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This tutorial defines the concepts of disease progression in the context of clinical pharmacology. Disease progression describes the natural history of disease, such as pain, or biomarker of drug response, such as blood pressure. The action of a drug, such as inhibiting an enzyme or activating a receptor, leads to a change in disease status over time. Two main types of drug response can be defined based on the pattern of the time course of disease status. The most common is a symptomatic effect equivalent to a shift up or down of the natural history curve. Less common but quite clinically important is a disease-modifying effect equivalent to a change in the rate of disease progression.
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Blood Pressure , Disease Progression , Natural History , Pharmacology, ClinicalABSTRACT
This tutorial defines the principles of the concentration - effect relationship which are the basis of pharmacodynamics. The two key parameters of pharmacodynamics are the maximum response (Emax) and the concentration producing 50% of Emax (C₅₀). The time course of effect is illustrated under the assumption that drug effects are immediately related to concentration in the central compartment e.g. plasma. The related idea of duration of drug action and its relationship to dose is shown to have a simple relationship with drug half-life.
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Half-Life , PlasmaABSTRACT
O Jatobá (Hymenaea courbaril L.) possui um amplo histórico de utilização, seus frutos são compostos por óleos essenciais, taninos, substâncias amargas, matérias resinosas e pécticas, amido e açúcares, O objetivo deste estudo foi avaliar a atividade antimicrobiana e moduladora do óleo essencial extraído da casca de frutos da Hymenaea courbaril L, (OEHc) sobre cepas de S, aureus oxacilina sensíveis (OSSA) de referência, Para a avaliação da atividade antimicrobiana foram determinadas as Concentrações Inibitória (CIM) e Letal Mínimas (CLM) do OEHc e o efeito do tempo de exposição a concentrações do OEHc, o efeito modulador do OEHc sobre antibióticos de uso clínico foi avaliado pelo teste de difusão em ágar modificado, OEHc inibiu o crescimento das cepas de S, aureus ATCC 6538P (CIM = CLM = 0,28% v/v) e S, aureus ATCC 14458 (CIM = 0,28% v/v, CLM = 0,56% v/v), A CLM do OEHc foi capaz de inviabilizar as cepas OSSA testadas em 8 horas (S, aureus ATCC 6538P) e 24 horas (S, aureus ATCC 14458) e a CIM inibiu o crescimento de S, aureus ATCC 14458 até 48h de exposição, A ação moduladora do OEHc na atividade de antibióticos de uso clínico variou com o ATM e com a cepa testada, Os resultados encontrados mostram que o OEHc possui uma boa atividade antimicrobiana sobre a espécie Gram-positivo S, aureus, revelando seu efeito modulador sinérgico quando associado a antibióticos de uso clínico, demonstrando ser o OEHc um forte candidato para o desenvolvimento de fármacos com atividade antimicrobiana...
Jatobá (Hymenaea courbaril L.) has an extensive history of use, its fruits are composed of essential oils, tannins, bitter substances, resinous and pectic materials, starch and sugars. The objective of this study was to evaluate antimicrobial activity and effect of essential oil extracted from the rind of fruits of Hymenaea courbaril l. (OEHc) about reference strains of S. aureus oxacillin susceptible (OSSA). For the evaluation of antimicrobial activity were determined Inhibitory (MIC) and Lethal (CLM) Minimum Concentrations from OEHc and the effect of time of exposure to concentrations of OEHc, OEHc modulator effect on antibiotics of clinical use was assessed by modified agar diffusion test. OEHc inhibited the growth of S. aureus strains ATCC 6538P (CIM = CLM = 0,28% v/v) and S. aureus ATCC 14458 (CIM = 0,28% v/v; CLM = 0,56% v/v). The CLM from OEHc was able to derail the OSSA strains tested in 8 hours (S. aureus ATCC 6538P) and 24 hours (S. aureus ATCC 14458) and the CIM inhibited the growth of S. aureus ATCC 14458 until 48 hours of exposure. The modulatory action of the antibiotic activity of OEHc clinical use ranged with the ATM and with the strain tested. The results show that the OEHc has a good antimicrobial activity on the species Gram-positive S. aureus, revealing its synergistic modulator effect when associated with antibiotics of clinical use, demonstrating the OEHc a strong candidate for the development of drugs with antimicrobial activity...
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Humans , Drug Synergism , Hymenaea/microbiology , Oils, Volatile , Microbial Sensitivity Tests , Plants, MedicinalABSTRACT
Objective: To observe effects of Yuzhang Decoction on in vitro proliferation of bone marrow CD_(34) cells in the patient of aplastic anemia (CAA) and its mechanism. Methods: To adopt monoclone antibody-immune magnetic beads separation system (MACS) to separate and purify CD_(34) cells in bone marrow of the patient of CAA, and make cell culture, applying ~3H-TdR incorporation to detect effect of Yuzhang Decoction on proliferation of CD_(34) cells of bone marrow. Results: CD_(34) cells of bone marrow showed concentration-dependent proliferation in the Yuzhang Decoction group with significantly differences (P
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In order to study on the theory of " phlegm and blood stasis having same source" and effects of drugs for resolving phlegm on blood rheology, effects of Ban Xia, Gua Lou, Zhe Bei Mu and Shi Chang Pu on whole blood viscosity, erythrocyte deformation index and plasma fibrinogen content in normal rats. Results indicated that the drugs.for resolving phlegm had functions of decreasing whole blood viscosity, inhibiting hemoagglutination (except Gua Lou) and increasing capability of erythrocyte deformation; at high shearing rate, Shi Chang Pu and Zhe Bei Mu could slightly increase whole blood viscosity: Shi Chang Pu increased slightly plasma fibrinogen content. It is suggested that resolving phlegm also can removing blood stasis, and the mechanism of the drug for resolving phlegm in decreasing blood viscosity is related with decrease of blood lipids and anti - peroxidation of lipids.
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The experiment was conducted on the actions of 5 kinds of reagents on HL - 60 cellular wither, viz. Yisuiling chloroform extract, rabbit serum chloroform extract, rabbit liver paste chloroform extract, Etoposide, and normal rabbit serum. Results revealed that after fluid incubation for a short period, the HL-60 cultured cells showed no wither in the former 4 groups under microscope and flowing cytometer. Among them, action was strongest in rabbit liver paste of Yisuiling extract group, similar to the positive control of Etoposide. Followed by rabbit serum, and the action was weak in Yisuiling chloroform extract. There was no obvious action of induced wither by normal rabbit serum. The mechanism of induced wither is still under investigation.
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By counting the amount of microbes inoculation of superficial fungus and MIC determination, 10 kinds of herbs distributed in China were observed for their bacteriostatic actions on 8 kinds of common superficial fungal infections. Among them, 5% water extracts from Cortex Moutan Radicis, Herba Artemisia, Cortex Dictamni Radicis, Cortex Fraxini Rhizoma Belamcandae and Radix Notopterigii, their average MIC were 11. 88%, indicating that they can be applied as wide - spectrum antifungal herbs for superficial mycotic infection.
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By applying advanced technique such as cytological CT the action of 926, a Chinese drug, on ascitis cervical cancer cells was observed. Results revealed that it destroys the DNA and RNA of cancer cell, prevent it from synthesis of nucleic acid and cellular proliferation. These has upgraded the experimental research to a new level.
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Objective:To observe effects of Fuzheng Huoxue Recipe on blood growth hormone (GH) and insulin growth factor(IGF-1) in chronic renal failure(CRF) rats.Methods:Platt method was adopted to make 5/6 kidney excision CRF model rat,and the rats were divided into model group,Huangqi group,Enalapril group,Danshen group,Fuzheng Huoxue Recipe group and normal control group according to the blood creatinine level after modeling.Effects of Fuzheng Huoxue Recipe on GH and IGF-1 levels in CRF rats with large quantity of urinal protein were investigated.Results:GH and IGF-1 levels in the model control group were significantly higher than that in normal control group,and after treatment of Fuzheng Huoxue Recipe,blood GH and IGF-1 levels were significantly decreased.Conclusion:Fuzheng Huoxue Recipe can decrease blood GH and IGF-1 levels in CRF rats,and can delay advances of CRF.
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Objective:To study on effect of Danshao Huaxian Capsule on proliferation of activated hepatic stellate cells(HSCs)in vivo and in vitro.Methods:(1)In vitro experiment:57 male Wistar rats were divided into a normal group,a model group and a treatment group.The rats of model group and treatment group were made hepatic fibrosis model with complex stimulation of CCl_4,drinking alcohol,high lipids and low protein diet for 8 weeks.The treatment group were treated for 8 weeks with intragastric perfusion of Danshao Huaxian Capsule,1g/kg.At the end of experiment,a part of the rats were used for detection of hepatic functions and hepatic fibrosis degrees,and another part of the rats were used to separate HSCs.Cell cycle percentage was detected with flow cytometry.(2)In vivo experiment:prepare Danshao Huaxian Capsule serum of the rat;separate cultured HSCs of the rat and divide into calf serum group,normal rat serum group and Danshao Huaxian Capsule serum group.5%,10% and 20% of the above serum was respectively added into the cultured HSCs.Primary HSCs proliferation was detected with MTT method.Results:(1)In vitro experiment:The hepatic function,hepatic fibrosis level and HSCs proliferation reduced significantly.(2)In vivo experiment: Danshao Huaxian Capstde serum group could significantly inhibit proliferation of HSCs as compared with calf serum group and normal rat serum group at the same content.The action showed dose-dependence.Conclusion:Danshao Huaxian Capsule can obviously inhibit proliferation of HSCs in vivo and in vitro.
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Objective:To observe effect of Xiaoyu Zhixue Tablets on expression of platelet membrane glucoprotein in the patient of hemorrhagic thrombopathy and probe into the mechanism of the therapy.Methods:148 cases of hemorrhagic thrombopathy were randomly divided into a Chinese drug group(n=98)treated by Xiaoyu Zhixue Tablets,and a Western medicine group(n=50) treated by adrenosem,vitamine C,K,P.They were treated for 6 months.After treatment the therapeutic effect of hemostasis and the recovery rate of platelet aggregation in the two group were observed and analyzed.Before and after treatment expressions of platelet membrane glucoproteins GP Ⅰ b/Ⅸ,GP Ⅱ b/Ⅲa,GP Ⅰ b,GP Ⅱ b,GP Ⅲ a and p-selectin expression were detected with flow cytometry in the two groups and in 34 healthy persons(normal group).Results:The total effecive rate of hemostasis was 89. 8% in the Chinese drug group and 54.0% in the Western medicine group,and the recovery rate of platelet aggegation was 72.4% in the Chinese drug group and 4.0% in the Western medicine group,with significant differences(both P0.05).Conclusion:Xiaoyu Zhixue Tablets can up-regulate platelet membrane glucoproteins GP Ⅰ b/Ⅸ,GP Ⅱ b/Ⅲ a,GP Ⅰ b,GP Ⅲ a and p-selectin expression,which is possibly one of the mechanisms for treatment of hemorrhagic thrombopathy.
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Objective:To study on effect of Jiantai Liquid on progesterone receptor(PR)in the uterus at the nidation stage in the mouse with disturbance of blastocyst nidation.Methods:The gestational mice were randomly divided into a normal group,a model group and a Chinese drug group.Mifepristone was used for inducing disturbance of blastocyst nidation in the mice,which were interfered with Jiantai Liquid.At the eighth week of pregnancy,the mice were killed and morphological changes of the endometrium were observed,and PR expression in the uterus was detected with immunohistochemical method and PR and PRmRNA expressions were detected with Western blot and PT-PCR methods.Results:The endometrium showed maldevelopment in the model group and normal development in the Chinese drug group,similar to the normal group;the gland,the PR expression range and intensity of PR expression in the interstitial substance in the Chinese drug group increased as compared with the model group(P0.05);expressions of PR protein and gene in the Chinese drug group were significantly higher than those in the model group(P0.05).Conclusion:Jiantai Liquid can promote development of the endometrium and improves blastocyst nidation via regulating expressions of PR and PRmRNA in the uterus in the mice with disturbance of blastocyst nidation.
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Objective:To observe effects of Shenkui Decoction on proliferation of ovarian cancer cell.Methods:The Shenkui Decoction- containing rat serum was prepared by using TCM serum pharmacological method,and effects of the drug containing serum on proliferation of ovarian cancer fresh parenchymatous tumor cells were investigated with 3H incorporation method,and effects of the drug-containing serum on proliferation of ovarian cancer cell line Tyk-nu cells were investigated by flow cytometry,cellular activity assay,cellular growth curve assay and cell colony formation rate assay.Results:The drug containing serum could inhibit proliferation of both fresh parenckymatous tumor cells and ovarian cancer cell line Tyk-nu cells,and the inhibitory rate raised with the increase of drug-containing serum content.Conclusion:The Shenkui Decoction-containing rat serum can inhibit proliferation of ovarian cancer fresh parenchymatous tumor cells and ovarian cancer cell line Tyk-nu cells.
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Objective:To study effects of 5 recipes for tonifing and supplementing on apoptosis and splenocytes in mice treated with cyclophosphamide.Methods:Apoptosis and cellular cycles of splenocytes were detected by flowcytometric analysis.Results:Sijunzi Decoction,Liuwei Dihuang Pill,Shengmai Powder,Jingui Shenqi Pill could antagonize the decline of proliferation induced by cyclophosphamide,and Sijunzi Decoction and Liuwei Dihuang Pill could resist the apoptosis of splenocytes caused by cyclophosphamide;and the recipes all could inhibit atrophy of the spleen induced by cyclophosphamide Conclusion:The 5 recipes for tonifying and supplementing all can improve the injury of the spleen induced by cyclopbosphamide in varying degrees,Sijunzi Decoction and Liuwei Dihuang Pill being the best.
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Two hundred cases of early pregnant women to receiveartificial abortion were randomly divided into 4groups,viz.analgesic solution,dicaine,normal saline,and blank control groups of which the action on dilata-tion of uterus and of mitigating the comprehensive re-actions to artificval abortion were observed.Resultsrevealed that the analgesic solution and dicaine groupshad better effect on dilatation of uterus and ameliorat-ing the reactions of artificial abortion,analgesic solu-tion was especially good at mitigating the comprehen-sive reactions to artificial abortion than the dicainegroup.
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The Decoction showed marked effect on manykinds of Icterus Neonatorum,Estimation on the activi-ty of superoxide dimutase,lipoperoxide,enzymes ofRBC,were made through histochemical staining andresistance of RBC membrane.Results revealed thatthe remedy has distinctive protective action on cellmembrane of RBC.
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Objective:To observe therapeutic effect of Xiaoyou Granule on Helicobacter Pylorum(Hp)related chronic gastritis.Methods:120 cases were randomly divided into 3 groups,40 cases in each group.They were treated respectively with Xiaoyou Granule,Weisu Granule and western medicine.Their therapeutic effects were observed.Results:Xiaoyou Granule was superior to the control group of TCM in improving clinical symptoms,eliminating inflammation of mucosa and the long-term therapeutic effect of removing Hp was superior to the control group of western medicine.Conclusion:Xiaoyou Granule has a definite therapeutic effect on Hp related chronic gastritis.
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Objective:To observe changes of cerebral nerve cell apoptosis of the rat after acute stroke and the preventive and treating effect of Jiannao Decoction on the apoptosis.Methods:SHRsp rats were used to establish the model of acute stroke,which were treated with Jiannao Decoction.Symptoms and signs of the nervous system and changes of pathological structures of the hipocampus were investigated before and after establishment of the model,and changes of cerebral nerve cell apoptosis before and after establishment of the model and medication were investigated with TUNEL,immunohistochamical and Western blot methods. Results:The incidence rate of stroke in the prevention group was significantly lower than that of the model group(P0.05).Conclusion:Jiannao Decoction has significant protective action on brain in the rat with stroke,which is related with inhibiting the effect of nerve cell apoptosis and conduction of apoptosis-related signals.
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The action of dl - tetrahydropal-matine(dl-THP) was studied in two preparations in vitro : the isolated rat gastric mucosa and parietal cells, dl-THP was found to inhibit significantly basal acid formation by the gastric mucosa in a dose - response fashion. The effect was reversible, acid secretion returning to control levels 1. 5~2h after the preparation underwent a double wash, dl - THP also produced asignificant and dose - dependent inhibition of histamine - induced secretion in the gastric mucosa and parietal cells, shifted the histamine dose -response cuver to the right and suppressed the maximum acid production, with pD_2~1 values of 4. 72 and 4. 70, respectively.