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Objective To compare the therapeutic effect of endoscopic variceal ligation (EVL) and β-blockers plus isosorbide mononitrate (ISMN) in prevention of esophageal varieeal re-bleeding. Methods The randomized clinical trials (RCTs) on EVL and β-blockers plus ISMN for the prevention of esophageal varieeal re-bleeding were searched, and only the results from those with Jadad score higher than 3 were eval-uated with RevMan 4. 2 software for odds ratio (OR) with 95% confidence intervals (95%C1). Analysis of sensitivity was performed on the quality of the data and publication bias was investigated with funnel plots. Results Four trials matched the criteria were recruited including 504 cases with a follow-up from 8 to 25 months. There was no significant difference in rates of re-bleeding (OR =0. 93, 95% CI =0. 41 ～ 2. 11 ; P = 0. 87), re-bleeding due to esophageal varices (OR = 0. 68, 95% CI = 0. 19 ～ 2. 37 ; P = 0. 54), therapy-re-lated adverse effects (OR = 1.12, 95% CI =0. 75 ～ 1.67, P = 0. 57), severe adverse events (OR = 0. 89, 95% CI =0. 47 ～ 1.67, P = 0. 71), bleeding-related mortality (OR = 2. 11, 95% CI = 0. 88 ～ 5.08, P = 0. 10), or overall mortality (OR = 1.46, 95% CI = 0. 95 ～ 2. 24, P = 0. 09) between EVL and β-blockers plus ISMN groups. However, a trend towards lower bleeding-related mortality and overall mortality favored drug therapy. There was no heterogeneity found in the outcomes apart from re-bleeding (P = 0. 003) or re-bleeding from esophageal varices (P <0. 0001). The result of sensitivity analysis remained statistically sta-ble. Symmetric funnel plots showed there was no evidence of publication bias. Conclusion EVL and β-blockers plus ISMN show an equivalent efficacy and safety for the prevention of esophageal variceal re-bleed-ing. There is a trend towards lower bleeding-related mortality and overall mortality in drug therapy. But EVL is free from drug-related side effects, and its adverse events are similar to those of drug therapy. Thus, either of the two approaches can be used as the first choice for prophylaxis of re-bleeding of esophageal varices.
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Objective To investigate the P2X3 receptor expression in L6-S1 dorsal root ganglion (DRG)and bladder detrusor in a rat model of neurogenic bladder and urethra. Methods Eighty Sprague-Dawley rats wererecruited and randomly divided into a sacral injury group, a suprasacral injury group and a control group. Spinal tran-section was performed to establish the animal model of neurogenic bladder and urethra in rats of the sacral injurygroup and suprasacral injury group. Check the P2X3 receptor expression in DBG and bladder detrusor among thethree groups by Western blot test at 20 days after model establishment. Results P2X3 receptor expression in L6-S1DRG of sacral injury group was significantly less than that of the suprasacral injury group, which was in turn signifi-cantly higher than that of the control group. P2X3 receptor expression in bladder detrusor of sacral injury group wassignificantly lower than that of the suprasacral injury group, which was in turn significantly higher than that of thecontrol group. Conclusion There was close relationship between P2X3 receptor expression and dysfunction of blad-der and urethra.
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The human ovarian mucinous cystadenocarcinoma (hOMC) cells were co-cultured with antisense oligodeoxynucleotide (antisense ODN), nonsense ODN, and follicle-stimulating hormone (FSH) at different concentrations for the purpose of observing the effects of antisense ODN to FSH receptor (FSHR) on the proliferation and apoptosis of cultured hOMC cells in vitro. The inhibitory rates of growth were measured by using MTT method on the 2nd, 4th, 6th, 8th and 10th days after the interference of antisense ODN, nonsense ODN, and FSH, respectively. The apoptotic rates and the cell cycles were determined by means of flow cytometry, the apoptosis indexes were detected by using TUNEL, and the expression of caspase-3 was measured by using SP immunohistochemistry. Compared with that in the control group, the proliferative activity of hOMC cells was increased obviously in FSH groups (P0.05). It was suggested that FSH may improve the development of hOMC cells. However, antisense ODN could inhibit proliferative activity and the FSH-promoted proliferative activity in hOMC cells, at the same time, antisense ODN could inhibit hOMC cell growth by inducing apoptosis.
ABSTRACT
The human ovarian mucinous cystadenocarcinoma (hOMC) cells were co-cultured with antisense oligodeoxynucleotide (antisense ODN), nonsense ODN, and follicle-stimulating hormone (FSH) at different concentrations for the purpose of observing the effects of antisense ODN to FSH receptor (FSHR) on the proliferation and apoptosis of cultured hOMC cells in vitro. The inhibitory rates of growth were measured by using MTT method on the 2nd, 4th, 6th, 8th and 10th days after the interference of antisense ODN, nonsense ODN, and FSH, respectively. The apoptotic rates and the cell cycles were determined by means of flow cytometry, the apoptosis indexes were detected by using TUNEL, and the expression of caspase-3 was measured by using SP immunohistochemistry. Compared with that in the control group, the proliferative activity of hOMC cells was increased obviously in FSH groups (P＜0.05 or P＜0.01), decreased distinctly in antisense ODN groups (P＜0.05 or P＜0.01), and unchanged in nonsense ODN groups, respectively. Meanwhile, antisense ODN could significantly antagonize the FSH-promoted cell proliferative activity (P＜0.01). Compared with those in the control group, the apoptotic rates and the expression of caspase-3 were dramatically increased in the mid- and high-dose antisense ODN groups (P＜0.05 or P＜0.01), while the number of cells in G1/G0 phase was significantly decreased and that in S phase distinctly increased (P＜0.01). There was no change in nonsense ODN groups (P＞0.05). It was suggested that FSH may improve the development of hOMC cells. However, antisense ODN could inhibit proliferative activity and the FSH-promoted proliferative activity in hOMC cells, at the same time, antisense ODN could inhibit hOMC cell growth by inducing apoptosis.
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The effects of antisense oligodeoxynucleotide (antisense ODN) to follicle-stimulating hormone receptor (FSHR) and follicle-stimulating hormone (FSH) on the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were studied in primary culture cells derived from human ovarian mucinous cystadenocarcinoma (OMC). The prlmary OMC cells were cultured with the enzyme digestion method, and the expression of pan Keratin protein and FSHR mRNA was detected for identification of the cells. OMC cells were co-cultured with antisense ODN, nonsense ODN and FSH with different concentrations for 48 h and 72 h. The expression of PCNA and VEGF was detected by using SP immunohistochemistry. Compared with that in the control group, the PCNA and VEGF expression was increased obviously in FSH groups (P＜0.05 or P＜ 0.01), while decreased significantly in antisense ODN groups (P＜0. 05 or P＜0.01) and unchanged in nonsense ODN groups, respectively. Meanwhile, antisense ODN could antagonize the increased expression of PCNA and VEGF caused by FSH significantly (P＜0.01). It was suggested that FSH might promotethe development of OMC to some extent. Antisense ODN could inhibit the proliferative activity of OMC cells and the promoting proliferative activity enhanced by FSH.
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AIM:The effective abortifacient drug,mifepristone,was incorporated in the solid lipid nanoparticles (SLNs). The aim of this paper was to study the influence of ratios of drug to lipid on the characteristics of SLNs.METHOD:The physicochemical properties of the fine dispersed systems,such as the size distribution,Zeta potential had been analyzed by laser diffractometry(LD).The measurements of entrapment efficiency(EE)and thermal analysis of DSC were performed as well.RESULT:It was showed if the weight of lipid remained unchanged,the mean particle size of SLNs increased with the increase of drug amount.Drug entrapment efficiency was the highest while about 50 mg drug was loaded on weight 1 g lipid.Simultaneously,the charge of Zeta potential agreed well with the amount of free drug in the colloidal system.DSC analysis results showed that the melting peak of mifepristone at approx.190 ℃ disappeared.CONCLUSION:It was evidence that the drug incorporation would affect the average particle size and Zeta potential of the colloidal systems and the physical state of crystalline drug mifepristone in SLNs was present in the amorphous form or molecularly dispersed at even so high adding amount of 250 mg/g(lipid),which there was no report about the physical state of the drug and SLN with so high drug-loading.It was suggested that the model drug mifepristone could influence the property of nanodispersion system and the crystalline character of the drug was altered by the nanometer carrier system vice versa.
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<p><b>OBJECTIVE</b>To study the effect of mifepristone on the expression of chorionic gonadotropin beta subunit (beta-CG) and collagen type IV in female Rhesus monkey decidua and villus during the first trimester of pregnancy.</p><p><b>METHODS</b>Eighteen sexually mature female Rhesus monkeys were allowed to cohabitate with their male counterparts and diagnosed as being pregnant by B-ultrasound at days 38-45 of the menstrual cycle. They were randomly divided into mifepristone treatment group (15 mg/ml.kg.day, 3 days), control group(no treatment) and CMC-Na treatment group(0.5% CMC-Na, 1 ml/kg.day, 3 days). The content and distribution of chorionic gonadotropin beta subunit and collagen type IV in the female Rhesus monkeys were examined by immunohistochemical technique.</p><p><b>RESULTS</b>Compared with the control group, the immunohistochemical reaction intensity of chorionic gonadotropin beta subunit in the plasm of stroma cells, glandular epithelial cells and decidual cells of decidua, and synctial trophoblast cells of villus significantly decreased in the mifepristone treatment group. The positive staining of collagen type IV surrounding the epithelial glandular basal membrane, decidual cells and blood vessels in decidua and surrounding the synctial trophoblast cells in villus were significantly reduced.</p><p><b>CONCLUSION</b>Mifepristone may have a strong effect in decreasing the bioactivity of beta-CG in decidua and the synthesis of beta-CG in villus, and in accelerating the degradation of collagen type IV in decidua and villus.</p>
Subject(s)
Animals , Female , Pregnancy , Chorionic Gonadotropin, beta Subunit, Human , Chorionic Villi , Chemistry , Collagen Type IV , Decidua , Chemistry , Immunohistochemistry , Macaca mulatta , Mifepristone , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To explore the association of spermatogenic arrest with the expression of AR and HSP90alpha.</p><p><b>METHODS</b>The two-step immunohistochemical method was used to examine the expression of AR and HSP90alpha in the testicular biopsy specimens of 57 infertile men with spermatogenic arrest, compared with those taken from 15 normal healthy men.</p><p><b>RESULTS</b>AR was expressed in the nuclei of the spermatogonia, spermatocytes and round spermatids of the normal testicular biopsy, but the intensity of the AR expression showed difference in each type of cells. Furthermore, the high expression of AR in spermatogonia and spermatids was on the margin of the cytoplasm, and perinuclear (forming a ring-like structure) were very distinctive in the spermatogenic arrest testicular biopsy specimens. HSP90alpha was expressed in spermatogonia, spermatocytes, Sertoli cells, Leydig cells and myoid cells in the normal testicular tissues, but highly expressed in the testicular tissues with spermatogenic arrest. The immunostaining intensity of HSP90alpha showed significant difference (P < 0.05) between the two kinds of testicular tissues.</p><p><b>CONCLUSION</b>The results indicate that the abnormal expression sites of AR may make the androgen receptor unable to mediate androgen into the nucleus, which may down-regulate the gene transcription activity of spermatogenic cells. It is possible that the high expression of HSP90alpha may lead to a dramatic decrease in AR stability and an increase in AR abiquitirylation.</p>
Subject(s)
Adult , Humans , Male , Case-Control Studies , HSP90 Heat-Shock Proteins , Immunohistochemistry , Infertility, Male , Metabolism , Oligospermia , Metabolism , Receptors, Androgen , Spermatogenesis , Testis , Metabolism , PathologyABSTRACT
In order to assess the impact of mRNA degradation on steady state levels of follicle-stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene expression, the stability and half-life of FSHR mRNA were determined in transfected cells expressing recombinant FSHR. Time-dependent changes in FSHR mRNA content were determined by nuclease protection-solution hybridization assay (NPA) or by qualitative reverse transcription-competitive polymerase chain reaction (RT-PCR) in cultured hFSHR-YI cells, cell lines stably transfected with a human FSHR cDNA. FSHR mRNA content remained constant during 8 h control incubations of hFSHR-Y1 cells (NPA, 2.9±0.3 μg/mg RNA; RT-PCR, 2.7±0.3 μg/mg RNA). Actinomycin D (ActD, 5 μg/ml) inhibited mRNA synthesis, as assessed by incorporation of ［3 H］uridine into total RNA, by 90 % within 1 h in hFSHR-Y1 cells. No effect of ActD on cellular morphology or viability was observed. ActD caused a time-dependent decrease in FSHR mRNA content in hFSHR-Y1 cell lines with a lag time of 1 h. There were no significant differences in the rate of FSHR mRNA degradation between the two methods of mRNA quantification. The half-life of hFSHR mRNA was 3.6±0.2 h by NPA and 3.1±0.1 h by RT-PCR. The results indicated that degradation of mRNA was an important process in maintenance of steady state expression of the FSHR gene in cells stably expressing recombinant receptor.
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In order to assess the impact of mRNA degradation on steady state levels of follicle-stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene expression, the stability and half-life of FSHR mRNA were determined in transfected cells expressing recombinant FSHR. Time-dependent changes in FSHR mRNA content were determined by nuclease protection-solution hybridization assay (NPA) or by qualitative reverse transcription-competitive polymerase chain reaction (RT-PCR) in cultured hFSHR-YI cells, cell lines stably transfected with a human FSHR cDNA. FSHR mRNA content remained constant during 8 h control incubations of hFSHR-Y1 cells (NPA, 2.9±0.3 μg/mg RNA; RT-PCR, 2.7±0.3 μg/mg RNA). Actinomycin D (ActD, 5 μg/ml) inhibited mRNA synthesis, as assessed by incorporation of ［3 H］uridine into total RNA, by 90 % within 1 h in hFSHR-Y1 cells. No effect of ActD on cellular morphology or viability was observed. ActD caused a time-dependent decrease in FSHR mRNA content in hFSHR-Y1 cell lines with a lag time of 1 h. There were no significant differences in the rate of FSHR mRNA degradation between the two methods of mRNA quantification. The half-life of hFSHR mRNA was 3.6±0.2 h by NPA and 3.1±0.1 h by RT-PCR. The results indicated that degradation of mRNA was an important process in maintenance of steady state expression of the FSHR gene in cells stably expressing recombinant receptor.
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The effects of mifepristone (RU486) on the productions of plasminogen activator and progesterone in rat granulosa cells and luteal cells were studied by fibrin overlay method and radioimmunoassay method. The results showed that RU486 could significantly antagonize tPA activity and progesterone production enhanced by human chorionic gonadotropin (hCG). Secretion of tPA from luteal cells was significantly promoted by RU486 with or without prostaglandin F2a (PGF2α), but progesterone production in luteal cells was markedly inhibited with the same treatment. With method of tissue culture, the results showed that RU486 was capable of stimulating tPA and urokinase (uPA) activity in endometrium of pregnant rats. These findings indicated that antifertility of RU486 might be partly mediated through plasminogen activator-plasminogen activator inhibitor system.