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1.
Zhonghua Yi Xue Za Zhi ; 103(20): 1563-1567, 2023 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-37246007

RESUMO

Objective: To evaluate the learning curve of the "Double Grooves-Double Rings" (DGDR) technique of transurethral Thulium laser enucleation of the prostate (ThuLEP) for benign prostatic hyperplasia (BPH) by a single surgeon. From June 2021 to July 2022, 84 patients mean age (69.0±8.0) years,preoperative prostate volume (90.9±40.3)ml with BPH underwent ThuLEP in the Department of Urology, Peking University First Hospital.Performed by a single surgeon who had no experience of transurethral resection of prostate (TURP) and any laser surgeries. The case scatter plots with the best fitting line were drawn to analyze the learning curve. According to the date of the surgeries, the patients were equally divided into three learning stages (28 patients for each group). The T-PSA,prostate volume,operative time,enucleation time, enucleation efficiency,catheter indwelling time, hemoglobin drop and perioperative complications (including re-TURP, blood transfusion, stress incontinence≥3 months and urethral stricture) were compared among the groups. The learning curve was divided into three stages, and the cutting point was shown on the 14th case. Except the prostate volume [stage1 (75.7±30.7) ml, stage2 (93.40±39.6)ml, stage3 (103.5±46.2) ml, P<0.05], there was no significant difference of the baseline data between three groups (P>0.05). Compared with those of stage 1(100.6±24.7) min,(0.55±0.22) g/min, a statistically significant improvement was observed in both of the operative time and the enucleation efficiency among stage 2[(84.5±36.6) min, (0.87±0.33) g/min and stage 3 (71.2±26.3) min, (1.27±0.45) g/min, P<0.05]. The learning curve of the DGDR technique for ThuLEP can be divided into three stages. A ThuLEP beginner can preliminarily master this technique after completing 14 cases.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Cirurgiões , Ressecção Transuretral da Próstata , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Lasers , Curva de Aprendizado , Próstata , Hiperplasia Prostática/cirurgia , Túlio , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento
2.
Zhonghua Yi Shi Za Zhi ; 51(2): 92-96, 2021 Mar 28.
Artigo em Chinês | MEDLINE | ID: mdl-34098701

RESUMO

The creation of oral contraceptives goes back 60 years. It has gone through a long and complex process from the discovery of sex hormones to their development into drugs to market. A correct understanding of the developmental history of oral contraceptives is of great importance for human reproduction. Gregory G Pincus successfully synthesized the first oral contraceptive Enovid based on research by Carl Djerassi, this was approved for marketing by the US Federal Drug Administration (FDA) in May 1960. However, due to the severe side effects of Enovid, the safer and more effective second generation oral contraceptives - Levonorgestrel and the third generation oral contraceptives - Pregnene are widely used and continue to be used to this day. The introduction of oral contraceptives not only dampened the explosive growth of the world's population, but also improved the social status of women, and catalyzed the sexual liberation movement.


Assuntos
Anticoncepcionais Orais , Levanogestrel , Feminino , Humanos
3.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4589-4597, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164422

RESUMO

The plants of the Trigonostemon sp. genus(Euphorbiaceae family) comprising about 50 species worldwide are mainly distributed in tropical and subtropical Asia, 10 species of which can be found in southern of China. Phytochemical studies on the plants in the genus have demonstrated a large amount of terpenoids and alkaloids. Modern pharmacological studies have demonstrated cytotoxicity, antivirus, antibacterial, anti-inflammation and other pharmacological activities. In this paper, chemical compositions and biological activities of Trigonostemon genus at home and abroad over the past decade were summarized, in order to provide scientific basis for the further development and utilization of Trigonostemon plants.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbiaceae , Ásia , China , Compostos Fitoquímicos
4.
Zhonghua Yi Shi Za Zhi ; 50(4): 246-249, 2020 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-32911923

RESUMO

"Fangji Zhuan"(, Biographies of Technicians), a chapter from Songshi(, History of the Song) uses time as a sequence and adopts a narrative method. It contains 42 talents, including ephemeris, five elements of law, medical practitioners, and Taoists. Among them, there are 25 good medical practitioners, which are rich in content and detailed in history. Based on the biographies of medical doctors in "Fangji Zhuan", this article summarizes and records the life history of 25 different types of medical doctors in terms of divisions, contributions, rewards and punishments, etc., which reflects the career status of medical doctors in the Song Dynasty to a certain extent. The role and contribution in medical development are of great significance.

5.
Artigo em Chinês | MEDLINE | ID: mdl-32842360

RESUMO

Objective: To investigate the damage and mechanism of artemisia annua pollen on tight junction of human nasal mucosa epithelial cells (HNEpC). Methods: HNEpC were cultured in vitro. Different concentrations of artemisia annua pollen (0, 20, 40, 80, 100, 160, 200 µg/ml) were used to intervene the cells for 24 h, and the cell proliferation activity was detected by the CCK-8 method. The expression and phosphorylation of p38MAPK signaling pathway were detected by Western Blot before and after the intervention of SB203580, a p38MAPK inhibitor in HNEpC. Immunofluorescence chemical staining, Western Blot and quantitative real-time PCR (qPCR) were used to observe the expression and distribution of tight junctions Occludin and Claudin-1. SPSS 21.1 software was used for statistical analysis. Results: CCK-8 results showed that, compared with the control group, the proliferation activity of HNEpC increased after 6 h intervention with different concentrations of artemisia annua pollen (all P<0.05). After 12 h of intervention, the proliferation activity of HNEpC in the 20, 40, 80, 100 and 160 µg/ml groups was not significantly changed (all P>0.05), while that in the 200 µg/ml group was decreased (P<0.05). After the intervention for 24 h, the proliferation activity of cells in the 20 and 40 µg/ml groups was not significantly changed (all P>0.05), while that in the 80, 100, 160 and 200 µg/ml groups was decreased (all P<0.05). Immunofluorescence staining showed that the Occludin and Claudin-1 proteins in the normal control group were localized on the cell membrane and expressed more and formed a ring structure around the cell membrane. However, under the intervention of high concentration artemisia annua pollen, its expression level decreased, appeared broken, fuzzy, and nonuniform distribution. Western Blot and qPCR results showed that after 24 h of intervention, the expression levels of HNEpC Claudin-1 protein and its mRNA in the pollen groups (40, 80, 100, 160, 200 µg/ml) of artemisia annua decreased compared with those of those of the control group (mRNA expression levels were 0.567±0.214, 0.443±0.109, 0.462±0.160, 0.497±0.134, 0.388±0.076 compared with 1.001±0.067, respectively, all P<0.05). However, the mRNA of Occludin protein and its mRNA only decreased in the 200 µg/ml treatment group (mRNA expression level was 0.631±0.109 compared with 1.016±0.026, P<0.05), while all the other treatment groups increased (mRNA expression levels were 1.258±0.134, 1.827±0.103, 2.429±0.077, 1.707±0.085, 1.477±0.066 compared with 1.016±0.026, respectively, all P<0.05). Western Blot showed that p-p38MAPK expression increased after intervention with 100, 160, 200 µg/ml artemisia annua pollen for 24 h. SB203580 could inhibit the decreasing expression of Occludin caused by artemisinin pollen (mRNA expression was 1.255±0.179 compared with 0.631±0.109, P<0.05), but had no effect on Claudin-1 protein expression. Conclusion: Pollen from artemisia annua may activate p38MAPK signaling pathway and destroy the close connection of HNEpC.


Assuntos
Artemisia annua , Células Epiteliais/metabolismo , Mucosa Nasal/metabolismo , Pólen/efeitos adversos , Junções Íntimas , Artemisia annua/efeitos adversos , Proliferação de Células , Células Cultivadas , Claudina-1/biossíntese , Claudina-1/metabolismo , Células Epiteliais/patologia , Imunofluorescência , Humanos , Mucosa Nasal/lesões , Mucosa Nasal/patologia , Ocludina/biossíntese , Ocludina/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/patologia
6.
Zhonghua Yi Shi Za Zhi ; 49(4): 224-228, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31495162

RESUMO

Taiping Yulan(, Imperial overview from the Taiping reign or Readings of the Taiping Era) was a large encyclopedia which compiled by Li Fang in the early Northern Song Dynasty. Its content was broad and the resources of quotation were varied. It contained a large number of medical knowledges. Among this book, the "Fangshu" volume consisted of 18 parts, the first five volumes of health and medical recorded 4 methods of health preservation (nurturing vitality), 88 practitioners, cited 59 kinds of literatures and 160 historical materials. It has important academic value to the study of ancient health preservation and inheritance development of medical school.


Assuntos
Livros , Faculdades de Medicina , China
7.
Zhonghua Nei Ke Za Zhi ; 58(8): 592-595, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31365981

RESUMO

Objective: To investigate the effects of chronic intermittent hypoxia on somatotropic axis hormone levels in rats. Methods: Mature male Wistar rats were exposed to air or intermittent hypoxia randomly.The serum levels of growth hormone-releasing hormone (GHRH), growth hormone (GH) and somatostatin (SS) were measured before exposure, at the 4th, 8th, and 12th week after exposure. Different hormone levels in two groups were compared and analyzed. Results: Compared with the control group, GHRH levels in chronic intermittent hypoxic group showed a significant decline at the 4th week [(732.77±46.99)pg/ml vs. (893.59±40.00) pg/ml, P<0.05], while SS levels at the 8th week [(30.71±2.27) pg/ml vs. (44.69±3.36) pg/ml, P<0.05] and GH levels at the 12th week [(1.20±0.29) ng/ml vs. (2.06±0.13) ng/ml, P<0.05] were similarly reduced. As the duration of intermittent hypoxia was prolonged, the GHRH levels did not decrease further [4th week (732.77±46.99) pg/ml vs. 8th week (607.54±131.61) pg/ml vs. 12th week (730.05±40.63) pg/ml, P>0.05].However, the serum SS levels decreased further from the 8th week to the 12th week [(30.71±2.27) pg/ml vs. (24.41±4.06) pg/ml, P<0.05]. Conclusion: Chronic intermittent hypoxia might inhibit the function of somatotropic axis. Hypothalamic hormones are the earlyonesto be influenced, thereafter the entire axis.


Assuntos
Hormônio Liberador de Hormônio do Crescimento/sangue , Hormônio do Crescimento/sangue , Hipotálamo , Hipóxia , Somatostatina/sangue , Animais , Masculino , Ratos , Ratos Wistar
8.
Zhonghua Yi Shi Za Zhi ; 48(3): 153-157, 2018 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-30317825

RESUMO

The theory of "Xiang Qi" (inspecting Qi or inspecting pneumata) is an important method of TCM inspection.It has important value in clinical diagnosis.The theoretical framework of "Xiang Qi" has been formed from the Huangdi Neijing (The Yellow Emperor's Classic of Medicine)《》. The many ideas were improved and developed in many dynasties such as Sui, Tang, Song, Jin and Yuan. Especially the theory of "Xiang Qi" has been inherited and applied in Ming and Qing dynasties, the theory of "Xiang Qi" became an important diagnostic method for the clinical practice.Especially Wang Hong()'s Wang Zhen Zun Jing(Inspection following the classics)《》 in Qing Dynasty was published.It perfected and developed the ten kinds of methods of "Xiang Qi" from three aspects. And it contained four diagnostic methods by examining Qi to determine the disease.It has promoted the value and the clinical application of "Xiang Qi" theory, and has contributed to the development of "Xiang Qi" theory.


Assuntos
Medicina Tradicional Chinesa , Qi , China , Humanos
9.
Nutr Res ; 54: 1-11, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29914662

RESUMO

The effects of resistant starch (RS) on serum cholesterol levels have been previously investigated. However, the results of those studies are inconsistent. The purpose of our meta-analysis was to determine if RS affects blood lipids based on the current literature. The methods included searching databases (PubMed, Embase, Scopus, and Cochrane Library) up to September 2017, as well as hand-searching reference lists of articles published in English. The initial search yielded 1228 articles. Of these, 14 articles (20 trials) were included in our investigation focusing on the effects of RS on total cholesterol (TC; 19 trials), triglycerides (TG; 19 trials), low-density lipoprotein cholesterol (LDL-C; 16 trials), and high-density lipoprotein cholesterol (17 trials). Methodological quality was assessed using TC, LDL-C, TGs, and high-density lipoprotein cholesterol. Pooled effects were calculated using a random-effects model. The meta-analysis of these data showed that RS supplementation has an effect on lowering TC and LDL-C (TC: mean difference, -7.33mg/dL [95% confidence interval -12.15 to -2.52mg/dL]; LDL-C: mean difference: -3.40mg/dL [95% confidence interval, -6.74 to -0.07mg/dL]). Subgroup meta-analysis revealed that a longer time (>4weeks) of RS supplementation can generate more obvious effects on TC and LDL-C levels, and higher dose (>20 g/d) of RS also had a lowering effect on TG level. Future research should focus on the relationship between RS type and cholesterol-lowering effects, and the effects on subjects of different health status or those with different baseline levels of serum lipids. Moreover, the mechanism for the cholesterol-lowering effects of RS should be further explored. In conclusion, RS can reduce serum TC and LDL-C levels, particularly when administered for a duration longer than 4 weeks.


Assuntos
LDL-Colesterol/sangue , Suplementos Nutricionais , Amido/farmacologia , Adulto , Colesterol/sangue , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
10.
Genet Mol Res ; 15(4)2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27819733

RESUMO

The matrix Gla (gamma-carboxyglutamic acid-rich) protein (MGP), a vitamin K-dependent and Gla-containing protein, is a calcification inhibitor that mainly functions in tissue calcification and mineralization. In this study, we obtained the complete cDNA sequence of MGP from the spinyhead croaker (Collichthys lucidus), which we named Cl-MGP. Cl-MGP was 923 bp long with a 384-bp open reading fragment that encoded 127 amino acids. The predicted MGP protein sequence contained a 19-residue hydrophobic signal peptide, suggesting that it possesses secretory characteristics. The Gla domain and the invariant unit ErraEtCedyspC, which has been identified in all known vitamin K-dependent vertebrate proteins, were highly conserved in Cl-MGP, suggesting that it uses the same mechanism to function as the known proteins. An alignment analysis revealed that Cl-MGP had the highest identity with Larimichthys crocea (93%), which had lost five amino acid residues in the C-terminal. A quantitative real-time polymerase chain reaction revealed that Cl-MGP expression was highest in the gill, followed by the cholecyst and spleen, with almost no expression in the blood, muscle, or testes. The high Cl-MGP expression in the gill is similar to that observed in other fish species, but the relatively high expression found in the cholecyst and spleen is not seen in all species. Future studies should investigate the tissue distributions of both mRNA and proteins in different species, in order to understand the function and evolution of MGP in different species.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica , Perciformes/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/metabolismo , Clonagem Molecular , DNA Complementar/genética , Proteínas da Matriz Extracelular/química , Proteínas da Matriz Extracelular/metabolismo , Perfilação da Expressão Gênica , Especificidade de Órgãos/genética , Filogenia , Alinhamento de Sequência , Proteína de Matriz Gla
11.
Cell Death Dis ; 4: e715, 2013 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-23846217

RESUMO

HeLa cells treated with celastrol, a natural compound with inhibitive effect on proteasome, exhibited increase in apoptotic rate and characteristics of apoptosis. To clarify the signal network activated by celastrol to induce apoptosis, both the direct target proteins and undirect target proteins of celastrol were searched in the present study. Proteasome catalytic subunit ß1 was predicted by computational analysis to be a possible direct target of celastrol and confirmed by checking direct effect of celastrol on the activity of recombinant human proteasome subunit ß1 in vitro. Undirect target-related proteins of celastrol were searched using proteomic studies including two-dimensional electrophoresis (2-DE) analysis and iTRAQ-based LC-MS analysis. Possible target-related proteins of celastrol such as endoplasmic reticulum protein 29 (ERP29) and mitochondrial import receptor Tom22 (TOM22) were found by 2-DE analysis of total cellular protein expression profiles. Further study showed that celastrol induced ER stress and ER stress inhibitor could ameliorate cell death induced by celastrol. Celastrol induced translocation of Bax into the mitochondria, which might be related to the upregulation of BH-3-only proteins such as BIM and the increase in the expression level of TOM22. To further search possible target-related proteins of celastrol in ER and ER-related fractions, iTRAQ-based LC-MS method was use to analyze protein expression profiles of ER/microsomal vesicles-riched fraction of cells with or without celastrol treatment. Based on possible target-related proteins found in both 2-DE analysis and iTRAQ-based LC-MS analysis, protein-protein interaction (PPI) network was established using bioinformatic analysis. The important role of glycogen synthase kinase-3ß (GSK3ß) in the signal cascades of celastrol was suggested. Pretreatment of LiCL, an inhibitor of GSK3ß, could significantly ameliorate apoptosis induced by celastrol. On the basis of the results of the present study, possible signal network of celastrol activated by celastrol leading to apoptosis was predicted.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/fisiologia , Inibidores de Proteassoma/farmacologia , Triterpenos/farmacologia , Proliferação de Células/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta , Células HeLa , Humanos , Medicina Tradicional Chinesa , Modelos Moleculares , Triterpenos Pentacíclicos , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Mapas de Interação de Proteínas , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteoma/metabolismo , Transdução de Sinais
12.
J Dairy Sci ; 95(9): 5127-5132, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22916918

RESUMO

Free gossypol residues in tissues or milk from feeding whole cottonseed and cottonseed meal were measured for their effect on health of dairy cows and humans. Forty lactating cows were randomly assigned to 5 treatments in a 60-d experiment to investigate the effects of sources and dietary level of gossypol on plasma and milk gossypol concentrations in lactating cows. Five experimental diets had identical net energy for lactation and crude protein content on a dry matter (DM) basis. Soybean meal was the main protein ingredient used in the control diet. Cottonseed meal (CSM) or whole cottonseed (WCS) substituted for part of the soybean meal in the other 4 diets. Gossypol levels in the 5 diets were 0 (control), 91.15 mg/kg of DM in CSM1, 117.31mg/kg of DM in CSM2, 385.43 mg/kg of DM in WCS1, and 611.13 mg/kg in WCS2. Yields of 3.5% fat-corrected milk were significantly higher for cows in the WCS2 group; cows in the CSM1 and WCS1 groups showed no differences but both were numerically higher than the control and CSM2 groups. Milk protein concentration was lower for cows consuming WCS1 compared with the control group. Lactose concentration was lower for cows in the CSM2 group compared with the WCS2 group, but no differences were observed among other diets. Aspartate aminotransferase in serum was significantly higher for the WCS2 group compared with the control and WCS1 groups, but no difference was observed with the CSM1 and CSM2 groups. Concentrations of gossypol in plasma and milk of cows in the WCS1 and WCS2 groups were both higher than those of the other groups. No adverse effects were observed on cows fed diets containing 12.0% CSM, and no gossypol was found in plasma and milk. When WCS comprised 15% of the diet DM, yields of 3.5% fat-corrected milk were increased in cows and gossypol was detected in plasma and milk but not at harmful levels.


Assuntos
Resíduos de Drogas/análise , Gossipol/farmacocinética , Leite/química , Ração Animal , Animais , Aspartato Aminotransferases/sangue , Bovinos , Óleo de Sementes de Algodão/metabolismo , Dieta , Proteínas Alimentares/metabolismo , Feminino , Gossipol/análise , Gossipol/sangue , Lactação/metabolismo , Lactose/análise , Proteínas do Leite/análise
13.
Leukemia ; 19(11): 1941-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16094422

RESUMO

The LYL1 gene encodes a basic helix-loop-helix transcription factor involved in T-cell acute lymphoblastic leukemia. Using real-time quantitative RT-PCR assay, we found that the expression of LYL1 was at higher levels in the majority cases of acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to normal bone marrow. Our study also showed that LYL1 was highly expressed in most AML cell lines and in CD34+ AML cells. To determine whether LYL1 had an affect on the phenotype and behavior of myeloid cells, we introduced full-length LYL1 cDNA into K562 cells using electroporation and U937 cells with retroviral infection. Both of the derivative cell lines with overexpression of LYL1 had an increased growth rate and clonogenecity. Forced expression of LYL1 in K562 cells enhanced spontaneous and hemin-induced erythroid differentiation but blocked spontaneous as well as PMA-induced megakaryocytic differentiation. Overexpression of LYL1 in U937 cells blocked all-trans retinoic acid-induced monocytic differentiation. The LYL1-transfected U937 cells were also more resistant to the cytotoxic drug cytarabine. These results demonstrate that LYL1 may play a role in early hematopoiesis and may be a potential oncogenic factor in AML.


Assuntos
Transformação Celular Neoplásica/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Antineoplásicos/farmacologia , Antineoplásicos Alquilantes/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Medula Óssea , Citarabina/farmacologia , DNA Complementar , Resistencia a Medicamentos Antineoplásicos , Eletroporação , Humanos , Síndromes Mielodisplásicas/genética , Fenótipo , Retroviridae , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tretinoína , Células Tumorais Cultivadas
14.
Magn Reson Chem ; 42(6): 564-6, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15137050

RESUMO

1H and 13C NMR spectra of 8-C-beta-D-[2-O-(E)-p-coumaroyl] glucopyranosyl-2-(2-hydroxy)propyl-7-methoxy-5-methylchromone were completely assigned by 2D NMR observations. Especially the 1H assignments of the glucosyl and hydroxyl protons were achieved by utilizing HMQC, HMBC, 1H-1H COSY and DEPT techniques together with a heavy water exchange 1H NMR experiment.


Assuntos
Aloe/metabolismo , Cromonas/análise , Cromonas/normas , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/normas , Modelos Químicos , Modelos Moleculares , Isótopos de Carbono , China , Cromonas/química , Simulação por Computador , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/normas , Prótons , Padrões de Referência
15.
Xenobiotica ; 34(1): 103-15, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14742139

RESUMO

1. The disposition of 3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl) propyl]-imidazolidin-1-yl]-3(S)-(6-methoxy-pyridin-3-yl)propionic acid (compound A), a potent and selective alpha(v)beta(3) antagonist, was characterized in several animal species in support of its selection for preclinical safety studies and potential clinical development. 2. Compound A exhibited marked species differences in pharmacokinetics; the plasma clearances and bioavailabilities ranged from 33-47 ml min(-1) kg(-1) in rats and mice to 4-9 ml min(-1) kg(-1) in dogs and monkeys, and about 20% in rats to 70-80% in dogs and monkeys, respectively. Both the intravenous (i.v.) and oral kinetics of compound A were linear over the dose range studied in dogs (0.1-5 mg kg(-1) i.v. and 0.25-20 mg kg(-1) orally [p.o.]) and rats (1-30 mg kg(-1) i.v. and 4-160 mg kg(-1) p.o.). 3. Compound A was eliminated substantially by urinary excretion; the urinary recovery of the unchanged drug was 67% in rhesus, 48% in dogs and about 30% in rats. In these animal species, biotransformation was modest. 4. Following i.v. administration of [(14)C]-compound A to rats, the radioactivity rapidly distributed to all tissues investigated, with high levels of the radioactivity detected in liver, kidney and intestine soon after the drug administration. The radioactivity declined rapidly, with less than 1% of the i.v. dose remaining at 30-h post-dose. 5. Compound A was moderately bound to plasma proteins, with unbound fractions of 26, 20, 14 and 5% for rats, dogs, monkeys and humans, respectively. It was bound primarily to human alpha(1)-acid glycoprotein (about 85% binding at 0.1% concentration), as compared with human albumin (< 50% binding at 4% concentration). 6. Using simple allometry, compound A was predicted to exhibit relatively low clearance (1-3 ml min(-1) kg(-1)) and low volume of distribution (0.1-0.3 l kg(-1)) in humans. Based on the predicted values, compound A was projected to exhibit a favourable oral pharmacokinetic profile in humans, with good bioavailability (50-80%). These predicted values provided a basis for compound selection for further development.


Assuntos
Integrina alfaVbeta3/antagonistas & inibidores , Naftiridinas/farmacocinética , Succinimidas/farmacocinética , Administração Oral , Animais , Proteínas Sanguíneas/metabolismo , Radioisótopos de Carbono , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Previsões , Humanos , Infusões Intravenosas , Integrina alfaVbeta3/metabolismo , Macaca mulatta , Masculino , Taxa de Depuração Metabólica , Camundongos , Naftiridinas/sangue , Naftiridinas/química , Naftiridinas/urina , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Succinimidas/sangue , Succinimidas/química , Succinimidas/urina
16.
Cell Res ; 11(3): 187-93, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11642403

RESUMO

Plants synthesize the osmoprotectant glycine betaine (GB) via choline-->betaine aldehyde-->glycine betaine[1]. Two enzymes are involved in the pathway, choline monooxygenase (CMO) and betaine aldehyde dehydrogenase (BADH). A full length CMO cDNA (1,643bp) was cloned from Amaranthus tricolor. The open reading frame encoded a 442-amino acid polypeptide, which showed 69% identity with CMOs in Spinacia oleracea L. and Beta vulgaris L. DNA gel blot analysis indicated the presence of one copy of CMO gene in the A. tricolor genome. The expressions of CMO and BADH proteins in A.tricolor leaves significantly increased under salinization, drought and heat stress (42 degrees C), as determined by immunoblot analysis, but did not respond to cold stress (4 degrees C), or exogenous ABA application. The increase of GB content in leaves was parallel to CMO and BADH contents.


Assuntos
Amaranthus/enzimologia , Regulação da Expressão Gênica de Plantas , Oxigenases/genética , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Amaranthus/genética , Amaranthus/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Betaína/metabolismo , Betaína-Aldeído Desidrogenase , DNA Complementar , Dados de Sequência Molecular , Peso Molecular , Oxigenases/química , Oxigenases/metabolismo , Folhas de Planta/química , Folhas de Planta/enzimologia , Alinhamento de Sequência , Cloreto de Sódio/farmacologia , Especificidade da Espécie , Temperatura , Água
17.
Zhonghua Gan Zang Bing Za Zhi ; 9(2): 75-7, 2001 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-11350681

RESUMO

OBJECTIVE: To identify aldosterone synthase gene-CYP11B2 mRNA expression in rat livers and evaluate the efficacy of antisterone. METHODS: One hundred and twenty male Wistar rats were divided into 3 groups: model group (subcutaneous injection of CCl(4), 0.25 ml/100 mg, 3 times/week), antisterone group (besides same dosage of CCl(4) given, gastropufusion of antisterone of 20mg x kg(-1) x d(-1)), and control group (subcutaneous injection of olive oil). The area of collagen was examined by image analyzing system. The expression of aldosterone synthase gene-CYP11B2 mRNA was detected by RT-PCR and in situ hybridization. RESULTS: The expression of CYP11B2 mRNA, which located in the endoplasm of HSC, was upregulated when fibrogenesis occurred. The grade of fibrosis and the area of collagen in antisterone group were less than those in model group before 6th week (P<0.05). After the 6th week however, there was no significant difference between the two groups (P>0.05). CONCLUSIONS: The expression of CYP11B2 mRNA is upregulated in fibrotic liver. Antisterone can partly have a fibrogenesis-inhibiting effect on the early stage of CCl(4)-induced hepatic fibrosis.


Assuntos
Citocromo P-450 CYP11B2/genética , Medicamentos de Ervas Chinesas/uso terapêutico , Regulação Enzimológica da Expressão Gênica , Cirrose Hepática Experimental/tratamento farmacológico , Fígado/enzimologia , Animais , Fígado/citologia , Cirrose Hepática Experimental/enzimologia , Masculino , Ratos , Ratos Wistar
18.
Cell Mol Life Sci ; 58(2): 321-42, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11289314

RESUMO

Ecdysteroid agonist and antagonist activities can be detected and quantified with the Drosophila melanogaster B(II) cell bioassay. This bioassay is convenient, sensitive and robust. We report the assessment with this bioassay of the activities of a wide range of compounds representing a number of classes of natural products. Many compounds were inactive over a wide concentration range (10(-8) to 10(-4) or 10(-3) M) or cytotoxic at high concentrations. However, antagonisitic activity was associated with several classes of compounds: cucurbitacins and withanolides (extending previous findings) and phenylalkanoids and certain alkaloids (described for the first time). A withanolide (withaperuvin D) is identified which possesses agonistic activity. Brassinosteroids, which have been ascribed (ant)agonistic properties in the past, were not found to be active in the B(II) bioassay, either as agonists or antagonists. Possible reasons for the prevalence of antagonists and for the low potency of the majority of them are discussed.


Assuntos
Bioensaio/métodos , Produtos Biológicos/farmacologia , Isoflavonas , Esteroides/agonistas , Esteroides/antagonistas & inibidores , Alcaloides/química , Alcaloides/farmacologia , Animais , Ligação Competitiva , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Bufanolídeos/química , Bufanolídeos/farmacologia , Cardenolídeos/química , Cardenolídeos/farmacologia , Linhagem Celular , Cucurbitacinas , Drosophila melanogaster/citologia , Ecdisteroides , Estrogênios não Esteroides/química , Estrogênios não Esteroides/farmacologia , Hormônios de Inseto/química , Hormônios de Inseto/farmacologia , Ligantes , Lignanas/química , Lignanas/farmacologia , Neurotransmissores/química , Neurotransmissores/farmacologia , Fitoestrógenos , Preparações de Plantas , Receptores de Esteroides/efeitos dos fármacos , Receptores de Esteroides/metabolismo , Saponinas/química , Saponinas/farmacologia , Esteroides/química , Esteroides/farmacologia , Triterpenos/química , Triterpenos/farmacologia
19.
Plant Mol Biol ; 45(3): 353-63, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11292080

RESUMO

Glycinebetaine is an important osmoprotectant in bacteria, plants, and animals, but only little information is available on the synthesis of glycinebetaine in tree plants. Among four mangrove species, glycinebetaine could be detected only in Avicennia marina. Pinitol was the main osmoprotectant in the other three species. The level of glycinebetaine in A. marina increased under high salinity. Betaine-aldehyde dehydrogenase (BADH) was detected in all four species, but choline monooxygenase could not be detected. A cDNA library was constructed from the leaves of A. marina. Two kinds of BADH cDNAs were isolated, one homologous to the spinach chloroplast BADH, and the other with unique residues SKL at the end of C-terminus. The BADH transcription levels of the former were higher than those of the latter. The levels of the former BADH increased at high salinity whereas those of the latter were independent of salinity. BADHs were expressed in Escherichia coli and purified. Two kinds of A. marina BADHs exhibited similar kinetic and stability properties, but were significantly different from those of spinach BADH. A. marina BADHs efficiently catalyzed the oxidation of betainealdehyde, but not the oxidation of omega-aminoaldehydes and were more stable at high temperature than the spinach BADH.


Assuntos
Aldeído Oxirredutases/genética , Betaína/metabolismo , Plantas Medicinais/genética , Aldeído Oxirredutases/metabolismo , Sequência de Aminoácidos , Betaína-Aldeído Desidrogenase , Cloreto de Cálcio/farmacologia , Metabolismo dos Carboidratos , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Relação Dose-Resposta a Droga , Estabilidade Enzimática , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Temperatura Alta , Isoenzimas/genética , Dados de Sequência Molecular , Concentração Osmolar , Oxirredução/efeitos dos fármacos , Oxigenases/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/enzimologia , Folhas de Planta/genética , Plantas Medicinais/enzimologia , Plantas Medicinais/metabolismo , Cloreto de Potássio/farmacologia , Prolina/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Cloreto de Sódio/farmacologia , Especificidade da Espécie , Spinacia oleracea/enzimologia , Especificidade por Substrato , Distribuição Tecidual , Ácido gama-Aminobutírico/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 25(3): 169-71, 2000 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-12212103

RESUMO

OBJECTIVE: To observe the effect of tonic herbs on the immune cell proliferation in stressed mice. METHODS: A model of stressed mice was built to observe the effect of such tonic herbs as Tusizi, Chuanduan; Nüzhenzi, Gouqizi on the calcium concentration in cytoplasm in the process of immune cell reproduction, as well as on the membrane fluidity of splenetic lymphocytes, IL-2, IL-2R and cell period. RESULTS: The tonic herbs could improve the proliferation ability of spleen lymphocyte in the stressed mice, reduce the calcium concentration, and recover the fluidity of cell membrane. They could also improve the activity of IL-2 and increase the amount of IL-2R cell(P < 0.01). The combination of the four tonic herbs proved more effective, facilitating the cell into DNA synthetic period and reducing the retention period in G0/G1 (P < 0.01). CONCLUSION: Tonic herbs can modulate the reproductive function of the spleen lymphocyte and relieve the unfavorable response of the stress on the organism.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Linfócitos/citologia , Plantas Medicinais , Estresse Fisiológico/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Cálcio/sangue , Divisão Celular/efeitos dos fármacos , Combinação de Medicamentos , Interleucina-2/metabolismo , Masculino , Fluidez de Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória
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