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Based on the idea of multi-target drug design, taking p-aminosalicylic acid (PAS) as the parent nucleus, the unreported target molecules TM1 and TM2 were designed with PAS, isonicotinic acid and fluoroquinolone as three structural units conjugated by different linkers. Sixteen target molecules were synthesized by multi-step reaction, and their activities against Mycobacterium tuberculosis and human pathogenic bacteria were evaluated. The results showed that the anti-tuberculosis activity of TM2a was stronger than those of the assayed fluoroquinolones, while TM1a was comparable to that of clinafloxacin, the most active compound of the positive control fluoroquinolones; TM1a showed the strongest inhibitory activity to all almost tested strains, TM1b and TM2a showed very strong inhibitory activity to most strains, and TM1h/2h had strong inhibitory activity to some strains; The inhibitory activities of TM1a/1h on Staphylococcus aureus ATCC14125 are much stronger than those of fluoroquinolones, which eminently deserves further study. The hemolysis test results showed that the highly active molecules TM1a and TM2a exhibited relative safety below the concentrations of 8 and 32 μg·mL-1, respectively. In this study, a new hybrid molecule of three molecular pharmacophores with PAS as the parent nucleus was synthesized for the first time, and some of which have highly strong antibacterial activity, which provides a new idea for the research and development of antibiotics.
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Objective To investigate the effects of milrinone on levels of inflammatory factors and liver and renal function after CPB in rheumatic heart disease patients for valve replacement.Methods From January 2014 to January 2016,80 patients received valve replacement in the Central Hospital of Chongqing Three Gorges were randomly divided into observation group and control group by block randomization grouping method,with 40 patients in each group.The patients in the observation group were pumped intravenously with milrinone 0.5μg · kg-1 · min-1 for 72h after surgery,while the patients in the control group were not pumped.The serum levels of IL-6,IL-8,IL-10,TNF-αwere detected by ELISA before operation and on 0d,1 d,3d,5d after operation,respectively.The levels of ALT,AST,Scr were also detected at the same time.Moreover,the time for operation,extracorporeal circulation,interruption,mechanical ventilation,ICU and hospital were also compared between the two groups.Results The levels of TNF-α,IL-6,IL-8 and IL-10 increased immediately after operation in both groups [control group:(14.97 ± 5.14)pg/mL,(52.45 ± 10.37) pg/mL,(34.10 ± 8.38) pg/mL,(32.27 ± 8.45) pg/mL;observation group:(16.05 ± 5.71) pg/mL,(54.39 ± 8.56) pg/mL,(33.80-7.69) pg/mL,(31.48 ± 5.94) pg/mL,t =-0.628,-0.644,0.116,0.342],and the peak values of TNF-α,IL-6 and IL-8 reached on the first day after operation in both two groups [control group:(52.07 ±10.18) pg/mL,(96.04 ±26.45) pg/mL,(91.14 ± 18.28)pg/mL,(48.10 ± 9.78) pg/mL;observation group:(50.37 ± 12.98) pg/mL,(93.66 ± 24.10) pg/mL,(83.16 ± 16.28) pg/mL,(46.68 ± 9.25) pg/mL,t =0.559,0.295,1.458,0.473],and the peak value of IL-10 reached on the 3rd day after operation (t =-3.577),the differences were statistically significant on the 3rd day after operation [control group:(36.03 ± 9.39)pg/mL,(59.56 ± 14.38) pg/mL,(53.91 ± 13.16) pg/mL,(85.55 ± 16.49) pg/mL;observation group:(36.70 ±4.33) pg/mL,(36.20 ± 3.85) pg/mL,(42.91 ± 7.30) pg/mL,(101.33 ± 10.81) pg/mL,t =-0.289,7.017,3.267,-3.577].The levels of ALT,AST and Scr increased immediately after operation in both groups [control group:(38.51 ±5.12) U/L,(40.23 ± 5.03) U/L,(62.27 ± 5.02) μmol/L;observation group:(39.20 ± 4.67) U/L,(39.6 ±4.94) U/L,(73.61 ± 4.04) μmol/L,t =0.114,0.243,0.630],there were tatistically significant difference between the two groups on the 5 th day after operation [control group:(61.45 ± 5.27) U/L,(54.20 ± 7.0) U/L,(86.45 ±9.01) μmol/L;observation group:(36.20 ± 3.85) U/L,(34.85 ± 7.12) U/L,(83.7 ± 11.07) μmol/L,t =11.231,9.224,5.647],and on the fifth day,the levels of ALT,AST and Scr in the observation group dropped to normal,while only the level of Scr in the control group dropped to normal.There were no statistically significant differences in the time of operation,extracorporeal circulation,interruption,mechanical ventilation between two groups (t =0.267,0.151,0.187,0.773,all P ＞ 0.05).However,there were statistically significant differences in the time of ICU and hospital [control group:(54.90 ± 16.84)h,(14.35 ± 3.01) d,observation group:(44.05 ±7.06)h,(10 ± 1.86)d,t =8.149,13.042,all P ＜ 0.05].Conclusion Milrinone can obviously improve the inflammatory reaction in surgical trauma tissues caused by IL-6,IL-8,IL-10,TNF-α,and can protect liver,renal tissue from injury,moreover,it can decrease the incidence of postoperative complications and the length of hospital stay.
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Objective To explore the pharmacokinetics of nimodipine in plasma of rats after intraocular administration.Methods Totally 135 SD rats were randomly divided into three groups according to drug administration routes:intraocular(io group),intravenous (iv group),and intragastric (ig group). The doses were 5.0 mg/kg for IO and IV groups and 10.0 mg/kg for IG group. The serum nimodipine level was analyzed by high performance liquid chromatography. The main pharmacokinetic parameters were calculated and compared.Results The pharmacokinetic parameters in io group were as follows:C:0.52 mg/ml;t:5.0 min;and AUC:21.10 mg/(ml·min). The main pharmacokinetic parameters in iv group were as follows:C:3.62 mg/ml;and AUC:52.58 mg/(ml·min). The main pharmacokinetic parameters in ig group were as follows:C:0.20 mg/ml;t:5.0 min;and AUC:5.98 mg/(ml·min).Conclusions Nimodipine is rapidly absorbed after io administration,and the ophthalmic formulation has a higher bioavailability than the oral solution. Therefore,the io route may help to improve the treatment effectiveness of cardiovascular diseases.
Subject(s)
Animals , Rats , Administration, Intravenous , Administration, Oral , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Nimodipine , Pharmacokinetics , Rats, Sprague-DawleyABSTRACT
Objective@#To investigate the effects of milrinone on levels of inflammatory factors and liver and renal function after CPB in rheumatic heart disease patients for valve replacement.@*Methods@#From January 2014 to January 2016, 80 patients received valve replacement in the Central Hospital of Chongqing Three Gorges were randomly divided into observation group and control group by block randomization grouping method, with 40 patients in each group.The patients in the observation group were pumped intravenously with milrinone 0.5μg·kg-1·min-1 for 72h after surgery, while the patients in the control group were not pumped.The serum levels of IL-6, IL-8, IL-10, TNF-α were detected by ELISA before operation and on 0d, 1d, 3d, 5d after operation, respectively.The levels of ALT, AST, Scr were also detected at the same time.Moreover, the time for operation, extracorporeal circulation, interruption, mechanical ventilation, ICU and hospital were also compared between the two groups.@*Results@#The levels of TNF-α, IL-6, IL-8 and IL-10 increased immediately after operation in both groups[control group: (14.97±5.14)pg/mL, (52.45±10.37)pg/mL, (34.10±8.38)pg/mL, (32.27±8.45)pg/mL; observation group: (16.05±5.71)pg/mL, (54.39±8.56)pg/mL, (33.80±7.69)pg/mL, (31.48±5.94)pg/mL, t=-0.628, -0.644, 0.116, 0.342], and the peak values of TNF-α, IL-6 and IL-8 reached on the first day after operation in both two groups[control group: (52.07±10.18)pg/mL, (96.04±26.45)pg/mL, (91.14±18.28)pg/mL, (48.10±9.78)pg/mL; observation group: (50.37±12.98)pg/mL, (93.66±24.10)pg/mL, (83.16±16.28)pg/mL, (46.68±9.25)pg/mL, t=0.559, 0.295, 1.458, 0.473], and the peak value of IL-10 reached on the 3rd day after operation(t=-3.577), the differences were statistically significant on the 3rd day after operation[control group: (36.03±9.39)pg/mL, (59.56±14.38)pg/mL, (53.91±13.16)pg/mL, (85.55±16.49)pg/mL; observation group: (36.70±4.33)pg/mL, (36.20±3.85)pg/mL, (42.91±7.30)pg/mL, (101.33±10.81)pg/mL, t=-0.289, 7.017, 3.267, -3.577]. The levels of ALT, AST and Scr increased immediately after operation in both groups[control group: (38.51±5.12)U/L, (40.23±5.03)U/L, (62.27±5.02)μmol/L; observation group: (39.20±4.67)U/L, (39.6±4.94)U/L, (73.61±4.04)μmol/L, t=0.114, 0.243, 0.630], there were tatistically significant difference between the two groups on the 5th day after operation[control group: (61.45±5.27)U/L, (54.20±7.0)U/L, (86.45±9.01)μmol/L; observation group: (36.20±3.85)U/L, (34.85±7.12)U/L, (83.7±11.07)μmol/L, t=11.231, 9.224, 5.647], and on the fifth day, the levels of ALT, AST and Scr in the observation group dropped to normal, while only the level of Scr in the control group dropped to normal.There were no statistically significant differences in the time of operation, extracorporeal circulation, interruption, mechanical ventilation between two groups (t=0.267, 0.151, 0.187, 0.773, all P>0.05). However, there were statistically significant differences in the time of ICU and hospital [control group: (54.90±16.84)h, (14.35±3.01)d, observation group: (44.05±7.06)h, (10±1.86)d, t=8.149, 13.042, all P<0.05].@*Conclusion@#Milrinone can obviously improve the inflammatory reaction in surgical trauma tissues caused by IL-6, IL-8, IL-10, TNF-α, and can protect liver, renal tissue from injury, moreover, it can decrease the incidence of postoperative complications and the length of hospital stay.
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Objective:To understand the basic situation of visible particles in Shengmai injection,and study the visible particles control and inspection for Shengmai injection. Methods: The samples of Shengmai injection were collected and the visible particles were checked by light inspection and light scattering,and the results were summarized and analyzed. The exogenous factors and endog-enous factors affecting the visible particles in Shengmai injection were investigated. Results:The positive inspection rate of visible par-ticles in Shengmai injection in market was low. Light,temperature and pH value had mild influence on the visible particles in Sheng-mai injection. Conclusion:The control measurement for the visible particles in Shengmai injection in every enterprise is effective,and the quality control is promising.
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To investigate the effect of jianpi-jiedu (JPJD) prescription-contained serum on colorectal cancer SW48 cell proliferation and the underlying mechanisms. Methods: Crude extract from JPJD was made by water extract method and the main components of crude extract from JPJD were analyzed by ultra-performance liquid phase high resolution time of flight mass spectrometry (UPLC-Q-TOF/MS). The low, medium, and high-concentration of JPJD-contained serum were prepared by the serum pharmacological method. The effect of serum containing JPJD on SW48 cell proliferation was determined by MTT assay. The cell cycle was detected by flow cytometric method. The protein levels of mammalian target of rapamycin (mTOR), phospho-mTOR, P-P53, and -P21, and the mRNA level of mTOR were examined by Western blot and RT-PCR, respectively. Results: Seven compounds including calycosin-7-glucoside, astragaloside, ginsenoside-Re, ginsenoside-Rb1, glycyrrhizinic acid, apigenin, atractylenolide-II were identified. MTT assays demonstrated that the SW48 cell proliferation was inhibited by medium and high concentration of JPJD-contained serum and the percentages of cells at G1 phase in SW48 cell cultured in the medium and high concentration of JPJD serum group were significantly higher than those in the control group (P<0.05). Meanwhile, the levels of mTOR mRNA and phospho-mTOR protein in the medium and high concentration of JPJD serum groups were substantially lower than those in the control group (P<0.05). Conversely, the expressions of phospho-P53 and P21 protein were significantly increased in the medium and high concentration of JPJD serum group compared with those in the control group. Conclusion: JPJD prescription-contained serum can inhibit SW48 cell proliferation, which may be related to mTOR-P53-P21 signaling pathways.
Subject(s)
Animals , Humans , Apigenin , Blotting, Western , Cell Cycle , Cell Division , Cell Proliferation , Genetics , Colorectal Neoplasms , Cyclin-Dependent Kinase Inhibitor p21 , Drugs, Chinese Herbal , Pharmacology , Flow Cytometry , Ginsenosides , Glycyrrhizic Acid , Lactones , Phosphorylation , Genetics , RNA, Messenger , Saponins , Sesquiterpenes , Signal Transduction , TOR Serine-Threonine Kinases , Triterpenes , Tumor Suppressor Protein p53ABSTRACT
To investigate the effect of the jianpi-jiedu formula (JPJD) on the expression of angiogenesis-relevant genes in colon cancer. Methods: Crude extract was obtained from JPJD by water extract method. The effect of JPJD crude extract on colon cancer cell proliferation capacity was determined by MTT assays. The IC50 value was calculated by GraphPad Prism5 software. Affymetrix gene expression profiling chip was used to detect significant differences in expressions of genes after JPJD intervention, and pathway enrichment analysis was performed to analyze the differentially expressed genes. Ingenuity Pathway Analysis software was applied to analyze differentially expressed genes relevant to tumor angiogenesis based on mammalian target of rapamycin (mTOR) signaling pathway and then the network diagram was built. Western blot was used to verify the protein levels of key genes related to tumor angiogenesis. Results: JPJD crud extract inhibited the proliferation capacity in colon cancer cells. The IC50 values in 24, 48, and 72 hours after treatment were 13.060, 9.646 and 8.448 mg/mL, respectively. The results of chip showed that 218 genes significantly upgraded, and 252 genes significantly downgraded after JPJD treatment. Most of the genes were related to the function of biosynthesis, metabolism, cell apoptosis, antigen extraction, angiogenesis and so on. There were 12 differentially expressed angiogenesis genes. IPA software analysis showed that the JPJD downregulated expression of sphingomyelin phosphodiesterase 3 (SMPD3), VEGF, vascular endothelial growth factor A (VEGFA), integrin subunit alpha 1 (ITGA1), cathepsin B (CTSB), and cathepsin S (CTSS) genes, while upregulated expressions of GAB2 and plasminogen activator, urokinase receptor (PLAUR) genes in the colorectal cancer cell. Western blot results demonstrated that JPJD obviously downregulated expressions of phospho-mTOR (P-mTOR), signal transducer and activator of transcription 3 (STAT3), hypoxia inducible factor-1α (HIF-1α), and VEGF proteins, while obviously upregulated the level of phospho-P53 (P-P53) protein. Conclusion: JPJD may inhibit colorectal tumor angiogenesis through regulation of the mTOR-HIF-1α-VEGF signal pathway.
Subject(s)
Animals , Humans , Blotting, Western , Cathepsin B , Metabolism , Cathepsins , Metabolism , Cell Line, Tumor , Colorectal Neoplasms , Genetics , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , Gene Expression Profiling , Methods , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Integrin alpha Chains , Metabolism , Neovascularization, Pathologic , Genetics , Receptors, Urokinase Plasminogen Activator , Metabolism , STAT3 Transcription Factor , Metabolism , Signal Transduction , Sphingomyelin Phosphodiesterase , Metabolism , TOR Serine-Threonine Kinases , Metabolism , Tumor Suppressor Protein p53 , Metabolism , Up-Regulation , Vascular Endothelial Growth Factor A , MetabolismABSTRACT
Objective:To improve the quality standard for Anweiyang capsules. Methods: TLC was used to identify Glycyrrhiza inflata Bat. Licochalcone A was determined by RP-HPLC. Using a C18 Column, the mobile phase consisted of acetonitrile-0. 1% phos-phoric acid(40:60), and the detection wavelength was at 376 nm. Results:The herb could be identified by TLC. For licochalcone A, the linear range was from 25. 563 to 1 533. 798 ng, and the average recovery was 99. 8%(n=9). Conclusion:The method is simple and accurate, which can be used to improve and control the quality of Anweiyang capsules.
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@#Pharmaceutical cocrystals are formed from the active pharmaceutical ingredients and cocrystal formers through hydrogen bonding or other noncovalent bonds, which have attracted much attention in pharmaceutical field in recent years. From the analysis of patent application situation, patent applicant, legal status, and patent application techniques, guiding directions for the future research and development of the pharmaceutical cocrystals are proposed in this article.
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Objective:To develop a method for determining deoxynivalenol in four kinds of traditional Chinese herbal medicines. Methods:After being extracted by water, purified by an immunoaffinity column, deoxynivalenol was analyzed by LC-MS-MS. Results:The calibration curve was linear within the range of 2-50 ng·ml-1 for deoxynivalenol. The recovery was 68. 7%-88. 3%. Conclusion:The method is simple, sensitive and accurate in the determination of deoxynivalenol in Semen Ziziphi Spinosae, Semen Sojae Praepara-tum, Semen Coicis and Fructus Psoraleae.
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BACKGROUND:The nature of graft rejective reaction is the antigen immunological reaction of recipient’s immune system in response to donor’s graft. OBJECTIVE:To observe the effect of chemical extraction on the immunogenicity of acellular peripheral urethral isografts. METHODS:Twenty urethras of Sprague-Dawley rats, 1 cm long, were included in this study. Ten urethras were treated with chemical acellular method to remove immunogenic component, thus prepared into acellular urethras;another ten urethras were fresh, without any acellular treatment. Acellular urethras were implanted into the back of ten Wistar rats, while fresh urethras into another ten rats. 6 weeks after transplantation, the specimens were harvested for gross and histological observations. RESULTS AND CONCLUSION:After acellular or fresh urethras were implanted into the rats, no autotomy was observed, the incision healed wel , the diet and activities of the rat were normal, and no ulcer formation was found. At 6 weeks, tissue membrane formed around the acellular urethra, while no formation was visible around fresh urethra by gross observation. Hematoxylin-eosin staining showed that, acellular urethras were gradual y absorbed and replaced by smooth muscular tissue. And unequal blood vessels grew in the acellular urethra, even formed blood sinusoid. In the control group, the urethras were not absorbed and no blood vessels were grown. The acellular urethras can gradual y form normal urethra in rats, indicating that the acellular urethral autograft has a lower antigenicity and can replace the cavernous body of normal urethra.
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AIM:To bring forward a method of determining aflatoxin G_2、G_1、B_2、B_1 in six kinds of traditional Chinese drugs by HPLC.METHODS:After being extracted by 70% methanol,purified by immunoaffinity column,aflatoxins were analysed by HPLC with fluorescence detection.RESULTS:Aflatoxin G_2、B_2 showed a good linear relationship at a range of 1.5-60pg,and Aflatoxin G_1、B_1 at a range of 5-200 pg,r＞0.999 9.The recovery was between 60%-120%.CONCLUSION:The method is simple,accurate and can be used to determine aflatoxin G_2、G_1、B_2、B_1 in Naoliqing Pill,Renshen Yangrong Pill,Rensen Jiapi Pill,Sanqi Tablet,Jinshuibao Capsule and Bailine Capsule.
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<p><b>OBJECTIVE</b>To observe the clinical effect of post-extension pulling massage in treating lumbar disc herniation.</p><p><b>METHODS</b>From January 2008 to December 2008, 61 patients with lumbar disc herniation, 34 males and 27 females, ranging in age from 17 to 67 years with an average of 42.6 years, were treated with post-extension pulling massage after continued traction for 30 minutes (on alternate days one time, 3 times as a course of treatment). There was bulging type in 9 cases, hernia type in 22, free type in 30. After a course of treatment, the clinical effects were evaluated according to standard of Macnab, the items included pain, lumbar activity, normal work and life of patients.</p><p><b>RESULTS</b>All patients were followed up from 1 to 9 months with an average of 4.6 months. After treatment, the symptoms and signs of patients had obviously improved in above aspects. According to standard of Macnab, 48 cases got excellent result, 10 good, 2 fair, 1 poor.</p><p><b>CONCLUSION</b>The post-extension pulling massage in treating lumbar disc herniation can obtain satisfactory results, which have localized site of action, small compression for vertebral body and can reduce accidental injury.</p>
Subject(s)
Female , Humans , Male , Diskectomy , Intervertebral Disc Displacement , Therapeutics , Lumbar Vertebrae , Pathology , Lumbosacral Region , Pathology , Massage , Methods , Spine , Traction , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between PPAR coactivator 1 (PGC-1), nuclear respiratory factor (NRF), mitochondrial transcription factor A (mtTFA) expressions of vascular smooth muscle cells (VSMC) and development of atherosclerosis in a rabbit model.</p><p><b>METHODS</b>Atherosclerotic model was established by feeding the rabbits with high-fat diet for 4, 8 and 12 weeks (n = 10 each). Another 8 rabbits fed with normal diet served as normal controls. Intima-media ratio, mRNA and protein expressions of PGC-1, NRF, mtTFA and SMemb, a marker for synthetic VSMC, were detected on aorta specimens.</p><p><b>RESULTS</b>With the blood lipid increased, the intima-media ratio rose from (0.031 +/- 0.010) microm up to (0.814 +/- 0.258) microm during 12 weeks. Increasing SMemb means that synthetic VSMC grew more and more. The expressions of PGC-1 became significant after 4 weeks (P < 0.01), while that of NRF-1 and mtTFA rose significantly after 8 weeks (P < 0.01).</p><p><b>CONCLUSIONS</b>The PGC-NRF-mtTFA pathway might play a critical role in VSMC proliferation and development of atherosclerosis.</p>
Subject(s)
Animals , Female , Male , Rabbits , Atherosclerosis , Blood , Metabolism , Pathology , DNA-Binding Proteins , Metabolism , Disease Models, Animal , Lipids , Blood , Mitochondrial Proteins , Metabolism , Muscle, Smooth, Vascular , Metabolism , Nuclear Respiratory Factor 1 , Metabolism , Trans-Activators , Metabolism , Transcription Factors , MetabolismABSTRACT
0.999 9.The recovery was between 60%-120%.CONCLUSION:The method is simple,accurate and can be used to determine aflatoxin G2、G1、B2、B1 in Naoliqing Pill,Renshen Yangrong Pill,Rensen Jiapi Pill,Sanqi Tablet,Jinshuibao Capsule and Bailine Capsule.