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OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.
Subject(s)
Humans , China , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Molecular Docking Simulation , Myocardial Infarction/drug therapy , Network PharmacologyABSTRACT
Surgery is the standard treatment for early resectable non-small cell lung cancer (NSCLC), but the recurrence rate is high. There is no effective cure for this. Immunological checkpoint inhibitors have altered the therapeutic model of patients with advanced gene therapy for advanced NSCLC, presenting new hope for early immunotherapy of NSCLC. Immunological checkpoint inhibitors have altered the therapeutic model of patients with driving gene-negative NSCLC patients, presenting new hope for early immunotherapy of NSCLC. Based on the analysis of the status of early NSCLC adjuvant therapy, the clinical study of immunological checkpoint inhibitors as a new adjuvant/adjuvant therapy in early operable NSCLC was explored in this paper.
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A method for determining dipropofol in the plasma of Beagle dogs was established by HPLC-MS/MS. We also studied the pharmacokinetic characteristics of two different forms of crystal tablets of dipropofol in Beagle dogs. All animal experiments were approved by the Animal Experimental Management, Welfare and Ethics Committee of Pharmacology Evaluation Research Center, Shanghai Institute of Pharmaceutical Industry. The results indicate that the maximum plasma concentration (Cmax) of dipropofol was 69.02 ± 20.16 μg·L-1 after 20 mg·kg-1 crystal form Ⅰ tablet taken orally, and the AUC0-t was 160.49 ± 55.26 μg·L-1·h. After 20 mg·kg-1 crystal form Ⅱ tablet taken, the Cmax of dipropofol was 92.58 ± 60.26 μg·L-1, and the AUC0-t was 243.59 ± 148.36 μg·L-1·h. The AUC0-t and Cmax of crystal form Ⅱ were significantly different from that of crystal form Ⅰ (P<0.05). Crystal form Ⅱ was the dominant crystal form. The results suggest that we should control crystal form during the development of dipropofol oral tablets.
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OBJECTIVE@#To investigate cognitive dysfunction in patients with carotid artery stenosis (CAS) and potential risk factors related to cognitive-especially memory-dysfunction.@*METHODS@#Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale (WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion (CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment.@*RESULTS@#Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males (P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower (P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test (P = 0.024), and their WMS scores were significantly lower (P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction (MMSE, P = 0.047, memory quotient score, P = 0.018).@*CONCLUSION@#A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.
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Adult , Aged , Female , Humans , Male , Middle Aged , Carotid Stenosis , China , Epidemiology , Cognition , Cognitive Dysfunction , Epidemiology , Psychology , Cohort Studies , Cross-Sectional Studies , Memory , Neuropsychological Tests , Risk FactorsABSTRACT
Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect.Nevertheless,the mechanism is not completely identified.This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats.The liver fibrosis model was made by the subcutaneous injection of CCl4.The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer.Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry.Expression levels of TGF-β1,Smad2/3,phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis.Results showed that melatonin suppressed CC14-induced liver fibrosis,along with an improvement in histological changes,significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver.Melatonin improved liver function indicated by decreased serum ALT and AST activities.In addition,melatonin exerted its anti-oxidant effects,as supported by decreased MDA levels and increased GPx activities in liver.Furthermore,melatonin inhibited TGF-β1/Smad pathway,as evidenced by decreased TGF-β1,Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver.In conclusion,melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway.It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.
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Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect.Nevertheless,the mechanism is not completely identified.This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats.The liver fibrosis model was made by the subcutaneous injection of CCl4.The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer.Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry.Expression levels of TGF-β1,Smad2/3,phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis.Results showed that melatonin suppressed CC14-induced liver fibrosis,along with an improvement in histological changes,significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver.Melatonin improved liver function indicated by decreased serum ALT and AST activities.In addition,melatonin exerted its anti-oxidant effects,as supported by decreased MDA levels and increased GPx activities in liver.Furthermore,melatonin inhibited TGF-β1/Smad pathway,as evidenced by decreased TGF-β1,Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver.In conclusion,melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway.It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.
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Objective To analyze the distribution of traditional Chinese medicine(TCM)syndromes in patients with acute pulmonary embolism(APE)and to summarize the medication rule,so as to supply evidence for the clinical diagnosis and treatment of APE. Methods A retrospective study was carried out in the APE inpatients admitted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine in recent 4 years. The general data, clinical manifestations at the attack of APE, TCM syndromes, treatment and prognosis of the included patients were input into the database for the analysis of TCM syndrome distribution and medication rule. Results A total of 139 cases of APE patients were included into the study. The main manifestations at admission were dominated by dyspnea and chest pain, pale or darkish red tongue, string pulse and deep pulse. TCM syndromes were divided into three types, phlegm turbidity syndrome, blood stasis syndrome and yang collapse syndrome. The blood stasis syndrome accounted for the largest proportion and then came the phlegm turbidity syndrome. In various age groups,the 3 syndrome types accounted the highest proportion in the age group of 51-70 years old, and accounted higher proportion in the age group over 71 years old. Blood stasis syndrome was frequently seen in the age group below 30 years old. Xuefu Zhuyu Decoction and Tao Hong Siwu Decoction were frequently used for the treatment of blood stasis syndrome, Gualou Xiebai Banxia Decoction and Wendan Decoction were often used for the phlegm turbidity syndrome, and Shenfu Injection was often used for yang collapse syndrome. Conclusion APE occurs in various clinical departments, and phlegm turbidity syndrome, blood stasis syndrome and yang collapse syndrome are the main syndrome patterns of APE. Blood stasis syndrome accounts the largest proportion in clinic. Therefore, Xuefu Zhuyu Decoction and Tao Hong Siwu Decoction, Gualou Xiebai Banxia Decoction and Wendan Decoction should be used as the indicated recipes for APE to activate blood and remove stasis, strengthen spleen and resolve phlegm.
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Objective To observe thecurative effect of moxibustion with plum blossom and ginger combined with auricular ap-plication pressure on insomnia by liver disease.Methods 80 patients with liver diseases-induced insomnia were randomly divided in-to two groups:the treatment group and control group,40 cases in each group.The treatment group was treated with the plum blossom and ginger moxibustion combined with auricular application pressure and the control group with auricular application pressure only.The two groups were compared in terms of curative effect two weeks after treatment. Result The curative effect of treatment group was signifi-cantly better than that of the control group (P＜0.05).Conclusion Plum blossom and ginger moxibustion combined with auricular ap-plication pressure is effective in the treatment of liver diseases-induced insomniais.
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BACKGROUND:A large number of clinical trials have found that the number of bone marrow stem cels at the femoral neck and proximal femur in patients with osteonecrosis of the femoral head is significantly reduced, accompanied by decreased activity, which causes a significant decrease in osteogenic capacity that the necrotic bone cannot be effectively repaired after absorption, leading to the colapse of the femoral head. OBJECTIVE:To probe into the early clinical efficacy of autologous peripheral blood mononuclear cel transplantation with porous core decompression for treatment of avascular necrosis of the femoral head. METHODS:Forty-five patients with avascular necrosis of the femoral head (49 hips) were enroled in this study, and underwent autologous peripheral blood mononuclear cel transplantation with porous core decompression. After treatment, pain scores, Harris hip score, scores on the satisfaction of patients were evaluated, as wel as X-ray, CT and MRI examinations. RESULTS AND CONCLUSION:Al the patients received a folow-up visit of 11-14 months, averagely (12.5±0.6) months. During the folow-up, there were no complications and serious adverse reactions. Postoperative pain scores and Harris scores were both improved significantly compared with preoperative ones (P < 0.05). At 12 months after treatment, the excelent satisfaction rate was up to 92%. Patient’s MRI low signal region accounting for a percentage of the volume of the femoral head was decreased from (40.1±7.34)% preoperatively to (20.23±5.4)% at 6 months postoperatively, and there was a significant difference (P < 0.05). These findings indicate that autologous peripheral blood mononuclear cel transplantation with porous core decompression for treatment of avascular necrosis of the femoral head has significantly clinical effects at early stage, which can obviously reduce joint pain, improve and restore hip joint function, and delay progression of disease.
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<p><b>OBJECTIVE</b>To construct plant expression pCAMBIA1301-PMI by substituting PMI for hygromycin resistance gene in pCAMBIA1301 and obtain transgenic Salvia miltiorrhiza f. alba using PMI-mannose selection system.</p><p><b>METHOD</b>The 6-phosphomannose isomerase gene (PMI) of Escherichia coli was amplified by PCR. Sequence analysis showed that it shared 100% amino acids identities with the sequences of PMI genes isolates reported in the NCBI. Based on pCAMBIA1305, the plant expression pCAMBIA1305-PMI was constructed successfully by substituting PMI for hygromycin resistance gene in pCAMBIA1305. pCAMBIA1305-PMI was transformed into Agrobacterium tumefaciens LBA4404, and then the leaves of S. miltiorrhiza f. alba were inoculated in LBA4404 with pCAMBIA1305-PMI.</p><p><b>RESULT</b>Plant expression pCAMBIA1301-PMI was successfully constructed and the leaves of S. miltiorrhiza f. alba inoculated in LBA4404 with pCAMBIA1305-PMI were selected on medium supplemented with a combination of 20 g x L(-1) mannose and 10 g x L(-1) sucrose as a carbon source. The transformation efficiency rate was 23.7%.</p><p><b>CONCLUSION</b>Genetic transformation was confirmed by PCR, indicating that a new method for obtaining transgenic S. miltiorrhiza f. alba plants was developed using PMI-mannose selection system.</p>
Subject(s)
Anti-Bacterial Agents , Pharmacology , Biomarkers , Cinnamates , Pharmacology , Escherichia coli , Genetics , Escherichia coli Proteins , Genetics , Metabolism , Gene Expression , Genetic Vectors , Genetics , Metabolism , Hygromycin B , Pharmacology , Mannose-6-Phosphate Isomerase , Genetics , Metabolism , Plants, Genetically Modified , Genetics , Metabolism , Salvia miltiorrhiza , Genetics , Metabolism , Transformation, GeneticABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy.</p><p><b>METHODS</b>Seventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients.</p><p><b>RESULTS</b>The median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores ≥ 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment ≥ 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed.</p><p><b>CONCLUSION</b>Chinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Aromatase Inhibitors , Therapeutic Uses , Bone Density Conservation Agents , Therapeutic Uses , Bone Neoplasms , Drug Therapy , Brain Neoplasms , Drug Therapy , Breast Neoplasms , Drug Therapy , Pathology , Radiotherapy , General Surgery , Carcinoma, Ductal, Breast , Drug Therapy , Pathology , Radiotherapy , General Surgery , Chemotherapy, Adjuvant , Diphosphonates , Therapeutic Uses , Drugs, Chinese Herbal , Therapeutic Uses , Follow-Up Studies , Imidazoles , Therapeutic Uses , Lung Neoplasms , Drug Therapy , Medicine, Chinese Traditional , Neoplasm Staging , Nitriles , Therapeutic Uses , Radiotherapy, Adjuvant , Radiotherapy, Conformal , Methods , Remission Induction , Retrospective Studies , Survival Rate , Treatment Failure , Triazoles , Therapeutic UsesABSTRACT
A new class of dendrimer polylysine poly(ethylene glycol)-lipid was designed and synthesized. The cationic polymer liposomes were prepared by the lipid film-extrusion and post-insertion two methods with these dendrimer polylysine poly(ethylene glycol)-lipid and other lipids. The structural properties of obtained cationic polymer liposomes were studied by laser light scattering and fluorescence spectrometer. It was demonstrated that the nano sized liposomes with different density of surface cationic charges can be prepared by either lipid film-extrusion or post-insertion methods, but post-insertion process did not affect drug loading, did not influence drug loading capacity and did not induce liposomal morphology and particle size. The density of positive charge does not affect the size and distribution of different liposomes size and distribution. It was the better choice for manufacture because post-insertion method did not cause early release of drug and size changes. Cell binding experiments show that cationic polymer liposomes, especially dendrimer polymer liposomes had higher local charge density, and therefore have dramatic non specific cell targeting ability.
Subject(s)
Animals , Cricetinae , Biological Transport , Cations , Cell Line , Drug Delivery Systems , Kinetics , Lipids , Chemistry , Pharmacokinetics , Liposomes , Chemistry , Pharmacokinetics , Molecular Structure , Nanoparticles , Particle Size , Polyethylene Glycols , Chemistry , Pharmacokinetics , Polymers , Chemistry , PharmacokineticsABSTRACT
The poly(ethylene glycol)-lipid derivatives were synthesized for constructing pH-sensitive liposomes. The polyethylene glycol polymer MePEG2000-NH2 and phospholipids POPA were connected by phosphorus-amide linkage. The poly(ethylene glycol)-lipid derivatives acidic sensitive liposomes were prepared. Factor effects on polymer insertion into liposomes were evaluated and the pH-sensitivity of the polymer associated liposomes were studied by calcein release assay. The poly(ethylene glycol)-lipid derivatives acidic sensitive liposomes were prepared successfully by the extruding linkage device. The liposomes constructing by poly(ethylene glycol)-lipid derivatives was stable at pH 6.5-7.5, the stability was closely related to phospholipid types and cholesterol content of the preparation of liposomes. At pH 5.0 occurred when divulging fluorescence occurred obviously, the leakage rate and the strength was with a positive correlation between time of in the acidic environment and intensity of acid. The acidic sensitive liposomes prepared by poly(ethylene glycol)-lipid derivatives were developed as a potential pH sensitive delivery system.
Subject(s)
Cholesterol , Chemistry , Drug Delivery Systems , Methods , Drug Stability , Hydrogen-Ion Concentration , Liposomes , Chemistry , Particle Size , Phospholipids , Chemistry , Polyethylene Glycols , Chemistry , PolymersABSTRACT
The fusion between liposome-liposome, liposome-biomembarnes induced by acid-sensitive polymers has been systematically investigated. The polymer-liposomes were constructed by post-insertion method with the poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives. The liposomal fusion was studied by use of fluorescence resonance energy transfer assay, particle size, fluorescent-photometer. The results indicated that the poly (2-ethylacrylic acid)-liposomes has very strong acidic induced fusion capability. Under acidic conditions, acid-sensitive polymer liposomes fused each other, the fusion closely related to the molecular weight of acid sensitivity polymer on the surface of liposomes. The acidic fusion of polymer-liposomes was dependent upon the lipids composition, the degree of fusion was reversely related to the cholesterol contents. Acid-en ci-nsitive polymer liposomes fused with erythrocyte ghosts. The liposomal fusion induced by acid-sensitive polymer associated with the increase of membrane permeability. The good acid-sensitivity of PEAA has been further demonstrated by membrane fusion in current experiments, and the liposomes prepared with lipid anchored-poly (2-ethylacrylic acid) were developeds s a potential pH sensitive delivery system.
Subject(s)
Humans , Acrylates , Chemistry , Alkylation , Drug Carriers , Drug Delivery Systems , Erythrocyte Membrane , Metabolism , Hydrogen-Ion Concentration , Lipids , Chemistry , Liposomes , Chemistry , Membrane Fusion , Molecular Weight , Particle Size , Polymers , TemperatureABSTRACT
The temperature-sensitive liposomes were constructed by poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives that were synthesized for partially modification of carboxylic groups. The thermal characteristics of liposomes were investigated by using fluorescent indicator, particle size device and fluorescence spectrophotometer system. The results showed that the liposome made of fatty amine-modified poly(2-ethylacrylate) had a marked thermal sensitive release of drugs, which is correlated with the structure of molecular of polymer and the initial ratio of composition of phospholipid. The PEAA-associated-liposomes were also shown pH-sensitive drug release under acidic condition. The poly (2-ethylacrylate) for the preparation of medium-induced thermal liposomes in vitro experiments showed a good thermal characteristics and the methods of preparing temperature-sensitive liposomes were convenient and stability.
Subject(s)
Acrylates , Chemistry , Cholesterol , Chemistry , Drug Carriers , Drug Delivery Systems , Methods , Fluoresceins , Hydrogen-Ion Concentration , Liposomes , Chemistry , Particle Size , Phosphatidylcholines , Chemistry , Polymers , Chemistry , TemperatureABSTRACT
Poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives were synthesized for constructing pH-sensitive liposomes by partially modification of carboxylic groups of PEAA with chemical reaction. These lipid derivatives of PEAA were synthesized by partially modification of carboxylic groups of PEAA with alkylamines. The acid-sensitive polymer associated liposomes were obtained by the method of polymer self-insertion in aqueous solutions through inserting hydrophobic lipid anchors of the polymer PEAA derivatives into the outer layer of vesicles. Factor effects on polymer insertion into liposomes were evaluated and the pH-sensitivity of the polymer associated liposomes was studied by calcein release assay. The PEAA-assoeiated-liposomes were prepared successfully by the methods of self-insertion. The PEAA-associated-liposomes are shown to be stable at neutral pH. (1) There was no correlate of anchor density of PEAA with length of the alkyl chain, but was positively correlated with the degree of PEAA modification. (2) Polymer insertion increased with initial ratio of polymer to lipid. (3) Unerting hydrophobic lipidr acidic conditions the associated polymer induces membrane disruption and fusion. (4) The PEAA-associated-liposomes shown pH-sensitive drug release property under acidic conditions. The anchored-poly (ethylacrylic acid) lipid derivatives can be useful in developing a potential pH sensitive drug delivery system.
Subject(s)
Animals , Acrylates , Pharmacokinetics , COS Cells , Chlorocebus aethiops , Drug Delivery Systems , Methods , Fluoresceins , Metabolism , Hydrogen-Ion Concentration , Liposomes , Chemistry , Pharmacokinetics , Particle Size , Polyunsaturated Alkamides , PharmacokineticsABSTRACT
BACKGROUND: There have been no reports available about the direct effect of beer on serum enzyme activity.OBJECTIVE: To observe the changes of the activity of various serum enzymes of the subjects in the in vivo and in vitro experiments after drinking bear.DESIGN: An observational controlled experiment.SETTING: The Institute of Basic Medicine of Taishan Medical College.PARTICIPANTS: The experiment was performed at the Institute of Basic Medicine of Taishan Medical College between March 2005 and April 2005.We selected 17 college students, aged 19 to 35 years, from Taishan Medical College, including undergraduate students and graduate students. In formed consents were obtained from the subjects before the experiment was conducted.METHODS: ① In vivo experiment: 3 mL of venous blood was collected from the subjects 3 hours after the ordinary diet as the control. Then, the subjects drank beer at an amount of 4 mL/kg according to their body mass immediately. 3 mL of blood was collected respectively 15, 30, 45, 60, 90,120, 80 minutes later to measure the changes of the activity of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, al kaline phosphatase, creatine kinase , lactate dehydrogenase, diastase and lipase. ② In vitro experiment: 17 fresh serum samples were added into two test tubes separately with 0.5 mL of serum in each tube. 20 μL of normal saline was added to the tube of the control and 20 μL of beer was added into the test tube. The direct effect of beer on the activity of various enzymes was observed.MAIN OUTCOME MEASURES: The changes of the activity of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, al kaline phosphatase, creatine kinase , lactate dehydrogenase, diastase and lipase of the serum on the in vivo and in vitro experiment .RESULTS: Totally 17 students were involved and all the students entered the stage of result analysis with no loss in the midway. ① In vivo experiment: Beer significantly decreased the activity of serum aspartate aminotransferase (418.08 ±58.68,383.41 ±63.01)nkat/L, significantly in creased the activity of serum alkaline phosphatase, (367 8.57±436.25,396 2.96±400.91)nkat/L (x2=19.00-20.00,P ＜ 0.01). The activity of other enzymes was all increased at different degrees. ② In vitro experiment: Beer inhibited the activity of various enzymes in vitro to a certain degree.CONCLUSION: Beer has some effect on enzyme activity in vivo and in vitro, thus affecting the body metabolism. Over drinking beer can affect health. In the routine detection of serum enzymes, attention should be given to avoid the interference caused by over drinking beer to make sure the experimental results are precise and reliable.
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<p><b>AIM</b>To study the biliary excretion of genistein and its metabolite at different doses in rats.</p><p><b>METHODS</b>Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography.</p><p><b>RESULTS</b>The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively.</p><p><b>CONCLUSION</b>The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.</p>
Subject(s)
Animals , Female , Male , Rats , Administration, Oral , Bile , Metabolism , Dose-Response Relationship, Drug , Genistein , Chemistry , Metabolism , Pharmacokinetics , Molecular Structure , Phytoestrogens , Metabolism , Pharmacokinetics , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Long-term excessive intake of beer might lead to change of intra-corporal tissue or activity of serum enzyme.OBJECTIVE: Observation on relations between intake of beer and fat synthesis of rats and activity of enzyme correlated with catabolism in rats.DESIGN: Matched observations randomly of animal experiments.SETTING: Basic Medical Institute of Taishan Medical College.MATERIALS: The experiments were completed in Basic Medical Institute of Taishan Medical College from December 2004 to February 2005. Totally 60 SD rats were selected and categorized into 6 groups with 10 rats in each group. The rats were perfused with 9 mL/kg, 18 mL/kg, 27 mL/kg, 36 mL/kg, and 45 mL/kg beer respectively according to their fat; The rats in control group were fed with water in stead of beer.METHODS: All rats in each groups were narcotized and executed after continuous feeding 1 week, biochemical analysis and enzyme assay were made respectively after blood samples were adopted, and liver, subcutaneous fat, mesentery fat tissue and gastrocnemius muscle were preserved.MAIN OUTCOME MEASURES: ① The level of fat, blood glucose, insulin and blood-lipid of rats in each group after feeding 1 week . ② The enzymatic activity of liver and fat tissue of rats in each group after feeding 1 week . ③ The activity of hormone sensitive lipase and lipoprotein lipase (LPL) of rats in each group after feeding 1 week.RESULTS: Totally 60 rats were channeled into result analysis without any loss. ① Comparison of the levels of fat and biochemical specifications of rats in each group after feeding 1 week: The contents of fat, serum free fatty acid (FFA), high-density of lipoprotein (LP) cholesterol, hepar triacylglycerol and liver cholesterol in beer 36 mL/kg group were higher than those in control groups (x2=19.44-20.01, P ＜ 0.01). ② Comparison of the levels of the enzymatic activity of liver and fat tissue of rats in each group after feeding 1 week: The activities of liver, subcutaneous fat, and liver microsome, I.e. Triacylglycerol alternation protein, phosphatidyl phosphohydrolase, malic enzyme, glucose-6-phasphate dehydrogenase (G6PD) of mesentery tissue in beer 36 mL/kg group were higher than those in control groups (x2=15.02-16.00, P ＜ 0.05). ③ The comparison on level of the activity of hormone sensitive lipase and lipoprotein lipase (LPL) of rats in each group after feeding 1 week: The activity of gastrocnemius muscle of hormone sensitive lipase in beer 36 mL/kg group were prominently lower than those of control groups (P ＜ 0.01), but the activity of lipoprotein lipase (LPL) (P ＜ 0.01) of subcutaneous fat were prominently higher than those in control groups (P ＜ 0.01). The activities of lipoprotein lipase (LPL)of mesentery fat tissue, subcutaneous fat and gastrocnemius muscle tissue in beer 36 mL/kg group were prominently higher than those in other beer groups and control groups (x2=19.00-20.00, P ＜ 0.01).CONCLUSION: The intake of a certain amount of beer (36 mL/kg) might promote the capability of liver in synthesis and the transport of triacylglycerol in rats. The acceleration of lipid synthesis and storage of fat tissue such as mesentery fat tissue and the increase of fat decomposition and mobilization in peripheral tissue such as muscular tissue and subcutaneous fat would finally lead to the increase of fat.
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<p><b>AIM</b>To study the pharmacokinetics of genistein at different doses in Beagle dogs.</p><p><b>METHODS</b>Suspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.</p><p><b>RESULTS</b>The plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.</p><p><b>CONCLUSION</b>Due to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.</p>