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

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

OBJECTIVETo compare the efficacy of intracoronary administration of combined high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction.

METHODSConsecutive 258 patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary PCI, treated with thrombus aspiration and then intracoronary tirofiban, were randomly divided into adenosine group (n = 130) and control group (n = 128). Adenosine group received 2 times intracoronary adenosine (2 mg) after thrombus aspiration and after stenting of the infarct-related artery through the aspiration catheter. Control group received placebo. The primary end point was myocardial blush grade (MBG) after PCI. Secondary end points were thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI, ST-segment elevation resolution (STR), and major adverse cardiac events (MACE) at 30 days and 12 months.

RESULTSTIMI flow grade post PCI did not differ between the 2 groups, while CTFC favored the adenosine-treated patients [(21.6 ± 6.5) frames] compared with the placebo-treated patients [(25.1 ± 7.8) frames, P = 0.001]. MBG 3 was more frequently observed in the adenosine compared to the control group [45.1% (55/122) vs.32.0% (39/122), P = 0.035]. Patients in the adenosine group had a trend of higher rate of compete STR after the procedure compared patients in the control group [53.6% (67/125) vs. 41.9% (52/124), P = 0.065]. The incidence of MACE was comparable between patients randomized to adenosine and placebo at 30 days [12.3% (16/130) vs. 17.2% (22/128), P = 0.295] and at 12 months [12.3% (16/130) vs. 18.0% (23/128), P = 0.227].

CONCLUSIONIntracoronary administration of high-dose adenosine combined with tirofiban provides further improvement on myocardial perfusion after primary PCI but does not affect the clinical outcomes in patients with STEMI.

Adenosine ; therapeutic use ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; therapeutic use ; Tyrosine ; analogs & derivatives ; therapeutic use

BACKGROUNDTransradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban.

METHODSPatients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n = 298) and transfemoral (n = 314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded.

RESULTSBaseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95%CI 0.35 - 0.91; P = 0.03).

CONCLUSIONSUsing transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.

Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Percutaneous Coronary Intervention ; methods ; Tyrosine ; analogs & derivatives ; therapeutic use

Alveolar Epithelial Cells ; cytology ; metabolism ; Animals ; Apoptosis ; Lung ; drug effects ; metabolism ; Nitric Oxide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tyrosine ; analogs & derivatives ; metabolism

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