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
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
BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel ...BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel and beneficial drug for DN,no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented.AIM To assess the effectiveness and safety of ER antagonists among patients with DN.METHODS The EMBASE,PubMed,MEDLINE,Cochrane,and ClinicalTrials.gov databases were searched without any language restrictions.Relative risks with 95%confidence intervals(CIs)for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software.Publication bias was assessed using Egger’s test with Stata/SE software.RESULTS We enrolled seven studies with six data sets and 5271 participants.The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40%reduction in urinary albumin-to-creatinine ratio than the control group(P<0.0001 and P=0.02,respectively).Subgroup analysis for reductions in estimated glomerular filtration rate(eGFR)showed that for the middle-dosage subgroup,the ER antagonists group exhibited lower eGFR reduction than the control group(P<0.00001;mean difference,0.7095%CI:0.66,0.74).Moreover,significant reductions in systolic and diastolic blood pressure were observed in the invention group.CONCLUSION ER blockades combined with angiotensin converting enzyme inhibitor/angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR.However,attention should be given to adverse events,including cardiac failure,anemia,and hypoglycemia,as well as serious adverse events.展开更多
Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing uro...Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.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
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
Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0. 44mg Cd/kg,ip), CPZ (5mg/kg, ip) or NIMO (8mg/kg, po) were ...Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0. 44mg Cd/kg,ip), CPZ (5mg/kg, ip) or NIMO (8mg/kg, po) were administered every day to Sprague-Dawley (S. D. ) rats for a week. Then, urinary N- acetyl-β-D- glucosaminidase (NAG ), uri -nary cadmium and bloocl cadmium were measured. The accumulation of cadmium in the kid-ney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proxi-mal convoluted tubules of rats were examined three weeks after the last administration. Re-sults indicated that the calcium antagonists partly protected against toxic effects induced bycadmium in different manners. These data provide further evidence for the new hypothesisthat the cross effect of cadmium and calcium in calmodulin regulated systems may be responsi-ble for the mechanism of cadmium intoxication. 'The results suggested that the calcium antag-onists could be a new and promising approach in the therapy of heavy metaLinduced diseases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
Feng Fengyi , Zhang Pin , He Youjian 1, Li Yuhong1 , Zhou Meizhen2 , Chen Gang2 and Li Lin2 The Cancer Hospital of the CAMS & PUMC, Beijing 1000211 The Cancer Hospital of Sun Yat Sen University of Medical Science...Feng Fengyi , Zhang Pin , He Youjian 1, Li Yuhong1 , Zhou Meizhen2 , Chen Gang2 and Li Lin2 The Cancer Hospital of the CAMS & PUMC, Beijing 1000211 The Cancer Hospital of Sun Yat Sen University of Medical Sciences, Guangzhou 5100602Beijing Hospital of the Ministry of Health, Beijing 100730展开更多
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
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.
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
Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatica...Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.展开更多
Background Triple therapy(TT)with vitamin K-antagonists(VKA),aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation(PCI-S)in patients w...Background Triple therapy(TT)with vitamin K-antagonists(VKA),aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation(PCI-S)in patients with an indication for oral anticoagulation.TT is associated with an increased risk of bleeding,but available evidence is flawed by important limitations,including the limited size and the retrospective design of most of the studies,as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding.Since the perceived high bleeding risk of TT may deny patients effective strategies,the determination of the true safety profile of TT is of paramount importance.Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed,and the weakness of the data was analyzed.Results The absolute incidence of major bleeding upon discharge at in-hospital,≤1 month,6 months,12 months and≥12 months was:3.3%±1.9%,5.1%±6.7%,8.0%±5.2%,9.0%±8.0,and 6.2%±7.8%,respectively,and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel.Conclusions While waiting for the ongoing,large-scale,registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT,this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented.展开更多
Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats...Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the effects of three kinds of adrenergic receptor blockers: Carvedilol (CAR) , Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypertrophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA)was used in this study. Thirty two male wistar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER. Hemodynamics, ventricular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ / Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ /Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ /Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was independent of beta-adrenergic receptor antagonist.展开更多
Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinica...Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.展开更多
Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors such as those of the prostate. Treatment modalities for prostate cancer in a localized stage or when ...Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors such as those of the prostate. Treatment modalities for prostate cancer in a localized stage or when it is still castration-sensitive yield good results in most patients. However, such treatments are only palliative in the advanced stage. Therefore, new therapeutic targets like growth hormone-releasing hormone receptor (GHRH-R) and its splice variants should be found in order to get effective treatments for more aggressive stages in prostate cancer. This review talks about the GHRH-R and its splice variants, the signaling pathways induced by GHRH to produce cancer, the structure activity relationship of GHRH-R antagonists and the resume of some <em>in vitro</em> and <em>in vivo</em> studies on the role of GHRH-R antagonists in the treatment of prostate cancer.展开更多
The potential use ofcomposted wood fibre waste （WFW） for the cultivation of bacterial antagonists of Sclerotinia minor was examined with the result that a mix of millet seed （20% w/w） and WFW, suitably amended wit...The potential use ofcomposted wood fibre waste （WFW） for the cultivation of bacterial antagonists of Sclerotinia minor was examined with the result that a mix of millet seed （20% w/w） and WFW, suitably amended with nutrients, proved to be an ideal matrix for the growth of some of these bacteria. Densities in terms ofcfu＇s ranged from 8.5 IOgl0 cfu/g dw to 10.5 logl0 cfu/g dw ullder sterile conditions after 14 days incubation. Lower population densities of the antagonists were achieved under non-sterile conditions in the compost： millet mix of between 7.9-9.3 logm cfu/g dw at the same period. However, when applied in a pot （glasshouse） trial to protect against S. minor, the millet seed appeared to stimulate the growth of this pathogen resulting in a high incidence of attack of lettuce plants after 2-3 weeks. Although the percentage of healthy seedlings increased following application of compost mix grown antagonists （at a rate of 5% v/v） when compared to the control treatment, these values were not statistically significant （p〉0.05） in most cases. Therefore, the use of millet seeds cannot be recommended as a nutrient supplement for the bacterial antagonist cultivation, if to be subsequently used to control fungal pathogens in the field.展开更多
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 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.
文摘BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel and beneficial drug for DN,no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented.AIM To assess the effectiveness and safety of ER antagonists among patients with DN.METHODS The EMBASE,PubMed,MEDLINE,Cochrane,and ClinicalTrials.gov databases were searched without any language restrictions.Relative risks with 95%confidence intervals(CIs)for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software.Publication bias was assessed using Egger’s test with Stata/SE software.RESULTS We enrolled seven studies with six data sets and 5271 participants.The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40%reduction in urinary albumin-to-creatinine ratio than the control group(P<0.0001 and P=0.02,respectively).Subgroup analysis for reductions in estimated glomerular filtration rate(eGFR)showed that for the middle-dosage subgroup,the ER antagonists group exhibited lower eGFR reduction than the control group(P<0.00001;mean difference,0.7095%CI:0.66,0.74).Moreover,significant reductions in systolic and diastolic blood pressure were observed in the invention group.CONCLUSION ER blockades combined with angiotensin converting enzyme inhibitor/angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR.However,attention should be given to adverse events,including cardiac failure,anemia,and hypoglycemia,as well as serious adverse events.
文摘Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.
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.
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.
文摘Protective effects of calcium antagonists, chlorpromazine (CPZ) and nimodepine (NI-MO), on cadmium-induced toxicity were investigated. After giving CdCl2 (0. 44mg Cd/kg,ip), CPZ (5mg/kg, ip) or NIMO (8mg/kg, po) were administered every day to Sprague-Dawley (S. D. ) rats for a week. Then, urinary N- acetyl-β-D- glucosaminidase (NAG ), uri -nary cadmium and bloocl cadmium were measured. The accumulation of cadmium in the kid-ney cortex, content of renal calmodulin, hemoglobin and the ultrastructural damage of proxi-mal convoluted tubules of rats were examined three weeks after the last administration. Re-sults indicated that the calcium antagonists partly protected against toxic effects induced bycadmium in different manners. These data provide further evidence for the new hypothesisthat the cross effect of cadmium and calcium in calmodulin regulated systems may be responsi-ble for the mechanism of cadmium intoxication. 'The results suggested that the calcium antag-onists could be a new and promising approach in the therapy of heavy metaLinduced diseases
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.
文摘Feng Fengyi , Zhang Pin , He Youjian 1, Li Yuhong1 , Zhou Meizhen2 , Chen Gang2 and Li Lin2 The Cancer Hospital of the CAMS & PUMC, Beijing 1000211 The Cancer Hospital of Sun Yat Sen University of Medical Sciences, Guangzhou 5100602Beijing Hospital of the Ministry of Health, Beijing 100730
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.
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.
文摘Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.
文摘Background Triple therapy(TT)with vitamin K-antagonists(VKA),aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation(PCI-S)in patients with an indication for oral anticoagulation.TT is associated with an increased risk of bleeding,but available evidence is flawed by important limitations,including the limited size and the retrospective design of most of the studies,as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding.Since the perceived high bleeding risk of TT may deny patients effective strategies,the determination of the true safety profile of TT is of paramount importance.Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed,and the weakness of the data was analyzed.Results The absolute incidence of major bleeding upon discharge at in-hospital,≤1 month,6 months,12 months and≥12 months was:3.3%±1.9%,5.1%±6.7%,8.0%±5.2%,9.0%±8.0,and 6.2%±7.8%,respectively,and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel.Conclusions While waiting for the ongoing,large-scale,registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT,this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented.
文摘Objective: To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform (α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the effects of three kinds of adrenergic receptor blockers: Carvedilol (CAR) , Metoprolol (MET) and Terazosin (TER) on these changes, and to elucidate the effects and new mechanism of CAR on left ventricular hypertrophy regression. Methods: A model of hypertrophy induced by coarctation of abdominal aorta(CAA)was used in this study. Thirty two male wistar rats were divided randomly into four groups 4 weeks after CAA operation: CAA, CAR, MET and TER. Hemodynamics, ventricular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expressions of Collagen Ⅰ / Ⅲ and Colligin were investigated in the four groups and sham operation group. Results: Left ventricle hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ /Ⅲ proteins and Colligin mRNA/protein increased( P < 0.05). CAR could ameliorate left ventricle hypertrophy prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ /Ⅲ and Colligin in both gene and protein levels ( P < 0.05), while MET and TER have no effect on them ( P > 0.05). Conclusion: The effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was independent of beta-adrenergic receptor antagonist.
文摘Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.
文摘Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors such as those of the prostate. Treatment modalities for prostate cancer in a localized stage or when it is still castration-sensitive yield good results in most patients. However, such treatments are only palliative in the advanced stage. Therefore, new therapeutic targets like growth hormone-releasing hormone receptor (GHRH-R) and its splice variants should be found in order to get effective treatments for more aggressive stages in prostate cancer. This review talks about the GHRH-R and its splice variants, the signaling pathways induced by GHRH to produce cancer, the structure activity relationship of GHRH-R antagonists and the resume of some <em>in vitro</em> and <em>in vivo</em> studies on the role of GHRH-R antagonists in the treatment of prostate cancer.
文摘The potential use ofcomposted wood fibre waste （WFW） for the cultivation of bacterial antagonists of Sclerotinia minor was examined with the result that a mix of millet seed （20% w/w） and WFW, suitably amended with nutrients, proved to be an ideal matrix for the growth of some of these bacteria. Densities in terms ofcfu＇s ranged from 8.5 IOgl0 cfu/g dw to 10.5 logl0 cfu/g dw ullder sterile conditions after 14 days incubation. Lower population densities of the antagonists were achieved under non-sterile conditions in the compost： millet mix of between 7.9-9.3 logm cfu/g dw at the same period. However, when applied in a pot （glasshouse） trial to protect against S. minor, the millet seed appeared to stimulate the growth of this pathogen resulting in a high incidence of attack of lettuce plants after 2-3 weeks. Although the percentage of healthy seedlings increased following application of compost mix grown antagonists （at a rate of 5% v/v） when compared to the control treatment, these values were not statistically significant （p〉0.05） in most cases. Therefore, the use of millet seeds cannot be recommended as a nutrient supplement for the bacterial antagonist cultivation, if to be subsequently used to control fungal pathogens in the field.
