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

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

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

BACKGROUNDModern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and a number of studies showed the appearance of increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) during and after noise exposure. This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea.

METHODThirty guinea pigs were used in this study. The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL (A-weighted) for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions, an exogenous NO and superoxide donor, for 30 minutes. Then the cochleae of the animals were dissected. Propidium iodide (PI), a DNA intercalating fluorescent probe, was used to trace morphological changes in OHC nuclei. The distribution of nitrotyrosine (NT) in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method. Whole mounts of organ of Corti were prepared. Morphological and fluorescent changes were examined under a confocal microscope.

RESULTSEither after noise exposure or after SIN1 perfusion, outer hair cells (OHCs) death with characteristics of both apoptotic and necrotic degradation appeared. Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals. After noise exposure, NT immunostaining became much greater than the control animals in OHCs. The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure. In the normal later wall of cochleae, relatively weak nitrotyrosine immunolabeling could be observed. After noise exposure, nitrotyrosine immunoactivity became stronger in stria vascularis.

CONCLUSIONNoise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear pathophysiology of noise-induced hearing loss.

Animals ; Cell Death ; Cochlea ; chemistry ; pathology ; Female ; Guinea Pigs ; Hair Cells, Auditory, Outer ; pathology ; Immunohistochemistry ; Male ; Noise ; adverse effects ; Organ of Corti ; chemistry ; pathology ; Tyrosine ; analogs & derivatives ; analysis

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

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

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