Salidroside, the 8-O-beta-D-glucoside of tyrosol, is a novel adaptogenic drug extracted from the medicinal plant Rhodiola sachalinensis A. Bor. Due to the scarcity of R. sachalinensis and its low yield of salidroside, there is great interest in enhancing the production of salidroside by biotechnological process. Glucosylation of tyrosol is thought to be the final step in salidroside biosynthesis. In our related works, three UGT clones were isolated from the roots and the cultured cells. Our intention was to combine the catalytic specificity of these UGTs in vitro in order to change the level of salidroside in vivo by over-expression of the above UGTs. However, as the aglycone substrate of salidroside, the biosynthetic pathway of tyrosol and its regulation are less well understood. The results of related studies revealed that there are two different possibilities for the tyrosol biosynthetic pathway. One possibility is that tyrosol is produced from a p-coumaric acid precursor, which is derived mainly from phenylalanine. The second possibility is that the precursor of tyrosol might be tyramine, which is synthesized from tyrosine. Our previous work demonstrated that over-expression of the endogenous phenylalanine ammonia-lyase gene (PALrs1) and accumulation of p-coumaric acid did not facilitate tyrosol biosynthesis. In contrast, the data presented in our recent work provide in vitro and in vivo evidence that the tyrosine decarboxylase (RsTyrDC) is most likely to have an important function in the initial reaction of the salidroside biosynthesis pathway in R. Sachalinensis.
Genetic Engineering ; Glucosides ; biosynthesis ; Glycosylation ; Phenols ; Phenylethyl Alcohol ; analogs & derivatives ; chemistry ; metabolism ; Rhodiola ; metabolism ; Tyrosine ; metabolism ; Tyrosine Decarboxylase ; metabolism

Acute Disease ; Humans ; Male ; Middle Aged ; Thrombocytopenia ; chemically induced ; Tyrosine ; adverse effects ; analogs & derivatives

Female ; Humans ; Male ; Myocardial Infarction ; drug therapy ; therapy ; Percutaneous Coronary Intervention ; methods ; Tyrosine ; analogs & derivatives

Acute Coronary Syndrome ; drug therapy ; Angioplasty, Balloon, Coronary ; Aspirin ; administration & dosage ; Humans ; Platelet Aggregation Inhibitors ; administration & dosage ; Thrombelastography ; Ticlopidine ; administration & dosage ; analogs & derivatives ; Tyrosine ; administration & dosage ; analogs & derivatives

Minor fibrillar collagen types V and XI, are those less abundant than the fibrillar collagen types I, II and III. The alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable region. Genomic variation and, in some cases, extensive alternative splicing contribute to the unique sequence characteristics of the variable region. While unique expression patterns in tissues exist, the functions and biological relevance of the variable regions have not been elucidated. In this review, we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and XI alpha chains. Analysis of biochemical similarities among the peptides encoded by each exon of the variable region suggests the potential for a shared function. The alternative splicing, conservation of biochemical characteristics in light of low sequence conservation, and evidence for intrinsic disorder, suggest modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function.
Alternative Splicing ; genetics ; Animals ; Fibrillar Collagens ; chemistry ; genetics ; metabolism ; Humans ; Sulfates ; chemistry ; metabolism ; Surface Properties ; Tyrosine ; analogs & derivatives ; chemistry ; metabolism

OBJECTIVETo investigate whether thrombus aspiration plus intra-infarct-related artery bolus administration of tirofiban via the aspiration catheter is superior to thrombus aspiration alone in improving myocardial perfusion in patients with ST-elevation myocardial infarction (STEMI) undergoing primary angioplasty.

METHODSIn this single center retrospective study, 108 patients with STEMI who underwent angioplasty after thrombus aspiration plus intra-infarction related artery 500 µg tirofiban administration, with subsequent 12-hour intravenous infusion of 0.1 µg×kg(-1)×min(-1) after angioplasty (thrombus aspiration + tirofiban group) and 108 matched control patients with STEMI who underwent angioplasty after thrombus aspiration (thrombus aspiration group). The primary end points included thrombolysis in myocardial infarction (TIMI) flow immediately after angioplasty, complete ST-segment elevation resolution (> 70%) at 90 minutes after angioplasty and the peak of creatine kinase-MB (CK-MB) and troponin I (TnI). The secondary end points were the left ventricular ejection fraction (LVEF) in the hospital and at 9 months follow-up as well as major adverse cardiac events (MACE: cardiac death, target vessel revascularization, re-infarction) at 9 months and any bleeding events.

RESULTSBaseline characteristics of the two groups were well-balanced. The TIMI 3 flow rate (97.22% vs. 87.04%, P = 0.011) and the complete ST-segment resolution rate (66.67% vs. 50.91%, χ(2) = 6.129, P = 0.047)were significantly higher in the thrombus aspiration + tirofiban group than in the thrombus aspiration group. The peak of CK-MB (83.9 U/L vs. 126.1 U/L, P = 0.034) and TnI (42.7 ng/ml vs. 72.5 ng/ml, P = 0.029) were significantly lower in the thrombus aspiration + tirofiban group than in the thrombus aspiration group. LVEF in the hospital favored thrombus aspiration + tirofiban the group (45.7% ± 10.8%, 42.9% ± 9.9%, t = 1.99, P = 0.049). There was a tendency to decreased MACE rate at 9-month follow-up, which favored thrombus aspiration + tirofiban the group (logrank χ(2) = 2.865, P = 0.09). Bleeding events were similar between the two groups.

CONCLUSIONThrombus aspiration plus intra-infarct-related artery bolus administration of tirofiban in patients with STEMI undergoing primary angioplasty may improve myocardium perfusion, attenuate myocardial ischemia and result in a better clinical prognosis compared to thrombus aspiration alone.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; methods ; Coronary Thrombosis ; therapy ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Retrospective Studies ; Tyrosine ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVETo observe the safety and efficiency of ultra-early glycoprotein IIb/IIIa receptor blockade tirofiban use in patients with acute ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI).

METHODSFrom April 2005 to April 2006, 158 consecutive AMI patients (117 males, mean age of 58.8 +/- 25.2 years) were randomly received tirofiban (10 microg/kg bolus i.v. followed by 0.15 microgxkg(-1)xmin(-1) for 36 hours) before PCI in emergency room (early, n = 78) or immediately before PCI in catheterization lab (late, n = 80). Clinical and angiographic features between 2 groups before and after PCI were analyzed.

RESULTSBaseline clinical characteristics before PCI were similar between the two groups. Tirofiban was administered 39.8 minutes earlier in early group than that in the late group. The TIMI 3 flow rate (23.1% vs. 10.0%, P = 0.032) and the combined TIMI 2 or 3 flow rate (39.7% vs. 23.8%, P = 0.040) at initial angiography before PCI were significantly higher in early group than that in late group. However, TIMI 3 flow rate, myocardial Blush grade or corrected TIMI frames immediately after PCI were similar between the groups. The combined incidence of death or recurrent MI as well as bleeding complications or thrombocytopenia rate during early follow-up were similar between the groups (P > 0.05).

CONCLUSIONSEarly initiation of tirofiban in patients with acute STEMI treated by primary PCI was safe. A better patency (TIMI 3 and TIMI 2-3 flow) in infarct related artery was obtained in patients with early tirofiban administration.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; methods ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; physiopathology ; therapy ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Tyrosine ; administration & dosage ; analogs & derivatives

Rapid arterial rethrombosis is associated with high-grade residual stenosis and usually occurs at the site of the initial occlusion, resulting in reocclusion of the recanalized artery. Platelets may play an active role in such rethrombosis after thrombolytic-induced clot lysis. Given that glycoprotein IIb/IIIa receptor blockers, like tirofiban, prevent thrombus formation by inhibiting the final common pathway of platelet aggregation, they may be helpful for treating rethrombosis after thrombolysis. A 64-year-old man presented with an acute ischemic stroke due to internal carotid artery (ICA) occlusion. The ICA was recanalized by intravenous thrombolysis but reoccluded shortly after recanalization. The reoccluded ICA was successfully recanalized using intra-arterial tirofiban. A carotid stent was subsequently inserted to relieve severe stenosis and to prevent recurrent stroke. Here, we report a case of rescue treatment of a successfully recanalized ICA by intra- arterial tirofiban. We suggest that rescue use of intra-arterial tirofiban may be effective and safe, especially in hemorrhage prone situations, due to the relatively lower dose of tirofiban compared with intravenous doses.
*Carotid Artery, Internal ; Carotid Stenosis/*drug therapy/radiography/surgery ; Emergency Treatment ; Humans ; Infusions, Intra-Arterial ; Male ; Middle Aged ; Stents ; Tyrosine/administration & dosage/*analogs & derivatives/therapeutic use

BACKGROUNDTirofiban has been widely used as an adjunctive pharmacologic agent for revascularization in patients undergoing percutaneous coronary intervention, and the outcomes appear attractive. However, the potential benefits from early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remain unclear.

METHODSWe conducted a search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to September 2012 without language restriction. A total of eight randomized trials (n = 1 577 patients) comparing early (emergency department or ambulance) versus late (catheterization laboratory) administration of tirofiban in STEMI patients undergoing PPCI were included in this meta-analysis. Risk ratio (RR) was computed from individual studies and pooled with random- or fixed-effect models.

RESULTSThere were no differences in post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and Corrected TIMI Frame Count (RR = 1.02, 95% confidence interval (CI): 0.99-1.05, P = 0.18; weighted mean difference (WMD) = -0.93, 95% CI: -5.37-3.52, P = 0.68, respectively) between the two groups. Similarly, there were no significant differences in the incidence of 30-day mortality (RR = 1.69, 95% CI: 0.69-4.13, P = 0.25) and re-myocardial infarction (RR = 0.71, 95% CI: 0.21-2.35, P = 0.57) between early and late administration of tirofiban. As to the safety end points, no significant difference was observed in hospital minor bleeding (RR = 1.08, 95% CI: 0.54-2.14, P = 0.83) and hospital and 30-day major bleeding between the two groups (RR = 0.98, 95% CI: 0.46-2.10, P = 0.96; RR = 1.32, 95% CI: 0.59-2.97, P = 0.49, respectively).

CONCLUSIONSEarly administration of tirofiban in patients undergoing PPCI for STEMI was safe, but no beneficial effects on post-procedural angiographic or clinical outcomes could be identified as compared with late administration. Besides the negative finding, more high-quality randomized clinical trials are still needed to explore the efficacy of adequate, earlier administration of tirofiban in patients undergoing PPCI.

Fibrinolytic Agents ; adverse effects ; therapeutic use ; Humans ; Myocardial Infarction ; drug therapy ; surgery ; Percutaneous Coronary Intervention ; methods ; Thrombolytic Therapy ; Tyrosine ; analogs & derivatives

Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; fms-Like Tyrosine Kinase 3 ; genetics