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1.
J Appl Toxicol ; 43(6): 789-798, 2023 06.
Article in English | MEDLINE | ID: mdl-36523111

ABSTRACT

Asiaticoside is a natural triterpene compound derived from Centella asiatica, possessing confirmed cardioprotective property. However, the roles of asiaticoside in regulating oxygen-glucose deprivation/reoxygenation (OGD/R)-caused cardiomyocyte dysfunction remain largely obscure. Human cardiomyocyte AC16 cells were stimulated with OGD/R to mimic myocardial ischemia/reperfusion injury and treated with asiaticoside. Cytotoxicity was investigated by CCK-8 assay and lactate dehydrogenase (LDH) release analysis. Autophagy- and Wnt/ß-catenin signaling-related protein levels were measured via western blotting. Asiaticoside (0-20 µM) did not induce cardiomyocyte cytotoxicity. Asiaticoside (20 µM) mitigated OGD/R-induced autophagy, cytotoxicity, oxidative stress, and myocardial injury. Rapamycin, an autophagy inductor, reversed the influences of asiaticoside on autophagy, cytotoxicity, oxidative stress, and myocardial injury, whereas 3-methyadanine, an autophagy inhibitor, played an opposite effect. Asiaticoside (20 µM) attenuated OGD/R-induced Wnt/ß-catenin signaling inactivation, which was reversed after transfection with si-ß-catenin. Transfection with si-ß-catenin attenuated the influences of asiaticoside on autophagy, cytotoxicity, oxidative stress, and myocardial injury. In conclusion, asiaticoside protected against OGD/R-induced cardiomyocyte cytotoxicity, oxidative stress, and myocardial injury via blunting autophagy through activating the Wnt/ß-catenin signaling, indicating the therapeutic potential of asiaticoside in myocardial ischemia/reperfusion injury.


Subject(s)
Myocardial Reperfusion Injury , Triterpenes , Humans , Myocytes, Cardiac , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , beta Catenin/metabolism , Oxygen/metabolism , Glucose/metabolism , Apoptosis , Triterpenes/pharmacology , Triterpenes/metabolism , Autophagy
2.
Small ; 18(21): e2200813, 2022 05.
Article in English | MEDLINE | ID: mdl-35445548

ABSTRACT

External light irradiation is usually required in bacterial infection theranostics; however, it is always accompanied by limited light penetration, imaging interference, and incomplete bacterial destruction. Herein, a feasible "image-launching therapy" strategy is developed to integrate real-time optical imaging and simultaneous photodynamic therapy (PDT) of bacterial infections into persistent luminescence (PL) nanoparticles (NPs). Mesoporous silica NPs are used as a substrate for in situ deposition of PL nanodots of ZnGa2 O4 :Cr3+ to obtain mPL NPs, followed by surface grafting with silicon phthalocyanine (Si-Pc) and electrostatic assembly of cyanine 7 (Cy7) to fabricate mPL@Pc-Cy NPs. The PL emission of light-activated mPL@Pc-Cy NPs is quenched by Cy7 assembly at physiological conditions through the fluorescence resonance energy transfer effect, but is rapidly restored after disassembly of Cy7 in response to bacterial infections. The self-illuminating capabilities of NPs avoid tissue autofluorescence under external light irradiation and achieve real-time colorimetric imaging of bacterial infections. In addition, the afterglow of mPL NPs can persistently excite Si-Pc photosensitizers to promote PDT efficacy for bacterial elimination and accelerate wound full recovery with normal histologic features. Thus, this study expands the theranostic strategy for precise imaging and simultaneous non-antibiotic treatment of bacterial infections without causing side effects to normal tissues.


Subject(s)
Bacterial Infections , Nanoparticles , Photochemotherapy , Bacterial Infections/diagnostic imaging , Bacterial Infections/drug therapy , Humans , Luminescence , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Precision Medicine
3.
J Cardiovasc Pharmacol ; 75(1): 84-90, 2020 01.
Article in English | MEDLINE | ID: mdl-31569121

ABSTRACT

Asiaticoside (AS), one of the main functional components of Centella asiatica, has been reported to protect neurons from ischemia-hypoxia-induced injury. However, the role of AS in myocardial oxygen-glucose deprivation/reoxygenation (OGD/R) injury has not been investigated. The aim of this study was to investigate the role of AS in OGD/R-treated H9c2 cardiomyocytes and the underlying mechanism involved. Cell viability was detected using MTT assay. Cell apoptosis was measured using flow cytometry. The oxidative stress was assessed by detecting the malonaldehyde (MDA) content and activities of superoxide dismutase, glutathione peroxidase, and catalase (CAT). The glucose consumption and lactate production were determined to reflect glycolysis rate. The expression levels of hexokinase II (HK2) were detected using reverse transcription quantitative polymerase chain reaction and Western blot. H9c2 cells were transfected with small interfering RNA targeting HK2 (si-HK2) to knockdown HK2. Results showed that AS improved cell viability and inhibited apoptosis in OGD/R-injured H9c2 cells. AS pretreatment prevented OGD/R-induced oxidative stress, as evidenced by the decreased MDA content, and increased activities of superoxide dismutase, glutathione peroxidase, and CAT. The decreased glucose consumption and lactate production in OGD/R-injured H9c2 cells were reversed after AS treatment. Mechanically, AS induced the expression of HK2 in OGD/R-injured H9c2 cells. Knockdown of HK2 abolished the protective effects of AS on OGD/R-injured H9c2 cells. In conclusion, the protective effects of AS on cardiomyocytes from OGD/R-induced injury were mediated at least partly by upregulating HK2.


Subject(s)
Antioxidants/pharmacology , Glycolysis/drug effects , Hexokinase/metabolism , Myocardial Reperfusion Injury/drug therapy , Myocytes, Cardiac/drug effects , Oxidative Stress/drug effects , Triterpenes/pharmacology , Animals , Apoptosis/drug effects , Cell Hypoxia , Cell Line , Cytoprotection , Glucose/deficiency , Hexokinase/genetics , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , Rats , Up-Regulation
4.
Cell Mol Biol Lett ; 24: 61, 2019.
Article in English | MEDLINE | ID: mdl-31768184

ABSTRACT

BACKGROUND: Ischemia/hypoxia-induced cardiomyocyte apoptosis has been considered as a main cause of myocardial infarction. Here, we aimed to investigate the functional role of miR-30b-5p in hypoxic cardiomyocytes. METHODS: AC16 human cardiomyocytes were cultured under hypoxia to simulate myocardial infarction. A qRT-PCR assay was performed to determine miR-30b-5p expression in hypoxic cardiomyocytes. Cell survival, injury and apoptosis were assessed by MTT, lactate dehydrogenase (LDH) release, and flow cytometry assays, respectively. The target gene of miR-30b-5p in hypoxic cardiomyocytes was validated by luciferase reporter assay and Western blotting. RESULTS: MiR-30b-5p expression was found to be significantly upregulated in hypoxic AC16 cells. The in vitro experiments showed that downregulation of miR-30b-5p effectively alleviated hypoxia-induced cardiomyocyte injury. Furthermore, Aven is a potential target gene of miR-30b-5p and its downregulation could partially reverse the influence of miR-30b-5p knockdown on AC16 cells under hypoxia. CONCLUSIONS: Inhibition of miR-30b-5p could protect cardiomyocytes against hypoxia-induced injury by targeting Aven.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Membrane Proteins/genetics , MicroRNAs/genetics , Myocytes, Cardiac/metabolism , Apoptosis , Cell Hypoxia , Cell Line , Cell Survival , Down-Regulation , Humans , Myocytes, Cardiac/cytology , Up-Regulation
5.
Med Sci Monit ; 24: 6544-6550, 2018 Sep 17.
Article in English | MEDLINE | ID: mdl-30223281

ABSTRACT

BACKGROUND The aim of this study was to investigate the optimal route of administration of diltiazem in emergency PCI and to provide the best clinical treatment for ASTEMI patients. MATERIAL AND METHODS A total of 90 patients with ASTEMI treated in our hospital from January 2015 to January 2016 were selected. Prior to thrombus aspiration, a thrombus aspiration catheter was used to perform diltiazem injection at the distal end of the infarct-related artery (IRA). We chose the acute ST-elevation myocardial infarction (ASTEMI) patients treated with direct PCI to compare different administration routes of diltiazem. The occurrence of major adverse cardiac events (MACEs) was closely observed during hospitalization and was obtained through outpatient visits or telephone follow-ups over the next 6 months. RESULTS Intracoronary infusion of diltiazem at the distal end of the culprit vessel, compared to conventional coronary mouth and intravenous injection, was significantly improved in thrombolysis in myocardial infarction (TIMI) frame count immediately after PCI stent implantation, ST-segment drop rate after 90 min, and left ventricular ejection fraction (LVEF) after 1 week. Furthermore, the peak value of high-sensitivity cardiac troponin I (hs-cTnI), a marker for myocardial injury, was the lowest. White blood cell count, neutrophil count, mean platelet volume (MPV), and high-sensitivity C-reactive protein (hs-CRP) were significantly lower than with the other 2 administration routes, and there was no effect on intracoronary pressure or heart rate. CONCLUSIONS Patients with ASTEMI who underwent emergency PCI treatment had good clinical outcomes using intracoronary diltiazem at the distal end of the culprit vessel.


Subject(s)
Diltiazem/administration & dosage , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/drug therapy , Acute Disease , Aged , Angioplasty, Balloon, Coronary/methods , China , Coronary Angiography , Diltiazem/pharmacology , Electrocardiography , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Treatment Outcome , Ventricular Function, Left
6.
Am J Physiol Heart Circ Physiol ; 310(5): H639-47, 2016 Mar 01.
Article in English | MEDLINE | ID: mdl-26747497

ABSTRACT

Although atherosclerosis has been widely investigated at carotid artery bifurcation, there is a lack of morphometric and hemodynamic data at different stages of the disease. The purpose of this study was to determine the lesion difference in patients with carotid artery disease compared with healthy control subjects. The three-dimensional (3D) geometry of carotid artery bifurcation was reconstructed from computed tomography angiography (CTA) images of Chinese control subjects (n = 30) and patients with carotid artery disease (n = 30). We defined two novel vector angles (i.e., angles 1 and 2) that were tangential to the reconstructed contour of the 3D vessel. The best-fit diameter was computed along the internal carotid artery (ICA) center line. Hemodynamic analysis was performed at various bifurcations. Patients with stenotic vessels have larger angles 1 and 2 (151 ± 11° and 42 ± 20°) and smaller diameters of the external carotid artery (ECA) (4.6 ± 0.85 mm) compared with control subjects (144 ± 13° and 36 ± 16°, 5.2 ± 0.57 mm) although there is no significant difference in the common carotid artery (CCA) (7.1 ± 1.2 vs. 7.5 ± 1.0 mm, P = 0.18). In particular, all patients with carotid artery disease have a stenosis at the proximal ICA (including both sinus and carina regions), while 20% of patients have stenosis at the middle ICA and 20% have stenosis expansion to the entire cervical ICA. Morphometric and hemodynamic analyses suggest that atherosclerotic plaques initiate at both sinus and carina regions of ICA and progress downstream.


Subject(s)
Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/physiopathology , Carotid Stenosis/diagnosis , Hemodynamics , Plaque, Atherosclerotic , Tomography, X-Ray Computed , Adult , Aged , Blood Flow Velocity , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/pathology , Carotid Stenosis/physiopathology , China , Computer Simulation , Disease Progression , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Models, Cardiovascular , Predictive Value of Tests , Radiographic Image Interpretation, Computer-Assisted , Regional Blood Flow , Retrospective Studies , Severity of Illness Index , Stress, Mechanical , Ultrasonography, Doppler
7.
Pak J Med Sci ; 32(2): 427-30, 2016.
Article in English | MEDLINE | ID: mdl-27182254

ABSTRACT

OBJECTIVE: To evaluate the effects of ischemic postconditioning on expressions of pentraxin-related protein 3 (PTX3) and neutrophil CD11b in the plasma of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: Fifty-six patients who had AMI with ST-segment elevation were randomly divided into a control group and an ischemic postconditioning group (n=28). Both groups received emergency PCI. After recanalization of infarct-related arteries, the control group did not receive intervention within three minutes, while the ischemic postconditioning group was treated by low-pressure filling and emptying of balloon within one minute. The plasma expressions of PTX3 before and 24 hour after PCI were detected by ELISA, and those of neutrophil CD11b were detected by flow cytometry. RESULTS: PTX3 and neutrophil CD11b expressions of the two groups were similar before PCI, but those of the ischemic postconditioning group significantly decreased 24 hour after PCI (P<0.05). CONCLUSION: Ischemic postconditioning lowered the expressions of PTX3 and neutrophil CD11b in AMI patients after PCI, inhibited inflammatory response, reduced the adhesion between leukocytes and endothelial cells, and protected the ischemic-reperfused myocardium.

8.
N Engl J Med ; 365(6): 527-36, 2011 Aug 11.
Article in English | MEDLINE | ID: mdl-21830967

ABSTRACT

BACKGROUND: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. In two trials, we aimed to determine the efficacy and safety of linaclotide in patients with chronic constipation. METHODS: We conducted two randomized, 12-week, multicenter, double-blind, parallel-group, placebo-controlled, dual-dose trials (Trials 303 and 01) involving 1276 patients with chronic constipation. Patients received either placebo or linaclotide, 145 µg or 290 µg, once daily for 12 weeks. The primary efficacy end point was three or more complete spontaneous bowel movements (CSBMs) per week and an increase of one or more CSBMs from baseline during at least 9 of the 12 weeks. Adverse events were also monitored. RESULTS: For Trials 303 and 01, respectively, the primary end point was reached by 21.2% and 16.0% of the patients who received 145 µg of linaclotide and by 19.4% and 21.3% of the patients who received 290 µg of linaclotide, as compared with 3.3% and 6.0% of those who received placebo (P<0.01 for all comparisons of linaclotide with placebo). Improvements in all secondary end points were significantly greater in both linaclotide groups than in the placebo groups. The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in both linaclotide groups. CONCLUSIONS: In these two 12-week trials, linaclotide significantly reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks and benefits of linaclotide in chronic constipation. (Funded by Ironwood Pharmaceuticals and Forest Research Institute; ClinicalTrials.gov numbers, NCT00765882 and NCT00730015.).


Subject(s)
Constipation/drug therapy , Laxatives/therapeutic use , Peptides/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Chronic Disease , Defecation/drug effects , Diarrhea/chemically induced , Double-Blind Method , Female , Guanylate Cyclase , Humans , Laxatives/adverse effects , Male , Middle Aged , Peptides/adverse effects , Quality of Life , Receptors, Guanylate Cyclase-Coupled/agonists , Withholding Treatment , Young Adult
9.
Cardiol J ; 30(2): 178-187, 2023.
Article in English | MEDLINE | ID: mdl-34581424

ABSTRACT

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD), the treatment strategy for non-infarct-related artery (non-IRA) remains controversial. Quantitative flow ratio (QFR) is a new angiography-based physiological assessment index. However, there is little evidence on the practical clinical application of QFR. METHODS: Two hundred and twenty-nine patients with STEMI and MVD were recruited for this study. Patients were randomly assigned to either receive QFR-guided complete revascularization (QFR-G-CR) of non-IRA or receive no further invasive treatment. The primary (1°) endpoint analyzed included death due to all causes, non-fatal myocardial infarction (MI), and ischemia-induced revascularization at 12 months post-surgery. Secondary (2°) endpoints included cardiovascular death, unstable angina, stent thrombosis, New York Heart Association (NYHA) class IV heart failure, and stroke at 1 year post surgery. Massive bleeding and contrast-associated acute kidney injury (CAKI) were used as safety endpoints. RESULTS: Around the 12 month follow up, the 1o outcome was recorded in 11/115 patients (9.6%) in the QFR-G-CR population, relative to 23/114 patients (20.1%) in the IRA-only PCI population (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.22-0.92; p = 0.025). Unstable angina in 6 (5.2%) and 16 (14.0%) patients (HR: 0.36; 95% CI: 0.14-0.92; p = 0.026), respectively. No marked alterations were found in the massive bleeding and CAKI categories. CONCLUSIONS: In conclusion, STEMI and MVD patients can benefit from QFR-G-CR of non-IRA lesions in the initial stages of acute MI. This can help reduce incidences of major adverse cardiovascular events and unstable angina, relative to IRA treatment only. Chinese Clinical Trial Registration number: ChiCTR2100044120.


Subject(s)
Coronary Artery Disease , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Pilot Projects , Treatment Outcome , Myocardial Infarction/etiology , Angina, Unstable , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Myocardial Revascularization
10.
Circulation ; 123(15): 1622-32, 2011 Apr 19.
Article in English | MEDLINE | ID: mdl-21464051

ABSTRACT

BACKGROUND: Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. METHODS AND RESULTS: We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase-MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk reduction in the active-treatment arm (odds ratio by fixed-effects model 0.56, 95% confidence interval, 0.44 to 0.71, P<0.00001). The rate of major adverse cardiac events at 30 days was significantly lower in the high-dose statin group (7.4% versus 12.6%, a 44% risk reduction; P<0.00001), and 1-month major adverse cardiac events, excluding periprocedural events, were also reduced (0.6% versus 1.4%; P=0.05). The benefit of high-dose statins was realized irrespective of clinical presentation (P for interaction=0.43) and was maintained across various subgroups but appeared greater in the subgroup with elevated baseline C-reactive protein levels (n=734; 68% risk reduction for periprocedural myocardial infarction versus 31% in those 1861 patients with normal CRP; P for quantitative interaction=0.025). CONCLUSIONS: High-dose statin pretreatment leads to a significant reduction in periprocedural myocardial infarction and 30-day adverse events in patients undergoing percutaneous coronary intervention. This strategy should be considered in all patients with planned percutaneous coronary intervention.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Percutaneous Coronary Intervention/adverse effects , Postoperative Complications/prevention & control , Preoperative Care/methods , Humans , Postoperative Complications/epidemiology , Randomized Controlled Trials as Topic/methods , Treatment Outcome
11.
Am J Gastroenterol ; 107(11): 1702-12, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22986437

ABSTRACT

OBJECTIVES: Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide treatment in patients with irritable bowel syndrome with constipation (IBS-C) over 26 weeks. METHODS: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 µg of oral linaclotide once daily for a 26-week treatment period. The primary and the secondary efficacy assessments were evaluated over the first 12 weeks of treatment. Primary end points included the Food and Drug Administration's (FDA's) end point for IBS-C (responder: a patient who reported (i) improvement of ≥ 30 % from baseline in average daily worst abdominal pain score and (ii) increase of ≥ 1 complete spontaneous bowel movement (CSBM) from baseline, both in the same week for ≥ 6 / 12 weeks) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored. RESULTS: In all, 804 patients (mean age = 44 years, female = 90 % , white = 78 % ) were evaluated; 33.7 % of linaclotide-treated patients were FDA end point responders, vs. 13.9 % of placebo-treated patients ( P < 0.0001) (number needed to treat = 5.1, 95 % confidence interval (CI): 3.9, 7.1). The pain responder criterion of the FDA end point was met by 48.9 % of linaclotide-treated patients vs. 34.5 % of placebo-treated patients (number needed to treat = 7.0, 95 % CI: 4.7, 13.1), and the CSBM responder criterion was met by 47.6 % of linaclotide-treated patients, vs. 22.6 % of placebo patients (number needed to treat = 4.0, 95 % CI: 3.2, 5.4). Remaining primary end points ( P < 0.0001) and all secondary end points ( P < 0.001), including abdominal pain, abdominal bloating, and bowel symptoms (SBM and CSBM rates, Bristol Stool Form Scale (BSFS) score, and straining), were also statistically significantly improved with linaclotide vs. placebo. Statistically significant differences from placebo were observed for responder and continuous end points over 26 weeks of treatment. AE incidence was similar between treatment groups, except for diarrhea, which caused discontinuation in 4.5 % of linaclotide patients vs. 0.2 % of placebo patients. CONCLUSIONS: Linaclotide 290 µg once daily significantly improved abdominal and bowel symptoms associated with IBS-C over 26 weeks of treatment.


Subject(s)
Constipation/drug therapy , Irritable Bowel Syndrome/drug therapy , Peptides/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Double-Blind Method , Endpoint Determination , Female , Humans , Male , Middle Aged , Peptides/adverse effects , Placebos , Treatment Outcome
12.
Am J Gastroenterol ; 107(11): 1714-24; quiz p.1725, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22986440

ABSTRACT

OBJECTIVES: Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C). METHODS: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 µ g oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period. There were four primary end points, the Food and Drug Administration ' s (FDA ' s) primary end point for IBS-C (responder: improvement of ≥ 30 % in average daily worst abdominal pain score and increase by ≥ 1 complete spontaneous bowel movement (CSBM) from baseline (same week) for at least 50 % of weeks assessed) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9 / 12 weeks. Adverse events (AEs) were monitored. RESULTS: The trial evaluated 800 patients (mean age = 43.5 years, female = 90.5 % , white = 76.9 % ). The FDA end point was met by 136 / 405 linaclotide-treated patients (33.6 % ), compared with 83 / 395 placebo-treated patients (21.0 % ) ( P < 0.0001) (number needed to treat: 8.0, 95 % confidence interval: 5.4, 15.5). A greater percentage of linaclotide patients, compared with placebo patients, reported for at least 6 / 12 treatment period weeks, a reduction of ≥ 30 % in abdominal pain (50.1 vs. 37.5 % , P = 0.0003) and an increase of ≥ 1 CSBM from baseline (48.6 vs. 29.6 % , P < 0.0001). A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points ( P < 0.05). Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points ( P < 0.001). During the RW period, patients remaining on linaclotide showed sustained improvement; patients re-randomized from linaclotide to placebo showed return of symptoms, but without worsening of symptoms relative to baseline. Diarrhea, the most common AE, resulted in discontinuation of 5.7 % of linaclotide and 0.3 % of placebo patients. CONCLUSIONS: Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period.


Subject(s)
Constipation/drug therapy , Irritable Bowel Syndrome/drug therapy , Peptides/therapeutic use , Abdominal Pain/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Double-Blind Method , Endpoint Determination , Female , Humans , Male , Middle Aged , Pain Measurement , Peptides/administration & dosage , Peptides/adverse effects , Placebos , Treatment Outcome
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(10): 1273-1276, 2022 Oct 15.
Article in Zh | MEDLINE | ID: mdl-36310466

ABSTRACT

Objective: To investigate the effectiveness of modified dorsal metacarpal artery reverse island flap based on two adjacent recurrent branches of dorsal metacarpal arteries in repairing large skin defect of the hand. Methods: Between September 2017 and March 2021, 15 cases of large skin defect of the hand were treated. There were 11 males and 4 females with an average age of 42 years (range, 24-66 years). The injury causes included machine twist injury in 6 cases, pound injury in 5 cases, and crush injury in 4 cases. The injured parts included 6 cases of finger skin defect and 9 cases of distal skin defect of palm and dorsum of hand, all of which had tendon, joint, and bone exposure. The interval from injury to operation ranged from 2 to 6 hours (mean, 4 hours). The defect sizes after thorough debridement ranged from 3.5 cm×3.0 cm to 8.0 cm×4.5 cm. The modified dorsal metacarpal artery reverse island flap with a range of 3.8 cm×3.3 cm to 9.0 cm×5.0 cm was used to repair the defect, and the flap donor site was repaired with full-thickness skin graft. Results: All the flaps survived successfully after operation, and the wounds in the recipient site and the skin grafts in the donor site healed by first intention. All patients were followed up 9-24 months, with an average of 14 months. The appearance of the flap was good, and its texture and color were similar to those of the surrounding normal tissue. There was no obvious scar contracture, depression, and pigmentation in the donor site. At last follow-up, the static two-point discrimination of the flap was 8-20 mm, with an average of 13.6 mm. According to the Michigan Hand Outcome Questionnaire, 5 patients were very satisfied with the appearance of the flap, and 10 patients were satisfied. Conclusion: The modified dorsal metacarpal artery reverse island flap based on two adjacent recurrent branches of dorsal metacarpal arteries has reliable blood supply, larger harvested area, simple procedure, and minimal donor site damage, which is suitable for emergency repair of large skin defect of the hand.


Subject(s)
Finger Injuries , Metacarpal Bones , Plastic Surgery Procedures , Soft Tissue Injuries , Male , Female , Humans , Adult , Skin Transplantation/methods , Finger Injuries/surgery , Metacarpal Bones/surgery , Plastic Surgery Procedures/methods , Surgical Flaps/blood supply , Arteries/surgery , Soft Tissue Injuries/surgery , Treatment Outcome
14.
ACS Appl Mater Interfaces ; 14(43): 49375-49388, 2022 Nov 02.
Article in English | MEDLINE | ID: mdl-36270272

ABSTRACT

Antibacterial wound dressings are confronted with the challenges in real-time imaging of infected wounds and effective removal of bacterial debris after sterilization to promote the healing process. Herein, injectable theranostic hydrogels were constructed from antimicrobial peptide ε-polylysine (ePL) and polydopamine (PDA) nanoparticles for real-time diagnosis of infected wounds, imaging-guided antibacterial photodynamic therapy (PDT), and on-demand removal of bacterial debris. Ureido-pyrimidinone was conjugated on ePL to produce PLU hydrogels through quadruple hydrogen bonding, and the inoculation of tetrakis(4-carboxyphenyl)porphyrin (TCPP)-loaded PDA (PTc) nanoparticles introduced Schiff base linkages in PLU@PTc hydrogels. The double-cross-linked networks enhance mechanical performance, adhesion strength, and self-healing properties of hydrogels, and the dynamic cross-linking enables their photothermal removal. The injection of PLU precursors and PTc NPs generates in situ sol-gel transformation, and the acid-triggered release of TCPP restores fluorescence emissions for real-time imaging of infected wounds under 410 nm illumination. Then, the released TCPP in the infected wounds is illuminated at 660 nm to launch a precise antibacterial PDT, which is strengthened by the bacterial capture on hydrogels. Hydrogels with wrapped bacterial debris are removed under illumination at 808 nm, and the hydrogel dressing change accelerates healing of infected wounds through simultaneous relief of oxidative stress, regulation of inflammatory factors, acceleration of collagen deposition, and promotion of angiogenesis. Thus, this study demonstrates a feasible strategy for wound infection theranostics through bacterial infection-triggered visual imaging, efficient nonantibiotic sterilization, and on-demand dressing change and bacterial debris removal.


Subject(s)
Photochemotherapy , Wound Infection , Humans , Hydrogels/chemistry , Precision Medicine , Wound Healing , Anti-Bacterial Agents/chemistry , Wound Infection/therapy
15.
J Biomed Nanotechnol ; 18(1): 288-292, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-35180923

ABSTRACT

This study aims to evaluate the clinical application value of two materials, drug-eluting stent, and biodegradable stent, in the treatment of coronary heart disease. The results show that the therapeutic effects of drug-eluting stents and biodegradable stents are similar. Both treatment methods have high safety and effectiveness. The ideal coronary artery stent should have good biocompatibility, safety, and possibility.


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Absorbable Implants , Biocompatible Materials , Coronary Artery Disease/drug therapy , Humans , Percutaneous Coronary Intervention/methods , Polymers , Prosthesis Design , Sirolimus , Stents , Treatment Outcome
16.
Tohoku J Exp Med ; 224(2): 91-7, 2011 06.
Article in English | MEDLINE | ID: mdl-21597242

ABSTRACT

ST-segment elevation myocardial infarction (STEMI) is the most severe type of heart attack, and primary percutaneous coronary intervention (PCI) is the first line treatment for STEMI. However, these patients are at higher risk of contrast-induced nephropathy (CIN), which increases the length of hospital stay and mortality rate. Anisodamine, an alkaloid extracted from a Chinese herb, has been shown to exert protective effects on the renal function. The aim of this study was to investigate the protective effect of anisodamine on CIN in STEMI patients undergoing primary PCI. A total of 126 consecutive STEMI patients were randomly assigned to receive anisodamine (n=60) or placebo (control, n=66) from admission to 24 hours after PCI. The serum creatinine (SCr) concentrations, estimated glomerular filtration rate (eGFR) and incidence of CIN were measured on admission, and 24, 48 and 72 hours after PCI between the two groups. We found that the renal function of all patients after PCI underwent a course from injury to recovery. The incidence of CIN was 5.0%, 8.3%, and 6.7% at 24, 48 and 72 hours, respectively, after primary PCI in anisodamine group, while in control group it was 16.7%, 22.7%, and 19.7%, respectively. The incidence of CIN in anisodamine group was lower than that in control group during 72 hours after PCI (all P<0.05). In conclusion, intravenous infusion of anisodamine before and after primary PCI may reduce the occurrence of CIN in STEMI patients undergoing primary PCI, without serious side effects.


Subject(s)
Angioplasty, Balloon, Coronary , Kidney/drug effects , Kidney/metabolism , Myocardial Infarction/physiopathology , Myocardial Infarction/surgery , Solanaceous Alkaloids/pharmacology , Adult , Aged , Creatinine/blood , Female , Free Radical Scavengers/pharmacology , Glomerular Filtration Rate , Humans , Kidney Function Tests , Male , Middle Aged , Placebos , Single-Blind Method
17.
Medicine (Baltimore) ; 100(42): e27446, 2021 Oct 22.
Article in English | MEDLINE | ID: mdl-34678874

ABSTRACT

BACKGROUND: Myocardial infarction is 1 of the most serious cardiovascular diseases. Early interventional therapy preserves the cardiac function of patients with myocardial infarction to the greatest extent, but it is far from meeting people's need only limited to cardiac revascularization. It is also necessary to help patients improve their quality of life, exercise tolerance, and reduce the incidence of acute cardiac recurrence as much as possible. All these depend on cardiac rehabilitation (CR) are based on exercise. Early and correct CR helps to improve the patient's heart function and improve living standards. Traditional Chinese exercise Tai Chi as an alternative form of CR has gradually become popular, but it lacks large samples and high-quality clinical studies to verify it. This study aims to explore the effect of Tai Chi on the cardiac function of patients with myocardial infarction, and to provide a strong basis for patients to choose which CR exercise. METHODS: This is a prospective randomized controlled trial. 272 patients with myocardial infarction will be randomly divided into an experimental group and a control group according to 1:1, with 136 cases in each group. The control group: conventional treatment; the experimental group: increase Tai Chi exercise on the basis of the control group. Both groups will receive standard treatment for 24 weeks and will be followed up for 3 months. Observation indicators include: total effective rate, 6 minutes walking test, brain natriuretic peptide, left ventricular ejection fraction, the adverse reaction rate, etc. The data will be analyzed by using SPSS 25.0 software. DISCUSSION: This study will evaluate the effect of Tai Chi on the cardiac function of patients with myocardial infarction. The results of this test will provide clinical evidence for patients to choose which CR exercise. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/QKWDP.


Subject(s)
Exercise Therapy/methods , Myocardial Infarction/rehabilitation , Tai Ji/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain , Prospective Studies , Quality of Life , Research Design , Severity of Illness Index , Tai Ji/adverse effects , Ventricular Function, Left , Walk Test
18.
Open Life Sci ; 16(1): 899-908, 2021.
Article in English | MEDLINE | ID: mdl-34553070

ABSTRACT

This research aimed to describe the functions of vascular endothelial cells (VECs) in protecting target organs and the anti-atherosclerotic effects of different enantiomers of amlodipine on a rabbit model of atherosclerosis. Thirty male New Zealand white rabbits were randomly allocated to four groups (nA = 9, nB = 7, nC = 7, and nD = 7 rabbits): rabbits in group-A (control group) were fed a high-fat diet, group-B rabbits were fed a high-fat diet plus 2.5 mg/kg/day S-amlodipine, group-C rabbits were fed a high-fat diet plus 2.5 mg/kg/day R-amlodipine, and group-D rabbits were fed a high-fat diet plus 5 mg/kg/day racemic amlodipine. Different enantiomers of amlodipine did not influence lipid profiles and serum level of eNOS in the rabbit atherosclerosis model but decreased ET-1 expression to some extent. The serum NO and iNOS levels in the drug intervention groups were significantly reduced. No significant differences in the rabbits' body weights were observed. At the 4th and 8th weeks, the serum lipid profiles significantly increased in high cholesterol diet groups. The serum ET-1 level was significantly increased in each group of rabbits at the 8th week. Both S-amlodipine and R-amlodipine may protect the endothelium by reducing the serum ET-1 level, downregulating iNOS expression.

19.
Acta Radiol ; 51(6): 641-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20438292

ABSTRACT

BACKGROUND: Contrast-induced nephropathy (CIN) is one of the leading causes of hospital-acquired renal failure and increase in the mortality and length of hospital stay after percutaneous coronary intervention (PCI). PURPOSE: To evaluate the protective effect of B-type natriuretic peptide (BNP) on CIN in patients with heart failure undergoing PCI. MATERIAL AND METHODS: In the prospective, placebo-controlled, randomized trial, 149 consecutive acute myocardial infarction (AMI) patients with heart failure undergoing primary PCI received recombinant human BNP (rhBNP) or placebo from the time of admission to 24 h after PCI. Serum creatinine (SCr) levels were measured to evaluate the protective effect of rhBNP on renal function. Estimated glomerular filtration rate (eGFR) was calculated by the simplified modification of diet in renal disease study equation. CIN was defined as a postprocedure peak increase in SCr of >0.5 mg/dl or >25% from baseline. RESULTS: The baseline characteristics were similar in the two groups. The SCr significantly increased after PCI, with the peak value at 48 h, and then began to decrease. At day 7 after PCI, the SCr had lowered to the baseline level in the BNP group, but it failed to do so in the control group. At 24, 48, and 72 h and 7 days after PCI, the SCr was lower in the BNP group than that in the control group. The eGFR decreased significantly after PCI, with the lowest value at 48 h, and then it began to increase. The eGFR after PCI was higher in the rhBNP group than that in the control group. The occurrence of CIN was significantly lower in the rhBNP group than in the control group. CONCLUSION: Periprocedural use of BNP could further promote the recovery of renal function and decrease the occurrence of CIN compared with routine treatment alone in patients with heart failure undergoing primary PCI.


Subject(s)
Angioplasty , Contrast Media/adverse effects , Heart Failure/surgery , Kidney Diseases/prevention & control , Natriuretic Peptide, Brain/therapeutic use , Protective Agents/therapeutic use , Aged , Creatinine/blood , Female , Glomerular Filtration Rate , Heart Failure/blood , Humans , Kidney Diseases/blood , Kidney Diseases/chemically induced , Male , Middle Aged
20.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 22(11): 669-73, 2010 Nov.
Article in Zh | MEDLINE | ID: mdl-21122202

ABSTRACT

OBJECTIVE: To evaluate the protective effect of recombinant human B-type natriuretic peptide (rhBNP) on cardiac and renal functions in heart failure (HF) patients as a result of acute anterior myocardial infarction (AAMI) in peri-operative period of primary percutaneous coronary intervention (pPCI). METHODS: One hundred and twenty-six patients with AAMI-HF were enrolled into this study. All patients undertaken pPCI were randomly assigned to the rhBNP group (n=62) or the control group (n=64). rhBNP or nitroglycerin was intravenously administered on the basis of conventional treatment from first day of admission to 24 hours after pPCI in both groups. Heart rate (HR), systolic blood pressure (SBP), B-type natriuretic peptide (BNP), estimated glomerular filtration rate (eGFR) and heart function were observed. All patients were followed up for 30 days for the observation of main adverse cardiac events (MACE). RESULTS: The HR was significantly decreased compared with that at admission in rhBNP group, but such condition was not found in the control group. The SBP was reduced obviously in both groups. The plasma level of BNP, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD) were improved significantly at different time points compared with those before administration in both groups. The improvement of above parameters in rhBNP group was more significant than that in the control group [BNP (ng/L) 30 hours after pPCI: 303.5±128.4 vs. 354.0±133.6, 14 days after pPCI: 157.8±78.6 vs. 201.1±91.7; LVEF 1 day after pPCI: 0.420±0.052 vs. 0.378±0.055, 14 days after pPCI : 0.444±0.050 vs. 0.393±0.055, 30 days after pPCI: 0.469±0.053 vs. 0.413±0.052; LVEDD (mm) 1 day after pPCI: 53.5±4.4 vs. 57.6±4.4, 14 days after pPCI : 49.6±5.1 vs. 53.4±4.6, 30 days after pPCI: 46.5±4.4 vs. 50.2±4.8, P<0.05 or P<0.01]. The eGFR was reduced obviously 1 day after pPCI than that at admission in both groups, and eGFR recovered to baseline 3 days after pPCI. The level of eGFR was significantly increased 7 days and 14 days after pPCI than that at admission, but there was no difference between rhBNP group and control group. The incidence of contrast-induced nephropathy showed a lowering tendency in the rhBNP group than that in the control group [19.4% (12/62) vs. 29.7% (19/64), P=0.178]. The incidence of ventricular arrhythmias was obviously lowered 7 days after pPCI in the rhBNP group than that in the control group [48.4% (30/62) vs. 75.0% (48/64), P<0.01]. The rate of MACE was lower in rhBNP group than that in control group in 30 days [12.9% (8/62) vs. 26.6% (17/64), P<0.05]. CONCLUSION: Administration of rhBNP can effectively improve the heart function in AAMI-HF patients undergoing pPCI, and it lowered the incidence of MACE in 30 days, without influence on renal function, and it can reduce the incidence of contrast-induced nephropathy.


Subject(s)
Anterior Wall Myocardial Infarction/therapy , Heart Failure/therapy , Natriuretic Peptide, Brain/therapeutic use , Recombinant Proteins/therapeutic use , Aged , Angioplasty, Balloon, Coronary/methods , Anterior Wall Myocardial Infarction/complications , Electrocardiography , Female , Heart Failure/complications , Humans , Kidney Function Tests , Male , Middle Aged , Prognosis
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