AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted ...AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model.RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs,1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vsstandard dose H2RAs, 1.59 (95%CI, 1.44-1.75);standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis.CONCLUSION: H2RAS are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.展开更多
AIM： To compare efficacy of proton pump inhibitors （PPIs） with H2-receptor antagonists （H2RA$） plus pro- kinetics （Proks） for dysmotility-like symptoms in func- tional dyspepsia （FD）. METHODS： Subjects were ...AIM： To compare efficacy of proton pump inhibitors （PPIs） with H2-receptor antagonists （H2RA$） plus pro- kinetics （Proks） for dysmotility-like symptoms in func- tional dyspepsia （FD）. METHODS： Subjects were randomized to receive openlabel treatment with either rabeprazole 10 mg od （n = 57） or famotidine 10 mg bid plus mosapride 5 mg tid （n = 57） for 4 wk. The primary efficacy endpoint was change （%） from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment. RESULTS： The improvement in dysmotility-like dyspep- sia symptom score on day 28 was significantly greater in the rabeprazole group （22.5% ± 29.2% of baseline） than the famotidine ＋ mosapride group （53.2%±58.6% of baseline, P 〈 0.0001）. The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine ＋ mosapride group （87.7% vs 59.6%, P = 0.0012）. Rabeprazole therapy was the only significant predictor of treatment response （P 〈 0.0001）, defined as a total symptom score improvement ≥ 50%. CONCLUSION： PPI monotherapy improves dysmotil- ity-like symptoms significantly better than H2RAs plus Proks, and should be the treatment of first choice for Japanese FD.展开更多
Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prev...Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prevalence of good anticoagulation in patients treated with VKA in Lomé and describe associated factors. Methods: This was a cross-sectional study conducted from November 2019 to October 2020 in the cardiology departments of two University teaching hospitals in Lomé (CHU Sylvanus Olympio and CHU Campus), involving patients on VKA for ≥3 months, with a target international normalized ratio (INR) of 2.5 and a therapeutic margin between 2 and 3. The quality of anticoagulation was assessed by the time in therapeutic range (TTR) which was assessed by the Rosendaal method. Good anticoagulation was defined by a TTR > 70%. Results: A total of 344 patients were included (mean age = 58 ± 13.8 years, women = 56.1%). Indications for VKA treatment were represented by venous thromboembolic disease (43.3%), supraventricular arrhythmia (28.2%), severe left ventricular systolic dysfunction (19.8%) and pulmonary hypertension (8.7%). The average TTR was 47.6 ± 20.8%. The rate of good anticoagulation was 17.7%. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol (OR = 11.17;95% CI: 3.2 - 39.6;p = 0.0002), concomitant low-dose aspirin (OR 4.44;95% CI: 1.4 - 13.9;p = 0.01) and INR monitoring exclusively by the patient himself (OR = 4.92;95% CI: 1.5 - 16.3;p = 0.008). The rate of thromboembolic and hemorrhagic complications was each 2.6% and was not correlated with the quality of anticoagulation. Quality of anticoagulation by VKAs was poor in our practice. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol, concomitant low-dose aspirin and monitoring of INR exclusively by the patient himself. Conclusion: The quality of oral anticoagulation by VKAs could be improved in our practice by the creation of anticoagulation clinics for better therapeutic education of patients and efficient management of VKA dose, and the use of prescription assistance software.展开更多
Abscisic acid(ABA),a plant hormone,is crucial for regulating various physiological and developmental processes in plants,including adaptation to biotic and abiotic stresses.Recent advancements have significantly contr...Abscisic acid(ABA),a plant hormone,is crucial for regulating various physiological and developmental processes in plants,including adaptation to biotic and abiotic stresses.Recent advancements have significantly contributed to our understanding of ABA's biosynthetic pathway,transport,signaling pathway,and metabolism.To overcome the limitations of natural ABA,scientists have developed broad-spectrum and highly active agonists of ABA receptors.However,the practical application of these receptor agonists as agrochemicals still faces several challenges.On the other hand,some ABA antagonists have also been developed to differentiate the functional differences among various receptors more accurately.This can help design ABA agonists that can selectively activate specific physiological responses,thereby eliminating the undesired physiological effects induced by ABA.This paper aims to provide a comprehensive overview of the current ABA receptor agonists and antagonists to assist in developing novel ABA functional analogs with improved efficacy and simpler chemical structures that are suitable for agricultural applications.展开更多
Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The ...Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The aim of this review is to assess the publishedevidence regarding the development of tachyphylaxiswith repeat usage of H_2RAs. PubMed and SCOPUS were searched across all years to identify clinical studies thatexamined the development of tachyphylaxis with repeated dosing of H_2RAs. Although a single (first) doseof an H_2RA can be effective for controlling gastric acidand preventing or relieving food-related heartburn, numerous studies confirm that tachyphylaxis, also knownas tolerance, is consistently detected at the first timepoint assessed after the first dose, including the second day and/or second dose. Even if symptom relief isachieved with an H_2RA, it may be due to desensitizationof the esophagus to acid exposure, potentially providingsymptom relief without significantly decreasing esophageal acid exposure. When recommending OTC drugsfor treatment of frequent heartburn, clinicians shouldbe aware of the potential for rapid development oftachyphylaxis in patients who use H_2RAs for 2 or more consecutive days. Even if symptom relief is achieved, it may be due to desensitization of the esophagus to acid by the H_2RA, potentially providing symptom relief without significantly decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump inhibitor, may be needed to optimize management of frequent heartburn.展开更多
A series of 1,3-substituted 8-styrylxanthines (11a-d) was synthesized, under chemo- and regioselective conditions, in a good overall yield. The compounds showed affinity towards both A1 and A2A-adenosine receptors by ...A series of 1,3-substituted 8-styrylxanthines (11a-d) was synthesized, under chemo- and regioselective conditions, in a good overall yield. The compounds showed affinity towards both A1 and A2A-adenosine receptors by radioligand binding by means of in vitro assays. The (E)-3-ethyl-1-propyl-8-styrylxanthine (11a) showed the greatest affinity towards the A2A receptor, whereas (E)-3-pentyl-1-propyl-8-styrylxanthine (11d) showed the greatest affinity for the A1 receptor. When the 8-styrylxanthines 11a (A15Et) and 11c (A15Bu) were administrated in rats, which were previously injured with 6-hydroxydopamine at the substantia nigra pars compacta (SNc), the turning behavior decreased 50%. Based on these results we propose to A15Et as a potential compound to treat some symptoms of Parkinson’s disease.展开更多
AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs ...AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.展开更多
AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLIN...AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.展开更多
A series of novel 3-alkylthio-4-arylideneamino-5-(2-furyl)-1, 2, 4-triazole derivatives were synthesized. Their chemical structures were confirmed with elemental analysis and spectral data. Endothelin(ET) receptor c...A series of novel 3-alkylthio-4-arylideneamino-5-(2-furyl)-1, 2, 4-triazole derivatives were synthesized. Their chemical structures were confirmed with elemental analysis and spectral data. Endothelin(ET) receptor competitive binding assay showed that some compounds exhibited high selective as potent ET-1 receptor antagonist.展开更多
It is necessary to understand the bacterial populations associated with rice so as to provide more information and natural resources for effective management of major diseases in rice. A survey on screening and identi...It is necessary to understand the bacterial populations associated with rice so as to provide more information and natural resources for effective management of major diseases in rice. A survey on screening and identification of gram-positive bacteria was conducted during 1998 2004. Seven hundred and fifty-six rice samples were collected from Zhejiang, Jiangsu, Fujian and Yunnan Provinces, China. Over 1000 bacterial isolates were isolated and tested for colony morphology, pathogenicity, and some characteristics of bacteriology including Gram staining, fluorescent pigment on Kings medium B and microscopic observation for endospore. Together with five standard reference strains, 74 representative gram-positive bacterial isolates were confirmed by Biolog and gas chromatographic analysis of fatty acid methyl esters. Five bacterial species of Bacillus and other three genera were identified and isolates from Bacillus sublitis and Bacillus megaterium, exhibited the most effective inhibition against the pathogens of sheath blight and bakanae disease of rice. A few isolates from Bacillus pumilus and Bacillus megaterium showed weak virulent on rice together with some virulent isolates, risk should be considered when isolates from these species were screened for biocontrol agents.展开更多
A series of arylpiperazinesquinazoline-2,4-diamine compounds were designed and synthesized based on pharmacophore for m-selective α1-adrenoceptor antagonists and 3D chemical database searching. The in vitro functiona...A series of arylpiperazinesquinazoline-2,4-diamine compounds were designed and synthesized based on pharmacophore for m-selective α1-adrenoceptor antagonists and 3D chemical database searching. The in vitro functional analysis showed that compounds 9 and 14 showed better and similar α1-AR antagonistic activity compared with prazosin.展开更多
Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bi...Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.展开更多
A simple, rapid, accurate and highly sensitive spectrofluorimetric method has been developed for determination of some angiotensin II receptor antagonists (AIIRA’s), namely Losartan potassium (Los-K), Irbesartan (Irb...A simple, rapid, accurate and highly sensitive spectrofluorimetric method has been developed for determination of some angiotensin II receptor antagonists (AIIRA’s), namely Losartan potassium (Los-K), Irbesartan (Irb), Valsartan (Val) and Candesartan cilexetil (Cand) in pure forms as well as in their pharmaceutical dosage forms. All the variables affecting the relative fluorescence intensity (RFI) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefflcients (0.9982–0.9991) were obtained over the concentration range from 0.006 mg/mL to 1.7 mg/mL. Good accuracy and precision were successfully obtained for the analysis of tablets containing each drug alone or combined with hydrochlorothiazide (HCTZ) without interferences from the co-formulated HCTZ or the additives commonly present in tablets.展开更多
Two series of 1-（benzoxazole-2-yl）piperazine （Sa-i） and 4-（benzoxazole-2-yl）piperidine compounds （10a-i） were designed, synthesized and evaluated for their α1-AR antagonistic activities. Biological assay in v...Two series of 1-（benzoxazole-2-yl）piperazine （Sa-i） and 4-（benzoxazole-2-yl）piperidine compounds （10a-i） were designed, synthesized and evaluated for their α1-AR antagonistic activities. Biological assay in vitro indicated that 10h showed slightly stronger α1-AR antagonistic activity to that of our lead compound 1.展开更多
A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin H AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonis...A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin H AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonism of angiotensin H, induced contraction in the rabbit thoracic aortic ring and the results showed that compounds 9a, 9g and 9j exhibited potent antagonistic activity of AT1 receptor.展开更多
A series of thiourea derivatives have been synthesized. Their structures were confirmed by MS and 1H NMR. Several compounds showed potent activities as antagonists of CCR4 receptor.
BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tub...BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus （TMn）, with regard to the sleep-wakefulness cycle, is poorly understood. OBJECTIVE： To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle. DESIGN, TIME AND SETTING： Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS： Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups（n = 5）： control, ventrolateral preoptic area （VLPO） lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma （St. Louis, USA）. METHODS： Four electroencephalogram screw electrodes were implanted into the skull at a frontal region （two） and parietal bones （two） on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette （10–20 mm tip diameter） containing ibotenic acid solution （10 nmol/L） was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline （10 nmol/L）, a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours. MAIN OUTCOME MEASURES： Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit （Micro1 401 mk2） and Data collection software （Spike Ⅱ）. RESULTS： VLPO lesion induced an increased duration of wakefulness （W, 13.17%） and light slow-wave sleep （SWS1, 28.9%）, respectively. Deep slow-wave sleep （SWS2, 43.74%） and paradoxical sleep （PS, 44.07%） were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion （P 〈 0.01）. Microinjection of bicuculline into the TMn following VLPO lesion at 10：00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% （P 〈 0.01） and 50.97% （P 〈 0.01）, respectively. In addition, SWS2 and PS were decreased by 68.08% （P 〈 0.01） and 39.92% （P 〈 0.05）, respectively, compared with prior to VLPO lesion. CONCLUSION： The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive （sleepiness） via local circuit to directly inhibit histaminergic neurons.展开更多
AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerul...AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP.METHODS: Male Wistar rats with caerulein-induced AP,lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w.of each antagonist. Edema, inflammatory infiltration,necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase,and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates.RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P＜0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P＜0.05) vs 0.58±0.06 in untreated AP. The nonselective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P＜0.01) vs 1.88±0.08in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum,autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups.%FAT/TPT in untreated AP increased about four times (18.4±3.8 vs4.8±1.3 in control group without AP, P＜0.001).Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation.CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/B and selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.展开更多
In this work, support vector classification （SVC） algorithm was used to build structure-activity relationship （SAR） model of the 5-hydroxytryptamine type 3 （5-HT3 ） receptor antagonists with 26 compounds. In a b...In this work, support vector classification （SVC） algorithm was used to build structure-activity relationship （SAR） model of the 5-hydroxytryptamine type 3 （5-HT3 ） receptor antagonists with 26 compounds. In a benchmark test, SVC was compared with several techniques of machine learning currently used in the field. The prediction performance of the model was discussed on the basis of the leave-one-out cross-validation. The results show that the accuracy of prediction of SVC model was higher than those of back propagation artificial neural network （BP ANN）, K-nearest neighbor （KNN） and Fisher methods.展开更多
基金Supported by the Gastroenterological Research Fund, University of Hong Kong, Hong Kong, China
文摘AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE).METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model.RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs,1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vsstandard dose H2RAs, 1.59 (95%CI, 1.44-1.75);standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis.CONCLUSION: H2RAS are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.
文摘AIM： To compare efficacy of proton pump inhibitors （PPIs） with H2-receptor antagonists （H2RA$） plus pro- kinetics （Proks） for dysmotility-like symptoms in func- tional dyspepsia （FD）. METHODS： Subjects were randomized to receive openlabel treatment with either rabeprazole 10 mg od （n = 57） or famotidine 10 mg bid plus mosapride 5 mg tid （n = 57） for 4 wk. The primary efficacy endpoint was change （%） from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment. RESULTS： The improvement in dysmotility-like dyspep- sia symptom score on day 28 was significantly greater in the rabeprazole group （22.5% ± 29.2% of baseline） than the famotidine ＋ mosapride group （53.2%±58.6% of baseline, P 〈 0.0001）. The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine ＋ mosapride group （87.7% vs 59.6%, P = 0.0012）. Rabeprazole therapy was the only significant predictor of treatment response （P 〈 0.0001）, defined as a total symptom score improvement ≥ 50%. CONCLUSION： PPI monotherapy improves dysmotil- ity-like symptoms significantly better than H2RAs plus Proks, and should be the treatment of first choice for Japanese FD.
文摘Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prevalence of good anticoagulation in patients treated with VKA in Lomé and describe associated factors. Methods: This was a cross-sectional study conducted from November 2019 to October 2020 in the cardiology departments of two University teaching hospitals in Lomé (CHU Sylvanus Olympio and CHU Campus), involving patients on VKA for ≥3 months, with a target international normalized ratio (INR) of 2.5 and a therapeutic margin between 2 and 3. The quality of anticoagulation was assessed by the time in therapeutic range (TTR) which was assessed by the Rosendaal method. Good anticoagulation was defined by a TTR > 70%. Results: A total of 344 patients were included (mean age = 58 ± 13.8 years, women = 56.1%). Indications for VKA treatment were represented by venous thromboembolic disease (43.3%), supraventricular arrhythmia (28.2%), severe left ventricular systolic dysfunction (19.8%) and pulmonary hypertension (8.7%). The average TTR was 47.6 ± 20.8%. The rate of good anticoagulation was 17.7%. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol (OR = 11.17;95% CI: 3.2 - 39.6;p = 0.0002), concomitant low-dose aspirin (OR 4.44;95% CI: 1.4 - 13.9;p = 0.01) and INR monitoring exclusively by the patient himself (OR = 4.92;95% CI: 1.5 - 16.3;p = 0.008). The rate of thromboembolic and hemorrhagic complications was each 2.6% and was not correlated with the quality of anticoagulation. Quality of anticoagulation by VKAs was poor in our practice. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol, concomitant low-dose aspirin and monitoring of INR exclusively by the patient himself. Conclusion: The quality of oral anticoagulation by VKAs could be improved in our practice by the creation of anticoagulation clinics for better therapeutic education of patients and efficient management of VKA dose, and the use of prescription assistance software.
基金supported by the National Natural Science Foundation of China(No.22077136).
文摘Abscisic acid(ABA),a plant hormone,is crucial for regulating various physiological and developmental processes in plants,including adaptation to biotic and abiotic stresses.Recent advancements have significantly contributed to our understanding of ABA's biosynthetic pathway,transport,signaling pathway,and metabolism.To overcome the limitations of natural ABA,scientists have developed broad-spectrum and highly active agonists of ABA receptors.However,the practical application of these receptor agonists as agrochemicals still faces several challenges.On the other hand,some ABA antagonists have also been developed to differentiate the functional differences among various receptors more accurately.This can help design ABA agonists that can selectively activate specific physiological responses,thereby eliminating the undesired physiological effects induced by ABA.This paper aims to provide a comprehensive overview of the current ABA receptor agonists and antagonists to assist in developing novel ABA functional analogs with improved efficacy and simpler chemical structures that are suitable for agricultural applications.
文摘Histamine_2-receptor antagonists(H_2RAs) are availableover-the-counter (OTC) for the treatment and prevention of heartburn, but more than occasional, singledose use can lead to rapid development of tachyphylaxis. The aim of this review is to assess the publishedevidence regarding the development of tachyphylaxiswith repeat usage of H_2RAs. PubMed and SCOPUS were searched across all years to identify clinical studies thatexamined the development of tachyphylaxis with repeated dosing of H_2RAs. Although a single (first) doseof an H_2RA can be effective for controlling gastric acidand preventing or relieving food-related heartburn, numerous studies confirm that tachyphylaxis, also knownas tolerance, is consistently detected at the first timepoint assessed after the first dose, including the second day and/or second dose. Even if symptom relief isachieved with an H_2RA, it may be due to desensitizationof the esophagus to acid exposure, potentially providingsymptom relief without significantly decreasing esophageal acid exposure. When recommending OTC drugsfor treatment of frequent heartburn, clinicians shouldbe aware of the potential for rapid development oftachyphylaxis in patients who use H_2RAs for 2 or more consecutive days. Even if symptom relief is achieved, it may be due to desensitization of the esophagus to acid by the H_2RA, potentially providing symptom relief without significantly decreasing esophageal acid exposure. Other strategies, such as an OTC proton pump inhibitor, may be needed to optimize management of frequent heartburn.
基金CONACyT-Mexico support (50682) (CB2011-169023 give to D.L.)
文摘A series of 1,3-substituted 8-styrylxanthines (11a-d) was synthesized, under chemo- and regioselective conditions, in a good overall yield. The compounds showed affinity towards both A1 and A2A-adenosine receptors by radioligand binding by means of in vitro assays. The (E)-3-ethyl-1-propyl-8-styrylxanthine (11a) showed the greatest affinity towards the A2A receptor, whereas (E)-3-pentyl-1-propyl-8-styrylxanthine (11d) showed the greatest affinity for the A1 receptor. When the 8-styrylxanthines 11a (A15Et) and 11c (A15Bu) were administrated in rats, which were previously injured with 6-hydroxydopamine at the substantia nigra pars compacta (SNc), the turning behavior decreased 50%. Based on these results we propose to A15Et as a potential compound to treat some symptoms of Parkinson’s disease.
文摘AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.
基金Supported by National Natural Science Funds of China,No.81102784/H2803the key project in scientific research from ministry of education,No.212032Liaoning Innovative Research Team in University,No.LT2013022
文摘AIM: To compare the therapeutic effects of proton pump inhibitors vs H2 receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and Pub Med for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration's tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios(OR) and mean difference with 95% confidence interval(CI). Rev Man 5.3.3 software and Stata 12.0 software were used for data analyses. RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors(PPI) group and the remaining 605 subjects were in the H2 receptor antagonists(H2RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H2 RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate(OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate(OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality(OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference(WMD),-0.70 unit; 95%CI:-1.64- 0.25] and the time that patients remained hospitalized [WMD,-0.77 d; 95%CI:-1.87- 0.34]. The Begg's test(P = 0.283) and Egger's test(P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H2 RA, PPI may be a more effective therapy.
文摘A series of novel 3-alkylthio-4-arylideneamino-5-(2-furyl)-1, 2, 4-triazole derivatives were synthesized. Their chemical structures were confirmed with elemental analysis and spectral data. Endothelin(ET) receptor competitive binding assay showed that some compounds exhibited high selective as potent ET-1 receptor antagonist.
基金the National Natural Science Foundation of China(30270891) National 863 Program(2002AA241261).
文摘It is necessary to understand the bacterial populations associated with rice so as to provide more information and natural resources for effective management of major diseases in rice. A survey on screening and identification of gram-positive bacteria was conducted during 1998 2004. Seven hundred and fifty-six rice samples were collected from Zhejiang, Jiangsu, Fujian and Yunnan Provinces, China. Over 1000 bacterial isolates were isolated and tested for colony morphology, pathogenicity, and some characteristics of bacteriology including Gram staining, fluorescent pigment on Kings medium B and microscopic observation for endospore. Together with five standard reference strains, 74 representative gram-positive bacterial isolates were confirmed by Biolog and gas chromatographic analysis of fatty acid methyl esters. Five bacterial species of Bacillus and other three genera were identified and isolates from Bacillus sublitis and Bacillus megaterium, exhibited the most effective inhibition against the pathogens of sheath blight and bakanae disease of rice. A few isolates from Bacillus pumilus and Bacillus megaterium showed weak virulent on rice together with some virulent isolates, risk should be considered when isolates from these species were screened for biocontrol agents.
文摘A series of arylpiperazinesquinazoline-2,4-diamine compounds were designed and synthesized based on pharmacophore for m-selective α1-adrenoceptor antagonists and 3D chemical database searching. The in vitro functional analysis showed that compounds 9 and 14 showed better and similar α1-AR antagonistic activity compared with prazosin.
基金The National Natural Science Foundation of China, No. 30772883
文摘Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.
文摘A simple, rapid, accurate and highly sensitive spectrofluorimetric method has been developed for determination of some angiotensin II receptor antagonists (AIIRA’s), namely Losartan potassium (Los-K), Irbesartan (Irb), Valsartan (Val) and Candesartan cilexetil (Cand) in pure forms as well as in their pharmaceutical dosage forms. All the variables affecting the relative fluorescence intensity (RFI) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefflcients (0.9982–0.9991) were obtained over the concentration range from 0.006 mg/mL to 1.7 mg/mL. Good accuracy and precision were successfully obtained for the analysis of tablets containing each drug alone or combined with hydrochlorothiazide (HCTZ) without interferences from the co-formulated HCTZ or the additives commonly present in tablets.
基金the National High-Tech Research and Development Plan(No.2002AA2Z3118)
文摘Two series of 1-（benzoxazole-2-yl）piperazine （Sa-i） and 4-（benzoxazole-2-yl）piperidine compounds （10a-i） were designed, synthesized and evaluated for their α1-AR antagonistic activities. Biological assay in vitro indicated that 10h showed slightly stronger α1-AR antagonistic activity to that of our lead compound 1.
基金We are thankful to the National Natural Science Foundation of China(No.30371688)Key Fund of Ministry of Education of China(No.03089)for financial support.
文摘A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin H AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonism of angiotensin H, induced contraction in the rabbit thoracic aortic ring and the results showed that compounds 9a, 9g and 9j exhibited potent antagonistic activity of AT1 receptor.
基金supported by the National High-Tech Research and Development Program of China(863 Program)(No.2006AA10A201)National Natural Science Foundation(No.30472093).
文摘A series of thiourea derivatives have been synthesized. Their structures were confirmed by MS and 1H NMR. Several compounds showed potent activities as antagonists of CCR4 receptor.
基金the National Natural Science Foundation of China, No. 30670677
文摘BACKGROUND： Neurons expressing gamma-aminobutyric acid （GABA） play an important role in the regulation of wakefulness to sleep, as well as the maintenance of sleep. However, the role of GABAergic neurons in the tuberomammillary nucleus （TMn）, with regard to the sleep-wakefulness cycle, is poorly understood. OBJECTIVE： To investigate the effects of GABAergic neurons in the TMn on the sleep-wakefulness cycle. DESIGN, TIME AND SETTING： Randomized controlled study, performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from July 2007 to February 2008. MATERIALS： Fifteen healthy, adult, male, Sprague Dawley rats were randomly divided into three groups（n = 5）： control, ventrolateral preoptic area （VLPO） lesion, and VLPO lesion plus GABAA receptor antagonist-treated. Ibotenic acid and bicuculline were provided by Sigma （St. Louis, USA）. METHODS： Four electroencephalogram screw electrodes were implanted into the skull at a frontal region （two） and parietal bones （two） on each side. Three flexible electromyogram wire electrodes were placed into the nuchal muscles. On day 8, a fine glass micropipette （10–20 mm tip diameter） containing ibotenic acid solution （10 nmol/L） was injected into the VLPO in both hemispheres following bone wax removal under anesthesia. One week after the second surgery, sleep-wakefulness states were recorded in rats from the VLPO lesion group. On day 10 after VLPO lesion, bicuculline （10 nmol/L）, a GABAA-receptor antagonist, was microinjected into the TMn and sleep-wakefulness states were recorded for 24 hours. MAIN OUTCOME MEASURES： Duration of the sleep-wakefulness cycle in each group using a Data acquisition unit （Micro1 401 mk2） and Data collection software （Spike Ⅱ）. RESULTS： VLPO lesion induced an increased duration of wakefulness （W, 13.17%） and light slow-wave sleep （SWS1, 28.9%）, respectively. Deep slow-wave sleep （SWS2, 43.74%） and paradoxical sleep （PS, 44.07%） were respectively decreased for 24 hours at day 9 post-lesion, compared with pre-lesion （P 〈 0.01）. Microinjection of bicuculline into the TMn following VLPO lesion at 10：00 am on the 10th day elicited a wake state for 40–55 minutes, with a latency of 15 minutes. However, 24-hour sleep-wake states demonstrated that the ratio of W and SWS1 were increased by 12.61% （P 〈 0.01） and 50.97% （P 〈 0.01）, respectively. In addition, SWS2 and PS were decreased by 68.08% （P 〈 0.01） and 39.92% （P 〈 0.05）, respectively, compared with prior to VLPO lesion. CONCLUSION： The evidence of decreased deep slow-wave sleep, which was induced by VLPO lesion, suggested that GABAergic neurons in the VLPO play an important role in maintaining sleep. Bicuculline microinjection into the TMn, following VLPO lesion, elicited wakefulness and sleep depression for 50 minutes, with contrary increased light slow-wave sleep for 24 hours, which suggested that GABAergic neurons in the TMn play a role in sleep drive （sleepiness） via local circuit to directly inhibit histaminergic neurons.
基金Supported by the Medical University of Bialystok within the Project #30-12770
文摘AIM: To assess the effect of non-selective ETA/B (LU 302872)and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP.METHODS: Male Wistar rats with caerulein-induced AP,lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w.of each antagonist. Edema, inflammatory infiltration,necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase,and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates.RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P＜0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P＜0.05) vs 0.58±0.06 in untreated AP. The nonselective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P＜0.01) vs 1.88±0.08in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum,autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups.%FAT/TPT in untreated AP increased about four times (18.4±3.8 vs4.8±1.3 in control group without AP, P＜0.001).Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation.CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/B and selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.
基金Project supported by National Natural Science Foundation of China（ Grant No. 20373040）
文摘In this work, support vector classification （SVC） algorithm was used to build structure-activity relationship （SAR） model of the 5-hydroxytryptamine type 3 （5-HT3 ） receptor antagonists with 26 compounds. In a benchmark test, SVC was compared with several techniques of machine learning currently used in the field. The prediction performance of the model was discussed on the basis of the leave-one-out cross-validation. The results show that the accuracy of prediction of SVC model was higher than those of back propagation artificial neural network （BP ANN）, K-nearest neighbor （KNN） and Fisher methods.
