 cDNA was transfected to COS-7 cells with rBAT cDNA, and the uptake and efflux of 14C-labeled amino acids were measured to determine the functional properties. The roles of protein kinase-dependent phosphorylation were investigated using inhibitors or activators of protein kinases. RESULTS: The hBAT1 gene was mapped to 19q12-13.1 on the human chromosome, which is the locus of nontype I cystinuria. hBAT1 message was expressed predominantly in kidney. hBAT1 protein was localized in the apical membrane of proximal tubules in human kidney. When expressed in COS-7 cells with a type II membrane glycoprotein rBAT (related to b(0,+)-amino acid transporter), hBAT1 exhibited the transport activity with the properties of amino acid transport system b(0,+), which transported cystine as well as basic and neutral amino acids presumably via a substrate exchange mechanism. BAT1-mediated transport was reduced by the protein kinase A activator and enhanced by the tyrosine kinase inhibitor. CONCLUSIONS: hBAT1 exhibited the properties expected for a transporter subserving the high-affinity cystine transport system in renal proximal tubules. The hBAT1 gene was mapped to the locus of nontype I cystinuria, confirming the involvement of hBAT1 in cystinuria.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Cistinúria/genética , Cistinúria/metabolismo , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , Sequência de Bases , Transporte Biológico Ativo , Células COS , Mapeamento Cromossômico , RNA Helicases DEAD-box , Primers do DNA/genética , DNA Complementar/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Técnicas In Vitro , Dados de Sequência Molecular , Fosforilação , Proteínas Quinases/metabolismo , RNA Helicases , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Xenopus
17.
J Ethnopharmacol ; 74(2): 133-40, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11167031

RESUMO

We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.


Assuntos
Anafilaxia/tratamento farmacológico , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Plantas Medicinais/química , Animais , Dinitrofenóis/antagonistas & inibidores , Histamina/sangue , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/imunologia , Indicadores e Reagentes , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/biossíntese , p-Metoxi-N-metilfenetilamina/farmacologia
18.
Am J Chin Med ; 29(3-4): 485-91, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11789591

RESUMO

SKI 306X is a purified extract from a mixture of three oriental herbal medicines (Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris) that have been widely used for the treatment of inflammatory diseases such as lymphadenitis and arthritis in far East Asia. A double-blind, controlled study was performed to evaluate the efficacy and safety of SKI 306X with placebo in 96 patients with classical osteoarthritis of the knee. Patients were randomized to four treatment groups: placebo, 200 mg, 400 mg and 600 mg of SKI 306X t.i.d.. Clinical efficacy and safety were evaluated for 4 weeks continuous treatment. SKI 306X demonstrated its clinical efficacy, as assessed by 100 mm visual analogue scale (VAS), Lequesne index and patients' and investigators opinion of the therapeutic effect compared with placebo (p<0.01). No significant adverse events were observed in patients treated with SKI 306X. This study demonstrated that SKI 306X, a new herbal anti-arthritic agent provided clinical efficacy in patients with osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Lamiaceae , Osteoartrite do Joelho/tratamento farmacológico , Ranunculaceae , Trichosanthes , Adulto , Idoso , Qualidade de Produtos para o Consumidor , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Resultado do Tratamento
19.
Arch Pharm Res ; 23(5): 459-60, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11059823

RESUMO

Separation of the alkaloids from the aerial parts of Corydalis ochotensis afforded a new spirobenzylisoquinoline alkaloid, 8-O-acetylcorysolidine along with two known spirobenzylisoquinoline alkaloids, isoochotensine and corysolidine.


Assuntos
Alcaloides/isolamento & purificação , Isoquinolinas/isolamento & purificação , Plantas Medicinais
20.
Chem Pharm Bull (Tokyo) ; 48(11): 1766-7, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11086909

RESUMO

A new cyanogenic glycoside, sutherlandin-5-trans-p-coumarate was isolated along with a known cardiosdiospermin-5-(4-hydroxy) benzoate fr the aerial parts of Sorbaria sorbifolia (L.) A. Br. var. stellipila MAX. (Rosaceae). The structure of the new compound was established based on spectral evidence.


Assuntos
Ácidos Cumáricos/isolamento & purificação , Glicosídeos/isolamento & purificação , Plantas Medicinais/química , China , Cromatografia por Troca Iônica , Ácidos Cumáricos/química , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
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