AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved.METHODS： Th...AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved.METHODS： The short-circuit current （Isc） technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis （RIA） and a special mouse model of cystic fibrosis.RESULTS： IMP stimulated a conoentration-dependent rise in ISCl, which was dependent on both Cl^- and HCO3^-, and inhibited by apical application of diphenylamine-2,2＇-dicarboxylic acid （DPC） and glibenclamide, but resistant to 4,4＇-diisothiocyanatostilbene-2,2＇-disulfonic acid disodium salt hydrate （DIDS）. Removal of Na^＋ from basolateral solution almost completely abolished the Isc response to TMP, but it was insensitive to apical Na^＋ replacement or apical Na^＋ channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca2＋ chelator, did not significantly alter the TMP-induced Iso No additive effect of forskolin and 3-isobutyl-l-methylxanthine （[BMX） was observed on the TMP-induced Isc, but it was significantly reduced by a protein kinase A inhibitor, H89.RIA results showed that TMP （1 mmol/L） elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin （10μmol/L）. The TMP-elicited Isc as well as forskolin- or IBMX-induced Isc were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator （CFTR） presenting defective CFTR functions and secretions.CONCLUSION： TMP may stimulate cAMP-dependent and CFTR-mediated Cl^- and HCO3^- secretion. This may have implications in the future development of alternative treatment for constipation.展开更多
Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrom...Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrome,and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns:A case of 25-year-old woman presented with abdominal pain,distention,dyspnea,and nausea with a 6.5 kg increase in weight from baseline.Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone(GnRH)agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis:Moderate/severe ovarian hyperstimulation syndrome.Interventions:The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome,and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin.On day 2,albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth.On day 1,Cabergoline was maintained,and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes:The woman’s clinical condition improved,and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons:Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support.Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.展开更多
Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in ...Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.展开更多
AIM:The rote of the sphincter of Oddi(SO)in ethanol (ETOH)-induced pancreatitis is controversial.Our aim was to characterise the effect of E-I-OH on basal and stimulated SO motility. METHODS:SOs removed from white rab...AIM:The rote of the sphincter of Oddi(SO)in ethanol (ETOH)-induced pancreatitis is controversial.Our aim was to characterise the effect of E-I-OH on basal and stimulated SO motility. METHODS:SOs removed from white rabbits were placed in an organ bath(Krebs solution,pH7.4,37℃).The effects of 2 mL/L,4 mL/L,6 mL/L and 8 mL/L of ETOH on the contractile responses of the sphincter were determined. SOs were stimulated with either 0.1 μmol/L carbachol,1 μmol/L erythromycin or 0.1 μmol/L cholecystokinin(CCK). RESULTS:ETOH at a dose of 4 mL/L significantly decreased the baseline contractile amplitude from 11.98±0.05 mN to 11.19±0.07 mN.However,no significant changes in the contractile frequency were observed.ETOH(0.6%) significantly decreased both the baseline amplitude and the frequency compared to the control group(10.50±0.01 mN, 12.13±0.10 mN and 3.53±0.13 c/min,5.5±0.13 cycles(c)/min, respectively).Moreover,0.8% of ETOH resulted in complete relaxation of the SO.Carbachol(0.1 μmol/L)or erythromycin (1 μmol/L)stimulated the baseline amplitudes(by 82% and 75%,respectively)and the contractile frequencies (by 150% and 106%,respectively).In the carbachol or erythromydn-stimulated groups 2-6 mL/L of E-IOH significantly inhibited both the amplitude and the frequency.Interestingly, a 4-5 min administration of 6 mL/L ETOH suddenly and completely relaxed the SO.CCK(0.1 μmol/L)stimulated the baseline amplitude from 12.37±0.05 mN to 27.40±1.82 mN within 1.60±0.24 min.After this peak,the amplitude decreased to 17.17±0.22 mN and remained constant during the experiment.The frequency peaked at 12.8±0.2 c/min, after which the constant frequency was 9.43±0.24 c/min throughout the rest of the experiment.ETOH at a dose of 4 mL/L significantly decreased the amplitude from 16.13±0.23 mN to 14.93±0.19 mN.However,no significant changes in the contractile frequency were observed.ETOH at a dose of 6 mL/L inhibited both the amplitudes and the frequencies in the CCK-stimulated group,while 8 mL/L of ETOH completely relaxed the展开更多
Background: Luteal phase support with GnRH agonist administration has been shown to be effective in improving the outcome of assisted reproductive technology. The goal of this study was to evaluate the effect of singl...Background: Luteal phase support with GnRH agonist administration has been shown to be effective in improving the outcome of assisted reproductive technology. The goal of this study was to evaluate the effect of single dose Triptrolin (a GnRH agonist) on the probability of the clinical pregnancy rate following embryo transfer (ET) in assisted reproductive techniques (ART). Methods: In this double blinded randomized clinical trial, 340 infertile women who were candidates for intra-cytoplasmic sperm injection (ICSI) were randomly assigned to receive GnRH agonist (Triptrolin) in the luteal phase or placebo. In the intervention group, 0.1 mg Triptrolin was injected subcutaneously, while the control group received normal saline. The clinical pregnancy and implantation rate were compared between the two groups using chi-2 and t-test. P-values less than 0.05 were considered significant. The registration number of this clinical trial is IRCT 2014030916912N1. Results: Administration of 0.1 mg Triptrolin on day 6 after oocyte pick up showed no superiority over placebo in implantation (16.9% - 14%, P = 0.40) and clinical pregnancy rates (32% - 29%, P = 0.66), but the rate of clinical pregnancy was higher in women who were below 27 years of age and those with PCO. Conclusion: Administration of Triptrolin was not superior to placebo for luteal phase support.展开更多
基金Supported by the Innovation and Technology Fund of Hong Kong, China
文摘AIM： To investigate the effect of tetramethylpyrazine （TMP）, an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved.METHODS： The short-circuit current （Isc） technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis （RIA） and a special mouse model of cystic fibrosis.RESULTS： IMP stimulated a conoentration-dependent rise in ISCl, which was dependent on both Cl^- and HCO3^-, and inhibited by apical application of diphenylamine-2,2＇-dicarboxylic acid （DPC） and glibenclamide, but resistant to 4,4＇-diisothiocyanatostilbene-2,2＇-disulfonic acid disodium salt hydrate （DIDS）. Removal of Na^＋ from basolateral solution almost completely abolished the Isc response to TMP, but it was insensitive to apical Na^＋ replacement or apical Na^＋ channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca2＋ chelator, did not significantly alter the TMP-induced Iso No additive effect of forskolin and 3-isobutyl-l-methylxanthine （[BMX） was observed on the TMP-induced Isc, but it was significantly reduced by a protein kinase A inhibitor, H89.RIA results showed that TMP （1 mmol/L） elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin （10μmol/L）. The TMP-elicited Isc as well as forskolin- or IBMX-induced Isc were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator （CFTR） presenting defective CFTR functions and secretions.CONCLUSION： TMP may stimulate cAMP-dependent and CFTR-mediated Cl^- and HCO3^- secretion. This may have implications in the future development of alternative treatment for constipation.
文摘Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrome,and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns:A case of 25-year-old woman presented with abdominal pain,distention,dyspnea,and nausea with a 6.5 kg increase in weight from baseline.Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone(GnRH)agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis:Moderate/severe ovarian hyperstimulation syndrome.Interventions:The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome,and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin.On day 2,albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth.On day 1,Cabergoline was maintained,and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes:The woman’s clinical condition improved,and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons:Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support.Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.
文摘Objective:To determine whether a single dose of gonadotropin-releasing hormone(GnRH)agonist administered subcutaneously in addition to the regular progesterone supplementation could provide a better luteal support in antagonist protocol fresh embryo transfer cycles.Methods:This prospective,multicentric,cohort study included total 140 women,70 in each group.Controlled ovarian stimulation was carried out as per fixed GnRH antagonist protocol.The trigger was given with hCG.In vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)was performed and day-3 embryos were transferred.Patients were divided into groups 1 and 2 based on computer generated randomization sheet.Six days following oocyte retrieval,group 1 received 0.2 mg decapeptyl subcutaneously in addition to regular progesterone support while group 2 received progesterone only.Luteal support was given for 14 days to both groups;if pregnancy was confirmed luteal support was continued till 12 weeks of gestation.The clinical pregnancy rate was the primary outcome.The implantation rate,miscarriage rate,live birth delivery rate,and multiple pregnancy rates were the secondary outcomes.Results:A total of 140 patients were analysed,70 in each group.Clinical pregnancy rates(47.1%vs.35.7%;P=0.17),implantation rates(23.4%vs.18.1%,P=0.24),live birth delivery rates(41.4%vs.27.1%,P=0.08),and multiple pregnancy rates(21.2%vs.16.0%,P=0.74)were higher in group 1 than in group 2.Group 1 had a lower miscarriage rate than group 2(5.7%vs.8.6%;P=0.75).However,these differences were not statistically significant between the two groups.Conclusions:Administration of a single dose of GnRH agonist in addition to regular natural micronized vaginal progesterone as luteal support in GnRH antagonist protocol cycles marginally improves implantation rates,clinical pregnancy rates,and live birth delivery rates.However,more studies with higher sample sizes are needed before any conclusive statements about GnRH agonist as luteal phase support can be made.
基金Supported by The Wellcome Trust (Grant No.022618),and by the Hungarian Scientific Research Fund (D42188,T43066 and T042589)
文摘AIM:The rote of the sphincter of Oddi(SO)in ethanol (ETOH)-induced pancreatitis is controversial.Our aim was to characterise the effect of E-I-OH on basal and stimulated SO motility. METHODS:SOs removed from white rabbits were placed in an organ bath(Krebs solution,pH7.4,37℃).The effects of 2 mL/L,4 mL/L,6 mL/L and 8 mL/L of ETOH on the contractile responses of the sphincter were determined. SOs were stimulated with either 0.1 μmol/L carbachol,1 μmol/L erythromycin or 0.1 μmol/L cholecystokinin(CCK). RESULTS:ETOH at a dose of 4 mL/L significantly decreased the baseline contractile amplitude from 11.98±0.05 mN to 11.19±0.07 mN.However,no significant changes in the contractile frequency were observed.ETOH(0.6%) significantly decreased both the baseline amplitude and the frequency compared to the control group(10.50±0.01 mN, 12.13±0.10 mN and 3.53±0.13 c/min,5.5±0.13 cycles(c)/min, respectively).Moreover,0.8% of ETOH resulted in complete relaxation of the SO.Carbachol(0.1 μmol/L)or erythromycin (1 μmol/L)stimulated the baseline amplitudes(by 82% and 75%,respectively)and the contractile frequencies (by 150% and 106%,respectively).In the carbachol or erythromydn-stimulated groups 2-6 mL/L of E-IOH significantly inhibited both the amplitude and the frequency.Interestingly, a 4-5 min administration of 6 mL/L ETOH suddenly and completely relaxed the SO.CCK(0.1 μmol/L)stimulated the baseline amplitude from 12.37±0.05 mN to 27.40±1.82 mN within 1.60±0.24 min.After this peak,the amplitude decreased to 17.17±0.22 mN and remained constant during the experiment.The frequency peaked at 12.8±0.2 c/min, after which the constant frequency was 9.43±0.24 c/min throughout the rest of the experiment.ETOH at a dose of 4 mL/L significantly decreased the amplitude from 16.13±0.23 mN to 14.93±0.19 mN.However,no significant changes in the contractile frequency were observed.ETOH at a dose of 6 mL/L inhibited both the amplitudes and the frequencies in the CCK-stimulated group,while 8 mL/L of ETOH completely relaxed the
文摘Background: Luteal phase support with GnRH agonist administration has been shown to be effective in improving the outcome of assisted reproductive technology. The goal of this study was to evaluate the effect of single dose Triptrolin (a GnRH agonist) on the probability of the clinical pregnancy rate following embryo transfer (ET) in assisted reproductive techniques (ART). Methods: In this double blinded randomized clinical trial, 340 infertile women who were candidates for intra-cytoplasmic sperm injection (ICSI) were randomly assigned to receive GnRH agonist (Triptrolin) in the luteal phase or placebo. In the intervention group, 0.1 mg Triptrolin was injected subcutaneously, while the control group received normal saline. The clinical pregnancy and implantation rate were compared between the two groups using chi-2 and t-test. P-values less than 0.05 were considered significant. The registration number of this clinical trial is IRCT 2014030916912N1. Results: Administration of 0.1 mg Triptrolin on day 6 after oocyte pick up showed no superiority over placebo in implantation (16.9% - 14%, P = 0.40) and clinical pregnancy rates (32% - 29%, P = 0.66), but the rate of clinical pregnancy was higher in women who were below 27 years of age and those with PCO. Conclusion: Administration of Triptrolin was not superior to placebo for luteal phase support.
