OBJECTIVE: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI). In current clinical situation, availability of different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) has enabled physicians to switch among therapies owing to specific clinical scenarios. Although optimum time, loading dose and interval of transition between P2Y12 inhibitors is still controversial and needs further evidence, switching between oral inhibitors frequently occurs in clinical practice for several reasons. DATA SOURCES: This review was based on data in articles published in PubMed up to June 2018, with the following keywords "antiplatelet therapy", "ACS", "PCI", "ticagrelor", and "clopidogrel". STUDY SELECTION: Original articles and critical reviews on de-escalation strategy in ACS patients after PCI were selected. References of the retrieved articles were also screened to search for potentially relevant papers. RESULTS: Safety concerns associated with switching between antiplatelet agents, has prompted the use of clopidogrel for patients with ACS especially after PCI as a de-escalation strategy. Practical considerations for de-escalating therapies in patients with ACS such as reducing dose of P2Y12 inhibitors or shortening duration of DAPT (followed by aspirin or P2Y12 receptor inhibitor monotherapy) as potential options are yet to be standardized and validated. CONCLUSIONS Current review will provide an overview of the pharmacology of common P2Y12 inhibitors, definitions of de-escalation and different de-escalating strategies and its outcomes, along with possible direction to be explored in de-escalation.
Acute Coronary Syndrome ; drug therapy ; therapy ; Aspirin ; therapeutic use ; Diamines ; therapeutic use ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; therapeutic use ; Purinergic P2Y Receptor Antagonists ; therapeutic use ; Thiazoles ; therapeutic use

OBJECTIVETo compare the clinical efficacy on knee osteoarthritis (KOA) at the early and middle stage between electroacupuncture (EA) and meloxicam.

METHODSNinety patients of KOA at the early and middle stage were randomized into an EA group and a meloxicam group, 45 cases in each one. In the EA group, EA was applied to Dubi (ST 35), Neixiyan (EX-LE 4), Liangqiu (ST 34), Heding (EX-LE 2), Xuehai (SP 10), Yan- glingquan (GB 34) and Zusanli (ST 36); the needles were retained for 20 min and EA was applied once every two days. In the meloxicam group, the meloxicam tablets were prescribed for oral administration, 7. 5 mg, once a day. The treatment lasted for 6 weeks in the two groups. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, rectus femoris muscle tension, the 8-foot walking test and 5-time sit-to-stand test were adopted to observe and compare the effects in the two groups.

RESULTSAfter treatment, every item score in WOMAC was reduced after treatment (all P < 0.05), but the difference was not significant between the two groups (all P > 0.05). In the EA group, the rectus femoris tension after treatment was reduced as compared with that before treatment (P < 0.05) and the reducing result was much more apparent as compared with that in the meloxicam group (P < 0.05). For the 8-foot walking test and 5-time sit-to-stand test, the time was shortened after treatment in the two groups (all P < 0.05) and the result in the EA group was much more obvious than that in the meloxicam group (both P < 0.05).

CONCLUSIONBoth EA and meloxicam are effective in the treatment of KOA at the early and middle stage. EA improves rectus femoris tension and recovers the internal mechanics balance and the efficacy is better than that of meloxicam.

Acupuncture Points ; Adult ; Aged ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; therapy ; Thiazines ; therapeutic use ; Thiazoles ; therapeutic use ; Treatment Outcome

PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia.
Biliary Atresia/complications/enzymology/*surgery ; Child ; Child, Preschool ; Chronic Disease ; Cyclooxygenase 2 Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/etiology/pathology/*prevention & control ; Male ; *Portoenterostomy, Hepatic ; Thiazines/*therapeutic use ; Thiazoles/*therapeutic use

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.

METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.

RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.

CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.

REGISTRATION NUMBERChiCTR-TRC-13003776.

Adult ; Blood Glucose ; drug effects ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Metformin ; administration & dosage ; adverse effects ; therapeutic use ; Middle Aged ; Thiazoles ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVETo evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).

METHODSTwenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA).

RESULTSLeft ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01).

CONCLUSIONSGarlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

Allyl Compounds ; pharmacology ; therapeutic use ; Animals ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Contrast Media ; Disease Models, Animal ; Disulfides ; pharmacology ; therapeutic use ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; complications ; diagnostic imaging ; drug therapy ; pathology ; Myocardial Reperfusion ; No-Reflow Phenomenon ; complications ; diagnostic imaging ; drug therapy ; pathology ; Swine ; Swine, Miniature ; Thiazoles ; metabolism ; Ultrasonography

No abstract available.
Base Sequence ; Benzamides/therapeutic use ; Bone Marrow/pathology ; Female ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/*genetics ; Middle Aged ; Philadelphia Chromosome ; Piperazines/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Sequence Analysis, DNA ; Thiazoles/therapeutic use ; Translocation, Genetic

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA> or =6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.
Adult ; Allopurinol/therapeutic use ; Antimetabolites/therapeutic use ; Benzbromarone/therapeutic use ; Cardiovascular Diseases/epidemiology/prevention & control ; Comorbidity ; Diabetes Mellitus, Type 2/epidemiology/prevention & control ; Enzyme Inhibitors/therapeutic use ; Female ; Gout/*drug therapy/*prevention & control ; Gout Suppressants/*therapeutic use ; Humans ; Hypertension/epidemiology/prevention & control ; Male ; Middle Aged ; Renal Insufficiency, Chronic/epidemiology/prevention & control ; Retrospective Studies ; Thiazoles/therapeutic use ; Uric Acid/*blood/metabolism ; Uricosuric Agents/therapeutic use ; Urolithiasis/epidemiology/prevention & control

This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.
Allopurinol ; therapeutic use ; Febuxostat ; Gout ; blood ; drug therapy ; Gout Suppressants ; therapeutic use ; Humans ; Thiazoles ; therapeutic use ; Uric Acid ; blood

PURPOSE: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. MATERIALS AND METHODS: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). RESULTS: Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85+/-0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. CONCLUSION: Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Butanones/therapeutic use ; Chronic Pain/*drug therapy ; Diclofenac/therapeutic use ; Female ; Muscles/drug effects ; Naproxen/therapeutic use ; Pelvic Floor/*pathology ; Pelvic Pain/*drug therapy ; Piroxicam/therapeutic use ; Rats ; Rats, Wistar ; Thiazines/therapeutic use ; Thiazoles/therapeutic use

BACKGROUNDAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis. A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis. Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases. But the role of PPARβ/δ in ALI remains uncertain. The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis.

METHODSCecal ligation and puncture (CLP) was used as a sepsis model. Rats were randomly divided into four groups, the control group (CON, n = 6), sham-operation group (SHAM, n = 12), cecal ligation and puncture group (CLP, n = 30), GW501516 group (CLP+GW, n = 25), which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight). Survival was monitored to 24 hours after operation. Blood pressure, serum creatinine, blood urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were measured after CLP. Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits. Lung tissue samples were stained with H&E and scored according to the degree of inflammation. Bacterial colonies were counted in the peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516 (0.15 µmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 µg/ml) for 2 hours. The TNF-α, IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting.

RESULTSGW501516 significantly increased the survival of septic rats, decreased histological damage of the lungs, reduced inflammatory cytokines in serum and lung tissues of septic rats and did not increase counts of peritoneal bacteria. In vitro, GW501516 and over-expression of PPARβ/δ attenuated gene expression of TNF-α, IL-1β and IL-6 in alveolar macrophages. Both in vivo and in vitro, PPARβ/δ inhibited the phosphorylation of STAT3.

CONCLUSIONPPARβ/δ plays a protective role in sepsis induced ALI via suppressing excessive inflammation.

Acute Lung Injury ; drug therapy ; etiology ; Animals ; Cells, Cultured ; Male ; PPAR delta ; agonists ; metabolism ; PPAR-beta ; agonists ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sepsis ; complications ; drug therapy ; Thiazoles ; therapeutic use