RESUMEN
Selenium (Se) is essential for successful male reproduction. However, the association of Se status with human semen quality remains controversial and the underlying mechanisms are poorly understood. We measured seminal plasma Se concentrations, sperm mitochondrial DNA copy number (mtDNAcn), and sperm quality parameters among healthy Chinese men screened as potential sperm donors. Linear mixed-effects models were used to investigate the associations of within-subject pooled seminal plasma Se concentrations (n = 1159) with repeated sperm quality parameters (n = 5617); mediation analyses were applied to evaluate the mediating role of sperm mtDNAcn (n = 989). Seminal plasma Se concentrations were positively associated with sperm concentration and total count (both P for trend < 0.001). In adjusted models, men in the top vs. bottom quartiles of seminal plasma Se concentrations had 70.1 % (95 % CI: 53.3 %, 88.9 %) and 59.1 % (95 % CI: 40.5 %, 80.2 %) higher sperm concentration and total count, respectively. Meanwhile, we observed inverse associations between seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm motility, concentration, and total count (all P for trend < 0.05). Mediation analyses suggested that sperm mtDNAcn mediated 19.7 % (95 % CI: 15.9 %, 25.3 %) and 23.1 % (95 % CI: 17.4 %, 33.4 %) of the associations between seminal plasma Se concentrations and sperm concentration and total count, respectively. Our findings suggest that Se is essential for male spermatogenesis, potentially by affecting sperm mtDNAcn.
Asunto(s)
Selenio , Semen , Masculino , Humanos , Semen/química , Análisis de Semen , Selenio/análisis , ADN Mitocondrial/genética , Variaciones en el Número de Copia de ADN , Motilidad Espermática , Espermatozoides , Recuento de EspermatozoidesRESUMEN
Information on the association between tea drinking and semen quality is limited. Little is reported on whether tea drinking is benefit to sperm quality. This cross-sectional and longitudinal study was conducted between April 2017 and July 2018. Participants were healthy men who were screened as potential sperm donors recruited at the Hubei Province Human Sperm Bank of China. A structured questionnaires containing sociodemographic information, daily habits, sperm collection-related information was completed for each participant at interview. Repeated semen samples were taken to examine the sperm parameters, including sperm volume, sperm concentration, sperm count, progressive motility, and total motility. A total of 1385 men with 6466 sperm samples were included in this study. Two groups were compared: tea drinking men (389, 28.1%) and non-tea drinking men (996, 71.9%). Compared with subjects who never drink tea, the analyses showed that sperm concentration and total sperm count were higher in tea-consuming subjects. A 10-year period or more duration of tea drinking significantly increased semen concentrations by 16.27% (P < 0.05). Sperm concentration was increased in subjects with a frequency of tea drinking of 3 days or more per week (P < 0.05) or, among men who were occasional alcohol drinkers, when tea concentration was weak (P < 0.05). No evidence of trend effects (P for trend > 0.05) or interaction effects (P for interaction > 0.05) between tea consumption and sperm quality, respectively. Our findings provide evidence that tea drinking may improve male reproductive health. Long-term, frequent, weak tea drinking tends to increase sperm quality among men with low BMI or health-related behaviors like smoking or alcohol intake.
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Análisis de Semen , Semen , China , Estudios Transversales , Humanos , Estudios Longitudinales , Masculino , Recuento de Espermatozoides , TéRESUMEN
Environmental metal exposure has been associated with decreasing semen quality, but the effects of multiple metal exposure on seminal plasma metabolome remain obscure. In this study, semen and repeated urine samples from 551 volunteers were collected in Wuhan City. Heavy metals and trace elements were measured using inductively coupled plasma mass spectrometer, and seminal plasma metabolomes were acquired using liquid chromatography coupled with high-resolution mass spectrometry. Weighted gene co-expression network analysis showed more than half of the seminal plasma metals were associated with specific metabolite modules, whereas only a few urine metals presented weak associations, indicating that seminal plasma may be an ideal biological sample for male reproductive biomarker discovery and exposure risk assessment. Seminal plasma zinc (Zn) and selenium (Se) concentrations were significantly associated with 22 metabolites (e.g., glycerophospholipids, acyl-carnitines and amino acid derivatives). Among these metabolites, acyl-carnitines were positively associated with semen quality and sperm concentration. Moreover, acyl-carnitines were associated with both Zn and Se exposure, indicating the potential role of carnitine pathway in their toxicity mechanism. Our findings suggest that seminal plasma metabolome connects Zn and Se exposure and sperm concentrations in Chinese men of reproductive age.
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Metales Pesados , Selenio , Adulto , China , Humanos , Masculino , Metaboloma , Metales Pesados/metabolismo , Metales Pesados/toxicidad , Selenio/metabolismo , Semen , Análisis de Semen , Motilidad Espermática , Espermatozoides , Zinc/metabolismoRESUMEN
OBJECTIVE: To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS: Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."
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Hipercolesterolemia , Biomarcadores , Colesterol , Medicamentos Herbarios Chinos , Femenino , Humanos , Hipercolesterolemia/tratamiento farmacológico , MenopausiaRESUMEN
This study aims to explore the active components and molecular mechanism of Shenmai Injection in the treatment of atrial fibrillation(AF) based on the application of network pharmacology and molecular docking technology. The chemical components of single herbs of Shenmai Injection were collected from TCMSP and TCMID, with the standard chemical name and PubChem CID(referred to as CID) obtained from PubChem database. The active components were screened using SwissADME, and their targets were predicted using SwissTargetPrediction. Targets related to AF treatment were identified using GeneCards, OMIM, and other databases. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. The single herb-active component-potential target network was constructed using Cytoscape, and the clusterProfiler R function package was used to perform the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The protein-protein interaction(PPI) network of intersection targets was generated based on the STRING database. The hub target protein was identified by visualization using Cytoscape, and then docked to its reverse-selected active components. The analysis showed that there were 65 active components with 681 corresponding targets in Shenmai Injection, 2 798 targets related to AF treatment, and 235 intersection targets involving 2 549 GO functions and 153 KEGG pathways. Finally, hub target proteins, including RAC-alpha serine/threonine-protein kinase(AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA), and estrogen receptor 1(ESR1), were screened out by PPI network visualization. The molecular docking was performed for 39 active components screened out in reverse, among which 30 active components de-monstrated high affinity. Among them, homoisoflavanoids CID 10871974, CID 5319742, and CID 10361149 had stronger affinity docking with AKT1. This study preliminarily indicates that Shenmai Injection treats AF through multiple components, multiple targets, and multiple pathways. Homoisoflavonoids of Ophiopogon japonicus are its important active components, which target AKT1 to regulate metabolism, inflammation, and apoptosis in AF treatment.
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Fibrilación Atrial , Medicamentos Herbarios Chinos , Fibrilación Atrial/tratamiento farmacológico , Combinación de Medicamentos , Humanos , Medicina Tradicional China , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: Essential elements such as iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), strontium (Sr), and molybdenum (Mo) are necessary for reproductive health. However, their associations with human semen quality remain inconclusive. OBJECTIVES: To investigate the associations of urinary Fe, Co, Cu, Zn, Se, Rb, Sr, and Mo concentrations with semen quality in healthy men screened as potential sperm donors and identify critical windows of susceptibility. METHODS: 1428 healthy men provided 3766 urine and 6527 semen samples, which were measured for urinary essential element concentrations and sperm quality parameters, respectively. Linear mixed models and cubic spline curves were used to evaluate associations between urinary essential elements and semen quality. Multiple informant models were used to identify potential critical windows of susceptibility. RESULTS: Linear mixed models and cubic spline curves showed positive dose-response relationships between urinary Zn and sperm concentration and total count and between urinary Mo and total sperm count [all False Discovery Rate (FDR) adjusted p-value for trend < 0.05]. In the multiple-element linear mixed models, the men in the highest versus lowest quartiles of urinary Zn and Mo had a higher sperm concentration of 17.5% (95% CI: 2.8%, 34.2%; p-value for trend = 0.006) and total sperm count of 18.3% (95% CI: 1.4%, 38.0%; p-value for trend = 0.027), respectively. Urinary Zn was also positively associated with total sperm count in a dose-dependent manner (p-value for trend = 0.036), though the percentile difference in total sperm count between men in the highest and lowest quartile was not statistically significant (16.4%, 95% CI: -1.7%, 37.9%). These associations appeared to be stronger when urinary Zn and Mo were measured at 0-9 days before the date of semen examination (i.e., corresponding to epididymal storage). CONCLUSIONS: Higher urinary Zn and Mo, particularly during the period of epididymal storage, were associated with greater sperm production.
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Selenio , Análisis de Semen , Humanos , Masculino , Semen , Recuento de Espermatozoides , Motilidad Espermática , EspermatozoidesRESUMEN
OBJECTIVE: To observe the influence of scalp-acupuncture on the expression of pentraxin 3 (PTX3), Interleukin (IL)-1ß, zonula occludens-1(ZO-1) mRNA and Occludin mRNA in striatum in acute ischemic cerebrovascular disease (AICD) rats, so as to investigate its mechanisms underlying improvement of AICD. METHODS: Forty-eight male SD rats were randomly allocated to control, model, IL-1Ra and IL-1Ra+scalp-acupuncture groups (n=12 rats in each group). The AICD model was established by occlusion of the middle cerebral artery (MCAO). Rats of the IL-1Ra group and IL-1Ra+scalp-acupuncture group received intraperitoneal injection of IL-1Ra (0.05 mg·kg-1·d-1), once daily for 6 days. Scalp acupuncture stimulation was applied to bilateral "Dingnieqianxiexian" (MS6) once daily for 6 days for rats in IL-1Ra+scalp-acupuncture group. Before and after intervention, the neurologic deficit score (NDS) was evalua-ted according to Longa's method. The expression of striatum PTX3 and IL-1ß was detected by immunohistochemistry, and ZO-1 mRNA and Occludin mRNA in the striatum tissue were detected by fluorescence quantitative real-time PCR. The Evans Blue (EB) tracer method was used to monitor the degree of blood-brain barrier (BBB) damage. RESULTS: Following modeling, the NDS, EB content and the expression of PTX3 and IL-1ß in the striatum tissue were significantly increased, and the ZO-1 mRNA and Occludin mRNA expression was considerably decreased in the model group compared with the control group (P<0.05). After the interventions and compared with the model group, the NDS, EB content in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra group were significantly down-regulated (P<0.05), while the striatum ZO-1 mRNA and Occludin mRNA expression in both IL-1Ra and IL-1Ra+scalp acupuncture groups, and PTX3 in the IL-1Ra+scalp acupuncture group were obviously up-regulated (P<0.05), and the expression of IL-1ß was obviously down-regulated in the IL-1Ra+scalp acupuncture group (P<0.05) rather than in the IL-1Ra group (P>0.05). The effects of scalp acupuncture combined with IL-1Ra were obviously superior to that of IL-1Ra in down-regulating NDS, EB content and IL-1ß expression level, and in up-regulating PTX3, ZO-1 mRNA and Occludin mRNA expression levels (P<0.05). CONCLUSION: Scalp acupuncture can improve neurological function and reduce the degree of BBB injury in AICD rats, which may be associated with its function in up-regulating the expression of PTX3 and in promoting the expression of ZO-1 mRNA and Occludin mRNA.
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Terapia por Acupuntura , Trastornos Cerebrovasculares , Animales , Proteína C-Reactiva , Cuerpo Estriado , Masculino , Ratas , Ratas Sprague-Dawley , Cuero Cabelludo , Componente Amiloide P SéricoRESUMEN
OBJECTIVE: To observe the clinical effect of ZHENG ' Guo-Yan-Re needling technique for diabetic fundus hemorrhage. METHODS: With before-after study design, 34 patients with diabetic eyeground hemorrhage were treated with basic treatment (oral administration of antidiabetic medication or insulin injections to ensure blood glucose in the normal range); in addition, acupuncture was given at bilateral Fengchi (GB 20), Taiyang (EX-HN 5), Jingming (BL 1), Cuanzhu (BL 2), Sanyinjiao (SP 6) and Hegu (LI 4). The ZHENG ' Guo-Yan-Re needling technique was applied at Fengchi (GB 20); the heat reinforcing needling technique was applied at Taiyang (EX-HN 5); the slow needle insertion technique was applied at Jingming (BL 1); and the Xique-Dengmei needling technique was applied at Cuanzhu (BL 2); the neutral supplementation and draining method was applied at remaining acupoints. The acupuncture was given once a day, 6 times as one course, and totally 4 courses were given with an interval of 1 day between courses. The follow-up visit was 6 months after treatment. The TCM symptom scores, fundus examination results and vision improvement were observed before and after treatment, and the effect was observed. RESULTS: Compared before treatment, the visual acuity, TCM symptom scores, fundus microaneurysm and hemorrhage points in 34 patients (68 eyes) were significantly improved after treatment (P<0.05). The total effective rate was 88.2% (60/68) after treatment; at follow-up visit, the visual acuity, TCM symptom scores and fundus pathological changes were all improved (P<0.05) and stable at the post-treatment level (P>0.05). CONCLUSION: ZHENG ' Guo-Yan-Re needling technique could improve symptoms, promote the absorption of fundus hemorrhage, and improve vision in patients with diabetic fundus hemorrhage.
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Terapia por Acupuntura , Diabetes Mellitus , Puntos de Acupuntura , Ojo , Femenino , Humanos , AgujasRESUMEN
Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals' 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01-0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals' long-term exposures.
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Cromo/orina , Hierro/orina , Manganeso/orina , Selenio/orina , Zinc/orina , Adulto , Biomarcadores/orina , China , Creatinina/orina , Exposición a Riesgos Ambientales/análisis , Humanos , Masculino , Análisis de Regresión , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Urinálisis , Adulto JovenRESUMEN
BACKGROUND: Metabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent models employ high fat, high cholesterol, high fructose, methionine/choline deficient diets or combinations of these to induce NAFLD/NASH. The FATZO mice spontaneously develop the above metabolic disorders and type 2 diabetes (T2D) when fed with a normal chow diet. The aim of the present study was to determine if FATZO mice fed a high fat and fructose diet would exacerbate the progression of NAFLD/NASH. METHODS: Male FATZO mice at the age of 8 weeks were fed with high fat Western diet (D12079B) supplemented with 5% fructose in the drinking water (WDF) for the duration of 20 weeks. The body weight, whole body fat content, serum lipid profiles and liver function markers were examined monthly along with the assessment of liver histology for the development of NASH. In addition, the effects of obeticholic acid (OCA, 30 mg/kg, QD) on improvement of NASH progression in the model were evaluated. RESULTS: Compared to normal control diet (CD), FATZO mice fed with WDF were heavier with higher body fat measured by qNMR, hypercholesterolemia and had progressive elevations in AST (~ 6 fold), ALT (~ 6 fold), liver over body weight (~ 2 fold) and liver triglyceride (TG) content (1.4-2.9 fold). Histological examination displayed evidence of NAFLD/NASH, including hepatic steatosis, lobular inflammation, ballooning and fibrosis in FATZO mice fed WDF. Treatment with OCA for 15 weeks in FATZO mice on WDF significantly alleviated hypercholesterolemia and elevation of AST/ALT, reduced liver weight and liver TG contents, attenuated hepatic ballooning, but did not affect body weight and blood TG levels. CONCLUSION: WDF fed FATZO mice represent a new model for the study of progressive NAFLD/NASH with concurrent metabolic dysregulation.
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Diabetes Mellitus Tipo 2/complicaciones , Dieta Alta en Grasa/efectos adversos , Dieta Occidental/efectos adversos , Modelos Animales de Enfermedad , Fructosa/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicaciones , Edulcorantes/efectos adversos , Animales , Progresión de la Enfermedad , Hígado/patología , Hígado/fisiopatología , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/fisiopatologíaRESUMEN
OBJECTIVE: To explore the optimal treatment selection for treating varicocele (VC) male infertility patients accompanied with oligozoospermia or azoospermia of different Chinese medical syndrome types by comparing the efficacies of integrative medicine. METHODS: One hundred and twenty male infertility patients with VC accompanied with oligozoospermia or azoospermia were assigned to Chinese medical treatment group (A) and the surgical group (B), each consisting of three Chinese medical syndrome types, i.e., damp-heat stagnation syndrome (DHSS), Shen-deficiency blood stasis syndrome (SDBSS), and blood stasis stagnation syndrome (BSSS), 20 in each group. Corresponding Chinese medical treatment was administered to those in Group A, C, and E, while microscopic ligation of internal vena spermatic was administered to those in Group B, D, and F. The routine analysis of semen, biochemical analysis of seminal plasma, and serum sex hormones (prolactin, testosterone, follicle stimulating hormone, luteinizing hormone, and estradiol) were performed before treatment and by the end of the 24th week after treatment. RESULTS: Totally 18 patients' spouses were pregnant. Of them, 1 in Group A of DHSS (abbreviated as Group A), 3 in Group B of DHSS (abbreviated as Group B), 4 in Group A of SDB-SS (abbreviated as Group C), 5 in Group A of SDBSS (abbreviated as Group D), 1 in Group A of BSSS (abbreviated as Group E), and 4 in Group B of BSSS (abbreviated as Group F). After 24-week treatment, the sperm concentration, class a sperm percentage, class a + b sperm percentage, the motility rate, the seminal plasma of fructose density, and the seminal plasma neutral alpha-glucosidase were more significantly improved in Group B, C, D and F, when compared with the same group before treatment (P <0. 01, P <0. 05). There was no statistical difference in the aforesaid indices between before and after treatment in Group A and Group E (P >0.05). As for the improvement percentage of seminal routine indices, the difference of the seminal plasma of fructose density, and the difference of seminal plasma neutral alpha-glucosidase between before and after treatment in the same Chinese medical syndrome types, better effects were obtained in Group B than in Group A (P <0.01), and better effects were obtained in Group F than in Group E (P <0.01). There was no statistical difference between Group C and D (P >0.05). There was no statistical difference in the 5 items of sex hormones in each group between before and after treatment (P >0.05). CONCLUSIONS: Surgical treatment could effectively improve the semen quality for male infertility VC patients accompanied with oligozoospermia or azoospermia. Of them, Chinese medical treatment could be recommended to those of SDBSS who would not receive surgical treatment.
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Infertilidad Masculina/diagnóstico , Infertilidad Masculina/terapia , Varicocele/diagnóstico , Varicocele/terapia , Adulto , Humanos , Infertilidad Masculina/etiología , Medicina Integrativa , Masculino , Medicina Tradicional China , Fitoterapia , Varicocele/complicacionesRESUMEN
OBJECTIVE: The Jinleng method is based on the principle of lowered temperature and diathermic action on the testis. The aim of this study is to investigate the effect and safety of the Jinleng method on oligospermia and asthenospermia. METHODS: We treated 39 infertile males with oligospermia or asthenospermia with Jinleng underpants (Jinleng method) bid for 3 months, observed the changes in the sperm parameters of the patients after the treatment and recorded the pregnancy outcomes of their wives. RESULTS: Of the 36 patients who accomplished the treatment, 31 showed significantly improvement in semen volume, sperm concentration, forward sperm motility, total sperm motility, total sperm count and total motile sperm count (P < 0.05), with an effectiveness rate of 86.1%. Five of the patients wives achieved pregnancy in the 2-month follow-up. Adverse effects were found in none of the patients. CONCLUSION: Jinleng method is effective and safe for the treatment of infertile males with oligospermia and asthenospermia.
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Astenozoospermia/terapia , Oligospermia/terapia , Fitoterapia , Adulto , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Resultado del TratamientoRESUMEN
Antiplatelet drugs are used to prevent aberrant platelet activation in pathophysiologic conditions such as myocardial infarction and ischemic stroke. The key role that ADP plays in this process has led to the development of antiplatelet drugs that target the P2Y12 receptor. The aim of this study was to characterize the pharmacodynamic (PD) and pharmacokinetic (PK) properties of the novel P2Y12 receptor antagonists, BX 667 and BX 048. BX 667 blocks ADP-induced platelet aggregation in human, dog and rat blood (IC50=97, 317 and 3000 nM respectively). BX 667 had nominal effects on collagen-induced aggregation and weakly inhibited arachidonic acid-induced aggregation. BX 667 has an active metabolite, BX 048, that also potently inhibits ADP-induced aggregation (IC50=290 nM) in human blood. BX 667 was shown to have high oral bioavailability in both dog and rat unlike BX 048. Administration of BX 667 resulted in a rapid and sustained inhibition of platelet aggregation where the extent and duration of platelet inhibition was directly proportional to circulating plasma levels. This report describes the PK/PD properties of BX 667 showing that it has the properties required for a potential antiplatelet therapeutic agent.
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Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Cetoácidos/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Antagonistas del Receptor Purinérgico P2 , Quinolinas/farmacocinética , Receptores Purinérgicos P2/metabolismo , Animales , Perros , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Humanos , Ligandos , Masculino , Modelos Biológicos , Agregación Plaquetaria/efectos de los fármacos , Unión Proteica , Ratas , Receptores Purinérgicos P2Y12 , Especificidad de la EspecieRESUMEN
ADP plays a key role in platelet aggregation which has led to the development of antiplatelet drugs that target the P2Y12 receptor. The aim of this study was to characterize the effects of two novel P2Y12 receptor antagonists, BX 667 and its active metabolite BX 048, on platelets. BX 667 and BX 048 block the binding of 2MeSADP to platelets and antagonize ADP-induced platelet aggregation in human, dog and rat washed platelets. Both compounds were shown to be reversible inhibitors of platelet aggregation. BX 048 prevents the decrease in cAMP induced by treatment of platelets with ADP. The specificity of BX 667 and BX 048 was demonstrated against cell lines expressing P2Y1 and P2Y6 as well as against a panel of receptors and enzymes. Taken all together these data show that both BX 048 and BX 667 are potent P2Y12 antagonists with high specificity which, in the accompanying paper are demonstrated to behave predictably in vivo.
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Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Cetoácidos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Antagonistas del Receptor Purinérgico P2 , Quinolinas/farmacología , Receptores Purinérgicos P2/metabolismo , Adenosina Difosfato/química , Animales , Calcio/metabolismo , Perros , Evaluación Preclínica de Medicamentos , Humanos , Técnicas In Vitro , Ligandos , Modelos Biológicos , Agregación Plaquetaria/efectos de los fármacos , Unión Proteica , Ratas , Receptores Purinérgicos P2Y12 , Especificidad de la EspecieRESUMEN
OBJECTIVE: To study effects of the cycle of light and exogenous plant growth regulators on growth of normal root and hairy root of Lycium barbarum and establish a long-term system of in vitro culture of L. barbarum roots. METHOD: Using normal roots from aseptic seedlings and hairy roots originated from Agrobacterium rhizogenes A4-mediated genetic transformation of L. barbarum, the growth of root segments was examined after 20 days of culture under different culture conditions. RESULT AND CONCLUSION: When cultured on the MS medium with different plant growth regulators (IAA, IBA, NAA), normal root segments of L. barbarum could elongate and branch, and the addition of 1 mg x L(-1) IBA into the medium was the most suitable for long-term in vitro culture of L. barbarum root. When cultured on MS medium without hormone, light promoted the elongation and lateral root formation of type II hairy root, but not of type I hairy root. Among three tested hormones, IAA at low concentration was the best for growth of type I hairy root, while 1 mg x L(-1) IBA was the most suitable for growth of type II hairy root. With the increase of hormone level added into MS medium, callusing frequencies of type I, II hairy roots were increased, at the same time, the formation of lateral root from hairy root or callus was inhibited.
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Iluminación , Lycium/crecimiento & desarrollo , Reguladores del Crecimiento de las Plantas/farmacología , Raíces de Plantas/crecimiento & desarrollo , Plantas Medicinales/crecimiento & desarrollo , Medios de Cultivo , Técnicas de Cultivo/métodos , Semillas/crecimiento & desarrolloRESUMEN
OBJECTIVE: To explore the change of serious abdominal traumatic patients' cellular immunity and the effect of Astragalus Injection (AI) on it. METHODS: Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with AI 20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. RESULTS: On the first day, in the conventional group and treated group, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/homologous leucocytic antigen-DR (HLA-DR(+)) were apparently lower than those in the healthy group (P < 0.05), while the CD(8)(+) was significantly higher than that in the healthy group (P < 0.05), and there was no significant difference between the conventional group and the treated group (P > 0.05); on the 14th days, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/HLA-DR(+) of the treated group got closed to healthy subject value, and got even higher than those of conventional group (P < 0.05); CD(8)(+) got close to that of healthy subjects, while obviously lower than that of conventional group (P < 0.05). CONCLUSION: After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.